[Federal Register Volume 61, Number 85 (Wednesday, May 1, 1996)]
[Proposed Rules]
[Pages 19476-19495]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-10732]
[[Page 19475]]
_______________________________________________________________________
Part VIII
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. 85 / Wednesday, May 1, 1996 /
Proposed Rules
[[Page 19476]]
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
Note: This document was originally published at 61 FR 14922,
Wednesday, April 3, 1996. Certain text inadvertently appeared in the
printed version. For the convenience of the reader, the document is
being republished in its entirety.
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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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
[[Page 19477]]
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 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. ``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 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
[[Page 19478]]
account any ecotoxicity data relevant to the issue.
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. 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 19479]]
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 19480]]
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.
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.
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.
Issuance of additional standards for biologic products (21 CFR parts
620 through 680) does not increase the use of a 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 submitted by industry under NEPA by
increasing the number of categorical exclusions for food and color
additives and generally recognized as safe (GRAS)
[[Page 19481]]
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 functional components of food-packaging materials are
low, the agency believes that future approvals will also result in
insignificant introductions into
[[Page 19482]]
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 by 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 in no case was
there potential for significant impacts on energy and natural
resources. These findings relied on one or more of the following
[[Page 19483]]
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
potential risk of being a plant pest, USDA conducts an environmental
analysis in compliance with its NEPA requirements that addresses plant
pest
[[Page 19484]]
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 relevant. 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 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
[[Page 19485]]
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.
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.
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
[[Page 19486]]
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 relevant
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 Sec. 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 categorical 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 additional EA each time the agency
considers approval of an application submitted under section 512(m) of
the act.
[[Page 19487]]
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 local emission
requirements. However, if information available to the agency or the
applicant establishes that the general or specific emission
[[Page 19488]]
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 Sec. Sec. 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 timeframes 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 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
[[Page 19489]]
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).
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
[[Page 19490]]
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 decision maker
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.-
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
[[Page 19491]]
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 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
[[Page 19492]]
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, 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
[[Page 19493]]
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.
(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.
[[Page 19494]]
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 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
[[Page 19495]]
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 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 approval of 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
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: April 17, 1996.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 96-10732 Filed 4-30-96; 8:45 am]
BILLING CODE 4160-01-F
