[Federal Register Volume 63, Number 94 (Friday, May 15, 1998)]
[Notices]
[Pages 27093-27094]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-12901]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 97D-0100]


Guidance for Industry on Providing Clinical Evidence of 
Effectiveness for Human Drugs and Biological Products; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a guidance for industry entitled ``Providing Clinical 
Evidence of Effectiveness for Human Drug and Biological Products.'' The 
purpose of this guidance is to clarify what clinical evidence of 
effectiveness should be provided in new drug applications, biological 
product license applications, and supplemental applications for new 
uses of drugs and biologics. The guidance is also intended to fulfill 
the requirements of certain provisions of the Food and Drug 
Administration Modernization Act of 1997 (the Modernization Act).

DATES: General comments on agency guidance documents are welcome at any 
time.

ADDRESSES: An electronic version of this guidance is available via the 
Internet at http://www.fda.gov/cder/guidance/index.htm and at http://
www.fda.gov/cber/guidelines.htm. Submit written comments on this 
guidance to the Dockets Management Branch (HFA-305), Food and Drug 
Administration, 12420 Parklawn Dr., rm. 1-23, Rockville, MD 20857. 
Comments are to be identified with the docket number found in brackets 
in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Joseph P. Griffin, Center for Drug 
Evaluation and Research (HFD-5), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-594-5400.

SUPPLEMENTARY INFORMATION: The draft guidance for industry entitled 
``Providing Clinical Evidence of Effectiveness for Human Drug and 
Biological Products'' (the draft guidance) was initially developed as 
part of an effort to get more information about valid uses of marketed 
drugs into the labeling of these drugs. Uncertainty on the part of the 
industry about the evidentiary requirements for demonstrating 
effectiveness for a supplemental indication was believed to be an 
obstacle to sponsors submitting applications for supplemental 
indications. The draft guidance was intended to clarify the amount and 
types of evidence that could be used to demonstrate effectiveness and 
thereby facilitate submission of additional supplemental applications. 
In the Federal Register of March 21, 1997 (62 FR 13650), FDA announced 
the availability of the draft guidance. The notice gave interested 
persons an opportunity to submit comments by May 20, 1997.
    On November 21, 1997, the President signed the Modernization Act 
(Pub. L. 105-115), which addressed both the standards for providing 
clinical evidence of effectiveness and the evidentiary requirements for 
supplemental applications. Section 115 of the Modernization Act amended 
the definition of substantial evidence in section 505(d) of the Federal 
Food,

[[Page 27094]]

Drug, and Cosmetic Act (the act) (21 U.S.C. 355(d)) to clarify that 
FDA, at its discretion, may make exception to the general requirement 
that there must be more than one adequate and well-controlled 
investigation to support an effectiveness determination. Section 115 of 
the Modernization Act provides in relevant part that ``[i]f the 
[agency] determines, based on relevant science, that data from one 
adequate and well-controlled clinical investigation and confirmatory 
evidence (obtained prior to or after such investigation) are sufficient 
to establish effectiveness, the [agency] may consider such data and 
evidence to constitute substantial evidence [of effectiveness].''
    In clarifying the standard for substantial evidence, Congress 
acknowledged the agency's position that there have been major advances 
in the science and practice of clinical drug development since the 
effectiveness requirement was added to the act in 1962, and confirmed 
FDA's interpretation of the substantial evidence of effectiveness 
standard, as explained in the draft guidance document.
    In addition to the provision on the evidence standard, the 
Modernization Act included section 403, ``Approval of Supplemental 
Applications for Approved Products.'' Section 403(a) of the 
Modernization Act requires FDA to publish in the Federal Register, 
within 180 days of enactment, standards for the prompt review of 
supplemental applications for drugs and biological products. These 
standards are included in a guidance document for which a notice of 
availability is published elsewhere in this issue of the Federal 
Register.
    Section 403(b) of the Modernization Act requires that FDA, within 
180 days of enactment, issue final guidances to clarify the 
requirements for, and facilitate the submission of data to support, the 
approval of supplemental applications for drugs and biologics. The 
guidance issued today fulfills this statutory requirement as it 
addresses the data requirements for both original drug and biological 
product applications and supplements to those applications.
    In addition, section 403(b)(1) of the Modernization Act requires 
that FDA provide guidance to ``clarify circumstances in which published 
matter may be the basis for approval of a supplemental application.'' 
Section III of the guidance describes the circumstances in which a 
sponsor may rely in part, or entirely, on published reports of studies 
to support approval of a supplemental application.
    Section 403(b)(2) of the Modernization Act requires that FDA 
provide guidance to ``specify data requirements that will avoid 
duplication of previously submitted data by recognizing the 
availability of data previously submitted in support of an original 
application.'' Section II of the guidance describes a range of 
circumstances in which existing data, whether or not previously 
submitted to an original application, may be used to support an 
application for a supplemental indication, thus permitting a sponsor to 
avoid developing unnecessary additional data.
    The agency received 13 submissions commenting on the draft 
guidance, including comments from pharmaceutical and biological 
products companies and their trade associations, individuals and 
organizations in academic medicine and clinical pharmacology, patient 
advocacy organizations, and a consumer. The response to the draft 
guidance was generally favorable. The guidance was viewed as a 
significant step forward by the agency in clarifying and better 
articulating its quantitative and qualitative evidentiary standards for 
evidence of effectiveness. Comments observed that the principles 
espoused were scientifically reasonable, practical, and appropriately 
flexible. The agency has considered all of the comments in making 
revisions to the guidance document.
    This guidance document is being issued as a Level 1 guidance 
consistent with FDA's good guidance practices (62 FR 8961, February 27, 
1997). It represents the agency's current thinking on clinical evidence 
of effectiveness for human drug and biological products. It does not 
create or confer any rights for or on any person and does not operate 
to bind FDA or the public. An alternative approach may be used if such 
approach satisfies the requirements of the applicable statute, 
regulations, or both.
    Submit written requests for single copies of the guidance for 
industry entitled ``Providing Clinical Evidence of Effectiveness for 
Human Drug and Biological Products'' to the Drug Information Branch 
(HFD-210), Center for Drug Evaluation and Research, Food and Drug 
Administration, 5600 Fishers Lane, Rockville, MD 20857; or the Office 
of Communication, Training and Manufacturers Assistance (HFM-40), 
Center for Biologics Evaluation and Research (CBER), Food and Drug 
Administration, 1401 Rockville Pike, Rockville, MD 20852-1448. Please 
send one self-addressed adhesive label to assist the offices in 
processing your request. The document may also be obtained by mail by 
calling the CBER Voice Information System at 1-800-835-4709 or 301-827-
1800, or by fax by calling the CBER FAX Information System at 1-888-
CBERFAX or 301-827-3844.
    Interested persons may at any time submit written comments on the 
guidance to the Dockets Management Branch (address above). Requests and 
comments should be identified with the docket number found in brackets 
in the heading of this notice. A copy of the guidance and received 
comments may be seen in the office above between 9 a.m. and 4 p.m., 
Monday through Friday.

    Dated: May 8, 1998.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 98-12901 Filed 5-14-98; 8:45 am]
BILLING CODE 4160-01-F