[Federal Register Volume 61, Number 65 (Wednesday, April 3, 1996)]
[Proposed Rules]
[Pages 14922-14942]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-8090]
[[Page 14921]]
_______________________________________________________________________
Part III
Department of Health and Human Services
_______________________________________________________________________
Food and Drug Administration
_______________________________________________________________________
21 CFR Part 25
National Environmental Policy Act: Proposed Revision of Policies and
Procedures; Proposed Rule
Federal Register / Vol. 61, No. 65 / Wednesday, April 3, 1996 /
Proposed Rules
[[Page 14922]]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 25
[Docket No. 96N-0057]
National Environmental Policy Act; Proposed Revision of Policies
and Procedures
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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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 by FDA and, consequently, reduce the number of findings of no
significant impact (FONSI's) the agency would be required to prepare.
Furthermore, the proposal will not compromise the environment because
the excluded actions have been found not to have a significant effect
on the environment, and the proposed rule would continue
[[Page 14923]]
to provide for the preparation of an EA under extraordinary
circumstances in which a categorically excluded action may have a
significant environmental impact. This proposal would enable FDA to
focus its resources in the environmental area on situations likely to
have an effect on the environment.
The agency is also proposing to revise its environmental
regulations to make them more concise and useful to the public and
regulated industry by reorganizing, simplifying, and eliminating
unnecessary and duplicative language. The proposed rule would
reorganize and renumber various sections so that information on certain
topics is grouped together. The agency solicits comments on and
suggestions for further improvement in these regulations.
III. Specific Proposed Changes
A. General Provisions
The proposed rule would eliminate unnecessary language in current
subpart A of part 25 by deleting the reference to the environmental
statutes listed in current Sec. 25.5 Policies, amending Sec. 25.15
Terminology (proposed Sec. 25.5), and making other minor revisions,
including combining Sec. 25.5 Policies and Sec. 25.10 NEPA planning
into proposed Sec. 25.10 Policies and NEPA planning.
In proposed Sec. 25.5 Terminology, FDA is proposing to remove
definitions listed in current Sec. 25.15 that are not used in part 25,
and add new definitions for ``active moiety'' and ``increased use'' of
a drug. ``Increased use'' of a drug will occur if the drug will be
administered at higher dosage levels, for longer duration, or for
different indications than were previously in effect, or if the drug is
a new molecular entity. ``Increased use'' encompasses consideration of
FDA-regulated articles that are disposed of by consumers.Eric Flamm
suggests wording: ``Increased use'' encompasses consideration of
disposal of FDA regulated articles by consumers. ``Active moiety'' has
been previously defined in FDA regulations (21 CFR 314.108(a)).
B. Agency Actions Requiring Environmental Consideration-
Proposed Sec. 25.15 would contain the general procedural
information now found in current Secs. 25.20 and 25.22.
The proposed rule would create new Sec. 25.l6 Public health and
safety emergencies using revised language now contained in current
Sec. 25.40(b).
Actions requiring preparation of an EA (proposed Sec. 25.20) would
remain essentially the same as current Sec. 25.22, except that: (1)
Current Sec. 25.22(a)(13), promulgation and enforcement of FDA
regulations relating to the control of communicable disease and to
interstate conveyance sanitation, has been deleted and is covered by
proposed Sec. 25.20(g); and (2) actions relating to approval of new
drug applications (NDA's) and abbreviated applications, actions on
investigational new drug applications (IND's) (current
Sec. 25.22(a)(14)), issuance of licenses for biologic products (current
Sec. 25.22(a)(16)), and approval of supplements to existing approvals
of FDA-regulated articles (Sec. 25.22(a)(8)) have been combined into
one provision (proposed Sec. 25.20(l)) and revised to reflect current
terminology.
The proposed regulations include new Sec. 25.21 Extraordinary
circumstances, which addresses circumstances under which categories of
actions that would ordinarily be categorically excluded would require
preparation of environmental documents. Proposed Sec. 25.21
incorporates current Sec. 25.23(b) and includes two examples of
circumstances under which an action would require the preparation of
environmental documents because it might have the potential to
significantly affect the environment. The examples of circumstances
that will cause an action not to qualify for categorical exclusion are:
(1) Actions for which data available establish that, at the expected
level of exposure, there is the potential for serious harm to the
environment (proposed Sec. 25.21(a)); and (2) actions that adversely
affect a species or the critical habitat of a species determined under
the Endangered Species Act or the Convention on International Trade in
Endangered Species of Wild Flora and Fauna to be endangered or
threatened, or wild flora or fauna that are entitled to special
protection under some other Federal law (proposed Sec. 25.21(b)). In
addition, the proposed rule references the CEQ regulations at 40 CFR
1508.27, which provide examples of circumstances in which significant
effects may occur. Extraordinary circumstances may be shown by either
data available to the agency or data available to the applicant or
petitioner and may be based on production, use, or disposal from use.
The two examples of extraordinary circumstances in proposed
Sec. 25.21 reflect Are they really disqualification criteria? If the
criteria are met, the exclusion is warranted. See 25.24(c)(1). Gail
concurs with this.criteria that appear in some of the categorical
exclusions listed in current Sec. 25.24. The language in the first
example, proposed Sec. 25.21(a), is derived from but differs slightly
from current Sec. 25.24 language relating to toxicity (see, e.g.,
Sec. 25.24(a)(10), (b)(2), and (c)(6)). The extraordinary circumstance
example in proposed Sec. 25.21(a) would revise the language in current
Sec. 25.24, ``the substance may be toxic to organisms in the
environment'' to read ``there may be harm to the environment.'' FDA is
revising this language to reflect that possible adverse environmental
effects other than toxicity should be considered. For example, some
biological agents that may be released may not be toxic to indigenous
organisms, but could have lasting effects on ecological community
dynamics.
FDA considers a substance to be toxic if it is harmful to some
biological mechanism or system. Although FDA recognizes that any
substance may produce damage to biological mechanisms or systems under
specific conditions, for the purposes of these regulations, FDA
considers a substance to be toxic if it is harmful to appropriate test
organisms at the expected level of exposure even though it may be
without effect in humans or other organisms at these concentrations,
and may even be used by humans because of its toxic properties.
As a result of the new language in proposed Sec. 25.21(a), the
words ``toxic'' and ``toxic substance'' are no longer used in the
proposed regulation. Therefore, FDA is proposing to remove the
definition of ``toxic substance'' at current Sec. 25.15(b)(6).
Furthermore, FDA no longer believes that the second part of the current
definition relating to toxicity of a substance is appropriate for the
following reasons: (1) Evaluation of the toxicity of a substance based
only on the concentration at the point of entry or point of highest
concentration ignores factors such as instantaneous dispersion that
typically takes place as a result of processes such as river flow and
wind, and that not all substances bioaccumulate. Consideration of such
dilution processes may be reasonable and scientifically sound in
estimating environmental concentrations for certain purposes; and (2)
the use of a factor of 1/100 of the concentration that causes 50-
percent mortality in a test organism to assess the toxicity of a
substance is not appropriate in all cases. The factors used to assess
toxicity should be directly related to the amount of valid ecotoxicity
data available. Although a factor of 1/100 may be appropriate in some
instances, it may be too much or too little in others. In evaluating
whether extraordinary circumstances exist, FDA will take into account
any ecotoxicity data relevant to the issue.
[[Page 14924]]
The second example of extraordinary circumstances relates to
instances in which the proposed action could adversely affect an
endangered or threatened species, or a species entitled to protection
under some other Federal law. FDA intends to closely examine proposed
actions that involve FDA-regulated articles obtained from wild flora
and fauna and will use the extraordinary circumstances provision to
require at least an EA in any instance in which it appears from an
examination of the proposed action that the action may cause a species
to become endangered or threatened.
In addition, the agency notes that the language in proposed
Sec. 25.21(a) includes the indirect effects as well as direct effects
of agency actions. For example, when the agency takes action to
prohibit or restrict the use of an FDA-regulated product, the agency
may consider whether the increased use of substitutes for the
prohibited or restricted product might, at the expected level of
exposure, result in harm to the environment.
FDA is proposing to remove current Sec. 25.25 (Retroactive
environmental consideration), because any request by FDA to an
applicant to submit additional information to an existing FDA approval
will be made under authority granted to FDA by the Federal Food, Drug,
and Cosmetic Act (the act) or the Public Health Service Act (the PHS
Act).
C. Categorical Exclusions
1. General
The proposed rule would increase the number of categorical
exclusions and reorganize the categorical exclusions into the following
five sections in proposed subpart C of part 25: Section 25.30 General;
Sec. 25.31 Human drugs and biologics; Sec. 25.32 Foods, food additives,
and color additives; Sec. 25.33 Animal drugs, and Sec. 25.34 Devices
and electronic products. The agency is also proposing to delete the
general introductory language from current Sec. 25.24 because it is
unnecessary to include this information in the regulation.-
The agency is proposing to retain most of the general categorical
exclusions listed in current Sec. 25.24(a) (proposed Sec. 25.30) and to
make certain revisions described below:
Current Sec. 25.24(a)(4) categorically excludes destruction or
disposition of any FDA-regulated article condemned after seizure,
following detention or recall at agency request, or the distribution or
use of which has been enjoined. In proposed Sec. 25.30(d), FDA is
proposing to revise the criteria for the categorical exclusion from
``if the method of destruction or disposition of the article, including
packaging material, will not result in the release of a toxic substance
into the environment'' to ``if the waste is disposed of in compliance
with all Federal, State, and local requirements.'' The agency is
proposing this revision to reflect current agency practice and because
the previous criterion is covered under paragraph (a) of proposed
Sec. 25.21 Extraordinary circumstances.
The agency is proposing to revise the categorical exclusion for
current good manufacturing practice (CGMP) regulations
(Sec. 25.24(a)(10), proposed Sec. 25.30(j)) to include regulations
based on the hazard analysis critical control points (HACCP)
principles. The HACCP concept is a systematic approach to the
identification, assessment of risk, and control of the biological,
chemical, and physical food safety hazards associated with a particular
food production process. The HACCP system is based upon the
implementation of a control plan developed by a food producer that
analyzes significant food safety hazards, identifies the points in the
production process where a hazard can be prevented, and determines the
preventive measures that are necessary for proper control.
The agency has recently issued regulations (60 FR 65096, December
18, 1995) that use HACCP principles to ensure the safe processing and
importing of seafood. The agency is also considering developing HACCP
regulations for other regulated food industries (59 FR 39888, August 4,
1994). FDA has found that the environmental considerations based on
HACCP principles are essentially identical to the environmental
considerations of regulations based on CGMP's. Neither type of
regulation is likely to have significant environmental impacts.
Therefore, the agency believes that it is appropriate to incorporate
into the categorical exclusion for CGMP regulations an exclusion of the
HACCP regulations.
FDA also is proposing to add a categorical exclusion (proposed
Sec. 25.30(m)) for actions relating to the disposal of the hazardous
laboratory waste materials generated in FDA laboratories (low-level
radioactive waste and chemical waste). Today, all of this hazardous
waste is disposed of under contract with a hazardous waste management
firm.We don't mention what the waste is--even though it is in the
codified part. The contractor is responsible for the collection,
handling, storage, packing, and ultimate disposal of the waste
materials at facilities permitted by the U.S. Environmental Protection
Agency (EPA) and/or facilities licensed by the Nuclear Regulatory
Commission (NRC). In awarding contracts, FDA takes into consideration
whether a prospective contractor has all applicable licenses, permits,
and insurance necessary to perform the work and transport the waste as
required under the contract. The contractor and all disposal facilities
must certify that they are in full compliance with all applicable
Federal, State, and local requirements, before FDA will award the
contract. Further, FDA requires the contractor to present a
comprehensive operational plan. FDA reviews this plan to determine if
the contractor's approach is complete, safe, appropriate, and
responsive to, among other things, FDA's requirements for waste
disposal. Further, the contractor must operate in full compliance with
appropriate regulations issued by EPA (Title 40), the Department of
Transportation (Title 49), the Department of Labor (Title 29), NRC
(Title 10), and with relevant State and local regulations governing the
disposal of hazardous and nonhazardous waste. Therefore, FDA is
proposing in Sec. 25.30(m) to categorically exclude disposal of low-
level radioactive waste materials and chemical waste materials
generated in laboratories serviced by FDA-administered contracts.
2. Human Drugs and Biologics
In the National Performance Report, ``Reinventing Drug and Medical
Device Regulations,'' April 1995, the President announced FDA's
proposal to reduce the number of EA's submitted by industry under NEPA
by increasing the number of categorical exclusions for those actions
relating to drugs and biologics that, as a class, have no individual or
cumulative significant effect on the environment. As described below,
in fulfillment of this commitment, FDA is proposing additional
categorical exclusions for classes of actions on drugs and biologic
products that, based on experience in reviewing these types of actions,
the Center for Drug Evaluation and Research (CDER) and the Center for
Biologics Evaluation and Research (CBER) have concluded do not have
significant effects on the human environment. All of the environmental
reviews of these categories of actions performed under the current
regulations have resulted in FONSI's.
The proposed new categorical exclusions in Sec. 25.31(a) and (b)
apply to actions on an NDA, abbreviated application or a supplement to
such
[[Page 14925]]
applications, or action on an over-the-counter (OTC) monograph. They
are divided into two sections: (1) Proposed Sec. 25.31(a), which
applies if FDA's action does not increase the use and disposal of the
drug; and (2) proposed Sec. 25.31(b), which applies if FDA's action
does increase the use and disposal of the drug. This is similar to the
distinction drawn in the existing regulations between actions that
increase use and actions that do not. Proposed Sec. 25.31(a) and (b)
use the term ``active moiety'' rather than substance, drug product, or
other terminology to clarify the exact focus of the environmental
review.
The categorical exclusion in proposed Sec. 25.31(a) is based on the
categorical exclusions in current Sec. 25.24(c)(1) and (c)(2) and the
fact that, if the action does not increase the use of a drug, there is
no change in the level of the substance in the environment. FDA has
defined ``increased use'' of a drug to include those circumstances
currently listed in Sec. 25.24(c)(1) and (c)(2). Because the
environmental effects, if any, associated with the use and disposal of
the drug were incurred when it was first approved, actions to approve
additional products may be categorically excluded if they do not
increase the use of the drug. Among the actions covered under this
categorical exclusion may be approvals of new dosage forms, prodrugs,
generic drug products, and manufacturing supplements that may change
the method or site of manufacture of a drug but not its use.
Actions under proposed Sec. 25.31(b) that may increase the use or
disposal of a drug product may be categorically excluded if the
concentration of the substance in the environment will be below 1 part
per billion (ppb), the level that FDA has found, based on past
experience, will not significantly affect the aquatic environment. This
reflects a change from current regulations that require an
environmental assessment in any case in which an action may increase
the use of a drug. The basis for this change is described below.
CDER performed a retrospective review of available toxicity
information from EA's that were previously submitted in support of
NDA's and NDA supplements. This information, which includes data from
each review division that are representative of pharmacological drug
classifications, has routinely demonstrated that there are no
significant observed effects on relevant standard test organisms in the
aquatic environment at concentrations below 1 ppb.
Based on the method of entry into the environment from use and
their physical and chemical characteristics (e.g., water solubility),
human drugs would be expected predominantly to enter the aquatic
environment, and the data submitted in EA's reviewed by CDER have
routinely supported this hypothesis. Human drugs and their metabolites
enter the environment from use by excretion from patients. The majority
of hospitals, clinics, and homes in the United States are serviced by a
wastewater treatment facility where compounds are subjected to some
form of aerobic and anaerobic decomposition. Drug and/or metabolites
that are not degraded in the wastewater treatment facility may be
discharged into surface water or removed from the wastewater treatment
plant in sludge.
The data also have routinely shown that in those cases in which an
applicant has provided toxicity results for terrestrial organisms in
addition to acute toxicity results for aquatic organisms, the drugs are
toxic to aquatic organisms at lower levels than they are to terrestrial
organisms, suggesting that the use of aquatic organisms is a
conservative approach.
CDER evaluates the potential for significant environmental effects
by relating the concentrations determined to have toxic effects on
relevant standard test organisms to the level of the substance expected
in the environment. CDER's retrospective review shows that drugs at
concentrations less than 1 ppb in the aquatic environment have no
significant effect on relevant standard test organisms and, therefore,
are unlikely to have a significant effect on the environment. The vast
majority of actions taken by CDER result in the substance being in the
aquatic environment at concentrations less than 1 ppb because the
majority of drugs are produced and used at low levels, and the use of
drugs is not typically localized but rather is spread throughout the
United States.
One of the criteria for determining that a drug is safe for human
use is consideration of its potential to bioaccumulate. The vast
majority of drugs do not have the physical or chemical characteristics
that would allow them to bioaccumulate in tissue because this would
raise safety concerns for use in humans. If a drug does have the
physical or chemical characteristics that would allow it to
bioaccumulate, there has to be a mechanism for the human body to
metabolize the compound to a substance that has lower bioaccumulation
potential so that it is cleared from the body. In the environmental
assessments that CDER reviewed, bioaccumulation has not been an issue.
Thus, FDA has determined that actions that may increase the use or
disposal of a drug should be categorically excluded if the
concentration of the substance in the environment from use will be less
than 1 ppb and no extraordinary circumstances exist. For example, even
under conditions in which an action would increase the use of a drug,
such as an efficacy supplement adding a new indication, the proposed
action may be categorically excluded under this proposal if the
substance in the environment will be below 1 ppb. CDER has provided
guidance on appropriate calculations for estimating environmental
concentrations (Guidance for Industry for the Submission of an
Environmental Assessment in Human Drug Applications and Supplements,
November 1995).
CDER will continue to critically review the environmental toxicity
information submitted for those actions requiring an EA. As additional
data become available to CDER, the agency may propose to modify the 1
ppb environmental concentration cut-off through notice and comment
rulemaking.
Proposed Sec. 25.31(a) and (b) include actions on NDA's. Under the
current regulations (Sec. 25.24(c)(1) and (c)(2)), abbreviated new drug
applications (ANDA's) and supplements may be categorically excluded,
but NDA's for the same type of action may not. Sometimes an applicant
has a choice whether to submit a proposed action as an NDA or ANDA
(e.g., a new dosage form may be submitted as an ANDA with a suitability
petition or as an NDA). Thus, the applicant's choice of submission
would determine whether an EA would need to be submitted. Proposed
Sec. 25.31(a) and (b) would permit FDA to treat NDA's, abbreviated
applications, and supplements alike based on the type of action being
affected by the application.
Current Sec. 25.24(c)(6) categorically excludes actions on OTC
monographs if the product is already marketed for the proposed use. FDA
is proposing to add OTC monographs to proposed Sec. 25.31(a) and (b)
because, by action on an OTC monograph, FDA permits the manufacture and
marketing of OTC drugs that meet the monograph. It should be noted that
actions to switch drugs from prescription to OTC use that are submitted
in an NDA or supplement would also be covered under these provisions.
Proposed Sec. 25.31(a) and (b) would also delete any reference to
``actions on amendments'' to clarify that the agency
[[Page 14926]]
does not take actions on amendments. Amendments are merely changes to a
pending application that are incorporated into the application. The
action the agency takes is on the application as a whole, not on the
amendment.
Proposed Sec. 25.31(a) and (b) applies to drugs regulated by CDER.
FDA is proposing a new categorical exclusion in Sec. 25.31(c) for
substances that occur naturally in the environment, that would apply to
both drugs and biologics. Proposed Sec. 25.31(b) would apply to actions
on an NDA, abbreviated application, application for marketing approval
of a biologic product, a supplement to such applications, or action on
an OTC monograph when the action is not expected to alter significantly
the concentration or distribution of the substance, its metabolites, or
degradation products in the environment. Under the current regulations,
FDA requires an abbreviated EA for a drug that occurs naturally in the
environment. These abbreviated EA's require information about the
production site and about whether the use of the product will
significantly alter the concentration, distribution, and effect of the
natural substance in the environment.
Since the publication of the NEPA regulations in 1985, FDA has
reviewed abbreviated EA's for substances that are naturally occurring.
FDA has found that actions on submissions for these substances will not
affect the environment if the action will not significantly alter the
concentration or distribution of the natural substance in the
environment. Under these circumstances, the agency has prepared
FONSI's. Both CDER and CBER routinely include in safety evaluations
evidence that a product and/or living system used to produce the
product are inactivated following production and prior to release into
the environment, if there is a reasonable possibility that the product
or living system may be harmful to the environment. Therefore, there
are not likely to be any environmental effects. The proposed
regulations would categorically exclude an action for a substance that
occurs naturally in the environment when the action will not alter
significantly the concentration or distribution of the substance in the
environment. FDA has access to information regarding metabolites and
degradation products to aid in determining if the categorical exclusion
request is appropriate.
When an action does alter significantly the concentration or
distribution of a naturally occurring substance, its metabolites, or
degradation products in the environment, e.g., when the use and
disposal will occur in a geographic area where the substance is not
naturally occurring, an EA may be required.
FDA is proposing in Sec. 25.31(d) to expand the categorical
exclusion provision for the withdrawal of approval of an NDA or
abbreviated application. The agency is proposing that all types of
withdrawals of approval, whether requested by industry or initiated by
the agency, be categorically excluded because, based on CDER's
experience, these types of actions will not result in the production or
distribution of any substances and, therefore, will not result in the
introduction of any substance into the environment.There would be no
increase in use of substitutes? See line 21 on page 38 (of 1/26 draft).
EIS considered increase of hydrocarbon propellants in anti-perspirant
aerosols.
Proposed Sec. 25.31(e) would revise the categorical exclusions for
actions on an IND. Current Sec. 25.24(c)(4) categorically excludes
actions on IND's if the drug shipped under such notice is intended to
be used for clinical studies or research in which waste will be
controlled or the amount of waste expected to enter the environment may
reasonably be expected to be nontoxic. Under proposed Sec. 25.31(e),
FDA would categorically exclude all IND's. In many cases, FDA's actions
on IND's do not significantly increase the use of the drug or the
amount of drug introduced into the environment because the drug is
being tested in few patients or is already being marketed for another
use. Therefore, no changes in environmental effects will occur. In
those cases in which an increase in the use of the drug may occur as a
result of an investigation under an IND, CDER's experience in reviewing
actions on IND's indicates that significant environmental effects will
not occur because the use of such drugs is limited and controlled.
The agency is proposing to delete the language ``if the drug
shipped * * * may reasonably be expected to be nontoxic'' because an
action that results in waste that is expected to be toxic would require
an EA under proposed Sec. 25.21 Extraordinary circumstances.Is that
what 25.21(a) means--that if waste is toxic, there may be harm and an
EA will be required?
Proposed Sec. 25.31(g) would add a categorical exclusion for the
testing and release by CBER of lots or batches of a licensed biologic
product. The effects on the environment of licensed biologic products
are evaluated during the safety evaluation and approval of the license
application. Therefore, conducting a separate NEPA review for the
testing and release by CBER of individual lots or batches is
unnecessary.
Proposed Sec. 25.31(i) would permit a categorical exclusion for the
establishment of a comparability determination for a biologic product
subject to licensing. Establishment of a comparability determination
does not result in introduction of a substance into the environment. A
substance will be introduced into the environment only when CBER has
made a comparability determination and subsequently approves a license
application for a specific biologic product. The environmental
considerations will be made in connection with the review of individual
license applications that meet the comparability criteria.
Proposed Sec. 25.31(j) incorporates current Sec. 25.24(c)(10), the
categorical exclusion for promulgation, amendment, or revocation of a
standard for a licensed biologic product, and would eliminate the
current requirement that there be no increased use of the product. The
standards normally explain how the product is to be manufactured and
any additional requirements for approval and marketing. Therefore, the
increased use criterion is unnecessary.
Proposed Sec. 25.31(k), regarding revocation of a biologic product,
would eliminate the current criteria in Sec. 25.24(c)(9) that the
biological product ``is no longer being marketed'' or that the action
is ``at the request of the license holder. The agency is proposing to
delete these criteria as unnecessary because revocation of a license
for a biologic product means that the product can no longer be
marketed. Marketing of the product after license revocation must cease
regardless of whether the revocation was at the request of the license
holder or initiated by the agency. Revocation of a license for a
biologic product under any circumstances will not result in the
introduction of any substance into the environment and, therefore, will
not significantly affect the environment.
The agency is also proposing other minor, nonsubstantive amendments
to delete unnecessary language, improve the accuracy and clarity of the
categorical exclusions, and reflect current terminology.
3. Foods, Food Additives, and Color Additives
In the President's National Performance Report, ``Reinventing Food
Regulations,'' January 1996, the President announced that FDA proposed
to reduce the number of EA's
[[Page 14927]]
submitted by industry under NEPA by increasing the number of
categorical exclusions for food and color additives and generally
recognized as safe (GRAS) substances based on little or no impact on
the environment from the use and disposal of these products. As
described below, in fulfillment of this commitment, FDA is proposing
additional categorical exclusions for actions on foods, food additives,
color additives, and GRAS substances which, based on experience in
reviewing these types of actions, the Center for Food Safety and
Applied Nutrition (CFSAN) has concluded will not significantly affect
the human environment.
As was explained previously, FDA is proposing to remove criteria
from certain exclusions in current Sec. 25.24. For actions involving
foods, food additives, color additives, and GRAS substances, the
criteria for the exclusions in current Sec. 25.24(a)(10), (b)(2),
(b)(3), (b)(7), (b)(8), and (b)(9) have been removed. These exclusions
can be located in proposed Secs. 25.30(j), and 25.32(b), (c), (f), (g),
and (h). This change is being made because the provisions in proposed
Sec. 25.21 Extraordinary circumstances could apply to any of the
agency's exclusions, making certain criteria for individual exclusions
unnecessary.
In addition, to reflect current FDA policy, the agency is removing
from part 25 the environmental review requirements for the
establishment of action levels for unavoidable poisonous or deleterious
substances in food or food packaging, and for natural or unavoidable
defects in food that present no health hazard. This change is discussed
below.
For the classes of actions proposed for categorical exclusion in
Sec. 25.32(i), (j), (k), (l), (o), (q), and (r), FDA has traditionally
required certain information to assess the potential environmental
impact of the production of the food additive, color additive, or GRAS
substance. In all cases, FDA has found in its reviews that the
production of these substances did not significantly affect the
environment. The agency has determined that FDA ordinarily will not
consider potential impacts at sites of production of FDA-regulated
products, as discussed in section III.D of this document.
a. Proposed Sec. 25.32(f). Currently, FDA's NEPA procedures in
Sec. 25.24(b)(7) provide for a categorical exclusion for actions
relating to the affirmation of a food substance as GRAS if the
substance is already marketed for the use for which affirmation is
sought. FDA is proposing to expand this categorical exclusion in
proposed Sec. 25.32(f) to include actions to establish and amend
regulations under part 181 (21 CFR part 181) for prior-sanctioned
ingredients that are already marketed in the United States. Actions
involving prior-sanctioned ingredients are similar to certain GRAS
affirmation actions in that the food substance is likely to be already
marketed in the United States for the proposed use at the time the
action is being considered and will continue to be marketed after the
regulation is published. As defined in Sec. 170.3(l) (21 CFR 170.3(l))
and Sec. 181.5(a), a prior sanction shall exist only for a specific use
of a substance for which there was explicit approval by FDA or the U.S.
Department of Agriculture (USDA) before September 6, 1958. Actions to
affirm substances as GRAS or prior-sanctioned for the specific uses for
which they were already marketed in the United States create little or
no change in the introduction of the substance into the environment.
Therefore, such actions have no significant effect on the environment.
b. Proposed Sec. 25.32(i). FDA is proposing to amend its NEPA
procedures to categorically exclude from the requirement to prepare an
EA actions to approve a food additive petition or grant a request for
exemption from regulation as a food additive under Sec. 170.39 (21 CFR
170.39) (threshold of regulation) when a food additive is a functional
component of finished food-packaging materials present at not greater
than 5 percent-by-weight. FDA based this proposed exclusion on its
review of 95 petitions for food additives in this class, all of which
resulted in FONSI's, and on the evaluation of the potential for future
petitions in this class to have significant environmental effects. FDA
has had limited experience in considering the environmental impact of
threshold of regulation submissions because the regulations
establishing a threshold of regulation policy were recently issued (60
FR 36582, July 17, 1995). However, because the information currently
required for such submissions is identical to the information required
for the food-packaging class of indirect food additives discussed in
this section, the agency believes that its experience with the 95 food
additive petitions is relevant to these threshold of regulation
submissions and that these submissions also warrant a categorical
exclusion.
The agency's evaluation of functional components of food-packaging
materials present at not greater than 5 percent-by-weight has
traditionally included consideration of potential impacts relating to
the disposal of food-packaging materials containing the additive and
the use of natural resources and energy.
To determine the potential for significant introductions of
substances into the environment at the site of disposal of food-
packaging materials, i.e., municipal solid waste landfill or combustion
sites, the agency currently requires an estimate of the maximum yearly
market volume for the proposed use of the food additive and the percent
of that amount that will become a component of the finished food-
packaging material. To determine the potential for significant
introductions at landfill sites, FDA estimated the concentration of the
additive that could be present in landfill leachate for each of the 95
petitions it reviewed for additives used as functional components of
food-packaging materials. FDA found that in virtually all cases, the
concentration of the additives in landfill leachate was less than 50
ppb. The concentration of the additives in surface or ground water
receiving landfill leachate was expected to be substantially less,
taking into consideration the mobility and degradation of the additives
in landfills and their dilution in receiving waters.
Consequently, FDA determined in all cases that these extremely low
levels would not have significant environmental impacts at landfill
sites. The agency believes that approvals of future petitions in this
class are even less likely to result in significant introductions of
substances at landfill sites because EPA published new landfill
regulations in the Federal Register of October 9, 1991 (56 FR 50978),
that require new and expanded landfills to have leachate collection
systems and liners to prevent leachate from entering surface or
groundwater. Although operators of existing landfills are not required
to retrofit liner systems, they are required to monitor groundwater
adjacent to existing landfills and to take corrective action as
appropriate.
The agency's evaluation of petitions for additives used as
functional components of food-packaging materials has also shown that
there is little potential for significant introductions from the
combustion of packaging materials containing the additives. These types
of additives are used at low levels in the packaging materials, <5 percent="" by="" weight,="" and,="" therefore,="" the="" additional="" amounts="" of="" combustion="" products="" emitted="" were="" found="" to="" be="" insignificant="" compared="" to="" the="" levels="" already="" being="" generated="" during="" municipal="" solid="" waste="" combustion.="" because="" fda's="" experience="" shows="" that="" the="" use="" levels="" for="" additives="" used="" as="" [[page="" 14928]]="" functional="" components="" of="" food-packaging="" materials="" are="" low,="" the="" agency="" believes="" that="" future="" approvals="" will="" also="" result="" in="" insignificant="" introductions="" into="" the="" environment="" at="" municipal="" solid="" waste="" combustor="" sites.="" under="" current="" part="" 25,="" fda="" requires="" no="" documentation="" to="" assess="" potential="" impact="" on="" energy="" and="" resource="" use="" if="" the="" proposed="" additive="" is="" intended="" for="" the="" same="" use="" as="" another="" additive="" already="" in="" use="" and="" will="" not="" materially="" change="" the="" potential="" uses="" of="" the="" packaging="" materials="" to="" which="" it="" is="" added.="" the="" agency="" has="" required="" sponsors="" to="" provide="" information="" in="" an="" abbreviated="" ea="" showing="" that="" these="" criteria="" are="" met.="" based="" on="" fda's="" experience="" in="" reviewing="" petitions="" for="" functional="" components="" of="" food-packaging="" materials,="" the="" agency="" has="" found="" that="" petitioners="" generally="" were="" able="" to="" demonstrate="" that="" a="" proposed="" additive="" would="" compete="" with="" and="" replace="" other,="" already="" regulated="" additives="" and="" that="" approval="" would="" not="" change="" the="" uses="" of="" the="" packaging="" materials="" to="" which="" they="" were="" added.="" in="" cases="" where="" a="" proposed="" additive="" did="" not="" compete="" with="" and="" replace="" an="" already="" regulated="" additive,="" the="" agency="" was="" still="" able="" to="" conclude="" that="" there="" would="" not="" be="" a="" significant="" impact="" on="" energy="" and="" natural="" resource="" use="" largely="" because="" use="" of="" the="" additive="" in="" food-contact="" articles="" represented="" a="" very="" small="" fraction="" of="" total="" usage.="" thus,="" based="" on="" the="" low="" levels="" of="" use="" of="" these="" functional="" components="" of="" food-packaging="" materials="" and="" on="" fda's="" experience="" reviewing="" abbreviated="" ea's="" for="" these="" functional="" components,="" the="" agency="" believes="" that="" approvals="" of="" future="" submissions="" for="" such="" additives="" are="" highly="" unlikely="" to="" have="" significant="" effects="" on="" the="" environment.="" therefore,="" under="" proposed="" sec.="" 25.32(i)="" a="" requestor="" need="" not="" ordinarily="" submit="" an="" ea.="" c.="" proposed="" sec.="" 25.32(j).="" fda="" is="" proposing="" to="" categorically="" exclude="" actions="" to="" approve="" a="" food="" additive="" and="" to="" grant="" a="" request="" for="" exemption="" from="" regulation="" as="" a="" food="" additive="" under="" sec.="" 170.39="" when="" the="" additive="" is="" a="" component="" of="" food-contact="" surfaces="" of="" permanent="" or="" semipermanent="" equipment="" or="" of="" other="" food-contact="" articles="" intended="" for="" repeated="" use="" (proposed="" sec.="" 25.32(j)).="" this="" proposed="" exclusion="" is="" based="" on="" fda's="" experience="" with="" 43="" petitions="" for="" additives="" used="" as="" components="" of="" repeat-use="" food-contact="" articles,="" all="" of="" which="" resulted="" in="" a="" fonsi.="" fda="" has="" had="" limited="" experience="" in="" considering="" the="" environmental="" impact="" of="" threshold="" of="" regulation="" submissions="" for="" components="" of="" repeat-use,="" food-contact="" articles="" because="" the="" regulations="" establishing="" a="" threshold="" of="" regulation="" policy="" were="" recently="" issued.="" however,="" because="" the="" information="" currently="" required="" for="" such="" submissions="" is="" identical="" to="" the="" information="" required="" for="" food="" additive="" petitions="" for="" these="" types="" of="" indirect="" food="" additives="" used="" in="" repeat-use,="" food-contact="" articles,="" the="" agency="" believes="" that="" its="" experience="" with="" the="" 43="" food="" additive="" petitions="" is="" relevant="" to="" these="" threshold="" of="" regulation="" submissions="" and="" that="" approval="" of="" these="" submissions="" warrants="" a="" categorical="" exclusion.="" in="" reviewing="" the="" petitions="" for="" components="" of="" repeat-use,="" food-="" contact="" articles,="" the="" agency's="" evaluation="" of="" environmental="" impact="" has="" traditionally="" included="" consideration="" of="" potential="" impacts="" relating="" to="" the="" disposal="" of="" the="" food-contact="" articles="" containing="" the="" additive.="" to="" determine="" the="" potential="" for="" significant="" introductions="" of="" substances="" into="" the="" environment="" at="" the="" sites="" of="" disposal="" of="" food="" additives="" that="" are="" used="" as="" components="" of="" the="" food-contact="" surfaces="" of="" permanent="" or="" semipermanent="" equipment,="" or="" of="" other="" repeat-use="" articles,="" the="" agency="" currently="" requires="" an="" estimate="" of="" the="" maximum="" yearly="" market="" volume="" for="" the="" proposed="" use="" of="" the="" additive.="" in="" reviewing="" abbreviated="" ea's="" for="" these="" additives,="" fda="" found="" that="" these="" additives="" ordinarily="" have="" limited="" potential="" for="" causing="" significant="" environmental="" effects="" as="" a="" result="" of="" their="" use="" and="" disposal.="" the="" potential="" for="" significant="" introductions="" of="" substances="" to="" the="" environment="" due="" to="" disposal="" is,="" in="" fact,="" very="" low="" because="" of="" the="" long="" service="" life="" of="" the="" food-contact="" equipment="" or="" other="" repeat-use="" articles,="" of="" which="" additives="" in="" this="" class="" are="" components,="" and="" the="" limited="" market="" volumes="" of="" the="" additives="" as="" estimated="" by="" the="" petitioners.="" because="" its="" actions="" on="" these="" petitions="" and="" requests="" will="" not="" significantly="" affect="" the="" environment,="" fda="" will="" not="" ordinarily="" require="" the="" preparation="" of="" an="" ea.="" d.="" proposed="" sec.="" 25.32(k).="" fda="" is="" proposing="" to="" categorically="" exclude="" actions="" to="" approve="" food="" additive,="" color="" additive,="" and="" gras="" affirmation="" petitions="" for="" substances="" added="" directly="" to="" food="" that="" are="" intended="" to="" remain="" in="" food="" through="" ingestion="" by="" consumers="" and="" that="" are="" not="" intended="" to="" replace="" macronutrients="" in="" food.="" this="" proposed="" exclusion="" is="" based="" on="" fda's="" experience="" reviewing="" 21="" petitions="" in="" this="" class,="" all="" of="" which="" resulted="" in="" a="" fonsi.="" examples="" of="" the="" types="" of="" additives="" and="" gras="" substances="" that="" belong="" to="" this="" class="" are="" the="" color="" additives="" added="" to="" foods="" listed="" in="" 21="" cfr="" parts="" 73="" and="" 74,="" most="" of="" the="" direct="" food="" additives="" listed="" in="" part="" 172="" (21="" cfr="" part="" 172),="" and="" certain="" gras="" substances="" listed="" in="" part="" 184="" (21="" cfr="" part="" 184).="" examples="" of="" substances="" that="" are="" not="" included="" in="" the="" class="" for="" which="" this="" categorical="" exclusion="" is="" being="" proposed="" are="" the="" substances="" intended="" to="" replace="" macronutrients="" in="" food="" (such="" as="" sweetening="" agents="" intended="" to="" replace="" sugar,="" e.g.,="" see="" secs.="" 172.800="" and="" 172.804,="" and="" fat="" substitutes,="" e.g.,="" sec.="" 184.1498).="" the="" agency's="" evaluation="" of="" the="" environmental="" effects="" of="" substances="" added="" directly="" to="" food="" has="" included="" consideration="" of="" the="" potential="" for="" impacts="" from="" the="" disposal="" of="" human="" waste="" products="" containing="" the="" petitioned="" substance="" and/or="" its="" products="" of="" digestion="" and="" metabolism,="" and="" from="" the="" use="" of="" natural="" resources="" and="" energy.="" the="" substances="" added="" directly="" to="" food="" considered="" here="" will="" be="" ingested="" by="" consumers="" as="" components="" of="" food="" containing="" these="" substances.="" after="" ingestion,="" these="" substances="" are="" either="" digested="" and/="" or="" metabolized="" to="" other="" substances="" or="" excreted="" largely="" intact.="" in="" all="" cases,="" the="" agency's="" review="" of="" past="" actions="" on="" substances="" added="" directly="" to="" food="" resulted="" in="" decisions="" to="" issue="" fonsi's.="" to="" address="" the="" potential="" for="" environmental="" impacts="" from="" disposal="" of="" this="" class="" of="" substances,="" the="" agency's="" fonsi's="" relied="" on="" one="" or="" more="" of="" the="" following="" scenarios:="" (1)="" the="" agency's="" approval="" of="" the="" petition="" resulted="" in="" very="" low="" levels="" (in="" the="" low="" ppb="" range="" or="" lower)="" of="" the="" substances="" in="" either="" effluents="" and/or="" sewage="" sludge="" from="" publicly="" owned="" wastewater="" treatment="" plants="" and="" these="" levels="" were="" determined="" not="" to="" be="" toxic="" to="" organisms="" in="" the="" environment;="" (2)="" the="" petitioned="" substance="" was="" digested="" and/or="" metabolized="" bypara.humans="" such="" that="" only="" products="" of="" digestion="" and="" metabolism="" were="" expected="" to="" be="" excreted="" and="" these="" products="" were="" the="" same="" as="" (or="" very="" similar="" to)="" the="" products="" of="" digestion="" and="" metabolism="" resulting="" from="" human="" food;="" such="" products="" should="" have="" no="" potential="" for="" significant="" environmental="" effects="" because="" wastewater="" treatment="" facilities="" are="" already="" designed="" to="" handle="" them;="" or="" (3)="" the="" petitioned="" substance="" was="" excreted="" largely="" intact="" but="" was="" rapidly="" degraded="" into="" nontoxic="" products="" either="" in="" wastewater="" treatment="" plants="" or="" in="" the="" environment.="" fda's="" experience="" shows="" that="" substances="" added="" directly="" to="" food="" and="" intended="" to="" remain="" with="" food="" through="" ingestion="" that="" are="" the="" subject="" of="" new="" petitions="" will="" have="" use="" and="" disposal="" patterns="" similar="" to="" those="" described="" above="" and="" will="" not="" be="" toxic="" to="" organisms="" in="" the="" environment="" at="" the="" expected="" levels="" of="" exposure.="" thus,="" use="" and="" disposal="" of="" such="" substances="" are="" not="" expected="" to="" result="" in="" significant="" environmental="" effects.="" the="" agency="" has="" also="" found,="" as="" a="" result="" of="" its="" review="" of="" petitions="" for="" substances="" in="" the="" class="" being="" considered="" here,="" that="" [[page="" 14929]]="" in="" no="" case="" was="" there="" potential="" for="" significant="" impacts="" on="" energy="" and="" natural="" resources.="" these="" findings="" relied="" on="" one="" or="" more="" of="" the="" following="" scenarios:="" (1)="" the="" substances="" were="" expected="" to="" compete="" with="" and="" replace="" other="" already="" regulated="" substances="" with="" no="" significant="" change="" in="" the="" overall="" use="" of="" natural="" resources="" or="" energy,="" (2)="" the="" substances="" are="" also="" used="" in="" nonfood="" contact="" situations="" and="" the="" food-="" contact="" usage="" represented="" a="" small="" increase="" in="" the="" overall="" production="" and="" usage="" of="" the="" substance="" such="" that="" the="" small="" increase="" in="" the="" uses="" of="" natural="" resources="" and="" energy="" was="" not="" significant,="" or="" (3)="" the="" predicted="" market="" volumes="" for="" the="" petitioned="" substances="" were="" very="" small="" so="" that="" the="" use="" of="" natural="" resources="" and="" energy="" for="" the="" petitioned="" substances="" was="" very="" limited.="" in="" no="" case="" did="" the="" agency="" find="" that="" there="" would="" be="" any="" effects="" on="" threatened="" or="" endangered="" species.="" because="" the="" use="" and="" disposal="" of="" substances="" added="" directly="" to="" foods="" and="" intended="" to="" remain="" with="" foods="" through="" ingestion="" has="" no="" significant="" effect="" on="" the="" environment="" and="" has="" very="" limited="" potential="" for="" significant="" effects="" on="" energy="" and="" natural="" resources,="" ea's="" for="" these="" substances="" will="" not="" ordinarily="" be="" required.="" e.="" proposed="" sec.="" 25.32(l).="" fda="" is="" proposing="" to="" categorically="" exclude="" actions="" to="" approve="" color="" additives="" used="" in="" contact="" lenses,="" sutures,="" polymethylmethacrylate="" filaments="" used="" in="" supporting="" haptics="" for="" intraocular="" lenses,="" bone="" cement,="" and="" in="" other="" fda-regulated="" products="" that="" involve="" similar="" low="" levels="" of="" use.="" the="" agency="" reviewed="" ea's="" for="" 20="" color="" additive="" petitions="" for="" these="" types="" of="" uses="" and="" found="" that="" all="" proposed="" uses="" involve="" small="" amounts="" of="" color="" additives.="" because="" of="" the="" nature="" of="" these="" uses,="" the="" highest="" annual="" market="" volume="" encountered="" for="" any="" of="" these="" color="" additives="" was="" 12="" kilograms="" (kg),="" while="" most="" of="" the="" petitioned="" uses="" involved="" considerably="" less="" than="" 5="" kg.="" consequently,="" the="" environmental="" introduction="" levels="" of="" the="" color="" additives="" from="" manufacture,="" use,="" and="" disposal="" would="" be="" exceedingly="" small.="" fda's="" experience="" shows="" that="" petitions="" for="" color="" additives="" in="" these="" types="" of="" applications="" will="" have="" very="" low="" market="" volumes="" such="" that="" only="" extremely="" low="" levels="" of="" substances="" will="" be="" introduced="" into="" the="" environment="" and="" will="" not="" cause="" significant="" environmental="" effects.="" therefore,="" fda="" is="" proposing="" to="" categorically="" exclude="" actions="" on="" such="" petitions="" from="" the="" requirement="" to="" prepare="" an="" ea.="" f.="" proposed="" sec.="" 25.32(m).="" fda="" is="" proposing="" to="" categorically="" exclude="" actions="" to="" prohibit="" or="" otherwise="" restrict="" or="" reduce="" the="" use="" of="" a="" substance="" in="" food,="" food="" packaging,="" or="" cosmetics,="" e.g.,="" the="" withdrawal="" of="" approval="" for="" the="" use="" of="" a="" food="" or="" color="" additive,="" removal="" of="" the="" use="" of="" a="" substance="" from="" a="" gras="" list="" (21="" cfr="" parts="" 182,="" 184,="" and="" 186),="" or="" prohibition="" of="" the="" use="" of="" a="" prior-sanctioned="" substance="" (defined="" under="" secs.="" 170.3(l)="" and="" 181.5(a)).="" the="" agency="" has="" prepared="" ea's="" for="" 12="" actions="" to="" withdraw="" approval="" for="" the="" use="" of="" a="" food="" or="" color="" additive="" or="" to="" prohibit="" the="" use="" of="" a="" substance="" in="" food.="" the="" agency="" has="" prepared="" only="" one="" eis="" for="" the="" withdrawal="" of="" approval="" of="" a="" food="" additive.="" in="" 1978,="" the="" agency="" prepared="" an="" eis="" for="" its="" action="" to="" prohibit="" the="" use="" of="" certain="" chlorofluorocarbons="" in="" food,="" food="" additive,="" drug,="" animal="" food,="" animal="" drug,="" cosmetic,="" and="" medical="" device="" products="" as="" propellants="" in="" self-pressurized="" containers="" (43="" fr="" 11301,="" march="" 17,="" 1978).="" the="" specified="" chlorofluorocarbons="" were="" prohibited="" because="" their="" continued="" use="" was="" predicted="" to="" result="" in="" the="" depletion="" of="" the="" stratospheric="" ozone="" layer.="" fda="" prepared="" the="" eis="" as="" part="" of="" an="" interagency="" effort="" to="" address="" this="" problem.="" ceq="" determined="" that="" an="" eis="" was="" necessary="" for="" this="" particular="" action="" because="" of="" the="" controversy="" surrounding="" the="" scientific="" issues="" associated="" with="" the="" potential="" effects="" of="" these="" chemicals="" on="" stratospheric="" ozone.="" the="" agency="" considers="" its="" action="" on="" chlorofluorocarbons="" to="" be="" an="" exception.="" it="" is="" the="" only="" action="" of="" this="" type="" that="" involved="" potentially="" significant="" effects="" on="" the="" environment.="" the="" effect="" of="" withdrawing="" approval="" or="" prohibiting="" the="" use="" of="" a="" substance="" is="" to="" reduce="" or="" eliminate="" environmental="" exposure="" to="" that="" substance.="" thus,="" no="" potential="" exists="" for="" direct="" adverse="" environmental="" effects="" from="" the="" agency's="" prohibition="" of="" the="" use="" of="" a="" substance.="" it="" may="" sometimes="" be="" necessary,="" however,="" to="" consider="" the="" potential="" indirect="" environmental="" effects="" that="" would="" result="" from="" increased="" use="" of="" substitutes="" for="" the="" prohibited="" substance.="" since="" the="" agency="" began="" considering="" the="" environmental="" impact="" of="" its="" actions="" under="" nepa,="" it="" has="" not="" found="" that="" significant="" adverse="" environmental="" effects="" would="" result="" from="" the="" increased="" use="" of="" a="" substitute="" for="" a="" food="" or="" color="" additive="" or="" other="" food="" substance="" that="" was="" being="" restricted.="" in="" the="" agency's="" evaluation="" of="" past="" actions="" in="" this="" class,="" the="" agency="" has="" found="" that="" there="" are="" frequently="" a="" number="" of="" substitutes="" for="" the="" prohibited="" substance.="" thus,="" the="" increase="" in="" production,="" use,="" or="" disposal="" of="" substitutes="" is="" spread="" among="" a="" number="" of="" substances.="" further,="" environmental="" exposure="" to="" any="" one="" substitute="" is="" minimal.="" in="" some="" cases,="" the="" agency="" has="" found="" that="" substitutes="" have="" been="" previously="" subjected="" to="" environmental="" review="" under="" nepa="" by="" the="" agency,="" and="" that="" this="" review="" encompassed="" the="" use="" of="" the="" substitute="" as="" a="" replacement="" for="" the="" prohibited="" substance="" and="" resulted="" in="" an="" ea="" and="" fonsi="" being="" prepared.="" any="" new="" food="" or="" color="" additive="" that="" may="" be="" developed="" to="" replace="" a="" prohibited="" one="" would="" undergo="" environmental="" review="" during="" the="" premarket="" approval="" process.="" g.="" proposed="" sec.="" 25.32(n).="" fda="" is="" proposing="" to="" categorically="" exclude="" actions="" to="" issue,="" amend,="" or="" revoke="" regulations="" pertaining="" to="" infant="" formulas.="" fda="" is="" proposing="" to="" exclude="" actions="" on="" infant="" formulas="" because="" they="" have="" little="" or="" no="" potential="" for="" adverse="" environmental="" effects.="" the="" preparation,="" distribution,="" and="" directions="" for="" use="" of="" infant="" formulas="" are="" carefully="" controlled="" by="" regulations="" in="" 21="" cfr="" parts="" 106="" and="" 107="" and,="" along="" with="" other="" foods,="" by="" the="" cgmp="" regulations="" in="" 21="" cfr="" part="" 110.="" in="" addition,="" the="" nature="" of="" this="" product,="" a="" food="" designed="" for="" infants,="" means="" that="" the="" product="" itself="" is="" very="" unlikely="" to="" cause="" adverse="" environmental="" impacts.="" infant="" formulas="" are="" expected="" to="" be="" used="" and="" disposed="" of="" in="" a="" manner="" similar="" to="" other="" human="" food,="" but="" infant="" formulas="" form="" only="" a="" small="" fraction="" of="" the="" total="" human="" food="" supply="" since="" they="" are="" used="" only="" in="" the="" first="" year="" or="" 2="" of="" human="" life.="" therefore,="" it="" is="" unlikely="" that="" future="" actions="" on="" infant="" formulas="" will="" have="" potential="" for="" significant="" environmental="" effects,="" and="" thus,="" fda="" is="" proposing="" to="" exclude="" them="" from="" the="" requirement="" to="" prepare="" an="" ea.="" h.="" proposed="" sec.="" 25.32(o).="" fda="" is="" proposing="" to="" exclude="" actions="" to="" approve="" a="" food="" additive="" petition="" when="" an="" additive="" is="" the="" intended="" expression="" product(s)="" present="" in="" food="" derived="" from="" new="" plant="" varieties.="" the="" proposed="" exclusion="" is="" based="" on="" our="" determination="" that="" the="" usda="" animal="" and="" plant="" health="" inspection="" service="" (aphis)="" has="" lead="" responsibility,="" under="" the="" federal="" plant="" pest="" act="" (7="" u.s.c.="" 150aa="" et="" seq.),="" to="" prevent="" the="" movement="" and="" dissemination="" in="" the="" united="" states="" of="" plant="" pests.="" under="" that="" authority,="" usda="" aphis="" addresses="" the="" potential="" of="" new="" plant="" varieties="" to="" pose="" a="" plant="" pest="" risk="" in="" accordance="" with="" the="" requirements="" mandated="" under="" nepa.="" usda="" considers="" the="" potential="" for="" risk="" in="" a="" very="" broad="" context,="" so="" that="" not="" only="" is="" direct="" disease="" or="" damage="" to="" plants="" and="" plant="" materials="" considered="" as="" a="" component="" of="" plant="" pest="" risk,="" but="" indirect="" effects="" on="" beneficial="" or="" other="" organisms="" in="" the="" agronomic="" context="" are="" also="" addressed.="" before="" issuing="" a="" determination="" of="" nonregulated="" status="" for="" an="" organism="" that="" has="" been="" subject="" to="" usda="" oversight="" because="" it="" was="" considered="" to="" present="" a="" [[page="" 14930]]="" potential="" risk="" of="" being="" a="" plant="" pest,="" usda="" conducts="" an="" environmental="" analysis="" in="" compliance="" with="" its="" nepa="" requirements="" that="" addresses="" plant="" pest="" risk="" characteristics,="" disease="" and="" pest="" susceptibilities,="" expression="" of="" any="" introduced="" gene="" products="" and="" effects="" thereof,="" new="" enzymes,="" or="" changes="" to="" plant="" metabolism,="" weediness="" of="" the="" plant,="" impact="" on="" the="" weediness="" of="" any="" other="" plant="" with="" which="" it="" can="" interbreed,="" agricultural="" or="" cultivation="" practices,="" effects="" of="" the="" plant="" on="" nontarget="" organisms,="" indirect="" plant="" pest="" effects="" on="" other="" agricultural="" products,="" transfer="" of="" genetic="" information="" to="" organisms="" with="" which="" it="" cannot="" interbreed,="" and="" any="" other="" information="" believed="" to="" be="" relevant="" to="" a="" determination.="" the="" issues="" considered="" by="" fda="" are="" the="" same="" or="" a="" subset="" of="" the="" issues="" that="" usda="" addresses="" as="" part="" of="" its="" nepa="" review.="" therefore,="" a="" nepa="" review="" by="" fda="" would="" be="" redundant.="" i.="" proposed="" sec.="" 25.32(p).="" fda="" is="" proposing="" to="" categorically="" exclude="" actions="" under="" part="" 101="" (21="" cfr="" part="" 101)="" to="" issue,="" amend,="" or="" revoke="" a="" regulation="" in="" response="" to="" a="" reference="" amount="" petition="" (sec.="" 101.12(h)),="" a="" nutrient="" content="" claim="" petition="" (sec.="" 101.69),="" a="" health="" claim="" petition="" (sec.="" 101.70),="" or="" a="" petition="" pertaining="" to="" the="" label="" declaration="" of="" ingredients="" (sec.="" 101.103).="" the="" agency="" has="" regulations="" pertaining="" to="" various="" aspects="" of="" food="" labeling="" in="" part="" 101.="" these="" regulations="" include="" provisions="" that="" enable="" interested="" persons="" to="" petition="" the="" agency="" to="" issue="" regulations="" on="" several="" subjects="" related="" to="" labeling,="" listed="" above.="" these="" petitions="" must="" include,="" under="" current="" regulations,="" either="" a="" claim="" for="" categorical="" exclusion="" under="" current="" sec.="" 25.24="" or="" an="" ea="" under="" current="" sec.="" 25.31.="" current="" sec.="" 25.24(a)(11)="" contains="" an="" exclusion="" for="" the="" establishment="" or="" repeal="" by="" regulation="" of="" labeling="" requirements="" for="" marketing="" articles,="" ``if="" there="" will="" be="" no="" increase="" in="" the="" existing="" levels="" of="" use="" or="" change="" in="" the="" intended="" uses="" of="" the="" product="" or="" its="" substitutes.``="" the="" criteria="" are="" intended="" to="" ensure="" that="" the="" excluded="" labeling="" actions="" will="" not="" cause="" significant="" environmental="" effects.="" this="" exclusion="" can="" be="" used="" with="" petitions="" of="" the="" type="" listed="" above,="" if="" petitioners="" demonstrate="" that="" the="" criteria="" are="" met.="" for="" those="" actions="" that="" would="" not="" qualify="" for="" exclusion="" under="" current="" sec.="" 25.24(a)(11)="" because="" there="" will="" be="" an="" increase="" in="" the="" use="" of="" the="" product,="" fda="" now="" believes="" that="" this="" increased="" use="" will="" not="" have="" significant="" environmental="" effects.="" thus,="" the="" agency="" has="" determined="" that="" a="" specific="" unqualified="" categorical="" exclusion="" for="" petitions="" related="" to="" food="" labeling="" is="" appropriate.="" when="" changes="" in="" the="" labeling="" on="" food="" products="" are="" allowed,="" there="" is="" a="" potential="" for="" changes="" in="" the="" levels="" of="" use,="" and="" in="" the="" intended="" uses,="" of="" such="" products="" or="" their="" substitutes.="" in="" fact,="" nutrient="" content="" claims="" and="" health="" claims="" are="" generally="" intended="" to="" increase="" the="" use="" of="" the="" labeled="" product.="" however,="" the="" changes="" that="" will="" result="" from="" fda's="" actions="" on="" the="" types="" of="" petitions="" listed="" above="" will="" be="" modifications="" of="" the="" purchasing="" and="" consumption="" habits="" of="" consumers.="" a="" food="" labeled="" in="" the="" newly="" allowed="" manner="" will="" be="" purchased="" and="" consumed="" instead="" of="" another="" food="" that,="" for="" a="" variety="" of="" reasons,="" will="" not="" be="" labeled="" in="" this="" new="" manner.="" the="" net="" result="" will="" be="" the="" substitution="" of="" one="" food="" for="" a="" similar="" food.="" thus,="" no="" significant="" adverse="" effects="" on="" the="" environment="" will="" result.="" therefore,="" the="" agency="" is="" proposing="" that="" its="" future="" actions="" on="" petitions="" for="" the="" issuance,="" amendment,="" or="" revocation="" of="" regulations="" on="" reference="" amounts="" customarily="" consumed="" per="" eating="" occasion="" (sec.="" 101.12(h)),="" on="" nutrient="" content="" claims="" (sec.="" 101.69),="" on="" health="" claims="" (sec.="" 101.70),="" and="" on="" the="" label="" declaration="" of="" ingredients="" (sec.="" 101.103)="" be="" categorically="" excluded="" from="" the="" preparation="" of="" an="" environmental="" assessment.="" j.="" proposed="" sec.="" 25.32(q).="" fda="" is="" proposing="" in="" sec.="" 25.32(q)="" to="" categorically="" exclude="" from="" the="" requirement="" to="" submit="" an="" ea="" actions="" to="" approve="" food="" additive="" petitions="" for="" substances="" registered="" by="" epa="" under="" the="" federal="" insecticide,="" fungicide,="" and="" rodenticide="" act="" (fifra)="" (7="" u.s.c.="" 136="" et="" seq.)="" for="" the="" same="" use="" requested="" in="" the="" petition.="" fda="" has="" had="" limited="" experience="" in="" considering="" the="" environmental="" impact="" of="" threshold="" of="" regulation="" submissions="" for="" substances="" registered="" by="" epa="" under="" fifra="" because="" the="" regulations="" establishing="" threshold="" of="" regulation="" policy="" were="" recently="" issued.="" however,="" because="" the="" information="" currently="" required="" for="" such="" submissions="" is="" identical="" to="" the="" information="" required="" for="" food="" additive="" petitions="" for="" these="" types="" of="" substances,="" the="" agency="" believes="" that="" its="" experience="" with="" food="" additive="" petitions="" is="" revelant.="" this="" proposed="" exclusion="" is="" based="" on="" fda's="" experience="" reviewing="" 12="" petitions="" in="" this="" class,="" all="" of="" which="" resulted="" in="" a="" fonsi.="" all="" of="" these="" petitions="" were="" for="" antimicrobial="" substances="" used="" either="" in="" the="" processing="" of="" food="" or="" in="" food-packaging="" materials.="" fda's="" evaluation="" of="" the="" potential="" environmental="" effects="" of="" antimicrobial="" substances="" has="" included="" consideration="" of="" potential="" impacts="" at="" the="" site="" of="" use="" and="" disposal="" of="" the="" antimicrobial="" substance,="" and="" from="" the="" use="" of="" natural="" resources="" and="" energy.="" currently,="" for="" the="" use="" sites="" of="" antimicrobial="" substances,="" petitioners="" are="" directed="" to="" rely="" on="" information="" in="" studies="" submitted="" to="" epa="" for="" registration="" of="" the="" product="" under="" fifra,="" and="" to="" describe="" any="" potential="" adverse="" environmental="" effects="" determined="" by="" epa.="" petitioners="" may="" submit="" a="" brief="" description="" and="" summary="" of="" results="" of="" epa="" studies="" in="" lieu="" of="" the="" complete="" test="" reports.="" for="" use="" sites,="" fda="" has="" based="" its="" environmental="" decision="" on="" a="" prediction="" of="" exposure="" levels,="" using="" introduction="" and="" fate="" information,="" that="" is="" compared="" with="" relevant="" toxicological="" data="" to="" determine="" the="" potential="" for="" significant="" environmental="" effects.="" the="" agency's="" experience="" with="" antimicrobial="" petitions="" has="" been="" that,="" before="" an="" antimicrobial="" product="" can="" be="" used="" in="" food-contact="" situations,="" epa="" will="" have="" already="" examined="" the="" environmental="" risks="" and="" benefits="" of="" registering="" the="" product="" under="" fifra.="" the="" parallel="" between="" epa's="" review="" and="" fda's="" environmental="" review="" is="" illustrated="" by="" fda's="" finding="" that="" it="" has="" not="" had="" to="" require="" environmental="" testing="" for="" antimicrobial="" products="" because="" such="" tests="" were="" already="" conducted="" as="" part="" of="" epa's="" review.="" in="" addition,="" antimicrobial="" substances="" that="" are="" used="" and="" discharged="" at="" point="" sources="" within="" the="" united="" states="" are="" subject="" to="" the="" requirements="" of="" national="" pollution="" discharge="" elimination="" system="" (npdes)="" permits="" under="" the="" clean="" water="" act="" (33="" u.s.c.="" 1251="" et="" seq.).="" in="" registering="" a="" product="" under="" fifra,="" epa="" requires="" the="" label="" to="" state="" that:="" (1)="" the="" product="" is="" not="" to="" be="" discharged="" into="" lakes,="" streams,="" ponds,="" estuaries,="" oceans,="" or="" other="" waters="" unless="" in="" accordance="" with="" the="" requirements="" of="" an="" npdes="" permit="" and="" unless="" the="" permitting="" authority="" has="" been="" notified="" in="" writing="" prior="" to="" discharge;="" and="" (2)="" the="" product="" is="" not="" to="" be="" discharged="" to="" sewer="" systems="" without="" previously="" notifying="" the="" local="" sewage="" treatment="" plant="" authority.="" epa="" also="" requires,="" if="" necessary,="" that="" labels="" contain="" information="" such="" as="" a="" warning="" of="" toxicity="" to="" fish="" and/or="" wildlife,="" as="" specified="" in="" 40="" cfr="" 156.10(h)(2)(ii).="" thus,="" fda="" has="" found="" that="" its="" assessment="" of="" the="" fate="" and="" effects="" of="" antimicrobial="" substances="" essentially="" duplicates="" the="" review="" by="" epa="" under="" fifra="" and,="" to="" some="" extent,="" the="" review="" by="" npdes="" permitting="" authorities="" under="" the="" clean="" water="" act.="" currently,="" petitioners="" must="" address="" the="" potential="" for="" impact="" on="" the="" use="" of="" natural="" resources="" and="" energy="" as="" required="" in="" an="" ea="" by="" specifying="" the="" natural="" resources="" and="" energy="" required="" to="" produce,="" transport,="" use,="" and/or="" dispose="" of="" a="" given="" amount="" of="" the="" product="" that="" is="" the="" subject="" of="" the="" action.="" fda's="" experience="" with="" this="" area="" of="" potential="" impacts="" is="" that="" these="" types="" of="" substances="" almost="" always="" compete="" with="" and="" replace="" other="" similar="" substances="" so="" that="" there="" is="" [[page="" 14931]]="" little="" or="" no="" change="" in="" the="" use="" of="" natural="" resources="" and="" energy.="" thus,="" fda="" believes="" that="" future="" food="" additive="" petitions="" for="" the="" same="" use="" as="" pesticides="" approved="" by="" epa="" under="" fifra="" will="" have="" little="" or="" no="" potential="" for="" significant="" environmental="" impacts="" and="" that="" fda's="" actions="" on="" these="" petitions="" warrant="" exclusion="" from="" the="" requirement="" to="" prepare="" an="" ea.="" k.="" removal="" of="" action="" levels.="" at="" the="" time="" the="" current="" environmental="" regulations="" were="" issued,="" the="" agency="" believed="" that="" the="" establishment="" of="" an="" action="" level="" required="" environmental="" review.="" thus,="" the="" agency="" included="" a="" paragraph="" for="" the="" establishment="" of="" action="" levels="" in="" current="" sec.="" 25.22(a)(11)="" and="" specified="" an="" ea="" format="" in="" current="" sec.="" 25.31d.="" fda="" also="" provided="" a="" categorical="" exclusion="" in="" current="" sec.="" 25.24(b)(6)="" for="" action="" levels="" for="" natural="" or="" unavoidable="" defects="" in="" food="" for="" humans="" or="" animals="" if="" these="" defects="" presented="" no="" health="" hazard.="" in="" 1987,="" in="" a="" limited="" holding,="" the="" court="" of="" appeals="" for="" the="" d.c.="" circuit="" in="" community="" nutrition="" institute="" v.="" young,="" 818="" f.2d="" 943="" (d.c.="" cir.="" 1987),="" found="" that="" fda="" was="" treating="" its="" action="" levels="" as="" substantive,="" legislative="" rules="" and,="" thus,="" action="" levels="" were="" subject="" to="" the="" notice-and-comment="" requirements="" of="" the="" administrative="" procedure="" act="" (5="" u.s.c.="" 551="" et="" seq.).="" the="" court="" recognized,="" however,="" that="" fda="" could="" proceed="" by="" action="" levels="" that="" are="" not="" binding="" rules.="" since="" the="" court's="" holding,="" fda="" has="" followed="" this="" approach.="" under="" its="" statutory="" authority="" under="" 21="" u.s.c.="" 342(a)(1),="" (a)(2)(a),="" and="" 346="" to="" limit="" the="" amount="" of="" poisonous="" or="" deleterious="" substances="" in="" food,="" fda="" establishes="" ``action="" levels''="" to="" inform="" food="" producers="" of="" the="" level="" of="" contaminants="" in="" food="" that="" may="" result="" in="" regulatory="" action.="" action="" levels="" are="" not="" intended="" to="" bind="" the="" public,="" or="" fda,="" or="" to="" create="" or="" confer="" any="" rights,="" privileges,="" immunities,="" or="" benefits="" on="" or="" for="" any="" private="" person,="" but="" are="" intended="" merely="" for="" internal="" fda="" guidance="" for="" deciding="" whether="" to="" bring="" an="" enforcement="" action.="" the="" establishment="" of="" an="" action="" level="" is="" not="" agency="" action="" and="" is="" not="" subject="" to="" nepa.="" moreover,="" under="" ceq="" regulations="" (40="" cfr="" 1508.18(a)),="" bringing="" judicial,="" administrative,="" civil,="" or="" criminal="" enforcement="" actions="" is="" not="" major="" federal="" action.="" because="" establishment="" of="" action="" levels="" is="" intended="" merely="" for="" internal="" guidance="" for="" deciding="" whether="" to="" bring="" an="" enforcement="" action,="" establishment="" of="" an="" action="" level="" is="" not="" major="" federal="" action.="" therefore,="" fda="" is="" proposing="" to="" remove="" all="" references="" to="" action="" levels="" from="" part="" 25.="" the="" agency="" will="" continue="" to="" apply="" these="" regulations="" to="" the="" establishment="" of="" tolerances="" for="" poisonous="" or="" deleterious="" substances="" in="" food="" for="" human="" or="" animal="" consumption="" or="" in="" packaging="" materials="" intended="" for="" use="" with="" human="" food="" and="" animal="" feeds.="" l.="" proposed="" sec.="" 25.32(r).="" fda="" is="" proposing="" to="" categorically="" exclude="" actions="" to="" approve="" a="" food="" additive,="" a="" color="" additive,="" or="" a="" gras="" affirmation="" petition="" for="" a="" substance="" that="" occurs="" naturally="" in="" the="" environment,="" when="" the="" action="" is="" not="" expected="" to="" alter="" significantly="" the="" concentration="" or="" distribution="" of="" the="" substance,="" its="" metabolites,="" or="" degradation="" products.="" this="" proposed="" exclusion="" is="" based="" on="" fda's="" review="" of="" 19="" petitions="" for="" substances="" in="" this="" class,="" all="" of="" which="" resulted="" in="" a="" finding="" of="" no="" significant="" impact.="" the="" agency="" currently="" requires="" limited="" information="" for="" substances="" that="" occur="" naturally="" in="" the="" environment,="" as="" specified="" in="" the="" abbreviated="" ea="" format="" in="" current="" sec.="" 25.31a(b)(5).="" this="" format="" focuses="" on="" whether="" the="" use="" of="" the="" substance="" can="" reasonably="" be="" expected,="" on="" the="" basis="" of="" all="" available="" evidence,="" to="" alter="" significantly="" the="" concentration="" and="" distribution="" of="" the="" substance,="" its="" metabolites,="" or="" degradation="" products="" in="" the="" environment="" and="" on="" information="" about="" the="" environmental="" effects="" of="" substances="" expected="" to="" be="" emitted="" into="" the="" environment.="" from="" its="" review="" of="" 19="" petitions,="" the="" agency="" has="" found="" that="" the="" use="" of="" naturally="" occurring="" substances="" as="" food="" additives,="" color="" additives,="" or="" gras="" substances="" did="" not="" alter="" significantly="" the="" concentration="" and="" distribution="" of="" the="" substance,="" its="" metabolites="" or="" degradation="" products="" in="" the="" environment,="" and="" therefore,="" substances="" emitted="" into="" the="" environment="" did="" not="" have="" adverse="" environmental="" effects.="" among="" the="" 19="" petitions="" for="" naturally="" occurring="" substances="" reviewed="" by="" the="" agency="" were="" several="" petitions="" for="" substances="" intended="" to="" replace="" macronutrients="" in="" food.="" in="" sec.="" 25.32(k),="" fda="" is="" not="" proposing="" to="" exclude="" from="" the="" requirement="" to="" prepare="" an="" ea="" petitions="" for="" substances="" intended="" to="" replace="" macronutrients.="" however,="" when="" a="" macronutrient="" replacement="" is="" also="" a="" substance="" that="" occurs="" naturally="" in="" the="" environment,="" the="" categorical="" exclusion="" proposed="" here="" will="" apply,="" unless="" the="" agency="" finds="" that="" extraordinary="" circumstances="" exist,="" as="" delineated="" in="" proposed="" sec.="" 25.21.="" 4.="" veterinary="" drugs="" and="" feed="" additives="" the="" national="" performance="" report,="" ``reinventing="" food="" regulations,''="" january="" 1996,="" announced="" fda's="" proposal="" to="" reduce="" the="" number="" of="" ea's="" submitted="" by="" industry="" under="" nepa="" by="" increasing="" the="" number="" of="" categorical="" exclusions="" for="" actions="" relating="" to="" animal="" drugs,="" animal="" feeds,="" and="" food="" and="" color="" additives,="" which="" as="" a="" class="" have="" no="" individual="" or="" cumulative="" significant="" effects="" on="" the="" environment.="" as="" described="" below,="" in="" fulfillment="" of="" this="" commitment,="" fda="" is="" proposing="" additional="" categorical="" exclusions="" for="" actions="" on="" animal="" drugs="" and="" feed="" additives="" that,="" based="" upon="" its="" experience="" in="" reviewing="" these="" types="" of="" actions,="" the="" center="" for="" veterinary="" medicine="" (cvm)="" has="" concluded="" will="" not="" significantly="" affect="" the="" human="" environment.="" under="" proposed="" sec.="" 25.33(a),="" actions="" relating="" to="" new="" animal="" drug="" applications="" (nada's),="" abbreviated="" applications,="" and="" supplements="" to="" such="" applications="" that="" do="" not="" increase="" the="" use="" and="" disposal="" of="" the="" substances="" are="" categorically="" excluded.="" proposed="" sec.="" 25.33(a)="" includes="" the="" categorical="" exclusions="" listed="" in="" current="" sec.="" 25.24(d)(1)="" and="" (d)(2),="" and="" broadens="" the="" categorical="" exclusion="" to="" allow="" fda="" to="" categorically="" exclude="" other="" actions="" that="" do="" not="" result="" in="" increased="" use="" of="" a="" drug="" and,="" consequently,="" do="" not="" result="" in="" an="" increase="" in="" the="" expected="" level="" of="" environmental="" exposure.="" for="" example,="" the="" approval="" of="" a="" supplement="" for="" a="" new="" manufacturing="" site="" is="" not="" specifically="" listed="" but="" may="" be="" categorically="" excluded="" if="" it="" is="" not="" expected="" to="" result="" in="" increased="" use="" of="" the="" substance="" for="" which="" the="" supplement="" was="" submitted.="" proposed="" sec.="" 25.33(a)(7)="" for="" animal="" drugs="" used="" in="" feeds="" is="" the="" same="" as="" current="" sec.="" 25.24(d)(2)="" but="" has="" been="" revised="" for="" clarity="" because="" fda="" approves="" animal="" drugs="" for="" use="" in="" animal="" feeds.what="" about="" 512(m)="" and="" proposed="" 25.24(e)?="" the="" categorical="" exclusions="" in="" proposed="" sec.="" 25.33(a)="" include="" actions="" relating="" to="" abbreviated="" new="" animal="" drug="" applications="" (anada's)="" in="" recognition="" of="" the="" creation="" of="" anada's="" under="" the="" 1988="" generic="" animal="" drug="" and="" patent="" term="" restoration="" act="" (gadptra)="" (21="" u.s.c.="" 301="" note).="" an="" anada="" is="" merely="" an="" abbreviated="" form="" of="" an="" nada="" and="" seeks="" to="" effectuate="" the="" same="" action,="" approval="" of="" an="" animal="" drug.="" therefore,="" the="" nature="" of="" environmental="" considerations="" is="" similar.="" for="" animal="" drugs="" not="" otherwise="" excluded="" in="" sec.="" 25.33(a),="" the="" agency="" is="" reserving="" sec.="" 25.33(b)="" to="" provide="" for="" a="" categorical="" exclusion="" analogous="" to="" that="" contained="" in="" proposed="" sec.="" 25.31(b)="" for="" human="" drugs.="" the="" categorical="" exclusion="" would="" be="" for="" actions="" that="" increase="" the="" use="" of="" an="" animal="" drug="" in="" the="" instance="" that="" the="" agency="" determines="" a="" level="" at="" or="" below="" which="" the="" concentration="" of="" the="" substance="" in="" the="" environment="" does="" not="" significantly="" affect="" the="" environment.="" [[page="" 14932]]="" fda="" recognizes="" that="" proposed="" sec.="" 25.31(b)="" for="" human="" drugs="" allows="" for="" a="" categorical="" exclusion="" for="" increased="" uses="" of="" human="" drugs="" if="" the="" concentration="" of="" the="" substance="" in="" the="" aquatic="" environment="" will="" be="" at="" or="" below="" 1="" ppb.="" at="" this="" time,="" fda="" is="" not="" adopting="" a="" specific="" environmental="" concentration="" from="" use="" of="" animal="" drugs="" because="" the="" agency="" is="" still="" conducting="" a="" retrospective="" review="" of="" environmental="" assessments="" for="" these="" products="" and="" a="" review="" of="" revelant="" environmental="" science.="" the="" animal="" health="" institute="" and="" fda/cvm="" held="" an="" environmental="" risk="" assessment="" workshop="" on="" february="" 20="" and="" 21,="" 1996,="" to="" establish="" a="" comprehensive="" ecological="" risk="" assessment="" process="" for="" the="" evaluation="" of="" animal="" health="" products.="" following="" this="" opportunity="" for="" public="" debate,="" and="" for="" drugs="" not="" otherwise="" excluded,="" fda="" will="" adopt="" a="" risk="" assessment="" paradigm="" for="" determining="" environmental="" introductions="" for="" animal="" drugs="" and="" an="" environmental="" concentration="" at="" or="" below="" which="" no="" meaningful="" environmental="" effects="" are="" expected="" to="" occur.="" proposed="" 25.33(c)="" would="" categorically="" exclude="" any="" action="" on="" an="" nada,="" abbreviated="" application,="" or="" a="" supplement="" to="" such="" actions="" for="" substances="" that="" occur="" naturally="" in="" the="" environment,="" when="" the="" action="" is="" not="" expected="" to="" alter="" significantly="" the="" concentration="" or="" distribution="" of="" the="" substance,="" its="" metabolites,="" or="" degradation="" products="" in="" the="" environment.="" currently,="" fda's="" regulations="" require="" an="" abbreviated="" ea="" for="" an="" animal="" drug="" substance="" that="" occurs="" naturally="" in="" the="" environment.="" these="" abbreviated="" ea's="" require="" information="" about="" the="" production="" site="" and="" about="" whether="" the="" use="" of="" the="" product="" will="" significantly="" alter="" the="" concentration,="" distribution,="" and="" effect="" of="" the="" natural="" substance="" in="" the="" environment.="" since="" the="" publication="" of="" the="" nepa="" regulations="" in="" 1985,="" fda="" has="" reviewed="" abbreviated="" ea's="" for="" substances="" that="" are="" naturally="" occurring.="" fda="" has="" found="" that="" actions="" on="" submissions="" for="" these="" substances="" will="" not="" affect="" the="" environment="" if="" the="" action="" will="" not="" significantly="" alter="" the="" concentration="" or="" distribution="" of="" the="" natural="" substance="" in="" the="" environment.="" under="" these="" circumstances,="" the="" agency="" has="" prepared="" fonsi's.="" therefore,="" the="" proposed="" regulations="" would="" categorically="" exclude="" actions="" on="" an="" nada,="" abbreviated="" application,="" or="" a="" supplement="" to="" such="" applications="" for="" substances="" that="" occur="" naturally="" in="" the="" environment="" when="" the="" action="" is="" not="" expected="" to="" alter="" significantly="" the="" concentration="" or="" distribution="" of="" the="" substance,="" its="" metabolites,="" or="" degradation="" products="" in="" the="" environment.="" fda="" has="" access="" to="" information="" regarding="" metabolites="" and="" degradation="" products="" to="" aid="" in="" determining="" if="" the="" categorical="" exclusion="" request="" is="" appropriate.="" neither="" an="" ea="" nor="" an="" eis="" would="" be="" required="" for="" such="" actions.="" when="" an="" action="" does="" alter="" significantly="" the="" concentration="" or="" distribution="" of="" the="" products,="" its="" metabolites,="" or="" degradation="" products="" in="" the="" environment,="" e.g.,="" when="" the="" use="" and="" disposal="" will="" occur="" in="" a="" geographic="" area="" where="" the="" substance="" is="" not="" naturally="" occurring,="" an="" environmental="" assessment="" may="" be="" required.="" proposed="" sec.="" 25.33(d)="" includes="" categorical="" exclusions="" for="" actions="" relating="" to="" approval="" of="" applications="" for="" animal="" drugs="" intended="" for="" use="" in="" nonfood="" animals,="" for="" local="" or="" general="" anesthesia,="" for="" ophthalmic="" or="" topical="" applications,="" for="" the="" treatment="" of="" a="" disease="" occurring="" in="" minor="" species="" animals,="" as="" defined="" in="" sec.="" 514.1(d)(1)(i)="" (21="" cfr="" 514.1(d)(1)(i)),="" and="" for="" use="" under="" prescription="" or="" veterinarian's="" order.="" under="" current="" sec.="" 25.31a(b)(4),="" fda="" requires="" abbreviated="" ea's="" to="" be="" submitted="" as="" part="" of="" any="" request="" for="" such="" approvals.="" these="" abbreviated="" ea's="" require="" environmental="" information="" for="" production="" sites.="" since="" the="" publication="" of="" the="" nepa="" regulation="" in="" 1985,="" cvm="" has="" reviewed="" many="" abbreviated="" ea's="" for="" these="" types="" of="" products.="" in="" every="" instance,="" the="" agency="" has="" prepared="" a="" fonsi="" because="" the="" manufacturing="" was="" determined="" to="" be="" in="" compliance="" and="" would="" remain="" in="" compliance="" with="" the="" federal,="" state,="" and="" local="" environmental="" requirements="" that="" apply="" to="" the="" site="" of="" manufacturing,="" and="" the="" market="" volume="" for="" such="" products="" was="" so="" low="" that="" fda="" found,="" based="" on="" its="" experience,="" the="" drugs="" would="" not="" significantly="" affect="" the="" environment.="" furthermore,="" as="" the="" agency="" explains="" in="" section="" iii.d.="" of="" this="" document,="" the="" agency="" has="" determined="" that="" ordinarily="" fda="" will="" not="" consider="" potential="" impacts="" at="" the="" site="" of="" production.="" the="" categorical="" exclusion="" for="" local="" and="" general="" anesthetic="" products="" applies="" only="" to="" those="" products="" that="" are="" administered="" individually.="" some="" anesthetic="" products="" may="" be="" intended="" to="" be="" administered="" to="" many="" animals="" or="" in="" significant="" quantities.="" in="" these="" instances,="" potential="" environmental="" effects="" exist="" that="" require="" environmental="" analysis.="" the="" exclusion="" for="" ophthalmic="" and="" topical="" products="" is="" limited="" to="" those="" products="" intended="" for="" nonsystemic="" use.="" products="" used="" systemically="" could="" result="" in="" greater="" environmental="" introductions="" that="" could="" potentially="" affect="" the="" environment="" and,="" therefore,="" require="" further="" environmental="" analysis.="" furthermore,="" fda="" is="" clarifying="" that="" the="" categorical="" exclusion="" for="" drugs="" for="" minor="" species="" applies="" only="" to="" those="" animal="" drugs="" that="" have="" been="" previously="" approved="" for="" use="" in="" another="" or="" the="" same="" species="" when="" similar="" animal="" management="" practices="" are="" used.="" when="" management="" practices="" are="" different,="" environmental="" introductions="" and="" impacts="" may="" also="" be="" different="" and="" require="" environmental="" analyses.="" minor="" species="" include="" wildlife="" and="" endangered="" species="" (sec.="" 514.1(d)(1)(ii)).="" the="" categorial="" exclusion="" for="" animal="" drugs="" used="" under="" prescription="" or="" veterinarian's="" order="" applies="" only="" to="" animal="" drugs="" for="" therapeutic="" uses="" as="" defined="" in="" section="" 201(g)(1)(b)="" of="" the="" act="" (21="" u.s.c.="" 321(g)(1)(b)).="" based="" on="" its="" experience="" in="" reviewing="" ea's="" for="" these="" products,="" fda="" has="" found="" that="" prescription="" products="" are="" generally="" administered="" individually="" to="" a="" limited="" number="" of="" animals="" for="" a="" limited="" amount="" of="" time.="" therefore,="" there="" are="" no="" significant="" environmental="" effects.="" however,="" fda="" may="" require="" an="" ea="" if="" the="" agency="" determines="" that="" there="" are="" extraordinary="" circumstances="" associated="" with="" the="" use="" of="" such="" a="" product.="" current="" sec.="" 25.24(d)(4)="" categorically="" excludes="" actions="" on="" an="" investigational="" new="" animal="" drug="" application="" (inad)="" if="" the="" drug="" to="" be="" shipped="" under="" such="" notice="" is="" intended="" to="" be="" used="" for="" clinical="" studies="" or="" research="" in="" which="" wastes="" will="" be="" controlled="" or="" the="" amount="" of="" wastes="" expected="" to="" enter="" the="" environment="" may="" reasonably="" be="" expected="" to="" be="" nontoxic.="" under="" proposed="" sec.="" 25.33(e),="" fda="" would="" categorically="" exclude="" all="" actions="" on="" inad's.="" in="" many="" cases,="" fda's="" actions="" on="" inad's="" do="" not="" significantly="" increase="" the="" use="" of="" the="" drug="" and,="" thus,="" the="" amount="" of="" drug="" introduced="" into="" the="" environment.="" therefore,="" no="" changes="" in="" environmental="" effects="" will="" occur.="" in="" those="" cases="" where="" an="" increase="" in="" use="" of="" a="" drug="" may="" occur="" as="" a="" result="" of="" an="" investigation="" under="" an="" inad,="" fda's="" experience="" from="" reviewing="" many="" actions="" on="" inad's="" shows="" that="" significant="" environmental="" effects="" will="" not="" occur="" because="" the="" use="" of="" such="" drugs="" is="" limited="" and="" controlled.="" proposed="" sec.="" 25.33(f)="" would="" categorically="" exclude="" actions="" on="" applications="" submitted="" under="" section="" 512(m)="" of="" the="" act="" (21="" u.s.c.="" 360b(m)).="" fda="" is="" proposing="" to="" exclude="" actions="" on="" such="" applications="" because="" they="" permit="" feed="" manufacturers="" to="" manufacture="" animal="" feed="" bearing="" or="" containing="" new="" animal="" drugs="" previously="" approved="" for="" use="" in="" feeds.="" the="" potential="" for="" environmental="" effects="" to="" occur="" is="" considered="" at="" the="" time="" the="" new="" animal="" drug="" is="" approved="" for="" use="" in="" feed.="" therefore,="" there="" is="" no="" need="" to="" require="" an="" [[page="" 14933]]="" additional="" ea="" each="" time="" the="" agency="" considers="" approval="" of="" an="" application="" submitted="" under="" section="" 512(m)="" of="" the="" act.="" current="" sec.="" 25.24(d)(3)="" categorically="" excludes="" withdrawals="" of="" approval="" of="" nada's="" when="" the="" drug="" is="" no="" longer="" marketed="" or="" at="" the="" request="" of="" the="" application="" holder.="" under="" proposed="" sec.="" 25.33(g),="" fda="" would="" categorically="" exclude="" withdrawals="" of="" approval="" of="" anada's,="" as="" well="" as="" withdrawals="" of="" approval="" of="" nada's,="" without="" conditions.="" fda="" has="" determined="" that="" withdrawal="" of="" an="" nada="" or="" anada="" approval="" does="" not="" significantly="" affect="" the="" environment="" because="" any="" change="" in="" introduction="" of="" the="" drug="" will="" generally="" be="" a="" decrease.="" under="" proposed="" sec.="" 25.33(h),="" fda="" would="" categorically="" exclude="" actions="" to="" withdraw="" the="" approval="" for="" uses="" of="" food="" additives="" in="" animal="" feeds="" or="" to="" remove="" substances="" for="" use="" in="" animal="" feeds="" from="" the="" gras="" list="" or="" to="" remove="" substances="" from="" the="" gras="" list="" (parts="" 182,="" 184,="" or="" 186).="" withdrawal="" or="" removal="" of="" a="" food="" additive="" substance="" that="" reduces="" or="" eliminates="" animal="" feed="" use="" will="" not="" significantly="" affect="" the="" environment="" because="" any="" change="" in="" introduction="" of="" the="" substance="" to="" the="" environment="" will="" generally="" be="" a="" decrease.="" in="" those="" cases="" where="" the="" withdrawal="" of="" the="" nada,="" anada,="" or="" fap,="" or="" gras="" substance="" has="" resulted="" in="" the="" use="" of="" a="" substitute="" product,="" the="" agency="" has="" found="" in="" all="" instances="" that="" the="" increased="" use="" of="" the="" substitutes="" will="" not="" significantly="" affect="" the="" environment.="" fda="" is="" proposing="" to="" eliminate="" the="" categorical="" exclusions="" under="" current="" sec.="" 25.24(d)(5)="" and="" (d)(6)="" because="" fda="" does="" not="" do="" testing="" and="" certification="" of="" batches="" of="" antibiotics="" for="" animal="" use,="" and="" fda="" does="" not="" use="" monographs="" for="" animal="" drugs.="" fda="" is="" proposing="" to="" eliminate="" current="" sec.="" 25.24(d)(7).="" this="" action="" takes="" place="" under="" an="" inad,="" and="" its="" effect="" is="" to="" set="" the="" standard="" for="" approving="" anada's.="" fda="" will="" determine="" whether="" it="" needs="" to="" consider="" environmental="" effects="" when="" it="" approves="" individual="" anada's.="" 5.="" devices="" and="" electronic="" products="" the="" agency="" is="" proposing="" to="" redesignate="" current="" sec.="" 25.24(e)="" as="" proposed="" sec.="" 25.34="" and="" to="" remove="" criteria="" in="" sec.="" 25.24(e)(4)="" and="" (e)(7),="" now="" incorporated="" in="" proposed="" sec.="" 25.21="" extraordinary="" circumstances.="" d.="" subpart="" d--preparation="" of="" environmental="" documents="" the="" proposed="" rule="" would="" reorganize="" current="" subpart="" c="" of="" part="" 25="" to="" improve="" the="" usefulness="" and="" readability="" of="" the="" current="" regulations.="" proposed="" sec.="" 25.40(b)="" would="" eliminate="" the="" ea="" and="" abbreviated="" ea="" formats="" and="" delete="" any="" reference="" to="" formats.="" after="" consultation="" with="" ceq,="" the="" agency="" has="" decided="" to="" remove="" the="" standard="" formats="" from="" part="" 25,="" and="" to="" provide="" appropriate="" formats="" in="" guidance="" documents.="" guidance="" documents,="" which="" do="" not="" bind="" the="" agency="" or="" the="" public,="" are="" more="" easily="" revised.="" use="" of="" such="" documents="" will="" give="" fda="" greater="" flexibility="" to="" tailor="" environmental="" documents="" to="" reflect="" state-of-the-art="" developments="" in="" environmental="" analysis="" and="" to="" assist="" companies="" in="" focusing="" on="" important="" environmental="" issues.="" information/guidance="" concerning="" the="" nature="" and="" scope="" of="" information="" that="" an="" applicant="" or="" petitioner="" should="" submit="" in="" an="" ea="" may="" be="" obtained="" from="" the="" center="" responsible="" for="" the="" action="" subject="" to="" environmental="" evaluation="" (proposed="" sec.="" 25.40(c)).="" in="" the="" federal="" register="" of="" january="" 11,="" 1996,="" fda="" announced="" the="" availability="" of="" a="" guidance="" document="" entitled,="" ``guidance="" for="" industry="" for="" the="" submission="" of="" an="" environmental="" assessment="" in="" human="" drug="" applications="" and="" supplements''="" (61="" fr="" 1031).="" the="" guidance,="" prepared="" by="" cder,="" is="" intended="" to="" assist="" industry="" by="" providing="" guidance="" on="" how="" to="" prepare="" ea's="" for="" submission="" to="" cder="" as="" part="" of="" nda's,="" antibiotic="" applications,="" anda's,="" abbreviated="" antibiotic="" applications,="" and="" ind's.="" this="" guidance="" will="" be="" amended="" to="" reflect="" the="" final="" regulations="" and="" categorical="" exclusions="" and="" to="" include="" biologic="" products="" subject="" to="" licensure="" under="" the="" phs="" act.="" the="" guidance="" document="" employs="" a="" tiered="" approach="" to="" testing="" and="" accepts="" the="" use="" of="" test="" methods="" recognized="" and="" recommended="" by="" competent="" authorities="" such="" as="" fda="" (see="" e.g.,="" fda's="" ea="" technical="" assistance="" handbook),="" epa="" (see="" 40="" cfr="" parts="" 796="" and="" 797)="" and="" the="" organization="" for="" economic="" co-operation="" and="" development.="" under="" the="" proposed="" rule,="" this="" approach="" will="" continue="" to="" be="" acceptable.="" the="" current="" formats="" in="" part="" 25="" focus="" the="" environmental="" analysis="" on="" the="" use="" and="" disposal="" from="" use="" of="" fda-regulated="" articles="" but="" also="" address="" production="" impacts.="" fda="" proposes="" to="" maintain="" this="" focus="" in="" the="" proposed="" revised="" regulations,="" but,="" for="" the="" following="" reasons,="" is="" proposing="" to="" change="" the="" way="" it="" addresses="" production="" impacts.="" to="" address="" the="" potential="" environmental="" impacts="" from="" production="" of="" fda-regulated="" articles,="" fda="" currently="" requires="" a="" limited="" amount="" of="" information="" to="" make="" sure="" that="" the="" article="" will="" be="" produced="" in="" compliance="" with="" applicable="" emissions="" requirements.="" specifically,="" the="" agency="" requires="" that="" the="" following="" information="" be="" included="" in="" an="" ea:="" a="" list="" of="" the="" substances="" expected="" to="" be="" emitted,="" the="" controls="" exercised,="" a="" citation="" of="" applicable="" emissions="" requirements="" and="" statement="" of="" compliance="" with="" these="" requirements,="" and="" a="" discussion="" of="" the="" effect="" the="" approval="" of="" the="" petition="" will="" have="" on="" compliance="" with="" these="" requirements.="" fda="" recognizes,="" however,="" that="" federal,="" state,="" and="" local="" environmental="" protection="" agencies="" have="" the="" responsibility="" for="" issuing="" regulations,="" permitting="" and="" licensing="" facilities,="" and="" enforcing="" compliance="" with="" the="" requirements="" that="" these="" agencies="" have="" determined="" are="" necessary="" to="" ensure="" adequate="" protection="" of="" the="" environment="" from="" emissions="" from="" production="" operations.="" regulating="" emissions="" from="" production="" sites="" requires="" balancing="" between="" air,="" water,="" and="" solid="" waste="" emissions="" for="" all="" production="" operations="" carried="" out="" at="" a="" production="" site="" and="" in="" the="" region="" with="" consideration="" of="" the="" costs="" of="" compliance="" and="" available="" technology="" that="" requires="" expertise="" found="" primarily="" in="" federal,="" state,="" and="" local="" environmental="" agencies.="" as="" required="" by="" environmental="" regulations="" and/or="" as="" conditions="" of="" retaining="" licenses="" and="" permits,="" manufacturers="" must="" obtain="" or="" modify="" permits="" and="" provide="" information="" to="" these="" agencies="" when="" production="" operations="" are="" initiated="" or="" changed.="" the="" information="" required="" to="" be="" provided="" to="" fda="" regarding="" production="" impacts="" and="" compliance="" with="" emission="" requirements="" is="" information="" that="" is="" generally="" required="" to="" be="" provided="" to="" or="" is="" known="" by="" other="" agencies="" whose="" responsibility="" is="" to="" monitor="" compliance.="" fda="" has="" reviewed="" hundreds="" of="" ea's="" in="" which="" information="" regarding="" the="" manufacturing="" site,="" such="" as="" emitted="" substances="" and="" emission="" controls,="" was="" provided.="" as="" a="" result="" of="" this="" review,="" fda="" has="" found="" that="" fda-regulated="" articles="" produced="" in="" compliance="" with="" all="" applicable="" emission="" requirements="" (e.g.,="" clean="" air="" act,="" clean="" water="" act,="" occupational="" safety="" and="" health="" act)="" will="" not="" significantly="" affect="" the="" environment.="" based="" on="" these="" findings,="" fda="" has="" determined="" that="" it="" is="" no="" longer="" necessary="" to="" review="" a="" company's="" compliance="" with="" federal,="" state,="" and="" local="" environmental="" laws="" and="" fda="" is="" proposing="" to="" delete="" the="" requirements="" for="" the="" submission="" of="" emission="" information="" for="" production="" sites.="" accordingly,="" under="" the="" proposed="" regulations,="" fda="" will="" continue="" to="" focus="" its="" environmental="" reviews="" on="" the="" use="" and="" disposal="" from="" use="" of="" fda-regulated="" articles,="" and="" fda="" will="" no="" longer="" routinely="" require="" submission="" of="" information="" regarding="" manufacturing="" sites="" or="" a="" certification="" of="" compliance="" with="" federal,="" state,="" and="" [[page="" 14934]]="" local="" emission="" requirements.="" however,="" if="" information="" available="" to="" the="" agency="" or="" the="" applicant="" establishes="" that="" the="" general="" or="" specific="" emission="" requirements="" promulgated="" by="" federal,="" state,="" or="" local="" environmental="" protection="" agencies="" do="" not="" address="" unique="" emission="" circumstances="" and="" the="" emissions="" may="" harm="" the="" environment,="" this="" would="" be="" sufficient="" grounds="" for="" requesting="" manufacturing="" information="" in="" an="" ea.="" fda="" generally="" requires="" manufacturing="" information="" to="" be="" submitted="" as="" part="" of="" applications="" or="" petitions="" for="" fda-regulated="" articles.="" this="" information="" will="" aid="" fda="" in="" determining="" if="" a="" categorical="" exclusion="" request="" is="" appropriate.="" proposed="" sec.="" 25.40(a)="" includes="" additional="" information="" found="" in="" the="" ceq="" regulations="" to="" clarify="" that="" the="" ea="" shall="" include="" brief="" discussions="" of="" the="" need="" for="" the="" proposal,="" alternatives,="" environmental="" impacts="" of="" the="" proposed="" action,="" and="" a="" listing="" of="" agencies="" and="" persons="" consulted,="" and="" include="" additional="" information="" to="" clarify="" the="" scope="" and="" focus="" of="" an="" ea.="" environmental="" documents="" shall="" concentrate="" on="" timely="" and="" significant="" issues,="" not="" amass="" needless="" detail.="" to="" that="" end,="" the="" agency="" has="" included="" some="" general="" information="" regarding="" the="" acceptability="" of="" using="" a="" tiered="" testing="" scheme.="" a="" tiered="" testing="" scheme="" results="" in="" test="" termination="" when="" sufficient="" data="" are="" available="" to="" assess="" the="" potential="" environmental="" fate="" and="" effects="" of="" an="" fda-regulated="" article="" in="" the="" environment.="" specific="" information="" regarding="" tiered="" testing="" will="" be="" provided="" in="" guidance="" documents.="" although="" the="" number="" of="" pages="" for="" any="" ea="" may="" vary="" in="" relation="" to="" the="" complexity="" of="" the="" issues,="" generally="" they="" should="" not="" exceed="" 30="" pages,="" not="" including="" test="" reports="" and="" data.="" the="" agency="" is="" proposing="" to="" add="" sec.="" 25.40(b)="" to="" clarify="" that="" ceq="" regulations="" (40="" cfr="" 1506.5(b))="" place="" ultimate="" responsibility="" on="" fda="" for="" the="" scope="" and="" content="" of="" environmental="" analyses.="" thus,="" fda="" may="" require="" additional="" information="" from="" applicants="" or="" may="" itself="" include="" additional="" information="" in="" environmental="" documents="" (ea's,="" fonsi's,="" or="" eis's)="" when="" warranted.="" proposed="" sec.="" 25.40(c)="" would="" include="" information="" found="" in="" current="" sec.="" 25.30(a)="" and="" encourages="" applicants="" or="" petitioners="" who="" submit="" ea's="" to="" fda="" to="" consult="" with="" fda="" regarding="" the="" appropriate="" scope="" and="" content="" for="" ea's="" for="" the="" requested="" action.="" proposed="" sec.="" 25.40(d)="" discusses="" incorporation="" of="" information="" in="" an="" ea="" by="" reference.="" proposed="" sec.="" 25.41="" would="" include="" information="" on="" fonsi's="" that="" is="" found="" in="" current="" sec.="" 25.32(a)="" and="" (c).="" the="" agency="" is="" proposing="" to="" delete="" the="" language="" on="" notices="" of="" intent="" and="" draft,="" final,="" and="" supplemental="" eis's,="" found="" in="" current="" secs.="" 25.33="" and="" 25.34,="" because="" the="" ceq="" regulations="" describe="" the="" process="" for="" determining="" the="" scope="" of="" an="" eis="" and="" provide="" detailed="" requirements="" for="" the="" preparation="" of="" draft="" and="" final="" eis's.="" thus,="" this="" information="" is="" duplicative="" and="" unnecessary="" in="" fda="" regulations="" (40="" cfr="" 1501.7="" and="" part="" 1502).="" proposed="" sec.="" 25.42="" would="" describe="" the="" subject="" matter="" that="" needs="" to="" be="" discussed="" in="" an="" eis="" and="" references="" the="" ceq="" regulations="" governing="" the="" requirements="" for="" preparation="" of="" an="" eis.="" proposed="" sec.="" 25.42(c)="" fulfills="" the="" ceq="" requirement="" under="" 40="" cfr="" 1502.9(c)="" that="" fda="" adopt="" procedures="" for="" introducing="" a="" supplement="" into="" its="" administrative="" record.="" the="" agency="" is="" proposing="" to="" add="" new="" sec.="" 25.43="" to="" clarify="" the="" agency's="" existing="" responsibility="" under="" the="" ceq="" regulations="" to="" prepare="" a="" concise="" public="" record="" of="" decision="" for="" cases="" requiring="" eis's="" (40="" cfr="" 1505.2).="" proposed="" sec.="" 25.44="" would="" include="" information="" found="" in="" current="" sec.="" 25.10(b),="" describing="" the="" responsibilities="" of="" lead="" and="" cooperating="" agencies.="" the="" agency="" is="" proposing="" to="" delete="" duplicative="" and="" unnecessary="" information="" on="" lead="" and="" cooperating="" agencies="" that="" is="" already="" found="" in="" the="" ceq="" regulations,="" and="" to="" delete="" the="" first="" sentence="" in="" current="" sec.="" 25.10(b)="" because="" it="" is="" self-evident="" that="" fda="" will="" be="" the="" lead="" agency="" for="" programs="" administered="" by="" fda.="" proposed="" sec.="" 25.45="" would="" include="" information="" from="" current="" sec.="" 25.42,="" describing="" who="" the="" responsible="" agency="" official="" will="" be="" and="" his="" or="" her="" responsibilities.="" the="" agency="" is="" proposing="" to="" remove="" information="" in="" current="" sec.="" 25.42="" that="" is="" duplicative="" of="" requirements="" already="" found="" in="" ceq="" regulations.="" e.="" subpart="" e--public="" participation="" and="" notification="" of="" environmental="" documents-="" the="" proposed="" rule="" would="" improve="" the="" usefulness="" and="" readability="" of="" the="" regulations="" by="" reorganizing="" current="" subpart="" d="" of="" part="" 25,="" ``agency="" decisionmaking''="" (now="" proposed="" ``public="" participation="" and="" notification="" of="" environmental="" documents'')="" by="" deleting="" unnecessary="" information="" that="" is="" duplicative="" of="" requirements="" found="" in="" the="" ceq="" regulations,="" and,="" as="" discussed="" above,="" moving="" information="" to="" other="" relevant="" sections.="" proposed="" subpart="" e="" would="" now="" address="" public="" participation="" in="" the="" nepa="" process="" and="" clarify="" circumstances="" under="" which="" environmental="" documents="" will="" publicly="" be="" disclosed.="" these="" revisions="" are="" consistent="" with="" our="" responsibilities="" under="" the="" ceq="" regulations="" and="" under="" executive="" order="" 12898,="" federal="" actions="" to="" address="" environmental="" justice="" in="" minority="" populations="" and="" low="" income="" populations,="" february="" 11,="" 1994.="" ceq="" regulations="" require="" that="" agency="" procedures="" ensure="" full="" compliance="" with="" nepa="" to="" the="" extent="" possible,="" unless="" existing="" law="" applicable="" to="" the="" agency's="" operations="" expressly="" prohibits="" or="" makes="" compliance="" impossible="" (40="" cfr="" 1500.6).="" proposed="" sec.="" 25.50="" clarifies="" that="" laws="" governing="" public="" disclosure="" may="" limit="" fda's="" ability="" to="" comply="" with="" nepa="" and="" ceq="" regulations.="" proposed="" sec.="" 25.51(a)="" and="" (b),="" public="" disclosure="" of="" fonsi's="" and="" ea's,="" would="" include="" the="" public="" disclosure="" information="" found="" in="" current="" sec.="" 25.30(b)="" and="" 25.41(b).="" the="" proposed="" rule="" would="" move="" the="" information="" relating="" to="" statutory="" time="" frames="" from="" current="" sec.="" 25.40(c)="" to="" proposed="" sec.="" 25.51(b)(1).="" proposed="" sec.="" 25.52="" would="" add="" new="" information="" relating="" to="" the="" public="" disclosure="" of="" eis's.="" f.="" subpart="" f--other="" requirements="" current="" subpart="" e="" will="" be="" renumbered="" as="" subpart="" f.="" the="" agency="" is="" not="" proposing="" to="" amend="" this="" subpart.="" iv.="" environmental="" impact="" considerations="" the="" agency="" has="" determined="" under="" current="" 21="" cfr="" 25.24(a)(8)="" that="" this="" action="" is="" of="" a="" type="" that="" does="" not="" individually="" or="" cumulatively="" have="" a="" significant="" effect="" on="" the="" human="" environment.="" therefore,="" neither="" an="" ea="" nor="" an="" eis="" is="" required.="" v.="" analysis="" of="" impacts="" fda="" has="" examined="" the="" impacts="" of="" the="" proposed="" rule="" under="" executive="" order="" 12866,="" under="" the="" regulatory="" flexibility="" act="" (pub.="" l.="" 96-354),="" and="" under="" the="" unfunded="" mandates="" reform="" act="" (pub.="" l.="" 104-4).="" executive="" order="" 12866="" directs="" agencies="" to="" assess="" all="" costs="" and="" benefits="" of="" available="" regulatory="" alternatives="" and,="" when="" regulation="" is="" necessary,="" to="" select="" regulatory="" approaches="" that="" maximize="" net="" benefits="" (including="" potential="" economic,="" environmental,="" public="" health="" and="" safety,="" and="" other="" advantages;="" distributive="" impacts="" and="" equity).="" the="" regulatory="" flexibility="" act="" requires="" agencies="" to="" analyze="" regulatory="" options="" that="" would="" minimize="" any="" significant="" impact="" of="" a="" rule="" on="" small="" entities.="" the="" unfunded="" mandates="" reform="" act="" requires="" (in="" section="" 202)="" that="" agencies="" prepare="" an="" assessment="" of="" anticipated="" costs="" and="" benefits="" before="" proposing="" any="" rule="" that="" may="" result="" in="" an="" annual="" expenditure="" by="" state,="" local,="" and="" tribal="" governments,="" in="" [[page="" 14935]]="" the="" aggregate,="" or="" by="" the="" private="" sector,="" of="" $100,000,000="" (adjusted="" annually="" for="" inflation).="" that="" act="" also="" requires="" (in="" section="" 205)="" that="" the="" agency="" identify="" and="" consider="" a="" reasonable="" number="" of="" regulatory="" alternatives="" and="" from="" those="" alternatives="" select="" the="" least="" costly,="" most="" cost="" effective,="" or="" least="" burdensome="" alternative="" that="" achieves="" the="" objective="" of="" the="" rule.="" the="" following="" analysis="" demonstrates="" that="" this="" proposed="" rule="" is="" consistent="" with="" the="" principles="" set="" forth="" in="" the="" executive="" order="" and="" in="" these="" two="" statutes.="" the="" proposed="" rule="" is="" not="" an="" economically="" significant="" regulatory="" action="" under="" executive="" order="" 12866.="" based="" on="" the="" approximate="" number="" of="" ea's="" that="" fda="" currently="" receives="" each="" year="" and="" the="" resources="" needed="" to="" prepare="" them,="" the="" agency="" estimates="" that="" the="" proposed="" reduced="" requirements="" for="" submitting="" ea's="" will="" result="" in="" an="" annual="" cost="" savings="" to="" industry="" of="" approximately="" $15.7="" million.="" the="" basis="" for="" this="" estimate="" is="" as="" follows:="" human="" pharmaceuticals:="" approximately="" 125="" ea's="" related="" to="" human="" pharmaceuticals="" would="" be="" eliminated="" annually="" under="" the="" proposal.="" about="" one-half="" of="" these="" are="" abbreviated="" ea's;="" the="" remainder="" are="" full="" assessments.="" fda="" assumes="" that="" the="" average="" cost="" of="" preparing="" an="" abbreviated="" assessment="" was="" approximately="" $40,000,="" while="" the="" average="" cost="" of="" a="" full="" assessment="" was="" approximately="" $200,000.="" these="" assumptions="" yield="" a="" cost="" savings="" of="" about="" $2.5="" million="" for="" abbreviated="" ea's="" and="" $12.5="" million="" for="" full="" ea's,="" for="" a="" total="" savings="" to="" industry="" from="" the="" reduced="" requirements="" of="" ea's="" relating="" to="" human="" pharmaceuticals="" of="" approximately="" $15="" million="" per="" year.="" veterinary="" products:="" the="" proposed="" changes="" would="" eliminate="" approximately="" 37="" abbreviated="" ea's="" for="" veterinary="" products="" each="" year,="" at="" an="" average="" cost="" of="" approximately="" $5,000="" each.="" about="" 77="" brief="" submissions,="" which="" currently="" require="" categorical="" exclusion="" criteria="" review,="" would="" also="" be="" eliminated;="" these="" cost="" an="" estimated="" $300="" each="" to="" prepare.="" total="" cost="" savings="" to="" the="" veterinary="" products="" industry="" under="" the="" proposal="" would="" thus="" be="" approximately="" $208,000="" per="" year.="" food="" products:="" about="" 36="" ea's="" per="" year="" received="" by="" cfsan="" would="" be="" eliminated="" under="" the="" proposal.="" approximately="" 28="" of="" these="" would="" have="" been="" abbreviated="" ea's="" and="" 8="" would="" have="" been="" full="" assessments="" under="" current="" rules.="" fda="" estimates="" that="" the="" cost="" of="" producing="" most="" abbreviated="" ea's="" for="" cfsan="" is="" approximately="" $2,500="" and="" the="" average="" cost="" of="" producing="" a="" full="" ea="" is="" approximately="" $50,000.="" these="" assumptions="" imply="" an="" annual="" cost="" savings="" of="" approximately="" $70,000="" for="" abbreviated="" ea's="" and="" $400,000="" for="" full="" ea's,="" for="" a="" total="" annual="" savings="" to="" the="" foods="" industry="" of="" approximately="" $470,000.="" in="" addition="" to="" these="" savings="" to="" industry,="" the="" proposed="" changes="" would="" improve="" fda="" efficiency="" by="" eliminating="" agency="" review="" costs="" of="" approximately="" $1="" million="" per="" year.="" the="" regulatory="" flexibility="" act="" requires="" agencies="" to="" analyze="" regulatory="" options="" that="" would="" minimize="" any="" significant="" impact="" of="" a="" rule="" of="" small="" entities.="" because="" these="" regulations="" will="" not="" impose="" significant="" new="" costs="" on="" any="" firms,="" the="" agency="" certifies="" that="" the="" proposed="" rule="" will="" not="" have="" a="" significant="" economic="" impact="" on="" a="" substantial="" number="" of="" small="" entities.="" therefore,="" under="" the="" regulatory="" flexibility="" act,="" no="" further="" analysis="" is="" required.="" vi.="" paperwork="" reduction="" act="" of="" 1995="" this="" proposed="" rule="" contains="" reporting="" requirements="" that="" are="" subject="" to="" public="" comment="" and="" review="" by="" the="" office="" of="" management="" and="" budget="" (omb)="" under="" the="" paperwork="" reduction="" act="" of="" 1995="" (44="" u.s.c.="" 3506="" and="" 3507).="" therefore,="" in="" accordance="" with="" 5="" cfr="" part="" 1320,="" a="" description="" of="" reporting="" requirements="" with="" an="" estimate="" of="" the="" annual="" collection="" of="" information="" burden="" is="" given="" below="" by="" cross="" reference="" to="" existing="" fda="" clearance="" submissions="" previously="" approved="" by="" omb="" which="" this="" proposed="" rule="" affects.="" fda="" is="" soliciting="" comments="" to:="" (1)="" evaluate="" whether="" the="" proposed="" collection="" of="" information="" is="" necessary="" for="" the="" proper="" performance="" of="" the="" functions="" of="" the="" agency,="" including="" whether="" the="" information="" will="" have="" practical="" utility;="" (2)="" evaluate="" the="" accuracy="" of="" the="" agency's="" estimate="" of="" the="" proposed="" collection="" of="" information;="" (3)="" evaluate="" the="" quality,="" utility,="" and="" clarity="" of="" the="" information="" to="" be="" collected;="" and="" (4)="" minimize="" the="" burden="" of="" the="" collection="" of="" information="" on="" those="" who="" are="" to="" respond.="" title:="" national="" environmental="" policy="" act;="" policies="" and="" procedures.="" description:="" fda="" has="" previously="" issued="" regulations="" that="" implement="" nepa="" (part="" 25).="" the="" proposed="" rule="" would="" reduce="" the="" number="" of="" nepa="" evaluations="" by="" providing="" for="" categorical="" exclusions="" for="" additional="" classes="" of="" actions="" that="" do="" not="" individually="" or="" cumulatively="" have="" a="" significant="" effect="" on="" the="" human="" environment="" and="" for="" which,="" therefore,="" neither="" an="" eis="" nor="" an="" ea="" is="" required.="" fda="" is="" also="" proposing="" to="" amend="" these="" regulations="" to="" ensure="" that="" the="" nepa="" procedures="" are="" more="" concise="" and="" understandable="" to="" the="" public="" and="" to="" reflect="" current="" fda="" policy="" with="" respect="" to="" environmental="" considerations.="" this="" proposed="" rule="" is="" in="" response="" to="" initiatives="" announced="" in="" the="" president's="" national="" performance="" reports,="" ``reinventing="" drug="" and="" medical="" device="" regulations,''="" april="" 1995,="" and="" ``reinventing="" food="" regulations,''="" january="" 1996.="" description="" of="" respondents:="" persons="" and="" businesses,="" including="" small="" businesses.="" estimated="" annual="" reporting="" and="" recordkeeping="" burden.="" the="" estimated="" burden="" associated="" with="" the="" information="" collection="" requirements="" for="" this="" proposed="" rule="" will="" be="" recognized="" in="" the="" individual="" fda="" clearances="" where="" nepa="" considerations="" apply.="" listed="" below="" are="" those="" clearances="" affected="" by="" this="" regulation,="" including="" the="" section="" of="" title="" 21="" cfr,="" the="" title,="" and="" the="" omb="" approval="" number:="" section="" 10.30,="" citizen="" petitions,="" 0910-0183;="" sec.="" 71.1,="" color="" additive="" petitions,="" 0910-0185;="" sec.="" 170.35,="" affirmation="" of="" generally="" recognized="" as="" safe="" (gras)="" status,="" 0910-0132;="" sec.="" 101.12,="" reference="" amounts="" customarily="" consumed="" per="" eating="" occasion,="" 0910-0286;="" sec.="" 101.69,="" petitions="" for="" nutrient="" content="" claims,="" 0910-0288;="" sec.="" 101.70,="" petitions="" for="" health="" claims,="" 0910-0287;="" sec.="" 170.39,="" threshold="" of="" regulation="" for="" substances="" used="" in="" food-contact="" articles,="" 0910-0298;="" sec.="" 171.1,="" food="" additive="" petitions,="" 0910-0016;="" sec.="" 312.23,="" conditions="" for="" exemption="" of="" new="" drugs="" for="" investigational="" use,="" 0910-="" 0014;="" sec.="" 511.1,="" new="" animal="" drugs="" for="" investigational="" use="" exempt="" from="" section="" 512(a)="" of="" the="" act,="" 0910-0117;="" sec.="" 514.1,="" new="" animal="" drug="" applications,="" 0910-0032;="" sec.="" 514.8,="" supplemental="" new="" animal="" drug="" applications,="" 0910-0032;="" sec.="" 571.1,="" food="" additive="" petitions,="" 0910-="" 0016;="" sec.="" 601.2="" product="" licenses-procedures="" for="" filing,="" 0910-0124;="" sec.="" 812.20,="" investigational="" device="" exemptions="" application,="" 0910-0078.="" the="" proposed="" rule="" would="" reduce="" these="" information="" collections="" that="" have="" already="" been="" reviewed="" and="" approved="" by="" the="" omb.-reporting="" burdens="" imposed="" by="" current="" part="" 25="" are="" approved="" by="" omb="" through="" december="" 31,="" 1997="" (see="" omb="" control="" number="" 0910-0190,="" ``national="" environmental="" policy="" act;="" policy="" and="" procedures--21="" cfr="" part="" 25'').="" the="" agency="" has="" submitted="" copies="" of="" the="" proposed="" rule="" to="" omb="" for="" its="" review="" of="" these="" reporting="" requirements.="" interested="" persons="" are="" requested="" to="" send="" comments="" regarding="" information="" collection="" by="" may="" 3,="" 1996,="" to="" the="" office="" of="" information="" and="" regulatory="" affairs,="" omb="" (address="" above).="" [[page="" 14936]]="" list="" of="" subjects="" in="" 21="" cfr="" part="" 25="" environmental="" impact="" statements,="" foreign="" relations,="" reporting="" and="" recordkeeping="" requirements.="" therefore,="" under="" the="" federal="" food,="" drug,="" and="" cosmetic="" act,="" the="" public="" health="" service="" act,="" and="" authority="" delegated="" to="" the="" commissioner="" of="" food="" and="" drugs,="" it="" is="" proposed="" that="" 21="" cfr="" part="" 25="" be="" revised="" to="" read="" as="" follows:="" part="" 25--environmental="" impact="" considerations="" subpart="" a--general="" provisions="" sec.="" 25.1="" purpose.="" 25.5="" terminology.="" 25.10="" policies="" and="" nepa="" planning.="" subpart="" b--agency="" actions="" requiring="" environmental="" consideration="" 25.15="" general="" procedures.="" 25.16="" public="" health="" and="" safety="" emergencies.="" 25.20="" actions="" requiring="" preparation="" of="" an="" environmental="" assessment.="" 25.21="" extraordinary="" circumstances.="" 25.22="" actions="" requiring="" preparation="" of="" an="" environmental="" impact="" statement.="" subpart="" c--categorical="" exclusions="" 25.30="" general.="" 25.31="" human="" drugs="" and="" biologics.="" 25.32="" foods,="" food="" additives,="" and="" color="" additives.="" 25.33="" animal="" drugs.="" 25.34="" devices="" and="" electronic="" products.--="" subpart="" d--preparation="" of="" environmental="" documents="" 25.40="" environmental="" assessments.-="" 25.41="" findings="" of="" no="" significant="" impact.="" 25.42="" environmental="" impact="" statements.="" 25.43="" records="" of="" decision.-="" 25.44="" lead="" and="" cooperating="" agencies.="" 25.45="" responsible="" agency="" official="" subpart="" e--public="" participation="" and="" notification="" of="" environmental="" documents---="" 25.50="" general="" information.="" 25.51="" environmental="" assessments="" and="" findings="" of="" no="" significant="" -="" impact.="" 25.52="" environmental="" impact="" statements.-="" subpart="" f--other="" requirements="" 25.60="" environmental="" effects="" abroad="" of="" major="" agency="" actions.="" authority:="" secs.="" 201-903="" of="" the="" federal="" food,="" drug,="" and="" cosmetic="" act="" (21="" u.s.c.="" 321-393);="" secs.="" 351,="" 354-361="" of="" the="" public="" health="" service="" act="" (42="" u.s.c.="" 262,="" 263b-264);="" 42="" u.s.c.="" 4321,="" 4332;="" 40="" cfr="" parts="" 1500-1508;="" e.o.="" 11514,="" 3="" cfr,="" 1966-1970="" comp.,="" p.="" 902,="" as="" amended="" by="" e.o.="" 11991,="" 3="" cfr,="" 1977="" comp.,="" p.="" 123;="" e.o.="" 12114,="" 3="" cfr,="" 1979="" comp.,="" p.="" 356.="" subpart="" a--general="" provisions="" sec.="" 25.1="" purpose.="" the="" national="" environmental="" policy="" act="" of="" 1969="" (nepa),="" as="" amended,="" directs="" that,="" to="" the="" fullest="" extent="" possible,="" the="" policies,="" regulations,="" and="" public="" laws="" of="" the="" united="" states="" shall="" be="" interpreted="" and="" administered="" in="" accordance="" with="" the="" policies="" set="" forth="" in="" nepa.="" all="" agencies="" of="" the="" federal="" government="" shall="" comply="" with="" the="" procedures="" in="" section="" 102(2)="" of="" nepa="" except="" where="" compliance="" would="" be="" inconsistent="" with="" other="" statutory="" requirements.="" the="" regulations="" in="" this="" part="" implement="" section="" 102(2)="" of="" nepa="" in="" a="" manner="" that="" is="" consistent="" with="" fda's="" authority="" under="" the="" federal="" food,="" drug,="" and="" cosmetic="" act="" and="" the="" public="" health="" service="" act.="" this="" part="" also="" supplements="" the="" regulations="" for="" implementing="" the="" procedural="" provisions="" of="" nepa="" that="" were="" published="" by="" the="" council="" on="" environmental="" quality="" (ceq)="" in="" 40="" cfr="" parts="" 1500="" through="" 1508="" and="" the="" procedures="" included="" in="" the="" ``hhs="" general="" administration="" manual,="" part="" 30:="" environmental="" protection''="" (45="" fr="" 76519="" to="" 76534,="" november="" 19,="" 1980).sec.="" 25.5="" terminology.="" (a)="" definitions="" that="" apply="" to="" the="" terms="" used="" in="" this="" part="" are="" set="" forth="" in="" the="" ceq="" regulations="" under="" 40="" cfr="" part="" 1508.="" the="" terms="" and="" the="" sections="" of="" 40="" cfr="" part="" 1508="" in="" which="" they="" are="" defined="" follow:="" (1)="" categorical="" exclusion="" (40="" cfr="" 1508.4).="" (2)="" cooperating="" agency="" (40="" cfr="" 1508.5).="" (3)="" cumulative="" impact="" (40="" cfr="" 1508.7).="" (4)="" effects="" (40="" cfr="" 1508.8).="" (5)="" environmental="" assessment="" (ea)="" (40="" cfr="" 1508.9).="" (6)="" environmental="" document="" (40="" cfr="" 1508.10).="" (7)="" environmental="" impact="" statement="" (eis)="" (40="" cfr="" 1508.11).="" (8)="" federal="" agency="" (40="" cfr="" 1508.12).="" (9)="" finding="" of="" no="" significant="" impact="" (40="" cfr="" 1508.13).="" (10)="" human="" environment="" (40="" cfr="" 1508.14).="" (11)="" lead="" agency="" (40="" cfr="" 1508.16).="" (12)="" legislation="" (40="" cfr="" 1508.17).="" (13)="" major="" federal="" action="" (40="" cfr="" 1508.18).="" (14)="" mitigation="" (40="" cfr="" 1508.20).="" (15)="" nepa="" process="" (40="" cfr="" 1508.21).="" (16)="" notice="" of="" intent="" (40="" cfr="" 1508.22).="" (17)="" proposal="" (40="" cfr="" 1508.23).="" (18)="" scope="" (40="" cfr="" 1508.25).="" (19)="" significantly="" (40="" cfr="" 1508.27).="" (b)="" the="" following="" terms="" are="" defined="" solely="" for="" the="" purpose="" of="" implementing="" the="" supplemental="" procedures="" provided="" by="" this="" part="" and="" are="" not="" necessarily="" applicable="" to="" any="" other="" statutory="" or="" regulatory="" requirements:-="" (1)="" abbreviated="" application="" applies="" to="" an="" abbreviated="" new="" drug="" application,="" an="" abbreviated="" antibiotic="" application,="" and="" an="" abbreviated="" new="" animal="" drug="" application.="" (2)="" active="" moiety="" means="" the="" molecule="" or="" ion,="" excluding="" those="" appended="" portions="" of="" the="" molecule="" that="" cause="" the="" drug="" to="" be="" an="" ester,="" salt="" (including="" a="" salt="" with="" hydrogen="" or="" coordination="" bonds),="" or="" other="" noncovalent="" derivative="" (such="" as="" a="" complex="" chelate="" or="" clathrate)="" of="" the="" molecule="" responsible="" for="" the="" physiological="" or="" pharmacological="" action="" of="" the="" drug="" substance.="" (3)="" agency="" means="" the="" food="" and="" drug="" administration="" (fda).="" (4)="" increased="" use="" of="" a="" drug="" or="" biologic="" product="" may="" occur="" if="" the="" drug="" will="" be="" administered="" at="" higher="" dosage="" levels,="" for="" longer="" duration="" or="" for="" different="" indications="" than="" were="" previously="" in="" effect,="" or="" if="" the="" drug="" is="" a="" new="" molecular="" entity.="" new="" molecular="" entity="" means="" a="" drug="" for="" which="" the="" active="" moiety="" (present="" as="" the="" unmodified="" (parent)="" compound,="" or="" an="" ester="" or="" a="" salt,="" clathrate,="" or="" other="" noncovalent="" derivative="" of="" the="" base="" (parent)="" compound)="" has="" not="" been="" previously="" approved="" or="" marketed="" in="" the="" united="" states="" for="" use="" in="" a="" drug="" product,="" either="" as="" a="" single="" ingredient="" or="" as="" part="" of="" a="" combination="" product="" or="" as="" part="" of="" a="" mixture="" of="" stereoisomers.="" the="" term="" ``use''="" also="" encompasses="" disposal="" of="" fda-regulated="" articles="" by="" consumers.="" (5)="" responsible="" agency="" official="" means="" the="" agency="" decisionmaker="" designated="" in="" part="" 5="" of="" this="" chapter.="" (c)="" the="" following="" acronyms="" are="" used="" in="" this="" part:="" (1)="" ceq--council="" on="" environmental="" quality.="" (2)="" cgmp--current="" good="" manufacturing="" practice.="" (3)="" ea--environmental="" assessment.="" (4)="" eis--environmental="" impact="" statement.="" (5)="" the="" act--federal="" food,="" drug,="" and="" cosmetic="" act.="" (6)="" fifra--federal="" insecticide,="" fungicide,="" and="" rodenticide="" act.="" (7)="" fonsi--finding="" of="" no="" significant="" impact.="" (8)="" glp--good="" laboratory="" practice.="" (9)="" gras--generally="" recognized="" as="" safe.="" (10)="" haccp--hazard="" analysis="" critical="" control="" point.="" (11)="" ide--investigational="" device="" exemption.="" (12)="" ind--investigational="" new="" drug="" application.="" (13)="" inad--investigational="" new="" animal="" drug="" application.="" (14)="" nada--new="" animal="" drug="" application.="" (15)="" nda--new="" drug="" application.="" (16)="" nepa--national="" environmental="" policy="" act="" of="" 1969.-="" (17)="" pdp--product="" development="" protocol.="" (18)="" pma--premarket="" approval="" application.-="" [[page="" 14937]]="" sec.="" 25.10="" policies="" and="" nepa="" planning.="" (a)="" all="" fda's="" policies="" and="" programs="" will="" be="" planned,="" developed,="" and="" implemented="" to="" achieve="" the="" policies="" declared="" by="" nepa="" and="" required="" by="" ceq's="" regulations="" to="" ensure="" responsible="" stewardship="" of="" the="" environment="" for="" present="" and="" future="" generations.="" (b)="" assessment="" of="" environmental="" factors="" continues="" throughout="" planning="" and="" is="" integrated="" with="" other="" program="" planning="" at="" the="" earliest="" possible="" time="" to="" ensure="" that="" planning="" and="" decisions="" reflect="" environmental="" values,="" to="" avoid="" delays="" later="" in="" the="" process,="" and="" to="" avoid="" potential="" conflicts.="" (c)="" for="" actions="" initiated="" by="" the="" agency,="" the="" nepa="" process="" will="" begin="" when="" the="" agency="" action="" under="" consideration="" is="" first="" identified.="" for="" actions="" initiated="" by="" applicants="" or="" petitioners,="" nepa="" planning="" begins="" when="" fda="" receives="" a="" submission="" from="" an="" applicant="" or="" petitioner="" seeking="" action="" by="" fda.="" fda="" may="" issue="" a="" public="" call="" for="" environmental="" data="" or="" otherwise="" consult="" with="" affected="" individuals="" or="" groups="" when="" a="" contemplated="" action="" in="" which="" it="" is="" or="" may="" be="" involved="" poses="" potential="" significant="" environmental="" effects.="" (d)="" environmental="" documents="" shall="" concentrate="" on="" timely="" and="" significant="" issues,="" not="" amass="" needless="" detail.="" (e)="" if="" a="" proposed="" action="" for="" which="" an="" eis="" will="" be="" prepared="" involves="" possible="" environmental="" effects="" that="" are="" required="" to="" be="" considered="" under="" statutes="" or="" executive="" orders="" other="" than="" those="" referred="" to="" under="" ``authority''="" in="" this="" part,="" these="" effects="" shall="" be="" considered="" in="" the="" nepa="" review,="" consistent="" with="" 40="" cfr="" 1502.25="" and="" the="" department="" of="" health="" and="" human="" services'="" general="" administration="" manual,="" part="" 30.="" subpart="" b--agency="" actions="" requiring="" environmental="" consideration="" sec.="" 25.15="" general="" procedures.="" (a)="" all="" applications="" or="" petitions="" requesting="" agency="" action="" require="" the="" submission="" of="" an="" ea="" or="" a="" claim="" of="" categorical="" exclusion.="" a="" claim="" of="" categorical="" exclusion="" shall="" include="" a="" certification="" of="" compliance="" with="" the="" categorical="" exclusion="" criteria="" and="" shall="" certify="" that="" to="" the="" applicant's="" knowledge,="" no="" extraordinary="" circumstances="" exist.="" failure="" to="" submit="" an="" adequate="" ea="" for="" an="" application="" or="" petition="" requesting="" action="" by="" the="" agency="" of="" a="" type="" specified="" in="" sec.="" 25.20,="" unless="" the="" agency="" can="" determine="" that="" the="" action="" qualifies="" for="" exclusion="" under="" secs.="" 25.30,="" 25.31,="" 25.32,="" 25.33,="" or="" 25.34,="" is="" sufficient="" grounds="" for="" fda="" to="" refuse="" to="" file="" or="" approve="" the="" application="" or="" petition.="" (b)="" the="" responsible="" agency="" officials="" will="" evaluate="" the="" information="" contained="" in="" the="" ea="" to="" determine="" whether="" it="" is="" accurate="" and="" objective,="" whether="" the="" proposed="" action="" may="" significantly="" affect="" the="" quality="" of="" the="" human="" environment,="" and="" whether="" an="" eis="" will="" be="" prepared.="" if="" significant="" effects="" requiring="" the="" preparation="" of="" an="" eis="" are="" identified,="" fda="" will="" prepare="" an="" eis="" for="" the="" action="" in="" accordance="" with="" the="" procedures="" in="" subparts="" d="" and="" e="" of="" this="" part.="" if="" significant="" effects="" requiring="" the="" preparation="" of="" an="" eis="" are="" not="" identified,="" resulting="" in="" a="" decision="" not="" to="" prepare="" an="" eis,="" the="" responsible="" agency="" official="" will="" prepare="" a="" fonsi="" in="" accordance="" with="" sec.="" 25.41.="" (c)="" classes="" of="" actions="" that="" individually="" or="" cumulatively="" do="" not="" significantly="" affect="" the="" quality="" of="" the="" human="" environment="" ordinarily="" are="" excluded="" from="" the="" requirement="" to="" prepare="" an="" ea="" or="" an="" eis.="" the="" classes="" of="" actions="" that="" qualify="" as="" categorical="" exclusions="" are="" set="" forth="" in="" secs.="" 25.30,="" 25.31,="" 25.32,="" 25.33,="" or="" 25.34.="" (d)="" a="" person="" submitting="" an="" application="" or="" petition="" of="" a="" type="" subject="" to="" categorical="" exclusion="" under="" secs.="" 25.30,="" 25.31,="" 25.32,="" 25.33,="" or="" 25.34,="" or="" proposing="" to="" dispose="" of="" an="" article="" as="" provided="" in="" secs.="" 25.30(d)="" or="" 25.32(h),="" is="" not="" required="" to="" submit="" an="" ea="" if="" the="" person="" certifies="" that="" the="" action="" requested="" qualifies="" for="" a="" categorical="" exclusion,="" citing="" the="" particular="" categorical="" exclusion="" that="" is="" claimed,="" and="" certifies="" that="" to="" the="" applicant's="" knowledge,="" no="" extraordinary="" circumstances="" exist.="" sec.="" 25.16="" public="" health="" and="" safety="" emergencies.="" there="" are="" certain="" regulatory="" actions="" that,="" because="" of="" their="" immediate="" importance="" to="" the="" public="" health="" or="" safety,="" may="" make="" adherence="" to="" the="" procedural="" provisions="" of="" nepa="" and="" ceq's="" regulations="" impossible.="" for="" such="" actions,="" the="" responsible="" agency="" official="" shall="" consult="" with="" ceq="" about="" alternative="" arrangements="" before="" the="" action="" is="" taken,="" or="" after="" the="" action="" is="" taken,="" if="" time="" does="" not="" permit="" prior="" consultation="" with="" ceq.="" sec.="" 25.20="" actions="" requiring="" preparation="" of="" an="" environmental="" assessment.="" any="" proposed="" action="" of="" a="" type="" specified="" in="" this="" section="" ordinarily="" requires="" at="" least="" the="" preparation="" of="" an="" ea,="" unless="" it="" is="" an="" action="" in="" a="" specific="" class="" that="" qualifies="" for="" exclusion="" under="" secs.="" 25.30,="" 25.31,="" 25.32,="" 25.33,="" or="" 25.34:="" (a)="" major="" recommendations="" or="" reports="" made="" to="" congress="" on="" proposals="" for="" legislation="" in="" instances="" where="" the="" agency="" has="" primary="" responsibility="" for="" the="" subject="" matter="" involved.="" (b)="" destruction="" or="" other="" disposition="" of="" articles="" condemned="" after="" seizure="" or="" whose="" distribution="" or="" use="" has="" been="" enjoined,="" unless="" categorically="" excluded="" in="" secs.="" 25.30(d)="" or="" 25.32(h).="" (c)="" destruction="" or="" other="" disposition="" of="" articles="" following="" detention="" or="" recall="" at="" agency="" request,="" unless="" categorically="" excluded="" in="" secs.="" 25.30(d)="" or="" 25.32(h).="" (d)="" disposition="" of="" fda="" laboratory="" waste="" materials,="" unless="" categorically="" excluded="" in="" sec.="" 25.30(m).="" (e)="" intramural="" and="" extramural="" research="" supported="" in="" whole="" or="" in="" part="" through="" contracts,="" other="" agreements,="" or="" grants,="" unless="" categorically="" excluded="" in="" sec.="" 25.30(e)="" or="" (f).="" (f)="" establishment="" by="" regulation="" of="" labeling="" requirements,="" a="" standard,="" or="" a="" monograph,="" unless="" categorically="" excluded="" in="" secs.="" 25.30(k)="" or="" 25.31(a),="" (b),="" (c),="" (h),="" (i),="" or="" (j),="" or="" 25.32(a)="" or="" (p).="" (g)="" issuance,="" amendment,="" and="" enforcement="" of="" fda="" regulations,="" or="" an="" exemption="" or="" variance="" from="" fda="" regulations,="" unless="" categorically="" excluded="" in="" secs.="" 25.30(h),="" (i),="" or="" (j),="" or="" 25.32(e),="" (g),="" (n),="" or="" (p).="" (h)="" withdrawal="" of="" existing="" approvals="" of="" fda-approved="" articles,="" unless="" categorically="" excluded="" in="" secs.="" 25.31(d)="" or="" (k),="" 25.32(m),="" or="" 25.33(g)="" or="" (h).="" (i)="" approval="" of="" food="" additive="" petitions="" and="" color="" additive="" petitions,="" approval="" of="" requests="" for="" exemptions="" for="" investigational="" use="" of="" food="" additives,="" and="" granting="" of="" requests="" for="" exemption="" from="" regulation="" as="" a="" food="" additive,="" unless="" categorically="" excluded="" in="" sec.="" 25.32(b),="" (c),="" (i),="" (j),="" (k),="" (l),="" (o),="" (q),="" or="" (r).="" (j)="" establishment="" of="" a="" tolerance="" for="" unavoidable="" poisonous="" or="" deleterious="" substances="" in="" food="" or="" in="" packaging="" materials="" to="" be="" used="" for="" food.--="" (k)="" affirmation="" of="" a="" food="" substance="" as="" gras="" for="" humans="" or="" animals,="" on="" fda's="" initiative="" or="" in="" response="" to="" a="" petition,="" under="" part="" 182,="" 184,="" 186,="" or="" 582="" of="" this="" chapter="" and="" establishment="" or="" amendment="" of="" a="" regulation="" for="" a="" prior-sanctioned="" food="" ingredient,="" as="" defined="" in="" secs.="" 170.3(l)="" and="" 181.5(a)="" of="" this="" chapter,="" unless="" categorically="" excluded="" in="" sec.="" 25.32(f),="" (k),="" or="" (r).="" (l)="" approval="" of="" nda's,="" abbreviated="" applications,="" applications="" for="" marketing="" approval="" for="" marketing="" of="" a="" biologic="" product,="" supplements="" to="" such="" applications,="" and="" actions="" on="" ind's,="" unless="" categorically="" excluded="" in="" sec.="" 25.31(a),="" (b),="" (c),="" (e),="" or="" (l).="" (m)="" approval="" of="" nada's,="" abbreviated="" applications,="" supplements,="" and="" actions="" on="" inad's,="" unless="" categorically="" excluded="" under="" sec.="" 25.33(a),="" (c),="" (d),="" or="" (e).="" (n)="" approval="" of="" pma's="" for="" medical="" devices,="" notices="" of="" completion="" of="" pdp's="" for="" medical="" devices,="" authorizations="" to="" commence="" clinical="" investigation="" under="" an="" approved="" pdp,="" or="" applications="" for="" an="" [[page="" 14938]]="" ide,="" unless="" categorically="" excluded="" in="" sec.="" 25.34.="" sec.="" 25.21="" extraordinary="" circumstances.="" as="" required="" under="" 40="" cfr="" 1508.4,="" fda="" will="" require="" at="" least="" an="" ea="" for="" any="" specific="" action="" that="" ordinarily="" would="" be="" excluded="" if="" extraordinary="" circumstances="" indicate="" that="" the="" specific="" proposed="" action="" may="" significantly="" affect="" the="" quality="" of="" the="" human="" environment="" (see="" 40="" cfr="" 1508.27="" for="" examples="" of="" significant="" impacts).="" examples="" of="" such="" extraordinary="" circumstances="" include:="" (a)="" actions="" for="" which="" available="" data="" establish="" that,="" at="" the="" expected="" level="" of="" exposure,="" there="" is="" the="" potential="" for="" serious="" harm="" to="" the="" environment;="" and="" (b)="" actions="" that="" adversely="" affect="" a="" species="" or="" the="" critical="" habitat="" of="" a="" species="" determined="" under="" the="" endangered="" species="" act="" or="" the="" convention="" on="" international="" trade="" in="" endangered="" species="" of="" wild="" flora="" and="" fauna="" to="" be="" endangered="" or="" threatened="" or="" wild="" flora="" or="" fauna="" that="" are="" entitled="" to="" special="" protection="" under="" some="" other="" federal="" law.="" sec.="" 25.22="" actions="" requiring="" the="" preparation="" of="" an="" environmental="" impact="" statement.="" (a)="" there="" are="" no="" categories="" of="" agency="" actions="" that="" routinely="" significantly="" affect="" the="" quality="" of="" the="" human="" environment="" and="" that="" therefore="" ordinarily="" require="" the="" preparation="" of="" an="" eis.="" (b)="" eis's="" are="" prepared="" for="" agency="" actions="" when="" evaluation="" of="" data="" or="" information="" in="" an="" ea="" or="" otherwise="" available="" to="" the="" agency="" leads="" to="" a="" finding="" by="" the="" responsible="" agency="" official="" that="" a="" proposed="" action="" may="" significantly="" affect="" the="" quality="" of="" the="" human="" environment.="" subpart="" c--categorical="" exclusions="" sec.="" 25.30="" general.="" the="" classes="" of="" actions="" listed="" in="" this="" section="" and="" secs.="" 25.31="" through="" 25.34="" are="" categorically="" excluded="" and,="" therefore,="" ordinarily="" do="" not="" require="" the="" preparation="" of="" an="" ea="" or="" an="" eis:="" (a)="" routine="" administrative="" and="" management="" activities,="" including="" inspections,="" and="" issuance="" of="" field="" compliance="" programs,="" program="" circulars,="" or="" field="" investigative="" assignments.="" (b)="" recommendation="" for="" an="" enforcement="" action="" to="" be="" initiated="" in="" a="" federal="" court.="" (c)="" agency="" requests="" for="" initiation="" of="" recalls.="" (d)="" destruction="" or="" disposition="" of="" any="" fda-regulated="" article="" condemned="" after="" seizure="" or="" the="" distribution="" or="" use="" of="" which="" has="" been="" enjoined="" or="" following="" detention="" or="" recall="" at="" agency="" request="" if="" the="" method="" of="" destruction="" or="" disposition="" of="" the="" article,="" including="" packaging="" material,="" is="" in="" compliance="" with="" all="" federal,="" state,="" and="" local="" requirements.="" (e)="" extramural="" contracts,="" other="" agreements,="" or="" grants="" for="" statistical="" and="" epidemiological="" studies,="" surveys="" and="" inventories,="" literature="" searches,="" and="" report="" and="" manual="" preparation,="" or="" any="" other="" studies="" that="" will="" not="" result="" in="" the="" production="" or="" distribution="" of="" any="" substance="" and,="" therefore,="" will="" not="" result="" in="" the="" introduction="" of="" any="" substance="" into="" the="" environment.="" (f)="" extramural="" contracts,="" other="" agreements,="" and="" grants="" for="" research="" for="" such="" purposes="" as="" to="" develop="" analytical="" methods="" or="" other="" test="" methodologies.="" (g)="" activities="" of="" voluntary="" federal-state="" cooperative="" programs,="" including="" issuance="" of="" model="" regulations="" proposed="" for="" state="" adoption.="" (h)="" issuance,="" amendment,="" or="" revocation="" of="" procedural="" or="" administrative="" regulations="" and="" guidelines,="" including="" procedures="" for="" submission="" of="" applications="" for="" product="" development,="" testing="" and="" investigational="" use,="" and="" approval.="" (i)="" corrections="" and="" technical="" changes="" in="" regulations.="" (j)="" issuance="" of="" cgmp="" regulations,="" haccp="" regulations,="" establishment="" standards,="" emergency="" permit="" control="" regulations,="" glp="" regulations,="" and="" issuance="" or="" denial="" of="" permits,="" exemptions,="" variances,="" or="" stays="" under="" these="" regulations.="" (k)="" establishment="" or="" repeal="" by="" regulation="" of="" labeling="" requirements="" for="" marketed="" articles="" if="" there="" will="" be="" no="" increase="" in="" the="" existing="" levels="" of="" use="" or="" change="" in="" the="" intended="" uses="" of="" the="" product="" or="" its="" substitutes.="" (l)="" routine="" maintenance="" and="" minor="" construction="" activities="" such="" as:="" (1)="" repair="" to="" or="" replacement="" of="" equipment="" or="" structural="" components="" (e.g.,="" door,="" roof,="" or="" window)="" of="" facilities="" controlled="" by="" fda;="" (2)="" lease="" extensions,="" renewals,="" or="" succeeding="" leases;="" (3)="" construction="" or="" lease="" construction="" of="" 10,000="" square="" feet="" or="" less="" of="" occupiable="" space;="" (4)="" relocation="" of="" employees="" into="" existing="" owned="" or="" currently="" leased="" space;="" (5)="" acquisition="" of="" 20,000="" square="" feet="" or="" less="" of="" occupiable="" space="" in="" a="" structure="" that="" was="" substantially="" completed="" before="" the="" issuance="" of="" solicitation="" for="" offers;="" and="" (6)="" acquisition="" of="" between="" 20,000="" square="" feet="" and="" 40,000="" square="" feet="" of="" occupiable="" space="" if="" it="" constitutes="" less="" than="" 40="" percent="" of="" the="" occupiable="" space="" in="" a="" structure="" that="" was="" substantially="" completed="" before="" the="" solicitation="" for="" offers.="" (m)="" disposal="" of="" low-level="" radioactive="" waste="" materials="" (as="" defined="" in="" the="" nuclear="" regulatory="" commission="" regulations="" at="" 10="" cfr="" 61.2)="" and="" chemical="" waste="" materials="" generated="" in="" the="" laboratories="" serviced="" by="" the="" contracts="" administered="" by="" fda,="" if="" the="" waste="" is="" disposed="" of="" in="" compliance="" with="" all="" applicable="" federal,="" state,="" and="" local="" requirements.="" sec.="" 25.31="" human="" drugs="" and="" biologics.="" the="" classes="" of="" actions="" listed="" in="" this="" section="" are="" categorically="" excluded="" and,="" therefore,="" ordinarily="" do="" not="" require="" the="" preparation="" of="" an="" ea="" or="" an="" eis:="" (a)="" action="" on="" an="" nda,="" abbreviated="" application,="" or="" a="" supplement="" to="" such="" application,="" or="" action="" on="" an="" otc="" monograph,="" if="" the="" action="" does="" not="" increase="" the="" use="" of="" the="" active="" moiety.="" (b)="" action="" on="" an="" nda,="" abbreviated="" application,="" or="" a="" supplement="" to="" such="" application,="" or="" action="" on="" an="" otc="" monograph,="" if="" the="" action="" increases="" the="" use="" of="" the="" active="" moiety,="" but="" the="" concentration="" of="" the="" substance="" in="" the="" environment="" will="" be="" below="" 1="" part="" per="" billion.="" (c)="" action="" on="" an="" nda,="" abbreviated="" application,="" application="" for="" marketing="" approval="" of="" a="" biologic="" product,="" or="" a="" supplement="" to="" such="" application,="" or="" action="" on="" an="" otc="" monograph,="" for="" substances="" that="" occur="" naturally="" in="" the="" environment="" when="" the="" action="" does="" not="" alter="" significantly="" the="" concentration="" or="" distribution="" of="" the="" substance,="" its="" metabolites,="" or="" degradation="" products="" in="" the="" environment.="" (d)="" withdrawal="" of="" approval="" of="" an="" nda="" or="" an="" abbreviated="" application.="" (e)="" action="" on="" an="" ind.="" (f)="" testing="" and="" certification="" of="" batches="" of="" an="" antibiotic="" or="" insulin.="" (g)="" testing="" and="" release="" by="" the="" center="" for="" biologics="" evaluation="" and="" research="" of="" lots="" or="" batches="" of="" a="" licensed="" biologic="" product.="" (h)="" issuance,="" revocation,="" or="" amendment="" of="" a="" monograph="" for="" an="" antibiotic="" drug.="" (i)="" establishment="" of="" bioequivalence="" requirements="" for="" a="" human="" drug="" or="" a="" comparability="" determination="" for="" a="" biologic="" product="" subject="" to="" licensing.="" (j)="" issuance,="" revocation,="" or="" amendment="" of="" a="" standard="" for="" a="" biologic="" product.="" (k)="" revocation="" of="" a="" license="" for="" a="" biologic="" product.="" (l)="" action="" on="" an="" application="" for="" marketing="" approval="" for="" marketing="" of="" a="" biologic="" product="" for="" transfusable="" human="" blood="" or="" blood="" components="" and="" plasma.="" sec.="" 25.32="" foods,="" food="" additives,="" and="" color="" additives.="" the="" classes="" of="" actions="" listed="" in="" this="" section="" are="" categorically="" excluded="" and,="" [[page="" 14939]]="" therefore,="" ordinarily="" do="" not="" require="" the="" preparation="" of="" an="" ea="" or="" an="" eis:="" (a)="" issuance,="" amendment,="" or="" repeal="" of="" a="" food="" standard.="" (b)="" action="" on="" a="" request="" for="" exemption="" for="" investigational="" use="" of="" a="" food="" additive="" if="" the="" food="" additive="" to="" be="" shipped="" under="" the="" request="" is="" intended="" to="" be="" used="" for="" clinical="" studies="" or="" research.="" (c)="" approval="" of="" a="" color="" additive="" petition="" to="" change="" a="" provisionally="" listed="" color="" additive="" to="" permanent="" listing="" for="" use="" in="" food,="" drugs,="" devices,="" or="" cosmetics.="" (d)="" testing="" and="" certification="" of="" batches="" of="" a="" color="" additive.="" (e)="" issuance="" of="" an="" interim="" food="" additive="" regulation.="" (f)="" affirmation="" of="" a="" food="" substance="" as="" gras="" for="" humans="" or="" animals="" on="" fda's="" initiative="" or="" in="" response="" to="" a="" petition,="" under="" parts="" 182,="" 184,="" 186,="" or="" 582="" of="" this="" chapter,="" and="" establishment="" or="" amendment="" of="" a="" regulation="" for="" a="" prior-sanctioned="" food="" ingredient,="" as="" defined="" in="" secs.="" 170.3(l)="" and="" 181.5(a)="" of="" this="" chapter,="" if="" the="" substance="" or="" food="" ingredient="" is="" already="" marketed="" in="" the="" united="" states="" for="" the="" proposed="" use.="" (g)="" issuance="" and="" enforcement="" of="" regulations="" relating="" to="" the="" control="" of="" communicable="" diseases="" or="" to="" interstate="" conveyance="" sanitation="" under="" parts="" 1240="" and="" 1250="" of="" this="" chapter.="" (h)="" approval="" of="" a="" request="" for="" diversion="" of="" adulterated="" or="" misbranded="" food="" for="" humans="" or="" animals="" to="" use="" as="" animal="" feeds.="" (i)="" approval="" of="" a="" food="" additive="" petition="" or="" the="" granting="" of="" a="" request="" for="" exemption="" from="" regulation="" as="" a="" food="" additive="" under="" sec.="" 170.39="" of="" this="" chapter="" when="" the="" additive="" is="" present="" in="" finished="" food-packaging="" material="" at="" not="" greater="" than="" 5="" percent-by-weight="" and="" is="" also="" a="" functional="" component="" of="" the="" finished="" packaging="" material.="" (j)="" approval="" of="" a="" food="" additive="" petition="" or="" the="" granting="" of="" a="" request="" for="" exemption="" from="" regulation="" as="" a="" food="" additive="" under="" sec.="" 170.39="" of="" this="" chapter="" when="" the="" additive="" is="" to="" be="" used="" as="" a="" component="" of="" a="" food-contact="" surface="" of="" permanent="" or="" semipermanent="" equipment="" or="" of="" another="" food-contact="" article="" intended="" for="" repeated="" use.="" (k)="" approval="" of="" a="" food="" additive,="" color="" additive,="" or="" gras="" petition="" for="" substances="" added="" directly="" to="" food="" that="" are="" intended="" to="" remain="" in="" food="" through="" ingestion="" by="" consumers="" and="" that="" are="" not="" intended="" to="" replace="" macronutrients="" in="" food.="" (l)="" approval="" of="" a="" petition="" for="" color="" additives="" used="" in="" contact="" lenses,="" sutures,="" filaments="" used="" as="" supporting="" haptics="" in="" intraocular="" lenses,="" bone="" cement,="" and="" in="" other="" fda-regulated="" products="" having="" similarly="" low="" levels="" of="" use.="" (m)="" action="" to="" prohibit="" or="" otherwise="" restrict="" or="" reduce="" the="" use="" of="" a="" substance="" in="" food,="" food="" packaging,="" or="" cosmetics.="" (n)="" issuance,="" amendment,="" or="" revocation="" of="" a="" regulation="" pertaining="" to="" infant="" formulas.="" (o)="" approval="" of="" a="" food="" additive="" petition="" for="" the="" intended="" expression="" product(s)="" present="" in="" food="" derived="" from="" new="" plant="" varieties.="" (p)="" issuance,="" amendment,="" or="" revocation="" of="" a="" regulation="" in="" response="" to="" a="" reference="" amount="" petition="" as="" described="" in="" sec.="" 101.12(h)="" of="" this="" chapter,="" a="" nutrient="" content="" claim="" petition="" as="" described="" in="" sec.="" 101.69="" of="" this="" chapter,="" a="" health="" claim="" petition="" as="" described="" in="" sec.="" 101.70="" of="" this="" chapter,="" or="" a="" petition="" pertaining="" to="" the="" label="" declaration="" of="" ingredients="" as="" described="" in="" sec.="" 101.103="" of="" this="" chapter.="" (q)="" approval="" of="" a="" food="" additive="" petition="" or="" the="" granting="" of="" a="" request="" for="" an="" exemption="" from="" regulation="" as="" a="" food="" additive="" under="" sec.="" 170.39="" of="" this="" chapter="" for="" a="" substance="" registered="" by="" the="" environmental="" protection="" agency="" under="" fifra="" for="" the="" same="" use="" requested="" in="" the="" petition.="" (r)="" approval="" of="" a="" food="" additive,="" color="" additive,="" or="" gras="" affirmation="" petition="" for="" a="" substance="" that="" occurs="" naturally="" in="" the="" environment,="" when="" the="" action="" does="" not="" alter="" significantly="" the="" concentration="" or="" distribution="" of="" the="" substance,="" its="" metabolites,="" or="" degradation="" products="" in="" the="" environment.="" sec.="" 25.33="" animal="" drugs.="" the="" classes="" of="" actions="" listed="" in="" this="" section="" are="" categorically="" excluded="" and,="" therefore,="" ordinarily="" do="" not="" require="" the="" preparation="" of="" an="" ea="" or="" an="" eis:="" (a)="" action="" on="" an="" nada,="" abbreviated="" application,="" or="" supplement="" to="" such="" applications,="" if="" the="" action="" does="" not="" increase="" the="" use="" of="" the="" drug.="" actions="" to="" which="" this="" categorical="" exclusion="" applies="" include:="" (1)="" an="" animal="" drug="" to="" be="" marketed="" under="" the="" same="" conditions="" of="" approval="" as="" a="" previously="" approved="" animal="" drug;="" (2)="" a="" combination="" of="" previously="" approved="" animal="" drugs;="" (3)="" a="" new="" premix="" or="" other="" formulation="" of="" a="" previously="" approved="" animal="" drug;="" (4)="" changes="" specified="" in="" sec.="" 514.8(a)(5),="" (a)(6),="" or="" (d)="" of="" this="" chapter;="" (5)="" a="" change="" of="" sponsor;="" (6)="" a="" previously="" approved="" animal="" drug="" to="" be="" contained="" in="" medicated="" feed="" blocks="" under="" sec.="" 510.455="" of="" this="" chapter="" or="" as="" a="" liquid="" feed="" supplement="" under="" sec.="" 558.5="" of="" this="" chapter;="" or="" (7)="" approval="" of="" a="" drug="" for="" use="" in="" animal="" feeds="" if="" such="" drug="" has="" been="" approved="" under="" sec.="" 514.2="" or="" 514.9="" of="" this="" chapter="" for="" other="" uses.="" (b)="" [reserved]="" (c)="" action="" on="" an="" nada,="" abbreviated="" application,="" or="" a="" supplement="" for="" substances="" that="" occur="" naturally="" in="" the="" environment="" when="" the="" action="" does="" not="" alter="" significantly="" the="" concentration="" or="" distribution="" of="" the="" substance,="" its="" metabolites,="" or="" degradation="" products="" in="" the="" environment.="" (d)="" action="" on="" an="" nada,="" abbreviated="" application,="" or="" a="" supplement="" to="" such="" applications,="" for:="" (1)="" drugs="" intended="" for="" use="" in="" nonfood="" animals;="" (2)="" anesthetics,="" both="" local="" and="" general,="" that="" are="" individually="" administered;="" (3)="" nonsystemic="" topical="" and="" ophthalmic="" animal="" drugs;="" (4)="" drugs="" for="" minor="" species,="" including="" wildlife="" and="" endangered="" species,="" when="" the="" drug="" has="" been="" previously="" approved="" for="" use="" in="" another="" or="" the="" same="" species="" where="" similar="" animal="" management="" practices="" are="" used;="" and="" (5)="" drugs="" intended="" for="" use="" under="" prescription="" or="" veterinarian's="" order="" for="" therapeutic="" use.="" (e)="" action="" on="" an="" inad.="" (f)="" action="" on="" an="" application="" submitted="" under="" section="" 512(m)="" of="" the="" act.="" (g)="" withdrawal="" of="" approval="" of="" an="" nada="" or="" an="" abbreviated="" nada.="" (h)="" withdrawal="" of="" approval="" of="" a="" food="" additive="" petition="" that="" reduces="" or="" eliminates="" animal="" feed="" uses="" of="" a="" food="" additive.="" sec.="" 25.34="" devices="" and="" electronic="" products.="" the="" classes="" of="" actions="" listed="" in="" this="" section="" are="" categorically="" excluded="" and,="" therefore,="" ordinarily="" do="" not="" require="" the="" preparation="" of="" an="" ea="" or="" an="" eis:="" (a)="" action="" on="" a="" device="" premarket="" notification="" submission="" under="" subpart="" e="" of="" part="" 807="" of="" this="" chapter.="" (b)="" classification="" or="" reclassification="" of="" a="" device="" under="" part="" 860="" of="" this="" chapter.="" (c)="" issuance,="" amendment,="" or="" repeal="" of="" a="" standard="" for="" a="" class="" ii="" medical="" device="" or="" an="" electronic="" product,="" and="" issuance="" of="" exemptions="" or="" variances="" from="" such="" a="" standard.="" (d)="" approval="" of="" a="" pma="" or="" a="" notice="" of="" completion="" of="" a="" pdp="" or="" amended="" or="" supplemental="" applications="" or="" notices="" for="" a="" class="" iii="" medical="" device="" if="" the="" device="" is="" of="" the="" same="" type="" and="" for="" the="" same="" use="" as="" a="" previously="" approved="" device.="" (e)="" changes="" in="" the="" pma="" or="" a="" notice="" of="" completion="" of="" a="" pdp="" for="" a="" class="" iii="" medical="" device="" that="" do="" not="" require="" submission="" of="" an="" amended="" or="" supplemental="" application="" or="" notice.="" (f)="" issuance="" of="" a="" restricted="" device="" regulation="" if="" it="" will="" not="" result="" in="" increases="" in="" the="" existing="" levels="" of="" use="" or="" changes="" in="" the="" intended="" uses="" of="" the="" product="" or="" its="" substitutes.="" [[page="" 14940]]="" (g)="" action="" on="" an="" application="" for="" an="" ide="" or="" an="" authorization="" to="" commence="" a="" clinical="" investigation="" under="" an="" approved="" pdp.="" (h)="" issuance="" of="" a="" regulation="" exempting="" from="" preemption="" a="" requirement="" of="" a="" state="" or="" political="" subdivision="" concerning="" a="" device,="" or="" a="" denial="" of="" an="" application="" for="" such="" exemption.="" subpart="" d--preparation="" of="" environmental="" documents="" sec.="" 25.40="" environmental="" assessments.-="" (a)="" as="" defined="" by="" ceq="" in="" 40="" cfr="" 1508.9,="" an="" ea="" is="" a="" concise="" public="" document="" that="" serves="" to="" provide="" sufficient="" evidence="" and="" analysis="" for="" an="" agency="" to="" determine="" whether="" to="" prepare="" an="" eis="" or="" a="" fonsi.="" the="" ea="" shall="" include="" brief="" discussions="" of="" the="" need="" for="" the="" proposal,="" of="" alternatives="" as="" required="" by="" section="" 102(2)(e)="" of="" nepa,="" of="" the="" environmental="" impacts="" of="" the="" proposed="" action="" and="" alternatives,="" and="" a="" listing="" of="" agencies="" and="" persons="" consulted.="" an="" ea="" shall="" be="" prepared="" for="" each="" action="" not="" categorically="" excluded="" in="" secs.="" 25.30,="" 25.31,="" 25.32,="" 25.33,="" or="" 25.34.="" the="" ea="" shall="" focus="" on="" relevant="" environmental="" issues="" and="" shall="" be="" a="" concise,="" objective,="" and="" well-balanced="" document="" that="" allows="" the="" public="" to="" understand="" the="" agency's="" decision.="" if="" potentially="" adverse="" environmental="" impacts="" are="" identified="" for="" an="" action="" or="" group="" of="" related="" actions,="" the="" ea="" shall="" discuss="" any="" reasonable="" alternative="" course="" of="" action="" that="" offers="" less="" environmental="" risk="" or="" that="" is="" environmentally="" preferable="" to="" the="" proposed="" action.="" the="" use="" of="" a="" scientifically="" justified="" tiered="" testing="" approach,="" in="" which="" testing="" may="" be="" stopped="" when="" the="" results="" suggest="" that="" no="" significant="" impact="" will="" occur,="" is="" an="" acceptable="" approach.="" (b)="" generally,="" fda="" requires="" an="" applicant="" to="" prepare="" an="" ea="" and="" make="" necessary="" corrections="" to="" it.="" ultimately,="" fda="" is="" responsible="" for="" the="" scope="" and="" content="" of="" ea's="" and="" may="" include="" additional="" information="" in="" environmental="" documents="" when="" warranted.="" (c)="" information="" concerning="" the="" nature="" and="" scope="" of="" information="" that="" an="" applicant="" or="" petitioner="" shall="" submit="" in="" an="" ea="" may="" be="" obtained="" from="" the="" center="" or="" other="" office="" of="" the="" agency="" having="" responsibility="" for="" the="" action="" that="" is="" the="" subject="" of="" the="" environmental="" evaluation.="" applicants="" and="" petitioners="" are="" encouraged="" to="" submit="" proposed="" protocols="" for="" environmental="" studies="" for="" technical="" review="" by="" agency="" staff.="" applicants="" and="" petitioners="" also="" are="" encouraged="" to="" consult="" applicable="" fda="" ea="" guidance="" documents,="" which="" provide="" additional="" advice="" on="" how="" to="" comply="" with="" fda="" regulations.="" (d)="" consistent="" with="" 40="" cfr="" 1500.4(j)="" and="" 1502.21,="" ea's="" may="" incorporate="" by="" reference="" information="" presented="" in="" other="" documents="" that="" are="" available="" to="" fda="" and="" to="" the="" public.="" (e)="" the="" agency="" evaluates="" the="" information="" contained="" in="" an="" ea="" and="" any="" public="" input="" to="" determine="" whether="" it="" is="" accurate="" and="" objective,="" whether="" the="" proposed="" action="" may="" significantly="" affect="" the="" quality="" of="" the="" human="" environment,="" and="" whether="" an="" eis="" or="" fonsi="" will="" be="" prepared.="" the="" responsible="" agency="" official="" designated="" in="" part="" 5="" of="" this="" chapter="" as="" responsible="" for="" the="" underlying="" action="" examines="" the="" environmental="" risks="" of="" the="" proposed="" action="" and="" the="" alternative="" courses="" of="" action,="" selects="" a="" course="" of="" action,="" and="" ensures="" that="" any="" necessary="" mitigating="" measures="" are="" implemented="" as="" a="" condition="" for="" approving="" the="" selected="" course="" of="" action.="" sec.="" 25.41="" findings="" of="" no="" significant="" impact.="" (a)="" as="" defined="" by="" the="" ceq="" regulations="" (40="" cfr="" 1508.13),="" a="" fonsi="" is="" a="" document="" prepared="" by="" a="" federal="" agency="" stating="" briefly="" why="" an="" action,="" not="" otherwise="" excluded,="" will="" not="" significantly="" affect="" the="" human="" environment="" and="" for="" which,="" therefore,="" an="" eis="" will="" not="" be="" prepared.="" a="" fonsi="" includes="" the="" ea="" or="" a="" summary="" of="" it="" and="" a="" reference="" to="" any="" other="" related="" environmental="" documents.="" (b)="" the="" agency="" official(s)="" responsible="" for="" approving="" the="" fonsi="" will="" sign="" the="" document,="" thereby="" establishing="" that="" the="" official(s)="" approve(s)="" the="" conclusion="" not="" to="" prepare="" an="" eis="" for="" the="" action="" under="" consideration.="" sec.="" 25.42="" environmental="" impact="" statements.="" (a)="" as="" defined="" by="" ceq="" regulations="" (40="" cfr="" 1508.11)="" and="" section="" 102(2)(c)="" of="" nepa,="" an="" eis="" should="" be="" a="" clear,="" concise,="" and="" detailed="" written="" statement="" describing:="" (1)="" the="" environmental="" impacts="" of="" a="" proposed="" action;="" (2)="" any="" adverse="" effects="" that="" cannot="" be="" avoided="" if="" the="" action="" is="" implemented;="" (3)="" alternatives="" to="" the="" action;="" (4)="" the="" relationship="" between="" local="" short-term="" uses="" of="" the="" environment="" and="" the="" maintenance="" and="" enhancement="" of="" long-term="" productivity;="" and="" (5)="" any="" irreversible="" and="" irretrievable="" commitments="" of="" resources="" that="" would="" be="" involved="" in="" the="" proposed="" action="" should="" it="" be="" implemented.="" (b)="" the="" ceq="" regulations="" (40="" cfr="" 1501.7="" and="" part="" 1502)="" describe="" the="" process="" for="" determining="" the="" scope="" of="" an="" eis="" and="" provide="" detailed="" requirements="" for="" the="" preparation="" of="" draft="" and="" final="" eis's.="" ceq="" format="" and="" procedures="" for="" preparing="" eis="" shall="" be="" followed.="" (c)="" under="" the="" conditions="" prescribed="" in="" 40="" cfr="" 1502.9,="" the="" agency="" will="" prepare="" a="" supplement="" for="" a="" draft="" or="" final="" eis="" and="" introduce="" the="" supplement="" into="" the="" administrative="" record.="" sec.="" 25.43="" records="" of="" decisions.="" (a)="" in="" cases="" requiring="" environmental="" impact="" statements,="" at="" the="" time="" of="" its="" decision,="" the="" agency="" shall="" prepare="" a="" concise="" public="" record="" of="" decision.="" (b)="" the="" record="" of="" decision="" shall:="" (1)="" state="" what="" the="" decision="" was;="" (2)="" identify="" and="" discuss="" alternatives="" considered="" by="" the="" agency="" in="" reaching="" its="" decision;="" (3)="" state="" whether="" all="" practicable="" means="" to="" avoid="" or="" minimize="" environmental="" harm="" have="" been="" adopted,="" and="" if="" not,="" why="" not;="" and="" (4)="" discuss="" and="" implement="" any="" monitoring="" and="" enforcement="" program="" necessary="" to="" affect="" mitigation.="" sec.="" 25.44="" lead="" and="" cooperating="" agencies.--="" for="" actions="" requiring="" the="" preparation="" of="" an="" eis,="" fda="" and="" other="" affected="" federal="" agencies="" will="" agree="" which="" will="" be="" the="" lead="" agency="" and="" which="" will="" be="" the="" cooperating="" agencies.="" the="" responsibilities="" of="" lead="" agencies="" and="" cooperating="" agencies="" are="" described="" in="" the="" ceq="" regulations="" (40="" cfr="" 1501.5="" and="" 1501.6,="" respectively).="" if="" an="" action="" affects="" more="" than="" one="" center="" within="" fda,="" the="" commissioner="" of="" food="" and="" drugs="" will="" designate="" one="" of="" these="" units="" to="" be="" responsible="" for="" coordinating="" the="" preparation="" of="" any="" required="" environmental="" documentation.="" sec.="" 25.45="" responsible="" agency="" official.="" (a)="" the="" person="" designated="" in="" part="" 5="" of="" this="" chapter="" as="" the="" responsible="" agency="" official="" for="" the="" underlying="" action="" is="" responsible="" for="" preparing="" environmental="" documents="" or="" ensuring="" that="" they="" are="" prepared.="" (b)="" the="" responsible="" agency="" official="" will="" weigh="" any="" environmental="" impacts="" of="" each="" alternative="" course="" of="" action,="" including="" possible="" mitigation="" measures,="" and="" will="" balance="" environmental="" impacts="" with="" the="" agency's="" objectives="" in="" choosing="" an="" appropriate="" course="" of="" action.="" the="" weighing="" of="" any="" environmental="" impacts="" of="" alternatives="" in="" selecting="" a="" final="" course="" of="" action="" will="" be="" reflected="" in="" the="" agency's="" record="" of="" formal="" decisionmaking="" as="" required="" by="" 40="" cfr="" 1505.2.="" subpart="" e--public="" participation="" and="" notification="" of="" environmental="" documents="" sec.="" 25.50="" general="" information.="" (a)="" to="" the="" extent="" actions="" are="" not="" protected="" from="" disclosure="" by="" existing="" law="" applicable="" to="" the="" agency's="" operation,="" fda="" will="" involve="" the="" public="" [[page="" 14941]]="" in="" preparing="" and="" implementing="" its="" nepa="" procedures="" and="" will="" provide="" public="" notice="" of="" nepa-related="" hearings,="" public="" meetings,="" and="" the="" availability="" of="" environmental="" documents.="" (b)="" many="" fda="" actions="" involving="" investigations,="" review,="" and="" approval="" of="" applications,="" and="" premarket="" notifications="" for="" human="" drugs,="" animal="" drugs,="" biologic="" products,="" and="" devices="" are="" protected="" from="" disclosure="" under="" the="" trade="" secret="" act,="" 18="" u.s.c.="" 1905,="" and="" 301(j)="" of="" the="" act.="" these="" actions="" are="" also="" protected="" from="" disclosure="" under="" fda's="" regulations="" including="" part="" 20,="" secs.="" 312.130(a),="" 314.430(b),="" 514.11(b),="" 514.12(a),="" 601.50(a),="" 601.51(a),="" 807.95(b),="" 812.38(a),="" and="" 814.9(b)="" of="" this="" chapter.="" even="" the="" existence="" of="" applications="" for="" human="" drugs,="" animal="" drugs,="" biologic="" products,="" and="" devices="" is="" protected="" from="" disclosure="" under="" these="" regulations.="" therefore,="" unless="" the="" existence="" of="" applications="" for="" human="" drugs,="" animal="" drugs,="" biologic="" products,="" or="" premarket="" notification="" for="" devices="" has="" been="" made="" publicly="" available,="" the="" release="" of="" the="" environmental="" document="" before="" approval="" of="" human="" drugs,="" animal="" drugs,="" biologic="" products,="" and="" devices="" is="" inconsistent="" with="" statutory="" requirements="" imposed="" on="" fda.="" appropriate="" environmental="" documents,="" comments,="" and="" responses="" will="" be="" included="" in="" the="" administrative="" record="" to="" the="" extent="" allowed="" by="" applicable="" laws.="" sec.="" 25.51="" environmental="" assessments="" and="" findings="" of="" no="" significant="" -="" impact.="" (a)="" data="" and="" information="" that="" are="" protected="" from="" disclosure="" by="" 18="" u.s.c.="" 1905="" or="" 21="" u.s.c.="" 331(j)="" or="" 360j(c)="" shall="" not="" be="" included="" in="" the="" portion="" of="" environmental="" documents="" that="" is="" made="" public.="" when="" such="" data="" and="" information="" are="" pertinent="" to="" the="" environmental="" review="" of="" a="" proposed="" action,="" an="" applicant="" or="" petitioner="" shall="" submit="" such="" data="" and="" information="" separately="" in="" a="" confidential="" section="" we="" have="" spend="" 20="" years="" trying="" to="" keep="" confidential="" information="" out="" of="" eas.="" i="" suggest="" the="" preceding="" revision.="" gail="" said="" she="" prefers="" confidential="" appendix="" to="" the="" ea.and="" shall="" summarize="" the="" confidential="" data="" and="" information="" in="" the="" ea="" to="" the="" extent="" possible.="" (b)="" fonsi's="" and="" ea's="" will="" be="" available="" to="" the="" public="" in="" accordance="" with="" 40="" cfr="" 1506.6="" as="" follows:="" (1)="" when="" the="" proposed="" action="" is="" the="" subject="" of="" a="" notice="" of="" proposed="" rulemaking="" or="" a="" notice="" of="" filing="" published="" in="" the="" federal="" register,="" the="" notice="" shall="" state="" that="" no="" eis="" is="" necessary="" and="" that="" the="" fonsi="" and="" the="" ea="" are="" available="" for="" public="" inspection="" at="" fda's="" dockets="" management="" branch.="" if="" the="" responsible="" agency="" official="" is="" unable="" to="" complete="" environmental="" consideration="" of="" the="" proposed="" action="" before="" a="" notice="" of="" filing="" of="" a="" food="" or="" color="" additive="" petition="" is="" required="" to="" be="" published="" under="" the="" act,="" and="" if="" the="" subsequent="" environmental="" analysis="" leads="" to="" the="" conclusion="" that="" no="" eis="" is="" necessary,="" the="" federal="" register="" document="" publishing="" the="" final="" regulation="" rather="" than="" the="" notice="" of="" filing="" shall="" state="" that="" no="" eis="" is="" necessary="" and="" that="" the="" fonsi="" and="" the="" ea="" are="" available="" upon="" request="" and="" filed="" in="" fda's="" dockets="" management="" branch.="" (2)="" for="" actions="" for="" which="" notice="" is="" not="" published="" in="" the="" federal="" register,="" the="" fonsi="" and="" the="" ea="" shall="" be="" made="" available="" to="" the="" public="" upon="" request="" according="" to="" the="" procedures="" in="" 40="" cfr="" 1506.6.="" (3)="" for="" a="" limited="" number="" of="" actions,="" the="" agency="" may="" make="" the="" fonsi="" and="" ea="" available="" for="" public="" review="" (including="" review="" by="" state="" and="" areawide="" information="" clearinghouses)="" for="" 30="" days="" before="" the="" agency="" makes="" its="" final="" determination="" whether="" to="" prepare="" an="" eis="" and="" before="" the="" action="" may="" begin,="" as="" described="" in="" 40="" cfr="" 1501.4(e).="" this="" procedure="" will="" be="" followed="" when="" the="" proposed="" action="" is,="" or="" is="" closely="" similar="" to,="" one="" that="" normally="" requires="" an="" eis="" or="" when="" the="" proposed="" action="" is="" one="" without="" precedent.="" sec.="" 25.52="" environmental="" impact="" statements.="" (a)="" if="" fda="" determines="" that="" an="" eis="" is="" necessary="" for="" an="" action="" involving="" investigations="" or="" approvals="" for="" drugs,="" animal="" drugs,="" biologic="" products,="" or="" devices,="" an="" eis="" will="" be="" prepared="" but="" will="" become="" available="" only="" at="" the="" time="" of="" the="" approval="" of="" the="" product.="" disclosure="" will="" be="" made="" in="" accordance="" with="" 40="" cfr="" 1506.6="" and="" part="" 20="" of="" this="" chapter.="" the="" eis="" will="" in="" all="" other="" respects="" conform="" to="" the="" requirements="" for="" eis's="" as="" specified="" in="" 40="" cfr="" part="" 1502="" and="" 1506.6(f).="" (b)="" comments="" on="" the="" eis="" may="" be="" submitted="" after="" the="" approvalof="" the="" drug,="" animal="" drug,="" biologic="" product,="" and="" device.="" those="" comments="" can="" form="" the="" basis="" for="" the="" agency="" to="" consider="" beginning="" an="" action="" to="" withdraw="" the="" approval="" of="" applications="" for="" a="" drug,="" animal="" drug,="" biologic="" product,="" or="" to="" withdraw="" premarket="" notifications="" or="" premarket="" approval="" applications="" for="" devices.="" (c)="" in="" those="" cases="" where="" the="" existence="" of="" applications="" and="" premarket="" notifications="" for="" drugs,="" animal="" drugs,="" biologic="" products,="" or="" devices="" has="" already="" been="" disclosed="" before="" the="" agency="" approves="" the="" action,="" the="" agency="" will="" make="" diligent="" effort="" (40="" cfr="" 1506.6)="" to="" involve="" the="" public="" in="" preparing="" and="" implementing="" the="" nepa="" procedures="" for="" eis's="" while="" following="" its="" own="" disclosure="" requirements="" including="" those="" listed="" in="" part="" 20,="" secs.="" 312.130(b),="" 314.430(d),="" 514.11(d),="" 514.12(b),="" 601.51(d),="" 807.95(e),="" 812.38(b),="" and="" 814.9(d)="" of="" this="" chapter.="" (d)="" draft="" and="" final="" eis's,="" comments,="" and="" responses="" will="" be="" included="" in="" the="" administrative="" record="" and="" will="" be="" available="" from="" the="" dockets="" management="" branch="" (hfa-305),="" food="" and="" drug="" administration,="" 12420="" parklawn="" dr.,="" rm.="" 1-23,="" rockville,="" md="" 20857.="" subpart="" f--other="" requirements="" sec.="" 25.60="" environmental="" effects="" abroad="" of="" major="" agency="" actions.="" (a)="" in="" accordance="" with="" executive="" order="" 12114,="" ``environmental="" effects="" abroad="" of="" major="" federal="" actions''="" of="" january="" 4,="" 1979="" (44="" fr="" 1957,="" january="" 9,="" 1977),="" the="" responsible="" agency="" official,="" in="" analyzing="" actions="" under="" his="" or="" her="" program,="" shall="" consider="" the="" environmental="" effects="" abroad,="" including="" whether="" the="" actions="" involve:="" (1)="" potential="" environmental="" effects="" on="" the="" global="" commons="" and="" areas="" outside="" the="" jurisdiction="" of="" any="" nation,="" e.g.,="" oceans="" and="" the="" upper="" atmosphere.="" (2)="" potential="" environmental="" effects="" on="" a="" foreign="" nation="" not="" participating="" with="" or="" otherwise="" involved="" in="" an="" fda="" activity.="" (3)="" the="" export="" of="" products="" (or="" emissions)="" that="" in="" the="" united="" states="" are="" prohibited="" or="" strictly="" regulated="" because="" their="" effects="" on="" the="" environment="" create="" a="" serious="" public="" health="" risk.="" (4)="" potential="" environmental="" effects="" on="" natural="" and="" ecological="" resources="" of="" global="" importance="" designated="" under="" the="" executive="" order.="" (b)="" before="" deciding="" on="" any="" action="" falling="" into="" the="" categories="" specified="" in="" paragraph="" (a)="" of="" this="" section,="" the="" responsible="" agency="" official="" shall="" determine="" in="" accordance="" with="" section="" 2-3="" of="" the="" executive="" order="" whether="" such="" actions="" may="" have="" a="" significant="" environmental="" effect="" abroad.="" (c)="" if="" the="" responsible="" agency="" official="" determines="" that="" an="" action="" may="" have="" a="" significant="" environmental="" effect="" abroad,="" the="" responsible="" agency="" official="" shall="" determine="" in="" accordance="" with="" section="" 2-4(a)="" and="" (b)="" of="" the="" executive="" order,="" whether="" the="" subject="" action="" calls="" for:="" (1)="" an="" eis;="" (2)="" a="" bilateral="" or="" multilateral="" environmental="" study;="" or="" (3)="" a="" concise="" environmental="" review.="" (d)="" in="" preparing="" environmental="" documents="" under="" this="" subpart,="" the="" responsible="" official="" shall:="" (1)="" determine,="" as="" provided="" in="" section="" 2-5="" of="" the="" executive="" order,="" whether="" proposed="" actions="" are="" subject="" to="" the="" exemptions,="" exclusions,="" and="" [[page="" 14942]]="" modification="" in="" contents,="" timing,="" and="" availability="" of="" documents.="" (2)="" coordinate="" all="" communications="" with="" foreign="" governments="" concerning="" environmental="" agreements="" and="" other="" arrangements="" in="" implementing="" the="" executive="" order.="" dated:="" march="" 19,="" 1996.="" william="" b.="" schultz,="" deputy="" commissioner="" for="" policy.="" [fr="" doc.="" 96-8090="" filed="" 4-2-96;="" 8:45="" am]="" billing="" code="" 4160-01-f="">