[Senate Report 104-284]
[From the U.S. Government Publishing Office]



                                                       Calendar No. 446
104th Congress                                                   Report
                                 SENATE

 2d Session                                                     104-284
_______________________________________________________________________


 
FOOD AND DRUG ADMINISTRATION PERFORMANCE AND ACCOUNTABILITY ACT OF 1995

                                _______
                                

                 June 20, 1996.--Ordered to be printed

_______________________________________________________________________


   Mrs. Kassebaum, from the Committee on Labor and Human Resources, 
                        submitted the following

                              R E P O R T

                             together with

                            ADDITIONAL VIEWS

                         [To accompany S. 1477]

    The Committee on Labor and Human Resources, to which was 
referred the bill (S. 1477) to amend the Federal Food, Drug, 
and Cosmetic Act and the Public Health Service Act to improve 
the regulation of food, drugs, devices, and biological 
products, and for other purposes, having considered the same, 
reports favorably thereon with an amendment in the nature of a 
substitute and recommends that the bill as amended do pass.

                                CONTENTS

                                                                   Page
   I. Purpose and summary.............................................1
  II. Background and need for the legislation.........................5
 III. Legislative history and votes in committee......................9
  IV. Explanation of the legislation and committee views.............15
   V. Cost estimate..................................................66
  VI. Regulatory impact statement....................................66
 VII. Section-by-section analysis....................................66
VIII. Additional views...............................................91
  IX. Changes in existing law.......................................104

                         I. Purpose and Summary

    Under the Federal Food, Drug, and Cosmetic Act, the Food 
and Drug Administration (FDA) has two important functions: (1) 
the review and approval of important new products that can 
improve the public health, such as life-saving drugs, 
biological products, and medical devices; and (2) the 
prevention of harm to the public from marketed products that 
are unsafe or ineffective. The Federal Food, Drug, and Cosmetic 
Act has been amended numerous times in the past 55 years to 
strengthen the FDA's function of enduring that unsafe or 
ineffective products are not marketed but has been changed only 
once, by the Prescription Drug user Fee Act of 1992 (PDUFA), to 
strengthen the FDA's function of reviewing and approving 
important new products that can improve the public health.
    The Food and Drug Administration Performance and 
Accountability Act of 1996, S. 1477, is designed to provide 
greater balance between these two FDA functions through reforms 
to expedite new product development, testing, and review. The 
legislation is designed to ensure the timely availability of 
safe and effective new products that will benefit the public 
and to ensure that our Nation continues to lead the world in 
new product innovation and development.
    The legislation buildings upon the numerous congressional, 
FDA, and outside investigations and reports that have 
identified problems with the current FDA product approval 
system and have recommended reasonable reforms to streamline 
and strengthen that system. It includes the following major 
provisions:

1. The legislation establishes a clearly defined, balanced mission for 
                                the FDA

    Current law contains no mission statement for the FDA. The 
legislation defined the mission of the FDA as that of 
protecting and promoting the public health. It further defined 
protecting and promoting the public health to include not only 
protecting the public from unsafe or ineffective products but 
also facilitating the rapid and efficient development and 
availability of new products that benefit the public.

 2. The legislation requires public accountability by the FDA for its 
                              performance

    Except as required under PUDFDA, current law provides no 
form of public accountability by the FDA for its performance of 
its statutory obligations. The legislation requires the 
Secretary of Health and Human Services to establish 
quantifiable performance standards for the FDA. The Secretary 
is required to publish an annual report in the Federal Register 
measuring in detail the FDA's actual performance against the 
standards and, if the agency is failing to meet the performance 
standards, setting forth a plan of corrective action.

    3. The legislation provides improved internal management systems

    Current law is silent on important aspects of FDA 
management. The legislation requires the Secretary to implement 
programs and policies to foster collaboration between the FDA, 
the National Institutes of Health, and other science-based 
agencies, to establish information systems, to reform its 
development and use of policy statements, to improve the 
scientific review group process, and to establish clear 
internal appeal mechanisms in order to make existing product 
regulation requirements more rational, consistent, and 
efficient.

   4. The legislation expedites access to products for seriously ill 
                                patients

    Although FDA's investigational drug and device regulations 
do allow for some expanded access to investigational drugs and 
devices, the Federal Food, Drug, and Cosmetic Act has no 
provisions to ensure that patients who cannot be treated 
effectively with existing approved therapies may have access to 
promising new therapies which are the subject of clinical 
trials or are undergoing FDA review. The legislation 
establishes a statutory right for individuals, acting through 
health professionals, to request and manufacturers to provide 
such therapies, provided certain conditions are met, and 
requires the FDA to expedite its review of applications for the 
approval of such therapies.

 5. The legislation is designed to revitalize the investigation of new 
                                products

    Current law focuses on the review of new products by the 
agency but does not currently include requirements that 
expedite and encourage the investigation of new products. The 
legislation establishes timely review and reasonable data 
requirements for initiating clinical investigations and 
establishes a collaborative relationship between the agency and 
product sponsors in the design of preclinical and clinical 
testing required for the approval of new products.

 6. The legislation establishes a process for efficient, accountable, 
                        and fair product review

    Current law contains no provisions to ensure that the 
agency meets statutory time periods for product review. The 
legislation establishes reasonable data requirements for new 
product approval applications, petitions, or other submissions, 
authorizes the agency to contract with outside experts to 
review all or parts of applications, requires the use of 
outside experts for some of the simpler applications, 
establishes procedures and policies to foster a collaborative 
review process between the agency and the applicant, provides 
for the use of accredited outside organizations to conduct good 
manufacturing practice inspections, eliminates environmental 
impact review except where appropriate, facilities the 
consideration of applications for the approval of new uses for 
already-approved products, and provides an incentive for the 
sponsors of new drugs and approved drugs to conduct pediatric 
studies to permit labeling for pediatric uses.

    7. The legislation streamlines the drug and biological products 
                           regulatory process

    Current law has not kept pace with new technology and 
scientific knowledge in the development and testing of drugs 
and biological products. In addition to reforming the product 
approval process, the legislation provides the FDA with the 
statutory flexibility to approve a new drug or biological 
product on the basis of one adequate and well-controlled 
clinical trial, permits the approval of drugs and biological 
products based upon small-scale manufacturing, expands the type 
of manufacturing changes that may be made without prior agency 
approval, repeals outdated requirements for agency preapproval 
of batches of insulin and antibiotics, and conforms the 
regulation of drugs and biological products.

     8. The legislation improves the regulation of medical devices

    Current law imposes a number of unnecessarily restrictive 
regulatory requirements on medical devices which require the 
agency to expend valuable resources reviewing premarket 
notifications for devices posing minimal risks. These 
requirements have substantially increased device review and 
clearance or approval times, delaying the public's access to 
these products and driving the medical device industry abroad. 
In addition to reforming the medical device approval process, 
the legislation eliminates premarket notification for the 
simplest devices, provides for scientific review group input on 
whether new devices should be classified as class III devices, 
provides greater flexibility for device modification without a 
new premarket notification or approval, establishes reasonable 
approval standards, requires device tracking and postmarket 
surveillance only where justified, eliminates distributor 
reporting requirements, establishes reasonable review 
requirements specific to devices, and provides the Secretary 
with authority to recognize appropriate performance standards 
developed by authoritative standards-setting organizations.

      9. The legislation reforms animal drug approval requirements

    Current law fails to reflect basic differences between 
animal and human drugs and current practices and scientific 
knowledge relating to animal drugs. In addition to reforming 
the new animal drug approval process, the legislation modifies 
the efficacy standard for new animal drugs to better reflect 
current scientific knowledge, reduce the regulatory burden on 
the development of drugs for minor uses and species, and 
establishes a new system of veterinary feed directive to 
reflect current and emerging practices in the use of medicated 
feeds.

 10. The legislation simplifies the food additive approval process and 
      provides a more reasonable standards for some health claims

    Current law requires the agency to preapprove indirect food 
additives, most of which pose little if any risk to human 
health. In addition to reforming the direct food additive 
petition process, the legislation replaces the preapproval 
process for indirect food additive with a simple notification 
requirement.
    The legislation also modifies the current law requirement 
for FDA preapproval of health claims for foods when claims are 
based on authoritative recommendations by the National 
Institutes of Health, the Centers for Disease Control and 
Prevention, the National Academy of Sciences, and other, 
similar bodies.

              II. Background and Need for the Legislation

                             a. background

    Over the years, Congress has dramatically expanded the 
reach and responsibilities of the FDA. The Federal Food and 
Drugs Act of 1906, the first national statute enacted by 
Congress to regulate the American food and drug supply, gave 
the agency the authority to police the market and remove 
adulterated or misbranded foods and drugs.
    In 1938, Congress passed the Federal Food, Drug, and 
Cosmetic Act, which expanded the agency's reach to the 
regulation of cosmetics and medical devices and, for the first 
time, provided the agency with the authority to review and 
assure the safety of a product--new drugs--prior to the 
marketing of that product. The 1938 statute required sponsors 
of new drugs to file a new drug application notifying the FDA 
prior to marketing a new human or animal drug. the new drug 
application became effective after 60 days (which could be 
extended to 180 days), unless the agency found that it had 
insufficient information to determine whether the drug was safe 
for its intended use.
    In the ensuing years, Congress enacted a series of statutes 
further expanding the FDA's regulatory reach. These included 
the 1944 Pitts Act, which gave the FDA the authority to 
regulate biological products, and the Miller Pesticide 
Amendments of 1954, which required FDA premarket approval for 
pesticides in or on raw or processed foods. The Food Additive 
Amendment of 1958 required premarket approval of food 
additives, and the Color Additive Amendments of 1960 required 
premarket approval of color additives in food, drugs, and 
cosmetics. The Drug Amendments of 1962 required that drugs be 
demonstrated to be effective as well as safe prior to 
marketing. The Animal Drug Amendments of 1968 consolidated the 
premarket approval requirements for new animal drugs and feed 
additives. The Medical Device Amendments of 1976 required 
premarket notification for devices substantially equivalent to 
those already on the market and premarket approval for new 
medical devices, and the Safe Medical Devices Act of 1990 
required the premarket approval of substantial equivalence 
notifications.
    From 1906 to the present, then, the FDA's role has expanded 
from one of removing adulterated or misbranded products from 
the market to one of preapproving the testing and marketing of 
products.

                      b. need for the legislation

    Over the years, and particularly with the enactment of 
requirements that the FDA determine that drugs and devices are 
effective as well as safe, the FDA's requirements for clinical 
testing and its premarket reviews of new products have grown 
increasingly complex, time-consuming, and costly. From the 
1960s to the 1990s, for example, the time required to complete 
clinical trials for new drugs has grown from 2.5 to nearly 6 
years. Applications for the approval of new drugs typically run 
to hundreds of thousands of pages in length. According to the 
most recent published study, from the beginning of the process 
to the end, it takes an average of 15 years and costs in the 
range of $500 million dollars to bring a new drug to market. 
[DiMasi, Trends in Drug Development Cost, Times, and Risks, 29 
Drug Information Journal 375, 382, April-June 1995.]
    By law, the FDA is required to review and act on 
applications for the approval of new drugs and devices within 
180 days. Today, however, it takes the agency on average 606 
days to complete its review of new medical devices and 570 days 
to complete its review of most new drugs. By law, the FDA is 
required to review and act on petitions for the approval of new 
food additives within 180 days. However, since 1970, the 
average time to approval of a direct food additive has been at 
least 600 days, and some petitions have been pending at the 
agency since the 1970s. Currently, the FDA reports that it has 
a backlog of 300 food additive petitions.
    These increases in the time, complexity, and cost of 
bringing new products to market are borne directly by the 
public, in delayed access to important new products--including 
lifesaving medical therapies--and in higher costs. They are a 
growing disincentive to continued investment in the development 
of innovative new products and a growing incentive for American 
companies to move research, development, and production abroad, 
threatening our Nation's continued world leadership in new 
product development, costing American jobs, and further 
delaying the public's access in important new products.
    Over the past 20 years, a bipartisan consensus has emerged 
on the need for reforms of the FDA premarket approval process 
to strike a better balance between the need to ensure that 
products are safe and effective, on the one hand, and to 
facilitate the timely availability of new products, on the 
other.
    During 1978 and 1979, Congress considered a wholesale 
revision of the new drug approval process. This committee led 
that effort, reporting legislation introduced by Senator 
Kennedy, the Drug Regulation Reform Act of 1979. That 
legislation was subsequently approved by the Senate but was not 
considered by the House of Representatives. A number of the 
provisions in that legislation are reflected in S. 1477, 
including provisions to permit new drug sponsors to obtain 
advice from the agency regarding their investigational plans; 
to require the FDA to issue written guidelines regarding 
protocols and methods for conducting drug investigations; to 
require the FDA to determine within 45 days whether new drug 
approval applications meet agency filing requirements; to 
require the FDA to take measures to ensure that reviews are 
conducted efficiently and expeditiously; and to require the use 
of advisory committees as part of the dispute resolution 
mechanism.
    Many of these same changes were recommended by the 
Commission on the Federal Drug Approval Process, convened at 
the request of then-Representative Albert Gore, Jr., chairman 
of the House Subcommittee on Investigations and Oversight and 
then-Representative James Scheuer, chairman of the House 
Subcommittee on Natural Resources, Agricultural Research and 
Environment. The Commission's 1982 report recommended such 
changes as simplication of the investigational new drug 
requirements; recognition that drug effectiveness could be 
demonstrated by one study in appropriate cases; greater 
utilization of outside expert advice; improving interactions 
with industry; tracking the review process to ensure 
timeliness; simplified procedures for the use of 
investigational drugs for therapeutic purposes; greater 
reliance upon expert judgment in determining the safety and 
effectiveness of drugs; concurrent review of portions of new 
drug applications by FDA; and greater reliance on foreign 
studies. These recommendations are incorporated in S. 1477.
    Concerned about the slow process for the development and 
approval of AIDS and cancer drugs, in 1988 Vice President Bush 
requested the President's Cancer Panel to establish a National 
Committee to Review Current Procedures for Approval of New 
Drugs for Cancer and AIDS. The Committee's final report, issued 
in 1990, recommended a national policy to foster the 
development of new drugs for AIDS and cancer; expediting 
approval of important new drugs; greater use of scientific 
judgment of qualified experts in determining the effectiveness 
of new drugs; the use of surrogate end points to establish drug 
effectiveness; a more open relationship between the FDA and the 
regulated industry in order to foster a spirit of mutual 
cooperation; responsiveness to the needs of patient advocacy 
groups; a fundamental restructuring of the FDA advisory 
committee system; more flexible use of investigational drugs 
for treatment; the right of patients to obtain investigational 
drugs under expanded access conditions; greater use by the FDA 
of outside review of new drug applications; and automatic 
approval of supplemental new drug applications for minor 
technical changes such as manufacturing modifications. Again, 
many of these recommendations are incorporated in S. 1477.
    In 1989, in response to serious questions that were being 
raised about the ability of the FDA to perform its job, 
Secretary of Health and Human Services, Dr. Louis Sullivan, 
chartered the Advisory Committee on the Food and Drug 
Administration. The committee was chaired by Dr. Charles 
Edwards, a former FDA commissioner, and Dr. David Kessler 
served on the committee until his appointment as FDA 
commissioner. The charter directed the committee to examine the 
mission, responsibilities, and structure of the FDA and to make 
recommendations for improving the agency's operations.
    One of the major findings of the committee was the need for 
the FDA to set forth a clear statement of its mission and goals 
and a plan for achieving the goals. In formulating a statement 
of purpose and program goals, the committee found that ``the 
agency should be guided by the principle that expeditious 
approval of useful and safe new products enhances the health of 
the American people. Approving such products can be as 
important as preventing the marketing of harmful or ineffective 
products. This is especially true for people with life-
threatening illnesses and for diseases for which alternative 
therapies have not been approved.'' This key recommendation is 
the informing principle of S. 1477.
    In 1991, the Council on Competitiveness, chaired by Vice 
President Dan Quayle, announced an important Administration 
initiative to improve the FDA's drug approval process. The 
initiative was designed to achieve three overarching goals by 
1994--a substantial reduction in the average development and 
approval time for all new drugs; a reduction in FDA approval 
time for important new drugs to 6 months; and a reduction in 
FDA approval time to 12 months for all other drugs.
    The Council on Competitiveness also recommended a number of 
specific reforms, including expanded use of outside reviews; 
expanded use of advisory committees; flexible interpretation of 
the efficacy standard; accelerated approval through a reduction 
in the number of clinical studies required prior to approval 
and the amount of time FDA requires to grant approval, 
including reliance on surrogate endpoints; enhanced 
computerization to track applications and expedite review; and 
enhanced internal management, including the measurement of 
progress in application review against statutory deadlines. 
Many of these recommendations are incorporated in S. 1477.
    Most recently, Vice President Gore has pressed for reform 
of the FDA product approval system as part of President 
Clinton's Reinventing Government initiative. The President and 
Vice President Gore have issued four reports, covering drugs 
and medical devices, drugs made from biotechnology, food, and 
cancer drugs, designed to improve the product approval system, 
eliminate outmoded regulations, and update the Federal Food, 
Drug, and Cosmetic Act to reflect advances in the science of 
new product development and testing. Many of the 
recommendations in these reports are incorporated in S. 1477.
    Every administration in the past 20 years has recognized 
the need for reforms of the FDA's product approval system to 
bring into better balance the need to ensure the safety and 
effectiveness of products and the need to facilitate the 
development, testing, and timely approval of safe and effective 
products that benefit the public. Until recently, the FDA has 
been very slow to respond, or has not responded at all, to 
recommendations for reform made by the distinguished advisory 
panels that have been convened over the years. At the four 
hearings that the committee held on FDA reform, witnesses who 
appeared before the committee--several of whom had served on 
these advisory panels--testified about the same problems that 
have been described in the reports summarized above and 
recommended many of the same solutions.
    America's pharmaceutical, biotech, medical device, and food 
industries are among our most innovative, dynamic, and 
productive. They contribute significantly to our Nation's high 
standards of health care and to our unparalleled supply of 
wholesome, abundant, and affordable food. They hold the promise 
of further breakthroughs in life-saving and enhancing therapies 
to combat the diseases and disabling conditions afflicting us 
today and those which may emerge in the future. They hold the 
promises of new food technologies that will enhance diets and 
improve health, provide natural resistance to pests, droughts, 
and other plagues, and help meet the nutritional needs of a 
growing world population. They are job-creating industries that 
contribute positively to our balance of trade.
    Formidable challenges must be met, however, if these 
opportunities are to be realized and America is to continue to 
lead the world in product innovation. Domestically, our health 
care system is rapidly reorganizing, consolidating, and moving 
into managed care, with potentially profound effects on the 
market for products and the revenues necessary for continued 
research and product development. Markets are becoming 
increasingly competitive, particularly as the European Union 
moves to adopt a uniform drug and device approval system.
    If we are to confront these challenges and realize the 
opportunities on today's and tomorrow's horizons, we cannot 
afford an overly complex, bureaucratic, time-consuming, and 
expensive regulatory system. Nor can we afford an adversarial 
relationship between the FDA and the industries it regulates or 
an agency pursuing so many agendas that it lacks a clearcut 
mission and sphere of responsibility. We must update our food 
and drug laws and our regulatory practices to reflect the 
scientific and technological advances that have occurred in the 
development and testing of new products and to ensure that the 
FDA is an agency committed to fostering innovation and ensuring 
timely public access to beneficial new products.
    It is no easy feat that Americans ask of the FDA. Americans 
want it to hold the gate to the market tightly shut against 
unsafe or ineffective products while opening it wide for the 
next generation of innovation--with all of its potential 
promise, but not without its risks. Clear statutory guidance is 
needed to assist the agency to find this delicate balance and 
to bring our food and drug laws and regulatory systems into the 
next century. The FDA Performance and Accountability Act of 
1996, S. 1477, embodies many of the bipartisan conclusions and 
recommendations reached by the expert panels for accomplishing 
this difficult task of balancing risk and promise.

            III. Legislative History and Votes in Committee

    ``The Food and Drug Administration Performance and 
Accountability Act of 1996,'' S. 1477, was introduced by 
Senator Kassebaum on December 13, 1995. Prior to the drafting 
of the legislation, the committee held 2 days of hearings on 
April 5 and 6, 1995, entitled. ``The FDA and the Future of the 
American Biomedical and Food Industries.'' These hearings 
examined the challenges and opportunities facing our Nation's 
pharmaceutical, biotech, medical device and food industries and 
ways that the FDA's regulation of these industries might need 
to be reformed to ensure that these challenges are met and 
opportunities realized.
    Following the introduction of S. 1477, the committee held a 
hearing on February 21, 1996, entitled ``Revitalizing New 
Product Development--From Clinical Trials Through FDA Review.'' 
This hearing focused on the underlying principle informing the 
provisions of S. 1477--that it is possible through reform to 
substantially reduce the time it currently takes to develop and 
test new drugs, biologics, medical devices, and food additives 
and the time it takes the FDA to review and approve these 
products.
    The committee held a second hearing on S. 1477 on February 
22, 1996, entitled ``More Information for Better Patient 
Care.'' This hearing focused on provisions in S. 1477 reforming 
the FDA's regulation of the dissemination of information about 
new uses for approved drugs, biological products, and medical 
devices.
    On March 27 and 28, 1996, the committee held executive 
sessions to consider S. 1477. Senator Kassebaum brought up and 
amendment in the nature of a substitute that was considered as 
original text for purposes of further amendment. Twelve 
amendments, including one ``sense of the committee'' amendment, 
and two motions were adopted in the executive sessions, and S. 
1477 was favorably reported by a roll call vote of 12 yeas to 4 
nays.

   A. AMENDMENTS AND MOTIONS ADOPTED BY VOICE VOTE DURING EXECUTIVE 
                                SESSIONS

    Seven amendments and two motions were adopted in the 
executive sessions by voice vote:
    1. Senator Frist offered an amendment to establish, under a 
new title of S. 1477, a peer-reviewed grant program to 
establish and operate three centers for education and research 
on drugs, devices, and biological products. The amendment 
provides that the program will be administered by the 
Secretary, acting through the Commissioner, sets forth 
mandatory and discretionary activities to be undertaken by the 
centers, establishes an oversight committee, requires a report 
to Congress on the impact of the centers on the safe use of 
drugs, biological products, and medical devices, and authorizes 
appropriations of $9 million in fiscal year 1997, $12 million 
in fiscal year 1998, $15 million in fiscal year 1999, and $15 
million in fiscal year 2000.
    2. Senators Simon and Frist offered an amendment to extend 
through fiscal year 1998 the authorization for a clinical 
pharmacology training pilot program originally authorized under 
P.L. 102-222. The amendment authorizes an appropriation of $1.9 
million in each fiscal years 1997 and 1998.
    3. Senator Kennedy offered an amendment to clarify the 
Secretary's authority to determine whether a new device is 
substantially equivalent to a legally marketed class I or class 
II device with a more general use than the new device.
    4. Senator Kennedy offered an amendment to strike a 
provision of S. 1477 that eliminated a requirement for device 
manufacturers to report to the Secretary, in some 
circumstances, removals of, or corrections made to, devices 
already on the market.
    5. Senator Kennedy offered an amendment to strike a section 
of S. 1477 relating to supplemental applications for the 
approval of new uses of approved drugs and devices and replace 
that section with alternative provisions to improve the FDA's 
supplemental application review process.
    6. Senator Gregg offered a sense of the committee amendment 
encouraging the Secretary of Health and Human Services, in 
consultation with the Secretary of Commerce, to move toward the 
acceptance of mutual recognition agreements reached between the 
European Union and the U.S. Food and Drug Administration.
    7. Senators Gregg, Ashcroft, and Frist offered an amendment 
to clarify the FDA's regulation of radiopharmacological 
products. The amendment requires the Secretary to issue a 
proposed and final regulation governing the approval of 
radiopharmaceuticals, sets forth several issues that must be 
included in the regulation, and requires that the regulation of 
radiopharmaceuticals be handled in a single office at the 
Center for Drug Evaluation and Research.
    8. Senator Kassebaum offered a motion to strike provisions 
in the amendment in the nature of a substitute reforming the 
FDA's regulation of dissemination of information about new uses 
for approved drugs, biological product, and devices, with the 
understanding that the committee would continue to work to come 
to consensus on this issue before the bill was brought to the 
Senate floor for consideration.
    9. Senator Kassebaum offered a motion to strike provisions 
in the amendment in the nature of a substitute relating to 
patient and industry representation on FDA scientific advisory 
groups with the understanding that the committee would continue 
to work to come to consensus on this issue before the bill was 
brought to the Senate floor for consideration.

         B. ROLLCALL VOTES TAKEN DURING THE EXECUTIVE SESSIONS

    Seven rollcall votes on amendments were taken during the 
executive session:
    1. Senator Coats offered an amendment on accredited-party 
participation to establish a 3-year pilot program for private 
sector review of premarket notifications and premarket approval 
applications for devices. The amendment was adopted by a 
rollcall vote of 11 yeas to 4 nays.
        YEAS                          NAYS
Kassebaum                           Kennedy
Coats                               Pell
Gregg                               Simon
Frist                               Harkin
DeWine
Ashcroft
Abraham
Gorton
Dodd
Mikulski
Wellstone

    2. Senator Kennedy offered an amendment to strike 
provisions in the amendment in the nature of a substitute to S. 
1477 which would require the Secretary to contract with experts 
for the review of product approval applications for which the 
Secretary had failed to meet the statutory period for agency 
action for at least 95 percent of the applications for approval 
for that product category. Senator Kennedy's amendment would 
instead have required that, in the event the Secretary fails to 
meet either statutory targets or targets set forth in the 
Prescription Drug User Fee Act for 90 percent of annual actions 
in a particular product category, then the Secretary must 
report an action plan to Congress and report every 6 months 
thereafter on progress toward achieving the plan. The amendment 
was defeated by a rollcall vote of 7 yeas to 9 nays.
        YEAS                          NAYS
Kennedy                             Kassebaum
Pell                                Jeffords
Dodd                                Coats
Simon                               Gregg
Harkin                              Frist
Mikulski                            DeWine
Wellstone                           Ashcroft
                                    Abraham
                                    Gorton

    3. Senator Coats offered an amendment to limit the 
Commissioner of the Food and Drug Administration to a term of 5 
years and to permit the removal of the Commissioner from office 
only pursuant to a finding of neglect of duty or malfeasance in 
office. The amendment was adopted by a rollcall vote of 9 yeas 
to 7 nays.
        YEAS                          NAYS
Kassebaum                           Kennedy
Jeffords                            Pell
Coats                               Dodd
Gregg                               Harkin
Frist                               Mikulski
DeWine                              Wellstone
Ashcroft                            Abraham
Gorton
Simon

    4. Senator Gregg offered an amendment to permit food 
manufacturers to make health claims for their products which 
have not been preapproved by the FDA if those claims are based 
on published statements, conclusions, or recommendations by a 
Federal agency with official responsibility for public health 
protection or research relating directly to human nutrition or 
the National Academy of Sciences or subdivisions of its 
scientific body. The amendment requires the manufacturer or 
distributor to notify the Secretary 90 days in advance of the 
first introduction of a food bearing such a claim. The 
amendment was adopted by a rollcall vote of 10 yeas to 6 nays.
        YEAS                          NAYS
Kassebaum                           Kennedy
Jeffords                            Pell
Coats                               Dodd
Gregg                               Simon
Frist                               Mikulski
DeWine                              Wellstone
Ashcroft
Abraham
Gorton
Harkin

    5. Senator Coats offered an amendment to require the 
Secretary to call on national organizations to develop a long-
range comprehensive action plan to achieve goals consistent 
with the goals of the FDA's proposed rule on ``Prescription 
Drug Product Labeling: Medication Guide Requirements'' relating 
to the provision of oral and written prescription information 
to consumers. The amendment prohibits the Secretary from 
implementing the proposed rule unless the national 
organizations fail to develop and begin to implement a 
comprehensive plan within 120 days. The amendment requires the 
Secretary to review the status of private-sector initiatives 
and if the goals of the FDA's proposed regulation have not been 
met, to seek public comment on other initiatives which may be 
taken to meet such goals. The amendment was adopted by a 
rollcall vote of 13 yeas to 3 nays.
        YEAS                          NAYS
Kassebaum                           Kennedy
Jeffords                            Pell
Coats                               Simon
Gregg
Frist
DeWine
Ashcroft
Abraham
Gorton
Dodd
Harkin
Mikulski
Wellstone

    6. Senator Harkin offered an amendment which incorporated 
the provisions of Senator Coats' amendment on accredited-party 
participation (see 1 above) but which required the Secretary to 
approve any compensation agreements reached by the accredited-
party and the device manufacturer or sponsor who engages the 
services of the accredited-party. The amendment was defeated on 
a rollcall vote of 5 yeas to 11 nays.
        YEAS                          NAYS
Kennedy                             Kassebaum
Pell                                Jeffords
Simon                               Coats
Harkin                              Gregg
Wellstone                           Frist
                                    DeWine
                                    Ashcroft
                                    Abraham
                                    Gorton
                                    Dodd
                                    Mikulski

    7. Senator Gregg offered an amendment to prohibit State and 
local governments from establishing or continuing any 
requirement relating to the regulation of a nonprescription 
drug which is different from, or in addition to, or otherwise 
not identical with Federal requirements. The amendment permits 
States to apply to the Secretary for an exemption from the 
prohibition and propose a requirement which is justified by 
compelling local conditions or protects an important public 
interest that would otherwise be unprotected, that would not 
cause the nonprescription drug to be in violation of any 
applicable requirement or prohibition under Federal law, and 
that would not unduly burden interstate commerce. The amendment 
was adopted on a rollcall vote of 10 yeas to 6 nays.
        YEAS                          NAYS
Kassebaum                           Kennedy
Jeffords                            Pell
Coats                               Simon
Gregg                               Harkin
Frist                               Wellstone
Ashcroft                            DeWine
Abraham
Gorton
Dodd
Mikulski

     C. FOUR AMENDMENTS OFFERED AND SUBSEQUENTLY WITHDRAWN WITHOUT 
                 CONSIDERATION DURING EXECUTIVE SESSION

    1. Senator Gregg offered and then withdrew an amendment to 
replace the Delaney clause, which sets a zero-risk carcinogenic 
safety standard for food additives, animal drugs, and color 
additives, with a negligible-risk standard.
    2. Senator Wellstone offered an amendment to strike 
language in the amendment in the nature of a substitute to S. 
1477 that required there to be a ``nonvoting public 
representative'' on all FDA scientific advisory groups and 
instead require there to be a ``voting consumer representative, 
including a patient or patient-nominated individual, who 
represents the perspective and reports back to the affected 
community.'' This amendment was withdrawn when Senator 
Kassebaum offered a motion to strike the language in the 
amendment in the nature of a substitute requiring that 
scientific advisory groups include a ``nonvoting industry 
representative and a nonvoting public representative.''
    3. Senator Harkin offered and then withdrew a second-degree 
amendment to Senator Coats' amendment providing for accredited-
party participation to establish a 3-year pilot program for the 
review of medical devices. The second-degree amendment would 
have prohibited review by accredited third parties of class III 
devices.
    4. Senator Kennedy offered and then withdrew an amendment 
to substantially revise provisions in the amendment in the 
nature of a substitute to S. 1477 relating to the 
responsibilities of manufacturers of drugs and biologics when 
they make changes in their manufacturing processes. Senator 
Kassebaum indicated to Senator Kennedy that she would work with 
him to develop a consensus on this matter before the bill is 
considered on the Senate floor.

         IV. Explanation of the Legislation and Committee Views

                  Title I--Mission and Accountability

Mission

    The first title of S. 1477 establishes in statute that the 
mission of the FDA is to promote and protect the health of the 
American public by facilitating the rapid and efficient 
development and availability of new products, protecting the 
public from unsafe or ineffective products, and enforcing 
applicable statutes and regulations in a timely, fair, 
consistent, and decisive manner.
    The committee concurs with the view of the Advisory 
Committee on the Food and Drug Administration (discussed above) 
that ``the Agency should be guided by the principle that 
expeditious approval of useful and safe new products enhances 
the health of the American people. Approving such products can 
be as important as preventing the marketing of harmful or 
ineffective products.''
    From the 1906 Food and Drugs Act through the 1990 Safe 
Medical Devices Act, food and drug law has emphasized that the 
duty of the FDA is to protect the public against unsafe or 
ineffective products. The purpose of this legislation, as 
reflected in the mission statement, is to give greater emphasis 
in the law to ensuring timely access to safe and effective 
products, while continuing to protect the public against unsafe 
or ineffective products.
    The committee hears often from seriously ill patients and 
their families who are intensely frustrated by the time that 
the agency takes to review applications for the approval of 
promising new therapies. Many must travel abroad to obtain 
promising new therapies that are still under development or 
awaiting approval in the United States, or which will never be 
available here because companies, daunted by the cost, time, 
and complexity of bringing a new product to market, have opted 
not to seek FDA approval.
    The committee has also received grave expressions of 
concern by the regulated industries about the impact the 
increasing complexity and costliness of FDA demands on product 
development and testing and lengthy delays in new product 
approval are having on the ability of small, highly innovative 
start-up companies to continue to pursue new product discovery 
and development. Stifling innovation is not in the best 
interests of public health. Nor are overly burdensome 
requirements which make it increasingly difficult for 
innovative domestic industries to continue to pursue research, 
development, and manufacturing in the United States while 
remaining competitive in international markets.
    By making explicit in law that facilitating the rapid and 
efficient development and availability of new products is a 
fundamental mission of the FDA, the committee is also hopeful 
that the FDA will feel more confident in weighing the potential 
benefits of a product against its potential risks. Because 
current law places such emphasis on protecting the public from 
unsafe and ineffective products and Congress has been quick to 
call the agency on the carpet when unsafe or ineffective 
products harm consumers, the committee believes the agency may 
have become overly risk-adverse in its evaluation of promising 
new products.
    The mission statement also reflects the importance the 
committee places on timely, fair, consistent, and decisive FDA 
action in enforcing the applicable statutes. The committee, for 
example, has received numerous reports of fundamental 
inconsistencies in the enforcement of requirements and 
regulations from region to region of the country and of field 
inspectors requiring manufacturing processes that differ from 
those that the agency has approved under new product approval 
applications or submissions.

FDA performance standards

    Current law contains no provisions designed to ensure that 
performance standards are set and that the agency is held 
accountable for adherence to those standards. The legislation 
requires the Secretary of Health and Human Services to set 
quantifiable performance standards for the FDA, after broad 
consultation with experts in the development, clinical testing, 
and regulation of products subject to the agency's regulation, 
representatives of patient and consumer advocacy groups, health 
professionals, and the regulated industries.
    The committee intends that the requirement for broad 
consultation with experts and those affected by FDA's actions 
be taken very seriously. The FDA regulates approximately 25 
percent of the Nation's economy, and its actions--or its 
failures to act--have profound implications for the lives of 
all Americans. In setting performance standards for the agency, 
the Secretary therefore must be as fully informed as possible 
of the state of the art of product development and regulation 
and of the potential impact of agency actions and decisions on 
individuals and the regulated industries.
    The legislation also requires the Secretary to publish an 
annual report in the Federal Register comparing the FDA's 
actual performance to the standards and if the agency is not in 
compliance with a standard or standards, setting forth a 
corrective action plan. The legislation specifically requires 
that the report include a full statistical presentation 
relating to applications and petitions for new products 
approved by the agency during the year. The committee concluded 
that requiring the report to be published in the Federal 
Register, as opposed to submitted to Congress, would result in 
greater public availability and more widespread consideration.
    Some advocates of FDA reform urged the committee to 
establish an independent review board to oversee the operations 
of the FDA and to ensure that the reforms in this legislation 
are implemented. The committee rejected this approach for 
several reasons. First, the committee believes that it is 
Congress' responsibility to oversee the FDA and to ensure that 
reforms are implemented. The committee believes that the 
performance standards and the annual report will provide 
Congress with tools for effectively carrying out these 
oversight responsibilities. Second, the committee was concerned 
that the logistics of convening an independent review board 
could well delay the implementation of reforms for a year or 
more.
    The performance standards are required to achieve 
particular objectives. First, backlogs on all applications must 
be reduced, with the objective of eliminating all backlogs by 
January 1, 1998. The performance standards must also establish 
a schedule to bring the FDA into full compliance with the 
statutory time deadlines for action on applications by July 1, 
1998.
    The committee believes that these objectives could be met 
without compromising the quality of review if the FDA pursues 
the new policies and procedures established in the legislation. 
First, and perhaps most importantly, the legislation provides 
for collaboration between the sponsors of new products and the 
FDA in the development of protocols for clinical investigation. 
Such collaboration early in the process should provide the FDA 
early on with information about the types of studies that are 
being done, the data that is being collected, and a better 
sense of whether the investigations are demonstrating that the 
product is effective. This collaboration through the clinical 
testing of new products should substantially reduce the burden 
on the agency once the new product application is filed for 
agency review. Collaboration on the design and conduct of 
clinical trials should also substantially reduce the tendency 
of new product sponsors to conduct many more trials than may be 
necessary because of their uncertainty about what the FDA will 
require to demonstrate safety and effectiveness, thereby 
reducing the number of studies and sheer weight of data 
submitted to the agency for review.
    The committee intends this legislation to encourage the FDA 
to adopt a team approach, under which the same persons who are 
working with new product sponsors early in the clinical testing 
phase would also be the persons responsible for reviewing the 
new product application once it is filed with the agency.
    The committee notes that the agency has implemented this 
collaborative, team approach to protocol design, clinical 
investigation, and agency review in its work with sponsors of 
new drugs for the treatment of AIDS and has achieved, as a 
result, a very substantial reduction in review times for these 
drugs.
    Second, the legislation requires the Secretary, in 
consultation with experts in product development and review, 
consumer and patient advocates, and the regulated industries, 
to reevaluate the types and amount of data that are required in 
support of new product applications and publish criteria on 
this matter in the Federal Register. The committee has received 
testimony indicating that advances in the sciences of new 
product development and statistical analysis would permit the 
agency to substantially reduce the types and amount of data and 
information it now requires without compromising its ability to 
evaluate product safety and effectiveness. Further, the 
publication of criteria should provide new product sponsors 
with greater certainty, thus reducing the number of trials and 
amount of data and information they may feel compelled to file 
with new product applications.
    Third, the legislation substantially reduces the number of 
applications subject to agency review to allow the agency to 
focus its review resources on products posing safety and 
effectiveness issues. For example, under this legislation, 
applications for FDA preapproval of many drug, biological 
products, and medical device manufacturing changes would no 
longer be required. Premarket notifications to the agency would 
no longer be required for most class I and many class II 
devices. Similarly, the burden of premarket approval of 
indirect food additives would be very substantially reduced.

Interagency collaboration and FDA facility consolidation

    The legislation requires the Secretary to implement 
programs and policies that will foster collaboration between 
the FDA, the National Institutes of Health, and other science-
based agencies to enhance the scientific expertise available to 
the Commissioner for the evaluation of emerging medical 
therapies, including complementary therapies, and advances in 
nutrition and food sciences.
    The committee includes this provision to help ensure that 
the FDA has available to it the expertise and assistance it may 
need to enhance its own capacity for the efficient evaluation 
of applications for the approval of products that pose 
substantial new scientific or technical issues.
    The committee strongly supports the consolidation of FDA 
facilities at White Oak, Maryland, as proposed by the FDA in 
consultation with the General Services Administration (GSA). 
The consolidation of FDA's facilities into state-of-the-art 
laboratory space and supporting office space has great 
significance not only to the FDA, but to the Nation as a whole.
    FDA laboratories and facilities are now scattered among 50 
buildings at 20 locations in the Washington, D.C., metropolitan 
area. Many of these facilities are old, poorly maintained, and 
do not meet accepted standards for laboratory research. These 
antiquated facilities and fragmentation of agency programs have 
proven burdensome in many ways. The cost of leasing space for 
FDA and the difficulty in managing programs that are so widely 
scattered in the Washington area is a tremendous burden for the 
FDA. The FDA cannot do its job if it does not have the tools it 
needs to accomplish its mission. The committee believes that 
providing the FDA with consolidated, modern, state-of-the-art 
facilities will enable the FDA to do its job faster and more 
efficiently, benefiting the taxpayer and the consumer.

Information system

    The committee is concerned by reports that it frequently 
receives from applicants for the approval of new products of 
the difficulties they encounter in determining the status of 
the agency's review of the application. In turn, FDA employees 
often complain that time which could be spent reviewing 
applications is taken up instead in responding to frequent 
calls from applicants with questions about the status of their 
applications. The committee is also concerned about frequent 
reports it receives from applicants of the FDA asking again for 
data or information that it has already received, but 
apparently has misplaced.
    To end this frustration and unproductive use of time, the 
legislation requires the Secretary to establish and maintain an 
information system to track the status and progress of 
applications or submissions for FDA approval or clearance of 
products subject to its regulation and requires that the system 
permit access by the applicant. Applicants will know the status 
of their applications and will be able to see where hurdles 
have been cleared or problems have arisen. The committee 
intends the product approval system to be collaborative. By 
opening up communications between the applicant and the agency, 
the need for formal letters will be reduced, the time and 
effort involved in review will be reduced, and the entire 
process will be expedited.

Policy statements

    In the past decade, the FDA has relied less on developing 
its policies and procedures through promulgating substantive 
regulations and more on the use of informal policy statements, 
including guidelines, points to consider, and memoranda. This 
has the advantage of consuming fewer agency resources than the 
cumbersome process of promulgating substantive regulations and 
permits the agency to respond more quickly and efficiently to 
requests for policy guidance.
    However, the FDA's increasing reliance on policy statements 
has also produced several problems. First, the FDA maintains no 
compilation of these documents. The regulated industries and 
the public may not be aware that they exist or where they can 
be found. Second, there is no systematic process for their 
adoption or amendment. There may or may not be an opportunity 
for interested outside individuals and organizations to have 
any input into their formulation or amendment. Third, there is 
inconsistency among FDA personnel in the use of these 
documents. Some FDA employees insist upon industry strictly 
following them, and others do not.
    This legislation is intended to ensure the uniform agency 
use of policy statements. The legislation requires the FDA to 
establish a clear procedure governing the development and use 
of informal policy statements that relate to the premarket 
approval process, requires that affected individuals be given 
the opportunity to participate in their development or 
amendment, and requires that the FDA periodically compile and 
publish all statements of general applicability. The committee 
wishes to emphasize that it is not the intent of these 
provisions to make informal policy statements into substantive 
rules subject to the notice and comment requirements of the 
Administrative Procedures Act.

Scientific review groups

    Scientific review groups have appropriately become an 
integral element in the FDA product premarket approval process. 
The FDA often relies on them heavily for expertise and 
judgment. Although they do not make final decisions, their 
conclusions and recommendations are followed more than 90 
percent of the time.
    The current provisions of the Federal Food, Drug, and 
Cosmetic Act require the use of scientific review groups in 
implementing the Radiation Control for Health and Safety Act of 
1968 and the Medical Device Amendments of 1976, but not in 
implementing other provisions of the act. This legislation 
expands the use of advisory committees and establishes 
requirements for their appointment and use.
    The committee agrees that scientific review groups are an 
important part of the product premarket approval process but 
has heard some serious concerns about the way they are 
appointed and used. First, it has been contended that 
scientific review groups have been too close to the FDA 
personnel that they advise and therefore have not provided 
sufficiently independent advice. Second, there has been concern 
that scientific review groups do not meet sufficiently often to 
provide timely advice on important matters. Third, many 
scientific review group members are not experienced with FDA 
issues and are not given adequate training for their 
responsibilities. Fourth, members of the public, including the 
regulated industries, often are not provided with an adequate 
opportunity for participation in scientific review group 
meetings. Finally, FDA action following scientific review group 
recommendations is often delayed substantially.
    This legislation builds on the authority provided to the 
Secretary under section 904 of the Federal Food, Drug, and 
Cosmetic Act to establish such technical and scientific review 
groups as are needed to carry out FDA functions. To enhance the 
independence of the scientific review groups, the legislation 
provides that the FDA Commissioner may not delegate the 
appointment and oversight authority relating to scientific 
review groups and that the FDA will consult with the groups in 
setting their agendas. The legislation requires that, to the 
extent feasible, meeting agendas must be publicly announced and 
published in the Federal Register at least 30 days in advance 
of meetings. The legislation requires that meetings be held 
regularly in order to assure that issues ready to come before a 
scientific review group are handled promptly. Groups are 
required to meet at least 3 times a year unless there are 
reasons to meet less frequently.
    To assure continuity, the legislation sets a term of 3 
years, which may be renewed, for scientific review group 
members and provides that the chairperson shall have served at 
least 3 years before assuming that position and therefore may 
serve a third term. The legislation also requires the FDA to 
provide adequate training to scientific review group members.
    To better ensure the independence of scientific review 
group conclusions and recommendations, the legislation requires 
the FDA to provide product sponsors with copies of all 
documents provided to scientific review groups in preparation 
for a meeting and to provide product sponsors the opportunity 
to submit documents to the members in response to the FDA's 
documents. Product sponsors are permitted to submit such 
documents to the FDA, which is required to provide them to the 
members immediately.
    To better ensure opportunities for public participation at 
meetings of scientific review groups, the legislation requires 
that meetings provide adequate time for initial presentations 
and for response to differing views and requires the 
encouragement of free and open participation by all interested 
parties.
    To address the concern about lengthy delays between the 
time that scientific review groups offer conclusions and 
recommendations and FDA action, the legislation requires the 
FDA to make a final determination within 60 days of receiving a 
scientific review group's conclusions or recommendations on a 
specific issue under review by the group.

Appeals within the FDA

    The legislation requires FDA to set forth three types of 
administrative appeals within the agency and to ensure that 
individuals are made aware of these appeal mechanisms.
    First, the FDA must establish an internal system for 
administrative appeals of any decision by an FDA employee, 
except for formal administrative or judicial proceedings. For a 
significant scientific issue, the final step will involve the 
right to request evaluation by an appropriate scientific review 
group.
    Second, sponsors of clinical investigations or applications 
for premarket product approvals are provided the right to 
request evaluation by a scientific review group of any 
significant scientific issue or decision relating to the 
research, development, investigation, or review of the product 
involved. The FDA is required to refer the request to the 
appropriate scientific review group to review the request and 
determine whether or not the scientific review group should 
conduct an evaluation. Any such scientific review group review 
must be conducted expeditiously, at the next meeting of the 
committee.
    The committee recognizes that providing the sponsors of new 
products the opportunity to request scientific review group 
review of significant scientific issues in dispute with the 
agency or decisions made by the agency significantly expands 
the responsibilities of the scientific review groups. The 
committee is sensitive to the concern that expanding the 
responsibilities of scientific review groups may make it more 
difficult to recruit individuals to serve on them. That is why 
the committee has included provisions giving the scientific 
review group the discretion to determine which issues or 
decisions the group will review. The committee believes that 
most issues can and should be pursued through the agency's 
internal appeals process and intends that the option of 
appealing directly to scientific review groups be used only for 
very serious scientific disagreements between the sponsors of 
new products and the agency.
    Third, for any scientific dispute, the FDA is authorized to 
use such additional procedures as may be considered useful. The 
legislation authorizes but does not require the use of panels 
of FDA officials or government employees who are not FDA 
employees and outside mediators and arbitrators. The committee 
believes that these approaches may also be useful for 
nonscientific issues that may arise during the regulatory 
process. The provisions of the Federal Advisory Committee Act, 
which require a Federal charter and public meetings, do not 
apply under these circumstances.
    For the same reasons that prompt decisions are required 
after scientific review group meetings, a decision must also be 
made within 60 days after any matter that is presented for 
resolution as part of the internal appeal system has been the 
subject of conclusions and recommendations.

Appointment and term of the commissioner of food and drugs

    At present, the commissioner of Food and Drugs is appointed 
by the President, with the advice and consent of the Senate, to 
serve an unlimited term and serves at the pleasure of the 
President. As part of the provisions to achieve greater FDA 
accountability to the American public and to congress, the 
legislation imposes a limit of 1 term, for 5 years, on future 
commissioners. The President could elect to reappoint a 
commissioner to another term, but the appointment would be 
subject to Senate reconfirmation. To insulate the position of 
the commissioner from political considerations, the legislation 
provides that the President may remove a Commissioner only on a 
finding of neglect of duty or malfeasance. These provisions do 
not apply to the individual serving as commissioner when this 
legislation is enacted.

   TITLE II--EXPEDITED ACCESS TO PRODUCTS FOR SERIOUSLY ILL PATIENTS

Access to unapproved therapies

    For many years, the rights of patients who need access to 
unapproved therapies went unrecognized under the Federal Food, 
Drug and Cosmetic Act. The FDA established informal policies 
relating to compassionate use of investigational products 
shortly after enactment of the 1938 act, but these policies 
remained informal and outside FDA regulations until recently.
    The committee commends the FDA for the programs it has put 
in place to ensure that individuals with AIDS have access to 
promising new investigational therapies and for its recently 
announced initiative to expand access to experimental therapies 
for cancer patients.
    The committee wishes to extend opportunities of this nature 
to every individual with a life-threatening or seriously 
debilitating illness for which there is not an effective, 
approved therapy. The legislation establishes in statute, the 
right of any person, through a licensed health care 
practitioner or licensed health care professional, to request 
access to an unapproved therapy, and the right of any 
manufacturer or distributor to provide that unapproved therapy, 
if it is for the diagnosis, monitoring, or treatment of a 
serious disease or condition, an immediately life-threatening 
or seriously debilitating disease or condition, or any other 
disease or condition designated by the FDA as appropriate for 
expanded access.
    The person requesting the unapproved therapy must show that 
there is no comparable or satisfactory alternative, the risk 
from the investigational product is not greater than the risk 
from the disease, there is an investigational protocol in 
effect under the Federal Food, Drug, and Cosmetic Act, and an 
expanded access protocol has been approved by the FDA. A 
manufacturer or distributor may decline to make an 
investigational product available under such a program.
    To induce manufacturers and distributors to make 
investigational therapies available for patients who need them 
under these circumstances, the legislation provides that they 
may charge for up to the amount necessary to recover the costs 
of manufacture and handling of the unapproved drug or device, 
provided the Secretary is notified in advance of assessing such 
charges.
    Consistent with the desire of the committee to help ensure 
that patients with serious conditions and no realistic 
alternative treatments have available to them investigational 
products that may offer some promise of help, the legislation 
requires the Commissioner to inform the medical profession and 
such groups as voluntary health associations about the 
availability of investigational products for expanded access 
use. Too often, patients and their physicians are unaware that 
new therapies are under investigation and are available for 
expanded use pending review by the FDA. This provision will 
help to ensure that all patients will have equal knowledge of 
and access to investigational products.
    The committee emphasizes that it has purposely used broad 
language in this section relating to ``serious'' conditions, 
without attempting to define them, in order to permit wide 
flexibility in implementation. Illnesses that do not cause 
death can nonetheless destroy the lives of both patients and 
their families. The committee therefore intends that the 
seriousness of an illness be given broad consideration, to take 
into account all of the circumstances involved.

Expanding humanitarian use of devices

    The Safe Medical Devices Act of 1990 included a new 
provision authorizing the use of devices for humanitarian 
purposes for small populations of targeted patients for whom 
products are not generally available to treat or cure a 
condition or disease. This provision permits device approval 
based on specified safety criteria and exempts effectiveness 
showings from approval requirements. The provision requires the 
Secretary to issue implementing regulations within 1 year. The 
Secretary proposed regulations in December 1992 but has not 
promulgated final regulations in the intervening 3\1/2\ years, 
despite repeated assurances that the regulations would be 
forthcoming. The legislation therefore terminates the 
requirement for final regulations and provides that the 
Secretary must approve or deny an application for a 
humanitarian device within 30 days--the same time period 
required for a response to an investigational device exemption 
application, which similarly requires a finding of safety by 
the agency.
    The legislation also eliminates current-law provisions that 
provide for an 18-month limit on the period that a humanitarian 
device exemption may be in effect and the current-law 
limitation of 5 years on the authority of the Secretary to 
provide humanitarian device exemptions.

Expediting approval of new drugs, biological products, and medical 
        devices for serious illnesses

    The legislation provides that, for a new drug, biological 
product, or device that is intended for use for a life-
threatening or serious disease or condition and that provides 
therapy or diagnosis not available from another approved 
product or offers significant improvement over another approved 
product, the Secretary must approve or deny the application 
within 180 days after receipt. It is the committee's intention 
that applications for the approval of breakthrough products be 
given priority within the agency.

       Title III--Revitalizing the Investigation of New Products

Timely review and reasonable data requirements for clinical research on 
        drugs and biological products

    The scientific process of discovery, research, development, 
investigation, and ultimate approval, is lengthy and costly for 
any new product subject to FDA premarket approval. It is 
essential to keep the discovery and investigational pipeline 
full of new products, because for every 5,000 drugs that enter 
the process, only one emerges as an approved new product. It is 
thus critical to facilitate and encourage the investigation of 
as many new products as possible, in order to enhance the 
likelihood of ultimate success. The public health is greatly 
benefitted by a vital and robust drug development and 
investigation system.
    The law governing the investigation of new drugs (which has 
always been applied to investigational biological products as 
well) has not been changed significantly since it was enacted 
in 1938. The FDA has imposed numerous administrative changes by 
regulation in the intervening years. This legislation codifies 
the FDA approach into the Federal Food, Drug, and Cosmetic Act 
and sets reasonable requirements to make the process work 
efficiently and expeditiously.
    As is true under current FDA regulations, under this 
legislation a clinical investigation of a new drug may begin 30 
days after the date the FDA receives an investigational new 
drug notification unless the Secretary informs the sponsor in 
writing that the investigation may not begin and specifies the 
basis for the decision and the information needed in order for 
the clinical investigation to begin. Over the years, the FDA 
has at times issued clinical holds by telephone or by informal 
correspondence rather than by a formal determination meeting 
the requirements of this provision, leaving the sponsor 
uncertain about what is required for the removal of the hold 
and when and if the FDA will allow the investigation to 
proceed. The legislation will end these informal practices and 
require strict adherence to the procedure specified to ensure 
full and open communication.
    Within 1 year after the date of enactment, the legislation 
requires the Secretary to consult with outside individuals and 
organizations and, based upon that collaborative process, 
publish in the Federal Register criteria for the type and 
amount of information relating to the safety of an 
investigational drug to be included in an investigational new 
drug notification under the legislation. These criteria must be 
periodically reviewed and may be revised to reflect the most 
recent agency experience.
    This provision has been adopted by the committee because of 
concern that excessive agency demands for information in an 
investigational new drug notification are discouraging sponsors 
from conducting research in the United States and making it 
more difficult for smaller, innovative sponsors to begin 
investigations. The committee commends the FDA for its recent 
publication of guidance on the requirements for initiating 
clinical investigations that substantially reduced the burden 
on investigators. However, the committee remains concerned that 
this burden could again increase and also believes that the 
collaborative process for reviewing and, the committee hopes, 
coming to consensus on reasonable data requirements could 
result in further reductions in requirements.
    The legislation permits the Secretary to place a clinical 
hold on any ongoing clinical investigation if the Secretary 
determines that such action is necessary for the protection of 
human subjects. The committee recognizes that the Secretary may 
well have concerns about the design of research protocols or 
other aspects of the investigation which do not put human 
subjects at risk. This legislation does not prevent the 
Secretary from communicating these concerns to investigators 
and sponsors and working collaboratively with investigators and 
sponsors on changes to address such concerns.
    The legislation establishes a specific procedure for the 
FDA to impose a clinical hold on a drug investigation. There 
must be an opportunity for a meeting within 10 days, and a 
written list of conditions for the withdrawal of the clinical 
hold within 10 days after that. Within 20 days after the FDA 
receives a written request from the sponsor requesting that the 
clinical hold be removed, the FDA must reply. These provisions 
are designed to ensure that the FDA promptly conveys the 
concerns that prompted it to place a hold on a drug 
investigation, that the investigators are informed of the steps 
necessary to resume investigations, and that the FDA responds 
promptly to requests to resume investigations.

Timely review and reasonable data requirements for clinical research on 
        devices

    The legislation adopts an approach for the investigation of 
medical devices that is consistent with that for drugs. The 
Secretary is required to amend current regulations, within 120 
days of the date of enactment, to incorporate the new 
provisions.
    It is rare that a new chemical entity would be changed in 
the course of an investigation, but medical devices are 
constantly modified throughout their investigation as part of 
the developmental process. To reflect this fundamental 
difference between drugs and devices, the legislation provides 
that the investigational device regulations permit 
insignificant developmental changes in devices, including 
manufacturing changes, during an investigation without 
requiring a supplement to or an additional approval of an 
investigational device notification. The legislation provides 
that the regulations also permit changes or modifications to 
clinical protocols for an investigational device that do not 
affect the validity of data or patient protection.
    Current law establishes two types of investigations for 
medical devices: those that may be conducted on the basis of 
institutional review board approval and those for which a 
notification of an investigational device exemption must be 
submitted to the FDA. This legislation does not change this 
basic approach.

Collaborative research design

    The committee strongly believes that the time it takes for 
the development and testing and for the FDA's review of 
applications for the premarket approval of new drugs and 
devices can be substantially reduced and the development, 
testing, and review processes made far more efficient if there 
is greater collaboration between the FDA and new product 
sponsors early in the investigational phase for drugs and 
devices to mutually determine the protocols for clinical 
testing. Such collaboration will provide new drug and device 
sponsors with a clearer understanding early in the process of 
what the FDA believes will be necessary to demonstrate safety 
and effectiveness and will familiarize FDA personnel with the 
new product and with the types of clinical investigations that 
are being undertaken and the results being obtained in the 
course of those investigations.
    Accordingly, the legislation permits a sponsor to request a 
meeting with the FDA to review one or more protocols. The 
request must be in writing and include the proposed protocol. 
The FDA must then meet with the sponsor within 30 days and 
provide a written review, including any deficiencies in the 
protocol. The FDA is required to provide a written summary of 
the meeting, including a written review of the protocol, which, 
upon the mutual agreement of the agency and the sponsor, then 
becomes a part of the FDA product review file.
    As a matter of sound science and patient protection, the 
legislation requires protocols to be designed to limit the 
number of patients and procedures to the number necessary to 
permit a determination of the safety and effectiveness of new 
products. The committee does not intend this requirement to 
conflict with the objective of including diversity within the 
patient population selected for clinical testing. The committee 
is aware of the need to include women, children, the elderly, 
and minorities in clinical testing, in order to provide 
adequate experience with a new drug or device on a wide range 
of patients.
    Sponsors of clinical trials often complain that, after 
receiving approval from one FDA employee for a clinical trial 
protocol and completing a study on that basis, a new or 
different FDA employee will conclude that the protocol is 
nonetheless inadequate or in any event insufficient for product 
approval. To address this problem, the committee has 
incorporated in the legislation a specific prohibition against 
any FDA modification of an agreement reached on a protocol 
between FDA and the sponsor of an investigation except by the 
director of the FDA office responsible for the regulation of 
the drug or device and only for a documented scientific or 
clinical need or patient safety. The committee intends that the 
FDA be held to its word on these matters unless there are sound 
reasons for changing its position. A written scientific 
explanation, setting forth a rationale that was not available 
at the time the original decision was made, or new scientific 
knowledge that has come to light, would ordinarily be required.
    It is essential that agreements of this type be made 
through a formal process, in writing, and become part of the 
established administrative record. Informal agreements that 
cannot be documented will not suffice. Neither the FDA nor 
sponsors of clinical investigations can be held accountable for 
undocumentedrecollections of oral statements months or even 
years after they were made.
    The FDA is required to issue guidelines to implement this 
provision. Repeated failure by a sponsor to follow the 
guidelines may be grounds for an FDA refusal to schedule a 
meeting under this provision.

       title iv--efficient, accountable, and fair product review

Content and review of an application

    The legislation establishes requirements that apply to all 
product premarket approval applications, including those for 
food additives, new drugs, medical devices, biological 
products, new animal drugs, animal feed bearing or containing a 
new animal drug, and color additives. It encompasses all forms 
of product applications, including petitions and notifications. 
The intent of the committee is to establish broad requirements 
for all of these forms of applications.
    Consistency in the FDA's handling of filing requirements 
for applications is extremely important. Differing requirements 
for competing products would undermine the FDA's credibility 
and the integrity of the premarket approval process itself. For 
that reason, the legislation requires the Commissioner within 
60 days of enactment to establish and publish in the Federal 
Register a mechanism to ensure the fair and consistent 
application of filing requirements. The FDA may establish one 
mechanism for all application, or separate mechanisms for 
separate centers within FDA, or even separate mechanisms for 
each type of product application. This is left to the 
discretionary of the agency, as long as applications for 
similar products receive the same consistent handling.
    It is often difficult for an applicant to determine the 
proper classification of a product as a drug, biological 
product, or device. Even where the classification of the 
product is known, the proper organizational center in the FDA 
where the application will be handled can be uncertain. The 
legislation therefore provides that, within 60 days of receipt 
of a written request, the FDA must provide an applicant with a 
written determination regarding the classification of the 
product or the component of FDA within which it will be 
handled, or both. This determination is binding. If the FDA 
fails to meet this requirement, the applicant's designation 
shall be final and binding.
    For the same reason that the legislation requires the FDA 
to establish criteria for the type and amount of information to 
be included in investigational applications, the legislation 
also requires within 1 year after the date of enactment that 
the agency publish criteria for the type and amount of 
information to be included in product approval applications. 
These criteria will be determined after a consultative process 
with individuals and organizations with knowledge, experience, 
and an interest in this matter. Different criteria will 
unquestionably be required for each of the product categories 
involved, to reflect the differences among them. The committee 
intends that the amount of safety and effectiveness data will 
be the minimum necessary to provide and adequate assurance that 
the statutory requirement for safety, and where appropriate 
effectiveness, will be satisfied. In developing these criteria, 
international experience will undoubtedly be relevant. For 
drugs, the FDA is required specifically to consider the 
recommendations of the International Conference on 
Harmonization of Technical Requirement for Registration of 
Pharmaceuticals for Human Use. The FDA participates in the 
international conference and in the development of these 
recommendations.
    For the reasons that have been discussed throughout this 
report, it is important to recognize the impact that the 
ultimate requirements for approval of a new product have upon 
the total research and development process. The approval 
criteria cannot be considered in isolation. Much research and 
development is driven by the final approval requirements. To 
the extent that those criteria and requirements are excessively 
onerous and stringent, the investment required for research and 
development will escalate, the time during which the products 
are unavailable to consumers will lengthen, and the resulting 
cost to the public will increase dramatically.
    On the other hand, the committee does not intend to reduce 
the safety or effectiveness of products subject to FDA 
regulation. It is important that there we be adequate assurance 
that new products are safe and work as intended, but not that 
there be overwhelming or excessive assurance. No amount of 
testing can provide complete assurance of either safety or 
effectiveness, because this ultimately can only be determined 
through widespread use after marketing begins.

Contracts for expert review

    For many years, the FDA has contracted with outside 
individuals and organizations to review part or all of product 
applications or agency decisions respecting the safety and 
effectiveness of marketed products. The FDA contracted with the 
National Academy of Sciences (NAS) to review the effectiveness 
of all new drugs for which new drug applications were made 
effective during 1938-1962 and with the Federation of American 
Societies for Experimental Biology (FASEB) to review the safety 
of all food substances that the agency had earlier determined 
to be generally recognized as safe for their intended use in 
food. the FDA has contracted with individual experts to review 
aspects of new drug applications and recently contracted with 
the Mitre Corporation (now incorporated as Mitretek 
Corporation) to review supplements to new drug applications. 
Finally, the FDA has developed a pilot program for third-party 
review of class I and class II medical device submissions a 
step beyond traditional agency contracting out activities.
    There are sound reasons for using outside individuals and 
organizations to review, evaluate, and make conclusions and 
recommendations to the FDA with respect to applications 
submitted to the FDA. In some instances, individuals outside 
the FDA have unique expertise not available to the agency. In 
other instances, the FDA's internal resources are inadequate to 
handle surges in the workload. In still other instances, 
internal FDA resources must be focused on priority matters and 
cannot be diverted to more routine matters that become 
backlogged. The FDA has in the past used outside individuals 
and organizations for these reasons.
    The legislation explicitly authorizes the FDA to contract 
with outside individuals and organizations with expertise in 
relevant disciplines to review, evaluate, and make conclusions 
and recommendations to the FDA on any form of submission made 
to the agency. Under this legislation, the FDA retains full 
authority to make any determinations with respect to the 
classification, approval, or disapproval of any product. Thus, 
although outside experts will assist and advise the FDA, they 
cannot commit or make any final decision for the agency. Final 
action must be a function solely within the power of the FDA. 
However, the FDA is advised not to arbitrarily or 
systematically disregard the recommendations of the reviewers 
it has accredited and qualified or to redo without cause the 
work completed by such reviewers.
    The legislation requires the FDA to use its authority to 
use outside experts under contract (on a basis other than a 
``pilot'' or ``demonstration'' basis) to ensure the efficiency, 
timeliness, and quality of the review of premarket approval 
applications, to ensure that the agency has the requisite 
scientific and technical expertise with respect to new 
therapies and technologies, and to assist the agency in 
managing its workload in the review of the large numbers of 
indirect food additive petitions and premarket notifications 
for medial devices under section 510(k) of the Federal Food, 
Drug, and Cosmetic Act filed with the agency every year. The 
FDA will determine which types of 510(k) notifications and 
indirect food additive petitions are reviewed by outside 
experts. Even where use of outside experts under contract is 
required, however, the FDA retains full authority to make any 
final decision regarding approval or disapproval. Accordingly, 
the process will be made more efficient and cost-effective 
without in any way undermining the credibility and integrity of 
the final FDA decision or public health and safety.
    The legislation requires the FDA to establish eligibility 
requirements through the promulgation of a regulation before 
any individual or organization can be included for 
consideration for a contract under this provision. The 
regulation must provide for the protection of confidential or 
proprietary information and prevent conflicts of interest. Any 
outside contracts of this nature would also be subject to the 
requirements of section 708 of the Federal Food, Drug, and 
Cosmetic Act, which similarly protects confidential information 
from disclosure by a person under contract with the agency.
    The committee expects the agency to quickly accredit and 
use expert outside individuals and organizations to improve the 
quality, timeliness, and efficiency of the review process. The 
committee recognizes, however, that in certain limited 
instances eligible contractors may not be immediately 
available.
    A continuing problem at the FDA has been its failure to 
respond in a timely manner to the recommendations of an outside 
evaluation. Some NAS and FASEB reports still remain 
unimplemented. Accordingly, the legislation requires that, upon 
receipt of any such evaluation, the responsible FDA official 
must personally review the matter and make a final decision 
within 60 days or such shorter period prescribed by the Federal 
Food, Drug, and Cosmetic Act for review of a submission. This 
will assure that expert conclusions and recommendations do not 
languish for months or years without an FDA decision.
    Within 2 years of the date of enactment, the FDA is 
required to provide Congress with a report on the use of this 
new authority. The report must evaluate the extent to which use 
of contracts with outside experts improves the efficiency of 
review and the expertise available to the FDA. The committee 
strongly recommends that this evaluation and report be 
conducted and prepared by an independent research organization. 
It is important that this new authority be approached openly 
and fairly by the FDA, that successes and failures be 
identified, that means of improving the approach be sought, and 
that the entire process be refined and improved in order better 
to serve the American public.

Prompt and efficient review

    Perhaps no other issue has generated as much consternation 
on the part of the public and the regulated industries as the 
long delays and uncertainties in the FDA's review of premarket 
notification and approval applications. To address these 
concerns, the legislation includes new procedures and 
requirements designed to assure a more efficient, predictable, 
and timely review without jeopardizing safety or effectiveness. 
These requirements apply to all premarket notification and 
approval submissions for products subject to FDA regulation.
    The legislation requires the FDA to establish procedures 
and policies to facilitate a truly collaborative review process 
that encourages open, informal, and prompt communications to 
resolve questions or problems that may arise during the review 
of a premarket approval submission. After observing the success 
of the collaborative review process the FDA has established for 
new AIDS drugs, the committee strongly believes that a 
collaborative review process will significantly improve the 
efficiency, timeliness, and quality of the review of other 
important new products, as well.
    To foster such collaboration between the FDA and applicants 
in promptly identifying and resolving potential problems or 
questions about an application for the premarket approval of a 
new product, the legislation requires periodic meetings 
throughout the FDA review process. Meetings must be held before 
the expiration of half the statutory time period for review and 
before three-quarters of such period, or within 15 days after 
an advisory committee has reviewed the application, unless both 
parties agree that such a meeting is unnecessary. By mutual 
consent, the two parties may establish a different schedule 
that might make better use of their time. Prior to the required 
meetings, the FDA must present to the applicant in writing a 
description of any deficiencies and the information necessary 
to make the application approvable. This provision is intended 
to encourage the FDA to focus on the real substantive issues 
involved and to require the applicant to respond with 
appropriate information.
    As discussed previously in this report, the committee 
understands the frustration and desperation of individuals who 
are seriously ill who must either do without promising new 
therapies or go abroad where such therapies have been approved 
in other countries, because the therapies are still under 
review by the FDA. The legislation provides that, beginning 
July 1, 1998, if the FDA fails to meet a statutory deadline for 
action on a premarket approval application for a product that 
offers a significant improvement over existing approved 
products or has the potential to make foods more wholesome and 
contribute to a healthier diet, and the product has already 
been approved for marketing in the European Union or the United 
Kingdom, then, at the request of the applicant, the FDA must 
within 30 days either approve or disapprove the application. 
Thus, this provision is only triggered by the failure of the 
agency to meet its statutory review obligations. Further, 
although the approval of certain products in England or Europe 
can trigger the requirement for a prompt FDA decision once the 
agency fails to meet a statutory deadline, the ultimate 
decision on approval or disapproval remains with FDA itself. 
Under the legislation, a foreign approval does not create a 
presumption of approvability. There is no provision for 
``deemed approval'' if the agency fails to act in a timely 
manner either to disapprove or approve a product. No product 
subject to premarket approval or clearance can reach the market 
without an affirmative FDA decision.
    If the FDA disapproves an application, the agency must 
notify the applicant of the reasons for the disapproval. The 
applicant may then appeal the disapproval as any other 
disapproval decision may be appealed under current law.
    The European Union has recently established a European 
Medicines Evaluation Agency (EMEA) and has adopted directives 
for determining the regulatory requirements for marketing other 
products subject to FDA jurisdiction. Although these regulatory 
systems are new, they build on long-standing, sophisticated 
systems and are responsible for regulating the safety and 
effectiveness of products for use by a larger population than 
in the United States. Accordingly, the committee recognizes 
that a European Union approval is also an appropriate trigger 
for requiring prompt FDA decision on an application once the 
agency has been unable to meet a statutory deadline.
    The FDA has itself recognized the validity of relying on 
foreign approval of important new drugs. As part of the FDA 
policies for implementing a Reinventing Government initiative 
to assist cancer patients, the FDA will encourage the 
manufacturers of cancer drugs which have been approved abroad 
and are under study in the United States to apply for expanded 
access protocols to make these drugs available to all 
appropriate American patients. The committee believes that this 
recognition should be expanded to all products that offer a 
significant improvement over a current therapy, whether for 
cancer or for other serious diseases or conditions.
    In addition, this committee gave recognition to the quality 
and sophistication of the European Union's and United Kingdom's 
regulatory systems, as well as those of several other 
countries, in its unanimous support of S. 593, the FDA Export 
Reform and Enhancement Act, which was recently signed into law 
by the President as P.L. 104-134.
    The legislation also requires the FDA, with the consent of 
the applicants, to contract for outside expert review of 
categories of applications when the FDA has in the immediate 
past fiscal year failed to meet the statutory deadline for 
action on at least 95 percent of the applications in a 
particular product category. This provision is intended to 
provide much-needed help to the agency in precisely those areas 
where it most needs resources. There may well be reasons why 
the FDA cannot meet the 95 percent compliance level, such as 
surge in applications in a particular product category or a 
lack of agency expertise in evaluating applications which pose 
new scientific or technical issues. This provision will help 
remedy such situations.
    It is important to note that under this provision, it is 
the FDA that selects and pays the outside reviewer. The 
committee expects that the FDA would select only highly 
qualified reviewers in whom it has full confidence to perform a 
high-quality confidential, thorough, and independent evaluation 
of an application.
    It is also important to note that the FDA ``starts'' the 
review clock itself when it accepts an application for filing. 
It is the committee's understanding that one reason the agency 
fails to meet statutory deadlines for action on applications is 
its acceptance of applications which are not complete or are 
not well-presented. The committee believes that applicants must 
bear the responsibility of submitting the best possible 
applications to the agency and that this provision will also 
serve to improve the applications coming into the agency for 
review.
    Finally, it is important to note that the FDA retains full 
and final authority either to approve or disapprove a product 
under this provision. A recommendation by an outside reviewer 
does not trigger a ``deemed approval.'' The provision requires 
the FDA to review the determination of the outside reviewer 
within 60 days of receiving it and either approve or disapprove 
the application. If the FDA disapproves it, the agency must 
notify the applicant in writing of the basis for disapproval. 
The applicant then has the right to appeal that disapproval as 
any other approval or disapproval decision may be appealed 
under current law.
    The committee emphasizes that it will monitor the 
statistical and regulatory practices that the FDA may use in 
complying with and measuring its compliance with statutory 
deadlines for new product reviews.

Good manufacturing practice inspection

    The Federal Food, Drug, and Cosmetic Act requires the 
manufacturers of drugs and devices to comply with good 
manufacturing practices (GMP), and the FDA has also promulgated 
GMP regulations for the food industry. When companies are under 
court order for failing to comply with GMP, it is routine 
practice for the FDA to suggest that they hire outside 
independent GMP consultants to work with them and to conduct 
inspections in order to bring them into compliance.
    The legislation reflects this background by authorizing the 
FDA to accredit outside organizations to conduct GMP 
inspections under the Federal Food, Drug, and Cosmetic Act. If 
the FDA decides to exercise this authority, the FDA is required 
to establish, by regulation, the requirements that an 
organization must meet to be eligible to be accredited as 
qualified to conduct GMP inspections for FDA. Like 
accreditation for outside expert review, the regulations must 
provide for the protection of confidential or proprietary 
information and protection against conflicts of interest.
    The legislation establishes a procedure for accreditation. 
The FDA must act upon an application for accreditation within 
90 days of receipt. The FDA may also revoke accreditation at 
any time for failure of an organization to comply with the 
applicable requirements.
    An accredited organization that conducts an inspection at 
the request to the FDA is required to apply the same GMP 
principles that the FDA applies. A report of the inspection 
must be provided to the FDA within 30 days, and must be 
provided immediately in the event of any observation that could 
cause or contribute to a significant threat to the public 
health.
    Like outside expert review of applications, GMP inspections 
by accredited organizations are intended to extend the 
resources available to the FDA to enforce the Federal Food, 
Drug, and Cosmetic Act. As with all government agencies, the 
future budget for the FDA remains in doubt. Resources may well 
be curtailed rather than extended. GMP inspections by qualified 
accredited organizations may therefore be a very efficient and 
effective way to assure that the regulated industries meet GMP 
standards even during a time of Federal Government budget 
constraints.
    The committee also directs the FDA to ensure that 
inspections provide maximum protection of public health by 
expanding product-specific training of inspectors and utilizing 
inspectors with product-specific expertise.
    An additional benefit from this approach is that utilizing 
third party inspections provides another step toward shaping a 
regulatory system in the United States that is more familiar to 
other industrialized nations. This, along with the amendment of 
the FDA's medical device GMP regulations to include pre-
production design validation and other quality system concepts 
from the International Standards Organization (ISO) standards, 
will increase the opportunity to obtain mutual recognition of 
inspection authorities and cooperative inspections. To the 
extent that countries rely on each other to inspect facilities, 
and trust the findings of such inspections, significant savings 
will accrue to governments and industry by avoiding duplicative 
foreign and domestic inspections. Although small steps, the 
Untied States' acceptance of inspections by accredited third 
parties and ISO quality system concepts is important in 
advancing the cause of international harmonization of 
regulatory systems.
    The committee encourages the FDA to take steps toward 
establishing global GMP inspection standards in a cooperative 
effort with foreign regulatory bodies.

Environmental impact review

    The National Environmental Policy Act requires that all 
Federal action be subject to environmental consideration. Some 
State laws also require a similar analysis. In only one 
instance, however, has the FDA ever determined that action on a 
new drug application might potentially have a significant 
environmental impact. Even in that instance, the importance of 
the drug involved to human health outweighed the environmental 
impact and the drug was therefore approved. In the meantime, 
new product sponsors are generally required to file 
environmental impact assessments and statements with new 
product approval applications, adding substantially to the cost 
of new product development, adding time to the development and 
approval process, and consuming valuable FDA review resources.
    The legislation ends the automatic requirement for filing 
environmental assessments, environmental impact statements, or 
other environmental considerations. New product sponsors would 
be required to conduct such assessments only if the director of 
the FDA office responsible for reviewing a product 
demonstrates, in writing and specifying the basis therefor, 
that there is a reasonable probability that the environmental 
impact of the action is sufficiently substantial and within the 
factors that the FDA is authorized to consider under the 
Federal Food, Drug, and Cosmetic Act and that consideration of 
that impact will directly affect the decision on the matter. 
This assures that, whenever environmental considerations are in 
fact significant, they will be fully analyzed and taken into 
account and that industry and agency resources will be focused 
on considering issues related to the safety and effectiveness 
of products.

Effectiveness, outcome, and cost-effectiveness standards

    The Federal Food, Drug, and Cosmetic Act requires 
applicants for premarket approval or clearance of a new product 
to submit adequate data and information to demonstrate the 
safety and effectiveness of a new drug, biological product, new 
animal drug, animal feed bearing or containing a new animal 
drug, or medical device. The proof of effectiveness under the 
Federal Food, Drug, and Cosmetic Act is directed to the 
labeling claims for the product. In some instances, however, 
FDA has required applicants to submit proof beyond that 
required to justify the requested labeling.
    First, the FDA has at times been concerned that a drug or 
device could be used for unapproved purposes and has required 
studies to support potential uses not included in the proposed 
product labeling. Second, the FDA has expressed concern about 
the potential cost of a new product, in comparison with 
existing therapy, and has required cost-effectiveness studies. 
Third, for some diagnostic devices, the FDA has required proof 
not only that the product performs as labeled but also that it 
results in a favorable clinical outcome. This legislation makes 
clear that these policies extend beyond the requirements of law 
and cannot be required by FDA employees.
    The FDA has no authority to require the regulated industry 
to investigate unapproved uses or to analyze the cost-
effectiveness of a product, unless explicit claims are made. 
The FDA's authority with respect to diagnostic devices resides 
only in determining whether the device performs as labeled. The 
clinical outcomes resulting from the use of the device properly 
fall within the realm of medical practice.
    The committee's effectiveness definition is not intended to 
diminish the scientific rigor with which the FDA will evaluate 
devices. Instead, it is intended to promote a common 
understanding between the agency and persons who make premarket 
submissions of product claims that require effectiveness 
information. By avoiding the evaluation of unstated clinical 
outcomes, or other claims not included in proposed labeling, 
the committee believes the premarket review process will work 
better by eliminating the guess work now associated with the 
scope of FDA's effectiveness review.

Definition of a day

    Because the legislation is designed to hold the FDA 
accountable for meeting statutory time deadlines for taking 
action on product premarket approval applications, it is 
important to define a ``day'' for purposes of those deadlines. 
The legislation defines the term ``day'' to mean a calendar day 
other than those days during which the applicant is responding 
to written questions from the FDA. Thus, the time between the 
day that the applicant receives a written request for 
information from the FDA, and the day on which the FDA receives 
the written response, is not included within the period 
established for the statutory deadline. Only the time for which 
the FDA is responsible is counted within the statutory period.

Approval of supplemental applications for approved products

    Once the FDA approves a new drug, biological product, or 
medical device for a particular use, the medical profession may 
lawfully prescribe it for other uses as well. Unapproved uses 
of approved new drugs account for perhaps half of the use of 
drugs in this country today. In some specialty areas, such as 
cancer, ``off-label'' uses can be 60 percent or higher.
    In order to place a new use of an approved drug or device 
on the product label, sponsors must file supplemental new drug 
or device applications for FDA review. Studies relating to the 
FDA's process for reviewing these applications have shown that 
it takes as long or longer for the FDA to review supplemental 
applications as the agency takes to review applications for 
initial product approvals. These lengthy review times serve as 
a disincentive to drug and device manufacturers to file 
supplemental applications. Thus, many drug and device labels do 
not reflect up-to-date information on new uses for approved 
products.
    The legislation addresses this problem in several ways. The 
FDA is required to establish performance standards for the 
review of supplemental applications and to issue guidelines 
clarifying the requirements and facilitating the submission of 
data. The guidelines must specify when the submission of a 
compilation of peer-reviewed studies on the new use of an 
approved product (a ``paper'' new drug or device application) 
can be sufficient to demonstrate safety and effectiveness.
    The legislation also requires the FDA to designate an 
individual in each of its centers (with the exception of the 
Center for Food Safety and Applied Nutrition) who is 
responsible for encouraging the prompt review of supplemental 
applications and working directly with the regulated industries 
to facilitate the development and submission of data in support 
of supplemental applications.
    Finally, the legislation requires the Secretary to 
implement programs and policies that will foster collaboration 
between the FDA, the NIH, professional medical and scientific 
societies, and others to identify published and unpublished 
studies that could support a supplemental application, and to 
encourage product sponsors to make application or conduct 
further research in support of an application based in whole or 
in part on such studies.

Pediatric studies for new drug applications

    When it comes to pharmaceuticals, our Nation's children are 
``therapeutic orphans.'' Currently, fewer than 30 percent of 
the prescription medications on the United States market are 
approved for use in the pediatric population and labeled for 
pediatric use. Pediatricians using drugs developed with adults 
in mind but which may also be effective or be the only option 
for treating the same illnesses and diseases in children must 
estimate dosages from dosages found to be safe and effective in 
adults. Such estimates are uncertain because children, and 
particularly those under 2 years of age, often metabolize drugs 
differently than do adults. Further, some drugs have different 
side effects and/or toxicities in children than in adults even 
when appropriate doses are used.
    For these reasons, pediatricians have long had an active 
interest in promoting clinical studies of drugs in pediatric 
populations so that the drugs may be labeled for pediatric use. 
However, there is little incentive for drug sponsors to perform 
studies for medications which they intend to market primarily 
for adults and whose use in children is expected to generate 
little additional revenue. Pediatric studies pose ethical and 
moral issues relating to using new unapproved drugs on young 
patients. Second, there are substantial product liability and 
medical malpractice issues. Third, pediatric patients are more 
difficult to attract into studies. Fourth, for some drugs, 
pediatric use represents more difficult issues of drug 
administration and patient compliance than adult use.
    The FDA has sought to address this problem by using its 
authority to approve labeling based upon the known 
pharmacokinetics of the drug, as opposed to requiring pediatric 
clinical trials for efficacy. The FDA has also issued 
regulations that embody this policy in an attempt to encourage 
pediatric labeling. These are clearly steps in the right 
direction, and the committee commends the FDA's initiatives in 
this area.
    The legislation takes a modest further step toward a better 
resolution of this problem by providing an additional 6 months 
of market exclusivity when a drug manufacturer, at the request 
of the FDA, conducts pediatric studies to support pediatric 
labeling for a drug, either before the new drug approval 
application is submitted or later.

Notifications for device market clearance

    The current language in section 510(k) refers to a 
``report'' to FDA with respect to the marketing of medical 
devices whereas the same submission is described in section 
513(i) as a ``notification.'' To conform these two provisions, 
a technical amendment is made in section 510(k) to replace the 
word ``report'' with the word ``notify.''

Pharmacoeconomic information dissemination

    While the committee did not address the dissemination of 
information by companies about the ``off label'' use of drugs 
and devices in the legislation reported by the committee, the 
committee believes that the FDA should allow companies to 
freely share pharmacoeconomic and comparative information about 
approved ``on label'' uses for products. This information is 
needed by managed care experts and other health care providers 
responsible for evaluating the benefits and costs of competing 
therapies. These health care experts use this information to 
significantly improve the quality of care by developing 
comprehensive protocols that teach physicians the best approach 
to treating a particular disease or condition. Health care 
providers also rely on companies to conduct studies in the 
providers' own populations to help the providers predict the 
specific benefits and costs of FDA-approved products for their 
particular organizations.
    Companies typically have the best and most information 
about the cost, effectiveness, and safety of their products. 
The FDA should not prevent the flow of that information to 
experts who need it. The competitive marketplace and other 
regulatory and legal controls over ``on label'' advertising 
safeguard the integrity of the information communicated in this 
sophisticated segment of the market. Restrictions on the 
ability of companies to make comparative claims on the basis of 
cost, effectiveness, or safety of approved uses of products 
actually encourage the sale and use of inferior products.

The FDA Export Reform and Enhancement Act, P.L. 104-134

    On August 22, 1995, the committee considered and approved 
S. 593, the FDA Export Reform and Enhancement Act, which was 
introduced by Senators Hatch and Gregg. A modified version of 
S. 593 developed by Senators Gregg and Kennedy was then 
included in the amendment in the nature of a substitute to S. 
1477. Subsequent to the committee's consideration and approval 
of the amendment in the nature of a substitute to S. 1477, the 
FDA export reform provisions were included in the conference 
report on H.R. 3019, the Balanced Budget Down Payment Act, II, 
and signed into law by the President on April 26, 1996, as P.L. 
104-134. As a conforming amendment, the FDA export reform 
provisions included in this legislation were eliminated.
    It should be noted, however, that the provisions of section 
801(e)(1) and section 802 of P.L. 104-134 represent separate 
and distinct alternative methods for exporting drugs. 
Pharmaceutical companies may opt to export drugs under section 
801(e)(1) if the drug meets the four criteria under that 
section and has been approved under section 505 for marketing 
in the United States. This is true even if the manufacturer 
adds labeling that complies with the requirements of the 
destination country and that new labeling differs from the FDA-
approved labeling. In that event, under section 801(f) the 
exporter must be sure to include the U.S. labeling and identify 
in the labeling any differences in the approved conditions for 
use. The section 801(f) labeling requirements only apply to 
products exported under section 801(e)(1). Through a drafting 
error, these labeling requirements were inadvertently applied 
to exports of insulin and antibiotics because these products 
fall within section 801(e)(1) as explained elsewhere in this 
report.

        title V--drug and biological products regulatory reform

New drug approval standard

    The drug amendments of 1962 added to the Federal Food, 
Drug, and Cosmetic Act the requirement that the effectiveness 
of a drug be established by ``substantial evidence,'' which is 
defined as adequate and well-controlled investigations, 
including clinical investigations, by qualified experts on the 
basis of which such experts could fairly and responsibly 
conclude that the drug will have the labeled effect.
    The FDA usually interprets the requirement to demonstrate 
substantial evidence of effectiveness to require two adequate 
and well-controlled clinical studies, but has shown flexibility 
and approved some drugs on the basis of one adequate and well-
controlled clinical study. The legislation confirms the current 
FDA interpretation that substantial evidence may, as 
appropriate, consist of data from one adequate and well-
controlled clinical investigation and confirmatory evidence 
(obtained before or after the investigation).

Pilot and small-scale manufacture

    An important part of applications for new drugs and 
biological products consists of the information on chemistry, 
manufacturing, and controls (CMC). During the investigation of 
a new product, only a relatively small amount of the drug is 
needed to support the preclinical and clinical trials. It is 
only after marketing approval is obtained from the FDA that 
large-scale manufacturing is justified.
    For some drugs, where the evidence of effectiveness is 
overwhelming, companies are prepared to scale up to large 
manufacturing facilities even before FDA approval is obtained. 
For small companies with modest capitalization, however, it is 
common practice to wait for FDA approval of the premarket 
approval application before scaling up to larger processes. 
This is particularly characteristic of startup biotechnology 
companies.
    In the past, the FDA has for some drugs required CMC data 
relating to large-scale manufacture before approval will be 
granted. This penalizes small companies and especially the 
biotechnology industry. The legislation therefore requires the 
FDA to review and approve new drugs and biological products on 
the basis of pilot and small-scale manufacturing, and to permit 
the company to scale up to a larger facility after the product 
has been approved. Scaling up can readily be undertaken on the 
basis of process validation, without additional clinical 
trials. Only in the very rare case where full-scale production 
is essential to ensure the validity of the CMC data prior to 
approval is the FDA given the authority to require such 
manufacture as a condition of approval. This is the approach 
that has been announced in the Reinventing Government 
initiative relating to drug and medical device regulations. The 
need for supplemental approval of the manufacturing changes 
needed to scale up to larger facilities is subject to the new 
requirements in section 604 of the legislation.

Manufacturing changes

    The manufacturing processes and facilities used to produce 
a new drug or biological product are under change throughout 
the investigation of the product and after marketing approval 
is obtained from the FDA. Innovations are sought to reduce 
impurities, increase yield, reduce the complexity and time 
required for manufacture, eliminate equipment, automate 
procedures, increase stability, and otherwise to improve the 
drug and reduce its cost. The benefits of these innovations are 
passed on to the consumer in the form of improved products and 
lower prices.
    In the past, the FDA has imposed very stringent limitations 
on the ability of the pharmaceutical industry to adopt new 
manufacturing procedures. For most manufacturing changes, FDA 
approval of a supplemental application is required. For only a 
few has the FDA permitted the change to be made immediately and 
simply reported to the FDA by a simultaneous supplement or in 
the annual report submitted to the FDA for the drug. For 
biological products, FDA has been even more stringent, 
requiring clinical trials to support new manufacturing 
processes in many situations. Supplemental applications for 
manufacturing changes have, moreover, traditionally been given 
a very low priority within the FDA. As a result, it can be 
years before a new manufacturing process can be used, even if 
it results in a substantial improvement in the drug.
    The impact of past FDA policy in this area on the 
pharmaceutical industry has been substantial. First, many 
companies have established manufacturing facilities abroad, 
where they can use a modern process to supply a drug to the 
rest of the world long before they can use the same process to 
supply the United States. Second, some companies have simply 
given up on important drug manufacturing improvements because 
of the cost and lengthy process required for approval. Third, 
drug prices have remained unnecessarily high because of the use 
of older technology and cannot be reduced even after new 
technology is approved because of the artificial regulatory 
cost imposed by the supplemental application process. Both 
technology and the public health and pocketbook have suffered.
    To address these problems, the legislation considered by 
the committee included a new approach to manufacturing changes 
for new drugs (including new animal drugs) and biological 
products. It was the intent of the committee in designing this 
new approach to permit manufacturers to make minor 
manufacturing changes without waiting for agency approval when 
those changes would not adversely affect safety and 
effectiveness. During the committee's consideration of the 
legislation, however, there was concern expressed that the 
approach needed further refinement to better define the types 
of changes that could affect safety and effectiveness and 
ensure that such changes were subject to FDA oversight or 
review and approval. The committee agreed that such refinements 
would be made before the legislation was brought to the Senate 
floor for consideration.

Insulin and antibiotics

    Separate provisions were added to the Food, Drug, and 
Cosmetic Act in 1941 to require the approval and certification 
of batches of insulin and in 1945 to provide for the approval 
and certification of the antibiotic drug, penicillin. 
Thereafter, two additional antibiotic drugs were added to this 
second provision, and in 1961 it was amended to apply to all 
antibiotic drugs. These separate provisions were thought 
appropriate because of the inherent variability of insulin and 
antibiotic products as they were made at that time and because 
it was thought that they could not adequately be characterized 
other than through individual batch certification to assure 
compliance with standards established by the FDA for safety and 
effectiveness.
    Pharmaceutical science has now changed dramatically. Both 
insulin and antibiotics can now be adequately characterized by 
chemical, physical, and biological means. Experience by the 
regulated industry of consistent compliance with insulin and 
antibiotic standards has led the FDA to exempt these categories 
of drugs from the requirement of batch certification. The 
legislation repeals both of these statutory provisions, with 
the result that insulin and antibiotics will in the future be 
subject to regulation as new drugs.
    There is only one exception to the regulation of insulin 
and antibiotics as new drugs. Previously, because they were 
regulated under the adulteration and misbranding provisions of 
the Food, Drug, and Cosmetic Act rather than under the new drug 
provisions, antibiotics and insulin were manufactured in the 
United States and exported for sale to countries throughout the 
world in compliance with section 801(e)(1) of the Federal Food, 
Drug, and Cosmetic Act rather than under section 802, 
whichpermits only limited exports. The legislation preserves that 
distinction. Otherwise, manufacturers of insulin and antibiotic who 
currently have their manufacturing plants in the United States would be 
forced immediately to build plants abroad in order to supply their 
products to other countries.

Modernization of regulation of biological products

    The provisions of section 351 of the Public Health Service 
Act that govern the FDA regulation of biological products were 
initially enacted by Congress in 1902 and were recodified in 
1944. Responsibility for implementing these provisions was 
initially in other parts of the Public Health Service until it 
was transferred to the FDA in 1972. The basic concept of the 
statutory requirements has not been revised in more than 90 
years.
    When FDA assumed responsibility for regulating biological 
products in 1972, it made two important policy decisions. 
First, it retained a separate organizational structure and 
regulatory focus for biological products, rather than combining 
these products with new drugs. Even when the two organizational 
structures were temporarily combined, the separate regulatory 
focus was maintained. Second, because biological products are 
also drugs, more recent regulatory concepts that were applied 
to new drugs, (e.g., compliance with drug GMP regulations) were 
incorporated into the older system for biological products. In 
the past 25 years, the two regulatory systems have become 
similar, although each retains its separate identity.
    The legislation takes this logical progression one step 
further. It substantially revises section 351 of the Public 
Health Service Act to make it much closer to the current 
approach for new drugs. Since 1902, the law has required that 
the applicant for a new biological product ordinarily obtain 
both a product license and an establishment license. In 
contrast, the applicant for approval of a new drug is required 
to submit only a single application, which covers both the 
product and the manufacturing processes in the establishment. 
The legislation adopts the same approach for biological 
products as for new drugs.
    The FDA is required to establish, by regulations, the 
requirements that an applicant must meet in order to obtain 
approval of a biological product license application. The 
biological product must meet the same standards for safety and 
effectiveness as a new drug as well as appropriate GMP 
requirements. Preapproval inspection for compliance with GMP is 
included.
    One of the most important biological products subject to 
FDA regulation is blood and products derived from blood. There 
are two basic categories of these products: (1) blood and blood 
components, and (2) products that are derived from blood and 
blood components. For blood and its components, the FDA has 
established appropriate standards to assure safety, purity, and 
where appropriate, potency. The legislation requires that blood 
and its components meet these standards, but there is no need 
for any additional product-specific license for this category 
of products. Blood and its components must also be obtained, 
held, processed, and utilized in accordance with GMP 
regulations that are specific to this type of product.
    In addition to blood and its components, and ever-
increasing number of products are derived from blood. For these 
biological products, the same requirements apply as for any 
other type of biological product. The safety and effectiveness 
of these products is subject to demonstration by appropriate 
scientific evidence.
    Establishments that collect, process, and use blood and its 
components are uniquely located at the local community level. 
There are more than a thousand of these blood establishments, 
located throughout the country, in contrast with the usual 
situation with other pharmaceutical establishments. This 
legislation intends that regulatory requirements be streamlined 
and made as efficient as possible so that the fewest number of 
license applications will be required to cover all of the 
individual locations under a single management. For example, a 
single application should be sufficient to permit all 
facilities under one management to utilize particular types of 
products or methods of processing, as long as all facilities 
are required to meet applicable requirements and standards for 
each separate facility is wasteful of both industry and 
government resources and achieves no useful public health 
purpose.
    In contrast, it is important that, when a problem is found 
at a particular facility, the FDA has adequate power to revoke 
whatever licenses are applicable with respect to that specific 
location. If ten facilities are under one management and the 
FDA discovers that two fail to meet GMP requirements, or two 
are not properly using products or processes for which all of 
the facilities are licensed, the proper remedy is for FDA to 
revoke the applicable license with respect to those two 
facilities but not to interfere with the activities of the 
other eight.
    The legislative includes specific procedures for the 
approval and revocation of biological product licenses. The FDA 
may at any time propose to revoke and approved license after an 
opportunity for a hearing on the record in accordance with 
section 554 of the Administrative Procedure Act. Before 
initiating such a proceeding, the FDA must review any written 
submission by the licensee responding to a notice of 
inspectional findings if received within 30 days after the 
inspection. If the licensee requests another inspection to 
demonstrate that it has now achieved compliance with applicable 
standards, the FDA must conduct an inspection within 30 days to 
determine the current status of the matter. If compliance is 
still not achieved, however, the licensee cannot again invoke 
this requirement.
    Special provisions are included in the legislation where 
there is not only a lack of compliance with regulatory 
requirements but also a determination that there a danger to 
health. Under those circumstances, the FDA is required to 
immediately suspend the license and then initiate the hearing 
process.
    Even before the FDA was delegated responsibility for the 
regulation of biological products, the FDA regulations 
governing investigational new drugs were used as the applicable 
requirements for the investigation of biological products as 
well. This practice is retained under the legislation. For 
biological products, the investigational drug notification will 
be submitted to the center responsible for regulating biologics 
rather than to the center responsible for drugs within FDA.
    To simplify the statutory language, the legislation 
incorporates a definition of ``biological product'' to 
encompass all of the products that are presently included 
within the Public Health Service Act provisions governing this 
category of products. That defined term is then used throughout 
the new provision as well as in sections of the Food, Drug, 
Cosmetic Act that apply to both new drugs and biological 
products.
    In accordance with customary practice for the past 25 
years, the requirements regarding labeling and advertising for 
drugs are applied to biological products and the provisions 
governing advisory committees are also applied to biological 
product advisory committees.

Regulation of human tissue

    The committee is aware that there is considerable debate 
between the FDA and the biotechnology industry about the 
appropriate level of regulation for an emerging and promising 
new technology, known as tissue engineering. Tissue 
engineering, which uses either a patient's own cells or 
compatible donor cells to repair and reconstruct injured or 
diseased tissue, is already being used to grow replacement skin 
for burn victims and replacement cartilage for injuries that 
result from accidents or athletics.
    The committee considered various options for addressing 
this issue but ultimately determined that it would be 
premature, given the emerging and changing nature of this new 
technology and the unanticipated issues which may arise in the 
future, to put into statute a particular regulatory scheme at 
this time.
    The Commissioner of the FDA has provided this committee 
with some guidance on this issue. Commenting on S. 1477 as 
introduced in testimony before the committee on February 21, 
1996, the Commissioner stated that the bill ``would 
dramatically limit the agency's ability to manage its resources 
efficiently.'' Specifically, the Commissioner stated, the bill 
``forces us to keep biologic product licenses, even when we are 
willing to eliminate them for some types of biologics . . . 
conversely, it eliminates establishment licenses, even for 
products that could be most simply and effectively regulated 
using ELAs [establishment license applications] . . . In 
addition, certain technologies may actually be more flexibly 
regulated by the use of the ELA, for example, cellular and gene 
therapies, and xenotransplantation (tissues and organs 
transplanted from animals to humans). GMP's alone would not be 
adequate to assure that proper controls are maintained to 
prevent the spread of infectious diseases.''
    The reported bill addresses the Commissioner's concerns by 
providing a very flexible approach to biological product 
regulation. Section 606 of the legislation explicitly 
authorizes the Secretary to issue a single license for 
biological products. The license may cover the product, the 
facility in which the product is manufactured, or both the 
product and the facility. This would provide, for example, the 
flexibility to regulate human tissue and similar cellular 
therapies in a manner consistent with the regulation of blood, 
for which regulation focuses on the facility rather than the 
particular product.
    The Committee anticipates that the Commissioner would use 
this flexibility to regulate the facilities in which a product 
is manufactured, as opposed to the product itself, for types of 
tissue that are used to provide structural support and/or 
maintain their original cellular function, particularly when 
the tissue is not transported from a donor but rather is grown 
from the patient's own tissue. The FDA has acknowledged that 
this type of tissue-known as autologous tissue--presents a very 
low level of patient risk and can properly be presumed 
effective to repair, reconstruct, augment, or replace native 
tissue when it has been processed to retain the native 
structure or function.

Effective medication guides

    The committee believes that it is essential that consumers 
receive useful oral and written information about prescription 
medications. Current, voluntary, private-sector initiatives 
between health care professionals (physicians, pharmacists, 
nurses), the pharmaceutical industry, patient drug information 
database companies, and consumer organizations, subject to 
State Board of Pharmacy regulation, are working well to provide 
the majority of consumers with useful oral and written 
information about their prescription medications.
    However, the FDA has issued a medication guide regulation 
that would centralize in the agency control of the distribution 
of written information and mandate rigid standards for the 
content and format of such information. The committee is 
concerned that this proposed regulation would divert attention 
from the real need for effective health professional-patient 
communication by disproportionately focusing on written 
information, by engendering a false impression that the goal of 
ensuring that as many consumers as possible receive 
informationabout their prescription medications has been obtained 
solely by providing written information, and by diverting FDA resources 
from more critical agency activities. Moreover, the FDA's proposed 
Medication Guide requirements fail to recognize the success of the 
private sector in addressing this issue, add liability and costs on 
health care providers and the pharmaceutical industry, and stifle 
innovation in the delivery of written patient information.
    The language adopted by the committee would prohibit the 
Secretary from finalizing this regulation or developing any 
type of standard format in the form of a policy statement or 
guidance document specifying a uniform content for written 
information provided to consumers about their prescription 
medications. Instead, the legislation directs the Secretary, 
within 30 days of enactment, to request a broad-based coalition 
of private-sector organizations to develop an action plan 
consistent with the goals specified in the proposed Medguide 
rule, namely the distribution of patient information to 75 
percent of individuals receiving new prescriptions by the year 
2000 and 95 percent by the year 2006. The committee believes 
the National Council on Patient Information and Education 
(NCPIE) is such an organization. In comments submitted in 
response to the FDS-proposed rule, NCPIE has outlined such a 
private-sector action plan. The American Medical Association is 
also developing such a plan.
    Within 120 days of enactment, if the private-sector action 
plan is not developed and implementation of such a plan 
commenced, the prohibition on the Secretary's authority to take 
further action relative to this issue is lifted.
    This provision should not be construed as prohibiting the 
FDA from using its existing statutory or regulatory authority 
to require as part of the manufacturer's approved product 
labeling the dispensing of written information inserts to 
consumers on a case-by-case basis with select prescription 
drugs to meet certain patient safety requirements.
    This provision should not be construed to prohibit the FDA 
from conducting a voluntary, informational, nonregulatory 
workshop in conjunction with the review of private-sector 
initiatives authorized under this provision.

Requirement of radiopharmaceuticals

    Radiopharmaceutical products are used for both diagnostic 
and therapeutic purposes. It is essential that the individuals 
in the FDA who regulate these products have knowledge and 
expertise in the field of nuclear medicine. It is also 
important that the review of radiopharmaceuticals take into 
account differences between these drugs and nonradioactive 
drugs with respect to their safety profiles, pharmacological 
activity, and clinical uses. The legislation therefore requires 
consolidation of review in a separate office within the Center 
for Drug Evaluation and Research, and the promulgation of 
separate regulations governing the review and approval of all 
radiopharmaceutical products and the development of FDA policy 
relating to these products. In addition, since diagnostic 
radiopharmaceuticals are frequently used to provide images of 
processes in the body that may be caused by a number of 
different disorders, the legislation requires the FDA to permit 
the labeling of radiopharmaceuticals in such cases to provide 
information on this manner of use rather than limiting label 
information to specific underlying disorders.

State and local requirements respecting nonprescription drugs intended 
        for human use

    Under the Federal Food, Drug, and Cosmetic Act and the Fair 
Packaging and Labeling Act (FPLA), Congress has required 
national uniformity with respect to most food labeling 
requirements but not with respect to other aspects of FDA 
regulation, such as its regulation of nonprescription drugs. 
Nonprescription drugs are subject to intense and comprehensive 
regulation by the FDA. Their labeling is controlled either by 
regulations that set forth nonprescription drug monographs or 
by new drug applications. The formulation is also subject to 
the requirements of detailed regulations that establish which 
active ingredients may be used and the permitted dosage. 
Additional warnings, limitations on active ingredients, or 
other regulatory requirements should therefore be imposed on a 
Federal level by FDA, not by individual State and local 
governments throughout the country. The committee voted in 
favor of national uniformity for nonprescription drugs. In 
doing so, the committee recognized that there should be a 
single, nationwide system for regulating the safety and 
labeling of nonprescription drugs and noted a willingness to 
consider other FDA-regulated products, such as foods, cosmetics 
and prescription drugs, that may also lend themselves to such a 
comprehensive system.
    The legislation therefore adopts, as a general rule, the 
requirement of national uniformity in the regulation of 
nonprescirption drugs. No State or local government is 
permitted to impose different requirements, whether by 
labeling, advertising, or any other form of communication.
    On the other hand, the committee recognizes that importance 
of States in regulating the food and drug supply in the United 
States. This legislation specifically provides that national 
uniformity does not affect the traditional authority of the 
States to place a nonprescription drug on prescription. It also 
authorizes States to petition for an exemption from the general 
rule of national uniformity where the State can demonstrate a 
compelling and unique local need that is different from the 
rest of the country. Under these circumstances, the FDA is 
authorized to grant an exemption by regulation, after thorough 
consideration of the matter, if the State can also show that 
the local requirement would not cause any nonprescription drug 
to be in violation of any applicable provision of Federal law 
and would not unduly burden interstate commerce. This assures 
adequatebalance. The primary jurisdiction of the FDA is clearly 
recognized, but the partnership role of the States is also given 
adequate attention. All States may, of course, vigorously enforce 
requirements for nonprescription drugs that are identical to the 
Federal requirements.

Regulation of nonprescription drugs

    The committee notes the importance of nonprescription drugs 
in the Nation's health care system. While consumers spend less 
than 2 cents of their health care dollar on nonprescription 
drugs, such drugs produce substantial savings to the individual 
and the health care system in reductions in physician visits, 
prescription drug costs, insurance costs, lost time from work, 
and travel. The committee notes that products switched from 
prescription to nonprescription status contribute significantly 
to these savings. For example, consumers saved over $1 billion 
in the first 3 years after the FDA switched the skin treatment 
0.5 percent hydrocortisone in 1979. Similarly, consumers save 
up to $750 million a year--and 110,000 doctors visits--from the 
switch of cough-cold medicines from prescription to 
nonprescription status.
    The committee therefore expects that the FDA, as part of 
its mission set forth in section 102 of this legislation of 
``facilitating the rapid and efficient development and 
availability of products subject to its regulation,'' will 
establish appropriate procedures and policies, including 
performance standards, to expedite the review of applications 
to switch prescription drugs to nonprescription status. The 
committee encourages the FDA to give strong consideration to 
establishing a separate office for nonprescription drugs and 
conferring on that office primary review and sign-off authority 
for applications to switch drugs from prescription to 
nonprescription status. At a minimum, the committee recommends 
that an individual or individuals within the Center for Drug 
Evaluation and Research be designated to ensure timely and 
efficient agency review and action on such applications and 
that the agency consider using the explicit authority granted 
to it to contract for outside expert review when such contracts 
would achieve more timely and efficient reviews.

                   Title VI--Device Regulatory Reform

Premarket notification

    Under the medical device provisions of the law that were 
enacted as part of the Medical Device Amendments of 1976 and 
amended under the Safe Medical Devices Act of 1990, 
approximately 97 percent of all devices were cleared for 
marketing through FDA's premarket notification program. When a 
device is found to be substantially equivalent to a legally 
marketed device, it may likewise be marketed after the FDA 
issues an order making that finding.
    After the enactment of the Safe Medical Devices Act of 
1990, severe backlogs of premarket notifications and premarket 
approval applications developed at the FDA. Recognizing that 
part of the problem was the sheer number of notifications the 
agency was receiving for class I or II products that posed very 
little risk, President Clinton announced a Reinventing 
Government initiative to eliminate the notification requirement 
for some devices posing a minimal risk, and the FDA has now 
acted to exempt a substantial number of such devices. By 
eliminating premarket notification reviews for some low-risk 
devices, agency resources could instead be used on more 
critical devices, including those subject to premarket approval 
applications.
    Building on the President's initiative, the legislation 
exempts all class I devices from premarket notification 
requirements, except those identified by the Secretary within 
15 days of the enactment of this legislation as requiring 
premarket notification to protect the public health. In 
addition, the FDA is required to review all class II products 
to determine those that should and should not be exempt from 
the section 510(k) process. The FDA is provided 30 days to 
complete this exemption process. Because the agency on its own 
initiative has already had this matter under review for several 
years, and because the committee put the agency on notice 
through multiple requests over the last several months for a 
list of any class I devices which the agency determines should 
continue to require premarket notification to protect the 
public health and any class II devices that the agency believes 
should be exempt from premarket notification, this is a 
reasonable time within which to complete the job.
    Finally, at any time, an interested person may petition the 
FDA to exempt a type of class II device from the section 510(k) 
process. The FDA is required to respond to any such petition 
within 120 days. By eliminating low-risk devices from the FDA's 
premarket review responsibility, FDA personnel will be better 
able to handle within the statutory deadlines the remaining 
section 510(k) notifications and premarket approval 
applications for devices that may pose a risk to public health 
and safety or provide health benefits to patients.
    It has become FDA practice to decline to take action on a 
section 510(k) notification when the agency has made an 
administrative determination that a company is not in 
compliance with a GMP requirement or other provision of the 
Federal Food, Drug, and Cosmetic Act. There is no statutory 
basis for this practice. If a violation of the Federal Food, 
Drug, and Cosmetic Act occurs that is in fact related to a 
substantial equivalence decision, that clearly provides a 
ground for an adverse FDA action on a section 510(k) 
notification. However, if there is a violation that is not 
related to the substantial equivalence decision, the FDA should 
proceed with the substantial equivalence decision on the merits 
and use its extensive existing remedies to correct the 
violation. The committee has acted to ensure that when a device 
is violative of the Federal Food, Drug, and Cosmetic Act, and 
it is substantially equivalent to a lawful predicate device, 
the agency shall issue a substantial equivalence order and use 
its existing statutory remedies to correct the violation.
    Currently under the Federal Food, Drug, and Cosmetic Act, 
when a new device is found to be not substantially equivalent 
to a legally marketed predicate device, it remains 
automatically classified into class III and requires premarket 
approval before marketing. The premarket approval process is 
the most expensive and resource-intensive device review process 
at the FDA. When devices that could be regulated by lesser 
means than product-by-product premarket approval reviews are 
nonetheless classified into class III because of their 
uniqueness and not their risk, there is substantial harm to the 
public health by needlessly diverting FDA resources into an 
intensive and lengthy premarket approval review.
    The Medical Device Amendments of 1976 included automatic 
classification into class III as an efficient means of 
classifying new devices that were not substantially equivalent 
to a device on the market prior to the 1976 amendments. Pre-
1976 amendment devices were classified by rulemaking after 
expert panel reviews and recommendations. Congress believed 
that such new devices would be reclassified to their 
appropriate level of regulation because manufacturers of such 
devices would have appropriate incentives to pursue a 
reclassification based on the Federal Food, Drug, and Cosmetic 
Act's risk-based classification definitions. However, 
reclassification has proven to be an extremely burdensome 
process for the FDA and an uncertain vehicle to achieve 
appropriate classifications for new, not substantially 
equivalent devices.
    The committee therefore determined that 20 years of device 
classification experience permits a mechanism to ensure that 
all devices are classified and regulated based on the risk-
based classification definitions in the Federal Food, Drug, and 
Cosmetic Act. The legislation permits a premarket notification 
submitter to request an advisory panel review and an initial 
risk-based classification by the FDA within 30 days of 
receiving a not-substantially-equivalent order from the agency. 
Once such a request is made, the device is not deemed to be 
classified until an advisory committee makes its classification 
recommendation to the FDA and the agency issues its order 
classifying the device. Both the advisory committee and the FDA 
will rely on the act's classification definitions to establish 
a classification for a device. The advisory committee will have 
60 days to formulate a recommendation, and the FDA will have 10 
days to act on that recommendation and classify the device.
    This approach will avoid a misallocation of agency 
resources on premarket application reviews and will also help 
facilitate the FDA's premarket notification decision-making 
because a not-substantially-equivalent decision will no longer 
necessarily commit FDA to a premarket approval application 
review. Moreover,this procedure will allow devices to be 
classified by risk without resorting to the costly and uncertain 
reclassification process. The committee expects that this provision 
should permit the FDA to be more efficient in classifying devices, and 
this, in turn, should permit the agency to better handle its large 
premarket device review responsibilities.
    The committee believes that this provision should also help 
address concerns it has received about the appropriate 
classification of in vitro diagnostic tests. In vitro 
diagnostic test systems accomplish their intended use by 
physiochemical action on a specimen outside of the body and are 
not intended for therapeutic purposes. The committee 
understands that in vitro diagnostic tests are distinctly 
different from other medical devices, in that they do not pose 
concerns about safety, they are not life-sustaining or life-
supporting, they do not introduce energy into the patient, and 
they are not injected or implanted in the body. The committee 
urges the FDA to consider these factors when determining the 
appropriate classification for these devices.
    Another concern addressed by this legislation is the 
apparent inconsistency with which the FDA interprets the 
intended use of predicate devices with general labeling. The 
FDA often will not permit a device with a general intended use 
to be used as a predicate for purposes of establishing the 
substantial equivalence of a device for a more specific use 
even when medical literature demonstrates the use of the device 
for specific applications is subsumed within the general use.
    However, at times the FDA will interpret a general 
predicate to include specific uses even when such uses could 
not have been included within the predicate device's 
preamendment uses. For example, the FDA cleared condoms through 
the premarket notification process with labeling including 
reference to AIDS and the HIV virus, even though AIDS and HIV 
were not known prior to the Medical Device Amendments of 1976. 
The FDA reasoned that preamendment condoms were intended for 
the prevention of sexually transmitted diseases and, therefore, 
the device was a suitable predicate for condoms intended for 
use to prevent the transmission of the HIV virus. In short, it 
appears that no standard exists regarding when the FDA should 
permit reliance on a general predicate for a newer device with 
a specific use, and when the agency should refuse to allow such 
reliance.
    Accordingly, the legislation identifies such a standard. 
When the FDA determines that a specific use is ``reasonably 
included within the general use'' of a predicate device, that 
use of the predicate device should be available for a 
substantial-equivalence comparison. Each person relying upon 
this provision must demonstrate the substantial equivalence of 
the newer device and the marketed device.
    The FDA's regulation governing when a change or 
modification in a marketed device requires a new premarket 
notification has provided uncertain guidance to manufacturers 
and has led to much confusion over the years. To respond to 
this continuing uncertainty, the committee has identified the 
two instances in which a new premarket notification will be 
required for a change or modification.
    Specifically, the legislation requires a new premarket 
notification for a marketed device when the person responsible 
for the device has made a major change or modification in the 
device's intended use or a significant change or modification 
in device design that has a significant effect on safety or 
effectiveness. Otherwise, the person responsible for the 
marketed device need not file a new premarket notification if 
that person possesses data or information that shows that the 
change or modification does not adversely affect safety or 
effectiveness.
    The committee considers a significant design change that 
has a significant effect on safety or effectiveness to be a 
change which alters the identity of a marketed device such that 
the modified device utilizes a new operating principle or 
technological characteristic. Design changes related to power 
source or product composition materials and components are only 
considered significant if they result in a new product line or 
a major redesign of a product, or the effect on safety and 
effectiveness cannot be readily demonstrated by bench testing.
    Importantly, the committee requires that data or 
information relied upon not to file a premarket notification 
for a device change or modification must be maintained for the 
expected life of a device or for 2 years, whichever is longer. 
The committee requires that such data will be available to the 
FDA upon request. The committee expects that if the FDA 
disagrees with the conclusion that the data or information 
demonstrates that the change will not adversely affect safety 
or effectiveness, the agency will use its extensive enforcement 
authorities to take appropriate regulatory action.
    Once again, the committee has adopted an approach that will 
assure continued emphasis on the safety and effectiveness of 
medical devices, but that will save FDA resources and focus 
them on the most important device review issues. FDA personnel 
who previously reviewed premarket notifications relating to 
device modifications that do not affect safety or effectiveness 
will now become available to spend their time and effort on 
those devices where questions about safety and effectiveness 
remain uncertain.

Medical device approval standards

    The statutory standard for proof of effectiveness of a 
medical device was purposely chosen in the Medical Device 
Amendments of 1976 to be different from that for new drugs. 
Different language was used for the express purpose of 
emphasizing this difference. As the Cooper Committee emphasized 
in its 1969 report, drugs and devices are different in nature 
and present different issues when considering safety and 
effectiveness. For medical devices, for example, the skill of 
the person using the device is often of paramount importance, 
in contrast with the use of new drugs. Accordingly, the 
committee confirms the legislative intent of the 1976 
amendments that the standard of proof of effectiveness for 
medical devices must be viewed as separate and distinct from 
that for new drugs.
    Indeed, the committee is informed that the amount of 
clinical evidence of safety and effectiveness for a device is 
often much less than that required for a new drug. Devices can 
be extensively evaluated by in vitro testing which can be used 
to assess virtually every aspect of device performance. This 
testing, in conjunction with a well-controlled clinical study, 
has been deemed adequate by the FDA in the past to demonstrate 
a reasonable assurance of effectiveness, and the agency should 
take care to maintain the distinction between the evaluation of 
device and new drug effectiveness. An important distinction 
that the FDA should keep in mind is that the method of control 
in a device study often can be historically based, and double 
blinding in new studies is typically unnecessary for devices.
    Specifically, device investigations often cannot be 
blinded, because the effect of the device is often immediately 
apparent. A ``phantom'' device is not often a realistic 
alternative. Further, requiring the use of a previous 
generation of a device to establish the effectiveness of a 
newer generation of the device raises ethical issues when the 
newer generation of the device may offer a substantial 
improvement in effectiveness or safety. Moreover, if an 
historical control is available, blinding is needlessly costly 
and without obvious benefit.
    The use of retrospective or historical data for purposes of 
a control, as the FDA does now in some cases, but 
inconsistently, is therefore desirable. The legislation 
provides that such historical data shall be adequate for that 
purpose if there are sufficient valid data to constitute a 
control, the effects of the device on the disease are clearly 
defined and well understood, and there is no compelling public 
health reason that would require concurrent controls. 
Additionally, historical data also can be used to demonstrate 
safety and effectiveness under the legislation.

Tracking

    The Safe Medical Devices Act of 1990 added a new provision 
to require device tracking for every device the failure of 
which would be reasonably likely to have serious adverse health 
consequences and which is a permanently implanted device or a 
life-sustaining device that is used outside a device user 
facility, as well as any other device designated by the FDA.
    This statutory mandate has proven to be uncertain with 
regard to which devices require mandatory tracking. The FDA's 
regulation for tracking identifies an illustrative list of 
devices subject to mandatory tracking, suggesting that the list 
is comprehensive, yet not complete.
    To address these problems, the legislation repeals 
mandatory tracking and instead provides the Secretary with the 
discretion to require by regulation the tracking of class II or 
class III devices the failure of which would be life 
threatening or have serious adverse health consequences and 
which are permanently implanted or life-sustaining and used 
outside a device user facility.
    The committee expects that the FDA, prior to promulgating 
such a regulation, will consult with the affected parties as 
part of the determination of the most efficient method for 
tracking.

Postmarket surveillance

    The Safe Medical Devices Act of 1990 also included a 
provision requiring a manufacturer to conduct postmarket 
surveillance for any device first marketed after January 1, 
1991, that is a permanent implant the failure of which may 
cause serious adverse health consequences or death, is intended 
for use in supporting or sustaining human life, or potentially 
presents a serious risk to human health. In addition to this 
mandatory surveillance, FDA was authorized to require 
postmarket surveillance for any device when the agency 
determined that surveillance is necessary to protect the public 
health or to provide safety or effectiveness data. All 
manufacturers subject to mandatory postmarket surveillance were 
required to submit protocols for FDA approval within 30 days of 
first marketing the device. The FDA was required to determine 
the adequacy of the principal investigator and the protocol and 
to approve the protocol after review by an appropriately 
qualified advisory committee.
    In practice, the provision for mandatory surveillance, like 
the one for mandatory tracking, is so broadly worded that it is 
causing a good deal of uncertainty about those devices which 
are subject to this requirement. The committee legislation 
repeals mandatory surveillance and provides the Secretary with 
broad discretion to implement postmarket surveillance 
requirements through regulations. Under current law, required 
surveillance is limited to devices first introduced into 
commerce after January 1, 1991. Under the legislation, subject 
to the Secretary's discretion, any device may be subject to 
surveillance if it is a permanent implant the failure of which 
may cause serious, adverse health consequences or death, or is 
intended for a use in supporting or sustaining life, or 
potentially presents a serious risk to human health or creates 
public health concerns.
    The legislation retains the requirement that, before a 
manufacturer who is required to conduct postmarket surveillance 
implements a surveillance protocol, it must be submitted to the 
FDA, subjected to review by a qualified scientific review 
committee, and approved by the FDA. This will continue to 
assure that any requirement of postmarket surveillance effort 
will be worthwhile.

Device distributor reporting

    Since 1976, and reinforced in 1990, the Federal Food, Drug, 
and Cosmetic Act has required medical device reporting by 
distributors as well as manufacturers. The Safe Medical Devices 
Act of 1990 added this requirement for device user facilities. 
As a result, there has been a substantial increase in reporting 
for medical devices, including much duplication. Further, the 
FDA, after request by the committee, has been unable to confirm 
that it either tracks distributor reports or acts on the basis 
of such reports. To avoid duplication and the costs associated 
with it, the legislation continues to require manufacturers and 
user facilities to report adverse events to the FDA but 
eliminates distributor reporting. Since user facilities and 
manufacturers submit medical device reports to the FDA, there 
is no need for additional reporting by distributors.

Premarket approval

    The committee has been concerned that class III devices 
that require approvals before marketing are not reviewed in a 
timely manner and that the data requirements for such approvals 
are uncertain and often too difficult to satisfy in a 
reasonable timeframe. To respond to this situation, the 
committee has set forth procedures and rules that will result 
in one 180-day review cycle with milestone events to help 
ensure the timely progression of reviews of premarket approval 
applications (PMAs). The committee has also included provisions 
that parallel those in the investigational device exemption 
section of this bill which require the Secretary to consider 
certain data resulting from studies in which immaterial changes 
to devices occurred. The amendments to section 515 of the 
Federal Food, Drug, and Cosmetic Act governing premarket 
approval application reviews are intended to promote prompt and 
efficient FDA consideration of devices, many of which make the 
largest contributions to the public health.
    The committee recognizes that devices are often changed 
during or after investigations based on information learned 
from investigational experience. When such changes occur, the 
committee believes that the data generated in the 
investigation, under certain circumstances, should be relied 
upon by the FDA in evaluating the safety and effectiveness of 
the modified device. Accordingly, the legislation requires the 
Secretary to accept and review such data if the modification of 
the device ``does not constitute a significant change in the 
design or the basic principles of operation of the device that 
would invalidate the data or information [from the 
investigation].'' This provision allows reliance on earlier 
versions of devices when the next generation is not 
significantly different from its predecessor. In this way, 
reviews can be made more efficient by avoiding duplication of 
data that remains applicable to a modified PMA device. 
Consistent with this theme, data and information supporting the 
approval of a device under section 515 will be available for 
use in subsequent PMA reviews, if the data are relevant to the 
design and intended use of the device subject to a pending PMA 
review.
    The committee receives frequent reports that FDA reviewers 
raise major new questions and concerns about a pending PMA late 
in the 180-day statutory review to ``stop the clock.'' 
Significant information requests result from these concerns, 
thus resetting the 180-day clock when a ``major'' amendment is 
submitted.
    The committee believes that a collaborative review process 
would help to address these problems. The legislation creates a 
new, more device-specific collaborative procedure under which 
premarket approval applications are to be reviewed. The 
legislation continues to require that the FDA take action on a 
medical device premarket approval application within 180 days 
of receipt. To facilitate the review by identifying potential 
problems with and questions regarding an application early in 
the review process, the FDA is required to meet with the 
applicant within 90 days of receipt of the application that has 
been filed for review. If the application is not in a form that 
would require approval, the FDA must provide in writing a 
description of the information required to bring the PMA into 
such a form.
    The FDA is then required to submit the application to an 
advisory committee, unless a referral is not needed, within 30 
days of that meeting or at the next scheduled advisory 
committee meeting, whichever is later. Within 15 days after the 
advisory committee meeting, the FDA and the applicant must 
again meet to discuss the status of the application and any 
action needed to bring it into a form that would require 
approval. The applicant may decline any such meeting if it 
concludes that a meeting is unnecessary.
    If no advisory committee review is required, the FDA must 
meet with the applicant, at the discretion of the applicant, 
not later than 135 days after the application is received and 
inform the applicant of whether or not the application is in a 
form that would require approval. If the application is in such 
a form, the FDA must present in writing to the applicant, at or 
before the meeting, a description of all additional information 
necessary for the application's approval. If the application is 
not in a form that would require approval, the FDA is required 
to deny the application, and prior to the meeting present in 
writing to the applicant each basis for denying approval and 
the additional information required to bring the application 
into a form that would require approval.
    Within 180 days of the receipt of an application that has 
been accepted for substantive review, the legislation requires 
the FDA either to approve or deny it. The 180-day period may 
not be enlarged by a PMA amendment.
    To implement these new, collaborative-review procedures, 
the FDA is required to revise its current regulations governing 
premarket approval.
    The committee recognizes that many are concerned that the 
agency will be unable to meet the 180-day statutory review time 
without user fees or another source of significant new 
revenues. However, the committee believes that this concern 
fails to take into account several important factors.
    First, the FDA controls the clock. The FDA determines 
whether or not to accept an application for review, thereby 
starting the clock. If reviewers are raising substantial 
questions and concerns well into the review process, the review 
probably has been wasteful because the application's 
deficiencies should have been identified early in the review 
process, as provided for under this legislation.
    Second, the legislation puts in place a collaborative 
process for designing clinical protocols. It encourages a team 
approach from the planning and initiation of clinical 
investigations through the review of the application. When such 
a process is in place, FDA reviewers should already be 
relatively familiar with the type of data and other information 
to be derived from the clinical investigation of the device 
and/or comfortable with the clinical investigation protocol. 
Hence, when an application comes into the agency, the reviewers 
should be more comfortable with it.
    Third, the legislation simply requires decisiveness. If at 
the end of the 180-day period the FDA is not satisfied that an 
application should be approved, it must deny it. This places 
pressure on the FDA, but also requires PMA applicants to submit 
meritorious, high-quality applications.
    Fourth, the legislation reduces the workload of the FDA's 
Center for Devices and Radiological Health substantially. Most 
class I and many class II devices will be exempt from review. 
The number of new 510(k) notifications and premarket approval 
applications being filed because minor changes have been made 
in an investigational or approved device will be sharply 
reduced. The FDA has the discretion under this legislation to 
determine just how sharply reduced its workload will be. The 
agency will determine, for example, how many class I devices 
should remain subject to premarket notification and how many 
class II devices will be exempted from premarket notification.
    The legislation also contains new provisions relating to 
supplemental applications for PMA devices. Supplemental 
applications that relate to manufacturing changes or product 
changes will not be required when data or information show the 
changes do not adversely affect safety or effectiveness. PMA 
holders must notify the FDA of significant changes and maintain 
data supporting changes in a device master file for the 
expected life of the device or 2 years, whichever is later. For 
the reasons discussed above, this will streamline the product 
premarket approval process and conserve FDA resources while 
continuing to assure the safety and effectiveness of the 
products involved.

Device performance standards

    Since before the enactment of the Medical Device Amendments 
of 1976, voluntary standards-setting organizations in the 
United States and abroad have established performance standards 
for categories and characteristics related to medical device 
products. These organizations include the American National 
Standards Institute (ANSI), the International Standards 
Organization (ISO), and the International Electrotechnical 
Commission (IEC), as well as others. Although standards from 
these organizations are recognized as authoritative, and are 
therefore followed throughout the world, the FDA has failed to 
establish any policy regarding their recognition and use under 
the Federal Food, Drug, and Cosmetic Act in this country. This 
legislation remedies that problem.
    The legislation requires the FDA to recognize appropriate 
medical device performance standards developed by organizations 
such as ANSI, ISO, IEC, and any other standards-setting 
organization certified by the agency. The legislation requires 
the FDA to establish a procedure governing certification of 
such organizations, which shall be based on specified criteria.
    It is important that all medical device performance 
standards recognized by the FDA under this new procedure be 
publicly listed, so that any interested person will know the 
regulatory status of the standard. Accordingly, the legislation 
requires FDA to publish in the Federal Register the name of all 
standards to which recognition has been given. Any standard not 
on the published list would not be accepted as recognized by 
the FDA under this provision.
    Just as the FDA may certify standard-setting organizations, 
it may revoke certification if the organization no longer meets 
certification requirements. In the event that the certification 
of an organization is revoked, the FDA is required to address 
the effect of this revocation on the agency's prior recognition 
of the organization's standards.
    Other provisions in the Federal Food, Drug, and Cosmetic 
Act authorize FDA to promulgate performance standards for 
medical devices using the procedures set forth in the law. This 
legislation does not in any way change the authority of FDA to 
promulgate such standards, which may differ from the standards 
established by certified organizations and recognized under 
this new provision.
    The FDA may not require conformity with any such standard 
as a condition for approving any type of medical device 
application if the applicant demonstrates that the device is 
substantially equivalent to a legally marketed predicate device 
or otherwise provides reasonable assurance of safety and 
effectiveness.
    The FDA may revoke a particular performance standard 
recognized under this legislation upon a determination that it 
is insufficient to provide reasonable assurance of safety and 
effectiveness. Upon revocation, the FDA must notify the 
certified organization and provide the basis for the action.
    The legislation requires that a recognized performance 
standard must include provisions that will provide reasonable 
assurance of the safe and effective performance of the device. 
Where necessary to provide such assurance, the standard must 
include provisions with respect to such elements as 
construction and components and such requirements as testing 
and performance measurement and results. Where appropriate, 
labeling may also be prescribed. These required elements are 
designed to assure that a recognized performance standard will 
provide sound public health protection.

Accredited-party participation

    In recent years, the FDA has consumed substantially more 
time for the review of medical devices. For example, FDA's 
average review time for premarket classifications has increased 
over the last 6 years by well over 200 percent (from 82 days to 
178 days for total review time; from 66 days to 137 days for 
time in the FDA's hands), while the number of applications has 
generally held steady. In addition, premarket approval times 
have increased from 348 to 773 total days (247 to 606 days in 
FDA's hands) on average, while submissions in the same 6-year 
period dropped from 84 to 43 (almost in half). It is important 
to note that by statute, premarket classifications are expected 
within 90 days and premarket approvals must be granted or 
denied within 180 days.
    This delay is in part a consequence of the agency's 
difficulty in maintaining the technological expertise and 
capability necessary to review applications within the 
statutory time frame. Also contributing to this delay is the 
FDA's management of its resources. The FDA has regularly made 
this committee and others aware of its desire to have more 
resources in order to address its inability to review products 
within the statutory time frame. In past years, Congress has 
responded with increasing appropriations. However, as resources 
available to the Federal Government have tightened, Congress 
has been pressed to find alternative sources of revenue.
    As a result, the committee decided to test, through a pilot 
program and a follow-up study, whether supplementing FDA 
resources with fees paid by a product sponsor to FDA-accredited 
reviewers and by supplementing FDA expertise with that of 
private parties would reduce delays in medical device approvals 
and improve the technical sophistication of those reviews. The 
legislation includes a provision under which accredited 
individuals and organizations with relevant expertise will, at 
the option of a product sponsor, be used to provide 
recommendations to the FDA regarding premarket notifications 
and premarket approval applications. The FDA will then review 
those recommendations and make final decision with respect to 
classification or approval or disapproval of the premarket 
approval application.
    This provision is consistent with the approach taken 
throughout this legislation: the FDA retains all of the 
authority it has under current law to make final product review 
decisions. This legislation does not authorize any other person 
or organization outside the agency to make such a final 
decision. Thus, in numerous respects, the provision maintains a 
strong, continued role for the FDA in the device approval 
process. For example, the FDA alone accredits the pool of 
qualified private parties to conduct the reviews and selects 
from that pool two or more accredited parties from whom the 
product sponsor may select. Although a product sponsor has the 
option to select an accredited party, it does so only from a 
list pre-selected and accredited by the FDA, thus limiting if 
not eliminating potential ``forum shopping.'' The FDA also 
establishes rules protecting the confidentiality and the 
proprietary nature of information contained in the review. The 
FDA promulgates the rules to prevent conflict of interest. The 
FDA has authority to ensure compliance by the accrediting party 
and has the ability to withdraw or suspend accreditation of 
parties not in compliance. In short, the FDA will have full 
control over the individuals and organizations eligible for 
selection.
    The FDA's role is not limited to accredited-party 
selection. In addition, the FDA alone will continue to set 
product review standards. Most significantly, the FDA conducts 
both an initial filing review to confirm completeness and basis 
for review and retains authority to make the final decision 
with respect to the classification or approval or disapproval 
of application. The FDA has no less than a total of 30 days (of 
the 90 days allotted under the statute) to review a submission 
under section 510(k) and 75 days (of the 180 days under the 
statute) to review premarket approval applications. Further, 
the FDA is not bound by an accredited party's determination--
there is no presumption given to the accredited party's 
recommendation of approvability or classification of a product.
    The program established under this provision would apply to 
all types of medical devices, including premarket approval 
applications and premarket notifications. The committee intends 
that a rule of reason be applied by the FDA so that the FDA 
does not unnecessarily accredit two or more organizations 
capable of reviewing only one type of product for which one or 
no applications will be filed during the course of the pilot 
program.
    To adequately supplement the resources available to the 
FDA, the product sponsor will directly contract with and pay 
the accredited party at the sponsor's own expense. This 
mechanism is similar to that proposed by the FDA in its own 
pilot project at the Center for Devices and Radiological 
Health.
    The program established under this provision will be 
subject to review within 3 years following the accreditation of 
the first party. A full analysis of the strengths and 
weaknesses of the program will be conducted and provided to 
Congress and the public, enabling Congress to extend or modify 
the program at that time.

                title vii--animal drug regulatory reform

    The committee is very concerned about the serious shortage 
of approved drugs for the treatment of both food-producing and 
companion animals. It is for that reason that the committee 
supported the approval of legislation in the 103rd Congress to 
permit veterinarians to legally prescribe animal and human 
drugs for uses other than their FDA-approved, labeled uses, 
recognizing, however, the need for further legislation to 
address the problems creating the shortage.
    Two of these problems are lengthy delays in the FDA Center 
for Veterinary Medicine's (CVM) review and approval process and 
the daunting cost of bringing a new animal drug to market or 
obtaining approval for additional uses of approved drugs (i.e., 
approval of a drug approved for use in horses to be used in 
dogs). The CVM's own internal study in 1993 found that it was 
taking the agency an average of 58 months to approve a new 
chemical entity for use in animals. Industry research indicates 
that the cost of bringing a new animal drug to market can at 
times approach $200 million. These delays and costs are 
discouraging research on and development of new animal drugs 
and additional uses for approved drugs.
    The committee is heartened by the much-needed recent steps 
the Center for Veterinary Medicine is taking to better ensure 
the timely review and approval of new animal drugs and by the 
commitment the Commissioner of the FDA gave in his February 21 
testimony before this committee to addressing the serious 
problems in the animal drug review process.
    This legislation incorporates a number of statutory and 
regulatory reforms that the committee believes are necessary to 
support the efforts of the Center for Veterinary Medicine and 
the commitment given by the Commissioner.

Evidence of effectiveness

    The committee found that much of the delay in new animal 
drug approvals and the cost of bringing a new animal drug to 
market can be tied to costly, duplicative requirements for 
demonstrating the effectiveness of new animal drugs. The 
Federal Food, Drug, and Cosmetic Act currently requires 
efficacy to be demonstrated through ``adequate and well-
controlled investigations, including field investigation.'' The 
FDA has interpreted this language to routinely require three 
field investigations, each in a different region of the Nation. 
The committee finds that this requirement has led to 
duplicative tests that are expensive and time-consuming for new 
drug sponsors but that often yield information of little 
benefit to the agency, veterinarians, and animal drug sponsors.
    The legislation amends the statutory definition of what 
constitutes evidence of effectiveness to allow the FDA to 
accept one or more scientifically sound studies, including in 
vitro studies, studies in laboratory animals, bioequivalence 
studies, and any other similar studies, that, taken together, 
provide reasonable assurance that the drug will have the 
claimed or intended effect. This is a far more flexible 
definition, permitting the FDA to adapt the types of studies it 
requires to demonstrate the effectiveness of the particular 
characteristics and proposed uses of the new animal drug. The 
legislation removes the statutory requirement for ``field 
investigation'' but provides the authority to the FDA to 
require field investigation when necessary.
    In reviewing the approval procedures for animal drugs used 
in combination with one another, the committee recognizes that 
the FDA needs greater flexibility in its approval requirements. 
Currently, the FDA treats all animal drug combinations as 
never-before-approved products, even when the drugs used in 
combination have each been approved by the FDA. The FDA 
requires that for combinations of approved animal drugs, all 
laboratory and field investigations be conducted again to 
determine the effectiveness of the combination. The FDA also 
requires that, if the combined products make the same claim, 
the combined effect must be greater than the effect of either 
product used alone. Further, the FDA requires that, if the 
combined products treat unique claims, sponsors must show that 
both products remain effective when they are combined. The 
committee finds these requirements to be redundant and 
unnecessarily time-consuming and expensive.
    The legislation reflects the committee's view that the 
primary concern raised by combination drugs is whether they 
will in combination exceed the tolerance levels set for human 
safety. Under the legislation, the FDA is limited in its 
evaluation of a combination drug comprised of two previously 
approved drugs or a drug that bears labeling that recommends 
use with another animal drug to the consideration of whether 
the drugs in combination affect human safety (i.e., whether the 
longest withdrawal time of any of the active ingredients is 
above its safe concentration) or interferes with a method of 
analysis of an ingredient.
    Both the FDA and the regulated industry have long struggled 
with the difficult problems raised by the use of new animal 
drugs in a minor species or for a limited use. The FDA has long 
recognized that some drugs have extraordinarily small markets 
because they are either used in a minor species or otherwise 
have very limited use. The FDA has attempted to encourage the 
development of these drugs by streamlining several of the 
effectiveness requirements for these drugs. For example, when a 
manufacturer seeks approval for a use in a minor species of a 
drug already being used in a major species, the FDA does not 
always require original effectiveness testing for the minor 
species use. It allows the sponsor to extrapolate from tests 
done of the drug in a major species.
    The committee commends the FDA for its efforts to encourage 
the development and availability of drugs for minor species and 
limited uses. The committee believes that the provisions in 
thelegislation are consistent with these efforts. The legislation 
exempts drugs for minor species and limited uses from the usual 
requirements for demonstrating substantial evidence of effectiveness if 
there is a previously approved animal drug application for the drug.
    The legislation requires that, when the FDA issues its 
revised regulations defining the requirement of ``substantial 
evidence'' of effectiveness, it must take into account the need 
to encourage the submission of new animal drug applications for 
three types of products for which there is a strong public 
policy justification: drugs that conserve food resources; drugs 
designed for use by veterinary practitioners in order to 
establish effective doses; and drugs for use in minor species, 
for limited uses, and for permitted unlabeled uses. In addition 
to providing an incentive for these three categories of drugs, 
the FDA is required to take into account a citizen petition 
submitted to the agency in October 1991 requesting the agency 
to adopt flexible labeling for veterinary prescription drugs 
that will recognize a range of safe and effective dosages 
within which veterinarians may use their training and 
experience to prescribe a particular dose for a specific 
animal. The labeling for many human drugs provides a dosage 
range rather than one particular dose and relies on the 
physician to exercise professional judgment in making a 
prescription. Regulation pertaining to animal drugs should 
follow this precedent.
    In addition to the applicable provisions requiring a 
collaborative process for the review of all new premarket 
approval applications contained in title IV of this act, the 
legislation provides specific requirements for applications 
relating to new animal drugs. The FDA is required to provide a 
new animal drug sponsor an opportunity for a conference prior 
to the submission of an application, in order to provide advice 
regarding the requirements that must be satisfied for approval 
of the product. That advice is binding unless FDA subsequently 
determines that a new documented scientific requirement 
essential to determination of the safety or effectiveness of 
the drug has appeared after the meeting. Within 10 days after 
any such meeting, if the FDA requires any type of study other 
than those specified in the new definition of substantial 
evidence of effectiveness, the agency must provide a written 
justification for that requirement, specific to the animal drug 
and its intended uses. This will assure both that the FDA has 
the flexibility to require whatever evidence of safety and 
effectiveness is scientifically justified for a particular drug 
and its intended uses and that the applicant will receive a 
full and detailed scientific justification for any requirement 
for a study other than those specified in the definition of 
substantial evidence, such as a well-controlled field trial.
    Once again, the legislation streamlines the premarket 
approval process and assures that a reasonable amount of 
scientific evidence will be required to establish safety and 
effectiveness, but at the same time provides adequate authority 
for the FDA to require whatever type of evidence is 
scientifically justified to establish that the drug is safe and 
effective for its intended uses. As is true throughout the 
legislation, efficiency is imposed but not at the expense of 
public protection.

Limitation of residues

    Under present law, the FDA may deny approval of a new 
animal drug application if the proposed tolerance limitation 
exceeds what is reasonably required to accomplish the physical 
or other technical effect for which the drug is intended. In 
practice, the FDA has interpreted the law to require that new 
animal drug sponsors identify the ``optimal'' dose for a drug--
the least amount of the drug necessary for the drug to be 
effective. This requirement adds greatly to the time and 
expense of developing and testing new animal drugs.
    The legislation would instead require the FDA to deny 
approval of a new animal drug if any use prescribed, 
recommended, or suggested in the proposed labeling for the drug 
would result in a residue in excess of a tolerance set by the 
FDA to be safe for the drug. It would in effect permit the 
sponsor to identify a dosage range for the drug which would not 
exceed tolerances set by the FDA.

Adulterated drugs

    As amended by the Drug Amendments of 1962, the law 
presently requires all drugs to be manufactured, processed, 
packed, and held in conformity with good manufacturing 
practices (GMP). The FDA has, in turn, promulgated GMP 
regulations for the preparation of all drug products, including 
both human and animal drugs.
    There are, however, differences between human and animal 
drugs that justify separate and distinct GMP regulations for 
these two different categories of products. The legislation 
therefore includes a revision of the drug adulteration 
provisions of the Food, Drug, and Cosmetic Act to require 
separate GMP regulations that are appropriate for animal drugs.

Veterinary feed directives

    Current provisions of the Federal Food, Drug, and Cosmetic 
Act provide for nonprescription animal drugs and prescription 
animal drugs. To date, nearly all drugs used in feed have been 
approved as nonprescription drugs. Requiring prescription 
status for such drugs would impose a significant burden on 
distribution. As a result, the animal feed industry has been 
limited in its ability to incorporate prescription veterinary 
drugs, and the animal husbandry industry has been limited to 
the use of veterinary prescription drugs in inefficient and 
costly ways.
    The legislation includes provisions reflecting an agreement 
reached by the FDA and the regulated industries to create a 
newanimal drug category, ``veterinary feed directive drugs,'' which 
includes all animal drugs intended for use in feed that are limited to 
use under the supervision of a licensed veterinarian. A veterinary feed 
directive drug must be fed to animals only upon a lawful veterinary 
feed directive issued by a licensed veterinarian in the course of the 
veterinarian's professional practice. The drugs, their labeling, and 
the directive under which they are used are all to be regulated by the 
FDA. Records must be kept as specified by the FDA and must be made 
available for FDA inspection. Any distributor on animal feed bearing or 
containing a veterinary feed directive drug must register with the FDA. 
Failure to follow FDA regulatory requirements will result in the same 
penalties as any other violation of the Federal Food, Drug, and 
Cosmetic Act.
    Adequate regulatory controls are therefore imposed to 
assure the safe and effective use of these veterinary 
prescription drugs while creating a more efficient and 
effective distribution system. This approach maintains public 
health protection but incorporates regulatory flexibility to 
accommodate the changing needs of the animal husbandry 
industry.

Timeframes for approval

    Present law requires FDA action on a new animal drug 
application within 180 days. With the substantive and 
procedural changes in the Federal Food, Drug, and Cosmetic Act 
under this legislation, unimportant submissions will no longer 
be required, long and complex applications will be replaced by 
shorter and more focused applications, the requirements for 
approval will be simplified, and thus the reviews by FDA can be 
substantially shortened. Particularly for animal drugs, the 
efficiencies created by this legislation will substantially 
reduce the time and effort needed to review product premarket 
approval applications. The committee concludes that 90 days is 
a reasonable statutory deadline for the future.

                   Title VIII--Food Regulatory Reform

Indirect food additives

    There are two major categories of food additives: direct 
food additives, which are directly incorporated into food and 
are intended to be ingested as part of the food supply; and 
indirect food additives, which are used as processing aids, 
packaging materials, or other food contact uses and are 
intended solely for these functional food contact purposes 
rather than for human ingestion. Residues of indirect food 
additives are in fact found in the food supply, but that is an 
incidental result of their use and not their intended purpose.
    Under the Food Additives Amendment of 1958, both of these 
two quite different categories of food additives are subject to 
the same procedures and requirements. Both require FDA 
premarket review and the publication of a regulation specifying 
the conditions under which they are approved for use.
    These two categories of food additives also result in 
distinctly different impacts on the FDA workload. There is an 
average of only about one new direct food additive approved by 
the FDA every 5 years. In contrast, there are dozens of 
indirect food additives under consideration at any time. The 
current backlog of indirect food additive petitions is 
substantial.
    Because indirect food additives are intended only for food 
contact rather than for any functional use as a component of 
the food supply, the risk that they present to the public 
health and safety is minimal. There is no documented case of 
human harm caused by an indirect food additive. Although public 
protection must continue to be assured, the committee concludes 
that a different procedure should be available for FDA review 
of indirect food additives than is adopted for direct food 
additives in title IV of this legislation.
    The legislation includes a simplified premarket 
notification procedure for indirect food additives in order to 
streamline the process without sacrificing consumer protection 
against unsafe substances in the food supply. Any person may 
submit a premarket notification to the FDA for an indirect food 
additive at least 90 days prior to marketing, with information 
demonstrating that the labeled use of the product is safe. 
Within 90 days, the FDA must either approve or disapprove the 
notification and publish a notice in the Federal Register. If 
the notification is approved, an appropriate food additive 
regulation must be promulgated.
    This simple procedure will allow the FDA to quickly dispose 
of its existing inventory. It retains adequate public 
protection but recognizes that reduced regulatory control is 
appropriate in light of the lower potential for public health 
risk. As is the case throughout this act, the FDA retains the 
authority and responsibility to either approve or disapprove 
indirect food additive petitions under this simplified 
approach.
    The FDA has recently initiated a ``threshold of 
regulation'' process for considering exemptions of indirect 
food additives from the requirement for premarket approval, 
after considering this approach for more than 25 years. Under 
the new FDA procedure, an applicant may submit an application 
for an exemption in lieu of an application for a regulation. 
Both approaches require an application and both approaches 
require an FDA evaluation and response. The savings in FDA time 
and effort cannot be determined at this time. Since the FDA 
has, after years of study, set a specific human exposure level 
that represents no potential safety risk (0.5 ppb in the daily 
diet), the committee encourages the agency to consider 
providing manufacturers with data demonstrating a lower 
exposure an automatic exemption from the need for a regulation 
on the condition that they maintain the documentation to 
support their exemption for as long as the product is marketed 
and make the data available to FDA upon request. It seems to 
the committee that this would be a more effective and efficient 
method of handling this matter. The committee will monitor the 
progress of the new threshold of regulation approach to 
determine whether legislation is needed to streamline it.

Health claims of food products

    Under section 403(r)(3)(a) of the Federal Food, Drug, and 
Cosmetic Act, adopted under the Nutrition Labeling and 
Education Act of 1990 (NLEA), health claims can be made for 
food products only if explicitly approved by the FDA. From the 
beginning, it has been the concern of Congress that health 
claims be authorized when they are supported by sound science 
and are stated in a truthful, nonmisleading manner in the 
context in which they are presented. Such claims can promote 
public health by promptly communicating the health benefits of 
foods as these benefits are discovered. Presenting them at the 
point of purchase through food labeling can dramatically and 
positively affect consumer purchasing decisions.
    Unfortunately, the promised benefits of the original health 
claims provisions of the NLEA have not been fully realized. The 
FDA has established unduly stringent criteria for approving 
health claims for food, resulting in the approval of very few 
health claims available for use in only limited circumstances. 
In addition, as is true with other areas of premarket approval, 
the health claims process has become a regulatory bottleneck, 
preventing useful claims from entering the market without undue 
delay.
    The promised benefits of health claims have also not been 
fully realized because the NLEA failed to give sufficient 
weight to the determinations of authoritative bodies outside 
the FDA concerning the validity of diet/disease relationships. 
There are a number of important federal public health agencies 
that, along with the National Academy of Sciences (NAS), 
regularly make authoritative statements concerning diet and 
disease relationships. The Surgeon General and the NAS have 
published authoritative books and reports on such 
relationships. The National Cancer Institute (NCI) publishes 
pamphlets recommending food choices that can help reduce the 
risk of cancer. The National Heart, Lung, and Blood Institute 
(NHLBI) publishes information on diets that will reduce the 
risk of heart disease. Nonetheless, the diet/disease 
relationships plainly recognized in these materials may not be 
communicated through food labeling unless the FDA first issues 
a rule specifically authorizing claims concerning the 
particular diet/disease relationship.
    The adverse impact this can have on public health came into 
focus when the Centers for Disease Control and prevention 
(CDC), recognizing the benefits of adequate folic acid intake 
among women of childbearing age, issued a recommendation in 
1992 stating:

          All women of childbearing age in the United States 
        who are capable of becoming pregnant should consume 0.4 
        mg of folic acid per day for the purpose of reducing 
        their risk of having a pregnancy affected with spina 
        bifida or other [neural tube defects]. [Centers for 
        Disease Control, 41 Mobidity and Mortality Weekly 
        Report (September 11, 1992).]

The CDC estimated that this recommendation could reduce the 
number of cases of spina bifida and other neural tube defects 
in the United States by 50 percent.
    Despite the substantial evidence supporting the CDC 
recommendation, manufacturers were prohibited from making 
claims about the folic acid/neural tube defect relationship 
until the FDA approved the claim. The FDA did not accept the 
CDC's position, issuing a rule in January, 1993, prohibiting 
folic acid/neural tube defect claims within months after the 
CDC's recommendation was issued. Several months later, despite 
any change in the scientific evidence, the agency reversed 
itself. It proposed to authorize such claims in October, 1993, 
and published a final authorizing regulation in March, 1996.
    There is no telling how many children were born with 
preventable neural tube defects as a result of the FDA's 
initial refusal to accept the CDC's recommendation and 
subsequent delay in promulgating a final regulation.
    The amendments the legislation makes to section 403(r) of 
the Federal Food, Drug, and Cosmetic Act would help to prevent 
problems such as the one witnessed with folic acid from 
occurring with respect to other diet/disease relationships. The 
legislation recognizes that authoritative scientific 
organizations within the Federal Government, as well as the 
NAS, represent a unique and important source of health 
information for the American public. Under the legislation, 
authoritative publications of these organizations can properly 
be used as the basis for a health claim in food labeling 
without the need for further FDA approval or the promulgation 
of a regulation. If this provision had been in effect, the 
information linking inadequate dietary folic acid to an 
increased risk of neural tube defects could have been made 
broadly available to the American public through food labeling 
more than 3 years earlier.
    While this legislation eliminates the need for FDA approval 
of information contained in authoritative publications issued 
by Federal public health agencies and the NAS, it retains the 
NLEA requirement that all health claims satisfy the 
``disqualifying nutrient levels'' established by the FDA. In 
addition, nothing in this legislation is intended to limit the 
FDA's power to prohibit false or misleading claims under 
sections 403(a) and 201(n) of the Federal Food, Drug, and 
Cosmetic Act. The agency may take action against a claim that 
is stated in such a manner as to mischaracterize the 
authoritative statement, conclusion, or recommendation upon 
which it is based, or that otherwise misleads.
    The legislation requires that, at least 90 days prior to 
introducing a food bearing a new health claim authorized under 
this section, a manufacturer or distributor notify the FDA of 
the basis for the claim. This notification requirement will 
enable the FDA to identify misleading claims and notify 
manufacturers or distributors where such claims may merit 
enforcement action. The FDA retains the full panoply of 
enforcement powers the agency has historically possessed to 
remedy misleading claims, including the powers of seizure, 
injunction, and criminal penalties. In addition, the FDA may 
initiate a rulemaking to define a health claim if the agency 
determines that such regulations are necessary to assure that 
specific claims are made in a truthful, nonmisleading manner.

Delaney clause reform

    During its consideration of S. 1477, the committee 
discussed a proposed amendment to reform the Delaney clause. 
Because there was inadequate time to consider the matter fully, 
the proposed amendment was withdrawn. The committee recognizes; 
however, the importance of this issue. Every recent FDA 
Commissioner, has supported a reevaluation and revision of the 
Delaney clause to reflect more recent scientific and technical 
advances. The Delaney clause made sound policy sense when it 
was enacted almost 40 years ago, but scientific advances in the 
intervening years have made it obsolete. Both the FDA and the 
EPA now rely on quantitative risk assessment and other forms of 
scientific analysis to regulate carcinogenic substances and 
have administratively adopted the approach of accepting 
insignificant or negligible risk rather than imposing a zero 
tolerance for potential carcinogens.

Incentive for research and development of new food and color additives

    The committee briefly discussed market exclusivity as an 
incentive for research and development of new food and color 
additive products. The provision would be similar to the 
existing law that applies to new prescription drugs. Due to 
time constraints, the matter was not formally presented to the 
committee. However, several members indicated an interest in 
pursuing this matter further.

   Title IX--Establishment for Centers for Education and Research on 
                Drugs, Devices, and Biological Products

Centers for education and research on drugs, devices, and biological 
        products

    As this report has noted, there are many not-yet-approved 
uses for new drugs, biological products, medical devices, and 
animal drugs, for which there is no economic incentive for the 
pharmaceutical industry to undertake research. To fill this 
gap, the legislation authorizes the appropriation of funds to 
establish a grant program administered by the FDA to establish, 
through awarding peer-reviewed grants, a consortium of at least 
three centers for research and education. It is expected that 
grants for these centers will be made to academic medical 
centers having programs, for example, in clinical pharmacology, 
with the requisite expertise to conduct appropriate educational 
and research programs. These centers will become responsible 
for conducting needed clinical and laboratory research on 
matters that otherwise would not receive adequate medical and 
scientific attention.
    It is the intention of the committee that this research not 
duplicate privately funded research or be conducted in areas 
where there are already incentives for such private research. 
The funds granted under this provision should be used to fill 
in the gaps of scientific and medical knowledge where 
information is now lacking and private research is unlikely. No 
organization has been established to conduct this type of 
research, and these funds will provide a modest beginning. In 
addition, coordinated educational programs will be conducted 
for health care providers, pharmacists, and the public on 
topics such as recognition and anticipation of adverse drug 
reactions and drug interactions, individualized dosage in the 
elderly, children, women, or patients with abnormal kidney, 
liver, or heart function and other areas not likely to be 
adequately addressed by currently available programs. The 
committee intends to review the progress made under this 
program in the coming years to determine whether it should be 
retained, modified, or revoked.

               Title X--Program in Clinical Pharmacology

    The legislation extends the authority and authorization of 
appropriations through fiscal year 1998 for a clinical 
pharmacology training program originally authorized under 
section 2(b) of Public Law 102-222.

                            V. Cost Estimate

    A Letter From Congressional Budget Office requested March, 
1996, has not been received to date, June 20, 1996. Due to time 
constraints, the CBO Report will be added to this report at a 
later date, when it is received.

                    VI. Regulatory Impact Statement

    The committee has determined that this legislation will 
reduce the regulatory burden of paperwork that currently exists 
in the FDA premarket approval of new products.

                    VII. Section-By-Section Analysis

Sec. 1. Short title

    Section 1 provides that the act be cited as the ``Food and 
Drug Administration Performance and Accountability Act of 
1996.''

Sec. 2. Table of contents

    Section 2 contains the table of contents.

Sec. 3. References

    Section 3 provides that all references are to the Federal 
Food, Drug, and Cosmetic Act (FFDCA) unless otherwise expressly 
provided.

                  Title I--Mission and Accountability

Sec. 101. Short title

    Section 101 provides that the title be cited as the ``Food 
and Drug Administration Regulatory Reform Act of 1996.''

Sec. 102. The mission of the Food and Drug Administration

    Section 102 amends section 903(a) of the FFDCA to provide 
that the mission of the FDA is to promote and protect the 
health of the American public by facilitating the rapid and 
efficient development and availability of products, protecting 
the public from unsafe or ineffective products, and enforcing 
the law in a timely, fair, consistent, and decisive manner.

Sec. 103. Performance standards and review

    Section 103 amends section 903(b) of the FFDCA to require 
the FDA within 180 days of enactment, after consultation with 
outside individuals and organizations, to establish 
quantifiable performance standards for action on certain 
submissions and applications and the scheduling of advisory 
committee meetings and action taken following those meetings. 
The performance standards shall be reviewed annually by the FDA 
and, after further consultation with outside individuals and 
organizations, may be revised. The performance standards shall 
establish objectives that expedite clinical investigation and 
applications for new products for an immediately life-
threatening disease or condition or for any other serious 
condition if the product provides therapy or a tool for 
diagnosis or monitoring such a disease or condition not 
available from other approved products or significant 
improvement over other approved products; reduce backlogs on 
all applications with the objective of eliminating backlogs by 
January 1, 1998; establish a schedule to bring the FDA into 
full compliance with statutory time periods by July 1, 1998, 
and improve the consistency and fairness of the FDA regulatory 
process. The FDA is required to prepare and publish in the 
Federal Register an annual report providing detailed data on 
the actual performance relating to each of the types of actions 
subject to a performance standard, comparing the actual 
performance with the standard, describing priorities, analyzing 
any failure to achieve a standard, identifying regulatory 
policies that have a significant impact on performance and 
analyzing how they could be modified in order to achieve 
compliance with the standards, and setting forth a plan to 
achieve compliance with the standards that have not been met. 
The report must include a full statistical presentation 
relating to all applications and petitions for product 
approval.

Sec. 104. Interagency collaboration

    Section 104 amends section 903(b) of the FFDCA to require 
the Secretary to foster collaboration with the National 
Institutes of Health and other science-based agencies to 
enhance the scientific expertise available to the FDA for the 
evaluation of emerging medical therapies and advancement in 
nutrition and food science.

Sec. 105. Information system

    Section 105 adds a new section 906 to the FFDCA to require 
the FDA to establish and maintain an information system to 
track the status and progress of all applications for product 
approval. The system must permit access by the applicant.

Sec. 106. Policy statements

    Section 106 amends section 701(a) of the FFDCA to provide 
that the FDA must establish a procedure governing the 
development and use of all policy statements of general 
applicability that provide guidance relating to the conduct of 
testing or the content of applications for product approval. 
The procedure must provide an opportunity for public 
participation prior to FDA adoption of a policy statement 
unless there is a public health need to issue the document 
immediately. The FDA is required to establish a procedure for 
the compilation and publication of all policy statements.

Sec. 107. Scientific review groups

    Section 107 amends section 904 of the FFDCA to establish 
requirements for scientific review groups that are used as 
advisory committees.
    Section 904(b) provides that the FDA Commissioner may not 
delegate the appointment and oversight authority for advisory 
committees.
    Section 904(c) provides membership and meeting requirements 
for advisory committees. The Commissioner is required to 
consult with an advisory committee in determining the matters 
that the committee will consider and in establishing an 
appropriate agenda. The specific matters and questions to be 
discussed in an advisory committee meeting shall, if feasible, 
be publicly announced in the Federal Register at least 30 days 
prior to the date of the meeting. Advisory committee members 
serve for a term of 3 years, which may be renewed for a second 
term. The chairperson must have served at least 3 years before 
becoming chairperson and may be renewed for a third term. 
Advisory committee members shall be given adequate education 
and training. Advisory committees shall have regular meetings, 
at appropriate intervals and for a sufficient length of time 
necessary to handle all matters that come before them. The 
meetings shall occur not less than 3 times each year unless 
there are reasons for fewer meetings.
    Section 904(d) provides for access information and 
participation by interested persons in advisory committee 
meetings. When an advisory committee reviews a product 
application, the FDA must provide the applicant with copies of 
all documents relating to the applicant's submission provided 
to the advisory committee, at the same time that they are given 
to the advisory committee. The applicant shall have an 
opportunity to provide its own documents to the advisory 
committee, through the FDA. Advisory committee meetings shall 
provide adequate time for initial presentations and for 
response to any differing views, and shall encourage free and 
open participation by all interested persons.
    Section 904(e) provides that, within 60 days after an 
advisory committee makes its conclusions and recommendations on 
any matter, the FDA official responsible for the matter must 
review those conclusions and recommendations, make a final 
determination, and notify the affected persons. If the FDA 
determination differs from the advisory committee conclusions 
and recommendations, the reasons for the difference must be 
specified.

Sec. 108. Appeals within the Food and Drug Administration

    Section 108 adds a new section 907 to the FFDC to provide 
for appeals within FDA.
    Section 907(a) provides that the FDA must establish a 
system for internal appeals from any decision by an employee, 
except for formal administrative or judicial proceedings. As 
the final stage in the internal appeals system, the FDA shall 
provide for the right to request an evaluation by an 
appropriate advisory committee on a matter involving a 
significant scientific issue. The FDA must make publicly known 
the existence of the internal appeal system and the procedures 
involved.
    Section 907(b) provides for appeal by an applicant or 
sponsor of any significant scientific issue to an advisory 
committee. The advisory committee shall review the request and 
determine whether to conduct an evaluation, within 30 days 
after the FDA receives the request. Significant scientific 
issues that an advisory committee may evaluate include, but are 
not limited to, matters involving an FDA hold on a clinical 
investigation, an FDA refusal to file a product application, a 
protocol design, and other decisions relating to pending 
product applications where the same issue has not previously 
been reviewed by an advisory committee. If the advisory 
committee agrees to evaluate an issue, it shall be scheduled 
for the next meeting.
    Section 907(c) provides for additional informal and formal 
appeal procedures. The FDA is authorized to sue such additional 
procedures as may be considered useful. These include, but are 
not limited to, panels of qualified FDA officials, panels of 
qualified government employees who are not FDA employees, and 
outside mediators and arbitrators. Such panels are not subject 
to the Federal Advisory Committee Act.
    Section 907(d) provides that, within 60 days after any 
matter appealed under this section has been the subject of 
conclusions and recommendations, the FDA official responsible 
for the matter shall personally review those conclusions and 
recommendations, make a final determination on the matter, and 
notify the parties. If the FDA determination differs from the 
conclusions and recommendations of the group that reviewed the 
matter, the reasons for the difference must be specified.

Sec. 109. Appointment and term of the Commissioner of Food and Drugs

    Section 109 amends section 903(b)(1) of the FFDCA to limit 
the term of the Commissioner of Food and Drugs to 1 term of 5 
years. The commissioner may be removed from office only 
pursuant to a finding by the President of neglect of duty or 
malfeasance in office. The present Commissioner is excluded 
from this provision.

   Title II--Expedited Access to Products for Seriously ill Patients

Sec. 201. Short title

    Section 201 provides that the title be cited as the 
``Patient Rights Regulatory Reform Act of 1996.''

Sec. 202. Access to unapproved therapies

    Section 202 adds a new section 551 to the FFDCA to provide 
for expanded access to unapproved therapies and diagnostics.
    Section 551(a) provides that any person, through a licensed 
health care practitioner or professional, may request from a 
manufacturer or distributor, and the manufacturer or 
distributor may provide after compliance with the 
investigational provisions of the FFDCA, an investigational 
drug (including a biological product) or device for the 
diagnosis, monitoring, or treatment of a serious disease or 
condition, an immediately life-threatening or seriously 
debilitating disease or conditions and any other disease or 
condition designated by the FDA as appropriate for expanded 
access. This provision applies only if the person has no 
comparable or satisfactory alternative therapy, the risk to the 
person from the investigational product is not greater than the 
risk from the disease or condition, and the sponsor and 
investigators comply with the requirements for an 
investigational drug or device.
    Section 551(b) provides that a manufacturer or distributor 
may submit to the FDA one or more expanded access protocols, 
subject to the requirements for investigational drugs and 
devices. The protocols may include any form of use of the drug 
or device outside a clinical investigation prior to approval 
for marketing, including protocols for treatment use, parallel 
track, single patient use, emergency use, and uncontrolled 
trials.
    Section 551(c) provides that a manufacturer or distributor 
may charge for an investigational drug or device under an 
expanded access protocol, but the price may not be more than 
necessary to recover the costs of manufacture and handling. The 
FDA must be notified in advance of assessing any such charge.
    Section 551(d) requires the FDA to inform national, State, 
and local medical associations and societies, voluntary health 
associations, and other appropriate persons about the 
availability of investigational drugs and devices under 
expanded access protocols.

Sec. 203. Expanding humanitarian use of devices

    Section 203 amends section 520(m) of the FFDCA to require 
the FDA to approve or deny a humanitarian device application 
within 30 days of receipt and to eliminate limitations upon the 
term of an expanded access protocol and the requirement for FDA 
regulations to implement the provision.

Sec. 204. Expediting approval of new drugs, biologics, and medical 
        devices for serious conditions

    Section 204(a) amends section 505(c)(1) of the FFDCA to 
provide that an application for approval for a new drug or 
biological product that is intended for use for an immediately 
life-threatening or serious disease or condition and that 
provides therapy or diagnosis not available for another 
approved drug or biological product or offers significant 
improvement over another approved drug or biological product 
shall be acted upon within 180 days after receipt.
    Section 204(b) amends section 515(d)(1)(A) of the FFDCA by 
similarly providing that applications for the approval of class 
III devices that meet these criteria shall also be acted upon 
within 180 days. This amendment is made effective on July 1, 
1998.

       title iii--revitalizing the investigation of new products

Sec. 301. Short title

    Section 301 provides that the title be cited as the 
``Investigational Products Regulatory Reform Act of 1996.''

Sec. 302. Timely review and reasonable data requirements for clinical 
        research on drugs and biological products

    Section 302 amends section 505(i) of the FFDCA to add two 
new paragraphs relating to the clinical investigation of new 
drugs.
    Section 505(i)(2) provides that a clinical investigation of 
a new drug (including a biological product) may begin 30 days 
after the FDA receives from the sponsor notification of the 
investigation, unless within the 30-day period the FDA informs 
the sponsor in writing that the investigation may not begin and 
specifies the basis for the decision and the information that 
is needed in order for the clinical investigation to commence. 
Within 1 year after the date of enactment, after consultation 
with individuals and organizations, the FDA is required to 
publish in the Federal Register criteria for the type and 
amount of information relating to the safety of an 
investigational drug that must be included in such a 
notification. In establishing these criteria, the FDA must take 
into account the recommendations of the International 
Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use. The FDA must 
periodically review, and may revise, these criteria. The FDA 
must also establish a mechanism to insure the fair and 
consistent application of safety standards for clinical 
investigations.
    Section 505(i)(3) provides that, in order to place a 
clinical hold on any ongoing investigation, the FDA must 
determine that such action is necessary for the protection of 
human subjects. If the FDA does place a clinical hold on an 
investigation, the agency must immediately advise the applicant 
in writing of such action and provide an opportunity to meet 
within 10 working days. The FDA is required to provide to the 
sponsor a written list of conditions for the withdrawal of the 
clinical hold. A written request from the sponsor for the 
removal of the clinical hold must receive an FDA decision in 
writing and specifying the reasons therefore within 20 days of 
the receipt of the request.

Sec. 303. Timely review and reasonable data requirements for clinical 
        research on devices

    Section 303 amends section 520(g) of the FFDCA, which 
relates to the clinical investigation of medical devices.
    Section 520(g)(6) provides that the provisions relating to 
the amount of information on the safety of an investigational 
drug, and insuring the fair and consistent application of 
safety standards for clinical investigations, in new sections 
505(i)(2) (B) and (C) shall apply to medical devices.
    Section 520(g)(7) provides that the FDA must, within 120 
days of enactment, amend its current regulations relating to 
investigational devices to reflect the new law. The regulations 
must permit developmental changes in devices in response to 
information collected during an investigation without the 
additional approval of an investigational device exemption or 
supplement if the sponsor determines that the changes do not 
constitute a significant change in design or basic principles 
of operation. The new regulations must also permit, without 
approval of a supplement, changes in clinical protocols that do 
not affect the validity of the data obtained from the approved 
protocol, if the changes do not affect patient protection.

Sec. 304. Sense of the committee concerning mutual recognition 
        agreements

    This section indicates that it is the sense of the 
committee that the Secretary of Health and Human Services, in 
consultation with the Secretary of Commerce, should move toward 
the acceptance of mutual recognition agreements reached between 
the European Union and the Food and Drug Administration.

Sec. 305. Collaborative research design

    Section 305 amends Chapter V the FFDCA to add a new section 
552 on collaborative research design.
    Section 552(a) provides that any person who intends to 
sponsor a preclinical or clinical investigation of a drug or 
device may request a meeting with the FDA to review one or more 
protocols. Such a request must be in writing and include the 
proposed protocol. The FDA must meet with the person within 30 
days and provide a written review of the protocol, including 
any deficiencies. A written summary shall be made of the 
meeting, which shall be made part of the FDA product review 
file.
    Section 552(b) provides that agreements reached through 
meetings with respect to a protocol may be modified only by 
mutual consent, by the sponsor unilaterally if the change would 
not require FDA approval, and by the DFA unilaterally only by 
the director of the responsible FDA office in writing, and 
specifying the scientific or clinical need.
    Section 552(c) provides that appeals from an adverse FDA 
decision disapproving or modifying a protocol may be made under 
new section 907 of the FFDCA.
    Section 552(d) provides that the FDA must issue guidelines 
under this provision, which shall address the responsibilities 
both of the person requesting the meeting and of the FDA. 
Repeated failure to follow the guidelines may be grounds for a 
refusal by the FDA to meet with a person.

       Title IV--Efficient, Accountable, and Fair Product Review

Sec. 401. Short title

    Section 401 provides that the title be cited as the 
``Product Review Regulatory Reform Act of 1996.''

Sec. 402. The content and review of an application

    Section 402 amends chapter VII of the FFDCA to add a new 
subchapter D on review of applications and to add a new section 
741 on content and review of an application.
    Section 741(a) provides that this section applies to any 
application or related submission for approval or clearance of 
a food additive, new drug, device, biological product, new 
animal drug, animal feed bearing or containing a new animal 
drug, or color additive.
    Section 741(b) requires the FDA to publish in Federal 
Register within 60 days of enactment a mechanism to insure the 
fair and consistent application of filing requirements.
    Section 741(c) establishes a proceed for determining the 
classification of a product as a drug, biological product, or 
device, or the organizational component of the FDA that will 
regulate the product. The FDA must provide a written statement 
of the classification of the product or the component of the 
FDA that will regulate the product upon request. The FDA 
statement is binding and may not be changed by the FDA except 
with the written agreement of the person. If the FDA does not 
provide the statement within 60 days, the classification and 
component designated by the person submitting the request shall 
be final and binding upon the FDA and may not be changed 
without the written agreement of the person.
    Section 741(d) provides that, within 1 year after 
enactment, the FDA must consult with individuals and 
organizations and publish in the Federal Register criteria for 
the type and amount of information relating to safety and 
effectiveness to be included in a product approval application. 
The FDA must consider any recommendations of the International 
Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use is establishing 
the criteria for drugs.

Sec. 403. Contracts for expert review

    Section 403 amends chapter VII of the FFDCA to add a new 
section 742 on contracts for expert review.
    Section 742(a) authorizes the FDA to contract with outside 
organizations and individuals with relevant expertise to 
review, evaluate, and make conclusions and recommendations to 
FDA on parts or all of any product application. The FDA retains 
full authority to make determinations with respect to the 
approval or disapproval of any product. User fee funds may be 
used for external review of any drug for which a user fee was 
paid.
    The FDA is required to use this authority to contract for 
the expert review of categories of indirect food additives and 
510(k) submissions. The FDA is also required to use this 
authority whenever contracts will improve the efficiency, 
timeliness, and quality of the review of applications, 
petitions, and notifications for the approval or clearance of 
new drugs, new animal drugs, biological products, or food 
additives; and whenever contracts will increase the scientific 
or technical expertise necessary to keep informed of emerging 
new therapies and technologies posing significant new 
scientific and technical issues. In all cases, the FDA retains 
full authority to make determinations with respect to the 
approval or disapproval of a product.
    Section 742(b) provides that, within 90 days of the date of 
enactment, the FDA shall by regulation establish the 
requirements an organization shall meet to be eligible to 
conduct expert reviews under subsection (a). The regulations 
are required to provide for the protection of confidential or 
proprietary information and for protection against conflicts of 
interest.
    Section 742(c) provides that, when expert review is used 
under this section, the FDA official responsible for the matter 
shall personally review the conclusions and recommendations of 
the expert review organization or individual and shall make a 
final decision regarding the matter within 60 days but not 
later than the applicable time prescribed for review of an 
application as set forth in other provisions of the FFDCA.
    Section 742(d) requires the FDA to provide a report to 
Congress on the use of outside individuals and organizations 
for expert reviews under this section. The report must include 
and evaluation of the extent to which such contracts improved 
the efficiency of review and expertise available to the FDA.

Sec. 404. Prompt and efficient review

    Section 404 amends chapter VII of the FFDCA to add a new 
section 743 on prompt and efficient review of product 
applications.
    Section 743(a) provides that the product review provisions 
in this section apply to all of the applications and other 
related submissions for human food additives, animal feed 
additives, new drugs, new animal drugs, animal feed bearing or 
containing a new animal drug, premarket notification for 
medical devices, premarket approval for medical devices, and 
color additive petitions.
    Section 743(b) requires the FDA to establish procedures and 
policies to facilitate a collaborative review process between 
the FDA and the applicant. This process must include open, 
informal, and prompt communications. Except for substantial 
equivalence determinations for devices, meetings must be held 
before the expiration of half of the statutory time period for 
review and before the expiration of three-quarters of such 
period, or within 15 days after an advisory committee has 
convened and made recommendations on an application, except for 
substantial equivalence determinations for medical devices. By 
mutual consent, the FDA and the applicant may establish a 
different schedule. Prior to these meetings, the FDA must 
present to the applicant in writing a description of any 
deficiencies and the information necessary to bring the 
application into a form which would require approval. Any 
agreement between the FDA and the applicant to supersede these 
procedures and policies must be in writing and specify the 
changes involved.
    Section 743(c) provides that, beginning July 1, 1998, if 
the FDA fails to meet a time period for action on an 
application for a new drug, device, biological product, or new 
animal drug that offers a significant improvement over existing 
products, or a petition for a direct food additive that has the 
potential to make foods more wholesome and contribute to a 
healthier diet, and the product has already been approved for 
marketing in the European Union or the United Kingdom, upon the 
request of the applicant the FDA shall within 30 days either 
approve or disapprove the application and notify the applicant. 
If the FDA disapproves the application, the notification must 
set forth the reasons for the disapproval.
    A person whose application has been disapproved may obtain 
judicial review under existing provisions in the FFDCA relating 
to judicial review.
    Section 743(d) provides that, beginning July 1, 1998, if 
the FDA in any fiscal year fails to meet the statutory time 
period for at least 95 percent of the applications in a 
particular product category, the FDA shall in the following 
year, with the consent of the applicant, contracts with expert 
individuals and organizations under section 742 to review new 
applications for that particular product category and any 
applications already under agency review for that particular 
product category. Within 60 days of receiving the outside 
review, but no later than the time period for review set forth 
in the FFDCA, the FDA must either approve or disapprove the 
application and, in the case of a disapproval, notify the 
applicant in writing of the basis for the disapproval.

Sec. 405. Good manufacturing practice inspection

    Section 405 amends chapter VII of the FFDCA to add a new 
section 744 governing good manufacturing practice (GMP) 
inspection.
    Section 744(a) provides that the FDA may accredit 
organizations to conduct inspections under section 704 to 
evaluate compliance with applicable GMP requirements.
    Section 744(b) provides that, if the FDA elects to accredit 
organizations to conduct GMP inspections under section 704, 
within 90 days of the date of enactment the agency shall 
establish the requirements that an organization shall meet to 
be eligible to be accredited. The regulation must provide for 
the protection of confidential or proprietary information and 
protection against conflicts of interest.
    Section 744(c) provides that, within 90 days after the FDA 
receives an application for accreditation, the agency shall 
review it and determine whether it is in compliance with the 
applicable requirements. The FDA shall grant accreditation, or 
shall deny accreditation and specify the reasons and the 
requirements that shall be met to obtain accreditation, within 
the 90 days.
    Section 744(d) authorizes the FDA at any time to revoke 
accreditation for failure to comply with applicable 
requirements, after specifying in writing the reasons for the 
revocation and the requirements that shall be met to retain 
accreditation and after an informal hearing on the revocation.
    Section 744(e) provides that an accredited organization 
that conducts an inspection under this section at the request 
of the FDA shall apply all relevant good manufacturing 
principles establish in the FFDCA and FDA regulations, provide 
to the FDA and the manufacturer within 30 days after the 
inspection a report of the findings, and immediately provide 
the FDA with a notice of any condition that would cause or 
contribute to a significant threat to the public health.

Sec. 406. Environmental impact review

    Section 406 amends chapter VII of the FFDCA to add a new 
section 745 dealing with environmental impact review.
    Section 745 provides that, notwithstanding any provision of 
other law, no action by the FDA under the FFDCA shall be 
subject to the requirement of an environmental assessment, 
environmental impact statement, or other environmental 
consideration unless the director of the FDA office responsible 
for the action involved demonstrates, in writing and specifying 
the basis, that there is a reasonable probability that the 
environmental impact of the action is sufficiently substantial 
and within the factors that the FDA is authorized to consider 
under the FFDCA and that consideration of that impact will 
directly affect the decision on the action.

Sec. 407. Effectiveness, outcome, and cost-effectiveness standards

    Section 407 amends section 741, as added by section 402, to 
add three limitations with respect to the determination of 
product effectiveness.
    Section 741(e) provides that, in reviewing an application 
for a new drug, biological products, new animal drug, animal 
feed bearing or containing a new animal drug, or device, the 
determination of effectiveness shall not include evaluation of 
any potential use not include in the labeling, the cost-
effectiveness of the product as compared to the cost-
effectiveness of a similar product unless the proposed labeling 
explicitly includes a representation about cost-effectiveness, 
and the clinical outcome resulting from the use of a diagnostic 
device unless the labeling explicitly includes a representation 
regarding clinical outcome.

Sec. 408. Definition of a day for purposes of product review

    Section 408 amends section 201 of the FFDCA to add to 
following definition of a ``day'' for purposes of reviewing 
product applications and similar submissions. The term ``day'' 
means a calendar day during which FDA has responsibility to 
review a submission, and excludes those days during which the 
applicant is responding to requests from the FDA.

 Sec. 409. Alternative approval of supplemental new drug applications

    Section 409 provides that the FDA shall establish in the 
ederal Register performance standards for the prompt review of 
supplemental applications for approved products within 180 days 
after enactment. The FDA must also issue guidance within 180 
days to clarify the requirements and facilitate the submission 
of data to support approval of such supplemental applications. 
The guidance shall clarify circumstances in which published 
studies may be the basis for approval, specify data 
requirements that will avoid duplication of previously 
submitted data, and define supplemental applications that are 
eligible for priority review. The FDA is required to designate 
an individual in each center (except food) with responsibility 
for encouraging prompt review of supplemental applications and 
working with sponsors to facilitate the development and 
submission of data to support such supplemental applications. 
The FDA shall implement programs and policies to foster 
collaboration between the FDA, the National Institutes of 
Health, and others, to identify published and unpublished 
studies to support supplemental applications and to encourage 
sponsors to make application or to conduct further research in 
support of an application based on such studies.

Sec. 410. Pediatric studies marketing exclusivity

    Section 410 amends chapter V of the FFDCA to add the 
following new section 505A regarding pediatric studies for new 
drug applications.
    Section 505A(a) provides for an additional 6 months of 
market exclusivity for a new drug for which reports of 
pediatric studies are included in an application after the date 
of enactment.
    Section 505A(b) provides for an additional 6 months of 
market exclusivity where FDA makes a written request for 
pediatric studies for a previously approved new drug and such 
studies are completed and accepted by the FDA.
    Section 505A(c) provides the criteria for the pediatric 
studies that are subject to this section. The FDA may enter 
into an agreement for specific studies to be conducted by an 
applicant. If the applicant and the FDA agree upon written 
protocols for such studies, the requirement for market 
exclusivity is satisfied upon the completion of the studies in 
accordance with the protocols and the submission of the reports 
of the FDA. Within 60 days after submission of the report of 
the studies, the FDA must determine if they were conducted in 
accordance with the written protocols and reported as required, 
and so notify the applicant. If there is no agreement in 
writing on the protocols for the studies, the requirement for 
market exclusivity is satisfied when the studies have been 
completed and the reports accepted by the FDA. Within 90 days 
after submission of the reports of the studies, the FDA shall 
accept or reject the reports and so notify the applicant. The 
FDA's responsibility in accepting or rejecting the reports 
shall be limited to determining that the studies fairly respond 
to the written request, that the studies have been conducted in 
accordance with commonly accepted scientific principles and 
protocols, and that they have been reported in accordance with 
the FDA requirements for filing.
    Section 505A(d) provides that, if a section 505(b)(2) new 
drug application or an abbreviated new drug application for a 
drug may be made effective after submission of reports of 
pediatric studies but before the FDA has determined whether the 
requirements of subsection (c) have been satisfied, the FDA may 
delay the effective date of any such other approvals until the 
determination is made under subsection (c), not to exceed 90 
days. If the requirements of subsection (c) are satisfied, the 
6-month market exclusivity period shall begin on the date that 
such other approvals would have been permitted absent action 
under this provision.
    Section 505A(e) requires the FDA to publish notice of any 
determination that the provisions of this section have been met 
and that additional market exclusivity has been granted.
    Section 505A(f) defines ``pediatric studies'' to mean at 
least one human clinical investigation in a population of 
adolescent age or younger. At the discretion of the FDA, 
pharmacokinetic studies may be considered as clinical 
investigations.

Sec. 411. Notifications for device market clearance

    Section 411 amends section 510(k) of the FFDCA to clarify 
that the submission to the FDA is a notification and not a 
report.

        title v--drug and biological products regulatory reform

Sec. 501. Short title

    Section 501 provides that the title be cited as the ``Drug 
and Biological Product Regulatory Reform Act of 1996.''

Sec. 502. New drug approval standard

    Section 501 amends section 505(d) of the FFDCA to add at 
the end thereof a new sentence which states that substantial 
evidence of effectiveness may consist of data from one adequate 
and well-controlled clinical investigation and confirmatory 
evidence (obtained either before or after such investigation).

Sec. 503. Pilot and small-scale manufacture

    Section 503 amends section 505(c) of the FFDCA to provide 
that a new drug or biological product may be approved by the 
FDA on the basis of manufacture in a pilot or other small 
facility prior to scaling up to a larger facility, unless the 
FDA demonstrates, in writing and specifying in detail the 
reasons after an informal hearing, that a full scale production 
facility is necessary to ensure safety or effectiveness.

Sec. 504. Manufacturing changes

    Section 504 amends chapter VII of the FFDCA, as amended by 
section 406, to add a new section 746 on manufacturing changes.
    Section 746(a) provides that the new section applies to new 
drugs, biological products, and new animal drugs.
    Section 746(b) provides that a change in the manufacture of 
a new drug, a biological product that is the subject of an 
official monograph or that can be adequately characterized by 
chemical, physical, or biological means, or a new animal drug, 
shall require validation. If there is no change in the approved 
qualitative and quantitative formulation or in the approved 
release specifications, or if any such change is of a type 
permitted by FDA regulations, the manufacturing change may be 
made at any time and shall be reported annually to the 
secretary. Any other change shall require completion of an 
appropriate study demonstrating equivalence according to 
criteria established by the FDA unless that requirement is 
waived by the FDA, may be made at any time, and shall be 
reported to the FDA through a supplement or amendment submitted 
at the time the change is made.
    Section 746(c) applies to changes in biological products 
that are not subject to an official monograph and cannot 
adequately characterized by chemical, physical, or biological 
means. These changes also require validation. If the change 
relates solely to the modification of the manufacturing 
facility or personnel, with no change in the process or release 
specifications, it may be made at any time and shall be 
reported annually to the secretary. Any other change shall 
require completion of a bioassay or other appropriate study 
demonstrating equivalence according to criteria established by 
the FDA unless such requirement is waived by the FDA, may be 
made at any time, and shall be reported to the FDA through an 
amendment submitted at the time the change is made.
    Section 746(d) provides that, prior to approval of a 
biological product, a determination shall be made whether the 
product can be adequately characterized for purposes of this 
section. Such a determination shall be made with respect to 
previously approved biological products within 90 days after 
the date of enactment. Any determination under this subsection 
is subject to change based upon new scientific information.

Sec. 505. Insulin and antibiotics

    Section 505 repeals sections 506 and 507 of the FFDCA, 
which currently govern the approval and certification of 
insulin and antibiotics. As a conforming amendment, section 802 
is amended to permit the continued exportation of unapproved 
insulin and antibiotic drugs without regard to the export 
provisions that otherwise apply to new drugs if they meet the 
requirements of section 801(e)(1).

 Sec. 506. Modernization of regulation of biological products

    Section 506 amends section 351 of the Public Health Service 
Act to revise the provisions under which biological products 
are regulated.
    Section 506(a) revises section 351(a) of the Public Health 
Service Act to require that no person shall introduce or 
deliver for introduction into interstate commerce any 
biological product unless a license is in effect and each 
package is properly marked. The license shall, as determined by 
the Secretary, cover the biological product or the facility in 
which the product is manufactured, or both. The FDA shall 
establish, by regulation, requirements for license 
applications. License applications shall be approved based upon 
a demonstration that the biological product is safe and 
effective in accordance with sections 505(c) and 505(d); or 
meets standards designed to ensure that the product is safe, 
pure, and where appropriate, potent and that the methods, 
facilities, and controls used for manufacture, processing, 
packing and holding meet designated standards. A license 
application that covers a facility shall ensure that the 
product meets appropriate standards. A license application for 
blood or a blood component shall be approved based on a 
demonstration that the product is safe, pure, and where 
appropriate, potent, and that the facility meets appropriate 
standards. Requirements for approval of biological products 
shall include preapproval inspection and agreement to permit 
facility inspections.
    An approved license for a biological product may be revoked 
after an opportunity for a hearing if the FDA determines that 
the requirements for approval are no longer met or that other 
public health reasons, prescribed by regulation, exist. 
Revocation may not occur prior to an opportunity for a written 
response submitted by the licensee within 30 days of the date 
of receipt of inspectional findings. Revocation of a product 
licenses shall not prevent the continued use of a licensed 
biological product unless the product is subject to recall. If 
the licensee requests an inspection before the FDA has taken 
final action to revoke a license, the FDA shall conduct an 
inspection within 30 days. If the inspection confirms that the 
licensee is not in compliance with applicable standards, the 
30-day requirement for inspection shall not apply to any 
subsequent request. If the inspection confirms that the 
licensee is in compliance with all applicable requirements, the 
FDA must withdraw any proposed action. Where the FDA determines 
that grounds for license revocation exist that constitute a 
danger to health, the FDA shall suspend the license and 
initiate the hearing process within 30 days.
    An investigational biological product subject to the 
investigational new drug provisions, including section 505(i) 
of the FFDCA.
    Section 506(b) amends section 351(d) of the Public Health 
Service Act to repeal the requirement for a separate 
establishment license.
    Section 506(c) amends section 251(b) of the Public Health 
Service Act to provide that no person shall falsely label any 
biological product.
    Section 506(d) amends section 351(c) of the Public Health 
Service Act to conform the language to the other changes made 
in this section.
    Section 506(e) amends section 351 of the Public Health 
Service Act to add a new subsection (i) to define the term 
``biological product.'' The definition conforms to existing 
provisions of law. Sections 505(i), 903, and 904 of the FFDCA 
Act, which relate to investigational new drugs and advisory 
committees, are applicable to biological products. Requirements 
involving labeling and advertising for biological products are 
required to be established in accordance with the provisions in 
sections 201(m) and 502(n) of the FFDCA, which apply to 
labeling and advertising for drugs.

Sec. 507. Effective medication guides

    Section 507 amends chapter IX of the FFDCA, as amended by 
section 108, to add a new section 908 regarding effective 
medication guides.
    Section 908(a) requires the FDA within 30 days of enactment 
to request national health care organizations to develop a 
long-range comprehensive plan relating to the provision of oral 
and written prescription drug information to consumers. The 
plan must be consistent with the goals of the recent FDA-
proposed regulation governing medication guide requirements for 
prescription drugs.
    Section 908(b) describes the requirements for the plan.
    Section 908(c) provides that the FDA shall have no 
authority to implement its proposed regulation or to develop 
any similar regulation or policy statement relating to the same 
subject if, within 120 days after enactment, the national 
organizations described in subsection (a) meet and begin to 
develop the plan described in that subsection.
    Section 908(d) provides that by January 1, 2001, the 
Secretary of HHS must review the status of private sector 
initiatives in this field to determine whether they achieve the 
goals of the plan described in subsection (a). If those goals 
are not achieved, the limitation above will no longer apply and 
the FDA will be free to seek public comment on other 
initiatives to meet those goals. The Secretary may not delegate 
this review.

Sec. 508. State and local requirements respecting nonprescritpion drugs 
        intended for human use

    Section 508 amends chapter V of the FFDCA to add a new 
section 523 regarding State and local requirements for 
nonprescription drugs intended for human use. Section 523(a) 
provides that no State or political subdivision may establish 
or continue in effect any requirement relating to human 
nonprescription drugs which is different from or in addition 
to, or otherwise not identical with, a requirement of the FFDCA 
Act or the Fair Packaging and Labeling Act (FLPA) and the 
administrative implementation thereunder. This provision covers 
any requirement relating to the subject matter in any provision 
of the two statutes involved and any requirement relating to 
the dissemination of information in any manner about 
nonprescription drugs, other than a State or local requirement 
switching a nonprescription drug to prescription status.
    Section 523(b) provides that a State may petition the FDA 
for an exemption from this authority. After providing notice 
and an opportunity for written and oral presentations, the FDA 
may by regulation grant an exemption from the general rule of 
national uniformity if the State requirement is justified by 
compelling local conditions or protects an important public 
interest, would not cause any nonprescription drug to be in 
violation of any applicable requirement or prohibition under 
Federal law, and would not unduly burden interstate commerce.

Sec. 509. Requirements of radiopharmaceuticals

    Section 509(a) provides, that, not later than 180 days 
after enactment, after consultation with individuals and 
organizations, the FDA must establish proposed regulations 
governing the premarket approval of radiopharmaceutical 
articles, taking into account their appropriate use, 
pharmacological and toxicological activity, and estimated 
absorbed radiation dose. Not later than 1 year after the date 
of enactment, the FDA must issue final regulations.
    Section 509(b) provides that, with regard to diagnostic 
radiopharmaceuticals, the approved indications may refer to 
specified manifestations of disease or may refer to a 
diagnostic procedure. All product premarket approval 
applications for radiopharmaceutical articles, and all other 
matters relating to radiopharmaceuticals, are required to be 
reviewed and acted upon by a single office in the FDA center 
responsible for drugs and that office shall report directly to 
the center director. A single advisory committee may provide 
conclusions and recommendations regarding any 
radiopharmaceutical matter.
    Section 509(c) defines the term ``radiopharmaceutical.''
    Section 509(d) provides that the FDA is required to 
establish quantifiable performance standards to measure the 
performance of the agency in approving radiopharmaceutical 
articles as part of its performance standards for all agency 
activities.

                   Title VI--Device Regulatory Reform

Sec. 601. Short title

    Section 601 provides that this title be cited as the 
``Medical Device Reform Act of 1996.''

Sec. 602. Premarket notification

    Section 602(a) amends section 510 of the FFDCA to exempt 
from premarket notification all class I devices (except those 
identified by the FDA under subsection (n) as requiring 
premarket notification to protect the public health) and those 
class II devices that FDA determines do not need such 
notification. Within 30 days of enactment, the FDA is required 
to publish in the Federal Register a list of each type of class 
II device that does not require premarket notification under 
section 510(k). Any person may petition the FDA to exempt other 
types of class II devices, and the FDA must respond within 180 
days of receipt of the petition. The FDA is also required to 
review and respond and respond to all premarket notifications 
within 90 days of receipt. The FDA may not withhold a 
determination regarding these matters because of a failure to 
comply with any provision of the FFDCA unrelated to a 
substantial equivalent decision.
    Section 602(b) amends section 513 of the FFDCA to allow a 
person who submits a premarket notification under section 
510(k) of the FFDCA to obtain advisory committee review with 
respect to the classification of a device into class III. The 
FDA has 10 days after receiving the conclusions and 
recommendations of the advisory committee to determine the 
final classification of the device.
    Section 602(c) amends section 513 of the FFDCA to provide 
that, for the purpose of determining the intended use of a 
predicate device for a substantial equivalent determination, 
each use reasonably included, as determined by the FDA, within 
a general use for the predicate device shall be deemed a 
legally marketed use.
    Section 602(d) amends section 513 of the FFDCA to provide 
that any change or modification to a device, other than a major 
change or modification in the intended use, or a significant 
change or modification in design that has a significant effect 
on safety or effectiveness, shall not require an additional 
premarket notification under section 510(k) if, prior to 
commercial distribution, the change is supported by appropriate 
data or information, including data or information 
demonstrating compliance with good manufacturing practice 
regulations promulgated under section 520(f), and is shown by 
such data or information not to adversely affect safety or 
effectiveness. All data to support such a change to the device 
shall be made available to the FDA upon request and shall be 
maintained for at least a period of time equal to the 
commercial life of the device.

Sec. 603. Medical device approval standards

    Section 603(a) amends section 513(a)(3) of the FFDCA to 
clarify that the FDA may determine the effectiveness of a 
device on the basis of one or more well-controlled 
investigations, including one or more clinical investigations.
    Section 603(b) amends section 513(a)(3) of the FFDCA to 
provide that the FDA shall accept retrospective or historical 
clinical data as a control in a study for use in determining 
the effectiveness of a device if sufficient valid data are 
available and the effects of the device are clearly defined and 
well understood. The FDA may not require clinical studies using 
prospective concurrent controls to support the effectiveness of 
a device unless the effects of the device are not clearly 
defined and well understood as determined by the FDA or 
retrospective or historical data are not available that meet 
the standards of the FDA for quality and completeness or there 
is a compelling public health reason not to rely on 
retrospective or historical data as a control.

Sec. 604. Tracking

    Section 604 amends section 519(e) of the FFDCA to authorize 
device tracking for a class II or class III device the failure 
of which would be life-threatening or have permanently 
debilitating effects and which is permanently implanted or 
life-sustaining or life-supporting and used outside a device 
user facility. Any patient receiving a device subject to 
tracking under this section may refuse to release or refuse 
permission to release identifying information for the purpose 
of tracking.

Sec. 605. Postmarket surveillance

    Section 605 revises section 522 of the FFDCA relating to 
postmarket surveillance of devices.
    Amended section 522(a) provides that the FDA may require a 
manufacturer to conduct postmarket surveillance for any device 
of the manufacturer that is a permanent implant the failure of 
which may cause serious, adverse health consequences or death, 
or that is intended for use in supporting or sustaining human 
life or that potentially presents a serious risk to human 
health.
    Amended section 552(b) provides that each manufacturer 
required to conduct surveillance of a device shall, within 30 
days of receiving notice from the FDA, submit to the FDA for 
approval a protocol for the required surveillance. Within 60 
days of receiving the protocol, the FDA shall determine if the 
principal investigator has sufficient qualifications and if the 
protocol will result in collection of useful data necessary to 
protect the public health and to provide safety and 
effectiveness information for the device. The FDA may not 
approve the protocol until it has been reviewed by a qualified 
FDA advisory committee.

Sec. 606. Device distributor reporting

    Section 519 of the FFDCA is amended to eliminate reporting 
requirements for device distributors.

Sec. 607. Premarket approval

    Section 607(a) amends section 515(d) of the FFDCA to 
establish new requirements and procedures with respect to 
premarket approval of class III devices. The FDA is required to 
accept data relating to safety and effectiveness from 
investigations if the data relate to an earlier version of the 
device which has been modified and the modification does not 
constitute a significant change that would invalidate the data, 
or the data are available for use under the FFDCA and are 
relevant to the design and intended use of the device. Each 
premarket application is required to be reviewed according to 
an established schedule. The FDA shall meet with an applicant 
within 90 days of the receipt of the premarket approval 
application. If the application does not appear in a form which 
would require approval under the FFDCA, the FDA must, in 
writing prior to the meeting, present to the applicant a 
description of the deficiencies and the information required to 
bring the application into such form. The FDA shall refer an 
application to an advisory committee for review unless this is 
not required. The FDA must meet with the applicant within 15 
days of the date of the advisory committee review to discuss 
the status of the application, including a discussion on what 
action is necessary to bring the application into a form that 
would require approval. Prior to that meeting, the FDA shall in 
writing set forth an agenda for the meeting and a full 
description of the additional information necessary for 
approval of the application. The applicant may decline any such 
meeting.
    Not later than 135 days after receipt of a premarket 
approval application, if an advisory committee is not required, 
the FDA shall inform the applicant whether the application is 
in a form that would require approval under this subsection. If 
the application is in a form which would require approval, the 
FDA shall present in writing to the applicant a description of 
all additional information necessary to receive approval. If 
the application is not in a form which would require approval, 
the FDA shall deny approval and, prior to the meeting, present 
in writing each basis for denying approval and the additional 
information required for approval. FDA must approve or deny an 
application within 180 days of receipt, or within 180 days of 
receipt for an application subject to expedited review. Review 
of a premarket approval application by the FDA shall not take 
more than the statutory time period, which may not be extended 
if the application is amended.
    Section 607(b) requires the FDA to amend its regulations 
governing premarket approval to conform to the new statutory 
requirements, including the provisions relating to changes 
relating to the product and its manufacturer that do not 
require a supplemental premarket approval application. The FDA 
shall require device manufacturers to maintain the information 
relied upon to support a change that is not subject to 
premarket approval of a supplement, which shall become part of 
the device master file, and give notice to the FDA of the 
change. The information shall be maintained for the expected 
life of the device but not less than 2 years after commercial 
distribution.

Sec. 608. Device performance standards

    Section 608(a) amends section 514 of the FFDCA to 
facilitate review of a device by recognition of appropriate 
medical device performance standards developed by organizations 
accredited by the American National Standards Institute (ANSI), 
the International Standards Organization (ISO), the 
International Electrotechnical Commission (IEC), and any other 
organization certified by the FDA for this purpose. For 
organizations other than ANSI, ISO, and IEC, the FDA is 
required to establish a procedure governing certification of 
the competence of any national or international standards-
setting organization to develop standards for medical devices. 
Certification must be based on formal written criteria that 
include specified elements. The FDA may impose a reasonable fee 
for certifying these organizations. The FDA is required to 
recognize standards adopted by ANSI, ISO, or IEC and must 
review and may recognize standards adopted by other 
organizations it has accredited. When the FDA recognizes a 
standard, it must publish a notice in the Federal Register 
listing the name of the standard and shall provide any person 
who so requests a copy of the standard. The FDA is required to 
promulgate regulations under which it may withdraw the 
certification it has granted to a standard-setting organization 
or may withdraw recognition of a standard adopted by ANSI, ISO, 
or IEC upon a determination that it no longer meets appropriate 
requirements. The FDA may also promulgate performance standards 
that differ from or are not established by certified 
organizations. The FDA may not require, as a condition for 
approving a medical device, conformity with a standard 
recognized under this section if the applicant demonstrates a 
reasonable assurance that the device is substantially 
equivalent to a legally marketed predicate device or provides 
reasonable assurance and that the device is safe and effective.
    The FDA may revoke recognition of performance standards 
previously recognized under this section upon a determination 
that the standard is insufficient to provide reasonable 
assurance of safety and effectiveness. The FDA must notify the 
standard-setting organization and specify the basis for the 
revocation.
    A performance standard recognized under this section is 
required to provide reasonable assurance of safety and 
effectiveness. Such a performance standard shall, where 
necessary, include provisions with respect to the construction, 
components, ingredients, and properties of the device and the 
compatibility of the device with power systems and connections 
to the systems, provisions for testing, provisions for 
measurement of performance, and provisions requiring that the 
results of the tests demonstrate conformity with the standard. 
A performance standard shall, where appropriate, require the 
use and prescribe the form and content for adequate labeling.
    In lieu of requiring data demonstrating conformity of a 
device with a standard under this section, the FDA shall accept 
a certification that the device conforms with each identified 
standard. Where appropriate, the FDA may require data 
demonstrating such conformity. The FDA shall require an 
applicant who certifies that a device conforms to an applicable 
standard to maintain data demonstrating such conformance for 
the life of the device and to make the data available to the 
FDA upon request.
    Section 608(b) amends section 501(e) of the FFDCA to 
provide that a device that is represented as certified to be in 
compliance with a standard recognized under section 514(c) is 
adulterated unless the device is in all respects in conformity 
with the standard.

Sec. 609. Accredited-party participation

    Section 609 amends subchapter A of chapter V of FFDCA to 
add a new section 523A to establish a 3-year pilot program on 
the use of accredited third parties to review and approve 
section 510(k) premarket notifications and section 515 
premarket approval applications.
    Section 523A(a) provides that, within 1 year after 
enactment, the FDA shall accredit individuals and organizations 
outside the Department of HHS to review and recommend to FDA 
approval or denial of premarket notifications under section 
510(k) and premarket approval applications under section 515.
    Section 523A(b) establishes procedures for accreditation of 
individuals and organizations qualified to conduct such 
reviews. The criteria for accreditation shall include criteria 
to avoid conflicts of interest and to assure confidentiality of 
submissions.
    Section 523A(c) authorizes the FDA to suspend or withdraw 
accreditation for failure to meet the criteria for 
accreditation
    Section 523A(d) provides that a person who submits to the 
FDA a premarket submission for a device for review and 
classification or for approval of the device must be given the 
option to select an accredited party to review such 
submissions. For persons electing to use this option, the FDA 
is required to identify no less than 2 accredited persons from 
whom the selection may be made. Compensation for accredited 
party review is to be determined by agreement between the 
accredited party and the person who engages the services of the 
accredited party.
    Section 523A(e) provides that, when a person submitting a 
premarket notification of premarket approval application 
exercises the option to obtain third party review, the person 
shall first submit the notification or application to the FDA 
for review to determine completeness for filing. No later than 
15 days after receipt of a premarket notification or 30 days 
after receipt of a premarket approval application, the FDA 
shall forward the submission to the accredited individual or 
organization. Upon receiving the conclusions and 
recommendations of the accredited individual or organization, 
the FDA shall have 15 days to act upon a premarket notification 
and 45 days to act upon a premarket approval application. If 
the FDA takes action different from that recommended by the 
accredited individual or organization, the agency must provide 
detailed reasons.
    Section 523A(f) provides that this program shall remain in 
force for 3 years from the date of the first FDA accreditation 
of an individual or organization.
    Section 523A(g) provides for reports to the committees of 
Congress with respect to FDA implementation of this program. 
After 2 years of operation, the FDA must contract with an 
independent research organization to examine the program and 
prepare a full evaluation.

                title vii--animal drug regulatory reform

Sec. 701. Short title

    Section 701 provides that the title be cited as the 
``Animal Drug Regulatory Reform Act of 1996.''

Sec. 702. Evidence of effectiveness

    Section 702(a) amends section 512(d) of the FFDCA to 
provide that substantial evidence of effectiveness for an 
animal drug means evidence from one or more scientifically 
sound studies, that taken together provide reasonable assurance 
that the drug will have the claimed or intended effect. A study 
shall be considered to be scientifically sound if it is 
designed and conducted in a manner that is consistent with 
generally recognized scientific procedures and principles.
    Section 702(b) amends section 512(d) of the FFDCA to 
provide that, where a new animal drug contains more than one 
already approved active ingredient or the labeling suggests use 
of the drug in combination with another already approved animal 
drug, the FDA may only consider with respect to the combination 
whether any of the active ingredients at the longest withdrawal 
time is above its safe concentration or interferes with the 
method of analysis for another active ingredient.
    Section 702(c) amends section 512(c)(2)(F)(iii) of the 
FFDCA by providing market exclusivity based upon substantial 
evidence of effectiveness rather than upon new clinical or 
field investigations and by providing that such studies must be 
required for approval rather than essential to approval.
    Section 702(d) amends section 512(d)(1) of the FFDCA to 
provide that the requirement of substantial evidence of 
effectiveness shall not apply to a claim for use of an animal 
drug in a minor species or for a minor use if there is an 
approved new animal drug application for the drug.
    Section 702(e) amends section 512(d)(1)(C) of the FFDCA to 
conform it to the new definition of substantial evidence of 
effectiveness.
    Section 702(f) provides that, not later than 6 months after 
enactment, the FDA shall issue proposed rules implementing the 
amendments made by this section. Not later than 18 months after 
the date of enactment, the FDA shall issue final regulations. 
In issuing regulations and reviewing new animal drug 
applications, the FDA is required to define ``substantial 
evidence'' of effectiveness in a manner that encourages the 
submission of applications for production drugs that conserve 
food resources, for veterinary prescription drugs whose use is 
designed to rely on the experience and training of 
practitioners, and of supplemental applications for uses in 
minor species, for minor uses, and for permitted unlabeled 
uses. The regulations must also take into account the citizen 
petition submitted by the American Veterinary Medical 
Association and the Animal Health Institute on October 21, 
1991, relating to labeling a veterinary prescription drug with 
a dosage rather than a single dosage level. Finally, the 
regulations must provide for the opportunity for a conference 
prior to the submission of a new animal drug application on 
investigational new animal drug application, and prior to the 
submission of a request for an investigational exemption, to 
make a decision establishing a submission or an investigational 
requirement. That decision shall bind the FDA and the applicant 
unless new scientific information requires a change. Not later 
than 10 days after each such conference, the FDA shall provide 
by written order a scientific justification specific to the 
animal drug and the intended uses under consideration for 
requiring studies of types other than the types of studies 
specified in section 512(d)(4) as being essential to provide 
substantial evidence of effectiveness for the intended uses of 
the animal drug.

Sec. 703. Limitation of residues

    Section 703 amends section 512(d)(1)(F) of the FFDCA to 
state that a new animal drug application may be disapproved on 
the basis of information that the labeled use will result in a 
residue in excess of a tolerance found by the FDA to be safe.

Sec. 704. Adulterated drugs

    Section 704 amends section 501(a)(2) of the FFDCA to 
specify separate GMP requirements for animal drugs that are 
appropriate for such drugs and that will ensure that the drug 
meets the requirements of the FFDCA for use in animals other 
than man.

Sec. 705. Veterinary feed directives

    Section 705(a) amends section 503(f)(1)(A) of the FFDCA to 
exclude veterinary feed directive drugs and animal food 
containing such drugs from the requirement for a veterinary 
prescription.
    Section 705(b) amends chapter V to add a new section 504 
governing veterinary feed directive drugs.
    Section 504(a) provides that a drug intended for use in or 
on animal feed which is limited to use under the professional 
supervision of a licensed veterinarian is a veterinary feed 
directive drug. Any animal feed containing such a drug shall be 
fed to animals only by or upon a lawful veterinary feed 
directive issued by a licensed veterinarian in the course of 
the veterinarian's professional practice. A veterinary feed 
directive drug is exempt from the requirement of a 
prescription. A veterinary feed directive is lawful if it 
contains the information required by the FDA and complies with 
the conditions and indications for use established for the 
drug. Appropriate records must be maintained relating to 
veterinary feed directive drugs and must be made available to 
the FDA upon request. A person who distributes animal feed 
containing a veterinary feed directive drug must notify the 
FDA.
    Section 504(b) provides that a veterinary feed directive 
drug and any feed bearing or containing such a drug shall be 
deemed to be misbranded if the drug and feed labeling fail to 
bear such cautionary statement and other information as the FDA 
may require or if the advertising fails to conform to the 
requirements of section 512(i) or other FDA requirements.
    Section 504(c) provides that a veterinary feed directive 
drug and an animal feed bearing or containing such a drug shall 
not be deemed to be a prescription article under any Federal or 
State law.
    Section 705(c) contains conforming amendments.
    Section 705(d) amends section 301(e) of the FFDCA to make a 
violation of section 504 of the FFDCA a prohibited act.

Sec. 706. Times frames for approval

    Section 706 amends section 512(c)(1) of the FFDCA to 
require action on a new animal drug application within 90 days 
rather than the present 180 days.

                   title viii--food regulatory reform

Sec. 801. Short title

    Section 801 provides that the title be cited as the ``Food 
Regulatory Reform Act of 1996.''

Sec. 802. Indirect food additives

    Section 802(a) amends section 409 of the FFDCA to add an 
alternative approval procedure for indirect food additives. Any 
person may submit a notification for an indirect food additive 
at least 90 days prior to the introduction or delivery for 
introduction of the additive in interstate commerce, 
demonstrating that the labeled use of the product is safe. 
Within 90 days after receipt of the notification, the FDA shall 
either approve or disapprove the notification and publish a 
notice of this determination in the Federal Register. If the 
notification is approved, the FDA shall promulgate an 
appropriate food additive regulation.
    Section 802(b) amends section 201 of the FFDCA, as amended 
by section 408, by adding a new definition of the term 
``indirect food additive,'' which means a food additive 
intended to contact food but that is not intended for 
consumption as a food ingredient.

Sec. 803. Health claims of food products

    Section 803 amends section 403(r)(3) of the FFDCA to 
authorize the use in food labeling of health claims consisting 
of information published by authoritative government scientific 
bodies. Any claim that is subject to the requirements for 
health claims established under the Nutrition Labeling and 
Education Act of 1990 and which would otherwise require 
specific authorization by the FDA prior to use may be used in 
food labeling without FDA authorization if it consists of or 
otherwise summarizes or reflects information contained in a 
publication by a Federal Government scientific organization or 
by the National Academy of Sciences or one of its component 
organizations. If any such claim is used a copy must be 
provided to the FDA, along with the published information on 
which it is based, at least 90 days prior to its first use. 
This provision applies to all food products, including dietary 
supplements.

title ix--establishment of centers for education and research on drugs, 
                    devices, and biological products

Sec. 901. Centers for education and research on drugs, devices, and 
        biological products

    Section 901 amends chapter IX of the FFDCA to add a new 
section 908 to establish centers for education and research on 
drugs, devices, and biological products.
    Section 908(a) requires the FDA to establish a consortium 
of three or more centers for research and education on drugs, 
devices, and biological products.
    Section 908(b) provides that the entities shall be selected 
by a peer review selection procedure.
    Section 908(c) provides for two types of grant activities. 
Required activities shall include state-of-the-art clinical and 
laboratory research that increases awareness of new uses of 
products and the unforeseen risks of new uses of products, 
provides objective clinical information, and improves the 
quality of health care while reducing the cost of health care 
through the prevention of adverse effects of these products and 
the consequences of such effects. Research on the comparative 
effectiveness and safety of these products is also a required 
activity. Discretionary activities includes surveillance of 
adverse effects, a study of new or unapproved uses for marketed 
products, and a study of the therapeutic characteristics of 
clinically special populations. No money awarded under this 
provision may be used to assist the FDA in the review of new 
drugs.
    Section 908(d) provides for grant applications to the FDA.
    Section 908(e) establishes an oversight committee within 
the FDA.
    Section 908(f) requires a report to Congress on the 
activities undertaken pursuant to this provision.
    Section 908(g) authorizes appropriations.

               title x--program in clinical pharmacology

    This title extends the authority for 2 fiscal years for a 
clinical pharmacology education program initially authorized 
under section 2(b) of public law 102-222.
                         VIII. Additional Views

         additional views of senators kennedy, pell, and simon

    The stated goal of S. 1477 is to better balance FDA's twin 
goals of protecting the American consumer from unsafe or 
ineffective drugs, devices, and foods and ensuring timely 
review and availability of new or improved medical products and 
better food technology. No one disputes that this balance is 
important. At the outset, we emphasize that certain provisions 
in S. 1477 are constructive. Among other useful provisions, the 
bill codifies regulatory reforms that FDA has already adopted, 
modernizes the legislative authority governing regulation of 
biologics, gives FDA flexibility to adopt other reforms, and 
creates new procedures to encourage collaboration, 
predictability, and efficiency in the testing and review of new 
products and new uses of approved products.
    Despite these constructive elements, S. 1477 in its current 
form fails the basic test of good regulatory reform, because it 
will put the health of the American people at risk. 
Unfortunately, even though many improvements have been made to 
S. 1477 since it was introduced late last year, provisions 
remain that would seriously undermine both FDA and the laws it 
enforces and expose American consumers to unsafe and 
ineffective drugs, devices, biologics, and food. If such 
provisions remain in the bill, FDA will not have the tools to 
prevent public health tragedies like DES (diethyl stilbestrol), 
the Dalkon Shield, the Shiley heart valve, the Cutter polio 
vaccine, and contaminated blood. Over the long run, the 
provisions of the bill could destroy FDA as an effective 
regulatory body.
    Although our concerns are spelled out in depth below, major 
provisions of S. 1477 that are unacceptable include:
    Prohibiting FDA from requiring prior review and approval of 
critical manufacturing changes--changes that, for example, 
could turn vaccine designed to prevent polio into one that 
causes it;
    Turning central regulatory decisions over to private 
industry, creating an inherent conflict of interest and 
draining FDA of the resources and expertise it needs to remain 
an effective guardian of public health;
    Establishing unrealistic timeframes for product review, but 
failing to provide adequate resources for FDA to achieve these 
goals and still carry out the thorough, careful review the 
public deserves;
    Creating new bureaucratic burdens that will make it more 
difficult for the agency to promptly review new products;
    Requiring FDA to give priority to products approved abroad, 
even if they are less important than products proposed for 
first-time approval in the United States. This not only will 
slow review of the highest priority products, but it will 
encourage U.S. companies to take their research abroad; and
    Weakening FDA's authority to require appropriate consumer 
labelling for drugs, thus denying consumers the reliable 
information they need to protect themselves against adverse 
drug reactions.
    S. 1477 unacceptably weakens essential FDA oversight of 
drug and biologic manufacturing. Section 604 eliminates FDA's 
ability to require pre-approval of any manufacturing changes 
for drugs and biologics, including blood and vaccines, even if 
the change has a substantial potential to harm public health. 
Instead, section 604 would require certain kinds of validation 
or testing and reporting to FDA, depending on the kind of 
product involved. However, history teaches that manufacturing 
changes can make a product unsafe or less effective and that 
validation or testing against finished product specifications 
may not detect problems and protect the public. For example, 
changing the solvent used to kill viruses like HIV or hepatitis 
in blood products can result in products that transmit life-
threatening diseases. A change in the filters or virus lines 
used to produce vaccines can turn a protective vaccine into a 
deadly one. A change in the filters used to produce the Cutter 
polio vaccine resulted in 200 cases of polio in the 1950's, 
before FDA required more rigorous standards. Even with the 
tight controls now in place, there have been 26 cases in just 
the last two years--including cases involving vaccines--where 
only FDA intervention prevented thousands of patients from 
being exposed to dangerous products.
    Because of the strict requirements now in place, every 
American patient who has an operation or receives a transfusion 
has confidence thatthe blood they will receive is safe, 
uncontaminated by HIV, hepatitis, or other diseases. Likewise, every 
parent whose child is vaccinated assumes that the vaccine will prevent 
illness, not cause it. If Section 604 becomes law, this confidence may 
no longer be justified. Not only may Americans be injured, but so will 
our pharmaceutical and biotechnology industries, which benefit from the 
justified confidence that Americans now have in the quality of products 
like blood and vaccines.
    S. 1477 turns critical functions of FDA over to private 
industry and drains the agency of the resources and expertise 
necessary to protect the public in a number of ways. Section 
709, which was described as a pilot to test third party review 
when offered in committee, actually allows device companies to 
have any medical device reviewed by third parties that they 
select and with whom they negotiate the price. The conflict of 
interest that occurs when a manufacturer that wants a product 
approved both hires and pays the reviewer who will determine 
whether the product is safe and effective is obvious and 
unacceptable.
    As written, the provision requires FDA to accredit third 
parties to review every kind of device. Once third parties are 
accredited, manufacturers are free to choose product review by 
these third parties, rather than FDA, even for products that 
involve totally new technologies, that are the most complex, or 
that are critical to the public health, including pacemakers, 
breast implants, heart valves, and blood screening kits. 
Section 709 does purport to give FDA final say over the 
decisions of private reviewers, but the time-frames for FDA 
action are so short and the erosion of FDA's expertise as the 
result of turning over its responsibilities to third-party 
reviewers would be so extensive, that it is hard to see how 
FDA's review would be much more than a rubber stamp.
    FDA is currently conducting a true pilot program to test 
the effectiveness of third party review on low risk devices 
with tight FDA oversight, clear provisions relating to 
conflicts of interest, and clear FDA authority for final 
approval. To mandate that FDA fully implement an unproven 
concept for all devices is unacceptable.
    In addition to requiring third party review for all medical 
devices, the bills strips FDA of its functions and turns them 
over to private industry in other ways. Under section 404, if 
FDA fails to meet timeframes for review (established by the 
legislation) for 95% of the products within a particular 
product class, FDA is required to contract out review of all 
products in that class to private organizations in the 
following fiscal year, at the request of the product sponsor. 
Contracting out would be required even if doing so would 
increase review costs or even if quality could not be assured. 
In many product classes, failure to review just one drug or 
device within the statutory time frame could trigger mandatory 
contracting out. Over time, FDA would be drained of the 
resources it needs to continue as an effective regulatory body.
    Section 403 further requires FDA to contract out review of 
food additive petitions and premarket notifications for class I 
and class II devices. In addition, section 403 could be 
interpreted as creating a presumption in favor of contracting 
out aspects of review of all products.
    The immediate effect of these provisions will be to turn 
the job of approving new products over to private businesses, 
even though there is no evidence that private review will 
provide the public with the same level of protection as FDA 
review and even though the case for private review is based on 
an outdated description of agency performance. Not only will 
these businesses lack the expertise that FDA has built up over 
decades of experience, but in many cases the conflict of 
interest will be such that it will be impossible for the public 
to have any confidence in their decisions.
    The long-term effect of these provisions can only be fully 
understood in light of the fact that S.1477 creates new, 
unreasonable timeframes, not only for product reviews, but for 
numerous other agency actions, and imposes a series of new 
bureaucratic requirements on the agency. These additional 
requirements are established without providing any new 
resources for the agency. For example, the bill shortens the 
period of review for non-priority drugs and biologics that was 
negotiated by FDA, Congress, and the industry as part of the 
Prescription Drug User Fee Amendments in 1992, to six months 
(from a year) and thus requires FDA to treat priority and non-
priority, ``me-too'' products the same. Similarly, S. 1477 cuts 
in half--from 180 days to 90 days--the time FDA has to review 
indirect food additives and new animal drugs, including those 
used in food-producing animals, even through the safety of 
these substances is critical to the millions of Americans who 
consumer them on a daily basis.
    Without additional resources, FDA will be unable to meet 
these targets. In addition, as it strives to come closer to 
these goals without enough funds or personnel it may be forced 
to perform a less than thorough review. Further, as noted 
above, if FDA does not meet the timeframes, FDA must, at the 
request of the applicant, pay a third party to review a 
product--further bleeding the agency of the resources it needs 
to meet the deadlines. It is hard to see how this catch-22 
benefits the American consumer.
    S. 1477 makes it even more unlikely that FDA will be able 
to conduct timely, thorough review of products by hamstringing 
the agency with a host of new bureaucratic requirements. The 
bill imposes eighteen separate requirements to publish and 
implement new policies, regulations, or procedures. It 
establishes thirty-one new statutory deadlines, and elaborate 
statutory meeting requirements. While some of these 
requirements will contribute to greater collaboration, 
predictability, and efficiency, others will only tie the agency 
up and slow down more important work. Taken as a whole, these 
additional bureaucratic requirements will divert resources from 
essential activities to administrative work. To cite one 
particularly egregious example, the bill burdens scientific 
advisory committees with the responsibility considering any 
appeal of a scientific issue raised by a company. Under Section 
108, appeals can be made at any time--even if the agency 
decision is not final and even if the company has not gone 
through the agency's own internal appeal procedures.
    Currently, advisory committees are invaluable to FDA when 
it needs advice from the most distinguished outside experts on 
important decisions. Advisory committees only meet two to four 
times a year--typically for two days. The distinguished 
physicians and scientists serving on committees are essentially 
donating time from very busy schedules. A review of the 
advisory committee system by the Institute of Medicine 
concluded that one of the major problems FDA faced was 
attracting the best people to serve and prioritizing the issues 
that the experts needed to consider, given the limited time 
they had available. The provisions of this bill make it likely 
that so many additional, unnecessary matters will come to 
advisory committees that FDA will be able neither to attract 
top scientists to serve, nor to assure that they consider the 
most important and pressing questions.
    Turning over important FDA functions to the private sector 
and bleeding the agency of resources threatens public health in 
other ways. At the same time as FDA is forced to comply with 
numerous new bureaucratic requirements, it will lose the 
independent, committed, expert, public servants on whose work 
public safety depends. FDA will no longer have expertise (now 
developed through the review of product applications and 
conducting facility inspections) to be an effective post-
approval guardian. Yet post-market surveillance has repeatedly 
protected Americans from harm. Among the problem drugs that FDA 
post-market surveillance efforts identifies are Oraflex, 
Selacryn, Zomax, Merital, and Omniflox. Device surveillance has 
resulted in critical corrections to such devices as pacemakers, 
infant ventilators, and patient restraints and the withdrawal 
from the market of Orcolon, an eye gel that caused causes of 
blindness. Surveillance was responsible for identifying 
potentially fatal allergic reactions to sulfites, which are a 
common preservative in food, and putting in place a warning. 
FDA surveillance picked up counterfeit infant formula that 
would have injured infants if consumed.
    S. 1477 also requires FDA to give priority to products 
approved in Europe. Under section 404, the agency is mandated 
to review certain products approved in Europe within six months 
and make a final decision within 30 days at the request of the 
manufacturer once the six months has elapsed. No comparable 
treatment is provided for drugs which are submitted for 
approval for the first time in the United States. Thus, FDA is 
forced to give priority to products approved in Europe at the 
expense of potentially more important products submitted for 
the first time in the U.S. Not only does this potentially 
undermine public health, it encourages companies to do their 
research in Europe rather than the United States in order to 
secure a priority here. This requirement for priority to 
European-approved products is particularly inappropriate since, 
as described below, the U.S. now approves drugs more quickly, 
on average, than European countries, and FDA's safety record is 
far superior to foreign drug approval authorities.
    Section 607 suspends FDA's authority to implement 
requirements for pharmacists to provide consumer labeling for 
prescription drugs and limits its ability to oversee any 
voluntary program, if within 120 days of enactment, industry 
proposes its own program. However, the provisions contain 
little in the way of standards for this voluntary program and 
do not provide for any review to determine if the voluntary 
plan is adequate. Authority (but only to propose a rule) is 
only reinstated if HHS finds that the industry is not complying 
with its vaguely described voluntary program. It is also 
unclear what effect this provision could have on FDA's legal 
authority to require manufacturers to provide consumer 
labeling. At a time when hospitalizations from improper use of 
prescription drugs by senior citizens now cost Medicare $20 
billion a year, it seems foolish to hamstring FDA and count on 
voluntary efforts that have been promised but not delivered 
since 1980.
    In addition to these major issues, there are a number of 
other important problems with S. 1477 that should be addressed 
before the bill is considered by the full Senate. For example, 
the bill purports to codify the current expanded access 
regulations of FDA allowing patients to receive unapproved 
drugs on a humanitarian basis if no other treatment is 
available. While this program is a laudable one, the 
legislation appears to leave out key parts of the regulation 
allowing the Secretary to suspend expanded access if new 
information indicates that the drug may be doing more harm than 
good or for other reasons.
    The primary justification for radical reforms included in 
S. 1477 is that FDA is too slow to approve products, thereby 
denying patients needed treatment already available in foreign 
countries. Although there may have been some basis for this 
concern a decade ago, it is not valid today. FDA cut average 
time to approval by 40% between 1987 and 1992. According to the 
General Accounting Office, in 1994, the U.S. was reviewing 
drugs as fast as, or faster than Great Britain and other 
foreign countries. Since the Prescription Drug User Fee Act 
(PDUFA) was negotiated by FDA, Congress, and industry and 
passed in 1992, review times have dropped even farther. In 
fact, drug user fees have proved an overwhelming success. 
According to FDA, median time to approval dropped farther in 
1995. Moreover, under PDUFA, by FY 97, FDA was to be conducting 
a complete review 90% of applications for priority drugs within 
six months and other drugs within twelve months. By FY 95, FDA 
had already surpassed the 1997 goal--by conducting a complete 
review of 96% of applications within these time limits.
    Nor is there any ``treatment'' lag with other countries 
when it comes to drugs. Of 40 new drugs that offer significant 
therapeutic advances over existing products and that were 
approved in the United States, Great Britain, Germany, or Japan 
between 1990 and 1994, all were approved in the U.S. and more 
than half were approved in this country first. Every new AIDS 
drug was approved in the United States first, and FDA recently 
announced steps to bring promising new cancer drugs to the 
market even more rapidly. Unlike foreign approval authorities, 
FDA has successfully combined speed with safety. Between 1970 
and 1992, a total of 56 drugs were introduced in France, 
Germany, Great Britain, and the United States that subsequently 
had to be withdrawn because they were unsafe. Only 9 of these 
56 drugs had been approved in this country, compared to 31 in 
France, 30 in Germany, and 23 in Great Britain.
    The agency's successes with devices also demonstrates how 
committed FDA is to trying to achieve the balance between speed 
and consumer protection. During the late 1980's and early 
1990's, FDA was under a series of investigations by Congress as 
a result of various problematic medical devices (e.g., heart 
valves, pacemaker leads, infant apnea monitors), see, e.g., S. 
Rep. No. 513, 101st Cong., 2d Sess. (1990); H.R. Rep. No. 808, 
101st Cong., 2d Sess. (1990). It was then required to implement 
the provisions of the Safe Medical Devices Act of 1990. As a 
result, FDA review time for medical devices slowed down 
considerably. In the last Congress, a significant amount of 
work was done by Congress, FDA, and the medical advice industry 
to put together a device user fee package to give FDA the 
additional resources needed to improve device review times. 
Unfortunately, chances for user fee legislation fell apart when 
part of the industry refused to support the proposal.
    Nevertheless, even without the additional resources that 
user fees would have provided, FDA has successfully decreased 
median review times for premarket notifications, the premarket 
submission used for 98% of all devices, to 91 days, only one 
day shy of the 90 days in regulation, while the average review 
time is 138 days. At the end of FY 95 only 9 premarket 
notifications were active and overdue (past 90 days), as 
compared with 460 at the end of FY 94 and 1,894 at the end of 
FY 93.
    In addition to speeding up review times, FDA has exempted a 
significant number (about 75%) of class I devices from the 
premarket notification process. This frees up agency resources 
to review more important products and relieves manufacturers of 
those devices of a regulatory burden. FDA has also devoted 
significant resources to working with manufacturers, so that 
investigational device exemption (IDE) can be approved on their 
first submission and investigations can begin quickly. This has 
required frequent meetings and communication between FDA and 
industry to identify and resolve questions regarding the IDE. 
According to FDA's annual report, in FY 95, FDA approved 57% of 
IDEs the first time through, up from 35% in FY 94 and 27% in FY 
93. In order to accomplish this, FDA states it held more than 
200 pre-submission meetings with companies and reviewed more 
than 100 pre-IDE submissions.
    FDA is by no means perfect, but it is still renowned as one 
of the most effective consumer protection agencies in the 
world. Under the leadership of Dr. David Kessler, FDA has 
already accomplished many reforms that have brought Americans 
improved, high-quality medical care, and its record of 
excellence in protecting the health of the American public 
remain unmatched. While some provisions in S. 1477 would help 
FDA move forward, too much remains that will undermine FDA's 
ability to ensure public health and safety.
    We are prepared to work with Senator Kassebaum and others 
to modify S. 1477 so that it is truly a responsible, moderate 
reform program that will improve the public health. While we 
respect the good-faith efforts that have been made to date, we 
must oppose passage of S. 1477 in its current form.

                                   Edward Kennedy.
                                   Paul Simon.
                                   Claiborne Pell.
        ADDITIONAL VIEWS OF SENATORS DODD, MIKULSKI, AND HARKIN

    Legislation, in our view, is needed to improve the 
efficiency and effectiveness of the U.S. Food and Drug 
Administration. Recognizing that regulatory delays put lives at 
risk just as surely as undue haste, we believe there is much 
that can be done to speed the FDA approval process without harm 
to public health and safety. S. 1477 is a strong step in that 
direction.
    We also recognize that further improvements to this 
legislation can and should be made before it is approved by the 
Senate and enacted into law. If FDA reform is to succeed and 
truly help patients, the legislation must be bi-partisan and 
moderate. We are encouraged by the spirit of bi-partisanship so 
far in the process and hope it continues as the bill is taken 
up on the Senate floor.
    The Chairman has indicated her willingness to work with us 
on a number of key areas. These include, but are not limited 
to:
    1. Time Frames and Enforcement of Time Frames (Hammers). S. 
1477 sets strict timelines for the agency that they must meet 
by 1998. If the time frames are not met, FDA must contract out 
all products at the request of the manufacturer. It is our view 
that the goal of the legislation is to make the agency work 
more efficiently and meet timelines. We do not believe that 
mandatory contracting out will necessarily achieve this end. We 
are concerned that the legislation is setting up the agency to 
fail in certain product areas and could undermine the very 
successful Prescription Drug User Fee Act. We believe in a 
strong role for FDA and do not want to see all its work farmed 
out to private parties whose track record on timeliness, 
efficiency, and cost effectiveness is yet untested. We 
therefore hope to work on better measures to ensure that the 
agency improves its record.
    2. Manufacturing Changes. We understand that S. 1477 was 
intended to allow pharmaceutical and biological product 
manufacturers to make minor manufacturing changes without 
waiting for agency approval as long as the changes would not 
affect safety and effectiveness. The Committee acknowledged 
during mark up that the language in the bill did not adequately 
reflect the Committee's intent and we hope to work in a bi-
partisan manner to revise the language.
    3. Access to Unapproved Therapies. While we strongly 
support expanding the ability of patients to have access to 
unapproved therapies that are being tested, we want to ensure 
that the study of these therapies continues with due diligence.
    4. Off Label Dissemination of Information. The issue of 
dissemination of information on off label uses was taken out of 
the bill with the expectation that a compromise could be 
reached. While we see the value in greater flow of information 
to patients and doctors, we have serious concerns about the 
original language of the provision. These include the need to 
ensure that the information that is provided is balanced and 
that some incentive exists for manufacturers to continue to 
conduct research on off label uses to determine whether or not 
they are safe and effective. Although negotiations had been 
proceeding well on this issue, agreement was not reached.
    It is our hope to work with the Chairman and members of the 
Committee to work out these and other controversial provisions 
in the bill. It is our view that those who want a bill this 
year should be able to work out these issues and pass bi-
partisan legislation that truly helps patients.

                                   Chistopher J. Dodd.
                                   Tom Harkin.
                                   Barbara A. Mikulski.
                   ADDITIONAL VIEWS OF SENATOR HARKIN

    In additional to the views I share with Senators Dodd and 
Mikulski I believe that improvements should be made to the 
provisions in S. 1477 regarding third party review of medical 
devices. The third party review provisions were added during 
Committee consideration of the bill and described by proponents 
as a ``pilot'' to test whether the use of third party reviewers 
would reduce delays in medical device approvals. But, these 
provisions are very broad in scope and it is my hope that the 
``pilot'' can be narrowed to address the concerns outlined 
below.
    The ``pilot'' in S. 1477 does not limit in any way the 
number of third parties to be accredited nor the number and 
types of products to be reviewed outside the agency. I believe 
that a test of third party review should be limited to less 
complex devices that pose a smaller potential risk to patients 
should they malfunction. This simply makes common sense--test 
an unproven process in a manner that, regardless of outcome, 
poses the least possible risk to public health and safety.
    Provisions in S. 1477 do give FDA final product review 
decisions. However, I am concerned that given the time-frames 
for FDA action, substantive and meaningful review by FDA will 
be extremely difficult, if not impossible.
    In addition, under S. 1477 the manufacturer of the device 
selects the reviewer and also directly pays the reviewer. 
Direct payment by the manufacturer to the reviewer, without 
approval or even review by FDA, creates obvious conflicts of 
interests. In S. 1477 the FDA is charged with promulgating 
rules to prevent conflicts of interest but such conflicts are 
inherent in a system that allows the manufacturer to both 
select and directly pay the reviewer. I believe the Secretary 
should approve payment agreements.
    I am not opposed to a pilot project to determine the 
effectiveness of third party review of devices but such a pilot 
should be limited and should not include high risk or life-
sustaining devices. Only after third party review has proven to 
be effective in the review of low risk devices should it be 
expanded to include all medical devices.

                                                        Tom Harkin.
               ADDITIONAL VIEWS OF SENATOR PAUL WELLSTONE

    While I strongly support responsible reform of the U.S. 
Food and Drug Administration, I voted against S. 1477 because 
it included some provisions which I believe would undermine the 
ability of the FDA to protect the public health. Senator 
Kassebaum has indicated a serious willingness to work on these 
provisions before the bill reaches the Senate floor. I look 
forward to ultimately supporting S. 1477 as I believe the 
legislation includes a number of very important and 
constructive reforms. It is my hope that responsible FDA reform 
that would improve the effectiveness and the timeliness of the 
regulatory process while maintaining the safety standards that 
Americans count on everyday will be signed into law this year.
    FDA approval is recognized around the world as ``the gold 
standard''. This standard has opened markets, increased demand 
for U.S. products, and protected consumers. But beyond looking 
to the FDA to protect us from unsafe products, American 
patients need the FDA to do its job in a timely manner. The 
technologies that the FDA regulates are changing rapidly and 
dramatically. Americans cannot afford a regulatory system ill-
equipped to speed those advances.
    While the FDA has made great strides in implementing the 
Reinventing Government initiatives and expediting review for 
certain breakthrough drugs, these efforts must be consistent 
across other new products and for patients suffering from all 
types of debilitating and life-threatening illnesses.
    Many of the provisions in S. 1477 would take a serious step 
toward addressing Americans' concerns with the FDA. The 
legislation would improve the predictability, timeliness and 
focus of the regulatory process for medical products. The 
legislation would also improve communication and collaboration 
between the FDA and the regulated industries. I strongly 
endorse the view that these objectives can be met and 
unnecessary regulatory burdens can be minimized without 
compromising the quality of the review.

                     collaborative process reforms

    Because of my interest in achieving a more collaborative 
process, I strongly support provisions in the legislation to 
encourage collaboration at the early stages of product 
development. The bill requires the FDA to provide applicants 
the opportunity to meet with FDA officials to develop and agree 
in writing on a protocol for clinical studies. In addition, to 
facilitate collaboration and communication throughout the 
review process, the bill requires the FDA to provide for 
periodic meetings to ensure the applicants would be promptly 
informed of any deficiencies in their application and that 
questions could be addressed right away.
    Importantly, the committee imposed a structured PMA review 
cycle on the FDA to ensure that benchmarks define the 
timeliness of the agency's review effort for breakthrough 
medical devices. I believe that improved communication and 
collaboration during the review process will significantly 
improve timeliness and benefit both patients and the regulated 
industries.
    In addition, these important provisions would go a long way 
towards answering concerns about the predictability of the 
approval process for medical products. An inability to predict 
processes, costs, and outcomes is about the worst thing that 
government can impose on business. Companies--especially small 
companies--must be able to budget for the review process, 
predict the process, and know that they are being treated 
fairly. Currently, manufacturers say that decisions and 
requests for data and additional information are made in an 
arbitrary manner. I am convinced that both the FDA and the 
industry would like to make their working relationship less 
adversarial and more collaborative; these proposals would 
facilitate that goal. Improving predictability, collaboration 
and timeliness would lower medical product development costs 
and enable patients to access new technologies faster.

                         effectiveness standard

    I strongly endorse the committee's view that the standard 
proof of effectiveness for medical devices must be viewed as 
separate and distinct from that for new drugs. Unlike drugs, 
medical devices tend to evolve incrementally with new device 
generations often adding new therapeutic and diagnostic 
features. In determining the effectiveness of a device, the FDA 
should accept retrospective data and historical data as a 
control if data are available that meet the FDA's standards for 
quality and completeness and the effect of the device on 
disease progression is well understood. This would leave the 
FDA the discretion it needs to conduct randomized trials when 
necessary while at the same time reducing costly and time-
consuming requirements on applicants and enabling new and 
innovative technologies to reach patients in a more timely 
manner.

   recognition of performance standards to facilitate medical device 
                                reviews

    I strongly endorse the requirement that the FDA recognize 
nationally and internationally recognized consensus performance 
standards and accept certification by a manufacturer that a 
device conforms to such standards for the purpose of 
facilitating medical device review. Currently, the lack of 
clear performance standards for the review of Class II and III 
devices is a barrier to the improvement of the quality, 
timeliness, and predictability of the review process. In 
addition, the harmonization of performance standards for 
devices would promote international trade. The FDA would retain 
full authority to withdraw recognition of a performance 
standard and to approve or disapprove a premarket application 
or notification.

                          outstanding concerns

    Provisions of the legislation that I believe would 
undermine the ability of the FDA to protect the public and that 
must be addressed include first and foremost a requirement that 
the Agency contract out applications in a particular product 
category if the Agency has failed to meet the statutory 
deadline for action on at least 95% of the applications in the 
product category. While I absolutely agree that the Agency 
should be held accountable for consistently meeting statutory 
deadlines, I believe that this provision is unnecessarily harsh 
and could actually aggravate the ability of the Agency to meet 
its goals and seriously jeopardize the public health. Under 
this provision, contracting out would be required even if doing 
so would increase review costs or if the quality of product 
reviews by the private contractors could not be assured.
    I am also concerned about the elimination of the FDA's 
ability to require pre-approval for critical manufacturing 
changes to drugs and biologics under S. 1477. While I 
understand the benefit of allowing and encouraging companies to 
make improvements in their manufacturing processes without 
having to wait for FDA approval, the current language in the 
bill unacceptably weakens essential oversight of drug and 
biologic manufacturing.
    Because I believe it is essential that we explore new 
approaches to improving our medical device review process. I 
voted in favor of Senator Coats' amendment to require the FDA 
to establish a three year pilot for third party review of Class 
II and III medical devices. Clearly conflict of interest 
concerns about arise in a situation where manufacturers are 
directly paying a private organization for the review of their 
device. However, this amendment requires that the program be 
eliminated to a three year pilot, that the FDA accredit the 
pool of qualified third parties to conduct the reviews, that 
the manufacturer only be able to choose an accredited reviewer 
from a list pre-selected by the FDA, and that the FDA retain 
full authority to make final product review decisions, 
regardless of the third party decision. It should also be noted 
that the FDA has already initiated a third party review pilot 
for medical devices and has taken precautions to mitigate 
against conflict of interest concerns.
    While changes may need to be made to the Coats amendment to 
clarify the scope of the pilot and ensure that ``every device 
at CDRH'' is not eligible for third party review, the intent of 
this amendment was that the FDA gather meaningful data through 
the pilot and thus include more types of devices than the 
current pilot--as long as suitable third parties are available 
that meet the FDA's accreditation standards. At the end of the 
three year pilot the FDA and Congress should have the data they 
will need to be able to evaluate in a meaningful way the 
quality, timeliness, cost, and potential conflict of interest 
concerns of third party review.
    I am committed to working with Senator Kassebaum and other 
members of the Committee to address these concerns and to 
improving some of the other provisions of the bill that may 
still need work. I have a strong desire to see FDA reform 
legislation that has the confidence and support of the American 
people signed into law this year.

                                                 Paul D. Wellstone.
                      IX. Changes in Existing Law

    In compliance with rule XXVI paragraph 12 of the Standing 
Rules of the Senate, the following provides a print of the 
statute or the part or section thereof to be amended or 
replaced (existing law proposed to be omitted is enclosed in 
black brackets, new matter is printed in italic, existing law 
in which no change is proposed is shown in roman):

                  FEDERAL FOOD, DRUG, AND COSMETIC ACT

                         CHAPTER II--DEFINTIONS

    Sec. 201. [321] For the purposes of this Act--
    (a)(1) * * *
          * * * * * * *
    (gg) For purposes of reviewing any application or 
submission (including a petition, notification, or any other 
similar form of request), or any document, with respect to an 
article that is a new drug, device, biological product, new 
animal drug, an animal feed bearing or containing a new animal 
drug, color additive, or food additive that is submitted to the 
Secretary to obtain marketing approval, to obtain 
classification of a device under section 513(f)(1), or to 
establish or clarify the regulatory status of the article, the 
term ``day'' means a calendar day in which the Secretary has 
responsibility to review such a submission (excluding any 
calendar day between the date of receipt by the submitter of a 
written communication from the Secretary setting forth the 
action of the Secretary on a submission and the date of receipt 
by the Secretary of the written response of the submitter to 
the action).
    (hh) The term ``indirect food additive'' means a food 
additive that is intended to contact food but that is not 
intended for consumption as a food ingredient.
          * * * * * * *

               CHAPTER III--PROHIBITED ACTS AND PENALTIES

                            Prohibited Acts

    Sec. 301. [331] The following acts and the causing thereof 
are hereby prohibited:
    (a) * * *
          * * * * * * *
    (e) The refusal to permit access to or copying of any 
record as required by [section 412] section 412, 504, or 703; 
or the failure to establish or maintain any record, or make any 
report, required [under section 412,] under section 412, 504, 
505 (i) or (k), 507(d) or (g), 512(a)(4)(C), 512 (j), (l) or 
(m), 515(f), or 519 or the refusal to permit access to or 
verification or copying of any such required record.
          * * * * * * *

                            Misbranded Food

    Sec. 403. [343] A food shall be deemed to be misbranded--
    (a) * * *
          * * * * * * *
          (C) Notwithstanding the provisions of subparagraphs 
        (A)(i) and (B), a claim of the type described in 
        paragraph (1)(B) which is not authorized by the 
        Secretary in a regulation promulgated in accordance 
        with subparagraph (B) shall be authorized and may be 
        made if--
                  (i) an authoritative scientific body of the 
                United States Government with official 
                responsibility for public health protection or 
                research directly relating to human nutrition 
                (such as the National Institutes of Health or 
                the Centers for Disease Control and 
                Prevention), the National Academy of Sciences, 
                or subdivisions of the scientific body or the 
                National Academy of Sciences, has published 
                statements, conclusions, or recommendations in 
                effect recognizing that the relationship 
                between the nutrient and disease or health-
                related condition to which the claim refers is 
                supported by pertinent scientific evidence; and
                  (ii) the manufacturer or distributor of the 
                food for which such claim is made has submitted 
                to the Secretary at least 90 days before the 
                first introduction of such food into interstate 
                commerce a notice of claim, including a concise 
                description of the basis upon which such 
                manufacturer or distributor relied for 
                determining that the requirements of clause (i) 
                have been satisfied.
          * * * * * * *

                             food additives

                         Unsafe Food Additives

    Sec. 409. [348] (a) * * *
          * * * * * * *

                     Alternative Approval Procedure

    (j)(1) As an alternative to the approval procedure 
established under subsection (b), any person may submit a 
notification for an indirect food additive under this 
subsection.
    (2) Any person who proposes to begin the introduction or 
delivery for introduction into interstate commerce of an 
article intended for use as an indirect food additive may 
submit to the Secretary, at least 90 days prior to making such 
introduction or delivery, a notification containing information 
demonstrating that the labeled use of the article is safe.
    (3) Within 90 days after the receipt of the notification by 
the Secretary, the Secretary shall--
          (A) either--
                  (i)(I) approve the notification if the 
                article is safe for its intended use; or
                  (II) disapprove the notification if the 
                article has not been shown to be safe for its 
                intended use; and
          (B) publish a notice of this determination in the 
        Federal Register and, if the notification is approved, 
        promulgate an appropriate regulation pursuant to 
        subsection (c).
          * * * * * * *

                      CHAPTER V--DRUGS AND DEVICES

                    SUBCHAPTER A--DRUGS AND DEVICES

                     adulterated drugs and devices

    Sec. 501. [351] A drug or device shall be deemed to be 
adulterated--
    (a)(1) If it consists in whole or in part of any filthy, 
putrid, or decomposed substance; or (2)(A) if it has been 
prepared, packed, or held under insanitary conditions whereby 
it may have been contaminated with filth, or whereby it may 
have been rendered injurious to [health; or] health; (B) if it 
is a drug and the methods used in, or the facilities or 
controls used for, its manufacture, processing, packing or 
holding do not conform to or are not operated or administered 
in conformity with current good manufacturing practice to 
assure that such drug meets the requirements of this Act as to 
safety and has the identify and strength, and meets the quality 
and purity characteristics, which it purports or is represented 
to [possess;] possess; or (C) if it is a drug intended for use 
by animals other than man and the methods used in, or the 
facilities or controls used for, its manufacture, processing, 
packing, or holding do not conform to or are not operated or 
administered in conformity with current good manufacturing 
practice requirements (appropriate for animal drugs) adopted 
pursuant to regulations issued by the Secretary to ensure that 
such drug meets the requirements of this Act as to safety and 
has the identity and strength, and meets the quality and purity 
characteristics, which it purports or is represented to posses 
for use in animals other than man; or (3) if its container is 
composed, in whole or in part, of any poisonous or deleterious 
substance which may render the contents injurious to health; or 
(4) it bears or contains, for purposes of coloring only, a 
color additive which is unsafe within the meaning of section 
721(a), or (B) it is a color additive the intended use of which 
in or on drugs or devices is for purposes of coloring only and 
is unsafe within the meaning of section 721(a); or (5) if it is 
a new animal drug which is unsafe within the meaning of section 
512; or (6) if it is an animal feed bearing or containing a new 
animal drug, and such animal feed is unsafe within the meaning 
of section 512.
          * * * * * * *
    [(e)] (e)(1) If it is, or purports to be or is represented 
as, a device which is subject to a performance standard 
established under [section 514] section 514(b), unless such 
device is in all respects in conformity with such standard.
    (2) If it is, or purports to be or is represented as, a 
device which is certified to be in compliance with any 
voluntary standard recognized under section 514(c), unless such 
a device is in all respects in conformity with such a standard.
          * * * * * * *

exemptions and consideration for certain drugs, devices, and biological 
                                products

    Sec. 503. [353] (a) * * *
          * * * * * * *
    (f)(1)(A) A drug intended for use by animals [other than 
man] other than man, other than a veterinary feed directive 
drug intended for use in animal feed or an animal feed bearing 
or containing a veterinary feed directive drug,
          * * * * * * *


                    veterinary feed directives drugs


    Sec. 504. (a)(1) A drug intended for use in or on animal 
feed that is limited by an approved application filed pursuant 
to section 512(b) to use under the professional supervision of 
a licensed veterinarian is a veterinary feed directive drug. 
Any animal feed bearing or containing a veterinary feed 
directive drug shall be fed to animals only by or upon the 
lawful veterinary feed directive issued by a licensed 
veterinarian in the course of the professional practice of the 
veterinarian. When labeled, distributed, held, and used in 
accordance with this section, a veterinary feed directive drug 
and any animal feed bearing or containing a veterinary feed 
directive drug shall be exempt from section 502(f).
    (2) A veterinary feed directive is lawful if it--
          (A) contains such information as the Secretary may, 
        by general regulation or by order, require; and
          (B) is in compliance with the conditions and 
        indications for use of the drug set forth in the notice 
        published pursuant to section 512(i).
    (3)(A) Any persons involved in the distribution or use of 
animal feed bearing or containing a veterinary feed directive 
drug, and the licensed veterinarian issuing the veterinary feed 
directive, shall maintain a copy of the veterinary feed 
directive applicable to each such feed, except in the case of a 
person distributing such feed to another person for further 
distribution, such person distributing the feed shall maintain 
a written acknowledgment from the person to whom the feed is 
shipped stating that that person shall not ship or move such 
feed to an animal production facility without a veterinary feed 
directive or ship such feed to another person for further 
distribution unless that person has provided the same written 
acknowledgment to the immediate supplier of that person.
    (B) Every person required under the subparagraph (A) to 
maintain records, and every person in charge or custody 
thereof, shall, upon request of an officer or employee 
designated by the Secretary, permit such officer or employee at 
all reasonable times to have access to and copy and verify such 
records.
    (C) Any person who distributes animal feed bearing or 
containing a veterinary feed directive drug shall upon first 
engaging in such distribution notify the Secretary of the name 
and place of business of that person. The failure to provide 
such notification shall be deemed to be an act which results in 
the drug being misbranded.
    (b) A veterinary feed directive drug and any feed bearing 
or containing a veterinary feed directive drug shall be deemed 
to be misbranded if the drug and feed labeling fails to bear 
such cautionary statement and such other information as the 
Secretary may, by general regulation or by order, prescribe, or 
the drug and feed advertising fails to conform to the 
conditions and indications for use published pursuant to 
section 512(i) or fails to contain the general cautionary 
statement prescribed by the Secretary.
    (c) Neither a drug subject to this section, nor animal feed 
bearing or containing such a drug, shall be deemed to be a 
prescription article under any Federal or State law.

                               new drugs

    Sec. 505. [355] (a) * * *
          * * * * * * *
    (c)(1) * * *
          * * * * * * *
In a case in which an application is submitted under subsection 
(b)(1) for a new drug, or section 351(a) of the Public Health 
Service Act for a biological product, that is intended for use 
for an immediately life-threatening or serious disease or 
condition and that provides therapy or diagnosis not available 
from another approved drug or biological product or offers 
significant improvement over another approved drug or 
biological product, the Secretary shall approve or deny 
approval of the application within 180 days after the receipt 
of the application.
          * * * * * * *
  (4) A new drug or biological product manufactured in a pilot 
or other small facility may be used to demonstrate the safety 
and effectiveness of the drug or product and to obtain approval 
prior to scaling up to a larger facility, unless the Secretary 
demonstrates in writing and specifies in detail the reasons, 
after an informal hearing, that a full scale production 
facility is necessary to ensure the safety or effectiveness of 
the drug or product.
    (d) If the Secretary finds, after due notice to the 
applicant in accordance with subsection (c) and giving him an 
opportunity for a hearing, in accordance with said subsection, 
that (1) the investigations, reports of which are required to 
be submitted to the Secretary pursuant to subsection (b), do 
not include adequate tests by all methods reasonably applicable 
to show whether or not such drug is safe for use under the 
conditions prescribed, recommended, or suggested in the 
proposed labeling thereof; (2) the results of such tests show 
that such drug is unsafe for use under such conditions or do 
not show that such drug is safe for use under such conditions; 
(3) the methods used in, and the facilities and controls used 
for, the manufacture, processing, and packing of such drug are 
inadequate to preserve its identity, strength, quality, and 
purity; (4) upon the basis of the information submitted to him 
as part of the application, or upon the basis of any other 
information before him with respect to such drug, he has 
insufficient information to determine whether such drug is safe 
for use under such conditions; or (5) evaluated on the basis of 
the information submitted to him as part of the application and 
any other information before him with respect to such drug, 
there is a lack of substantial evidence that the drug will have 
the effect it purports or is represented to have under the 
conditions of use prescribed, recommended, or suggested in the 
proposed labeling thereof; or (6) the application failed to 
contain the patent information prescribed by subsection (b); or 
(7) based on a fair evaluation of all material facts, such 
labeling is false or misleading in any particular; he shall 
issue an order refusing to approve the application. If, after 
such notice and opportunity for hearing, the Secretary finds 
that clauses (1) through (6) do not apply, he shall issue an 
order approving the application. As used in this subsection and 
subsection (e), the term ``substantial evidence'' means 
evidence consisting of adequate and well-controlled 
investigations, including clinical investigations, by experts 
qualified by scientific training and experience to evaluate the 
effectiveness of the drug involved, on the basis of which it 
could fairly and responsibly be concluded by such experts that 
the drug will have the effect it purports or is presented to 
have under the conditions of use prescribed, recommended, or 
suggested in the labeling or proposed labeling thereof. 
Substantial evidence may consist of data from 1 well-controlled 
clinical investigation and confirmatory evidence obtained prior 
to, or after, such investigation.
          * * * * * * *
    [(i) The] (i)(1) The Secretary shall promulgate regulations 
for exempting from the operation of the foregoing subsections 
of this section drugs intended solely for investigational use 
by experts qualified by scientific training and experience to 
investigate the safety and effectiveness of drugs. Such 
regulations may, within the discretion of the Secretary, among 
other conditions relating to the protection of the public 
health, provide for conditioning such exemption upon--
          [(1)] (A) the submission to the Secretary, before any 
        clinical testing of a new drug is undertaken, of 
        reports, by the manufacturer or the sponsor of the 
        investigation of such drug, or preclinical tests 
        (including tests on animals) of such drug adequate to 
        justify the proposed clinical testing;
          [(2)] (B) the manufacturer or the sponsor of the 
        investigation of a new drug proposed to be distributed 
        to investigators for clinical testing obtaining a 
        signed agreement from each of such investigators that 
        patients to whom the drug is administered will be under 
        his personal supervision, or under the supervision of 
        investigators responsible to him, and that he will not 
        supply such drug to any other investigator, or to 
        clinics, for administration to human beings; and
          [(3)] (C) the establishment and maintenance of such 
        records, and the making of such reports to the 
        Secretary, by the manufacturer or the sponsor of the 
        investigation of such drug, of data (including but not 
        limited to analytical reports by investigators) 
        obtained as the result of such investigational use of 
        such drug, as the Secretary finds will enable him to 
        evaluate the safety and effectiveness of such drug in 
        the event of the filing of an application pursuant to 
        subsection (b).
          * * * * * * *
    (2)(A) A clinical investigation of a new drug (including a 
biological product) may begin 30 days after the date on which 
the Secretary receives from the sponsor of the investigation a 
notification containing information about the drug and the 
clinical investigation unless, prior to the 30-day period, the 
Secretary informs the sponsor in writing that the investigation 
may not begin, and specifies the basis for the decision and the 
information needed in order for the clinical investigation to 
commence.
    (B) Not later than 1 year after the date of enactment of 
the Food and Drug Administration Performance and Accountability 
Act of 1996, the Secretary, after consultation with experts in 
the development, clinical investigation, and regulation of 
drugs, physicians and other health care practitioners, and 
representatives of patient and consumer advocacy groups and the 
regulated industries, shall publish in the Federal Register 
criteria for the type and amount of information relating to the 
safety of an investigational drug to be included in a 
notification described in subparagraph (A). In the 
establishment of the criteria, the Secretary shall take into 
account the recommendations of the International Conference on 
Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use. The Secretary shall periodically 
review, and may revise, the criteria.
    (C) The Secretary shall establish a mechanism to ensure the 
fair and consistent application of safety standards for 
clinical investigations.
    (3)(A) The Secretary may place a clinical hold on any 
ongoing clinical investigation if the Secretary determines that 
such action is necessary for the protection of human subjects.
    (B) If the Secretary places a clinical hold on a clinical 
investigation, the Secretary shall immediately advise the 
sponsor for the investigation in writing of such action, and 
provide the sponsor an opportunity to meet with the Secretary 
not later than 10 business days after the receipt of such a 
communication to discuss the clinical hold. Not later than 10 
days after such a meeting, the Secretary shall provide to the 
sponsor in writing the conditions for the withdrawal of the 
clinical hold. Any written request received by the Secretary 
from the sponsor requesting that a clinical hold be removed 
shall receive a decision, in writing and specifying the reasons 
therefor, not later than 20 days after the receipt of the 
request.
          * * * * * * *

SEC. 505A. PEDIATRIC STUDIES FOR NEW DRUG APPLICATIONS.

    (a) Market Exclusivity for Approved Applications With 
Pediatric Studies Submitted by an Applicant.--If an application 
submitted under section 505(b)(1) is approved on or after the 
date of enactment of this section, and such application 
includes reports of pediatric studies described and requested 
in subsection (c), and such studies are completed and the 
reports thereof submitted in accordance with subsection (c)(2) 
or completed and the reports thereof accepted in accordance 
with subsection (c)(3), the Secretary may not make the approval 
of an application submitted under section 505(b)(2) or 505(j) 
that refers to the drug for which the section 505(b)(1) 
approval is granted effective prior to the expiration of 6 
months from the earliest date on which the approval of such 
application for the drug under section 505(b)(2) or 505(j), 
respectively, could otherwise be made effective under the 
applicable provisions of this chapter.
    (b) Market Exclusivity for Approved Applications With 
Pediatric Studies Requested by the Secretary.--If the Secretary 
makes a written request for pediatric studies described in 
subsection (c) to the holder of an approval under section 
505(b)(1) for a drug, and such studies are completed and the 
reports thereof submitted in accordance with subsection (c)(2) 
or completed and the reports thereof accepted in accordance 
with subsection (c)(3), the Secretary may not make the approval 
of an application submitted under section 505(b)(2) or 505(j) 
that refers to the drug subject to the section 505(b)(1) 
approval effective prior to the expiration of 6 months from the 
earliest date on which an approval of such application under 
section 505(b)(2) or 505(j), respectively, could otherwise be 
made effective under the applicable provisions of this chapter. 
Nothing in this subsection shall affect the ability of the 
Secretary to make effective a section 505(b)(2) or 505(j) 
approval for a subject drug if such approval is proper under 
such section and is made effective prior to the submission of 
the reports of pediatric studies described in subsection (c).
    (c) Conduct of Pediatric Studies.--
          (1) Agreement for studies.--The Secretary may, 
        pursuant to a written request for studies after 
        consultation with the sponsor of an application or 
        holder of an approval for a drug under section 
        505(b)(1), agree with the sponsor or holder concerning 
        the conduct of pediatric studies for such drug.
          (2) Written protocols to meet the studies 
        requirement.--If the sponsor or holder and the 
        Secretary agree upon written protocols for such 
        studies, the studies requirement of subsection (a) or 
        (b) is satisfied upon the completion of the studies in 
        accordance with the protocols and the submission of the 
        reports thereof to the Secretary. Not later than 60 
        days after the submission of the report of the studies, 
        the Secretary shall determine if such studies were or 
        were not conducted in accordance with the written 
        protocols and reported in accordance with the 
        requirements of the Secretary for filing and so notify 
        the sponsor or holder.
          (3) Other methods to meet the studies requirement.--
        If the sponsor or holder and the Secretary have not 
        agreed in writing on the protocols for the studies, the 
        studies requirement of subsection (a) or (b) is 
        satisfied when such studies have been completed and the 
        reports accepted by the Secretary. Not later than 90 
        days after the submission of the reports of the 
        studies, the Secretary shall accept or reject such 
        reports and so notify the sponsor or holder. The 
        Secretary's only responsibility in accepting or 
        rejecting the reports shall be to determine, within 90 
        days, that the studies fairly respond to the written 
        request, that such studies have been conducted in 
        accordance with commonly accepted scientific principles 
        and protocols, and that such studies have been reported 
        in accordance with the requirements of the Secretary 
        for filing.
    (d) Delay of Effective Date for Certain Applications; 
Period of Market Exclusivity.--If the Secretary determines that 
an approval of an application under section 505(b)(2) or 505(j) 
for a drug may be made effective after submission of reports of 
pediatric studies under this section but before the Secretary 
has determined whether the requirements of subsection (c) have 
been satisfied, the Secretary may delay the effective date of 
any approval under section 505(b)(2) or 505(j), respectively, 
until the determination under subsection (c) is made, but such 
delay shall not exceed 90 days. In the event that the 
requirements of this section are satisfied, the 6-month period 
referred to in subsection (a) or (b) shall be deemed to have 
begun on the date an approval of an application under section 
505(b)(2) or 505(j), respectively, would have been permitted 
absent action under this subsection.
    (e) Notice of Determinations on Studies Requirement.--The 
Secretary shall publish notice of any determination that the 
requirements of paragraph (2) or (3) of subsection (c) have 
been met and that approvals under section 505(b)(2) or section 
505(j) for a drug will be subject to deferred effective dates 
under this section.
    (f) Definitions.--As used in this section, the term 
`pediatric studies' or `studies' means at least 1 human 
clinical investigation in a population of adolescent age or 
younger. At the Secretary's discretion, pharmacokinetic studies 
may be considered as clinical investigations.

               [CERTIFICATION OF DRUGS CONTAINING INSULIN

    [Sec. 506. [356] (a) The Secretary, pursuant to regulations 
promulgated by him, shall provide for the certification of 
batches of drugs composed wholly or partly of insulin. A batch 
of any such drug shall be certified if such drug has such 
characteristics of identity and such batch has such 
characteristics of strength, quality, and purity, as the 
Secretary prescribes in such regulations as necessary to 
adequately insure safety and efficacy of use, but shall not 
otherwise be certified. Prior to the effective date of such 
regulations the Secretary, in lieu of certification, shall 
issue a release for any batch which, in his judgment, may be 
released without risk as to the safety and efficacy of its use. 
Such release shall prescribe the date of its expiration and 
other conditions under which it shall cease to be effective as 
to such batch and as to portions thereof.
    [(b) Regulations providing for such certification shall 
contain such provisions as are necessary to carry out the 
purposes of this section, including provisions prescribing (1) 
standards of identity and of strength, quality, and purity; (2) 
tests and methods of assay to determine compliance with such 
standards; (3) effective periods for certificates, and other 
conditions under which they shall cease to be effective as to 
certified batches and as to portions thereof; (4) 
administration and procedure; and (5) such fees, specified in 
such regulations, as are necessary to provide, equip, and 
maintain an adequate certification service. Such regulations 
shall prescribe no standard of identity or of strength, 
quality, or purity for any drug different from the standard of 
identity, strength, quality, or purity set forth for such drug 
in official compendium.
    [(c) Such regulations, insofar as they prescribe tests or 
methods of assay to determine strength, quality, or purity of 
any drug, different from the tests or methods of assay set 
forth for such drug in an official compendium, shall be 
prescribed, after notice and opportunity for revision of such 
compendium, in the manner provided in the second sentence of 
section 501(b). The provisions of subsections (e), (f), and (g) 
of section 701 shall be applicable to such portion of any 
regulation as prescribes any such different test or methods, 
but shall not be applicable to any other portion of any such 
regulation.

                     [certification of antibiotics

    [Sec. 507. [537] (a) The Secretary, pursuant to regulations 
promulgated by him, shall provide for the certification of 
batches of drugs (except drugs for use in animals other than 
man) composed wholly or partly of any kind of penicillin, 
streptomycin, chlortetracycline, chloramphenicol, bacitracin, 
or any other antibiotic drug, or any derivative thereof. A 
batch of any such drug shall be certified if such drug has such 
characteristics of identity and such batch has such 
characteristics of strength, quality, and purity, as the 
Secretary prescribes in such regulations as necessary to 
adequately insure safety and efficacy of use, but shall not 
otherwise be certified. Prior to the effective date of such 
regulations the Secretary, in lieu of certification, shall 
issue a release for any batch which, in his judgment, may be 
released without risk as to the safety and efficacy of its use. 
Such release shall prescribe the date of its expiration and 
other conditions under which it shall cease to be effective as 
to such batch and as to portions thereof. For purposes of this 
section and of section 502(l), the term ``antibiotic drug'' 
means and drug intended for use by man containing any quantity 
of any chemical substance which is produced by a micro-organism 
and which has the capacity to inhibit or destroy micro-
organisms in dilute solution (including the chemically 
synthesized equivalent of any such substance).
    [(b) Regulations providing for such certifications shall 
contain such provisions as are necessary to carry out the 
purposes of this section, including provisions prescribing (1) 
standards of identity and of strength, quality, and purity; (2) 
tests and methods of assay to determine compliance with such 
standards; (3) effective periods for certificates, and other 
conditions under which they shall cease to be effective as to 
certified batches and as to portions thereof; (4) 
administration and procedure; and (5) such fees, specified in 
such regulations, as are necessary to provide, equip, and 
maintain an adequate certification service. Such regulations 
shall prescribe only such tests and methods of assay as will 
provide for certification or rejection within the shortest time 
consistent with the purposes of this section.
    [(c) Whenever in the judgment of the Administrator, the 
requirements of this section and of section 502(l) with respect 
to any drug or class of drugs are not necessary to insure 
safety and efficacy of use, the Administrator \1\ shall 
promulgate regulations exempting such drug or class of drugs 
from such requirements. In deciding whether an antibiotic drug, 
or class of antibiotic drugs, is to be exempted from the 
requirement of certification the Secretary shall give 
consideration, among other relevant factors, to--
          [(1) whether such drug or class of drugs is 
        manufactured by a person who has, or hereafter shall 
        have, produced fifty consecutive batches of such drug 
        or class of drugs in compliance with the regulations 
        for the certification therefore within a period of not 
        more than eighteen calendar months, upon the 
        application by such person to the Secretary; or
          [(2) whether such drug or class of drugs is 
        manufactured by any person who has otherwise 
        demonstrated such consistency in the production of such 
        drug or class of drugs, in compliance with the 
        regulations for the certification thereof, as in the 
        judgment of the Secretary is adequate to endure the 
        safety and efficacy of use thereof.
When an antibiotic drug or a drug manufacturer has been 
exempted from the requirement of certification, the 
manufacturer may still obtain certification of a batch or 
batches of that drug if he applies for an meets the 
requirements for certification. Nothing in this Act shall be 
deemed to prevent a manufacturer or distributor of an 
antibiotic drug from making a truthful statement in labeling or 
advertising of the product as to whether it has been certified 
or exempted from the requirement of certification.
    [(d) The Administrator shall promulgate regulations 
exempting from any requirement of this section and of section 
502(l), (1) drugs which are to be stored, processed, labeled, 
or repacked at establishments other than those where 
manufactured, on condition that such drugs comply with all such 
requirements upon removal from such establishments; (2) drugs 
which conform to applicable standards of identity, strength, 
quality, and purity prescribed by these regulations and are 
intended for use in manufacturing other drugs; and (3) drugs 
which are intended solely for investigational use by experts 
qualified by scientific training and experience to investigate 
the safety and efficacy of drugs. Such regulations may, within 
the discretion of the Secretary, among other conditions 
relating to the protection of the public health, provide for 
conditioning the exemption under clause (3) upon--
          [(1) the submission to the Secretary, before any 
        clinical testing of a new drug is undertaken, of 
        reports, by the manufacturer or the sponsor of the 
        investigation of such drug, of preclinical tests 
        (including tests on animals) of such drug adequate to 
        justify the proposed clinical testing;
          [(2) the manufacturer or the sponsor of the 
        investigation of a new drug proposed to be distributed 
        to investigators for clinical testing obtaining a 
        signed agreement from each of such investigators that 
        patients to whom the drug is administered will be under 
        his personal supervision, or under the supervision of 
        investigators responsible to him, and that he will not 
        supply such drug to any other investigator, or to 
        clinics, for administration to human beings; and
          [(3) the establishment and maintenance of such 
        records, and the making of such reports to the 
        Secretary, by the manufacturer or the sponsor of the 
        investigation of such drug, of data (including but not 
        limited to analytical reports by investigators) 
        obtained as the result of such investigational use of 
        such drug, as the Secretary finds will enable him to 
        evaluate the safety and effectiveness of such drug in 
        the event of the filing of an application for 
        certification or release pursuant to subsection (a).
Such regulations shall provide that such exemption shall be 
conditioned upon the manufacturer, or the sponsor of the 
investigation, requiring that experts using such drugs for 
investigational purposes certify to such manufacturer or 
sponsor that they will inform any human beings to whom such 
drugs, or any controls used in connection therewith, are being 
administered, or their representatives, that such drugs are 
being used for investigational purposes and will obtain the 
consent of such human beings or their representatives, except 
where they deem it not feasible or, in their professional 
judgment, contrary to the best interests of such human beings. 
Nothing in this subsection shall be construed to require any 
clinical investigator to submit directly to the Secretary 
reports on the investigational use of drugs.
    [(e) No drug which is subject to this section shall be 
deemed to be subject to any provision of section 505 except a 
new drug exempted from the requirements of this section and of 
section 502(l) pursuant to regulations promulgated by the 
Secretary. For purposes of section 505, the initial request for 
certification, as thereafter duly amended, pursuant to this 
section, of a new drug so exempted shall be considered a part 
of the application filed pursuant to section 505(b) with 
respect to the person filing such request and to such drug as 
of the date of the exemption. Compliance of any drug subject to 
section 502(l) or this section with section 501(b) and 502(g) 
shall be determined by the application of the standards of 
strength, quality, and purity, the tests and methods of assay, 
and the requirements of packaging, and labeling, respectively, 
prescribed by regulations promulgated under this section.
    [(f) Any interested person may file with the Administrator 
a petition proposing the issuance, amendment, or repeal of any 
regulation contemplated by this section. The petition shall set 
forth the proposal in general terms and shall state reasonable 
grounds therefor. The Administrator shall give public notice of 
the proposal and an opportunity for all interested persons to 
present their views thereon, orally or in writing, and as soon 
as practicable thereafter shall make public his action upon 
such proposal. At any time prior to the thirtieth day after 
such action is made public any interested person may file 
objections to such action, specifying with particularity the 
changes desired, stating reasonable grounds therefor, and 
requesting a public hearing upon such objections. The 
Administrator shall thereupon, after due notice, hold such 
public hearing. As soon as practicable after completion of the 
hearing, the Administrator shall by order make public his 
action on such objections. The Administrator shall base his 
order only on substantial evidence of record at the hearing and 
shall set forth as part of the order detailed findings of fact 
on which the order is based. The order shall be subject to the 
provision of section 701 (f) and (g).
    [(g)(1) Every person engaged in manufacturing, compounding, 
or processing any drug within the purview of this section with 
respect to which a certificate or release has been issued 
pursuant to this section shall establish and maintain such 
records, and make such reports to the Secretary, of data 
relating to clinical experience and other data or information, 
received or otherwise obtained by such person with respect to 
such drug, as the Secretary may by general regulation, or by 
order with respect to such certification or release, prescribe 
on the basis of a finding that such records and reports are 
necessary in order to enable the Secretary to make, or to 
facilitate, a determination as to whether such certification or 
release should be rescinded or whether any regulation issued 
under this section should be amended or repealed. Regulations 
and orders issued under this subsection and under clause (3) of 
subsection (d) shall have due regard for the professional 
ethics of the medical profession and the interests of patients 
and shall provide, where the Secretary deems it to be 
appropriate, for the examination, upon request, by the persons 
to whom such regulations or orders are applicable, of similar 
information received or otherwise obtained by the Secretary.
    [(2) Every person required under this section to maintain 
records, and every person having charge or custody thereof, 
shall, upon request of an officer or employee designated by the 
Secretary, permit such officer or employee at all reasonable 
times to have access to and copy and verify such records.
    [(h) In the case of a drug for which, on the day 
immediately preceding the effective date of this subsection, a 
prior approval of an application under section 505 had not been 
withdrawn under section 505(e), the initial issuance of 
regulations providing for certification or exemption of such 
drug under this section shall, with respect to the conditions 
of use prescribed, recommended, or suggested in the labeling 
covered by such application, not be conditioned upon an 
affirmative finding of the efficacy of such drug. Any 
subsequent amendment or repeal of such regulations so as no 
longer to provide for such certification or exemption on the 
ground of a lack of efficacy of such drug for use under such 
conditions of use may be effected only on or after that 
effective date of clause (3) of the first sentence of section 
505(e) which would be applicable to such drug under such 
conditions of use if such drug were subject to section 505(e), 
and then only if (1) such amendment or repeal is made in 
accordance with the procedure specified in subsection (f) of 
this section (except that such amendment or repeal may be 
initiated either by a proposal of the Secretary or by a 
petition of any interested person) and (2) the Secretary finds, 
on the basis of new information with respect to such drug 
evaluated together with the information before him when the 
application under section 505 became effective or was approved, 
that there is a lack of substantial evidence (as defined in 
section 505(d)) that the drug has the effect it purports or is 
represented to have under such conditions of use.]

             registration of producers of drugs and devices

    Sec. 510. [360] (a) As used in this section--
          * * * * * * *
    (k) Each person who is required to register under this 
section and who proposes to begin the introduction or delivery 
for introduction into interstte commerce for commercial 
distribution of a device [intended for human use] intended for 
human use (except a device that is classified inot class I 
under section 513 or 520 and is not identified in a list under 
subsection (n), or a device that is classified into class II 
under section 513 or 520 and is except from the requirements of 
this subsection under subsection (l)) shall, at least ninety 
days before making such introduction or delivery, [report to] 
shall notify the Secretary to report to the Secretary (in such 
form and manner as the Secretary shall by regulation 
prescribe)--
          * * * * * * *
The Secretary shall review the notification required by this 
subsection and make a determination under section 513(f)(1)(A) 
within 90 days of receiving the notification.
    (l) Not later than 30 days after the date of enactment of 
this subsection, the Secretary shall publish in the Federal 
Register a list of each type of class II device that does not 
require a notification under subsection (k) to provide 
reasonable assurance of safety and effectiveness. Each type of 
class II device so identified by the Secretary not to require 
the notification shall be exempt from the requirement to 
provide notification under subsection (k) as of the date of the 
publication of the list in the Federal Register. Beginning on 
the date that is 1 day after the date of the publication of a 
list under this subsection, any person may petition the 
Secretary to exempt a type of class II device from the 
notification requirement of subsection (k). The Secretary shall 
respond to the petition within 120 days of the receipt of the 
petition and determine whether or not to grant the petition in 
whole or in part.
    (m) The Secretary may not withhold a determination of the 
initial classification of a device under section 513(f)(1) 
because of a failure to comply with any provision of this Act 
unrelated to a substantial equivalent decision, including a 
failure to comply with good manufacturing practices under 
section 520(f).
    (n) Not later than 15 days after the date of enactment of 
this subsection, the Secretary shall publish in the Federal 
Register a list of each type of class I device that shall not 
be considered exempt from the notification requirement of 
section 510(k) because such notification is necessary to 
protect the public health. If the Secretary fails to publish 
the list within 15 days after the date of enactment of this 
subsection, all types of class I devices shall be exempt from 
the requirement to provide notification under subsection 
510(k).
          * * * * * * *

                            New Animal Drugs

    Sec. 512. [306b] (a)(1) * * *
          * * * * * * *
          (C) such animal feed, [its labeling] its labeling, 
        its distribution, its holding, and such use conform to 
        the conditions and indications of use published 
        pursuant to subsection (i) of this section and to the 
        application with respect thereto approved under 
        subsection (m) of this section.
          * * * * * * *
    (c)(1) Within [one hundred and eighty] 90 days after the 
filing of an application pursuant to subsection (b), or such 
additional period as may be agreed upon by the Secretary and 
the applicant, the Secretary shall either (A) issue an order 
approving the application if he then finds that none of the 
grounds for denying approval specified in subsection (d) 
applies, or (B) give the applicant notice of an opportunity for 
a hearing before the Secretary under subsection (d) on the 
question whether such application is approvable. If the 
applicants elects to accept the opportunity for a hearing by 
written request within thirty days after such notice, such 
hearing shall commence not more than ninety days after the 
expiration of such thirty days unless the Secretary and the 
applicant otherwise agree. Any such hearing shall thereafter be 
conducted on an expedited basis and the Secretary's order 
thereon shall be issued within ninety days after the date fixed 
by the Secretary for filing final briefs.
          * * * * * * *
                  (iii) If a supplement to an application 
                approved under subsection (b)(1) is approved 
                after the date of enactment of this paragraph 
                and the supplement contains [reports of new 
                clinical or field investigations (other than 
                bioequivalence or residue studies) and] 
                substnatial evidence of effectiveness as 
                defined in subsection (d)(4), any study of 
                animal safety, or, in the case of food 
                producing animals, human food safety studies 
                (other than bioequivalence or residue studies) 
                [essential to] required for the approval of the 
                supplement and conducted or sponsored by the 
                person submitting the supplement, the Secretary 
                may not make the approval of an application 
                submitted under subsection (b)(2) for a change 
                approved in the supplement effective before the 
                expiration of 3 years from the date of the 
                approval of the supplement.
          * * * * * * *
    (d)(1) * * *
          * * * * * * *
          [(F) upon the basis of the information submitted to 
        him as part of the application or any other information 
        before him with respect to such drug, the tolerance 
        limitation proposed, if any, exceeds that reasonably 
        required to accomplish the physical or other technical 
        effect for which the drug is intended;]
          (F) on the basis of information submitted to the 
        Secretary as part of the application or any other 
        information before the Secretary with respect to such 
        drug, any use prescribed, recommended, or suggested in 
        labeling proposed for such drug will result in a 
        residue of such drug in excess of a tolerance found by 
        the Secretary to be safe for such drug;
          * * * * * * *
he shall issue an order refusing to approve the application, 
If, after such notice and opportunity for hearing, the 
Secretary finds that subparagraphs (A) through (I) do not 
apply, he shall issue an order approving the application. 
Subparagraph (E) shall not apply to a claim for use of the drug 
described in subparagraph (E) in a minor species, or for a 
minor use of the drug, as the terms ``minor species'' and 
``minor use'' are defined in regulations issued by the 
Secretary, if there is an application filed under subsection 
(b) for the drug, and the application is approved, prior to the 
submission of the claim.
          * * * * * * *
    [(3) As used in this subsection and subsection (e), the 
term ``substantial evidence'' means evidence consisting of 
adequate and well-controlled investigations, including field 
investigation, by experts qualified by scientific training and 
experience to evaluate the effectiveness of the drug involved, 
on the basis of which it could fairly and reasonably be 
concluded by such experts that the drug will have the effect it 
purports or is represented to have under the conditions of use 
prescribed, recommended, or suggested in the labeling or 
proposed labeling thereof.
    (3) In a case in which a new animal drug contains more than 
1 active ingredient, or the labeling of the drug prescribes, 
recommends, or suggests use of the drug in combination with 
another animal drug, and the active ingredients or drugs in the 
combination have been separately approved for particular uses 
and species prior to the approval of the application for the 
same uses and species in combination (or, in the absence of 
such approvals, after evaluating the safety and efficacy of the 
combination itself), the Secretary may only consider with 
respect to the combination whether any of the active 
ingredients or any of the drugs in the combination, 
respectively, at the longest withdrawal time of any of the 
active ingredients or drugs in the combination, respectively--
          (A) is above its safe concentration (such as 
        exceeding its established tolerance, as measured by its 
        marker residue); or
          (B) interferes with the methods of analysis for 
        another of the active ingredients or drugs in the 
        combination, respectively.
    (4)(A) As used in this subsection and subsections 
(c)(2)(F)(iii) and (e)(1)(C), the term ``substantial evidence'' 
means evidence from 1 or more scientifically sound studies, 
including as appropriate in vitro studies, studies in 
laboratory animals (including a target species), bioequivalence 
studies, and any studies voluntarily undertaken by or for the 
applicant, that taken together provide reasonable assurance 
that the drug will have the claimed or intended effect of the 
drug.
    (B) For purposes of subparagraph (A), a study shall be 
considered to be scientifically sound if the study is designed 
and conducted in a manner that is consistent with generally 
recognized scientific procedures and principles.
    (e)(1) * * *
          * * * * * * *
    (C) on the basis of new information before him with respect 
to such drug, evaluated together with the evidence available to 
him when the application was approved, that there is a lack of 
substantial evidence (as defined in subsection (d)(4)) that 
such drug will have the effect if purports or is represented to 
have under the conditions of use prescribed, recommended, or 
suggested in the labeling thereof;
          * * * * * * *
    (i) When a new animal drug application filed pursuant to 
subsection (b) is approved, the Secretary shall by notice, 
which upon publication shall be effective as a regulation, 
publish in the Federal Register the name and address of the 
applicant and the conditions and indications of use of the new 
animal drug covered by such application, including any 
tolerance and withdrawal period or other use restrictions and, 
if such new animal drug is intended for use in animal feed, 
appropriate purposes and conditions of use (including special 
labeling [requirements)] requirements and any requirement that 
an animal feed bearing or containing the new animal drug be 
limited to use under the professional supervision of a licensed 
veterinarian) applicable to any animal feed for use in which 
such drug is approved, and such other information, upon the 
basis of which such application was approved, as the Secretary 
deems necessary to assure the safe and effective use of such 
drug. Upon withdrawal of approval of such new animal drug 
application or upon its suspension, the Secretary shall 
forthwith revoke or suspend, as the case may be, the regulation 
published pursuant to this subsection (i) insofar as it is 
based on the approval of such application.
          * * * * * * *
    (m)(1) * * *
          * * * * * * *
                  (i) that the applicant has failed to 
                establish a system for maintaining required 
                records, or has repeatedly or deliberately 
                failed to maintain such records or to make 
                required reports in accordance with a 
                regulation or order under [paragraph (5)(A) of 
                this subsection] paragraph (5)(A) or under 
                section 504(a)(3)(A), or the applicant has 
                refused to permit access to, or copying or 
                verification of, such records as required by 
                [subparagraph (B) of such paragraph] paragraph 
                (5)(B) or section 504(a)(3)(B);
          * * * * * * *

            classification of devices intended for human use

                             Device Classes

    Sec. 513. [360c] (a)(1) * * *
          * * * * * * *
    (3)(A) Except as authorized by subparagraph (B), the 
effectiveness of devices is, for purposes of this section and 
sections 514 and 515, to be determined, in accordance with 
regulations promulgated by the Secretary, on the basis of 
[well-controlled] one or more well-controlled investigations, 
including [clinical investigations] one or more clinical 
investigations where appropriate, by experts qualified by 
training and experience to evaluate the effectiveness of the 
device, from which investigations it can fairly and responsibly 
be concluded by qualified experts that the device will have the 
effect it purports or is represented to have under the 
conditions of use prescribed, recommended, or suggested in the 
labeling of the device.
          * * * * * * *
    (C) The Secretary shall accept, for the purpose of 
facilitating a review of a premarket application, a supplement 
to a premarket application, or a premarket notification of a 
device, retrospective or historical clinical data as a control, 
or for use, in determining whether there is a reasonable 
assurance of effectiveness of a device if sufficient valid data 
are available and the effects of the device on the cure, 
mitigation, treatment, or prevention of a disease are clearly 
defined and well understood.
    (D) The Secretary may not require a person intending to 
conduct clinical trials to conduct clinical trials using 
prospective concurrent controls in determining whether there is 
a reasonable assurance of effectiveness for a device or whether 
a device is substantially equivalent to a predicate device 
unless--
          (i) the effects of the device on the cure, 
        mitigation, treatment, or prevention of a disease or 
        condition are not clearly defined and well understood 
        as determined by the Secretary; or
          (ii) retrospective or historical data are not 
        available that meet the standards of the Secretary for 
        quality and completeness; or
          (iii) there is a compelling public health reason to 
        not rely on retrospective or historical data as a 
        control.
          * * * * * * *

     Initial Classification and Reclassification of Certain Devices

    (f)(1) * * *
          * * * * * * *
A device classified in class III under this paragraph shall be 
classified in that class until the effective date of an order 
of the Secretary under paragraph (2) classifying the device in 
class I or II[.], unless within 30 days of receiving an order 
classifying the device into class III, the individual who 
submits a notification under section 510(k) requests an 
advisory committee review and recommendation with respect to 
the classification of the device and a final order of 
classification from the Secretary. After the request, a device 
classified into class III under this paragraph shall not be 
deemed to be finally classified until an advisory committee 
established under subsection (b) reviews the request with 
respect to the classification of the device and, within 60 days 
of the date of receiving the request, recommends to the 
Secretary a classification for the device based on the 
classification criteria set forth in subparagraphs (A) through 
(C) of subsection(a)(1). Thereafter, the Secretary shall have 
10 days after the date of receiving the recommendation of the 
advisory committee to determine by order the final 
classification of the device by applying the classification 
criteria set forth in subparagraphs (A) through (C) of 
subsection(a)(1).
          * * * * * * *

                        Substantial Equivalence

    (i)(1)(A) For purposes of determinations of substantial 
equivalence under subsection (f) and section 520(l), the term 
``substantially equivalent'' or ``substantial equivalence'' 
means, with respect to a device being compared to a predicate 
device, that the device has the same intended use, which, as 
determined by the Secretary, shall include each use reasonably 
included within a general use, as the predicate device and that 
the Secretary by order has found that the device--
          * * * * * * *
    (4)(A) Any change or modification to a device initially 
classified under section 513(f), other than a major change 
(including any major modification) in the intended use or a 
change or modification in design that is significant and 
significantly affects safety or effectiveness, shall not 
require an additional notification under section 510(k) if, 
prior to the commercial distribution of the device--
          (i) the change or modification is supported by 
        appropriate data or information, (including data or 
        information demonstrating compliance with good 
        manufacturing practice regulations promulgated under 
        section 520(f)); and
          (ii) the change or modification is shown by such data 
        or information to not adversely affect the safety or 
        effectiveness of the device.
    (B) All data or information relied upon to document that a 
change to (including any modification of) the device does not 
require an additional notification under section 510(k) shall 
be made available to the Secretary upon request and shall be 
maintained, at least for a period of time equal to the expected 
life of the device or 2 years after the date of commercial 
distribution of the device by the manufacturer, whichever is 
greater.
          * * * * * * *

                         Performance Standards

                        Provisions of Standards

    Sec. 514. [360d] (a)(1) * * *
          * * * * * * *

        Performance Standards of Standard-Setting Organizations

    (c)(1) For the purpose of facilitating a review of a device 
under sections 510(k), 513(f), 515, or 520, the Secretary shall 
recognize appropriate device performance standards developed by 
any standard setting organization accredited by the American 
National Standards Institute (ANSI), the International 
Standards Organization (ISO), or the International 
Electrotechnical Commission (IEC).
    (2)(A) For any standard-setting organization not identified 
in paragraph (1), and for the purpose of facilitating a review 
of devices under sections 510(k), 513(f), 515, or 520, the 
Secretary shall establish a procedure governing the 
certification by the Food and Drug Administration of the 
competence of such an organization to develop standards for 
devices.
    (B) A certification of a standard-setting organization not 
identified in paragraph (1) shall be based on formal, written 
criteria that include requirements with respect to the role of 
the organization in the scientific community, scientific or 
medical expertise, standard writing experience, conflict of 
interest considerations, and the openness of the standard 
setting process of the organization.
    (C) The Secretary may impose a reasonable one-time fee on 
the standard-setting organization for certification pursuant to 
this paragraph.
    (3)(A) Upon being notified by a standard-setting 
organization described in paragraph (1) that a standard has 
been adopted by the organization, the Secretary shall recognize 
the standard by publishing a notice in the Federal Register 
listing the name of the standard.
    (B) Upon being notified by a standard-setting organization 
certified under paragraph (2) that a standard has been adopted 
by the organization, the Secretary shall review and may 
recognize the standard by publishing a notice in the Federal 
Register listing the name of the standard.
    (4) The Secretary may withdraw recognition of a performance 
standard adopted by a standard-setting organization described 
in paragraph (1) or a standard-setting organization certified 
under paragraph (2) if the Secretary determines that the 
standard is insufficient to facilitate a review of a device. 
The Secretary shall notify the standard-setting organization 
and specify the basis for the withdrawal.
    (5) The Secretary shall promulgate regulations under which 
the Secretary may withdraw the certification of a standard-
setting organization described in paragraph (2), or may no 
longer rely upon standards adopted by a standard-setting 
organization described in paragraph (1), if the Secretary 
determines that such organization no longer possesses the 
appropriate scientific or medical expertise, conflict of 
interest practices, standard-writing experience, or any other 
qualification necessary to the development of device standards.
    (6) As provided for in this section, the Secretary may 
promulgate performance standards for a device that differs from 
or is not established by, an organization described in 
paragraph (1) or an organization certified under paragraph (2).
    (7) The Secretary shall not require, as a condition for 
approving an application under section 515 or 520 or 
classifying a device under sections 510(k) and 513(f), 
conformity with a device standard recognized under this 
subsection if the person requesting such approval or 
classification submits evidence to demonstrate a reasonable 
assurance that the device is substantially equivalent to a 
legally marketed predicate device or provides reasonable 
assurance that the device is safe and effective.
    (8) A performance standard recognized pursuant to this 
subsection for a device--
          (A) shall include provisions to provide reasonable 
        assurance of the safe and effective performance of the 
        device;
          (B) shall, where necessary to provide reasonable 
        assurance of the safe and effective performance of the 
        device, include--
                  (i) provisions with respect to the 
                construction, components, ingredients, and 
                properties of the device and the compatibility 
                of the device with power systems and 
                connections to the systems;
                  (ii) provisions for the testing (on a sample 
                basis or, if necessary, on an individual basis) 
                of the device or, if it is determined that no 
                other more practicable means are available to 
                the Secretary to assure the conformity of a 
                device to the standard, provisions for the 
                testing (on a sample basis or, if necessary, on 
                an individual basis) of the device by the 
                Secretary or by another person at the direction 
                of the Secretary;
                  (iii) provisions for the measurement of the 
                performance characteristics of the device; and
                  (iv) provisions requiring that the results of 
                each or certain of the tests of the device 
                required to be made under clause (ii) 
                demonstrate that the device is in conformity 
                with those portions of the standard for which 
                the test or tests were required; and
          (C) shall, where appropriate, require the procedures, 
        for the proper installation, maintenance, operation, 
        and use of the device.
    (9) The Secretary shall accept a certification by a person 
who has made a submission pursuant to section 510(k), 515, or 
520 that the device conforms with each standard identified in 
the certification. The Secretary may, where appropriate, 
require data demonstrating conformity with a standard 
recognized under this subsection.
    (10) The Secretary shall require a person who makes a 
certification under paragraph (9) that a device conforms to an 
applicable performance standard recognized under this 
subsection or who makes a certification that a device conforms 
to a standard established under subsection (a) or (b) to 
maintain data demonstrating conformity of the device to the 
standard for a period of time equal to the period of time for 
the design and expected life of the device. Such data shall be 
made available to the Secretary upon request.

                           premarket approval

                          General Requirement

    Sec. 515. [360e] (a) A class III device--
          * * * * * * *

            Action on an Application for Premarket Approval

    (d)(1)(A) As promptly as possible, but in no event later 
than one hundred and eighty days after the receipt of an 
application under subsection (c) (except as provided in section 
520(l)(3)(D)(ii) or unless, in accordance with subparagraph 
(B)(i), an additional period as agreed upon by the Secretary 
and the applicant), the Secretary, after considering the report 
and recommendation submitted under [paragraph (2) of such 
subsection] paragraph (4), shall--
          (i) issue an order approving the application if he 
        finds that none of the grounds for denying approval 
        specified in [paragraph (2) of this subsection] 
        paragraph (4) applies; or
          (ii) deny approval of the application if he finds 
        (and sets forth the basis for such finding as part of 
        or accompanying such denial) that one or more grounds 
        for denial specified in [paragraph (2) of this 
        subsection] paragraph (4) apply. With respect to an 
        application submitted under this subsection for a 
        device for a life-threatening disease or condition, a 
        seriously debilitating disease or condition, or for any 
        other serious disease or condition that provides 
        therapy or diagnosis not available from another 
        approved device or offers a significant improvement 
        over another approved device, the Secretary shall 
        approve or deny the approval of the application within 
        180 days after the receipt of the application.
          (iii) The Secretary shall accept and review data and 
        any other information from investigations conducted 
        under the authority of regulations required by section 
        520(g) to make a determination of whether there is a 
        reasonable assurance of safety and effectiveness of a 
        device subject to a pending application under this 
        section if--
                  (I) the data or information is derived from 
                investigations of an earlier version of the 
                device, the device has been modified during or 
                after the investigations, and the modification 
                of the device does not constitute a significant 
                change in the design or in the basic principles 
                of operation of the device that would 
                invalidate the data or information; or
                  (II) the data or information on a device 
                approved under this section is available for 
                use under this Act and is relevant to the 
                design and intended use of the device subject 
                to the pending application.
    (2) Each application received under section 515(c) shall be 
reviewed in the following manner to achieve final action on the 
application within 180 days of the receipt of the application:
          (A) The Secretary shall meet with an applicant within 
        90 days of the receipt of the application to discuss 
        the review status of the application. If the 
        application does not appear in a form that would 
        require an approval under this subsection, the 
        Secretary shall in writing, and prior to the meeting, 
        present to the applicant a description of any 
        deficiencies in the application and what information is 
        required to bring the application into a form that 
        would require an approval.
          (B) The Secretary shall refer an application to a 
        panel established under section 513 for review and an 
        approval recommendation, (unless a panel is not 
        required under subsection (c)(2)) within 30 days of the 
        date of the meeting referred to in subparagraph (A) or 
        at the next scheduled panel meeting following the 
        meeting referred to in subparagraph (A), whichever 
        occurs first.
          (C) The Secretary shall meet with the applicant 
        within 15 days of the date of the panel review to 
        discuss the status of the application, including a 
        discussion on what action is necessary to bring the 
        application into a form that would require approval 
        under this subsection. Prior to the meeting, the 
        Secretary shall in writing, set forth an agenda for the 
        meeting (including a complete description of the 
        subject matter to be discussed at the meeting), and a 
        full description of the additional information 
        necessary to bring the application into a form that 
        would require an approval under this subsection. 
        Participation of the applicant at such a meeting shall 
        be at the discretion of the applicant.
          (D) The Secretary shall meet with the applicant not 
        later than 135 days after the receipt of an application 
        under subsection (c), if an advisory panel is not 
        required under subsection (c)(2), and inform the 
        applicant whether or not the application is in a form 
        that would require approval under this subsection. If 
        the application is in such form, the Secretary shall, 
        at or prior to the meeting, present in writing to the 
        applicant a description of all additional information 
        necessary to require an approval of the application 
        under this subsection. If the application is not in 
        such form, the Secretary shall deny approval of the 
        application and prior to the meeting, present in 
        writing to the applicant each basis for denying 
        approval of the application and the additional 
        information required to bring the application into a 
        form that would require approval.
          (E) The Secretary shall issue an order approving or 
        denying an application within 180 days of the receipt 
        of the application under subsection (c).
    (3) The time for the review of an application by the 
Secretary under this subsection shall not take more than 180 
days and such time may not be extended if the application is 
amended.
    [(2)] (4) The Secretary shall deny approval of an 
application for a device if, upon the basis of the information 
submitted to the Secretary as part of the application and any 
other information before him with respect to such device, the 
Secretary finds that--
          * * * * * * *
    [(3)] (5) An applicant whose application has been denied 
approval may, by petition filed on or before the thirtieth day 
after the date upon which he receives notice of such denial, 
obtain review thereof in accordance with either paragraph (1) 
or (2) of subsection (g), and any interested person may obtain 
review, in accordance with paragraph (1) or (2) of subsection 
(g), of an order of the Secretary approving an application.
          * * * * * * *

                     records and reports on devices

                              General Rule

    Sec. 519. [360i] (a) Every person who is a manufacturer[, 
importer, or distributor] or importer of a device intended for 
human use shall establish and maintain such records, make such 
reports, and provide such information, as the Secretary may be 
regulation reasonably require to assure that such device is not 
adulterated or misbranded and to otherwise assure its safety 
and effectiveness. Regulations prescribed under the preceding 
sentence--
          * * * * * * *
          (4) shall not impose requirements unduly burdensome 
        to a device manufacturer[, importer, or distributor] or 
        importer taking into account his cost of complying with 
        such requirements and the need for the protection of 
        the public health and the implementation of this Act;
          * * * * * * *
          (7) may not require that the identity of any patient 
        be disclosed in records, reports, or information 
        required under this subsection unless required for the 
        medical welfare of an individual, to determine the 
        safety or effectiveness of a device, or to verify a 
        record, report, or information submitted under this 
        Act[;]; and
          (8) may not require a manufacturer[, importer, or 
        distributor] or importer of a class I device to--
                  (A) maintain for such a device records 
                respecting information not in the possession of 
                the manufacturer[, importer, or distributor], 
                or importer, or
                  (B) to submit for such a device to the 
                Secretary any report or information--
                          (i) not in the possession of the 
                        manufacturer[, importer, or 
                        distributor], or importer, or
                          (ii) on a periodic basis,
        unless such report or information is necessary to 
        determine if the device should be reclassified or if 
        the device is adulterated or misbranded[; and].
          [(9) shall require distributors who submit such 
        reports to submit copies of the reports to the 
        manufacturer of the device for which the report was 
        made.]
          * * * * * * *

                             Certification

    (d) Each manufacturer[, importer, or distributor] and 
importer required to make reports under subsection (a) shall 
submit to the Secretary annually a statement certifying that--
          (1) the manufacturer[, importer, or distributor] or 
        importer did file a certain number of such reports, or
          (2) the manufacturer[, importer, or distributor] or 
        importer did not file any report under subsection (a).

                            [Device Tracking

    [(e) Every person who registers under section 510 and is 
engaged in the manufacture of--
          [(1) a device the failure of which would be 
        reasonably likely to have serious adverse health 
        consequences and which is (A) a permanently implantable 
        device, or (B) a life sustaining or life supporting 
        device used outside a device user facility, or
          [(2) any other device which the Secretary may 
        designate,
shall adopt a method of device tracking.]

                            Device Tracking

    (e) The Secretary may by regulation require a manufacturer 
to adopt a method of tracking a class II or class III device--
          (1) the failure of which would be reasonably likely 
        to be life-threatening or have serious adverse health 
        consequences; and
          (2) which is--
                  (A) permanently implantable; or
                  (B) life sustaining or life supporting and 
                used outside a device user facility.
Any patient receiving a device subject to tracking under this 
section may refuse to release, or refuse permission to release, 
the patient's name, address, social security number, or other 
identifying information for the purpose of tracking.

                  Reports of Removals and Corrections

    (f)(1) Except as provided in paragraph (2), the Secretary 
shall by regulation require a manufacturer[, importer, or 
distributor] or importer of a device to report promptly to the 
Secretary any correction or removal of a device undertaken by 
such manufacturer, importer, or distributor if the removal or 
correction was undertaken--
          (A) to reduce a risk to health posed by the device, 
        or
          (B) to remedy a violation of this Act caused by the 
        device which may present a risk to health.
A manufacturer[, importer, or distributor] or importer of a 
device who undertakes a correction or removal of a device which 
is not required to be reported under this paragraph shall keep 
a record of such correction or removal.
          * * * * * * *

general provisions respecting control of devices intended for human use

                              General Rule

    Sec. 520. [360j] (a) * * *
          * * * * * * *
    (m)(1) * * *
          * * * * * * *
The request shall be in the form of an application submitted to 
the Secretary. Not later than 30 days after the date of the 
receipt of the application, the Secretary shall issue an order 
approving or denying the application.
          * * * * * * *
    [(5) An exemption under paragraph (2) shall be for a term 
of 18 months and may only be initially granted in the 5-year 
period beginning on the date regulations under paragraph (6) 
take effect. The Secretary may extend such an exemption for a 
period of 18 months if the Secretary is able to make the 
findings set forth in paragraph (2) and if the applicant 
supplies information demonstrating compliance with paragraph 
(3). An exemption may be extended more than once and may be 
extended after the expiration of such 5-year period.
    [(6) Within one year of the date of the enactment of this 
subsection, the Secretary shall issue regulations to implement 
this subsection.]
          * * * * * * *
    (6) The procedures and conditions prescribed pursuant to 
paragraph (2)(A) shall be subject to subparagraphs (B) and (C) 
of section 505(i)(2), except that the provision of subparagraph 
(B) of such section relating to the consideration of the 
recommendations of the International Conference on 
Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use shall not apply to this 
paragraph.
    (7) The Secretary shall, not later than 120 days after the 
date of enactment of this paragraph, by regulation amend the 
content of parts 812 and 813 of title 21 of the Code of Federal 
Regulations to update the procedures and conditions under which 
devices intended for human use may upon application be granted 
an exemption from certain requirements under this Act. The 
regulation shall--
          (A) permit developmental changes in devices, 
        including manufacturing changes, in response to 
        information collected during an investigation without 
        requiring an additional approval of an application for 
        an investigational device exemption or the approval of 
        a supplement to the application, if the sponsor of the 
        investigation determines that, prior to making any 
        changes, the changes do not constitute a significant 
        change in design or a significant change in basic 
        principles of operation; and
          (B) permit, without approval of a supplement to an 
        application for an investigational device exemption, 
        changes or modifications to clinical protocols that do 
        not affect the validity of data or information 
        resulting from the completion of an approved protocol 
        so long as such changes do not affect any patient 
        protection provisions of the protocol.
          * * * * * * *

                        [POSTMARKET SURVEILLANCE

    [Sec. 522. [3601] (a) In General.--
          [(1) Requested surveiliance.--The Secretary shall 
        require a manufacturer to conduct postmarket 
        surveillance for any device of the manufacturer first 
        introduced or delivered for introducion into interstate 
        commerce after January 1, 1991, that--
                  [(A) is a permanent implant the failure of 
                which may cause serious, adverse health 
                consequewnces or death,
                  [(B) is intended for a use in supporting or 
                sustaining human life, or
                  [(C) potentially presents a serious risk to 
                human health.
          [(2) Discretionary surveillance.--The Secretary may 
        require a manufacturer to conduct postmarket 
        surveillance for a device of the manufacturer if the 
        Secretary determines that postmarket surveillance of 
        the device is necessary to protect the public health or 
        to provide safey or effectiveness data for the device.
    [(b) Surveillance Approval.--Each manufacturer required to 
conduct a surveillance of a device under subsection (a)(1) 
shall, within 30 days of the first introduction or delivery for 
introduction of such device into interstate commerce, submit, 
for the approval of the Secretary, a protocol for the required 
surveillance. Each manufacturer required to conduct a 
surveillance of a device under subsection (a)(2) shall, within 
30 days after receiving notice that the manufacturer is 
required to conduct such surveillance, submit, for the approval 
of the Secretary, a protocol for the required surveillance. The 
Secretary, within 60 days of the receipt of such protocol, 
shall determine if the principal investigator proposed to be 
used in the surveillance has sufficient qualifications and 
experience to conduct such surveillance and if such protocol 
will result in collection of useful data or other information 
necessary to protect the public health and to provide safety 
and effectiveness information for the device. The Secretary may 
not approve such a protocol until it has been reviewed by an 
appropriately qualified scientific and technical review 
committee established by the Secretary.]

SEC. 522. POSTMARKET SURVEILLANCE.

  (a) In General.--The Secretary may require a manufacturer to 
conduct postmarket surveillance for any device of the 
manufacturer that--
          (1) is a permanent implant the failure of which may 
        cause serious, adverse health consequences or death;
          (2) is intended for a use in supporting or sustaining 
        human life; or
          (3) potentially presents a serious risk to human 
        health or creates public health concerns that justify 
        surveillance under this section.
    (b) Surveillance Approval.--Each manufacturer required to 
conduct a surveillance of a device under subsection (a) shall, 
within 30 days of receiving notice from the Secretary that the 
manufacturer is required under this section to conduct the 
surveillance, submit for the approval of the Secretary, a 
protocol for the required surveillance. The Secretary, within 
60 days of the date of the receipt of the protocol, shall 
determine if the principal investigator proposed to be used in 
the surveillance has sufficient qualifications and experience 
to conduct the surveillance and if the protocol will result in 
collection of useful data or other information necessary to 
protect the public health and to provide safety and 
effectiveness information for the device. The Secretary may not 
approve the protocol until the protocol has been reviewed by a 
qualified scientific and technical review committee established 
by the Secretary.

SEC. 523. STATE AND LOCAL REQUIREMENTS RESPECTING NONPRESCRIPTION DRUGS 
                    INTENDED FOR HUMAN USE.

    (a) Limitation.--
          (1) In general.--Except as provided in subsection 
        (b), no State or political subdivision thereof may 
        establish or continue in effect any requirement--
                  (A) that relates to the regulation of a drug 
                intended for human use that is not subject to 
                the requirements of section 503(b)(1); and
                  (B) that is different from or in addition to, 
                or that is otherwise not identical with, a 
                requirement of this Act or the Fair Packaging 
                and Labeling Act (15 U.S.C. 1451 et seq.), and 
                the administrative implementation of such Act.
          (2) Special rule.--For purposes of this section, a 
        requirement relating to the regulation of a drug 
        described in paragraph (1) shall be deemed to include 
        any requirement relating to the subject matter in any 
        provision of this Act, the Fair Packaging and Labeling 
        Act (15 U.S.C. 1451 et seq.), and any requirement 
        relating to the dissemination of information in any 
        manner about such drug, but shall not include any 
        requirement relating to the dispensing of a drug only 
        upon prescription of a practitioner licensed by law to 
        administer such drug.
    (b) Exemption.--Upon application of a State, the Secretary 
may by regulation, after providing notice and an opportunity 
for written and oral presentation of views, exempt from the 
provisions of subsection (a), under such conditions as the 
Secretary may impose, a proposed requirement relating to the 
regulation of a drug intended for human use--
          (1) that is justified by compelling local conditions 
        or protects an important public interest that would 
        otherwise be unprotected;
          (2) that would not cause any drug intended for human 
        use that is not subject to the requirements of section 
        503(b)(1) to be in violation of any applicable 
        requirement or prohibition under Federal law; and
          (3) that would not unduly burden interstate commerce.

SEC. 523A. ACCREDITED-PARTY PARTICIPATION.

  (a) In General.--Not later than 1 year after the date of 
enactment of this section, the Secretary shall accredit 
persons, including any entity or any individual who is not an 
employee of the Department to review and initially classify 
devices under section 513(f)(1) that are subject to a report 
under section 510(k) and to review and recommend to the 
Secretary approval or denial of applications submitted under 
section 515(c)(1).
  (b) Accreditation.--Not later than 6 months after the date of 
enactment of this section, the Secretary shall establish and 
publish in the Federal Register requirements to accredit or 
deny accreditation to a person who makes a request for 
accreditation to carry out the activities described in 
subsection (a). The requirements shall, at a minimum, advise 
such person how to become accredited, and set forth criteria 
for accreditation including criteria to avoid conflicts of 
interest and to ensure that persons to be accredited are 
capable of maintaining the confidentiality of submissions 
consistent with section 552 of title 5, United States Code, and 
the regulations of the Food and Drug Administration. The 
Secretary shall respond to a request for accreditation not 
later than 60 days after the receipt of the request. The 
accreditation of a person shall specify the activities under 
subsection (a) which such person is authorized to carry out in 
the place of the Secretary.
  (c) Withdrawal of Accreditation.--The Secretary may suspend 
or withdraw accreditation of any person accredited under this 
section, after providing notice and an opportunity for an 
informal hearing, if such person acts or fails to act in a 
manner that is substantially inconsistent with the purposes of 
this section, including the failure to avoid conflicts of 
interest, the failure to protect confidentiality of 
information, or the failure to competently review premarket 
submissions for devices.
  (d) Selection and Compensation.--A person who submits a 
premarket submission for a device to the Secretary for review 
and classification, or approval of a device, shall have the 
option to select an accredited person to review such 
submission. The Secretary shall identify for the person no less 
than 2 accredited persons from whom the selection may be made. 
Compensation for an accredited person shall be determined by 
agreement between the accredited person and the person who 
engages the services of the accredited person.
  (e) Review by Secretary.--
          (1) In general.--If a person exercises the option to 
        obtain review of a premarket submission that is an 
        application or a notification by an accredited person, 
        the Secretary shall complete a filing review for a 
        premarket approval application under section 515(c)(1) 
        not later than 30 days after receipt of such 
        application, or shall ensure the completeness of a 
        premarket notification submission under section 510(k) 
        not later than 15 days after receipt of such 
        submission, prior to referring the premarket submission 
        for review by the accredited person selected by the 
        person submitting the premarket submission.
          (2) Report on classification, approval, or denial.--
        The Secretary shall require an accredited person, upon 
        recommending a classification of a device or approval 
        or denial of an application for a device, to report to 
        the Secretary the reasons of the accredited person for 
        such classification or approval or denial. For devices 
        reviewed and initially classified under section 
        513(f)(1) and subject to a report under section 510(k), 
        the Secretary shall have not more than 15 days to 
        review the submission. For applications submitted under 
        section 515(c)(1), the Secretary shall have not more 
        than 45 days to review the application. The Secretary 
        may change the classification under section 513(f)(1), 
        or the approval or disapproval of the application under 
        section 515(d), that is recommended by the accredited 
        person, and in such case shall notify the person making 
        the submission of the detailed reasons for the change.
  (f) Duration.--This section shall remain in force for a 
period of 3 years from the date on which the Secretary 
accredits the first person to conduct initial classifications 
under section 513(f)(1) and to conduct premarket approval 
reviews under section 515.
    (g) Reports.--
          (1) Implementation of accreditation process.--Not 
        later than 1 year after the date of enactment of this 
        section, the Secretary shall prepare and submit to the 
        committees of Congress with oversight authority over 
        the Food and Drug Administration a report concerning 
        each action the Secretary has taken to implement the 
        accreditation of persons to undertake the activities 
        described in subsection (a).
          (2) Examination of the use of accredited persons.--
                  (A) In general.--Not later than 2 years after 
                the date on which the Secretary accredits the 
                first person to conduct initial classifications 
                under section 513(f)(1) and to conduct 
                premarket approval reviews under section 515, 
                the Secretary shall contract with an 
                independent research organization to prepare 
                and submit to the Secretary a written report 
                examining the use of accredited persons under 
                this section. The Secretary shall submit the 
                report to the committees described in paragraph 
                (1) not later than 30 months after the date on 
                which the Secretary accredits the first person 
                to conduct initial classifications under 
                section 513(f)(1) and to conduct premarket 
                approval reviews under section 515.
                  (B) Contents.--The report by the independent 
                research organization described in subparagraph 
                (A) shall identify the benefits or detriments 
                to public and patient health of using 
                accredited persons to conduct such reviews, and 
                shall summarize all relevant data, including 
                data on the review of accredited persons 
                (including review times, recommendations, and 
                compensation), and data on the review of the 
                Secretary (including review times, changes, and 
                reasons for changes).
          * * * * * * *

 Subchapter D--Unapproved Therapies and Diagnostics and Collaborative 
                                Research

SEC. 551. EXPANDED ACCESS TO UNAPPROVED THERAPIES AND DIAGNOSTICS.

    (a) In General.--Any person, through a licensed health care 
practitioner or licensed health care professional, may request 
from a manufacturer or distributor, and any manufacturer or 
distributor may provide to a person after compliance with the 
provisions of this section, an investigational drug (including 
a biological product) or investigational device for the 
diagnosis, monitoring, or treatment of a serious disease or 
condition, an immediately life-threatening or seriously 
debilitating disease or condition, or any other disease or 
condition designated by the Secretary as appropriate for 
expanded access under this section if--
          (1) the person has no comparable or satisfactory 
        alternative therapy available to treat, diagnose, or 
        monitor the disease or condition;
          (2) the risk to the person from the investigational 
        drug or device is not greater than the risk from the 
        disease or condition; and
          (3) an exemption for the investigational drug or 
        device is in effect under a regulation promulgated 
        pursuant to section 505(i) or 520(g) and the sponsor 
        and investigators comply with such regulation.
    (b) Protocols.--A manufacturer or distributor may submit to 
the Secretary 1 or more expanded access protocols covering 
expanded access use of a drug or device described in subsection 
(a). The protocols shall be subject to the provisions of 
section 505(i) for a drug and section 520(g) for a device and 
may include any form of use of the drug or device outside a 
clinical investigation, prior to approval of the drug or device 
for marketing, including protocols for treatment, use, parallel 
track, emergency use, uncontrolled trials, and single patient 
protocols.
    (c) Fees.--A manufacturer or distributor may assess a fee 
for an investigational drug or device under an expanded access 
protocol so long as the fee is not more than that necessary to 
recover the costs of the manufacture and handling of the drug 
or device. The Secretary shall be notified in advance of the 
assessing of any such charges.
    (d) Notification of Availability.--The Commissioner shall 
inform national, State, and local medical associations and 
societies, voluntary health associations, and other appropriate 
persons about the availability of an investigational drug or 
device under expanded access protocols under this section. Such 
notification shall identify--
          (1) the investigational drug or device;
          (2) the expanded access use of the investigational 
        drug or device; and
          (3) the name and address of the manufacturer or 
        distributor that is providing the investigational drug 
        or device for expanded access use.

SEC. 552. COLLABORATIVE RESEARCH DESIGN.

  (a) Review of Design.--
          (1) Request.--Any person who intends to sponsor a 
        preclinical or clinical investigation of a drug 
        (including a biological product) or device may request 
        a meeting with the Secretary to review the design of 1 
        or more protocols for the preclinical or clinical 
        testing of the drug or device.
          (2) Form.--A request described in paragraph (1) shall 
        be in writing and shall include any protocol for which 
        the review is requested. A protocol shall be designed 
        so that the fewest number of patients and procedures 
        necessary to obtain data necessary for the approval of 
        a new drug, biological product, or device is required, 
        consistent with public health and safety.
          (3) Written review.--The Secretary shall meet with 
        the person within 30 days after the request and shall 
        provide to the person a written review of the protocol, 
        including any deficiencies in the protocol. A written 
        summary shall be made of the meeting. The summary shall 
        include the written review of the protocol and, after 
        agreement by the person and the Secretary, shall be 
        made part of the product review file maintained by the 
        Food and Drug Administration.
  (b) Modification of Agreements.--Any agreements reached 
through meetings with respect to the design of any protocol 
under subsection (a) may be modified only in accordance with 
the following provisions:
          (1) An agreement may be modified at any time by 
        mutual consent of the sponsor of a preclinical or 
        clinical investigation and the Secretary.
          (2) An agreement may be modified by the sponsor 
        unilaterally, if the change is to a protocol and the 
        change is one that would not require the approval of 
        the Secretary under the applicable regulations.
          (3) An agreement may be modified by the Secretary 
        unilaterally, if the change to the agreement is--
                  (A) made by the director of the office of the 
                Food and Drug Administration responsible for 
                regulating the drug or device that is the 
                subject of the agreement; and
                  (B) set forth in writing, including an 
                explanation of the scientific or clinical need 
                for the change.
The director described in paragraph (3)(A) may not delegate the 
regulatory responsibility described in such paragraph.
  (c) Appeals.--Any person requesting a meeting under 
subsection (a) may appeal the decision of the Secretary to 
disapprove or modify an agreement or protocol under section 
907.
  (d) Guidelines and Limitation.--The Secretary shall issue 
guidelines to implement this section. Such guidelines shall 
address the responsibilities of the person requesting the 
meeting, as well as the responsibilities of the Secretary. 
Repeated failure to follow the guidelines may be grounds for a 
refusal by the Secretary to meet with a person requesting a 
meeting under this section.
          * * * * * * *

                     CHAPTER VII--GENERAL AUTHORITY

            Subchapter A--General Administrative Provisions

                        regulations and hearings

    Sec. 701. [371] [(a) The] (a)(1) The authority to 
promulgate regulations for the efficient enforcement of this 
Act, except as otherwise provided in this section, is hereby 
vested in the Secretary.
  (2)(A) Not later than 180 days after the date of enactment of 
the Food and Drug Administration Performance and Accountability 
Act of 1996, the Secretary shall establish a procedure 
governing the development and use of all policy statements of 
general applicability that provide guidance relating to the 
conduct of preclinical or clinical investigations or other 
testing to support an application or submission (including a 
petition, notification, or any other similar form of request) 
under section 409, 505, 510(k), 512, 515, or 721 or that 
provide guidance on the submission of an application or 
submission (including a petition, notification, or any other 
similar form of request) under section 409, 505, 510(k), 512, 
515, or 721 (including any guidance, guideline, points-to-
consider, protocol, recommendation, or similar document 
regardless of the form or designation). The procedure shall 
provide an opportunity for affected persons to participate in 
the development and continued use of a policy statement by 
sharing expertise or experience, or providing comment, before 
the policy statement is adopted and after the policy statement 
is implemented, except that if the Secretary determines that 
there is a public health need to issue the policy statement 
immediately, the Secretary shall provide an opportunity for 
affected persons to provide comment promptly after the policy 
statement is issued.
  (B) The Secretary shall establish a procedure for the 
periodic compilation and publication of all policy statements 
of general applicability (including any guideline, points-to-
consider, protocol, recommendation, or similar document 
regardless of the form or designation).
          * * * * * * *

Subchapter D--Review of Applications, Inspections, Environmental Impact 
                   Reviews, and Manufacturing Changes

SEC. 741. CONTENT AND REVIEW OF AN APPLICATION.

    (a) In General.--This section applies to an application or 
submission (including a petition, notification, or any other 
similar form of request) submitted for approval or clearance of 
a new drug, device, biological product, new animal drug, animal 
feed bearing or containing a new animal drug, color additive, 
or food additive.
    (b) Filing Requirements.--Not later than 60 days after the 
date of enactment of this section, the Commissioner shall 
establish and publish in the Federal Register a mechanism to 
ensure the fair and consistent application of filing 
requirements.
    (c) Classification of a Product.--Not later than 60 days 
after the receipt of a written request of a person who submits 
an application or submission (including a petition, 
notification, or any other similar form of request) for 
information respecting the classification of an article as a 
drug, biological product, or device or the component of the 
Food and Drug Administration that will regulate the article 
(including a request respecting a combination product subject 
to section 503(g)), the Secretary shall provide the person a 
written statement that identifies the classification of the 
article or the component of the Food and Drug Administration 
that will regulate the article. The Secretary's statement shall 
be binding and may not be modified by the Secretary except with 
the written agreement of the person who submitted the request. 
If the Secretary does not provide the statement within the 60-
day period, the classification and component designated by the 
person submitting the request shall be final and binding and 
may not be modified by the Secretary except with the written 
agreement of the person.
    (d) Reasonable Data Requirements.--Not later than 1 year 
after the date of enactment of the Food and Drug Administration 
Performance and Accountability Act of 1996, the Secretary, 
after consultation with experts in the development and testing 
of articles that are new drugs, biological products, devices, 
food additives, new animal drugs, animal feed bearing or 
containing a new animal drug, color additives, or food 
additives, experts in the regulation of such articles, consumer 
and patient advocacy groups, and the regulated industries, 
shall publish in the Federal Register criteria for the type and 
amount of information relating to safety or effectiveness to be 
included in an application for the approval of an article that 
is a new drug, biological product, device, food additive, new 
animal drug, animal feed bearing or containing a new animal 
drug, color additive, or food additive, or a new use of an 
approved article that is a new drug, biological product, 
device, food additive, new animal drug, animal feed bearing or 
containing a new animal drug, color additive, or food additive. 
In establishing the criteria for drugs, the Secretary shall 
consider any recommendations of the International Conference on 
Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use.
    (e) Limitation on Determination of Effectiveness.--In a 
review of an application for an article that is a new drug, 
device, biological product, new animal drug, or animal feed 
bearing or containing a new animal drug, the determination of 
effectiveness shall not include the evaluation of--
          (1) any potential use not included in the labeling;
          (2) the cost-effectiveness of an article described in 
        this subsection, unless the proposed labeling 
        explicitly includes a representation about cost-
        effectiveness; and
          (3) the clinical outcome resulting from the use of a 
        diagnostic device, unless the labeling explicitly 
        includes a representation regarding clinical outcome.

SEC. 742. CONTRACTS FOR EXPERT REVIEW.

  (a) In General.--
          (1) Authority.--The Secretary may contract with 
        outside organizations and individuals, with expertise 
        in relevant disciplines, to review, evaluate, and make 
        conclusions and recommendations to the Secretary on 
        parts or all of any application or submission 
        (including a petition, notification, or any other 
        similar form of request). The Secretary shall retain 
        full authority to make determinations with respect to 
        the approval or disapproval of any article, or the 
        classification of a device under section 513(f)(1). Any 
        such contract shall be subject to the requirements of 
        section 708. Funds obtained under part 2 of subchapter 
        C may be used for external review of any drug 
        (including a biological product) for which a user fee 
        was paid.
          (2) Increased efficiency and expertise through 
        contracts.--The Secretary shall use the authority 
        granted in paragraph (1)--
                  (A) for the review of categories of indirect 
                food additive petitions and notifications for 
                clearance under section 510(k);
                  (B) whenever contracts will improve the 
                efficiency, timeliness, and quality of the 
                review of applications or submissions 
                (including petitions, notifications, or any 
                other similar form of requests) for the 
                approval or clearance of new drugs, new animal 
                drugs, biological products, devices, and food 
                additives; and
                  (C) whenever contracts will increase the 
                scientific and technical expertise that is 
                necessary to keep informed of emerging new 
                therapies and technologies that pose 
                significant new scientific and technical 
                issues.
        The Secretary shall retain full authority to make 
        determinations with respect to the approval or 
        disapproval of an article, or the classification of an 
        article as a device under section 513(f)(1).
  (b) Eligibility Requirements.--Not later than 90 days after 
the date of enactment of this section, the Secretary shall by 
regulation establish the requirements that an organization or 
individual shall meet to be eligible to conduct reviews under 
subsection (a). Such regulations shall provide for the 
protection of confidential or proprietary information and shall 
provide for protection against conflicts of interest.
  (c) Review of Expert's Evaluation.--
          (1) In general.--Subject to paragraph (2), the 
        official of the Food and Drug Administration 
        responsible for any matter for which expert review is 
        used pursuant to this section shall personally review 
        the conclusions and recommendations of the expert 
        review organization or individual and shall make a 
        final decision regarding the matter under review within 
        60 days after receiving the conclusions and 
        recommendation.
          (2) Limitation.--A final decision under paragraph (1) 
        shall be made within the applicable prescribed time 
        period for review of an application as set forth in 
        this Act.
  (d) Report to Congress.--Not later than 2 years after the 
date of enactment of this section, the Secretary shall prepare 
and submit to Congress a report on the use of the authority to 
contract with outside organizations and individuals for expert 
reviews. Such report shall include an evaluation of the extent 
to which such contracting improves the efficiency of review and 
the expertise available to the Food and Drug Administration.

SEC. 743. PROMPT AND EFFICIENT REVIEW.

  (a) In General.--The provisions of this section shall apply 
to any of the following applications, petitions, and 
notifications:
          (1) An petition for the issuance of a regulation 
        prescribing the safe use of a human food additive or 
        animal feed additive under section 409.
          (2) An application for approval of a new drug under 
        section 505.
          (3) An application for approval of a new animal drug 
        or an animal feed bearing or containing a new animal 
        drug under subsection (b) or (m) of section 512, 
        respectively.
          (4) A notification submitted under section 510(k) for 
        classification of a device.
          (5) An application for approval of a device under 
        section 515.
          (6) An petition for issuance of a regulation for the 
        listing of a color additive under section 721.
  (b) Review Procedures and Policies.--The Secretary shall 
establish procedures and policies to facilitate a collaborative 
review process between the Food and Drug Administration and the 
applicant, petitioner, or person who submits a notification 
with respect to an application, petition, or notification 
described in subsection (a). As part of this collaborative 
process--
          (1) open, informal, and prompt communications shall 
        be encouraged;
          (2) meetings (except that meetings shall not be 
        required with respect to matters relating to a 
        notification submitted under section 510(k)) shall be 
        held before the expiration of one-half of the statutory 
        time period for review of the application or petition 
        and before the expiration of three-quarters of such 
        period, or within 15 days after a scientific review 
        group has convened and made recommendations on an 
        application or petition, unless the Commissioner and 
        the applicant or petitioner determine that a meeting is 
        unnecessary;
          (3) by mutual consent, the Commissioner and the 
        applicant or petitioner may establish a different 
        schedule for meetings required under paragraph (2); and
          (4) the Secretary shall, prior to the meetings 
        described in paragraph (2), present to the applicant or 
        petitioner in writing a description of any deficiencies 
        of the application or petition and the information 
        necessary to bring the application or petition into a 
        form that would require approval.
The Secretary and the applicant or petitioner may agree to 
supersede any procedures and policies adopted under this 
section and the requirements of paragraphs (2) and (3). Any 
such agreement shall be in writing, and shall specify how any 
such agreement shall be modified or set aside.
    (c) Approval, Disapproval, and Classification.--
          (1) Consideration of international approvals.--
        Beginning July 1, 1998, if the Secretary fails to meet 
        a time period for action on an application or 
        notification for the approval or clearance of an 
        article that is a new drug, device, biological product, 
        or new animal drug that offers a significant 
        improvement over an existing approved article or a 
        petition for the approval of a direct food additive 
        that has the potential to make foods more wholesome and 
        contribute to a healthier diet, , and such an article 
        has been approved for marketing in the European Union 
        or the United Kingdom, the Secretary shall, within 30 
        days after a request of a person who submits an 
        application, notification, or petition described in 
        this paragraph, either approve or disapprove the 
        application, notification, or petition and notify the 
        person in writing of that decision. In the case of a 
        disapproval, or a determination that a device is not 
        substantially equivalent,such notification shall set 
        forth the reasons for the disapproval or the 
        determination.
          (2) Appeal.--A person whose application, 
        notification, or petition has been disapproved 
        (including a determination that a device does not meet 
        the requirements relating to substantial equivalence) 
        under paragraph (1) may obtain judicial review under--
                  (A) section 505(h) for the disapproval of a 
                new drug under paragraph (1);
                  (B) section 517 for the disapproval of a 
                device or a determination of not substantially 
                equivalent relating to a device under paragraph 
                (1);
                  (C) chapter VII of title 5, United States 
                Code, for the disapproval of a license for a 
                biological product under paragraph (1);
                  (D) section 512(h) for the disapproval of a 
                new animal drug under paragraph (1); and
                  (E) section 409(g) for the disapproval of a 
                direct food additive under paragraph (1).
    (d) Contracts for Expert Review.--
          (1) In general.--Beginning July 1, 1998, if the 
        Secretary in any fiscal year fails to meet the 
        statutory time period for action on an application, 
        notification, or petition for at least 95 percent of 
        the applications, notifications, and petitions 
        submitted in a particular product category, the 
        Secretary shall--
                  (A) in the following fiscal year contract 
                with expert organizations and individuals under 
                section 742, to review applications, 
                notifications, and petitions of persons who 
                submit the applications, notifications, and 
                petitions in that following fiscal year and who 
                consent to the review; and
                  (B) in the following fiscal year and with the 
                consent of the persons described in this 
                subparagraph, contract with expert 
                organizations and individuals under section 
                742, to review applications, notifications, and 
                petitions that were submitted by persons in any 
                preceding fiscal year and that the Secretary 
                has failed to review within the statutory time 
                period of action on the applications, 
                notifications, and petitions with respect to 
                the particular product category.
          (2) Approval.--If an organization or individual 
        selected to conduct a review under paragraph (1) 
        recommends the approval or clearance of an application, 
        notification, or petition described in paragraph (1), 
        the Secretary shall, within 60 days after receiving the 
        determination of the organization or individual (but 
        not later than the time period for review set forth in 
        this Act), either approve or disapprove the 
        application, notification, or petition, and, in the 
        case of a disapproval, notify the person who submitted 
        the application, notification, or petition in writing 
        of the basis for the disapproval. The person may appeal 
        an adverse decision under subsection (c)(2).

SEC. 744. GOOD MANUFACTURING PRACTICE INSPECTION.

    (a) In General.--In order to comply with the inspection 
requirements of this Act, the Secretary may accredit 
organizations to conduct inspections under section 704 to 
evaluate compliance of a manufacturer with applicable 
requirements for good manufacturing practice.
    (b) Eligibility Requirements.--If the Secretary elects to 
accredit organizations to conduct inspections under section 
704, the Secretary shall by regulation, within 90 days after 
the date of enactment of this section, establish the 
requirements that an organization shall meet to be eligible to 
be accredited to participate as a qualified organization to 
conduct inspections under subsection (a). Such regulation shall 
provide for the protection of confidential or proprietary 
information and shall provide for protection against conflicts 
of interest.
    (c) Accreditation.--Not later than 90 days after the date 
on which the Secretary receives an application for 
accreditation under this section, the Secretary shall review 
the application and determine whether an applicant is in 
compliance with the requirements established under this 
section. Within the 90-day period, the Secretary shall grant 
accreditation or shall deny accreditation and specify in 
writing the reasons for the denial and the requirements that 
shall be met to obtain accreditation.
    (d) Revocation of Accreditation.--The Secretary may at any 
time revoke accreditation granted under subsection (c) for 
failure to comply with the requirements established under this 
section after specifying in writing the reasons for the 
revocation and the requirements that shall be met to retain 
accreditation and after an informal hearing on the revocation.
    (e) Inspections.--Any organization accredited under this 
subsection that conducts an inspection under this subsection at 
the request of the Secretary shall--
          (1) apply all relevant principles of good 
        manufacturing practice established in this Act and in 
        regulations promulgated by the Secretary;
          (2) provide to the Secretary and the manufacturer 
        within 30 days after the completion of the inspection 
        an adequate report of the findings of the inspection; 
        and
          (3) immediately provide the Secretary with a notice 
        of any condition that could cause or contribute to a 
        significant threat to the public health.

SEC. 745. ENVIRONMENTAL IMPACT REVIEW.

    Notwithstanding any other provision of law, no action by 
the Secretary pursuant to this Act shall be subject to an 
environmental assessment, an environmental impact statement, or 
other environmental consideration unless the director of the 
office responsible for the action demonstrates, in writing--
          (1) that there is a reasonable probability that the 
        environmental impact of the action is sufficiently 
        substantial and within the factors that the Secretary 
        is authorized to consider under this Act; and
          (2) that consideration of the environmental impact 
        will directly affect the decision on the action.

SEC. 746. MANUFACTURING CHANGES.

    (a) In General.--A change in the manufacture of a new drug, 
biological product, or new animal drug, may be made in 
accordance with this section.
    (b) Drug and Biological Product.--A change in the 
manufacture of a new drug, a biological product that is the 
subject of a monograph in an official compendium, a biological 
product that can be adequately characterized by chemical, 
physical, or biological means, or a new animal drug--
          (1) shall require validation; and
          (2)(A) if there is no change in the approved 
        qualitative and quantitative formulation relating to 
        the new drug, biological product, or new animal drug or 
        in the approved release specifications relating to the 
        new drug, biological product, or new animal drug, or if 
        there is a change in the approved qualitative or 
        quantitative formula or in the approved release 
        specifications of a type permitted by the Secretary by 
        regulation, may be made at any time so long as the 
        change is reported annually to the Secretary; or
          (B) in the case of a change other than a change 
        described in subparagraph (A), shall require completion 
        of an appropriate study demonstrating equivalence 
        according to criteria established by the Secretary 
        (unless such requirement is waived by the Secretary), 
        may be made at any time, and shall be reported to the 
        Secretary through a supplement or amendment submitted 
        at the time the change is made.
    (c) Biological Product Not Subject to a Monograph.--A 
change in the manufacture of a biological product that is not 
the subject of a monograph in an official compendium and cannot 
be adequately characterized by chemical, physical, or 
biological means--
          (1) shall require validation; and
          (2)(A) if the change relates solely to a modification 
        of the manufacturing facility or change in personnel, 
        with no change in the approved manufacturing process or 
        release specifications, may be made at any time so long 
        as the change is reported annually to the Secretary; 
        and
          (B) in the case of a change other than a change 
        described in subparagraph (A), shall require completion 
        of a bioassay or other appropriate study demonstrating 
        equivalence according to criteria established by the 
        Secretary (unless such requirement is waived by the 
        Secretary), may be made at any time, and shall be 
        reported to the Secretary through an amendment 
        submitted at the time the change is made.
    (d) Special Determination for a Biological Product.--A 
determination shall be made, prior to approval of a biological 
product under section 351(a) of the Public Health Service Act 
(42 U.S.C. 262(a)), whether the product can be adequately 
characterized for purposes of this subsection. With respect to 
biological products approved prior to the date of enactment of 
the Food and Drug Administration Performance and Accountability 
Act of 1996, the determination shall be made not later than 90 
days after the date of enactment of such Act. Any determination 
made under this subsection is subject to change based upon new 
scientific information.
          * * * * * * *

                 exports of certain unapproved products

    Sec. 802. [382] (a) * * *
          * * * * * * *
    (h) Exportation of Unapproved Products.--Insulin and 
antibiotics may be exported without regard to the requirements 
in this section if the insulin and antibiotics meet the 
requirements of section 801(e)(1).
    [(h)] (i) For purposes of this section--
          ``(1) a reference to the Secretary shall in the case 
        of a biological product which is required to be 
        licensed under the Act of March 4, 1913 (37 Stat. 832-
        833) (commonly known as the Virus-Serum Toxin Act) be 
        considered to be a reference to the Secretary of 
        Agriculture, and
          (2) the term ``drug'' includes drugs for human use as 
        well as biologicals under section 351 of the Public 
        Health Service Act or the Act of March 4, 1913 (37 
        Stat. 832-833) (commonly known as the Virus-Serum Toxin 
        Act).
          * * * * * * *

SEC. 903. [393] FOOD AND DRUG ADMINISTRATION.

    (a) In General.--There is established in the Department of 
Health and Human Services the Food and Drug Administration 
(hereinafter in this section referred to as the 
``Administration''). The mission of the Administration is to 
promote and protect the public health by--
          (1) facilitating the rapid and efficient development 
        and availability of articles subject to the regulation 
        of the Administration;
          (2) protecting the public from unsafe or ineffective 
        articles subject to the regulation of the 
        Administration; and
          (3) enforcing the applicable statutes and regulations 
        in a timely, fair, consistent, and decisive manner.
    (b) Commissioner.--
          (1) Appointment.--There shall be in the 
        Administration a Commissioner of Food and Drugs 
        (hereinafter in this section referred to as the 
        ``Commissioner'') who shall be appointed by the 
        President by and with the advice and consent of [the 
        Senate.] the Senate for a term of 5 years. The 
        Commissioner shall be appointed to serve 1 term. An 
        individual serving in the office of Commissioner may be 
        removed from office only pursuant to a finding by the 
        President of neglect of duty or malfeasance in office.
          * * * * * * *
          (3) Performance standards and review.--
                  (A) In general.--Not later than 180 days 
                after the date of enactment of this paragraph, 
                the Secretary, after consultation with experts 
                in the development, clinical investigation, and 
                regulation of drugs, biological products, new 
                animal drugs, devices, food additives, and 
                color additives and representatives of patient 
                and consumer advocacy groups, health and 
                technology professionals, and the regulated 
                industries, shall develop and publish in the 
                Federal Register quantifiable performance 
                standards for action by the Administration on--
                          (i) applications or submissions 
                        (including petitions, notifications, or 
                        any other similar form of request) for 
                        review of a protocol, a product 
                        investigation, a product approval, a 
                        new use approval, a manufacturing 
                        change, a change in labeling, or any 
                        other form of regulatory action 
                        relating to the review of an article 
                        that is a new drug, biological product, 
                        new animal drug, device, food additive, 
                        or color additive and that is subject 
                        to premarket review or approval under 
                        this Act; and
                          (ii) the scheduling of advisory 
                        committee meetings, and the action 
                        taken by the Administration following 
                        an advisory committee recommendation, 
                        relating to the applications and 
                        submissions described in clause (i).
                  (B) Review of performance standards.--The 
                performance standards required by subparagraph 
                (A) shall be reviewed annually by the 
                Secretary, and after consultation with experts 
                in the development, clinical investigation, and 
                regulation of drugs, biological products, new 
                animal drugs, devices, food additives, and 
                color additives, and representatives of patient 
                and consumer advocacy groups, health and 
                technology professionals, and the regulated 
                industries, may be revised, annually by the 
                Secretary.
                  (C) Agency objectives.--The performance 
                standards required by subparagraph (A) shall 
                establish objectives for the Administration 
                that--
                          (i) expedite the clinical 
                        investigation of an article that is a 
                        new drug, device, or biological product 
                        through closer collaboration between 
                        the Administration and the sponsor of 
                        the investigation;
                          (ii) expedite the review of an 
                        application for a new drug, device, or 
                        biological product--
                                  (I) for an immediately life-
                                threatening disease or 
                                condition; or
                                  (II) for any other serious 
                                condition if the new drug, 
                                device, or biological product 
                                provides therapy that is not 
                                available from other approved 
                                therapy or offers significant 
                                improvement over other approved 
                                therapy or diagnostic or 
                                monitoring agents;
                          (iii) reduce backlogs in the review 
                        of all applications with the objective 
                        of eliminating all backlogs in the 
                        review of applications by January 1, 
                        1998;
                          (iv) establish a schedule to bring 
                        the Administration into full compliance 
                        by July 1, 1998, with the time periods 
                        specified in this Act for the review of 
                        all applications; and
                          (v) improve the consistency and 
                        fairness of the regulatory process of 
                        the Administration.
                The Secretary shall issue such other 
                performance standards that the Secretary 
                determines will contribute to the efficient, 
                fair, and effective operation of the 
                Administration.
                  (D) Annual report.--The Secretary shall 
                prepare and publish in the Federal Register for 
                public comment an annual report that--
                          (i) provides detailed data on the 
                        actual performance of the 
                        Administration relating to the action 
                        taken by the Administration with 
                        respect to the applications and 
                        submissions described in subparagraph 
                        (A)(i) and the activities relating to 
                        advisory committees described in 
                        subparagraph (A)(ii);
                          (ii) compares the performance of the 
                        Administration with each applicable 
                        performance standard developed and 
                        published under subparagraph (A);
                          (iii) describes--
                                  (I) any priorities 
                                established with respect to 
                                action to be taken by the 
                                Administration on matters 
                                relating to the applications 
                                and submissions described in 
                                subparagraph (A)(i) and the 
                                activities relating to advisory 
                                committees described in 
                                subparagraph (A)(ii);
                                  (II) how such priorities are 
                                implemented, and
                                  (III) the data on each 
                                priority category;
                          (iv) analyzes any failure to achieve 
                        any of the performance standards;
                          (v) identifies regulatory policies 
                        that have a significant impact on 
                        compliance with the performance 
                        standards and analyzes how such 
                        policies could be modified in order to 
                        achieve compliance with the performance 
                        standards; and
                          (vi) sets forth a plan to achieve 
                        compliance with the performance 
                        standards that have not been met.
                  (E) Statistical information.--The report 
                described in subparagraph (D) shall include a 
                full statistical presentation relating to all 
                applications, petitions, or notifications for a 
                new drug, device, biological product, new 
                animal drug, food additive, or color additive 
                approved by the Administration during the year, 
                taking into account the date of--
                          (i) the submission of any 
                        investigational application;
                          (ii) the application of any clinical 
                        hold;
                          (iii) the submission of any 
                        application, petition, or notification 
                        for approval or clearance;
                          (iv) the acceptance for filing of any 
                        application, petition, or notification 
                        for approval or clearance;
                          (v) the occurrence of any 
                        unapprovable action;
                          (vi) the occurrence of any approvable 
                        action; and
                          (vii) the approval or clearance of 
                        any application, petition, or 
                        notification.
          (4) Interagency collaboration.--The Secretary shall 
        implement programs and policies that will foster 
        collaboration between the Administration, the National 
        Institutes of Health, and other science-based agencies, 
        to enhance the scientific expertise available to the 
        Commissioner for the evaluation of emerging medical 
        therapies, including complementary therapies, and 
        advances in nutrition and food science.
          * * * * * * *

SEC. 904. [394] SCIENTIFIC REVIEW GROUPS.

    [Without] (a) In General.--Without regard to the provisions 
of title 5, United States Code, governing appointments in the 
competitive service and without regard to the provisions of 
chapter 51 and subchapter III of chapter 53 of such title 
relating to classification and General Schedule pay rates, the 
Commissioner of Food and Drugs may--
          * * * * * * *
  (b) Delegation of Appointment Authority.--The Commissioner 
may not delegate the appointment and oversight authority 
granted under subsection (a).
  (c) Membership and Meeting Requirements.--
          (1) Scope.--The Commissioner shall consult with a 
        scientific review group in determining the matters that 
        the group will consider at the meetings of the 
        scientific review group.
          (2) Notification of scope of discussion.--To the 
        extent feasible, the specific matters (including 
        questions) to be discussed at a meeting of a scientific 
        review group shall be publicly announced and published 
        in the Federal Register at least 30 days prior to the 
        date of the meeting.
          (3) Terms.--A member of a scientific review group 
        shall serve for a term of 3 years, and may have such 
        membership renewed for not more than 1 additional term. 
        An individual may serve on more than one scientific 
        review group. The chairperson of a scientific review 
        group shall be a member who has served on the 
        scientific group for at least 3 years. The term of the 
        chairperson may be renewed for not more than 3 terms.
          (4) Training.--Prior to service on a scientific 
        review group, a member of the group shall be given 
        adequate education and training relating to the 
        responsibilities of the member.
          (5) Frequency of meetings.--The Secretary shall take 
        whatever action is necessary to ensure that regular 
        meetings are held by scientific review groups, at 
        appropriate intervals and for a sufficient length of 
        time. The meetings shall occur not less than 3 times 
        each year unless the Secretary determines that there 
        are sufficient reasons for fewer meetings.
  (d) Access to Information; Participation by Interested 
Persons in Meetings.--
          (1) In general.--When a scientific review group 
        reviews an application or submission (including a 
        petition, notification, or any other similar form of 
        request) for approval or clearance, or some part 
        thereof, submitted for an article under section 409, 
        505, 510(k), 513(f), 512, 515, or 721, the Secretary 
        shall provide the person who submitted the application 
        or submission with copies of all documents provided to 
        the members of the scientific review group in 
        preparation for a meeting of the scientific review 
        group. The Secretary shall provide such documents to 
        the person at the same time such documents are provided 
        to the members of the scientific review group. Before 
        the meeting, the person shall have an opportunity to 
        submit documents to the members of the scientific 
        review group in response to the Secretary's documents. 
        The person shall provide the documents to the 
        Secretary, who shall immediately provide copies of the 
        documents to the members of the scientific review 
        group.
          (2) Participation in meetings.--Any meeting of a 
        scientific review group shall include adequate time for 
        initial presentations and for response to any differing 
        views and the group shall encourage free and open 
        participation by all interested persons.
  (e) FDA Actions.--Not later than 60 days after the date a 
scientific review group makes its conclusions and 
recommendations on any matter under review of the group, the 
official of the Food and Drug Administration responsible for 
the matter shall review the conclusions and recommendations of 
the group, make a final determination on the matter, and notify 
the affected persons of the determination in writing and, if 
the determination differs from the conclusions and 
recommendations of the group, include the reasons for the 
difference.
          * * * * * * *

SEC. 906. INFORMATION SYSTEM.

  The Secretary shall establish and maintain an information 
system to track the status and progress of each application or 
submission (including a petition, notification, or other 
similar form of request) for the approval or clearance of a 
drug, biological product, new animal drug, device, food 
additive, or color additive submitted to the Food and Drug 
Administration. The system shall permit access by the 
applicant, petitioner, or the person who submits a 
notification.

SEC. 907. APPEALS WITHIN THE FOOD AND DRUG ADMINISTRATION.

    (a) Employee Decisions.--The Secretary shall by regulation 
establish an internal appeal system within the Food and Drug 
Administration for the appeal of any decision made by an 
employee of the Food and Drug Administration, except that this 
subsection shall not apply to decisions involving formal 
administrative or judicial proceedings. As the final stage in 
the internal appeal system, the Secretary shall provide for the 
right to request an evaluation by an appropriate scientific 
review group of a final decision of the Secretary on an appeal 
involving a significant scientific issue. Upon receipt of such 
a request, the Secretary shall refer the request to the 
chairperson of the appropriate scientific review group, or a 
member designated by the chairperson, who shall review the 
request and determine whether the scientific review group 
should conduct an evaluation. The Secretary shall make publicly 
known the existence of the internal appeal system and the 
procedures for an internal appeal.
    (b) Review by Scientific Review Group.--
          (1) In general.--The sponsor of a preclinical or 
        clinical investigation, or the applicant for the 
        approval or clearance of an application or submission 
        (including a petition, notification, or any other 
        similar form of request), shall have the right to 
        request an evaluation by an appropriate scientific 
        review group established under section 904 of any 
        significant scientific issue pending before, or any 
        significant scientific decision made by, the Secretary 
        under this Act. An appropriate scientific review group 
        shall review the request and determine whether to 
        conduct an evaluation within 30 days after the date the 
        request is received by the Secretary.
          (2) Scope.--The significant scientific issues that a 
        scientific review group may evaluate include matters 
        involving a decision by the Secretary not to permit a 
        clinical investigation to begin or to continue, a 
        refusal by the Secretary to file an application, a 
        protocol design, and decisions relating to a pending 
        application or submission (including a petition, 
        notification, or any other similar form of request). 
        The significant scientific issues shall not have been 
        previously reviewed by a scientific review group.
          (3) Time limitation.--If a scientific review group 
        agrees to conduct an evaluation on an issue under 
        paragraph (1), the evaluation shall be scheduled for 
        the next meeting of the group.
    (c) Additional Informal and Formal Procedures.--
          (1) In general.--For purposes of obtaining 
        conclusions and recommendations regarding the 
        resolution of any significant scientific dispute, the 
        Secretary is authorized to use such additional informal 
        and formal procedures as may be considered useful. The 
        procedures may include the use of--
                  (A) panels of qualified Food and Drug 
                Administration officials to make conclusions 
                and recommendations regarding the resolution of 
                any significant scientific dispute;
                  (B) panels of qualified Federal Government 
                employees who are not employees of the Food and 
                Drug Administration to make conclusions and 
                recommendations regarding the resolution of any 
                significant scientific dispute; and
                  (C) outside mediators and arbitrators who are 
                not Federal Government employees to make 
                conclusions and recommendations regarding the 
                resolution of any significant scientific 
                dispute.
          (2) Application of faca.--The Federal Advisory 
        Committee Act (5 U.S.C. App. 2) shall not apply to a 
        panel described in paragraph (1).
    (d) Review of Recommendations.--Not later than 60 days 
after the date on which a matter that is presented for 
resolution under this section has been the subject of 
conclusions and recommendations, the official of the Food and 
Drug Administration responsible for the matter shall review the 
conclusions and recommendations, make a final determination on 
the matter, and notify the parties of the determination in 
writing and if the determination differs from the conclusions 
and recommendations, the reasons for the difference.

SEC. 908. EFFECTIVE MEDICATION GUIDES.

    (a) In General.--Not later than 30 days after the date of 
enactment of this section, the Secretary shall request that 
national organizations representing health care professionals, 
consumer organizations, voluntary health agencies, the 
pharmaceutical industry, drug wholesalers, patient drug 
information database companies, and other relevant parties 
collaborate to develop a long-range comprehensive action plan 
to achieve goals consistent with the goals of the proposed rule 
of the Food and Drug Administration on ``Prescription Drug 
Product Labeling: Medication Guide Requirements'' (60 Fed. Reg. 
44182; relating to the provision of oral and written 
prescription information to consumers).
    (b) Plan.--The plan described in subsection (a) shall--
          (1) identify the plan goals;
          (2) assess the effectiveness of the current private-
        sector approaches used to provide oral and written 
        prescription information to consumers;
          (3) develop guidelines for providing effective oral 
        and written prescription information consistent with 
        the findings of any such assessment;
          (4) develop a mechanism to assess periodically the 
        quality of the oral and written prescription 
        information and the frequency with which the 
        information is provided to consumers; and
          (5) provide for compliance with relevant State board 
        regulations.
    (c) Limitation on the Authority of the Secretary.--The 
Secretary shall have no authority to implement the proposed 
rule described in subsection (a), or to develop any similar 
regulation, policy statement, or other guideline specifying a 
uniform content or format for written information voluntarily 
provided to consumers about prescription drugs if, not later 
than 120 days after the date of enactment of this section, the 
national organizations described in subsection (a) develop and 
begin to implement a comprehensive, long-range action plan (as 
described in subsection (a)) regarding the provision of oral 
and written prescription information.
    (d) Secretary Review.--Not later than January 1, 2001, the 
Secretary shall review the status of private-sector initiatives 
designed to achieve the goals of the plan described in 
subsection (a), and if such goals are not achieved, the 
limitation in subsection (c) shall not apply, and the Secretary 
shall seek public comment on other initiatives that may be 
carried out to meet such goals. The Secretary shall not 
delegate such review authority to the Commissioner.

SEC. 909. CENTERS FOR EDUCATION AND RESEARCH ON DRUGS, DEVICES, AND 
                    BIOLOGICAL PRODUCTS.

    (a) In General.--The Secretary, acting through the 
Commissioner, shall establish a consortium of 3 or more centers 
for research and education on drugs, devices, and biological 
products in accordance with subsection (b).
    (b) Grant Authority.--The Secretary, acting through the 
Commissioner, shall make grants to 3 or more private entities 
to assist each of the entities in the establishment and 
operation of a center for research and education on drugs, 
devices, and biological products. In awarding a grant under 
this subsection, the Secretary shall use a peer-review 
selection procedure.
    (c) Authorized Grant Activities.--
          (1) Required activities.--A grant awarded under 
        subsection (b) shall be used to--
                  (A) conduct state-of-the-art clinical and 
                laboratory research that--
                          (i) increases awareness of new uses 
                        of drugs, devices, or biological 
                        products and the unforeseen risks of 
                        new uses of drugs, devices, or 
                        biological products;
                          (ii) provides objective clinical 
                        information to--
                                  (I) health care practitioners 
                                or other providers of health 
                                care goods or services;
                                  (II) pharmacy benefit 
                                managers;
                                  (III) health maintenance 
                                organizations or other managed 
                                health care organizations; and
                                  (IV) health care insurers or 
                                governmental agencies; and
                          (iii) improves the quality of health 
                        care while reducing the cost of health 
                        care through the prevention of adverse 
                        effects of drugs, devices, or 
                        biological products and the 
                        consequences of such effects, such as 
                        unnecessary hospitalizations; and
                  (B) conduct research on the comparative 
                effectiveness and safety of drugs, devices, or 
                biological products.
          (2) Discretionary activities.--A grant awarded under 
        subsection (b) may be used to conduct--
                  (A) surveillance of the adverse effects of 
                drugs, devices, or biological products;
                  (B) a study of new or unapproved uses for 
                marketed drugs, devices, or biological 
                products; or
                  (C) a study of the therapeutic 
                characteristics of clinically special 
                populations, such as children, women, and 
                elderly individuals.
          (3) Limitation.--A grant awarded under subsection (b) 
        may not be used to assist the Secretary in the review 
        of new drugs.
    (d) Application.--An entity that desires to receive a grant 
under this section shall submit to the Secretary an application 
at such time, in such manner, and accompanied by such 
information as the Secretary may require.
    (e) Establishment of an Oversight Committee.--The Secretary 
shall establish within the Food and Drug Administration a 
committee to provide oversight of the research and educational 
activities of the consortium of centers described in subsection 
(a). The committee shall be composed of--
          (1) a representative from each of the centers;
          (2) a representative from the Food and Drug 
        Administration;
          (3) a representative from consumer advocacy groups; 
        and
          (4) a representative from the pharmaceutical, device, 
        or biological products industry.
    (f) Report.--Not later than September 30, 1999, the 
Secretary shall prepare and submit to the Chairmen and Ranking 
Members of the Committee on Labor and Human Resources of the 
Senate and the Committee on Commerce of the House of 
Representatives a report on the activities of the consortium of 
centers established pursuant to this section. The report shall 
include an analysis on the impact of the centers on the safe 
use of drugs, devices, and biological products and 
recommendations on whether the funding for the centers should 
be extended and increased.
    (g) Authorization of Appropriations.--There are authorized 
to be appropriated to carry out this section $9,000,000 for 
fiscal year 1997, $12,000,000 for fiscal year 1998, $15,000,000 
for fiscal year 1999, and $15,000,000 for fiscal year 2000.
          * * * * * * *

                       PUBLIC HEALTH SERVICE ACT

          * * * * * * *

    Part F--Licensing--Biological Products and Clinical Laboratories

                     Subpart 1--Biological Products

                   regulation of biological products

    [Sec. 351. [262] (a) No person shall sell, barter, or 
exchange, or offer for sale, barter, or exchange in the 
District of Columbia, or send, carry, or bring for sale, 
barter, or exchange from any State or possession into any other 
State or possession or into any foreign country, or from any 
foreign country into any State or possession, any virus, 
therapeutic serum, toxin, antitoxin, vaccine, blood, blood 
component or derivative, allergenic product, or analogous 
product, of arsphenamine or its derivatives (or any other 
trivalent organic arsenic compound), applicable to the 
prevention, treatment, or cure of diseases or injuries of man, 
unless (1) such virus, serum, toxin, antitoxin, vaccine, blood, 
blood component or derivative, allergenic product, or other 
product has been propagated or manufactured and prepared at an 
establishment holding an unsuspended and unrevoked license, 
issued by the Secretary as hereinafter authorized, to propagate 
or manufacture, and prepare such virus, serum, toxin, 
antitoxin, vaccine, blood, blood component or derivative, 
allergenic product, or other product for sale in the District 
of Columbia, or for sending, bringing, or carrying from place 
to place aforesaid; and (2) each package of such virus, serum, 
toxin, antitoxin, vaccine, blood, blood component or 
derivative, allergenic product, or other product is plainly 
marked with the proper name of the article contained therein, 
the name, address, and license number of the manufacturer, and 
the date beyond which the contents cannot be expected beyond 
reasonable doubt to yield their specific results. The 
suspension or revocation of any license shall not prevent the 
sale, barter, or exchange of any virus, serum, toxin, 
antitoxin, vaccine, blood, blood component or derivative, 
allergenic product, or other product aforesaid which has been 
sold and delivered by the licensee prior to such suspension or 
revocation, unless the owner or custodian of such virus, serum, 
toxin, antitoxin, vaccine, blood, blood component or 
derivative, allergenic product, or other product aforesaid has 
been notified by the Secretary not to sell, barter, or exchange 
the same.]
  Sec. 351. (a)(1) Except as provided in paragraph (6), no 
person shall introduce or deliver for introduction into 
interstate commerce any biological product unless--
          (A) a license is in effect for the biological 
        product; and
          (B) each package of the biological product is plainly 
        marked with the proper name of the biological product 
        contained therein, the name, address, and applicable 
        license number of the manufacturer of the biological 
        product, and the expiration date of the biological 
        product.
  (2) The license required under paragraph (1)(A) shall, as 
determined by the Secretary, cover the biological product, any 
facility in which the biological product is manufactured, 
processed, packed, or held, or both the product and facility.
  (3)(A) The Secretary shall establish, by regulation, 
requirements for license applications for biological products.
  (B) Except as provided in subparagraph (D), a license 
application that covers a biological product shall be approved 
based upon a demonstration that--
          (i) the product that is the subject of the 
        application is safe and effective in accordance with 
        sections 505(c) and 505(d) of the Federal Food, Drug, 
        and Cosmetic Act (21 U.S.C. 355 (c) and (d)), or meets 
        standards designed to ensure that the product is safe, 
        pure, and where appropriate, potent; and
          (ii) the methods used in, and the facilities and 
        control used for, the manufacture, processing, packing, 
        and holding of such product meet standards designed to 
        ensure that the product continues to meet the 
        requirements of clause (i).
  (C) A license application that covers a facility shall ensure 
that the product and the facility meet standards designed to 
ensure that the product meets applicable requirements of 
subparagraph (B).
  (D) A license application for blood or a blood component 
(including plasma) shall be approved based on a demonstration 
that the product is safe, pure, and where appropriate, potent, 
and that the facility in which the product is manufactured, 
processed, packed, or held meets standards designed to ensure 
that such product is safe, pure, and where appropriate, potent.
  (4)(A) Requirements prescribed under paragraph (3) shall 
include a requirement for preapproval inspection under 
subsection (c).
  (B) A license shall be approved only on condition that the 
licensee agrees to permit inspection of the facility of 
licensee in accordance with subsection (c).
  (5)(A) Except as provided in subparagraph (C), an approved 
license for a biological product may be revoked if the 
Secretary determines, on the record after providing opportunity 
for a hearing in accordance with section 554 of title 5, United 
States Code, that the requirements for approval specified in 
paragraph (3) are no longer met with respect to such product, 
or that other public health reasons, prescribed by regulation, 
exist. No action to revoke a license based on findings of an 
inspection shall be initiated prior to the submission and 
review by the Secretary of a written response submitted by the 
licensee to a notice of inspectional findings so long as such 
written response is received within 30 days after the date of 
receipt by the licensee of the findings. The revocation of any 
product license shall not prevent the continued use of any 
licensed biological product that has been sold and delivered by 
the licensee unless the biological product is subject to recall 
under subsection (d).
  (B) If at any time before the Secretary has taken final 
action to revoke a license, the licensee requests an inspection 
by the Secretary to determine whether the licensee is in 
compliance with applicable standards, the Secretary shall 
conduct an inspection within 30 days after the date of the 
request. If the requested inspection confirms that the licensee 
is not in compliance with applicable standards, the 30-day 
requirement for inspection shall not apply to any subsequent 
request by the licensee under this subparagraph for inspection. 
If the inspection confirms that the licensee is in compliance 
with all applicable requirements, the Secretary shall withdraw 
any proposed action within 30 days after the inspection.
  (C) If the Secretary determines that conditions exist that 
constitute a danger to health, the Secretary shall suspend the 
license, notify the licensee that the licensee's license is 
suspended, and require notification of the suspension to any 
consignee. Within 30 days thereafter, the Secretary shall 
initiate the hearing process under subparagraph (A).
    (6) The requirements of paragraph (1) do not apply to a 
biological product for which there is in effect an 
investigational new drug application under section 505(i) of 
the Federal Food, Drug, and Cosmetic Act.
    [(b) No person shall falsely label or mark any package or 
container or any virus, serum, toxin, antitoxin, vaccine, 
blood, blood component or derivative, allergenic product, or 
other product aforesaid; nor alter any label or mark on any 
package or container of any virus, serum, toxin, antitoxin, 
vaccine, blood, blood component or derivative, allergenic 
product, or other product aforesaid so as to falsify such label 
or mark.]
    (b) No person shall falsely label or mark any package or 
container of any biological product or alter any label or mark 
on the package so as to falsify the label or mark.
    (c) Any officer, agent, or employee of the Department of 
Health and Human Services, authorized by the Secretary for the 
purpose, may during all reasonable hours enter and inspect any 
establishment for the propagation or manufacturer and 
preparation of any [virus, serum, antitoxin, vaccine, blood, 
blood component or derivative, allergenic product, or other 
product aforesaid] biological product for sale, barter, or 
brought from any State or possession into any other State or 
possession or into any foreign country, or from any foreign 
country into any State or possession.
    [(d)(1) Licenses for the maintenance of establishments for 
the propagation or manufacture and preparation of products 
described in subsection (a) of this section may be issued only 
upon a showing that the establishment and the products for 
which a license is desired meet standards, designed to insure 
the continued safety, purity, and potency of such products, 
prescribed in regulations, and they meet such standards. All 
such licenses shall be issued, suspended, and revoked as 
prescribed by regulations and all licenses issued for the 
maintenance of establishment for the propagation or manufacture 
and preparation, in any foreign country, of any such products 
for sale, barter, or exchange in any State or possession shall 
be issued upon condition that the licenses will permit the 
inspection of their establishments in accordance with 
subsection (c) of this section.]
    [(2)(A)] (d)(1) Upon a determination that a batch, lot, or 
other quantity of a product licensed under this section 
presents an imminent or substantial hazard to the public 
health, the Secretary shall issue an order immediately ordering 
the recall of such batch, lot, or other quantity of such 
product. An other under this paragraph shall be issued in 
accordance with section 554 of title 5, United States Code.
    [(B)] (2) Any violation of [subparagraph (A)] paragraph (1) 
shall subject the violator to a civil penalty of up to $100,000 
per day of violation. The amount of a civil penalty under this 
subparagraph shall, effective December 1 of each year beginning 
1 year after the effective date of this subparagraph, be 
increased by the percent change in the Consumer Price Index for 
the base quarter of such year over the Consumer Price Index for 
the base quarter of the preceding year, adjusted to the nearest 
\1/10\ of 1 percent. For purposes of this subparagraph, the 
term ``base quarter'', as used with respect to a year, means 
the calendar quarter ending on September 30 of such year and 
the price index for a base quarter is the arithmetical mean of 
such index for the 3 months comprising such quarter.
          * * * * * * *
    (i) For purposes of this section, the term ``biological 
product'' means a virus, therapeutic serum, toxin, antitoxin, 
vaccine, blood, blood component or derivative, allergenic 
biologic product, or arsphenamine or its derivative (or any 
other analogous biological product) applicable to the 
prevention, treatment, or cure of diseases or conditions of 
human beings.
    (j)(1) Sections 505(i), 903, and 904 of the Federal Food, 
Drug, and Cosmetic Act shall apply to all biological products, 
and references in such sections to new drug applications shall 
be deemed to include product license applications for 
biological products.
    (2) Requirements involving labeling or advertising for 
biological products shall be established in accordance with 
sections 201(m) and 502(n) of the Federal Food, Drug, and 
Cosmetic Act.
          * * * * * * *

                           PUBLIC LAW 102-222

          * * * * * * *

SECTION 1. HEALTH EDUCATION ASSISTANCE LOANS.

          * * * * * * *

SEC. 2. PILOT PROGRAM IN CLINICAL PHARMACOLOGY.

    (a) Establishment.--* * *
          * * * * * * *
    (b) Authorization of Appropriations.--There is authorized 
to be appropriated for fiscal years 1992 through 1996 $750,000 
for each fiscal year [to carry out this section], and fiscal 
years 1997 and 1998 $1,900,000 for each fiscal year, to carry 
out this section.
          * * * * * * *

                                
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