[Federal Register Volume 61, Number 65 (Wednesday, April 3, 1996)]
[Proposed Rules]
[Pages 14922-14942]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-8090]




[[Page 14921]]

_______________________________________________________________________

Part III





Department of Health and Human Services





_______________________________________________________________________



Food and Drug Administration



_______________________________________________________________________



21 CFR Part 25



National Environmental Policy Act: Proposed Revision of Policies and 
Procedures; Proposed Rule

  Federal Register / Vol. 61, No. 65 / Wednesday, April 3, 1996 / 
Proposed Rules  

[[Page 14922]]


DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 25

[Docket No. 96N-0057]


National Environmental Policy Act; Proposed Revision of Policies 
and Procedures

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is proposing to amend 
its regulations governing compliance with the National Environmental 
Policy Act of 1969 (NEPA) as implemented by the regulations of the 
Council on Environmental Quality (CEQ). The primary purpose of this 
proposed rule is to increase the efficiency of FDA's implementation of 
NEPA and reduce the number of NEPA evaluations by providing for 
categorical exclusions for additional classes of actions that do not 
individually or cumulatively have a significant effect on the human 
environment and for which, therefore, neither an environmental impact 
statement (EIS) nor an environmental assessment (EA) is required. FDA 
is also proposing to amend its regulations to make its NEPA procedures 
more concise and understandable to the public and to reflect current 
FDA policy with respect to environmental considerations. This proposed 
rule is in response to initiatives announced in the President's 
National Performance Reports, ``Reinventing Drug and Medical Device 
Regulations,'' April 1995, and ``Reinventing Food Regulations,'' 
January 1996.

DATES: Submit written comments on the proposed rule by July 2, 1996. 
Submit written comments on the information collection requirements by 
May 3, 1996.
ADDRESSES: Submit written comments on the proposed rule to the Dockets 
Management Branch (HFA-305), Food and Drug Administration, rm. 1-23, 
12420 Parklawn Dr., Rockville, MD 20857. Submit written comments on the 
information collection requirements to the Office of Information and 
Regulatory Affairs, Office of Management and Budget (OMB), New 
Executive Office Building, 725 17th St. NW., rm. 10235, Washington, DC 
20503, Attn.: Desk Officer for FDA.
FOR FURTHER INFORMATION CONTACT: For information regarding human drugs: 
Nancy Sager, Center for Drug Evaluation and Research (HFD-357),-Food 
and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-
594-6740.
    For information regarding biologics: Nancy Roscioli, Center for 
Biologics Evaluation and Research (HFM-205), Food and Drug 
Administration, 1401 Rockville Pike, Rockville, MD 20852, 301-827-3031.
    For information regarding veterinary medicines: Charles E. Eirkson, 
Center for Veterinary Medicine (HFV-150), Food and Drug Administration, 
7500 Standish Pl., Rockville, MD 20855, 301-594-1683.
    For information regarding foods: Buzz L. Hoffmann, Center for Food 
Safety and Applied Nutrition (HFS-246), Food and Drug Administration, 
200 C St. SW.,Washington, DC 20204, 202-418-3005.
    For information regarding medical devices and radiological health: 
Mervin Parker,-Center for Devices and Radiological Health (HFZ-402), 
Food and Drug Administration, 9200 Corporate Blvd., Rockville, MD 
20850, 301-594-2186.
SUPPLEMENTARY INFORMATION:

I. Background

    NEPA requires all Federal agencies to assess the environmental 
impact of their actions and to ensure that the interested and affected 
public is informed of environmental analyses. CEQ is responsible for 
overseeing Federal efforts to comply with NEPA. Both CEQ and FDA have 
issued regulations governing agency obligations and responsibilities 
under NEPA. In the Federal Register of March 15, 1973 (38 FR 7001), FDA 
issued its first regulations to implement NEPA. FDA amended these 
regulations in the Federal Register of April 15, 1977 (42 FR 19986), 
based on consideration of revised guidelines for preparing EIS's issued 
by CEQ. In 1978, CEQ replaced its guidelines with regulations 
implementing the procedural requirements of NEPA (40 CFR parts 1500 to 
1508). To comply with CEQ regulations, in the Federal Register of April 
26, 1985 (50 FR 16636), FDA revised its NEPA policies and procedures in 
part 25 (21 CFR part 25).
    The CEQ regulations, which are binding on all Federal executive 
agencies, establish formal guidance on the requirements of NEPA. 
Agencies must adopt procedures to supplement them. In adopting NEPA-
implementing procedures, Federal agencies are directed by CEQ to reduce 
paperwork (40 CFR 1500.4 and 1500.2(b)) and to reduce delay (40 CFR 
1500.5) by using several means including the use of categorical 
exclusions. CEQ defines categorical exclusions as categories of actions 
which do not individually or cumulatively have a significant effect on 
the human environment and for which neither an EA nor an EIS is 
required (40 CFR 1508.4). The CEQ regulations also state that agencies 
shall continue to review their policies and procedures and, in 
consultation with CEQ, revise them as necessary to ensure full 
compliance with the purpose and provisions of NEPA (40 CFR 1507.3).

II. Overview of the Proposed Rule

    Since FDA's NEPA policies and supplemental procedures were 
published in 1985, the agency has prepared EA's for many agency-
initiated actions and has reviewed hundreds of EA's for a variety of 
industry requests for agency action. Based on FDA's experience 
reviewing EA's and on its evaluation and knowledge of other relevant 
environmental science, FDA has determined that certain classes of 
actions normally do not cause significant environmental effects, and 
therefore, should be added to the list of actions that are excluded 
from the requirement to prepare an EA or an EIS. Some of these actions 
had already been identified by FDA as unlikely to cause significant 
environmental effects, as evidenced by the fact that the agency has 
been requiring less information to support these actions, i.e., an 
abbreviated EA rather than a full EA (see Sec. 25.31a(b)).
    Thus, in response to the President's reinventing Government 
initiatives announced in the President's National Performance Reports, 
``Reinventing Drug and Medical Device Regulations,'' April 1995, and 
``Reinventing Food Regulations,'' January 1996, FDA, in consultation 
with CEQ, is now proposing to increase the efficiency of FDA's 
implementation of NEPA and to substantially reduce the number of NEPA 
evaluations by providing for categorical exclusions for additional 
classes of actions that do not individually or cumulatively have a 
significant impact on the human environment and for which, therefore, 
neither an EA nor an EIS is required. This proposal would substantially 
reduce the number of EA's required to be submitted by industry and 
reviewed by FDA and, consequently, reduce the number of findings of no 
significant impact (FONSI's) the agency would be required to prepare. 
Furthermore, the proposal will not compromise the environment because 
the excluded actions have been found not to have a significant effect 
on the environment, and the proposed rule would continue

[[Page 14923]]
to provide for the preparation of an EA under extraordinary 
circumstances in which a categorically excluded action may have a 
significant environmental impact. This proposal would enable FDA to 
focus its resources in the environmental area on situations likely to 
have an effect on the environment.
    The agency is also proposing to revise its environmental 
regulations to make them more concise and useful to the public and 
regulated industry by reorganizing, simplifying, and eliminating 
unnecessary and duplicative language. The proposed rule would 
reorganize and renumber various sections so that information on certain 
topics is grouped together. The agency solicits comments on and 
suggestions for further improvement in these regulations.

III. Specific Proposed Changes

A. General Provisions

    The proposed rule would eliminate unnecessary language in current 
subpart A of part 25 by deleting the reference to the environmental 
statutes listed in current Sec. 25.5 Policies, amending Sec. 25.15 
Terminology (proposed Sec. 25.5), and making other minor revisions, 
including combining Sec. 25.5 Policies and Sec. 25.10 NEPA planning 
into proposed Sec. 25.10 Policies and NEPA planning.
    In proposed Sec. 25.5 Terminology, FDA is proposing to remove 
definitions listed in current Sec. 25.15 that are not used in part 25, 
and add new definitions for ``active moiety'' and ``increased use'' of 
a drug. ``Increased use'' of a drug will occur if the drug will be 
administered at higher dosage levels, for longer duration, or for 
different indications than were previously in effect, or if the drug is 
a new molecular entity. ``Increased use'' encompasses consideration of 
FDA-regulated articles that are disposed of by consumers.Eric Flamm 
suggests wording: ``Increased use'' encompasses consideration of 
disposal of FDA regulated articles by consumers. ``Active moiety'' has 
been previously defined in FDA regulations (21 CFR 314.108(a)).

B. Agency Actions Requiring Environmental Consideration-

    Proposed Sec. 25.15 would contain the general procedural 
information now found in current Secs. 25.20 and 25.22.
    The proposed rule would create new Sec. 25.l6 Public health and 
safety emergencies using revised language now contained in current 
Sec. 25.40(b).
    Actions requiring preparation of an EA (proposed Sec. 25.20) would 
remain essentially the same as current Sec. 25.22, except that: (1) 
Current Sec. 25.22(a)(13), promulgation and enforcement of FDA 
regulations relating to the control of communicable disease and to 
interstate conveyance sanitation, has been deleted and is covered by 
proposed Sec. 25.20(g); and (2) actions relating to approval of new 
drug applications (NDA's) and abbreviated applications, actions on 
investigational new drug applications (IND's) (current 
Sec. 25.22(a)(14)), issuance of licenses for biologic products (current 
Sec. 25.22(a)(16)), and approval of supplements to existing approvals 
of FDA-regulated articles (Sec. 25.22(a)(8)) have been combined into 
one provision (proposed Sec. 25.20(l)) and revised to reflect current 
terminology.
    The proposed regulations include new Sec. 25.21 Extraordinary 
circumstances, which addresses circumstances under which categories of 
actions that would ordinarily be categorically excluded would require 
preparation of environmental documents. Proposed Sec. 25.21 
incorporates current Sec. 25.23(b) and includes two examples of 
circumstances under which an action would require the preparation of 
environmental documents because it might have the potential to 
significantly affect the environment. The examples of circumstances 
that will cause an action not to qualify for categorical exclusion are: 
(1) Actions for which data available establish that, at the expected 
level of exposure, there is the potential for serious harm to the 
environment (proposed Sec. 25.21(a)); and (2) actions that adversely 
affect a species or the critical habitat of a species determined under 
the Endangered Species Act or the Convention on International Trade in 
Endangered Species of Wild Flora and Fauna to be endangered or 
threatened, or wild flora or fauna that are entitled to special 
protection under some other Federal law (proposed Sec. 25.21(b)). In 
addition, the proposed rule references the CEQ regulations at 40 CFR 
1508.27, which provide examples of circumstances in which significant 
effects may occur. Extraordinary circumstances may be shown by either 
data available to the agency or data available to the applicant or 
petitioner and may be based on production, use, or disposal from use.
    The two examples of extraordinary circumstances in proposed 
Sec. 25.21 reflect Are they really disqualification criteria? If the 
criteria are met, the exclusion is warranted. See 25.24(c)(1). Gail 
concurs with this.criteria that appear in some of the categorical 
exclusions listed in current Sec. 25.24. The language in the first 
example, proposed Sec. 25.21(a), is derived from but differs slightly 
from current Sec. 25.24 language relating to toxicity (see, e.g., 
Sec. 25.24(a)(10), (b)(2), and (c)(6)). The extraordinary circumstance 
example in proposed Sec. 25.21(a) would revise the language in current 
Sec. 25.24, ``the substance may be toxic to organisms in the 
environment'' to read ``there may be harm to the environment.'' FDA is 
revising this language to reflect that possible adverse environmental 
effects other than toxicity should be considered. For example, some 
biological agents that may be released may not be toxic to indigenous 
organisms, but could have lasting effects on ecological community 
dynamics.
    FDA considers a substance to be toxic if it is harmful to some 
biological mechanism or system. Although FDA recognizes that any 
substance may produce damage to biological mechanisms or systems under 
specific conditions, for the purposes of these regulations, FDA 
considers a substance to be toxic if it is harmful to appropriate test 
organisms at the expected level of exposure even though it may be 
without effect in humans or other organisms at these concentrations, 
and may even be used by humans because of its toxic properties.
    As a result of the new language in proposed Sec. 25.21(a), the 
words ``toxic'' and ``toxic substance'' are no longer used in the 
proposed regulation. Therefore, FDA is proposing to remove the 
definition of ``toxic substance'' at current Sec. 25.15(b)(6). 
Furthermore, FDA no longer believes that the second part of the current 
definition relating to toxicity of a substance is appropriate for the 
following reasons: (1) Evaluation of the toxicity of a substance based 
only on the concentration at the point of entry or point of highest 
concentration ignores factors such as instantaneous dispersion that 
typically takes place as a result of processes such as river flow and 
wind, and that not all substances bioaccumulate. Consideration of such 
dilution processes may be reasonable and scientifically sound in 
estimating environmental concentrations for certain purposes; and (2) 
the use of a factor of 1/100 of the concentration that causes 50-
percent mortality in a test organism to assess the toxicity of a 
substance is not appropriate in all cases. The factors used to assess 
toxicity should be directly related to the amount of valid ecotoxicity 
data available. Although a factor of 1/100 may be appropriate in some 
instances, it may be too much or too little in others. In evaluating 
whether extraordinary circumstances exist, FDA will take into account 
any ecotoxicity data relevant to the issue.

[[Page 14924]]

    The second example of extraordinary circumstances relates to 
instances in which the proposed action could adversely affect an 
endangered or threatened species, or a species entitled to protection 
under some other Federal law. FDA intends to closely examine proposed 
actions that involve FDA-regulated articles obtained from wild flora 
and fauna and will use the extraordinary circumstances provision to 
require at least an EA in any instance in which it appears from an 
examination of the proposed action that the action may cause a species 
to become endangered or threatened.
    In addition, the agency notes that the language in proposed 
Sec. 25.21(a) includes the indirect effects as well as direct effects 
of agency actions. For example, when the agency takes action to 
prohibit or restrict the use of an FDA-regulated product, the agency 
may consider whether the increased use of substitutes for the 
prohibited or restricted product might, at the expected level of 
exposure, result in harm to the environment.
    FDA is proposing to remove current Sec. 25.25 (Retroactive 
environmental consideration), because any request by FDA to an 
applicant to submit additional information to an existing FDA approval 
will be made under authority granted to FDA by the Federal Food, Drug, 
and Cosmetic Act (the act) or the Public Health Service Act (the PHS 
Act).

C. Categorical Exclusions

1. General
    The proposed rule would increase the number of categorical 
exclusions and reorganize the categorical exclusions into the following 
five sections in proposed subpart C of part 25: Section 25.30 General; 
Sec. 25.31 Human drugs and biologics; Sec. 25.32 Foods, food additives, 
and color additives; Sec. 25.33 Animal drugs, and Sec. 25.34 Devices 
and electronic products. The agency is also proposing to delete the 
general introductory language from current Sec. 25.24 because it is 
unnecessary to include this information in the regulation.-
    The agency is proposing to retain most of the general categorical 
exclusions listed in current Sec. 25.24(a) (proposed Sec. 25.30) and to 
make certain revisions described below:
    Current Sec. 25.24(a)(4) categorically excludes destruction or 
disposition of any FDA-regulated article condemned after seizure, 
following detention or recall at agency request, or the distribution or 
use of which has been enjoined. In proposed Sec. 25.30(d), FDA is 
proposing to revise the criteria for the categorical exclusion from 
``if the method of destruction or disposition of the article, including 
packaging material, will not result in the release of a toxic substance 
into the environment'' to ``if the waste is disposed of in compliance 
with all Federal, State, and local requirements.'' The agency is 
proposing this revision to reflect current agency practice and because 
the previous criterion is covered under paragraph (a) of proposed 
Sec. 25.21 Extraordinary circumstances.
    The agency is proposing to revise the categorical exclusion for 
current good manufacturing practice (CGMP) regulations 
(Sec. 25.24(a)(10), proposed Sec. 25.30(j)) to include regulations 
based on the hazard analysis critical control points (HACCP) 
principles. The HACCP concept is a systematic approach to the 
identification, assessment of risk, and control of the biological, 
chemical, and physical food safety hazards associated with a particular 
food production process. The HACCP system is based upon the 
implementation of a control plan developed by a food producer that 
analyzes significant food safety hazards, identifies the points in the 
production process where a hazard can be prevented, and determines the 
preventive measures that are necessary for proper control.
    The agency has recently issued regulations (60 FR 65096, December 
18, 1995) that use HACCP principles to ensure the safe processing and 
importing of seafood. The agency is also considering developing HACCP 
regulations for other regulated food industries (59 FR 39888, August 4, 
1994). FDA has found that the environmental considerations based on 
HACCP principles are essentially identical to the environmental 
considerations of regulations based on CGMP's. Neither type of 
regulation is likely to have significant environmental impacts. 
Therefore, the agency believes that it is appropriate to incorporate 
into the categorical exclusion for CGMP regulations an exclusion of the 
HACCP regulations.
    FDA also is proposing to add a categorical exclusion (proposed 
Sec. 25.30(m)) for actions relating to the disposal of the hazardous 
laboratory waste materials generated in FDA laboratories (low-level 
radioactive waste and chemical waste). Today, all of this hazardous 
waste is disposed of under contract with a hazardous waste management 
firm.We don't mention what the waste is--even though it is in the 
codified part. The contractor is responsible for the collection, 
handling, storage, packing, and ultimate disposal of the waste 
materials at facilities permitted by the U.S. Environmental Protection 
Agency (EPA) and/or facilities licensed by the Nuclear Regulatory 
Commission (NRC). In awarding contracts, FDA takes into consideration 
whether a prospective contractor has all applicable licenses, permits, 
and insurance necessary to perform the work and transport the waste as 
required under the contract. The contractor and all disposal facilities 
must certify that they are in full compliance with all applicable 
Federal, State, and local requirements, before FDA will award the 
contract. Further, FDA requires the contractor to present a 
comprehensive operational plan. FDA reviews this plan to determine if 
the contractor's approach is complete, safe, appropriate, and 
responsive to, among other things, FDA's requirements for waste 
disposal. Further, the contractor must operate in full compliance with 
appropriate regulations issued by EPA (Title 40), the Department of 
Transportation (Title 49), the Department of Labor (Title 29), NRC 
(Title 10), and with relevant State and local regulations governing the 
disposal of hazardous and nonhazardous waste. Therefore, FDA is 
proposing in Sec. 25.30(m) to categorically exclude disposal of low-
level radioactive waste materials and chemical waste materials 
generated in laboratories serviced by FDA-administered contracts.
2. Human Drugs and Biologics
    In the National Performance Report, ``Reinventing Drug and Medical 
Device Regulations,'' April 1995, the President announced FDA's 
proposal to reduce the number of EA's submitted by industry under NEPA 
by increasing the number of categorical exclusions for those actions 
relating to drugs and biologics that, as a class, have no individual or 
cumulative significant effect on the environment. As described below, 
in fulfillment of this commitment, FDA is proposing additional 
categorical exclusions for classes of actions on drugs and biologic 
products that, based on experience in reviewing these types of actions, 
the Center for Drug Evaluation and Research (CDER) and the Center for 
Biologics Evaluation and Research (CBER) have concluded do not have 
significant effects on the human environment. All of the environmental 
reviews of these categories of actions performed under the current 
regulations have resulted in FONSI's.
    The proposed new categorical exclusions in Sec. 25.31(a) and (b) 
apply to actions on an NDA, abbreviated application or a supplement to 
such

[[Page 14925]]
applications, or action on an over-the-counter (OTC) monograph. They 
are divided into two sections: (1) Proposed Sec. 25.31(a), which 
applies if FDA's action does not increase the use and disposal of the 
drug; and (2) proposed Sec. 25.31(b), which applies if FDA's action 
does increase the use and disposal of the drug. This is similar to the 
distinction drawn in the existing regulations between actions that 
increase use and actions that do not. Proposed Sec. 25.31(a) and (b) 
use the term ``active moiety'' rather than substance, drug product, or 
other terminology to clarify the exact focus of the environmental 
review.
    The categorical exclusion in proposed Sec. 25.31(a) is based on the 
categorical exclusions in current Sec. 25.24(c)(1) and (c)(2) and the 
fact that, if the action does not increase the use of a drug, there is 
no change in the level of the substance in the environment. FDA has 
defined ``increased use'' of a drug to include those circumstances 
currently listed in Sec. 25.24(c)(1) and (c)(2). Because the 
environmental effects, if any, associated with the use and disposal of 
the drug were incurred when it was first approved, actions to approve 
additional products may be categorically excluded if they do not 
increase the use of the drug. Among the actions covered under this 
categorical exclusion may be approvals of new dosage forms, prodrugs, 
generic drug products, and manufacturing supplements that may change 
the method or site of manufacture of a drug but not its use.
    Actions under proposed Sec. 25.31(b) that may increase the use or 
disposal of a drug product may be categorically excluded if the 
concentration of the substance in the environment will be below 1 part 
per billion (ppb), the level that FDA has found, based on past 
experience, will not significantly affect the aquatic environment. This 
reflects a change from current regulations that require an 
environmental assessment in any case in which an action may increase 
the use of a drug. The basis for this change is described below.
    CDER performed a retrospective review of available toxicity 
information from EA's that were previously submitted in support of 
NDA's and NDA supplements. This information, which includes data from 
each review division that are representative of pharmacological drug 
classifications, has routinely demonstrated that there are no 
significant observed effects on relevant standard test organisms in the 
aquatic environment at concentrations below 1 ppb.
    Based on the method of entry into the environment from use and 
their physical and chemical characteristics (e.g., water solubility), 
human drugs would be expected predominantly to enter the aquatic 
environment, and the data submitted in EA's reviewed by CDER have 
routinely supported this hypothesis. Human drugs and their metabolites 
enter the environment from use by excretion from patients. The majority 
of hospitals, clinics, and homes in the United States are serviced by a 
wastewater treatment facility where compounds are subjected to some 
form of aerobic and anaerobic decomposition. Drug and/or metabolites 
that are not degraded in the wastewater treatment facility may be 
discharged into surface water or removed from the wastewater treatment 
plant in sludge.
    The data also have routinely shown that in those cases in which an 
applicant has provided toxicity results for terrestrial organisms in 
addition to acute toxicity results for aquatic organisms, the drugs are 
toxic to aquatic organisms at lower levels than they are to terrestrial 
organisms, suggesting that the use of aquatic organisms is a 
conservative approach.
    CDER evaluates the potential for significant environmental effects 
by relating the concentrations determined to have toxic effects on 
relevant standard test organisms to the level of the substance expected 
in the environment. CDER's retrospective review shows that drugs at 
concentrations less than 1 ppb in the aquatic environment have no 
significant effect on relevant standard test organisms and, therefore, 
are unlikely to have a significant effect on the environment. The vast 
majority of actions taken by CDER result in the substance being in the 
aquatic environment at concentrations less than 1 ppb because the 
majority of drugs are produced and used at low levels, and the use of 
drugs is not typically localized but rather is spread throughout the 
United States.
    One of the criteria for determining that a drug is safe for human 
use is consideration of its potential to bioaccumulate. The vast 
majority of drugs do not have the physical or chemical characteristics 
that would allow them to bioaccumulate in tissue because this would 
raise safety concerns for use in humans. If a drug does have the 
physical or chemical characteristics that would allow it to 
bioaccumulate, there has to be a mechanism for the human body to 
metabolize the compound to a substance that has lower bioaccumulation 
potential so that it is cleared from the body. In the environmental 
assessments that CDER reviewed, bioaccumulation has not been an issue.
    Thus, FDA has determined that actions that may increase the use or 
disposal of a drug should be categorically excluded if the 
concentration of the substance in the environment from use will be less 
than 1 ppb and no extraordinary circumstances exist. For example, even 
under conditions in which an action would increase the use of a drug, 
such as an efficacy supplement adding a new indication, the proposed 
action may be categorically excluded under this proposal if the 
substance in the environment will be below 1 ppb. CDER has provided 
guidance on appropriate calculations for estimating environmental 
concentrations (Guidance for Industry for the Submission of an 
Environmental Assessment in Human Drug Applications and Supplements, 
November 1995).
    CDER will continue to critically review the environmental toxicity 
information submitted for those actions requiring an EA. As additional 
data become available to CDER, the agency may propose to modify the 1 
ppb environmental concentration cut-off through notice and comment 
rulemaking.
    Proposed Sec. 25.31(a) and (b) include actions on NDA's. Under the 
current regulations (Sec. 25.24(c)(1) and (c)(2)), abbreviated new drug 
applications (ANDA's) and supplements may be categorically excluded, 
but NDA's for the same type of action may not. Sometimes an applicant 
has a choice whether to submit a proposed action as an NDA or ANDA 
(e.g., a new dosage form may be submitted as an ANDA with a suitability 
petition or as an NDA). Thus, the applicant's choice of submission 
would determine whether an EA would need to be submitted. Proposed 
Sec. 25.31(a) and (b) would permit FDA to treat NDA's, abbreviated 
applications, and supplements alike based on the type of action being 
affected by the application.
    Current Sec. 25.24(c)(6) categorically excludes actions on OTC 
monographs if the product is already marketed for the proposed use. FDA 
is proposing to add OTC monographs to proposed Sec. 25.31(a) and (b) 
because, by action on an OTC monograph, FDA permits the manufacture and 
marketing of OTC drugs that meet the monograph. It should be noted that 
actions to switch drugs from prescription to OTC use that are submitted 
in an NDA or supplement would also be covered under these provisions.
    Proposed Sec. 25.31(a) and (b) would also delete any reference to 
``actions on amendments'' to clarify that the agency

[[Page 14926]]
does not take actions on amendments. Amendments are merely changes to a 
pending application that are incorporated into the application. The 
action the agency takes is on the application as a whole, not on the 
amendment.
    Proposed Sec. 25.31(a) and (b) applies to drugs regulated by CDER. 
FDA is proposing a new categorical exclusion in Sec. 25.31(c) for 
substances that occur naturally in the environment, that would apply to 
both drugs and biologics. Proposed Sec. 25.31(b) would apply to actions 
on an NDA, abbreviated application, application for marketing approval 
of a biologic product, a supplement to such applications, or action on 
an OTC monograph when the action is not expected to alter significantly 
the concentration or distribution of the substance, its metabolites, or 
degradation products in the environment. Under the current regulations, 
FDA requires an abbreviated EA for a drug that occurs naturally in the 
environment. These abbreviated EA's require information about the 
production site and about whether the use of the product will 
significantly alter the concentration, distribution, and effect of the 
natural substance in the environment.
    Since the publication of the NEPA regulations in 1985, FDA has 
reviewed abbreviated EA's for substances that are naturally occurring. 
FDA has found that actions on submissions for these substances will not 
affect the environment if the action will not significantly alter the 
concentration or distribution of the natural substance in the 
environment. Under these circumstances, the agency has prepared 
FONSI's. Both CDER and CBER routinely include in safety evaluations 
evidence that a product and/or living system used to produce the 
product are inactivated following production and prior to release into 
the environment, if there is a reasonable possibility that the product 
or living system may be harmful to the environment. Therefore, there 
are not likely to be any environmental effects. The proposed 
regulations would categorically exclude an action for a substance that 
occurs naturally in the environment when the action will not alter 
significantly the concentration or distribution of the substance in the 
environment. FDA has access to information regarding metabolites and 
degradation products to aid in determining if the categorical exclusion 
request is appropriate.
    When an action does alter significantly the concentration or 
distribution of a naturally occurring substance, its metabolites, or 
degradation products in the environment, e.g., when the use and 
disposal will occur in a geographic area where the substance is not 
naturally occurring, an EA may be required.
    FDA is proposing in Sec. 25.31(d) to expand the categorical 
exclusion provision for the withdrawal of approval of an NDA or 
abbreviated application. The agency is proposing that all types of 
withdrawals of approval, whether requested by industry or initiated by 
the agency, be categorically excluded because, based on CDER's 
experience, these types of actions will not result in the production or 
distribution of any substances and, therefore, will not result in the 
introduction of any substance into the environment.There would be no 
increase in use of substitutes? See line 21 on page 38 (of 1/26 draft). 
EIS considered increase of hydrocarbon propellants in anti-perspirant 
aerosols.
    Proposed Sec. 25.31(e) would revise the categorical exclusions for 
actions on an IND. Current Sec. 25.24(c)(4) categorically excludes 
actions on IND's if the drug shipped under such notice is intended to 
be used for clinical studies or research in which waste will be 
controlled or the amount of waste expected to enter the environment may 
reasonably be expected to be nontoxic. Under proposed Sec. 25.31(e), 
FDA would categorically exclude all IND's. In many cases, FDA's actions 
on IND's do not significantly increase the use of the drug or the 
amount of drug introduced into the environment because the drug is 
being tested in few patients or is already being marketed for another 
use. Therefore, no changes in environmental effects will occur. In 
those cases in which an increase in the use of the drug may occur as a 
result of an investigation under an IND, CDER's experience in reviewing 
actions on IND's indicates that significant environmental effects will 
not occur because the use of such drugs is limited and controlled.
    The agency is proposing to delete the language ``if the drug 
shipped * * * may reasonably be expected to be nontoxic'' because an 
action that results in waste that is expected to be toxic would require 
an EA under proposed Sec. 25.21 Extraordinary circumstances.Is that 
what 25.21(a) means--that if waste is toxic, there may be harm and an 
EA will be required?
    Proposed Sec. 25.31(g) would add a categorical exclusion for the 
testing and release by CBER of lots or batches of a licensed biologic 
product. The effects on the environment of licensed biologic products 
are evaluated during the safety evaluation and approval of the license 
application. Therefore, conducting a separate NEPA review for the 
testing and release by CBER of individual lots or batches is 
unnecessary.
    Proposed Sec. 25.31(i) would permit a categorical exclusion for the 
establishment of a comparability determination for a biologic product 
subject to licensing. Establishment of a comparability determination 
does not result in introduction of a substance into the environment. A 
substance will be introduced into the environment only when CBER has 
made a comparability determination and subsequently approves a license 
application for a specific biologic product. The environmental 
considerations will be made in connection with the review of individual 
license applications that meet the comparability criteria.
    Proposed Sec. 25.31(j) incorporates current Sec. 25.24(c)(10), the 
categorical exclusion for promulgation, amendment, or revocation of a 
standard for a licensed biologic product, and would eliminate the 
current requirement that there be no increased use of the product. The 
standards normally explain how the product is to be manufactured and 
any additional requirements for approval and marketing. Therefore, the 
increased use criterion is unnecessary.
    Proposed Sec. 25.31(k), regarding revocation of a biologic product, 
would eliminate the current criteria in Sec. 25.24(c)(9) that the 
biological product ``is no longer being marketed'' or that the action 
is ``at the request of the license holder. The agency is proposing to 
delete these criteria as unnecessary because revocation of a license 
for a biologic product means that the product can no longer be 
marketed. Marketing of the product after license revocation must cease 
regardless of whether the revocation was at the request of the license 
holder or initiated by the agency. Revocation of a license for a 
biologic product under any circumstances will not result in the 
introduction of any substance into the environment and, therefore, will 
not significantly affect the environment.
    The agency is also proposing other minor, nonsubstantive amendments 
to delete unnecessary language, improve the accuracy and clarity of the 
categorical exclusions, and reflect current terminology.
3. Foods, Food Additives, and Color Additives
    In the President's National Performance Report, ``Reinventing Food 
Regulations,'' January 1996, the President announced that FDA proposed 
to reduce the number of EA's

[[Page 14927]]
submitted by industry under NEPA by increasing the number of 
categorical exclusions for food and color additives and generally 
recognized as safe (GRAS) substances based on little or no impact on 
the environment from the use and disposal of these products. As 
described below, in fulfillment of this commitment, FDA is proposing 
additional categorical exclusions for actions on foods, food additives, 
color additives, and GRAS substances which, based on experience in 
reviewing these types of actions, the Center for Food Safety and 
Applied Nutrition (CFSAN) has concluded will not significantly affect 
the human environment.
    As was explained previously, FDA is proposing to remove criteria 
from certain exclusions in current Sec. 25.24. For actions involving 
foods, food additives, color additives, and GRAS substances, the 
criteria for the exclusions in current Sec. 25.24(a)(10), (b)(2), 
(b)(3), (b)(7), (b)(8), and (b)(9) have been removed. These exclusions 
can be located in proposed Secs. 25.30(j), and 25.32(b), (c), (f), (g), 
and (h). This change is being made because the provisions in proposed 
Sec. 25.21 Extraordinary circumstances could apply to any of the 
agency's exclusions, making certain criteria for individual exclusions 
unnecessary.
    In addition, to reflect current FDA policy, the agency is removing 
from part 25 the environmental review requirements for the 
establishment of action levels for unavoidable poisonous or deleterious 
substances in food or food packaging, and for natural or unavoidable 
defects in food that present no health hazard. This change is discussed 
below.
    For the classes of actions proposed for categorical exclusion in 
Sec. 25.32(i), (j), (k), (l), (o), (q), and (r), FDA has traditionally 
required certain information to assess the potential environmental 
impact of the production of the food additive, color additive, or GRAS 
substance. In all cases, FDA has found in its reviews that the 
production of these substances did not significantly affect the 
environment. The agency has determined that FDA ordinarily will not 
consider potential impacts at sites of production of FDA-regulated 
products, as discussed in section III.D of this document.
    a. Proposed Sec. 25.32(f). Currently, FDA's NEPA procedures in 
Sec. 25.24(b)(7) provide for a categorical exclusion for actions 
relating to the affirmation of a food substance as GRAS if the 
substance is already marketed for the use for which affirmation is 
sought. FDA is proposing to expand this categorical exclusion in 
proposed Sec. 25.32(f) to include actions to establish and amend 
regulations under part 181 (21 CFR part 181) for prior-sanctioned 
ingredients that are already marketed in the United States. Actions 
involving prior-sanctioned ingredients are similar to certain GRAS 
affirmation actions in that the food substance is likely to be already 
marketed in the United States for the proposed use at the time the 
action is being considered and will continue to be marketed after the 
regulation is published. As defined in Sec. 170.3(l) (21 CFR 170.3(l)) 
and Sec. 181.5(a), a prior sanction shall exist only for a specific use 
of a substance for which there was explicit approval by FDA or the U.S. 
Department of Agriculture (USDA) before September 6, 1958. Actions to 
affirm substances as GRAS or prior-sanctioned for the specific uses for 
which they were already marketed in the United States create little or 
no change in the introduction of the substance into the environment. 
Therefore, such actions have no significant effect on the environment.
    b. Proposed Sec. 25.32(i). FDA is proposing to amend its NEPA 
procedures to categorically exclude from the requirement to prepare an 
EA actions to approve a food additive petition or grant a request for 
exemption from regulation as a food additive under Sec. 170.39 (21 CFR 
170.39) (threshold of regulation) when a food additive is a functional 
component of finished food-packaging materials present at not greater 
than 5 percent-by-weight. FDA based this proposed exclusion on its 
review of 95 petitions for food additives in this class, all of which 
resulted in FONSI's, and on the evaluation of the potential for future 
petitions in this class to have significant environmental effects. FDA 
has had limited experience in considering the environmental impact of 
threshold of regulation submissions because the regulations 
establishing a threshold of regulation policy were recently issued (60 
FR 36582, July 17, 1995). However, because the information currently 
required for such submissions is identical to the information required 
for the food-packaging class of indirect food additives discussed in 
this section, the agency believes that its experience with the 95 food 
additive petitions is relevant to these threshold of regulation 
submissions and that these submissions also warrant a categorical 
exclusion.
    The agency's evaluation of functional components of food-packaging 
materials present at not greater than 5 percent-by-weight has 
traditionally included consideration of potential impacts relating to 
the disposal of food-packaging materials containing the additive and 
the use of natural resources and energy.
    To determine the potential for significant introductions of 
substances into the environment at the site of disposal of food-
packaging materials, i.e., municipal solid waste landfill or combustion 
sites, the agency currently requires an estimate of the maximum yearly 
market volume for the proposed use of the food additive and the percent 
of that amount that will become a component of the finished food-
packaging material. To determine the potential for significant 
introductions at landfill sites, FDA estimated the concentration of the 
additive that could be present in landfill leachate for each of the 95 
petitions it reviewed for additives used as functional components of 
food-packaging materials. FDA found that in virtually all cases, the 
concentration of the additives in landfill leachate was less than 50 
ppb. The concentration of the additives in surface or ground water 
receiving landfill leachate was expected to be substantially less, 
taking into consideration the mobility and degradation of the additives 
in landfills and their dilution in receiving waters.
    Consequently, FDA determined in all cases that these extremely low 
levels would not have significant environmental impacts at landfill 
sites. The agency believes that approvals of future petitions in this 
class are even less likely to result in significant introductions of 
substances at landfill sites because EPA published new landfill 
regulations in the Federal Register of October 9, 1991 (56 FR 50978), 
that require new and expanded landfills to have leachate collection 
systems and liners to prevent leachate from entering surface or 
groundwater. Although operators of existing landfills are not required 
to retrofit liner systems, they are required to monitor groundwater 
adjacent to existing landfills and to take corrective action as 
appropriate.
    The agency's evaluation of petitions for additives used as 
functional components of food-packaging materials has also shown that 
there is little potential for significant introductions from the 
combustion of packaging materials containing the additives. These types 
of additives are used at low levels in the packaging materials, <5 
percent by weight, and, therefore, the additional amounts of combustion 
products emitted were found to be insignificant compared to the levels 
already being generated during municipal solid waste combustion. 
Because FDA's experience shows that the use levels for additives used 
as

[[Page 14928]]
functional components of food-packaging materials are low, the agency 
believes that future approvals will also result in insignificant 
introductions into the environment at municipal solid waste combustor 
sites.
    Under current part 25, FDA requires no documentation to assess 
potential impact on energy and resource use if the proposed additive is 
intended for the same use as another additive already in use and will 
not materially change the potential uses of the packaging materials to 
which it is added. The agency has required sponsors to provide 
information in an abbreviated EA showing that these criteria are met. 
Based on FDA's experience in reviewing petitions for functional 
components of food-packaging materials, the agency has found that 
petitioners generally were able to demonstrate that a proposed additive 
would compete with and replace other, already regulated additives and 
that approval would not change the uses of the packaging materials to 
which they were added. In cases where a proposed additive did not 
compete with and replace an already regulated additive, the agency was 
still able to conclude that there would not be a significant impact on 
energy and natural resource use largely because use of the additive in 
food-contact articles represented a very small fraction of total usage.
    Thus, based on the low levels of use of these functional components 
of food-packaging materials and on FDA's experience reviewing 
abbreviated EA's for these functional components, the agency believes 
that approvals of future submissions for such additives are highly 
unlikely to have significant effects on the environment. Therefore, 
under proposed Sec. 25.32(i) a requestor need not ordinarily submit an 
EA.
    c. Proposed Sec. 25.32(j). FDA is proposing to categorically 
exclude actions to approve a food additive and to grant a request for 
exemption from regulation as a food additive under Sec. 170.39 when the 
additive is a component of food-contact surfaces of permanent or 
semipermanent equipment or of other food-contact articles intended for 
repeated use (proposed Sec. 25.32(j)). This proposed exclusion is based 
on FDA's experience with 43 petitions for additives used as components 
of repeat-use food-contact articles, all of which resulted in a FONSI. 
FDA has had limited experience in considering the environmental impact 
of threshold of regulation submissions for components of repeat-use, 
food-contact articles because the regulations establishing a threshold 
of regulation policy were recently issued. However, because the 
information currently required for such submissions is identical to the 
information required for food additive petitions for these types of 
indirect food additives used in repeat-use, food-contact articles, the 
agency believes that its experience with the 43 food additive petitions 
is relevant to these threshold of regulation submissions and that 
approval of these submissions warrants a categorical exclusion.
    In reviewing the petitions for components of repeat-use, food-
contact articles, the agency's evaluation of environmental impact has 
traditionally included consideration of potential impacts relating to 
the disposal of the food-contact articles containing the additive. To 
determine the potential for significant introductions of substances 
into the environment at the sites of disposal of food additives that 
are used as components of the food-contact surfaces of permanent or 
semipermanent equipment, or of other repeat-use articles, the agency 
currently requires an estimate of the maximum yearly market volume for 
the proposed use of the additive. In reviewing abbreviated EA's for 
these additives, FDA found that these additives ordinarily have limited 
potential for causing significant environmental effects as a result of 
their use and disposal. The potential for significant introductions of 
substances to the environment due to disposal is, in fact, very low 
because of the long service life of the food-contact equipment or other 
repeat-use articles, of which additives in this class are components, 
and the limited market volumes of the additives as estimated by the 
petitioners. Because its actions on these petitions and requests will 
not significantly affect the environment, FDA will not ordinarily 
require the preparation of an EA.
    d. Proposed Sec. 25.32(k). FDA is proposing to categorically 
exclude actions to approve food additive, color additive, and GRAS 
affirmation petitions for substances added directly to food that are 
intended to remain in food through ingestion by consumers and that are 
not intended to replace macronutrients in food. This proposed exclusion 
is based on FDA's experience reviewing 21 petitions in this class, all 
of which resulted in a FONSI. Examples of the types of additives and 
GRAS substances that belong to this class are the color additives added 
to foods listed in 21 CFR parts 73 and 74, most of the direct food 
additives listed in part 172 (21 CFR part 172), and certain GRAS 
substances listed in part 184 (21 CFR part 184). Examples of substances 
that are not included in the class for which this categorical exclusion 
is being proposed are the substances intended to replace macronutrients 
in food (such as sweetening agents intended to replace sugar, e.g., see 
Secs. 172.800 and 172.804, and fat substitutes, e.g., Sec. 184.1498).
    The agency's evaluation of the environmental effects of substances 
added directly to food has included consideration of the potential for 
impacts from the disposal of human waste products containing the 
petitioned substance and/or its products of digestion and metabolism, 
and from the use of natural resources and energy.
    The substances added directly to food considered here will be 
ingested by consumers as components of food containing these 
substances. After ingestion, these substances are either digested and/
or metabolized to other substances or excreted largely intact. In all 
cases, the agency's review of past actions on substances added directly 
to food resulted in decisions to issue FONSI's. To address the 
potential for environmental impacts from disposal of this class of 
substances, the agency's FONSI's relied on one or more of the following 
scenarios: (1) The agency's approval of the petition resulted in very 
low levels (in the low ppb range or lower) of the substances in either 
effluents and/or sewage sludge from publicly owned wastewater treatment 
plants and these levels were determined not to be toxic to organisms in 
the environment; (2) the petitioned substance was digested and/or 
metabolized bypara.humans such that only products of digestion and 
metabolism were expected to be excreted and these products were the 
same as (or very similar to) the products of digestion and metabolism 
resulting from human food; such products should have no potential for 
significant environmental effects because wastewater treatment 
facilities are already designed to handle them; or (3) the petitioned 
substance was excreted largely intact but was rapidly degraded into 
nontoxic products either in wastewater treatment plants or in the 
environment.
    FDA's experience shows that substances added directly to food and 
intended to remain with food through ingestion that are the subject of 
new petitions will have use and disposal patterns similar to those 
described above and will not be toxic to organisms in the environment 
at the expected levels of exposure. Thus, use and disposal of such 
substances are not expected to result in significant environmental 
effects.
    The agency has also found, as a result of its review of petitions 
for substances in the class being considered here, that

[[Page 14929]]
in no case was there potential for significant impacts on energy and 
natural resources. These findings relied on one or more of the 
following scenarios: (1) The substances were expected to compete with 
and replace other already regulated substances with no significant 
change in the overall use of natural resources or energy, (2) the 
substances are also used in nonfood contact situations and the food-
contact usage represented a small increase in the overall production 
and usage of the substance such that the small increase in the uses of 
natural resources and energy was not significant, or (3) the predicted 
market volumes for the petitioned substances were very small so that 
the use of natural resources and energy for the petitioned substances 
was very limited. In no case did the agency find that there would be 
any effects on threatened or endangered species. Because the use and 
disposal of substances added directly to foods and intended to remain 
with foods through ingestion has no significant effect on the 
environment and has very limited potential for significant effects on 
energy and natural resources, EA's for these substances will not 
ordinarily be required.
    e. Proposed Sec. 25.32(l). FDA is proposing to categorically 
exclude actions to approve color additives used in contact lenses, 
sutures, polymethylmethacrylate filaments used in supporting haptics 
for intraocular lenses, bone cement, and in other FDA-regulated 
products that involve similar low levels of use. The agency reviewed 
EA's for 20 color additive petitions for these types of uses and found 
that all proposed uses involve small amounts of color additives. 
Because of the nature of these uses, the highest annual market volume 
encountered for any of these color additives was 12 kilograms (kg), 
while most of the petitioned uses involved considerably less than 5 kg. 
Consequently, the environmental introduction levels of the color 
additives from manufacture, use, and disposal would be exceedingly 
small. FDA's experience shows that petitions for color additives in 
these types of applications will have very low market volumes such that 
only extremely low levels of substances will be introduced into the 
environment and will not cause significant environmental effects. 
Therefore, FDA is proposing to categorically exclude actions on such 
petitions from the requirement to prepare an EA.
    f. Proposed Sec. 25.32(m). FDA is proposing to categorically 
exclude actions to prohibit or otherwise restrict or reduce the use of 
a substance in food, food packaging, or cosmetics, e.g., the withdrawal 
of approval for the use of a food or color additive, removal of the use 
of a substance from a GRAS list (21 CFR parts 182, 184, and 186), or 
prohibition of the use of a prior-sanctioned substance (defined under 
Secs. 170.3(l) and 181.5(a)). The agency has prepared EA's for 12 
actions to withdraw approval for the use of a food or color additive or 
to prohibit the use of a substance in food. The agency has prepared 
only one EIS for the withdrawal of approval of a food additive. In 
1978, the agency prepared an EIS for its action to prohibit the use of 
certain chlorofluorocarbons in food, food additive, drug, animal food, 
animal drug, cosmetic, and medical device products as propellants in 
self-pressurized containers (43 FR 11301, March 17, 1978). The 
specified chlorofluorocarbons were prohibited because their continued 
use was predicted to result in the depletion of the stratospheric ozone 
layer. FDA prepared the EIS as part of an interagency effort to address 
this problem. CEQ determined that an EIS was necessary for this 
particular action because of the controversy surrounding the scientific 
issues associated with the potential effects of these chemicals on 
stratospheric ozone. The agency considers its action on 
chlorofluorocarbons to be an exception. It is the only action of this 
type that involved potentially significant effects on the environment.
    The effect of withdrawing approval or prohibiting the use of a 
substance is to reduce or eliminate environmental exposure to that 
substance. Thus, no potential exists for direct adverse environmental 
effects from the agency's prohibition of the use of a substance. It may 
sometimes be necessary, however, to consider the potential indirect 
environmental effects that would result from increased use of 
substitutes for the prohibited substance. Since the agency began 
considering the environmental impact of its actions under NEPA, it has 
not found that significant adverse environmental effects would result 
from the increased use of a substitute for a food or color additive or 
other food substance that was being restricted. In the agency's 
evaluation of past actions in this class, the agency has found that 
there are frequently a number of substitutes for the prohibited 
substance. Thus, the increase in production, use, or disposal of 
substitutes is spread among a number of substances. Further, 
environmental exposure to any one substitute is minimal. In some cases, 
the agency has found that substitutes have been previously subjected to 
environmental review under NEPA by the agency, and that this review 
encompassed the use of the substitute as a replacement for the 
prohibited substance and resulted in an EA and FONSI being prepared. 
Any new food or color additive that may be developed to replace a 
prohibited one would undergo environmental review during the premarket 
approval process.
    g. Proposed Sec. 25.32(n). FDA is proposing to categorically 
exclude actions to issue, amend, or revoke regulations pertaining to 
infant formulas. FDA is proposing to exclude actions on infant formulas 
because they have little or no potential for adverse environmental 
effects. The preparation, distribution, and directions for use of 
infant formulas are carefully controlled by regulations in 21 CFR parts 
106 and 107 and, along with other foods, by the CGMP regulations in 21 
CFR part 110. In addition, the nature of this product, a food designed 
for infants, means that the product itself is very unlikely to cause 
adverse environmental impacts. Infant formulas are expected to be used 
and disposed of in a manner similar to other human food, but infant 
formulas form only a small fraction of the total human food supply 
since they are used only in the first year or 2 of human life. 
Therefore, it is unlikely that future actions on infant formulas will 
have potential for significant environmental effects, and thus, FDA is 
proposing to exclude them from the requirement to prepare an EA.
    h. Proposed Sec. 25.32(o). FDA is proposing to exclude actions to 
approve a food additive petition when an additive is the intended 
expression product(s) present in food derived from new plant varieties. 
The proposed exclusion is based on our determination that the USDA 
Animal and Plant Health Inspection Service (APHIS) has lead 
responsibility, under the Federal Plant Pest Act (7 U.S.C. 150aa et 
seq.), to prevent the movement and dissemination in the United States 
of plant pests. Under that authority, USDA APHIS addresses the 
potential of new plant varieties to pose a plant pest risk in 
accordance with the requirements mandated under NEPA. USDA considers 
the potential for risk in a very broad context, so that not only is 
direct disease or damage to plants and plant materials considered as a 
component of plant pest risk, but indirect effects on beneficial or 
other organisms in the agronomic context are also addressed. Before 
issuing a determination of nonregulated status for an organism that has 
been subject to USDA oversight because it was considered to present a

[[Page 14930]]
potential risk of being a plant pest, USDA conducts an environmental 
analysis in compliance with its NEPA requirements that addresses plant 
pest risk characteristics, disease and pest susceptibilities, 
expression of any introduced gene products and effects thereof, new 
enzymes, or changes to plant metabolism, weediness of the plant, impact 
on the weediness of any other plant with which it can interbreed, 
agricultural or cultivation practices, effects of the plant on 
nontarget organisms, indirect plant pest effects on other agricultural 
products, transfer of genetic information to organisms with which it 
cannot interbreed, and any other information believed to be relevant to 
a determination. The issues considered by FDA are the same or a subset 
of the issues that USDA addresses as part of its NEPA review. 
Therefore, a NEPA review by FDA would be redundant.
    i. Proposed Sec. 25.32(p). FDA is proposing to categorically 
exclude actions under part 101 (21 CFR part 101) to issue, amend, or 
revoke a regulation in response to a reference amount petition 
(Sec. 101.12(h)), a nutrient content claim petition (Sec. 101.69), a 
health claim petition (Sec. 101.70), or a petition pertaining to the 
label declaration of ingredients (Sec. 101.103). The agency has 
regulations pertaining to various aspects of food labeling in part 101. 
These regulations include provisions that enable interested persons to 
petition the agency to issue regulations on several subjects related to 
labeling, listed above. These petitions must include, under current 
regulations, either a claim for categorical exclusion under current 
Sec. 25.24 or an EA under current Sec. 25.31.
    Current Sec. 25.24(a)(11) contains an exclusion for the 
establishment or repeal by regulation of labeling requirements for 
marketing articles, ``if there will be no increase in the existing 
levels of use or change in the intended uses of the product or its 
substitutes.`` The criteria are intended to ensure that the excluded 
labeling actions will not cause significant environmental effects. This 
exclusion can be used with petitions of the type listed above, if 
petitioners demonstrate that the criteria are met. For those actions 
that would not qualify for exclusion under current Sec. 25.24(a)(11) 
because there will be an increase in the use of the product, FDA now 
believes that this increased use will not have significant 
environmental effects. Thus, the agency has determined that a specific 
unqualified categorical exclusion for petitions related to food 
labeling is appropriate.
    When changes in the labeling on food products are allowed, there is 
a potential for changes in the levels of use, and in the intended uses, 
of such products or their substitutes. In fact, nutrient content claims 
and health claims are generally intended to increase the use of the 
labeled product. However, the changes that will result from FDA's 
actions on the types of petitions listed above will be modifications of 
the purchasing and consumption habits of consumers. A food labeled in 
the newly allowed manner will be purchased and consumed instead of 
another food that, for a variety of reasons, will not be labeled in 
this new manner. The net result will be the substitution of one food 
for a similar food. Thus, no significant adverse effects on the 
environment will result. Therefore, the agency is proposing that its 
future actions on petitions for the issuance, amendment, or revocation 
of regulations on reference amounts customarily consumed per eating 
occasion (Sec. 101.12(h)), on nutrient content claims (Sec. 101.69), on 
health claims (Sec. 101.70), and on the label declaration of 
ingredients (Sec. 101.103) be categorically excluded from the 
preparation of an environmental assessment.
    j. Proposed Sec. 25.32(q). FDA is proposing in Sec. 25.32(q) to 
categorically exclude from the requirement to submit an EA actions to 
approve food additive petitions for substances registered by EPA under 
the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) (7 
U.S.C. 136 et seq.) for the same use requested in the petition. FDA has 
had limited experience in considering the environmental impact of 
threshold of regulation submissions for substances registered by EPA 
under FIFRA because the regulations establishing threshold of 
regulation policy were recently issued. However, because the 
information currently required for such submissions is identical to the 
information required for food additive petitions for these types of 
substances, the agency believes that its experience with food additive 
petitions is revelant. This proposed exclusion is based on FDA's 
experience reviewing 12 petitions in this class, all of which resulted 
in a FONSI. All of these petitions were for antimicrobial substances 
used either in the processing of food or in food-packaging materials.
    FDA's evaluation of the potential environmental effects of 
antimicrobial substances has included consideration of potential 
impacts at the site of use and disposal of the antimicrobial substance, 
and from the use of natural resources and energy. Currently, for the 
use sites of antimicrobial substances, petitioners are directed to rely 
on information in studies submitted to EPA for registration of the 
product under FIFRA, and to describe any potential adverse 
environmental effects determined by EPA. Petitioners may submit a brief 
description and summary of results of EPA studies in lieu of the 
complete test reports. For use sites, FDA has based its environmental 
decision on a prediction of exposure levels, using introduction and 
fate information, that is compared with relevant toxicological data to 
determine the potential for significant environmental effects.
    The agency's experience with antimicrobial petitions has been that, 
before an antimicrobial product can be used in food-contact situations, 
EPA will have already examined the environmental risks and benefits of 
registering the product under FIFRA. The parallel between EPA's review 
and FDA's environmental review is illustrated by FDA's finding that it 
has not had to require environmental testing for antimicrobial products 
because such tests were already conducted as part of EPA's review. In 
addition, antimicrobial substances that are used and discharged at 
point sources within the United States are subject to the requirements 
of National Pollution Discharge Elimination System (NPDES) permits 
under the Clean Water Act (33 U.S.C. 1251 et seq.). In registering a 
product under FIFRA, EPA requires the label to state that: (1) The 
product is not to be discharged into lakes, streams, ponds, estuaries, 
oceans, or other waters unless in accordance with the requirements of 
an NPDES permit and unless the permitting authority has been notified 
in writing prior to discharge; and (2) the product is not to be 
discharged to sewer systems without previously notifying the local 
sewage treatment plant authority. EPA also requires, if necessary, that 
labels contain information such as a warning of toxicity to fish and/or 
wildlife, as specified in 40 CFR 156.10(h)(2)(ii). Thus, FDA has found 
that its assessment of the fate and effects of antimicrobial substances 
essentially duplicates the review by EPA under FIFRA and, to some 
extent, the review by NPDES permitting authorities under the Clean 
Water Act.
    Currently, petitioners must address the potential for impact on the 
use of natural resources and energy as required in an EA by specifying 
the natural resources and energy required to produce, transport, use, 
and/or dispose of a given amount of the product that is the subject of 
the action. FDA's experience with this area of potential impacts is 
that these types of substances almost always compete with and replace 
other similar substances so that there is

[[Page 14931]]
little or no change in the use of natural resources and energy. Thus, 
FDA believes that future food additive petitions for the same use as 
pesticides approved by EPA under FIFRA will have little or no potential 
for significant environmental impacts and that FDA's actions on these 
petitions warrant exclusion from the requirement to prepare an EA.
    k. Removal of action levels. At the time the current environmental 
regulations were issued, the agency believed that the establishment of 
an action level required environmental review. Thus, the agency 
included a paragraph for the establishment of action levels in current 
Sec. 25.22(a)(11) and specified an EA format in current Sec. 25.31d. 
FDA also provided a categorical exclusion in current Sec. 25.24(b)(6) 
for action levels for natural or unavoidable defects in food for humans 
or animals if these defects presented no health hazard.
    In 1987, in a limited holding, the Court of Appeals for the D.C. 
Circuit in Community Nutrition Institute v. Young, 818 F.2d 943 (D.C. 
Cir. 1987), found that FDA was treating its action levels as 
substantive, legislative rules and, thus, action levels were subject to 
the notice-and-comment requirements of the Administrative Procedure Act 
(5 U.S.C. 551 et seq.). The court recognized, however, that FDA could 
proceed by action levels that are not binding rules. Since the court's 
holding, FDA has followed this approach. Under its statutory authority 
under 21 U.S.C. 342(a)(1), (a)(2)(A), and 346 to limit the amount of 
poisonous or deleterious substances in food, FDA establishes ``action 
levels'' to inform food producers of the level of contaminants in food 
that may result in regulatory action. Action levels are not intended to 
bind the public, or FDA, or to create or confer any rights, privileges, 
immunities, or benefits on or for any private person, but are intended 
merely for internal FDA guidance for deciding whether to bring an 
enforcement action. The establishment of an action level is not agency 
action and is not subject to NEPA.
    Moreover, under CEQ regulations (40 CFR 1508.18(a)), bringing 
judicial, administrative, civil, or criminal enforcement actions is not 
major Federal action. Because establishment of action levels is 
intended merely for internal guidance for deciding whether to bring an 
enforcement action, establishment of an action level is not major 
Federal action.
    Therefore, FDA is proposing to remove all references to action 
levels from part 25. The agency will continue to apply these 
regulations to the establishment of tolerances for poisonous or 
deleterious substances in food for human or animal consumption or in 
packaging materials intended for use with human food and animal feeds.
    l. Proposed Sec. 25.32(r). FDA is proposing to categorically 
exclude actions to approve a food additive, a color additive, or a GRAS 
affirmation petition for a substance that occurs naturally in the 
environment, when the action is not expected to alter significantly the 
concentration or distribution of the substance, its metabolites, or 
degradation products. This proposed exclusion is based on FDA's review 
of 19 petitions for substances in this class, all of which resulted in 
a finding of no significant impact.
    The agency currently requires limited information for substances 
that occur naturally in the environment, as specified in the 
abbreviated EA format in current Sec. 25.31a(b)(5). This format focuses 
on whether the use of the substance can reasonably be expected, on the 
basis of all available evidence, to alter significantly the 
concentration and distribution of the substance, its metabolites, or 
degradation products in the environment and on information about the 
environmental effects of substances expected to be emitted into the 
environment. From its review of 19 petitions, the agency has found that 
the use of naturally occurring substances as food additives, color 
additives, or GRAS substances did not alter significantly the 
concentration and distribution of the substance, its metabolites or 
degradation products in the environment, and therefore, substances 
emitted into the environment did not have adverse environmental 
effects.
    Among the 19 petitions for naturally occurring substances reviewed 
by the agency were several petitions for substances intended to replace 
macronutrients in food. In Sec. 25.32(k), FDA is not proposing to 
exclude from the requirement to prepare an EA petitions for substances 
intended to replace macronutrients. However, when a macronutrient 
replacement is also a substance that occurs naturally in the 
environment, the categorical exclusion proposed here will apply, unless 
the agency finds that extraordinary circumstances exist, as delineated 
in proposed Sec. 25.21.
4. Veterinary Drugs and Feed Additives
    The National Performance Report, ``Reinventing Food Regulations,'' 
January 1996, announced FDA's proposal to reduce the number of EA's 
submitted by industry under NEPA by increasing the number of 
categorical exclusions for actions relating to animal drugs, animal 
feeds, and food and color additives, which as a class have no 
individual or cumulative significant effects on the environment. As 
described below, in fulfillment of this commitment, FDA is proposing 
additional categorical exclusions for actions on animal drugs and feed 
additives that, based upon its experience in reviewing these types of 
actions, the Center for Veterinary Medicine (CVM) has concluded will 
not significantly affect the human environment.
    Under proposed Sec. 25.33(a), actions relating to new animal drug 
applications (NADA's), abbreviated applications, and supplements to 
such applications that do not increase the use and disposal of the 
substances are categorically excluded.
    Proposed Sec. 25.33(a) includes the categorical exclusions listed 
in current Sec. 25.24(d)(1) and (d)(2), and broadens the categorical 
exclusion to allow FDA to categorically exclude other actions that do 
not result in increased use of a drug and, consequently, do not result 
in an increase in the expected level of environmental exposure. For 
example, the approval of a supplement for a new manufacturing site is 
not specifically listed but may be categorically excluded if it is not 
expected to result in increased use of the substance for which the 
supplement was submitted. Proposed Sec. 25.33(a)(7) for animal drugs 
used in feeds is the same as current Sec. 25.24(d)(2) but has been 
revised for clarity because FDA approves animal drugs for use in animal 
feeds.What about 512(m) and proposed 25.24(e)?
    The categorical exclusions in proposed Sec. 25.33(a) include 
actions relating to abbreviated new animal drug applications (ANADA's) 
in recognition of the creation of ANADA's under the 1988 Generic Animal 
Drug and Patent Term Restoration Act (GADPTRA) (21 U.S.C. 301 note). An 
ANADA is merely an abbreviated form of an NADA and seeks to effectuate 
the same action, approval of an animal drug. Therefore, the nature of 
environmental considerations is similar. For animal drugs not otherwise 
excluded in Sec. 25.33(a), the agency is reserving Sec. 25.33(b) to 
provide for a categorical exclusion analogous to that contained in 
proposed Sec. 25.31(b) for human drugs. The categorical exclusion would 
be for actions that increase the use of an animal drug in the instance 
that the agency determines a level at or below which the concentration 
of the substance in the environment does not significantly affect the 
environment.

[[Page 14932]]

    FDA recognizes that proposed Sec. 25.31(b) for human drugs allows 
for a categorical exclusion for increased uses of human drugs if the 
concentration of the substance in the aquatic environment will be at or 
below 1 ppb. At this time, FDA is not adopting a specific environmental 
concentration from use of animal drugs because the agency is still 
conducting a retrospective review of environmental assessments for 
these products and a review of revelant environmental science. The 
Animal Health Institute and FDA/CVM held an Environmental Risk 
Assessment Workshop on February 20 and 21, 1996, to establish a 
comprehensive ecological risk assessment process for the evaluation of 
animal health products. Following this opportunity for public debate, 
and for drugs not otherwise excluded, FDA will adopt a risk assessment 
paradigm for determining environmental introductions for animal drugs 
and an environmental concentration at or below which no meaningful 
environmental effects are expected to occur.
    Proposed 25.33(c) would categorically exclude any action on an 
NADA, abbreviated application, or a supplement to such actions for 
substances that occur naturally in the environment, when the action is 
not expected to alter significantly the concentration or distribution 
of the substance, its metabolites, or degradation products in the 
environment. Currently, FDA's regulations require an abbreviated EA for 
an animal drug substance that occurs naturally in the environment. 
These abbreviated EA's require information about the production site 
and about whether the use of the product will significantly alter the 
concentration, distribution, and effect of the natural substance in the 
environment.
    Since the publication of the NEPA regulations in 1985, FDA has 
reviewed abbreviated EA's for substances that are naturally occurring. 
FDA has found that actions on submissions for these substances will not 
affect the environment if the action will not significantly alter the 
concentration or distribution of the natural substance in the 
environment. Under these circumstances, the agency has prepared 
FONSI's.
     Therefore, the proposed regulations would categorically exclude 
actions on an NADA, abbreviated application, or a supplement to such 
applications for substances that occur naturally in the environment 
when the action is not expected to alter significantly the 
concentration or distribution of the substance, its metabolites, or 
degradation products in the environment. FDA has access to information 
regarding metabolites and degradation products to aid in determining if 
the categorical exclusion request is appropriate. Neither an EA nor an 
EIS would be required for such actions. When an action does alter 
significantly the concentration or distribution of the products, its 
metabolites, or degradation products in the environment, e.g., when the 
use and disposal will occur in a geographic area where the substance is 
not naturally occurring, an environmental assessment may be required.
    Proposed Sec. 25.33(d) includes categorical exclusions for actions 
relating to approval of applications for animal drugs intended for use 
in nonfood animals, for local or general anesthesia, for ophthalmic or 
topical applications, for the treatment of a disease occurring in minor 
species animals, as defined in Sec. 514.1(d)(1)(i) (21 CFR 
514.1(d)(1)(i)), and for use under prescription or veterinarian's 
order. Under current Sec. 25.31a(b)(4), FDA requires abbreviated EA's 
to be submitted as part of any request for such approvals. These 
abbreviated EA's require environmental information for production 
sites. Since the publication of the NEPA regulation in 1985, CVM has 
reviewed many abbreviated EA's for these types of products. In every 
instance, the agency has prepared a FONSI because the manufacturing was 
determined to be in compliance and would remain in compliance with the 
Federal, State, and local environmental requirements that apply to the 
site of manufacturing, and the market volume for such products was so 
low that FDA found, based on its experience, the drugs would not 
significantly affect the environment. Furthermore, as the agency 
explains in section III.D. of this document, the agency has determined 
that ordinarily FDA will not consider potential impacts at the site of 
production.
    The categorical exclusion for local and general anesthetic products 
applies only to those products that are administered individually. Some 
anesthetic products may be intended to be administered to many animals 
or in significant quantities. In these instances, potential 
environmental effects exist that require environmental analysis. The 
exclusion for ophthalmic and topical products is limited to those 
products intended for nonsystemic use. Products used systemically could 
result in greater environmental introductions that could potentially 
affect the environment and, therefore, require further environmental 
analysis. Furthermore, FDA is clarifying that the categorical exclusion 
for drugs for minor species applies only to those animal drugs that 
have been previously approved for use in another or the same species 
when similar animal management practices are used. When management 
practices are different, environmental introductions and impacts may 
also be different and require environmental analyses. Minor species 
include wildlife and endangered species (Sec. 514.1(d)(1)(ii)).
    The categorial exclusion for animal drugs used under prescription 
or veterinarian's order applies only to animal drugs for therapeutic 
uses as defined in section 201(g)(1)(B) of the act (21 U.S.C. 
321(g)(1)(B)). Based on its experience in reviewing EA's for these 
products, FDA has found that prescription products are generally 
administered individually to a limited number of animals for a limited 
amount of time. Therefore, there are no significant environmental 
effects. However, FDA may require an EA if the agency determines that 
there are extraordinary circumstances associated with the use of such a 
product.
    Current Sec. 25.24(d)(4) categorically excludes actions on an 
investigational new animal drug application (INAD) if the drug to be 
shipped under such notice is intended to be used for clinical studies 
or research in which wastes will be controlled or the amount of wastes 
expected to enter the environment may reasonably be expected to be 
nontoxic. Under proposed Sec. 25.33(e), FDA would categorically exclude 
all actions on INAD's. In many cases, FDA's actions on INAD's do not 
significantly increase the use of the drug and, thus, the amount of 
drug introduced into the environment. Therefore, no changes in 
environmental effects will occur. In those cases where an increase in 
use of a drug may occur as a result of an investigation under an INAD, 
FDA's experience from reviewing many actions on INAD's shows that 
significant environmental effects will not occur because the use of 
such drugs is limited and controlled.
    Proposed Sec. 25.33(f) would categorically exclude actions on 
applications submitted under section 512(m) of the act (21 U.S.C. 
360b(m)). FDA is proposing to exclude actions on such applications 
because they permit feed manufacturers to manufacture animal feed 
bearing or containing new animal drugs previously approved for use in 
feeds. The potential for environmental effects to occur is considered 
at the time the new animal drug is approved for use in feed. Therefore, 
there is no need to require an

[[Page 14933]]
additional EA each time the agency considers approval of an application 
submitted under section 512(m) of the act.
    Current Sec. 25.24(d)(3) categorically excludes withdrawals of 
approval of NADA's when the drug is no longer marketed or at the 
request of the application holder. Under proposed Sec. 25.33(g), FDA 
would categorically exclude withdrawals of approval of ANADA's, as well 
as withdrawals of approval of NADA's, without conditions. FDA has 
determined that withdrawal of an NADA or ANADA approval does not 
significantly affect the environment because any change in introduction 
of the drug will generally be a decrease.
    Under proposed Sec. 25.33(h), FDA would categorically exclude 
actions to withdraw the approval for uses of food additives in animal 
feeds or to remove substances for use in animal feeds from the GRAS 
list or to remove substances from the GRAS list (parts 182, 184, or 
186). Withdrawal or removal of a food additive substance that reduces 
or eliminates animal feed use will not significantly affect the 
environment because any change in introduction of the substance to the 
environment will generally be a decrease.
    In those cases where the withdrawal of the NADA, ANADA, or FAP, or 
GRAS substance has resulted in the use of a substitute product, the 
agency has found in all instances that the increased use of the 
substitutes will not significantly affect the environment.
    FDA is proposing to eliminate the categorical exclusions under 
current Sec. 25.24(d)(5) and (d)(6) because FDA does not do testing and 
certification of batches of antibiotics for animal use, and FDA does 
not use monographs for animal drugs. FDA is proposing to eliminate 
current Sec. 25.24(d)(7). This action takes place under an INAD, and 
its effect is to set the standard for approving ANADA's. FDA will 
determine whether it needs to consider environmental effects when it 
approves individual ANADA's.
5. Devices and Electronic Products
    The agency is proposing to redesignate current Sec. 25.24(e) as 
proposed Sec. 25.34 and to remove criteria in Sec. 25.24(e)(4) and 
(e)(7), now incorporated in proposed Sec. 25.21 Extraordinary 
circumstances.

D. Subpart D--Preparation of Environmental Documents

    The proposed rule would reorganize current subpart C of part 25 to 
improve the usefulness and readability of the current regulations.
    Proposed Sec. 25.40(b) would eliminate the EA and abbreviated EA 
formats and delete any reference to formats. After consultation with 
CEQ, the agency has decided to remove the standard formats from part 
25, and to provide appropriate formats in guidance documents. Guidance 
documents, which do not bind the agency or the public, are more easily 
revised. Use of such documents will give FDA greater flexibility to 
tailor environmental documents to reflect state-of-the-art developments 
in environmental analysis and to assist companies in focusing on 
important environmental issues. Information/guidance concerning the 
nature and scope of information that an applicant or petitioner should 
submit in an EA may be obtained from the center responsible for the 
action subject to environmental evaluation (proposed Sec. 25.40(c)).
    In the Federal Register of January 11, 1996, FDA announced the 
availability of a guidance document entitled, ``Guidance for Industry 
for the Submission of an Environmental Assessment in Human Drug 
Applications and Supplements'' (61 FR 1031). The guidance, prepared by 
CDER, is intended to assist industry by providing guidance on how to 
prepare EA's for submission to CDER as part of NDA's, antibiotic 
applications, ANDA's, abbreviated antibiotic applications, and IND's. 
This guidance will be amended to reflect the final regulations and 
categorical exclusions and to include biologic products subject to 
licensure under the PHS Act. The guidance document employs a tiered 
approach to testing and accepts the use of test methods recognized and 
recommended by competent authorities such as FDA (see e.g., FDA's EA 
Technical Assistance Handbook), EPA (see 40 CFR parts 796 and 797) and 
the Organization for Economic Co-operation and Development. Under the 
proposed rule, this approach will continue to be acceptable.
    The current formats in part 25 focus the environmental analysis on 
the use and disposal from use of FDA-regulated articles but also 
address production impacts. FDA proposes to maintain this focus in the 
proposed revised regulations, but, for the following reasons, is 
proposing to change the way it addresses production impacts. To address 
the potential environmental impacts from production of FDA-regulated 
articles, FDA currently requires a limited amount of information to 
make sure that the article will be produced in compliance with 
applicable emissions requirements. Specifically, the agency requires 
that the following information be included in an EA: A list of the 
substances expected to be emitted, the controls exercised, a citation 
of applicable emissions requirements and statement of compliance with 
these requirements, and a discussion of the effect the approval of the 
petition will have on compliance with these requirements.
    FDA recognizes, however, that Federal, State, and local 
environmental protection agencies have the responsibility for issuing 
regulations, permitting and licensing facilities, and enforcing 
compliance with the requirements that these agencies have determined 
are necessary to ensure adequate protection of the environment from 
emissions from production operations. Regulating emissions from 
production sites requires balancing between air, water, and solid waste 
emissions for all production operations carried out at a production 
site and in the region with consideration of the costs of compliance 
and available technology that requires expertise found primarily in 
Federal, State, and local environmental agencies. As required by 
environmental regulations and/or as conditions of retaining licenses 
and permits, manufacturers must obtain or modify permits and provide 
information to these agencies when production operations are initiated 
or changed. The information required to be provided to FDA regarding 
production impacts and compliance with emission requirements is 
information that is generally required to be provided to or is known by 
other agencies whose responsibility is to monitor compliance.
    FDA has reviewed hundreds of EA's in which information regarding 
the manufacturing site, such as emitted substances and emission 
controls, was provided. As a result of this review, FDA has found that 
FDA-regulated articles produced in compliance with all applicable 
emission requirements (e.g., Clean Air Act, Clean Water Act, 
Occupational Safety and Health Act) will not significantly affect the 
environment. Based on these findings, FDA has determined that it is no 
longer necessary to review a company's compliance with Federal, State, 
and local environmental laws and FDA is proposing to delete the 
requirements for the submission of emission information for production 
sites. Accordingly, under the proposed regulations, FDA will continue 
to focus its environmental reviews on the use and disposal from use of 
FDA-regulated articles, and FDA will no longer routinely require 
submission of information regarding manufacturing sites or a 
certification of compliance with Federal, State, and

[[Page 14934]]
local emission requirements. However, if information available to the 
agency or the applicant establishes that the general or specific 
emission requirements promulgated by Federal, State, or local 
environmental protection agencies do not address unique emission 
circumstances and the emissions may harm the environment, this would be 
sufficient grounds for requesting manufacturing information in an EA. 
FDA generally requires manufacturing information to be submitted as 
part of applications or petitions for FDA-regulated articles. This 
information will aid FDA in determining if a categorical exclusion 
request is appropriate.
    Proposed Sec. 25.40(a) includes additional information found in the 
CEQ regulations to clarify that the EA shall include brief discussions 
of the need for the proposal, alternatives, environmental impacts of 
the proposed action, and a listing of agencies and persons consulted, 
and include additional information to clarify the scope and focus of an 
EA. Environmental documents shall concentrate on timely and significant 
issues, not amass needless detail. To that end, the agency has included 
some general information regarding the acceptability of using a tiered 
testing scheme. A tiered testing scheme results in test termination 
when sufficient data are available to assess the potential 
environmental fate and effects of an FDA-regulated article in the 
environment. Specific information regarding tiered testing will be 
provided in guidance documents. Although the number of pages for any EA 
may vary in relation to the complexity of the issues, generally they 
should not exceed 30 pages, not including test reports and data.
    The agency is proposing to add Sec. 25.40(b) to clarify that CEQ 
regulations (40 CFR 1506.5(b)) place ultimate responsibility on FDA for 
the scope and content of environmental analyses. Thus, FDA may require 
additional information from applicants or may itself include additional 
information in environmental documents (EA's, FONSI's, or EIS's) when 
warranted. Proposed Sec. 25.40(c) would include information found in 
current Sec. 25.30(a) and encourages applicants or petitioners who 
submit EA's to FDA to consult with FDA regarding the appropriate scope 
and content for EA's for the requested action. Proposed Sec. 25.40(d) 
discusses incorporation of information in an EA by reference.
    Proposed Sec. 25.41 would include information on FONSI's that is 
found in current Sec. 25.32(a) and (c). The agency is proposing to 
delete the language on notices of intent and draft, final, and 
supplemental EIS's, found in current Secs. 25.33 and 25.34, because the 
CEQ regulations describe the process for determining the scope of an 
EIS and provide detailed requirements for the preparation of draft and 
final EIS's. Thus, this information is duplicative and unnecessary in 
FDA regulations (40 CFR 1501.7 and part 1502).
    Proposed Sec. 25.42 would describe the subject matter that needs to 
be discussed in an EIS and references the CEQ regulations governing the 
requirements for preparation of an EIS. Proposed Sec. 25.42(c) fulfills 
the CEQ requirement under 40 CFR 1502.9(c) that FDA adopt procedures 
for introducing a supplement into its administrative record.
    The agency is proposing to add new Sec. 25.43 to clarify the 
agency's existing responsibility under the CEQ regulations to prepare a 
concise public record of decision for cases requiring EIS's (40 CFR 
1505.2).
    Proposed Sec. 25.44 would include information found in current 
Sec. 25.10(b), describing the responsibilities of lead and cooperating 
agencies. The agency is proposing to delete duplicative and unnecessary 
information on lead and cooperating agencies that is already found in 
the CEQ regulations, and to delete the first sentence in current 
Sec. 25.10(b) because it is self-evident that FDA will be the lead 
agency for programs administered by FDA.
    Proposed Sec. 25.45 would include information from current 
Sec. 25.42, describing who the responsible agency official will be and 
his or her responsibilities. The agency is proposing to remove 
information in current Sec. 25.42 that is duplicative of requirements 
already found in CEQ regulations.

E. Subpart E--Public Participation and Notification of Environmental 
Documents-

    The proposed rule would improve the usefulness and readability of 
the regulations by reorganizing current subpart D of part 25, ``agency 
decisionmaking'' (now proposed ``Public Participation and Notification 
of Environmental Documents'') by deleting unnecessary information that 
is duplicative of requirements found in the CEQ regulations, and, as 
discussed above, moving information to other relevant sections. 
Proposed subpart E would now address public participation in the NEPA 
process and clarify circumstances under which environmental documents 
will publicly be disclosed. These revisions are consistent with our 
responsibilities under the CEQ regulations and under Executive Order 
12898, Federal Actions to Address Environmental Justice in Minority 
Populations and Low Income Populations, February 11, 1994.
    CEQ regulations require that agency procedures ensure full 
compliance with NEPA to the extent possible, unless existing law 
applicable to the agency's operations expressly prohibits or makes 
compliance impossible (40 CFR 1500.6). Proposed Sec. 25.50 clarifies 
that laws governing public disclosure may limit FDA's ability to comply 
with NEPA and CEQ regulations.
    Proposed Sec. 25.51(a) and (b), public disclosure of FONSI's and 
EA's, would include the public disclosure information found in current 
Sec. 25.30(b) and 25.41(b). The proposed rule would move the 
information relating to statutory time frames from current 
Sec. 25.40(c) to proposed Sec. 25.51(b)(1).
    Proposed Sec.  25.52 would add new information relating to the 
public disclosure of EIS's.

F. Subpart F--Other Requirements

    Current subpart E will be renumbered as subpart F. The agency is 
not proposing to amend this subpart.

IV. Environmental Impact Considerations

    The agency has determined under current 21 CFR 25.24(a)(8) that 
this action is of a type that does not individually or cumulatively 
have a significant effect on the human environment. Therefore, neither 
an EA nor an EIS is required.

V. Analysis of Impacts

    FDA has examined the impacts of the proposed rule under Executive 
Order 12866, under the Regulatory Flexibility Act (Pub. L. 96-354), and 
under the Unfunded Mandates Reform Act (Pub. L. 104-4). Executive Order 
12866 directs agencies to assess all costs and benefits of available 
regulatory alternatives and, when regulation is necessary, to select 
regulatory approaches that maximize net benefits (including potential 
economic, environmental, public health and safety, and other 
advantages; distributive impacts and equity). The Regulatory 
Flexibility Act requires agencies to analyze regulatory options that 
would minimize any significant impact of a rule on small entities. The 
Unfunded Mandates Reform Act requires (in section 202) that agencies 
prepare an assessment of anticipated costs and benefits before 
proposing any rule that may result in an annual expenditure by State, 
local, and tribal governments, in

[[Page 14935]]
the aggregate, or by the private sector, of $100,000,000 (adjusted 
annually for inflation). That act also requires (in section 205) that 
the agency identify and consider a reasonable number of regulatory 
alternatives and from those alternatives select the least costly, most 
cost effective, or least burdensome alternative that achieves the 
objective of the rule. The following analysis demonstrates that this 
proposed rule is consistent with the principles set forth in the 
Executive Order and in these two statutes. The proposed rule is not an 
economically significant regulatory action under Executive Order 12866.
    Based on the approximate number of EA's that FDA currently receives 
each year and the resources needed to prepare them, the agency 
estimates that the proposed reduced requirements for submitting EA's 
will result in an annual cost savings to industry of approximately 
$15.7 million. The basis for this estimate is as follows:
    Human pharmaceuticals: Approximately 125 EA's related to human 
pharmaceuticals would be eliminated annually under the proposal. About 
one-half of these are abbreviated EA's; the remainder are full 
assessments. FDA assumes that the average cost of preparing an 
abbreviated assessment was approximately $40,000, while the average 
cost of a full assessment was approximately $200,000. These assumptions 
yield a cost savings of about $2.5 million for abbreviated EA's and 
$12.5 million for full EA's, for a total savings to industry from the 
reduced requirements of EA's relating to human pharmaceuticals of 
approximately $15 million per year.
    Veterinary products: The proposed changes would eliminate 
approximately 37 abbreviated EA's for veterinary products each year, at 
an average cost of approximately $5,000 each. About 77 brief 
submissions, which currently require categorical exclusion criteria 
review, would also be eliminated; these cost an estimated $300 each to 
prepare. Total cost savings to the veterinary products industry under 
the proposal would thus be approximately $208,000 per year.
    Food products: About 36 EA's per year received by CFSAN would be 
eliminated under the proposal. Approximately 28 of these would have 
been abbreviated EA's and 8 would have been full assessments under 
current rules. FDA estimates that the cost of producing most 
abbreviated EA's for CFSAN is approximately $2,500 and the average cost 
of producing a full EA is approximately $50,000. These assumptions 
imply an annual cost savings of approximately $70,000 for abbreviated 
EA's and $400,000 for full EA's, for a total annual savings to the 
foods industry of approximately $470,000.
    In addition to these savings to industry, the proposed changes 
would improve FDA efficiency by eliminating agency review costs of 
approximately $1 million per year.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
of small entities. Because these regulations will not impose 
significant new costs on any firms, the agency certifies that the 
proposed rule will not have a significant economic impact on a 
substantial number of small entities. Therefore, under the Regulatory 
Flexibility Act, no further analysis is required.

VI. Paperwork Reduction Act of 1995

    This proposed rule contains reporting requirements that are subject 
to public comment and review by the Office of Management and Budget 
(OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3506 and 
3507). Therefore, in accordance with 5 CFR part 1320, a description of 
reporting requirements with an estimate of the annual collection of 
information burden is given below by cross reference to existing FDA 
clearance submissions previously approved by OMB which this proposed 
rule affects.
    FDA is soliciting comments to: (1) Evaluate whether the proposed 
collection of information is necessary for the proper performance of 
the functions of the agency, including whether the information will 
have practical utility; (2) evaluate the accuracy of the agency's 
estimate of the proposed collection of information; (3) evaluate the 
quality, utility, and clarity of the information to be collected; and 
(4) minimize the burden of the collection of information on those who 
are to respond.
    Title: National Environmental Policy Act; Policies and Procedures.
    Description: FDA has previously issued regulations that implement 
NEPA (part 25). The proposed rule would reduce the number of NEPA 
evaluations by providing for categorical exclusions for additional 
classes of actions that do not individually or cumulatively have a 
significant effect on the human environment and for which, therefore, 
neither an EIS nor an EA is required. FDA is also proposing to amend 
these regulations to ensure that the NEPA procedures are more concise 
and understandable to the public and to reflect current FDA policy with 
respect to environmental considerations. This proposed rule is in 
response to initiatives announced in the President's National 
Performance Reports, ``Reinventing Drug and Medical Device 
Regulations,'' April 1995, and ``Reinventing Food Regulations,'' 
January 1996.
    Description of Respondents: Persons and businesses, including small 
businesses.
    Estimated Annual Reporting and Recordkeeping Burden. The estimated 
burden associated with the information collection requirements for this 
proposed rule will be recognized in the individual FDA clearances where 
NEPA considerations apply. Listed below are those clearances affected 
by this regulation, including the section of title 21 CFR, the title, 
and the OMB approval number:
    Section 10.30, Citizen Petitions, 0910-0183; Sec. 71.1, Color 
Additive Petitions, 0910-0185; Sec. 170.35, Affirmation of Generally 
Recognized As Safe (GRAS) Status, 0910-0132; Sec. 101.12, Reference 
amounts customarily consumed per eating occasion, 0910-0286; 
Sec. 101.69, Petitions for nutrient content claims, 0910-0288; 
Sec. 101.70, Petitions for health claims, 0910-0287; Sec. 170.39, 
Threshold of regulation for substances used in food-contact articles, 
0910-0298; Sec. 171.1, Food Additive Petitions, 0910-0016; Sec. 312.23, 
Conditions for Exemption of New Drugs for Investigational Use, 0910-
0014; Sec. 511.1, New Animal Drugs for Investigational Use Exempt From 
Section 512(a) of the Act, 0910-0117; Sec. 514.1, New Animal Drug 
Applications, 0910-0032; Sec. 514.8, Supplemental New Animal Drug 
Applications, 0910-0032; Sec. 571.1, Food Additive Petitions, 0910-
0016; Sec. 601.2 Product Licenses-Procedures for Filing, 0910-0124; 
Sec. 812.20, Investigational Device Exemptions Application, 0910-0078.
    The proposed rule would reduce these information collections that 
have already been reviewed and approved by the OMB.-Reporting burdens 
imposed by current part 25 are approved by OMB through December 31, 
1997 (see OMB control number 0910-0190, ``National Environmental Policy 
Act; Policy and Procedures--21 CFR Part 25'').
    The agency has submitted copies of the proposed rule to OMB for its 
review of these reporting requirements. Interested persons are 
requested to send comments regarding information collection by May 3, 
1996, to the Office of Information and Regulatory Affairs, OMB (address 
above).

[[Page 14936]]


List of Subjects in 21 CFR Part 25

    Environmental impact statements, Foreign relations, Reporting and 
recordkeeping requirements.
    Therefore, under the Federal Food, Drug, and Cosmetic Act, the 
Public Health Service Act, and authority delegated to the Commissioner 
of Food and Drugs, it is proposed that 21 CFR part 25 be revised to 
read as follows:

PART 25--ENVIRONMENTAL IMPACT CONSIDERATIONS

Subpart A--General Provisions

Sec.
25.1   Purpose.
25.5   Terminology.
25.10   Policies and NEPA planning.

Subpart B--Agency Actions Requiring Environmental Consideration

25.15   General procedures.
25.16   Public health and safety emergencies.
25.20   Actions requiring preparation of an environmental 
assessment.
25.21   Extraordinary circumstances.
25.22   Actions requiring preparation of an environmental impact 
statement.

Subpart C--Categorical Exclusions

25.30   General.
25.31   Human drugs and biologics.
25.32   Foods, food additives, and color additives.
25.33   Animal drugs.
25.34   Devices and electronic products.--

Subpart D--Preparation of Environmental Documents

25.40   Environmental assessments.-
25.41   Findings of no significant impact.
25.42   Environmental impact statements.
25.43   Records of decision.-
25.44   Lead and cooperating agencies.
25.45   Responsible agency official

Subpart E--Public Participation and Notification of Environmental 
Documents---

25.50   General information.
25.51   Environmental assessments and findings of no significant -
impact.
25.52   Environmental impact statements.-

Subpart F--Other Requirements

25.60   Environmental effects abroad of major agency actions.
    Authority: Secs. 201-903 of the Federal Food, Drug, and Cosmetic 
Act (21 U.S.C. 321-393); secs. 351, 354-361 of the Public Health 
Service Act (42 U.S.C. 262, 263b-264); 42 U.S.C. 4321, 4332; 40 CFR 
parts 1500-1508; E.O. 11514, 3 CFR, 1966-1970 Comp., p. 902, as 
amended by E.O. 11991, 3 CFR, 1977 Comp., p. 123; E.O. 12114, 3 CFR, 
1979 Comp., p. 356.

Subpart A--General Provisions


Sec. 25.1  Purpose.

    The National Environmental Policy Act of 1969 (NEPA), as amended, 
directs that, to the fullest extent possible, the policies, 
regulations, and public laws of the United States shall be interpreted 
and administered in accordance with the policies set forth in NEPA. All 
agencies of the Federal Government shall comply with the procedures in 
section 102(2) of NEPA except where compliance would be inconsistent 
with other statutory requirements. The regulations in this part 
implement section 102(2) of NEPA in a manner that is consistent with 
FDA's authority under the Federal Food, Drug, and Cosmetic Act and the 
Public Health Service Act. This part also supplements the regulations 
for implementing the procedural provisions of NEPA that were published 
by the Council on Environmental Quality (CEQ) in 40 CFR Parts 1500 
through 1508 and the procedures included in the ``HHS General 
Administration Manual, Part 30: Environmental Protection'' (45 FR 76519 
to 76534, November 19, 1980).Sec. 25.5 Terminology.
    (a) Definitions that apply to the terms used in this part are set 
forth in the CEQ regulations under 40 CFR part 1508. The terms and the 
sections of 40 CFR part 1508 in which they are defined follow:
    (1) Categorical exclusion (40 CFR 1508.4).
    (2) Cooperating agency (40 CFR 1508.5).
    (3) Cumulative impact (40 CFR 1508.7).
    (4) Effects (40 CFR 1508.8).
    (5) Environmental assessment (EA) (40 CFR 1508.9).
    (6) Environmental document (40 CFR 1508.10).
    (7) Environmental impact statement (EIS) (40 CFR 1508.11).
    (8) Federal agency (40 CFR 1508.12).
    (9) Finding of no significant impact (40 CFR 1508.13).
    (10) Human environment (40 CFR 1508.14).
    (11) Lead agency (40 CFR 1508.16).
    (12) Legislation (40 CFR 1508.17).
    (13) Major Federal action (40 CFR 1508.18).
    (14) Mitigation (40 CFR 1508.20).
    (15) NEPA process (40 CFR 1508.21).
    (16) Notice of intent (40 CFR 1508.22).
    (17) Proposal (40 CFR 1508.23).
    (18) Scope (40 CFR 1508.25).
    (19) Significantly (40 CFR 1508.27).
    (b) The following terms are defined solely for the purpose of 
implementing the supplemental procedures provided by this part and are 
not necessarily applicable to any other statutory or regulatory 
requirements:-
    (1) Abbreviated application applies to an abbreviated new drug 
application, an abbreviated antibiotic application, and an abbreviated 
new animal drug application.
    (2) Active moiety means the molecule or ion, excluding those 
appended portions of the molecule that cause the drug to be an ester, 
salt (including a salt with hydrogen or coordination bonds), or other 
noncovalent derivative (such as a complex chelate or clathrate) of the 
molecule responsible for the physiological or pharmacological action of 
the drug substance.
    (3) Agency means the Food and Drug Administration (FDA).
    (4) Increased use of a drug or biologic product may occur if the 
drug will be administered at higher dosage levels, for longer duration 
or for different indications than were previously in effect, or if the 
drug is a new molecular entity. New molecular entity means a drug for 
which the active moiety (present as the unmodified (parent) compound, 
or an ester or a salt, clathrate, or other noncovalent derivative of 
the base (parent) compound) has not been previously approved or 
marketed in the United States for use in a drug product, either as a 
single ingredient or as part of a combination product or as part of a 
mixture of stereoisomers. The term ``use'' also encompasses disposal of 
FDA-regulated articles by consumers.
    (5) Responsible agency official means the agency decisionmaker 
designated in part 5 of this chapter.
    (c) The following acronyms are used in this part:
    (1) CEQ--Council on Environmental Quality.
    (2) CGMP--Current good manufacturing practice.
    (3) EA--Environmental assessment.
    (4) EIS--Environmental impact statement.
    (5) The act--Federal Food, Drug, and Cosmetic Act.
    (6) FIFRA--Federal Insecticide, Fungicide, and Rodenticide Act.
    (7) FONSI--Finding of no significant impact.
    (8) GLP--Good laboratory practice.
    (9) GRAS--Generally recognized as safe.
    (10) HACCP--Hazard analysis critical control point.
    (11) IDE--Investigational device exemption.
    (12) IND--Investigational new drug application.
    (13) INAD--Investigational new animal drug application.
    (14) NADA--New animal drug application.
    (15) NDA--New drug application.
    (16) NEPA--National Environmental Policy Act of 1969.-
    (17) PDP--Product development protocol.
    (18) PMA--Premarket approval application.-
    
[[Page 14937]]



Sec. 25.10  Policies and NEPA planning.

    (a) All FDA's policies and programs will be planned, developed, and 
implemented to achieve the policies declared by NEPA and required by 
CEQ's regulations to ensure responsible stewardship of the environment 
for present and future generations.
    (b) Assessment of environmental factors continues throughout 
planning and is integrated with other program planning at the earliest 
possible time to ensure that planning and decisions reflect 
environmental values, to avoid delays later in the process, and to 
avoid potential conflicts.
    (c) For actions initiated by the agency, the NEPA process will 
begin when the agency action under consideration is first identified. 
For actions initiated by applicants or petitioners, NEPA planning 
begins when FDA receives a submission from an applicant or petitioner 
seeking action by FDA. FDA may issue a public call for environmental 
data or otherwise consult with affected individuals or groups when a 
contemplated action in which it is or may be involved poses potential 
significant environmental effects.
    (d) Environmental documents shall concentrate on timely and 
significant issues, not amass needless detail.
    (e) If a proposed action for which an EIS will be prepared involves 
possible environmental effects that are required to be considered under 
statutes or Executive Orders other than those referred to under 
``AUTHORITY'' in this part, these effects shall be considered in the 
NEPA review, consistent with 40 CFR 1502.25 and the Department of 
Health and Human Services' General Administration Manual, part 30.

Subpart B--Agency Actions Requiring Environmental Consideration


Sec. 25.15  General procedures.

    (a) All applications or petitions requesting agency action require 
the submission of an EA or a claim of categorical exclusion. A claim of 
categorical exclusion shall include a certification of compliance with 
the categorical exclusion criteria and shall certify that to the 
applicant's knowledge, no extraordinary circumstances exist. Failure to 
submit an adequate EA for an application or petition requesting action 
by the agency of a type specified in Sec. 25.20, unless the agency can 
determine that the action qualifies for exclusion under Secs. 25.30, 
25.31, 25.32, 25.33, or 25.34, is sufficient grounds for FDA to refuse 
to file or approve the application or petition.
    (b) The responsible agency officials will evaluate the information 
contained in the EA to determine whether it is accurate and objective, 
whether the proposed action may significantly affect the quality of the 
human environment, and whether an EIS will be prepared. If significant 
effects requiring the preparation of an EIS are identified, FDA will 
prepare an EIS for the action in accordance with the procedures in 
subparts D and E of this part. If significant effects requiring the 
preparation of an EIS are not identified, resulting in a decision not 
to prepare an EIS, the responsible agency official will prepare a FONSI 
in accordance with Sec. 25.41.
    (c) Classes of actions that individually or cumulatively do not 
significantly affect the quality of the human environment ordinarily 
are excluded from the requirement to prepare an EA or an EIS. The 
classes of actions that qualify as categorical exclusions are set forth 
in Secs. 25.30, 25.31, 25.32, 25.33, or 25.34.
    (d) A person submitting an application or petition of a type 
subject to categorical exclusion under Secs. 25.30, 25.31, 25.32, 
25.33, or 25.34, or proposing to dispose of an article as provided in 
Secs. 25.30(d) or 25.32(h), is not required to submit an EA if the 
person certifies that the action requested qualifies for a categorical 
exclusion, citing the particular categorical exclusion that is claimed, 
and certifies that to the applicant's knowledge, no extraordinary 
circumstances exist.


Sec. 25.16  Public health and safety emergencies.

    There are certain regulatory actions that, because of their 
immediate importance to the public health or safety, may make adherence 
to the procedural provisions of NEPA and CEQ's regulations impossible. 
For such actions, the responsible agency official shall consult with 
CEQ about alternative arrangements before the action is taken, or after 
the action is taken, if time does not permit prior consultation with 
CEQ.


Sec. 25.20  Actions requiring preparation of an environmental 
assessment.

    Any proposed action of a type specified in this section ordinarily 
requires at least the preparation of an EA, unless it is an action in a 
specific class that qualifies for exclusion under Secs. 25.30, 25.31, 
25.32, 25.33, or 25.34:
    (a) Major recommendations or reports made to Congress on proposals 
for legislation in instances where the agency has primary 
responsibility for the subject matter involved.
    (b) Destruction or other disposition of articles condemned after 
seizure or whose distribution or use has been enjoined, unless 
categorically excluded in Secs. 25.30(d) or 25.32(h).
    (c) Destruction or other disposition of articles following 
detention or recall at agency request, unless categorically excluded in 
Secs. 25.30(d) or 25.32(h).
    (d) Disposition of FDA laboratory waste materials, unless 
categorically excluded in Sec. 25.30(m).
    (e) Intramural and extramural research supported in whole or in 
part through contracts, other agreements, or grants, unless 
categorically excluded in Sec. 25.30(e) or (f).
    (f) Establishment by regulation of labeling requirements, a 
standard, or a monograph, unless categorically excluded in 
Secs. 25.30(k) or 25.31(a), (b), (c), (h), (i), or (j), or 25.32(a) or 
(p).
    (g) Issuance, amendment, and enforcement of FDA regulations, or an 
exemption or variance from FDA regulations, unless categorically 
excluded in Secs. 25.30(h), (i), or (j), or 25.32(e), (g), (n), or (p).
    (h) Withdrawal of existing approvals of FDA-approved articles, 
unless categorically excluded in Secs. 25.31(d) or (k), 25.32(m), or 
25.33(g) or (h).
    (i) Approval of food additive petitions and color additive 
petitions, approval of requests for exemptions for investigational use 
of food additives, and granting of requests for exemption from 
regulation as a food additive, unless categorically excluded in 
Sec. 25.32(b), (c), (i), (j), (k), (l), (o), (q), or (r).
    (j) Establishment of a tolerance for unavoidable poisonous or 
deleterious substances in food or in packaging materials to be used for 
food.--
    (k) Affirmation of a food substance as GRAS for humans or animals, 
on FDA's initiative or in response to a petition, under part 182, 184, 
186, or 582 of this chapter and establishment or amendment of a 
regulation for a prior-sanctioned food ingredient, as defined in 
Secs. 170.3(l) and 181.5(a) of this chapter, unless categorically 
excluded in Sec. 25.32(f), (k), or (r).
    (l) Approval of NDA's, abbreviated applications, applications for 
marketing approval for marketing of a biologic product, supplements to 
such applications, and actions on IND's, unless categorically excluded 
in Sec. 25.31(a), (b), (c), (e), or (l).
    (m) Approval of NADA's, abbreviated applications, supplements, and 
actions on INAD's, unless categorically excluded under Sec. 25.33(a), 
(c), (d), or (e).
    (n) Approval of PMA's for medical devices, notices of completion of 
PDP's for medical devices, authorizations to commence clinical 
investigation under an approved PDP, or applications for an

[[Page 14938]]
IDE, unless categorically excluded in Sec. 25.34.


Sec. 25.21  Extraordinary circumstances.

    As required under 40 CFR 1508.4, FDA will require at least an EA 
for any specific action that ordinarily would be excluded if 
extraordinary circumstances indicate that the specific proposed action 
may significantly affect the quality of the human environment (see 40 
CFR 1508.27 for examples of significant impacts). Examples of such 
extraordinary circumstances include:
    (a) Actions for which available data establish that, at the 
expected level of exposure, there is the potential for serious harm to 
the environment; and
    (b) Actions that adversely affect a species or the critical habitat 
of a species determined under the Endangered Species Act or the 
Convention on International Trade in Endangered Species of Wild Flora 
and Fauna to be endangered or threatened or wild flora or fauna that 
are entitled to special protection under some other Federal law.


Sec. 25.22  Actions requiring the preparation of an environmental 
impact statement.

    (a) There are no categories of agency actions that routinely 
significantly affect the quality of the human environment and that 
therefore ordinarily require the preparation of an EIS.
    (b) EIS's are prepared for agency actions when evaluation of data 
or information in an EA or otherwise available to the agency leads to a 
finding by the responsible agency official that a proposed action may 
significantly affect the quality of the human environment.

Subpart C--Categorical Exclusions


Sec. 25.30  General.

    The classes of actions listed in this section and Secs. 25.31 
through 25.34 are categorically excluded and, therefore, ordinarily do 
not require the preparation of an EA or an EIS:
    (a) Routine administrative and management activities, including 
inspections, and issuance of field compliance programs, program 
circulars, or field investigative assignments.
    (b) Recommendation for an enforcement action to be initiated in a 
Federal court.
    (c) Agency requests for initiation of recalls.
    (d) Destruction or disposition of any FDA-regulated article 
condemned after seizure or the distribution or use of which has been 
enjoined or following detention or recall at agency request if the 
method of destruction or disposition of the article, including 
packaging material, is in compliance with all Federal, State, and local 
requirements.
    (e) Extramural contracts, other agreements, or grants for 
statistical and epidemiological studies, surveys and inventories, 
literature searches, and report and manual preparation, or any other 
studies that will not result in the production or distribution of any 
substance and, therefore, will not result in the introduction of any 
substance into the environment.
    (f) Extramural contracts, other agreements, and grants for research 
for such purposes as to develop analytical methods or other test 
methodologies.
    (g) Activities of voluntary Federal-State cooperative programs, 
including issuance of model regulations proposed for State adoption.
    (h) Issuance, amendment, or revocation of procedural or 
administrative regulations and guidelines, including procedures for 
submission of applications for product development, testing and 
investigational use, and approval.
    (i) Corrections and technical changes in regulations.
    (j) Issuance of CGMP regulations, HACCP regulations, establishment 
standards, emergency permit control regulations, GLP regulations, and 
issuance or denial of permits, exemptions, variances, or stays under 
these regulations.
    (k) Establishment or repeal by regulation of labeling requirements 
for marketed articles if there will be no increase in the existing 
levels of use or change in the intended uses of the product or its 
substitutes.
    (l) Routine maintenance and minor construction activities such as:
    (1) Repair to or replacement of equipment or structural components 
(e.g., door, roof, or window) of facilities controlled by FDA;
    (2) Lease extensions, renewals, or succeeding leases;
    (3) Construction or lease construction of 10,000 square feet or 
less of occupiable space;
    (4) Relocation of employees into existing owned or currently leased 
space;
    (5) Acquisition of 20,000 square feet or less of occupiable space 
in a structure that was substantially completed before the issuance of 
solicitation for offers; and
    (6) Acquisition of between 20,000 square feet and 40,000 square 
feet of occupiable space if it constitutes less than 40 percent of the 
occupiable space in a structure that was substantially completed before 
the solicitation for offers.
    (m) Disposal of low-level radioactive waste materials (as defined 
in the Nuclear Regulatory Commission regulations at 10 CFR 61.2) and 
chemical waste materials generated in the laboratories serviced by the 
contracts administered by FDA, if the waste is disposed of in 
compliance with all applicable Federal, State, and local requirements.


Sec. 25.31  Human drugs and biologics.

    The classes of actions listed in this section are categorically 
excluded and, therefore, ordinarily do not require the preparation of 
an EA or an EIS:
    (a) Action on an NDA, abbreviated application, or a supplement to 
such application, or action on an OTC monograph, if the action does not 
increase the use of the active moiety.
    (b) Action on an NDA, abbreviated application, or a supplement to 
such application, or action on an OTC monograph, if the action 
increases the use of the active moiety, but the concentration of the 
substance in the environment will be below 1 part per billion.
    (c) Action on an NDA, abbreviated application, application for 
marketing approval of a biologic product, or a supplement to such 
application, or action on an OTC monograph, for substances that occur 
naturally in the environment when the action does not alter 
significantly the concentration or distribution of the substance, its 
metabolites, or degradation products in the environment.
    (d) Withdrawal of approval of an NDA or an abbreviated application.
    (e) Action on an IND.
    (f) Testing and certification of batches of an antibiotic or 
insulin.
    (g) Testing and release by the Center for Biologics Evaluation and 
Research of lots or batches of a licensed biologic product.
    (h) Issuance, revocation, or amendment of a monograph for an 
antibiotic drug.
    (i) Establishment of bioequivalence requirements for a human drug 
or a comparability determination for a biologic product subject to 
licensing.
    (j) Issuance, revocation, or amendment of a standard for a biologic 
product.
    (k) Revocation of a license for a biologic product.
    (l) Action on an application for marketing approval for marketing 
of a biologic product for transfusable human blood or blood components 
and plasma.


Sec. 25.32  Foods, food additives, and color additives.

    The classes of actions listed in this section are categorically 
excluded and,

[[Page 14939]]
therefore, ordinarily do not require the preparation of an EA or an 
EIS:
    (a) Issuance, amendment, or repeal of a food standard.
    (b) Action on a request for exemption for investigational use of a 
food additive if the food additive to be shipped under the request is 
intended to be used for clinical studies or research.
    (c) Approval of a color additive petition to change a provisionally 
listed color additive to permanent listing for use in food, drugs, 
devices, or cosmetics.
    (d) Testing and certification of batches of a color additive.
    (e) Issuance of an interim food additive regulation.
    (f) Affirmation of a food substance as GRAS for humans or animals 
on FDA's initiative or in response to a petition, under parts 182, 184, 
186, or 582 of this chapter, and establishment or amendment of a 
regulation for a prior-sanctioned food ingredient, as defined in 
Secs. 170.3(l) and 181.5(a) of this chapter, if the substance or food 
ingredient is already marketed in the United States for the proposed 
use.
    (g) Issuance and enforcement of regulations relating to the control 
of communicable diseases or to interstate conveyance sanitation under 
parts 1240 and 1250 of this chapter.
    (h) Approval of a request for diversion of adulterated or 
misbranded food for humans or animals to use as animal feeds.
    (i) Approval of a food additive petition or the granting of a 
request for exemption from regulation as a food additive under 
Sec. 170.39 of this chapter when the additive is present in finished 
food-packaging material at not greater than 5 percent-by-weight and is 
also a functional component of the finished packaging material.
    (j) Approval of a food additive petition or the granting of a 
request for exemption from regulation as a food additive under 
Sec. 170.39 of this chapter when the additive is to be used as a 
component of a food-contact surface of permanent or semipermanent 
equipment or of another food-contact article intended for repeated use.
    (k) Approval of a food additive, color additive, or GRAS petition 
for substances added directly to food that are intended to remain in 
food through ingestion by consumers and that are not intended to 
replace macronutrients in food.
    (l) Approval of a petition for color additives used in contact 
lenses, sutures, filaments used as supporting haptics in intraocular 
lenses, bone cement, and in other FDA-regulated products having 
similarly low levels of use.
    (m) Action to prohibit or otherwise restrict or reduce the use of a 
substance in food, food packaging, or cosmetics.
    (n) Issuance, amendment, or revocation of a regulation pertaining 
to infant formulas.
    (o) Approval of a food additive petition for the intended 
expression product(s) present in food derived from new plant varieties.
    (p) Issuance, amendment, or revocation of a regulation in response 
to a reference amount petition as described in Sec. 101.12(h) of this 
chapter, a nutrient content claim petition as described in Sec. 101.69 
of this chapter, a health claim petition as described in Sec. 101.70 of 
this chapter, or a petition pertaining to the label declaration of 
ingredients as described in Sec. 101.103 of this chapter.
    (q) Approval of a food additive petition or the granting of a 
request for an exemption from regulation as a food additive under 
Sec. 170.39 of this chapter for a substance registered by the 
Environmental Protection Agency under FIFRA for the same use requested 
in the petition.
    (r) Approval of a food additive, color additive, or GRAS 
affirmation petition for a substance that occurs naturally in the 
environment, when the action does not alter significantly the 
concentration or distribution of the substance, its metabolites, or 
degradation products in the environment.


Sec. 25.33  Animal drugs.

    The classes of actions listed in this section are categorically 
excluded and, therefore, ordinarily do not require the preparation of 
an EA or an EIS:
    (a) Action on an NADA, abbreviated application, or supplement to 
such applications, if the action does not increase the use of the drug. 
Actions to which this categorical exclusion applies include:
    (1) An animal drug to be marketed under the same conditions of 
approval as a previously approved animal drug;
    (2) A combination of previously approved animal drugs;
    (3) A new premix or other formulation of a previously approved 
animal drug;
    (4) Changes specified in Sec. 514.8(a)(5), (a)(6), or (d) of this 
chapter;
    (5) A change of sponsor;
    (6) A previously approved animal drug to be contained in medicated 
feed blocks under Sec. 510.455 of this chapter or as a liquid feed 
supplement under Sec. 558.5 of this chapter; or
    (7) Approval of a drug for use in animal feeds if such drug has 
been approved under Sec. 514.2 or 514.9 of this chapter for other uses.
    (b) [Reserved]
    (c) Action on an NADA, abbreviated application, or a supplement for 
substances that occur naturally in the environment when the action does 
not alter significantly the concentration or distribution of the 
substance, its metabolites, or degradation products in the environment.
    (d) Action on an NADA, abbreviated application, or a supplement to 
such applications, for:
    (1) Drugs intended for use in nonfood animals;
    (2) Anesthetics, both local and general, that are individually 
administered;
    (3) Nonsystemic topical and ophthalmic animal drugs;
    (4) Drugs for minor species, including wildlife and endangered 
species, when the drug has been previously approved for use in another 
or the same species where similar animal management practices are used; 
and
    (5) Drugs intended for use under prescription or veterinarian's 
order for therapeutic use.
    (e) Action on an INAD.
    (f) Action on an application submitted under section 512(m) of the 
act.
    (g) Withdrawal of approval of an NADA or an abbreviated NADA.
    (h) Withdrawal of approval of a food additive petition that reduces 
or eliminates animal feed uses of a food additive.


Sec. 25.34  Devices and electronic products.

    The classes of actions listed in this section are categorically 
excluded and, therefore, ordinarily do not require the preparation of 
an EA or an EIS:
    (a) Action on a device premarket notification submission under 
subpart E of part 807 of this chapter.
    (b) Classification or reclassification of a device under part 860 
of this chapter.
    (c) Issuance, amendment, or repeal of a standard for a class II 
medical device or an electronic product, and issuance of exemptions or 
variances from such a standard.
    (d) Approval of a PMA or a notice of completion of a PDP or amended 
or supplemental applications or notices for a class III medical device 
if the device is of the same type and for the same use as a previously 
approved device.
    (e) Changes in the PMA or a notice of completion of a PDP for a 
class III medical device that do not require submission of an amended 
or supplemental application or notice.
    (f) Issuance of a restricted device regulation if it will not 
result in increases in the existing levels of use or changes in the 
intended uses of the product or its substitutes.

[[Page 14940]]

    (g) Action on an application for an IDE or an authorization to 
commence a clinical investigation under an approved PDP.
    (h) Issuance of a regulation exempting from preemption a 
requirement of a State or political subdivision concerning a device, or 
a denial of an application for such exemption.

Subpart D--Preparation of Environmental Documents


Sec. 25.40  Environmental assessments.-

    (a) As defined by CEQ in 40 CFR 1508.9, an EA is a concise public 
document that serves to provide sufficient evidence and analysis for an 
agency to determine whether to prepare an EIS or a FONSI. The EA shall 
include brief discussions of the need for the proposal, of alternatives 
as required by section 102(2)(E) of NEPA, of the environmental impacts 
of the proposed action and alternatives, and a listing of agencies and 
persons consulted. An EA shall be prepared for each action not 
categorically excluded in Secs. 25.30, 25.31, 25.32, 25.33, or 25.34. 
The EA shall focus on relevant environmental issues and shall be a 
concise, objective, and well-balanced document that allows the public 
to understand the agency's decision. If potentially adverse 
environmental impacts are identified for an action or group of related 
actions, the EA shall discuss any reasonable alternative course of 
action that offers less environmental risk or that is environmentally 
preferable to the proposed action. The use of a scientifically 
justified tiered testing approach, in which testing may be stopped when 
the results suggest that no significant impact will occur, is an 
acceptable approach.
    (b) Generally, FDA requires an applicant to prepare an EA and make 
necessary corrections to it. Ultimately, FDA is responsible for the 
scope and content of EA's and may include additional information in 
environmental documents when warranted.
    (c) Information concerning the nature and scope of information that 
an applicant or petitioner shall submit in an EA may be obtained from 
the center or other office of the agency having responsibility for the 
action that is the subject of the environmental evaluation. Applicants 
and petitioners are encouraged to submit proposed protocols for 
environmental studies for technical review by agency staff. Applicants 
and petitioners also are encouraged to consult applicable FDA EA 
guidance documents, which provide additional advice on how to comply 
with FDA regulations.
    (d) Consistent with 40 CFR 1500.4(j) and 1502.21, EA's may 
incorporate by reference information presented in other documents that 
are available to FDA and to the public.
    (e) The agency evaluates the information contained in an EA and any 
public input to determine whether it is accurate and objective, whether 
the proposed action may significantly affect the quality of the human 
environment, and whether an EIS or FONSI will be prepared. The 
responsible agency official designated in part 5 of this chapter as 
responsible for the underlying action examines the environmental risks 
of the proposed action and the alternative courses of action, selects a 
course of action, and ensures that any necessary mitigating measures 
are implemented as a condition for approving the selected course of 
action.


Sec. 25.41  Findings of no significant impact.

    (a) As defined by the CEQ regulations (40 CFR 1508.13), a FONSI is 
a document prepared by a Federal agency stating briefly why an action, 
not otherwise excluded, will not significantly affect the human 
environment and for which, therefore, an EIS will not be prepared. A 
FONSI includes the EA or a summary of it and a reference to any other 
related environmental documents.
    (b) The agency official(s) responsible for approving the FONSI will 
sign the document, thereby establishing that the official(s) approve(s) 
the conclusion not to prepare an EIS for the action under 
consideration.


Sec. 25.42  Environmental impact statements.

    (a) As defined by CEQ regulations (40 CFR 1508.11) and section 
102(2)(C) of NEPA, an EIS should be a clear, concise, and detailed 
written statement describing:
    (1) The environmental impacts of a proposed action;
    (2) Any adverse effects that cannot be avoided if the action is 
implemented;
    (3) Alternatives to the action;
    (4) The relationship between local short-term uses of the 
environment and the maintenance and enhancement of long-term 
productivity; and
    (5) Any irreversible and irretrievable commitments of resources 
that would be involved in the proposed action should it be implemented.
    (b) The CEQ regulations (40 CFR 1501.7 and part 1502) describe the 
process for determining the scope of an EIS and provide detailed 
requirements for the preparation of draft and final EIS's. CEQ format 
and procedures for preparing EIS shall be followed.
    (c) Under the conditions prescribed in 40 CFR 1502.9, the agency 
will prepare a supplement for a draft or final EIS and introduce the 
supplement into the administrative record.


Sec. 25.43  Records of decisions.

    (a) In cases requiring environmental impact statements, at the time 
of its decision, the agency shall prepare a concise public record of 
decision.
    (b) The record of decision shall:
    (1) State what the decision was;
    (2) Identify and discuss alternatives considered by the agency in 
reaching its decision;
    (3) State whether all practicable means to avoid or minimize 
environmental harm have been adopted, and if not, why not; and
    (4) Discuss and implement any monitoring and enforcement program 
necessary to affect mitigation.


Sec. 25.44  Lead and cooperating agencies.--

    For actions requiring the preparation of an EIS, FDA and other 
affected Federal agencies will agree which will be the lead agency and 
which will be the cooperating agencies. The responsibilities of lead 
agencies and cooperating agencies are described in the CEQ regulations 
(40 CFR 1501.5 and 1501.6, respectively). If an action affects more 
than one center within FDA, the Commissioner of Food and Drugs will 
designate one of these units to be responsible for coordinating the 
preparation of any required environmental documentation.


Sec. 25.45  Responsible agency official.

    (a) The person designated in part 5 of this chapter as the 
responsible agency official for the underlying action is responsible 
for preparing environmental documents or ensuring that they are 
prepared.
    (b) The responsible agency official will weigh any environmental 
impacts of each alternative course of action, including possible 
mitigation measures, and will balance environmental impacts with the 
agency's objectives in choosing an appropriate course of action. The 
weighing of any environmental impacts of alternatives in selecting a 
final course of action will be reflected in the agency's record of 
formal decisionmaking as required by 40 CFR 1505.2.

Subpart E--Public Participation and Notification of Environmental 
Documents


Sec. 25.50  General information.

    (a) To the extent actions are not protected from disclosure by 
existing law applicable to the agency's operation, FDA will involve the 
public

[[Page 14941]]

in preparing and implementing its NEPA procedures and will provide 
public notice of NEPA-related hearings, public meetings, and the 
availability of environmental documents.
    (b) Many FDA actions involving investigations, review, and approval 
of applications, and premarket notifications for human drugs, animal 
drugs, biologic products, and devices are protected from disclosure 
under the Trade Secret Act, 18 U.S.C. 1905, and 301(j) of the act. 
These actions are also protected from disclosure under FDA's 
regulations including part 20, Secs. 312.130(a), 314.430(b), 514.11(b), 
514.12(a), 601.50(a), 601.51(a), 807.95(b), 812.38(a), and 814.9(b) of 
this chapter. Even the existence of applications for human drugs, 
animal drugs, biologic products, and devices is protected from 
disclosure under these regulations. Therefore, unless the existence of 
applications for human drugs, animal drugs, biologic products, or 
premarket notification for devices has been made publicly available, 
the release of the environmental document before approval of human 
drugs, animal drugs, biologic products, and devices is inconsistent 
with statutory requirements imposed on FDA. Appropriate environmental 
documents, comments, and responses will be included in the 
administrative record to the extent allowed by applicable laws.


Sec. 25.51  Environmental assessments and findings of no significant -
impact.

    (a) Data and information that are protected from disclosure by 18 
U.S.C. 1905 or 21 U.S.C. 331(j) or 360j(c) shall not be included in the 
portion of environmental documents that is made public. When such data 
and information are pertinent to the environmental review of a proposed 
action, an applicant or petitioner shall submit such data and 
information separately in a confidential section We have spend 20 years 
trying to keep confidential information out of Eas. I suggest the 
preceding revision. Gail said she prefers confidential appendix to the 
EA.and shall summarize the confidential data and information in the EA 
to the extent possible.
    (b) FONSI's and EA's will be available to the public in accordance 
with 40 CFR 1506.6 as follows:
    (1) When the proposed action is the subject of a notice of proposed 
rulemaking or a notice of filing published in the Federal Register, the 
notice shall state that no EIS is necessary and that the FONSI and the 
EA are available for public inspection at FDA's Dockets Management 
Branch. If the responsible agency official is unable to complete 
environmental consideration of the proposed action before a notice of 
filing of a food or color additive petition is required to be published 
under the act, and if the subsequent environmental analysis leads to 
the conclusion that no EIS is necessary, the Federal Register document 
publishing the final regulation rather than the notice of filing shall 
state that no EIS is necessary and that the FONSI and the EA are 
available upon request and filed in FDA's Dockets Management Branch.
    (2) For actions for which notice is not published in the Federal 
Register, the FONSI and the EA shall be made available to the public 
upon request according to the procedures in 40 CFR 1506.6.
    (3) For a limited number of actions, the agency may make the FONSI 
and EA available for public review (including review by State and 
areawide information clearinghouses) for 30 days before the agency 
makes its final determination whether to prepare an EIS and before the 
action may begin, as described in 40 CFR 1501.4(e). This procedure will 
be followed when the proposed action is, or is closely similar to, one 
that normally requires an EIS or when the proposed action is one 
without precedent.


Sec. 25.52  Environmental impact statements.

    (a) If FDA determines that an EIS is necessary for an action 
involving investigations or approvals for drugs, animal drugs, biologic 
products, or devices, an EIS will be prepared but will become available 
only at the time of the approval of the product. Disclosure will be 
made in accordance with 40 CFR 1506.6 and part 20 of this chapter. The 
EIS will in all other respects conform to the requirements for EIS's as 
specified in 40 CFR part 1502 and 1506.6(f).
    (b) Comments on the EIS may be submitted after the approvalof the 
drug, animal drug, biologic product, and device. Those comments can 
form the basis for the agency to consider beginning an action to 
withdraw the approval of applications for a drug, animal drug, biologic 
product, or to withdraw premarket notifications or premarket approval 
applications for devices.
    (c) In those cases where the existence of applications and 
premarket notifications for drugs, animal drugs, biologic products, or 
devices has already been disclosed before the agency approves the 
action, the agency will make diligent effort (40 CFR 1506.6) to involve 
the public in preparing and implementing the NEPA procedures for EIS's 
while following its own disclosure requirements including those listed 
in part 20, Secs. 312.130(b), 314.430(d), 514.11(d), 514.12(b), 
601.51(d), 807.95(e), 812.38(b), and 814.9(d) of this chapter.
    (d) Draft and final EIS's, comments, and responses will be included 
in the administrative record and will be available from the Dockets 
Management Branch (HFA-305), Food and Drug Administration, 12420 
Parklawn Dr., rm. 1-23, Rockville, MD 20857.

Subpart F--Other Requirements


Sec. 25.60  Environmental effects abroad of major agency actions.

    (a) In accordance with Executive Order 12114, ``Environmental 
Effects Abroad of Major Federal Actions'' of January 4, 1979 (44 FR 
1957, January 9, 1977), the responsible agency official, in analyzing 
actions under his or her program, shall consider the environmental 
effects abroad, including whether the actions involve:
    (1) Potential environmental effects on the global commons and areas 
outside the jurisdiction of any nation, e.g., oceans and the upper 
atmosphere.
    (2) Potential environmental effects on a foreign nation not 
participating with or otherwise involved in an FDA activity.
    (3) The export of products (or emissions) that in the United States 
are prohibited or strictly regulated because their effects on the 
environment create a serious public health risk.
    (4) Potential environmental effects on natural and ecological 
resources of global importance designated under the Executive Order.
    (b) Before deciding on any action falling into the categories 
specified in paragraph (a) of this section, the responsible agency 
official shall determine in accordance with section 2-3 of the 
Executive Order whether such actions may have a significant 
environmental effect abroad.
    (c) If the responsible agency official determines that an action 
may have a significant environmental effect abroad, the responsible 
agency official shall determine in accordance with section 2-4(a) and 
(b) of the Executive Order, whether the subject action calls for:
    (1) An EIS;
    (2) A bilateral or multilateral environmental study; or
    (3) A concise environmental review.
    (d) In preparing environmental documents under this subpart, the 
responsible official shall:
    (1) Determine, as provided in section 2-5 of the Executive Order, 
whether proposed actions are subject to the exemptions, exclusions, and

[[Page 14942]]
modification in contents, timing, and availability of documents.
    (2) Coordinate all communications with foreign governments 
concerning environmental agreements and other arrangements in 
implementing the Executive Order.

    Dated: March 19, 1996.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 96-8090 Filed 4-2-96; 8:45 am]
BILLING CODE 4160-01-F