19476 Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 25

[Docket No. 96N–0057]

National Environmental Policy Act;

Proposed Revision of Policies and

Procedures

Note: This document was originally

published at 61 FR 14922, Wednesday, April

3, 1996. Certain text inadvertently appeared

in the printed version. For the convenience

of the reader, the document is being

republished in its entirety.

AGENCY: Food and Drug Administration,

HHS.

ACTION: Proposed rule.

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 § 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
Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules 19477

by FDA and, consequently, reduce the

number of findings of no significant

impact (FONSI’s) the agency would be

required to prepare. Furthermore, the

proposal will not compromise the

environment because the excluded

actions have been found not to have a

significant effect on the environment,

and the proposed rule would continue

to provide for the preparation of an EA

under extraordinary circumstances in

which a categorically excluded action

may have a significant environmental

impact. This proposal would enable

FDA to focus its resources in the

environmental area on situations likely

to have an effect on the environment.

The agency is also proposing to revise

its environmental regulations to make

them more concise and useful to the

public and regulated industry by

reorganizing, simplifying, and

eliminating unnecessary and

duplicative language. The proposed rule

would reorganize and renumber various

sections so that information on certain

topics is grouped together. The agency

solicits comments on and suggestions

for further improvement in these

regulations.

III. Specific Proposed Changes

A. General Provisions

The proposed rule would eliminate

unnecessary language in current subpart

A of part 25 by deleting the reference to

the environmental statutes listed in

current § 25.5 Policies, amending

§ 25.15 Terminology (proposed § 25.5),

and making other minor revisions,

including combining § 25.5 Policies and

§ 25.10 NEPA planning into proposed

§ 25.10 Policies and NEPA planning.

In proposed § 25.5 Terminology, FDA

is proposing to remove definitions listed

in current § 25.15 that are not used in

part 25, and add new definitions for

‘‘active moiety’’ and ‘‘increased use’’ of

a drug. ‘‘Increased use’’ of a drug will

occur if the drug will be administered

at higher dosage levels, for longer

duration, or for different indications

than were previously in effect, or if the

drug is a new molecular entity.

‘‘Increased use’’ encompasses

consideration of FDA-regulated articles

that are disposed of by consumers.

‘‘Active moiety’’ has been previously

defined in FDA regulations (21 CFR

314.108(a)).

B. Agency Actions Requiring

Environmental Consideration

Proposed § 25.15 would contain the

general procedural information now

found in current §§ 25.20 and 25.22.

The proposed rule would create new

§ 25.l6 Public health and safety

emergencies using revised language now

contained in current § 25.40(b).

Actions requiring preparation of an

EA (proposed § 25.20) would remain

essentially the same as current § 25.22,

except that: (1) Current § 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 § 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 § 25.22(a)(14)), issuance

of licenses for biologic products (current

§ 25.22(a)(16)), and approval of

supplements to existing approvals of

FDA-regulated articles (§ 25.22(a)(8))

have been combined into one provision

(proposed § 25.20(l)) and revised to

reflect current terminology.

The proposed regulations include

new § 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 § 25.21

incorporates current § 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 § 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

§ 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 § 25.21

reflect criteria that appear in some of the

categorical exclusions listed in current

§ 25.24. The language in the first

example, proposed § 25.21(a), is derived

from but differs slightly from current

§ 25.24 language relating to toxicity (see,

e.g., § 25.24(a)(10), (b)(2), and (c)(6)).

The extraordinary circumstance

example in proposed § 25.21(a) would

revise the language in current § 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 § 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 § 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
19478 Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules

account any ecotoxicity data relevant to

the issue.

The second example of extraordinary

circumstances relates to instances in

which the proposed action could

adversely affect an endangered or

threatened species, or a species entitled

to protection under some other Federal

law. FDA intends to closely examine

proposed actions that involve FDAregulated 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 § 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 FDAregulated 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

§ 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; § 25.31 Human drugs

and biologics; § 25.32 Foods, food

additives, and color additives; § 25.33

Animal drugs, and § 25.34 Devices and

electronic products. The agency is also

proposing to delete the general

introductory language from current

§ 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 § 25.24(a)

(proposed § 25.30) and to make certain

revisions described below:

Current § 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 § 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 § 25.21

Extraordinary circumstances.

The agency is proposing to revise the

categorical exclusion for current good

manufacturing practice (CGMP)

regulations (§ 25.24(a)(10), proposed

§ 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

§ 25.30(m)) for actions relating to the

disposal of the hazardous laboratory

waste materials generated in FDA

laboratories (low-level radioactive waste

and chemical waste). Today, all of this

hazardous waste is disposed of under

contract with a hazardous waste

management firm. The contractor is

responsible for the collection, handling,

storage, packing, and ultimate disposal

of the waste materials at facilities

permitted by the U.S. Environmental

Protection Agency (EPA) and/or

facilities licensed by the Nuclear

Regulatory Commission (NRC). In

awarding contracts, FDA takes into

consideration whether a prospective

contractor has all applicable licenses,

permits, and insurance necessary to

perform the work and transport the

waste as required under the contract.

The contractor and all disposal facilities

must certify that they are in full

compliance with all applicable Federal,

State, and local requirements, before

FDA will award the contract. Further,

FDA requires the contractor to present

a comprehensive operational plan. FDA

reviews this plan to determine if the

contractor’s approach is complete, safe,

appropriate, and responsive to, among

other things, FDA’s requirements for

waste disposal. Further, the contractor

must operate in full compliance with

appropriate regulations issued by EPA

(Title 40), the Department of

Transportation (Title 49), the

Department of Labor (Title 29), NRC

(Title 10), and with relevant State and

local regulations governing the disposal

of hazardous and nonhazardous waste.

Therefore, FDA is proposing in

§ 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 § 25.31(a) and (b) apply to

actions on an NDA, abbreviated

application or a supplement to such
Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules 19479

applications, or action on an over-thecounter (OTC) monograph. They are

divided into two sections: (1) Proposed

§ 25.31(a), which applies if FDA’s action

does not increase the use and disposal

of the drug; and (2) proposed § 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 § 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

§ 25.31(a) is based on the categorical

exclusions in current § 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

§ 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 § 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 § 25.31(a) and (b) include

actions on NDA’s. Under the current

regulations (§ 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 § 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 § 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 § 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 § 25.31(a) and (b) would

also delete any reference to ‘‘actions on

amendments’’ to clarify that the agency
19480 Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules

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 § 25.31(a) and (b) applies to

drugs regulated by CDER. FDA is

proposing a new categorical exclusion

in § 25.31(c) for substances that occur

naturally in the environment, that

would apply to both drugs and

biologics. Proposed § 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 § 25.31(d) to

expand the categorical exclusion

provision for the withdrawal of

approval of an NDA or abbreviated

application. The agency is proposing

that all types of withdrawals of

approval, whether requested by industry

or initiated by the agency, be

categorically excluded because, based

on CDER’s experience, these types of

actions will not result in the production

or distribution of any substances and,

therefore, will not result in the

introduction of any substance into the

environment.

Proposed § 25.31(e) would revise the

categorical exclusions for actions on an

IND. Current § 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 § 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 § 25.21

Extraordinary circumstances.

Proposed § 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 § 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 § 25.31(j) incorporates

current § 25.24(c)(10), the categorical

exclusion for promulgation,

amendment, or revocation of a standard

for a licensed biologic product, and

would eliminate the current

requirement that there be no increased

use of the product. Issuance of

additional standards for biologic

products (21 CFR parts 620 through 680)

does not increase the use of a product.

The standards normally explain how the

product is to be manufactured and any

additional requirements for approval

and marketing. Therefore, the increased

use criterion is unnecessary.

Proposed § 25.31(k), regarding

revocation of a biologic product, would

eliminate the current criteria in

§ 25.24(c)(9) that the biological product

‘‘is no longer being marketed’’ or that

the action is ‘‘at the request of the

license holder.’’ The agency is

proposing to delete these criteria as

unnecessary because revocation of a

license for a biologic product means that

the product can no longer be marketed.

Marketing of the product after license

revocation must cease regardless of

whether the revocation was at the

request of the license holder or initiated

by the agency. Revocation of a license

for a biologic product under any

circumstances will not result in the

introduction of any substance into the

environment and, therefore, will not

significantly affect the environment.

The agency is also proposing other

minor, nonsubstantive amendments to

delete unnecessary language, improve

the accuracy and clarity of the

categorical exclusions, and reflect

current terminology.

3. Foods, Food Additives, and Color

Additives

In the President’s National

Performance Report, ‘‘Reinventing Food

Regulations,’’ January 1996, the

President announced that FDA

proposed to reduce the number of EA’s

submitted by industry under NEPA by

increasing the number of categorical

exclusions for food and color additives

and generally recognized as safe (GRAS)
Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules 19481

substances based on little or no impact

on the environment from the use and

disposal of these products. As described

below, in fulfillment of this

commitment, FDA is proposing

additional categorical exclusions for

actions on foods, food additives, color

additives, and GRAS substances which,

based on experience in reviewing these

types of actions, the Center for Food

Safety and Applied Nutrition (CFSAN)

has concluded will not significantly

affect the human environment.

As was explained previously, FDA is

proposing to remove criteria from

certain exclusions in current § 25.24.

For actions involving foods, food

additives, color additives, and GRAS

substances, the criteria for the

exclusions in current § 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 §§ 25.30(j),

and 25.32(b), (c), (f), (g), and (h). This

change is being made because the

provisions in proposed § 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 § 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 § 25.32(f). Currently,

FDA’s NEPA procedures in § 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 § 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 priorsanctioned 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 § 170.3(l) (21

CFR 170.3(l)) and § 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 priorsanctioned 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 § 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

§ 170.39 (21 CFR 170.39) (threshold of

regulation) when a food additive is a

functional component of finished foodpackaging 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 foodpackaging 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-byweight has traditionally included

consideration of potential impacts

relating to the disposal of foodpackaging 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 foodpackaging material. To determine the

potential for significant introductions at

landfill sites, FDA estimated the

concentration of the additive that could

be present in landfill leachate for each

of the 95 petitions it reviewed for

additives used as functional

components of food-packaging

materials. FDA found that in virtually

all cases, the concentration of the

additives in landfill leachate was less

than 50 ppb. The concentration of the

additives in surface or ground water

receiving landfill leachate was expected

to be substantially less, taking into

consideration the mobility and

degradation of the additives in landfills

and their dilution in receiving waters.

Consequently, FDA determined in all

cases that these extremely low levels

would not have significant

environmental impacts at landfill sites.

The agency believes that approvals of

future petitions in this class are even

less likely to result in significant

introductions of substances at landfill

sites because EPA published new

landfill regulations in the Federal

Register of October 9, 1991 (56 FR

50978), that require new and expanded

landfills to have leachate collection

systems and liners to prevent leachate

from entering surface or groundwater.

Although operators of existing landfills

are not required to retrofit liner systems,

they are required to monitor

groundwater adjacent to existing

landfills and to take corrective action as

appropriate.

The agency’s evaluation of petitions

for additives used as functional

components of food-packaging materials

has also shown that there is little

potential for significant introductions

from the combustion of packaging

materials containing the additives.

These types of additives are used at low

levels in the packaging materials, ≤5

percent by weight, and, therefore, the

additional amounts of combustion

products emitted were found to be

insignificant compared to the levels

already being generated during

municipal solid waste combustion.

Because FDA’s experience shows that

the use levels for additives used as

functional components of foodpackaging materials are low, the agency

believes that future approvals will also

result in insignificant introductions into
19482 Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules

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 foodpackaging 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 § 25.32(i) a requestor

need not ordinarily submit an EA.

c. Proposed § 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

§ 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 § 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 repeatuse, 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 § 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 §§ 172.800 and 172.804,

and fat substitutes, e.g., § 184.1498).

The agency’s evaluation of the

environmental effects of substances

added directly to food has included

consideration of the potential for

impacts from the disposal of human

waste products containing the

petitioned substance and/or its products

of digestion and metabolism, and from

the use of natural resources and energy.

The substances added directly to food

considered here will be ingested by

consumers as components of food

containing these substances. After

ingestion, these substances are either

digested and/or metabolized to other

substances or excreted largely intact. In

all cases, the agency’s review of past

actions on substances added directly to

food resulted in decisions to issue

FONSI’s. To address the potential for

environmental impacts from disposal of

this class of substances, the agency’s

FONSI’s relied on one or more of the

following scenarios: (1) The agency’s

approval of the petition resulted in very

low levels (in the low ppb range or

lower) of the substances in either

effluents and/or sewage sludge from

publicly owned wastewater treatment

plants and these levels were determined

not to be toxic to organisms in the

environment; (2) the petitioned

substance was digested and/or

metabolized by humans such that only

products of digestion and metabolism

were expected to be excreted and these

products were the same as (or very

similar to) the products of digestion and

metabolism resulting from human food;

such products should have no potential

for significant environmental effects

because wastewater treatment facilities

are already designed to handle them; or

(3) the petitioned substance was

excreted largely intact but was rapidly

degraded into nontoxic products either

in wastewater treatment plants or in the

environment.

FDA’s experience shows that

substances added directly to food and

intended to remain with food through

ingestion that are the subject of new

petitions will have use and disposal

patterns similar to those described

above and will not be toxic to organisms

in the environment at the expected

levels of exposure. Thus, use and

disposal of such substances are not

expected to result in significant

environmental effects.

The agency has also found, as a result

of its review of petitions for substances

in the class being considered here, that

in no case was there potential for

significant impacts on energy and

natural resources. These findings relied

on one or more of the following
Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules 19483

scenarios: (1) The substances were

expected to compete with and replace

other already regulated substances with

no significant change in the overall use

of natural resources or energy, (2) the

substances are also used in nonfood

contact situations and the food-contact

usage represented a small increase in

the overall production and usage of the

substance such that the small increase

in the uses of natural resources and

energy was not significant, or (3) the

predicted market volumes for the

petitioned substances were very small

so that the use of natural resources and

energy for the petitioned substances was

very limited. In no case did the agency

find that there would be any effects on

threatened or endangered species.

Because the use and disposal of

substances added directly to foods and

intended to remain with foods through

ingestion has no significant effect on the

environment and has very limited

potential for significant effects on

energy and natural resources, EA’s for

these substances will not ordinarily be

required.

e. Proposed § 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 FDAregulated 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 § 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 priorsanctioned substance (defined under

§§ 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 selfpressurized 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 § 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 § 25.32(o). FDA is

proposing to exclude actions to approve

a food additive petition when an

additive is the intended expression

product(s) present in food derived from

new plant varieties. The proposed

exclusion is based on our determination

that the USDA Animal and Plant Health

Inspection Service (APHIS) has lead

responsibility, under the Federal Plant

Pest Act (7 U.S.C. 150aa et seq.), to

prevent the movement and

dissemination in the United States of

plant pests. Under that authority, USDA

APHIS addresses the potential of new

plant varieties to pose a plant pest risk

in accordance with the requirements

mandated under NEPA. USDA

considers the potential for risk in a very

broad context, so that not only is direct

disease or damage to plants and plant

materials considered as a component of

plant pest risk, but indirect effects on

beneficial or other organisms in the

agronomic context are also addressed.

Before issuing a determination of

nonregulated status for an organism that

has been subject to USDA oversight

because it was considered to present a

potential risk of being a plant pest,

USDA conducts an environmental

analysis in compliance with its NEPA

requirements that addresses plant pest
19484 Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules

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 § 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 (§ 101.12(h)), a nutrient content

claim petition (§ 101.69), a health claim

petition (§ 101.70), or a petition

pertaining to the label declaration of

ingredients (§ 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

§ 25.24 or an EA under current § 25.31.

Current § 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

§ 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

(§ 101.12(h)), on nutrient content claims

(§ 101.69), on health claims (§ 101.70),

and on the label declaration of

ingredients (§ 101.103) be categorically

excluded from the preparation of an

environmental assessment.

j. Proposed § 25.32(q). FDA is

proposing in § 25.32(q) to categorically

exclude from the requirement to submit

an EA actions to approve food additive

petitions for substances registered by

EPA under the Federal Insecticide,

Fungicide, and Rodenticide Act (FIFRA)

(7 U.S.C. 136 et seq.) for the same use

requested in the petition. FDA has had

limited experience in considering the

environmental impact of threshold of

regulation submissions for substances

registered by EPA under FIFRA because

the regulations establishing threshold of

regulation policy were recently issued.

However, because the information

currently required for such submissions

is identical to the information required

for food additive petitions for these

types of substances, the agency believes

that its experience with food additive

petitions is relevant. This proposed

exclusion is based on FDA’s experience

reviewing 12 petitions in this class, all

of which resulted in a FONSI. All of

these petitions were for antimicrobial

substances used either in the processing

of food or in food-packaging materials.

FDA’s evaluation of the potential

environmental effects of antimicrobial

substances has included consideration

of potential impacts at the site of use

and disposal of the antimicrobial

substance, and from the use of natural

resources and energy. Currently, for the

use sites of antimicrobial substances,

petitioners are directed to rely on

information in studies submitted to EPA

for registration of the product under

FIFRA, and to describe any potential

adverse environmental effects

determined by EPA. Petitioners may

submit a brief description and summary

of results of EPA studies in lieu of the

complete test reports. For use sites, FDA

has based its environmental decision on

a prediction of exposure levels, using

introduction and fate information, that

is compared with relevant toxicological

data to determine the potential for

significant environmental effects.

The agency’s experience with

antimicrobial petitions has been that,

before an antimicrobial product can be

used in food-contact situations, EPA

will have already examined the

environmental risks and benefits of

registering the product under FIFRA.

The parallel between EPA’s review and

FDA’s environmental review is

illustrated by FDA’s finding that it has

not had to require environmental testing

for antimicrobial products because such

tests were already conducted as part of

EPA’s review. In addition, antimicrobial

substances that are used and discharged

at point sources within the United

States are subject to the requirements of

National Pollution Discharge

Elimination System (NPDES) permits

under the Clean Water Act (33 U.S.C.

1251 et seq.). In registering a product

under FIFRA, EPA requires the label to

state that: (1) The product is not to be

discharged into lakes, streams, ponds,

estuaries, oceans, or other waters unless

in accordance with the requirements of

an NPDES permit and unless the

permitting authority has been notified

in writing prior to discharge; and (2) the

product is not to be discharged to sewer

systems without previously notifying

the local sewage treatment plant

authority. EPA also requires, if

necessary, that labels contain

information such as a warning of

toxicity to fish and/or wildlife, as

specified in 40 CFR 156.10(h)(2)(ii).

Thus, FDA has found that its assessment

of the fate and effects of antimicrobial

substances essentially duplicates the

review by EPA under FIFRA and, to

some extent, the review by NPDES

permitting authorities under the Clean

Water Act.

Currently, petitioners must address

the potential for impact on the use of

natural resources and energy as required

in an EA by specifying the natural

resources and energy required to

produce, transport, use, and/or dispose

of a given amount of the product that is

the subject of the action. FDA’s

experience with this area of potential

impacts is that these types of substances

almost always compete with and replace

other similar substances so that there is

little or no change in the use of natural

resources and energy. Thus, FDA

believes that future food additive

petitions for the same use as pesticides
Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules 19485

approved by EPA under FIFRA will

have little or no potential for significant

environmental impacts and that FDA’s

actions on these petitions warrant

exclusion from the requirement to

prepare an EA.

k. Removal of action levels. At the

time the current environmental

regulations were issued, the agency

believed that the establishment of an

action level required environmental

review. Thus, the agency included a

paragraph for the establishment of

action levels in current § 25.22(a)(11)

and specified an EA format in current

§ 25.31d. FDA also provided a

categorical exclusion in current

§ 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 noticeand-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 § 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 § 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 § 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 § 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 § 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 § 25.33(a) includes the

categorical exclusions listed in current

§ 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 § 25.33(a)(7) for animal drugs

used in feeds is the same as current

§ 25.24(d)(2) but has been revised for

clarity because FDA approves animal

drugs for use in animal feeds.

The categorical exclusions in

proposed § 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

§ 25.33(a), the agency is reserving

§ 25.33(b) to provide for a categorical

exclusion analogous to that contained in

proposed § 25.31(b) for human drugs.

The categorical exclusion would be for

actions that increase the use of an

animal drug in the instance that the

agency determines a level at or below

which the concentration of the

substance in the environment does not

significantly affect the environment.

FDA recognizes that proposed

§ 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
19486 Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules

environment will be at or below 1 ppb.

At this time, FDA is not adopting a

specific environmental concentration

from use of animal drugs because the

agency is still conducting a

retrospective review of environmental

assessments for these products and a

review of relevant environmental

science. The Animal Health Institute

and FDA/CVM held an Environmental

Risk Assessment Workshop on February

20 and 21, 1996, to establish a

comprehensive ecological risk

assessment process for the evaluation of

animal health products. Following this

opportunity for public debate, and for

drugs not otherwise excluded, FDA will

adopt a risk assessment paradigm for

determining environmental

introductions for animal drugs and an

environmental concentration at or

below which no meaningful

environmental effects are expected to

occur.

Proposed § 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 § 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 § 514.1(d)(1)(i)

(21 CFR 514.1(d)(1)(i)), and for use

under prescription or veterinarian’s

order. Under current § 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 (§ 514.1(d)(1)(ii)).

The categorical exclusion for animal

drugs used under prescription or

veterinarian’s order applies only to

animal drugs for therapeutic uses as

defined in section 201(g)(1)(B) of the act

(21 U.S.C. 321(g)(1)(B)). Based on its

experience in reviewing EA’s for these

products, FDA has found that

prescription products are generally

administered individually to a limited

number of animals for a limited amount

of time. Therefore, there are no

significant environmental effects.

However, FDA may require an EA if the

agency determines that there are

extraordinary circumstances associated

with the use of such a product.

Current § 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 § 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 § 25.33(f) would

categorically exclude actions on

applications submitted under section

512(m) of the act (21 U.S.C. 360b(m)).

FDA is proposing to exclude actions on

such applications because they permit

feed manufacturers to manufacture

animal feed bearing or containing new

animal drugs previously approved for

use in feeds. The potential for

environmental effects to occur is

considered at the time the new animal

drug is approved for use in feed.

Therefore, there is no need to require an

additional EA each time the agency

considers approval of an application

submitted under section 512(m) of the

act.
Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules 19487

Current § 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

§ 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 § 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

§ 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 § 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 § 25.24(e) as

proposed § 25.34 and to remove criteria

in § 25.24(e)(4) and (e)(7), now

incorporated in proposed § 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 § 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

§ 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 FDAregulated articles, FDA currently

requires a limited amount of

information to make sure that the article

will be produced in compliance with

applicable emissions requirements.

Specifically, the agency requires that the

following information be included in an

EA: A list of the substances expected to

be emitted, the controls exercised, a

citation of applicable emissions

requirements and statement of

compliance with these requirements,

and a discussion of the effect the

approval of the petition will have on

compliance with these requirements.

FDA recognizes, however, that

Federal, State, and local environmental

protection agencies have the

responsibility for issuing regulations,

permitting and licensing facilities, and

enforcing compliance with the

requirements that these agencies have

determined are necessary to ensure

adequate protection of the environment

from emissions from production

operations. Regulating emissions from

production sites requires balancing

between air, water, and solid waste

emissions for all production operations

carried out at a production site and in

the region with consideration of the

costs of compliance and available

technology that requires expertise found

primarily in Federal, State, and local

environmental agencies. As required by

environmental regulations and/or as

conditions of retaining licenses and

permits, manufacturers must obtain or

modify permits and provide information

to these agencies when production

operations are initiated or changed. The

information required to be provided to

FDA regarding production impacts and

compliance with emission requirements

is information that is generally required

to be provided to or is known by other

agencies whose responsibility is to

monitor compliance.

FDA has reviewed hundreds of EA’s

in which information regarding the

manufacturing site, such as emitted

substances and emission controls, was

provided. As a result of this review,

FDA has found that FDA-regulated

articles produced in compliance with all

applicable emission requirements (e.g.,

Clean Air Act, Clean Water Act,

Occupational Safety and Health Act)

will not significantly affect the

environment. Based on these findings,

FDA has determined that it is no longer

necessary to review a company’s

compliance with Federal, State, and

local environmental laws and FDA is

proposing to delete the requirements for

the submission of emission information

for production sites. Accordingly, under

the proposed regulations, FDA will

continue to focus its environmental

reviews on the use and disposal from

use of FDA-regulated articles, and FDA

will no longer routinely require

submission of information regarding

manufacturing sites or a certification of

compliance with Federal, State, and

local emission requirements. However,

if information available to the agency or

the applicant establishes that the

general or specific emission
19488 Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules

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 § 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

§ 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 § 25.40(c) would include

information found in current § 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 § 25.40(d) discusses

incorporation of information in an EA

by reference.

Proposed § 25.41 would include

information on FONSI’s that is found in

current § 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

§ § 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 § 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 § 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

§ 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 § 25.44 would include

information found in current § 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

§ 25.10(b) because it is self-evident that

FDA will be the lead agency for

programs administered by FDA.

Proposed § 25.45 would include

information from current § 25.42,

describing who the responsible agency

official will be and his or her

responsibilities. The agency is

proposing to remove information in

current § 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 § 25.50 clarifies that laws

governing public disclosure may limit

FDA’s ability to comply with NEPA and

CEQ regulations.

Proposed § 25.51(a) and (b), public

disclosure of FONSI’s and EA’s, would

include the public disclosure

information found in current § 25.30(b)

and 25.41(b). The proposed rule would

move the information relating to

statutory timeframes from current

§ 25.40(c) to proposed § 25.51(b)(1).

Proposed § 25.52 would add new

information relating to the public

disclosure of EIS’s.

F. Subpart F—Other Requirements

Current subpart E will be renumbered

as subpart F. The agency is not

proposing to amend this subpart.

IV. Environmental Impact

Considerations

The agency has determined under

current 21 CFR 25.24(a)(8) that this

action is of a type that does not

individually or cumulatively have a

significant effect on the human

environment. Therefore, neither an EA

nor an EIS is required.

V. Analysis of Impacts

FDA has examined the impacts of the

proposed rule under Executive Order

12866, under the Regulatory Flexibility

Act (Pub. L. 96–354), and under the

Unfunded Mandates Reform Act (Pub.

L. 104–4). Executive Order 12866

directs agencies to assess all costs and

benefits of available regulatory

alternatives and, when regulation is

necessary, to select regulatory

approaches that maximize net benefits

(including potential economic,

environmental, public health and safety,

and other advantages; distributive

impacts and equity). The Regulatory

Flexibility Act requires agencies to

analyze regulatory options that would

minimize any significant impact of a

rule on small entities. The Unfunded

Mandates Reform Act requires (in

section 202) that agencies prepare an

assessment of anticipated costs and

benefits before proposing any rule that

may result in an annual expenditure by

State, local, and tribal governments, in

the aggregate, or by the private sector, of

$100,000,000 (adjusted annually for

inflation). That act also requires (in

section 205) that the agency identify and
Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules 19489

consider a reasonable number of

regulatory alternatives and from those

alternatives select the least costly, most

cost effective, or least burdensome

alternative that achieves the objective of

the rule. The following analysis

demonstrates that this proposed rule is

consistent with the principles set forth

in the Executive Order and in these two

statutes. The proposed rule is not an

economically significant regulatory

action under Executive Order 12866.

Based on the approximate number of

EA’s that FDA currently receives each

year and the resources needed to

prepare them, the agency estimates that

the proposed reduced requirements for

submitting EA’s will result in an annual

cost savings to industry of

approximately $15.7 million. The basis

for this estimate is as follows:

Human pharmaceuticals:

Approximately 125 EA’s related to

human pharmaceuticals would be

eliminated annually under the proposal.

About one-half of these are abbreviated

EA’s; the remainder are full

assessments. FDA assumes that the

average cost of preparing an abbreviated

assessment was approximately $40,000,

while the average cost of a full

assessment was approximately

$200,000. These assumptions yield a

cost savings of about $2.5 million for

abbreviated EA’s and $12.5 million for

full EA’s, for a total savings to industry

from the reduced requirements of EA’s

relating to human pharmaceuticals of

approximately $15 million per year.

Veterinary products: The proposed

changes would eliminate approximately

37 abbreviated EA’s for veterinary

products each year, at an average cost of

approximately $5,000 each. About 77

brief submissions, which currently

require categorical exclusion criteria

review, would also be eliminated; these

cost an estimated $300 each to prepare.

Total cost savings to the veterinary

products industry under the proposal

would thus be approximately $208,000

per year.

Food products: About 36 EA’s per

year received by CFSAN would be

eliminated under the proposal.

Approximately 28 of these would have

been abbreviated EA’s and 8 would have

been full assessments under current

rules. FDA estimates that the cost of

producing most abbreviated EA’s for

CFSAN is approximately $2,500 and the

average cost of producing a full EA is

approximately $50,000. These

assumptions imply an annual cost

savings of approximately $70,000 for

abbreviated EA’s and $400,000 for full

EA’s, for a total annual savings to the

foods industry of approximately

$470,000.

In addition to these savings to

industry, the proposed changes would

improve FDA efficiency by eliminating

agency review costs of approximately $1

million per year.

The Regulatory Flexibility Act

requires agencies to analyze regulatory

options that would minimize any

significant impact of a rule of small

entities. Because these regulations will

not impose significant new costs on any

firms, the agency certifies that the

proposed rule will not have a significant

economic impact on a substantial

number of small entities. Therefore,

under the Regulatory Flexibility Act, no

further analysis is required.

VI. Paperwork Reduction Act of 1995

This proposed rule contains reporting

requirements that are subject to public

comment and review by the Office of

Management and Budget (OMB) under

the Paperwork Reduction Act of 1995

(44 U.S.C. 3506 and 3507). Therefore, in

accordance with 5 CFR part 1320, a

description of reporting requirements

with an estimate of the annual

collection of information burden is

given below by cross reference to

existing FDA clearance submissions

previously approved by OMB which

this proposed rule affects.

FDA is soliciting comments to: (1)

Evaluate whether the proposed

collection of information is necessary

for the proper performance of the

functions of the agency, including

whether the information will have

practical utility; (2) evaluate the

accuracy of the agency’s estimate of the

proposed collection of information; (3)

evaluate the quality, utility, and clarity

of the information to be collected; and

(4) minimize the burden of the

collection of information on those who

are to respond.

Title: National Environmental Policy

Act; Policies and Procedures.

Description: FDA has previously

issued regulations that implement

NEPA (part 25). The proposed rule

would reduce the number of NEPA

evaluations by providing for categorical

exclusions for additional classes of

actions that do not individually or

cumulatively have a significant effect on

the human environment and for which,

therefore, neither an EIS nor an EA is

required. FDA is also proposing to

amend these regulations to ensure that

the NEPA procedures are more concise

and understandable to the public and to

reflect current FDA policy with respect

to environmental considerations. This

proposed rule is in response to

initiatives announced in the President’s

National Performance Reports,

‘‘Reinventing Drug and Medical Device

Regulations,’’ April 1995, and

‘‘Reinventing Food Regulations,’’

January 1996.

Description of Respondents: Persons

and businesses, including small

businesses.

Estimated Annual Reporting and

Recordkeeping Burden: The estimated

burden associated with the information

collection requirements for this

proposed rule will be recognized in the

individual FDA clearances where NEPA

considerations apply. Listed below are

those clearances affected by this

regulation, including the section of title

21 CFR, the title, and the OMB approval

number:

Section 10.30, Citizen Petitions,

0910–0183; § 71.1, Color Additive

Petitions, 0910–0185; § 170.35,

Affirmation of Generally Recognized As

Safe (GRAS) Status, 0910–0132;

§ 101.12, Reference amounts

customarily consumed per eating

occasion, 0910–0286; § 101.69, Petitions

for nutrient content claims, 0910–0288;

§ 101.70, Petitions for health claims,

0910–0287; § 170.39, Threshold of

regulation for substances used in foodcontact articles, 0910–0298; § 171.1,

Food Additive Petitions, 0910–0016;

§ 312.23, Conditions for Exemption of

New Drugs for Investigational Use,

0910–0014; § 511.1, New Animal Drugs

for Investigational Use Exempt From

Section 512(a) of the Act, 0910–0117;

§ 514.1, New Animal Drug Applications,

0910–0032; § 514.8, Supplemental New

Animal Drug Applications, 0910–0032;

§ 571.1, Food Additive Petitions, 0910–

0016; § 601.2 Product LicensesProcedures for Filing, 0910–0124;

§ 812.20, Investigational Device

Exemptions Application, 0910–0078.

The proposed rule would reduce

these information collections that have

already been reviewed and approved by

the OMB. Reporting burdens imposed

by current part 25 are approved by OMB

through December 31, 1997 (see OMB

control number 0910–0190, ‘‘National

Environmental Policy Act; Policy and

Procedures—21 CFR Part 25’’).

The agency has submitted copies of

the proposed rule to OMB for its review

of these reporting requirements.

Interested persons are requested to send

comments regarding information

collection by May 3, 1996, to the Office

of Information and Regulatory Affairs,

OMB (address above).

List of Subjects in 21 CFR Part 25

Environmental impact statements,

Foreign relations, Reporting and

recordkeeping requirements.

Therefore, under the Federal Food,

Drug, and Cosmetic Act, the Public

Health Service Act, and authority
19490 Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules

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

§ 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).

§ 25.5 Terminology.

(a) Definitions that apply to the terms

used in this part are set forth in the CEQ

regulations under 40 CFR part 1508. The

terms and the sections of 40 CFR part

1508 in which they are defined follow:

(1) Categorical exclusion (40 CFR

1508.4).

(2) Cooperating agency (40 CFR

1508.5).

(3) Cumulative impact (40 CFR

1508.7).

(4) Effects (40 CFR 1508.8).

(5) Environmental assessment (EA)

(40 CFR 1508.9).

(6) Environmental document (40 CFR

1508.10).

(7) Environmental impact statement

(EIS) (40 CFR 1508.11).

(8) Federal agency (40 CFR 1508.12).

(9) Finding of no significant impact

(40 CFR 1508.13).

(10) Human environment (40 CFR

1508.14).

(11) Lead agency (40 CFR 1508.16).

(12) Legislation (40 CFR 1508.17).

(13) Major Federal action (40 CFR

1508.18).

(14) Mitigation (40 CFR 1508.20).

(15) NEPA process (40 CFR 1508.21).

(16) Notice of intent (40 CFR 1508.22).

(17) Proposal (40 CFR 1508.23).

(18) Scope (40 CFR 1508.25).

(19) Significantly (40 CFR 1508.27).

(b) The following terms are defined

solely for the purpose of implementing

the supplemental procedures provided

by this part and are not necessarily

applicable to any other statutory or

regulatory requirements:

(1) Abbreviated application applies to

an abbreviated new drug application, an

abbreviated antibiotic application, and

an abbreviated new animal drug

application.

(2) Active moiety means the molecule

or ion, excluding those appended

portions of the molecule that cause the

drug to be an ester, salt (including a salt

with hydrogen or coordination bonds),

or other noncovalent derivative (such as

a complex chelate or clathrate) of the

molecule responsible for the

physiological or pharmacological action

of the drug substance.

(3) Agency means the Food and Drug

Administration (FDA).

(4) Increased use of a drug or biologic

product may occur if the drug will be

administered at higher dosage levels, for

longer duration or for different

indications than were previously in

effect, or if the drug is a new molecular

entity. New molecular entity means a

drug for which the active moiety

(present as the unmodified (parent)

compound, or an ester or a salt,

clathrate, or other noncovalent

derivative of the base (parent)

compound) has not been previously

approved or marketed in the United

States for use in a drug product, either

as a single ingredient or as part of a

combination product or as part of a

mixture of stereoisomers. The term

‘‘use’’ also encompasses disposal of

FDA-regulated articles by consumers.

(5) Responsible agency official means

the agency decision maker designated in

part 5 of this chapter.

(c) The following acronyms are used

in this part:

(1) CEQ—Council on Environmental

Quality.

(2) CGMP—Current good

manufacturing practice.

(3) EA—Environmental assessment.

(4) EIS—Environmental impact

statement.

(5) The act—Federal Food, Drug, and

Cosmetic Act.

(6) FIFRA—Federal Insecticide,

Fungicide, and Rodenticide Act.

(7) FONSI—Finding of no significant

impact.

(8) GLP—Good laboratory practice.

(9) GRAS—Generally recognized as

safe.

(10) HACCP—Hazard analysis critical

control point.

(11) IDE—Investigational device

exemption.

(12) IND—Investigational new drug

application.

(13) INAD—Investigational new

animal drug application.

(14) NADA—New animal drug

application.

(15) NDA—New drug application.

(16) NEPA—National Environmental

Policy Act of 1969.

(17) PDP—Product development

protocol.

(18) PMA—Premarket approval

application.

§ 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
Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules 19491

stewardship of the environment for

present and future generations.

(b) Assessment of environmental

factors continues throughout planning

and is integrated with other program

planning at the earliest possible time to

ensure that planning and decisions

reflect environmental values, to avoid

delays later in the process, and to avoid

potential conflicts.

(c) For actions initiated by the agency,

the NEPA process will begin when the

agency action under consideration is

first identified. For actions initiated by

applicants or petitioners, NEPA

planning begins when FDA receives a

submission from an applicant or

petitioner seeking action by FDA. FDA

may issue a public call for

environmental data or otherwise consult

with affected individuals or groups

when a contemplated action in which it

is or may be involved poses potential

significant environmental effects.

(d) Environmental documents shall

concentrate on timely and significant

issues, not amass needless detail.

(e) If a proposed action for which an

EIS will be prepared involves possible

environmental effects that are required

to be considered under statutes or

Executive Orders other than those

referred to under ‘‘Authority’’ in this

part, these effects shall be considered in

the NEPA review, consistent with 40

CFR 1502.25 and the Department of

Health and Human Services’ General

Administration Manual, part 30.

Subpart B—Agency Actions Requiring

Environmental Consideration

§ 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 § 25.20, unless the

agency can determine that the action

qualifies for exclusion under §§ 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

§ 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 §§ 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 §§ 25.30,

25.31, 25.32, 25.33, or 25.34, or

proposing to dispose of an article as

provided in §§ 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.

§ 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.

§ 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

§§ 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 §§ 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 §§ 25.30(d) or 25.32(h).

(d) Disposition of FDA laboratory

waste materials, unless categorically

excluded in § 25.30(m).

(e) Intramural and extramural

research supported in whole or in part

through contracts, other agreements, or

grants, unless categorically excluded in

§ 25.30(e) or (f).

(f) Establishment by regulation of

labeling requirements, a standard, or a

monograph, unless categorically

excluded in §§ 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 §§ 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 §§ 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

§ 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 priorsanctioned food ingredient, as defined

in §§ 170.3(l) and 181.5(a) of this

chapter, unless categorically excluded

in § 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

§ 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 § 25.33(a), (c), (d), or (e).

(n) Approval of PMA’s for medical

devices, notices of completion of PDP’s

for medical devices, authorizations to

commence clinical investigation under

an approved PDP, or applications for an

IDE, unless categorically excluded in

§ 25.34.

§ 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
19492 Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules

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.

§ 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

§ 25.30 General.

The classes of actions listed in this

section and §§ 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 FederalState 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.

§ 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.

§ 25.32 Foods, food additives, and color

additives.

The classes of actions listed in this

section are categorically excluded and,

therefore, ordinarily do not require the

preparation of an EA or an EIS:

(a) Issuance, amendment, or repeal of

a food standard.

(b) Action on a request for exemption

for investigational use of a food additive

if the food additive to be shipped under
Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules 19493

the request is intended to be used for

clinical studies or research.

(c) Approval of a color additive

petition to change a provisionally listed

color additive to permanent listing for

use in food, drugs, devices, or

cosmetics.

(d) Testing and certification of batches

of a color additive.

(e) Issuance of an interim food

additive regulation.

(f) Affirmation of a food substance as

GRAS for humans or animals on FDA’s

initiative or in response to a petition,

under parts 182, 184, 186, or 582 of this

chapter, and establishment or

amendment of a regulation for a priorsanctioned food ingredient, as defined

in §§ 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 § 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 § 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 § 101.12(h) of this chapter, a nutrient

content claim petition as described in

§ 101.69 of this chapter, a health claim

petition as described in § 101.70 of this

chapter, or a petition pertaining to the

label declaration of ingredients as

described in § 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 § 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.

§ 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 § 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 § 510.455 of this chapter or

as a liquid feed supplement under

§ 558.5 of this chapter; or

(7) Approval of a drug for use in

animal feeds if such drug has been

approved under § 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.

§ 25.34 Devices and electronic products.

The classes of actions listed in this

section are categorically excluded and,

therefore, ordinarily do not require the

preparation of an EA or an EIS:

(a) Action on a device premarket

notification submission under subpart E

of part 807 of this chapter.

(b) Classification or reclassification of

a device under part 860 of this chapter.

(c) Issuance, amendment, or repeal of

a standard for a class II medical device

or an electronic product, and issuance

of exemptions or variances from such a

standard.

(d) Approval of a PMA or a notice of

completion of a PDP or amended or

supplemental applications or notices for

a class III medical device if the device

is of the same type and for the same use

as a previously approved device.

(e) Changes in the PMA or a notice of

completion of a PDP for a class III

medical device that do not require

submission of an amended or

supplemental application or notice.

(f) Issuance of a restricted device

regulation if it will not result in

increases in the existing levels of use or

changes in the intended uses of the

product or its substitutes.

(g) Action on an application for an

IDE or an authorization to commence a

clinical investigation under an approved

PDP.

(h) Issuance of a regulation exempting

from preemption a requirement of a

State or political subdivision concerning

a device, or a denial of an application

for such exemption.
19494 Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules

Subpart D—Preparation of Environmental

Documents

§ 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 §§ 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.

§ 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.

§ 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.

§ 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.

§ 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.

§ 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

§ 25.50 General information.

(a) To the extent actions are not

protected from disclosure by existing

law applicable to the agency’s

operation, FDA will involve the public

in preparing and implementing its

NEPA procedures and will provide

public notice of NEPA-related hearings,

public meetings, and the availability of

environmental documents.

(b) Many FDA actions involving

investigations, review, and approval of

applications, and premarket

notifications for human drugs, animal

drugs, biologic products, and devices

are protected from disclosure under the
Federal Register / Vol. 61, No. 85 / Wednesday, May 1, 1996 / Proposed Rules 19495

Trade Secret Act, 18 U.S.C. 1905, and

301(j) of the act. These actions are also

protected from disclosure under FDA’s

regulations including part 20,

§§ 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.

§ 25.51 Environmental assessments and

findings of no significant impact.

(a) Data and information that are

protected from disclosure by 18 U.S.C.

1905 or 21 U.S.C. 331(j) or 360j(c) shall

not be included in the portion of

environmental documents that is made

public. When such data and information

are pertinent to the environmental

review of a proposed action, an

applicant or petitioner shall submit

such data and information separately in

a confidential section and shall

summarize the confidential data and

information in the EA to the extent

possible.

(b) FONSI’s and EA’s will be available

to the public in accordance with 40 CFR

1506.6 as follows:

(1) When the proposed action is the

subject of a notice of proposed

rulemaking or a notice of filing

published in the Federal Register, the

notice shall state that no EIS is

necessary and that the FONSI and the

EA are available for public inspection at

FDA’s Dockets Management Branch. If

the responsible agency official is unable

to complete environmental

consideration of the proposed action

before a notice of filing of a food or

color additive petition is required to be

published under the act, and if the

subsequent environmental analysis

leads to the conclusion that no EIS is

necessary, the Federal Register

document publishing the final

regulation rather than the notice of

filing shall state that no EIS is necessary

and that the FONSI and the EA are

available upon request and filed in

FDA’s Dockets Management Branch.

(2) For actions for which notice is not

published in the Federal Register, the

FONSI and the EA shall be made

available to the public upon request

according to the procedures in 40 CFR

1506.6.

(3) For a limited number of actions,

the agency may make the FONSI and EA

available for public review (including

review by State and areawide

information clearinghouses) for 30 days

before the agency makes its final

determination whether to prepare an

EIS and before the action may begin, as

described in 40 CFR 1501.4(e). This

procedure will be followed when the

proposed action is, or is closely similar

to, one that normally requires an EIS or

when the proposed action is one

without precedent.

§ 25.52 Environmental impact statements.

(a) If FDA determines that an EIS is

necessary for an action involving

investigations or approvals for drugs,

animal drugs, biologic products, or

devices, an EIS will be prepared but will

become available only at the time of the

approval of the product. Disclosure will

be made in accordance with 40 CFR

1506.6 and part 20 of this chapter. The

EIS will in all other respects conform to

the requirements for EIS’s as specified

in 40 CFR part 1502 and 1506.6(f).

(b) Comments on the EIS may be

submitted after the approval of the drug,

animal drug, biologic product, and

device. Those comments can form the

basis for the agency to consider

beginning an action to withdraw the

approval of applications for a drug,

animal drug, biologic product, or to

withdraw premarket notifications or

premarket approval applications for

devices.

(c) In those cases where the existence

of applications and premarket

notifications for drugs, animal drugs,

biologic products, or devices has

already been disclosed before the

agency approves the action, the agency

will make diligent effort (40 CFR

1506.6) to involve the public in

preparing and implementing the NEPA

procedures for EIS’s while following its

own disclosure requirements including

those listed in part 20, §§ 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

§ 25.60 Environmental effects abroad of

major agency actions.

(a) In accordance with Executive

Order 12114, ‘‘Environmental Effects

Abroad of Major Federal Actions’’ of

January 4, 1979 (44 FR 1957, January 9,

1977), the responsible agency official, in

analyzing actions under his or her

program, shall consider the

environmental effects abroad, including

whether the actions involve:

(1) Potential environmental effects on

the global commons and areas outside

the jurisdiction of any nation, e.g.,

oceans and the upper atmosphere.

(2) Potential environmental effects on

a foreign nation not participating with

or otherwise involved in an FDA

activity.

(3) The export of products (or

emissions) that in the United States are

prohibited or strictly regulated because

their effects on the environment create

a serious public health risk.

(4) Potential environmental effects on

natural and ecological resources of

global importance designated under the

Executive Order.

(b) Before deciding on any action

falling into the categories specified in

paragraph (a) of this section, the

responsible agency official shall

determine in accordance with section 2–

3 of the Executive Order whether such

actions may have a significant

environmental effect abroad.

(c) If the responsible agency official

determines that an action may have a

significant environmental effect abroad,

the responsible agency official shall

determine in accordance with section 2–

4(a) and (b) of the Executive Order,

whether the subject action calls for:

(1) An EIS;

(2) A bilateral or multilateral

environmental study; or

(3) A concise environmental review.

(d) In preparing environmental

documents under this subpart, the

responsible official shall:

(1) Determine, as provided in section

2–5 of the Executive Order, whether

proposed actions are subject to the

exemptions, exclusions, and

modification in contents, timing, and

availability of documents.

(2) Coordinate all communications

with foreign governments concerning

environmental agreements and other

arrangements in implementing the

Executive Order.

Dated: April 17, 1996.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 96–10732 Filed 4–30–96; 8:45 am]

BILLING CODE 4160–01–F