National Environmental Policy Act; Proposed Revision of Policies and Procedures

SUMMARY: The Food and Drug Administration (FDA) is proposing to amend

its regulations governing compliance with the National Environmental

Policy Act of 1969 (NEPA) as implemented by the regulations of the

Council on Environmental Quality (CEQ). The primary purpose of this

proposed rule is to increase the efficiency of FDA's implementation of

NEPA and reduce the number of NEPA evaluations by providing for

categorical exclusions for additional classes of actions that do not

individually or cumulatively have a significant effect on the human

environment and for which, therefore, neither an environmental impact

statement (EIS) nor an environmental assessment (EA) is required. FDA

is also proposing to amend its regulations to make its NEPA procedures

more concise and understandable to the public and to reflect current

FDA policy with respect to environmental considerations. This proposed

rule is in response to initiatives announced in the President's

National Performance Reports, ``Reinventing Drug and Medical Device

Regulations,'' April 1995, and ``Reinventing Food Regulations,''

January 1996.

DATES: Submit written comments on the proposed rule by July 2, 1996.

Submit written comments on the information collection requirements by

May 3, 1996.

ADDRESSES: Submit written comments on the proposed rule to the Dockets

Management Branch (HFA-305), Food and Drug Administration, rm. 1-23,

12420 Parklawn Dr., Rockville, MD 20857. Submit written comments on the

information collection requirements to the Office of Information and

Regulatory Affairs, Office of Management and Budget (OMB), New

Executive Office Building, 725 17th St. NW., rm. 10235, Washington, DC

20503, Attn.: Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT: For information regarding human drugs:

Nancy Sager, Center for Drug Evaluation and Research (HFD-357),-Food

and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-

594-6740.

For information regarding biologics: Nancy Roscioli, Center for

Biologics Evaluation and Research (HFM-205), Food and Drug

Administration, 1401 Rockville Pike, Rockville, MD 20852, 301-827-3031.

For information regarding veterinary medicines: Charles E. Eirkson,

Center for Veterinary Medicine (HFV-150), Food and Drug Administration,

7500 Standish Pl., Rockville, MD 20855, 301-594-1683.

For information regarding foods: Buzz L. Hoffmann, Center for Food

Safety and Applied Nutrition (HFS-246), Food and Drug Administration,

200 C St. SW.,Washington, DC 20204, 202-418-3005.

For information regarding medical devices and radiological health:

Mervin Parker,-Center for Devices and Radiological Health (HFZ-402),

Food and Drug Administration, 9200 Corporate Blvd., Rockville, MD

20850, 301-594-2186.

SUPPLEMENTARY INFORMATION:

I. Background

NEPA requires all Federal agencies to assess the environmental

impact of their actions and to ensure that the interested and affected

public is informed of environmental analyses. CEQ is responsible for

overseeing Federal efforts to comply with NEPA. Both CEQ and FDA have

issued regulations governing agency obligations and responsibilities

under NEPA. In the Federal Register of March 15, 1973 (38 FR 7001), FDA

issued its first regulations to implement NEPA. FDA amended these

regulations in the Federal Register of April 15, 1977 (42 FR 19986),

based on consideration of revised guidelines for preparing EIS's issued

by CEQ. In 1978, CEQ replaced its guidelines with regulations

implementing the procedural requirements of NEPA (40 CFR parts 1500 to

1508). To comply with CEQ regulations, in the Federal Register of April

26, 1985 (50 FR 16636), FDA revised its NEPA policies and procedures in

part 25 (21 CFR part 25).

The CEQ regulations, which are binding on all Federal executive

agencies, establish formal guidance on the requirements of NEPA.

Agencies must adopt procedures to supplement them. In adopting NEPA-

implementing procedures, Federal agencies are directed by CEQ to reduce

paperwork (40 CFR 1500.4 and 1500.2(b)) and to reduce delay (40 CFR

1500.5) by using several means including the use of categorical

exclusions. CEQ defines categorical exclusions as categories of actions

which do not individually or cumulatively have a significant effect on

the human environment and for which neither an EA nor an EIS is

required (40 CFR 1508.4). The CEQ regulations also state that agencies

shall continue to review their policies and procedures and, in

consultation with CEQ, revise them as necessary to ensure full

compliance with the purpose and provisions of NEPA (40 CFR 1507.3).

II. Overview of the Proposed Rule

Since FDA's NEPA policies and supplemental procedures were

published in 1985, the agency has prepared EA's for many agency-

initiated actions and has reviewed hundreds of EA's for a variety of

industry requests for agency action. Based on FDA's experience

reviewing EA's and on its evaluation and knowledge of other relevant

environmental science, FDA has determined that certain classes of

actions normally do not cause significant environmental effects, and

therefore, should be added to the list of actions that are excluded

from the requirement to prepare an EA or an EIS. Some of these actions

had already been identified by FDA as unlikely to cause significant

environmental effects, as evidenced by the fact that the agency has

been requiring less information to support these actions, i.e., an

abbreviated EA rather than a full EA (see Sec. 25.31a(b)).

Thus, in response to the President's reinventing Government

initiatives announced in the President's National Performance Reports,

``Reinventing Drug and Medical Device Regulations,'' April 1995, and

``Reinventing Food Regulations,'' January 1996, FDA, in consultation

with CEQ, is now proposing to increase the efficiency of FDA's

implementation of NEPA and to substantially reduce the number of NEPA

evaluations by providing for categorical exclusions for additional

classes of actions that do not individually or cumulatively have a

significant impact on the human environment and for which, therefore,

neither an EA nor an EIS is required. This proposal would substantially

reduce the number of EA's required to be submitted by industry and

reviewed by FDA and, consequently, reduce the number of findings of no

significant impact (FONSI's) the agency would be required to prepare.

Furthermore, the proposal will not compromise the environment because

the excluded actions have been found not to have a significant effect

on the environment, and the proposed rule would continue

[[Page 14923]]

to provide for the preparation of an EA under extraordinary

circumstances in which a categorically excluded action may have a

significant environmental impact. This proposal would enable FDA to

focus its resources in the environmental area on situations likely to

have an effect on the environment.

The agency is also proposing to revise its environmental

regulations to make them more concise and useful to the public and

regulated industry by reorganizing, simplifying, and eliminating

unnecessary and duplicative language. The proposed rule would

reorganize and renumber various sections so that information on certain

topics is grouped together. The agency solicits comments on and

suggestions for further improvement in these regulations.

III. Specific Proposed Changes

A. General Provisions

The proposed rule would eliminate unnecessary language in current

subpart A of part 25 by deleting the reference to the environmental

statutes listed in current Sec. 25.5 Policies, amending Sec. 25.15

Terminology (proposed Sec. 25.5), and making other minor revisions,

including combining Sec. 25.5 Policies and Sec. 25.10 NEPA planning

into proposed Sec. 25.10 Policies and NEPA planning.

In proposed Sec. 25.5 Terminology, FDA is proposing to remove

definitions listed in current Sec. 25.15 that are not used in part 25,

and add new definitions for ``active moiety'' and ``increased use'' of

a drug. ``Increased use'' of a drug will occur if the drug will be

administered at higher dosage levels, for longer duration, or for

different indications than were previously in effect, or if the drug is

a new molecular entity. ``Increased use'' encompasses consideration of

FDA-regulated articles that are disposed of by consumers.Eric Flamm

suggests wording: ``Increased use'' encompasses consideration of

disposal of FDA regulated articles by consumers. ``Active moiety'' has

been previously defined in FDA regulations (21 CFR 314.108(a)).

B. Agency Actions Requiring Environmental Consideration-

Proposed Sec. 25.15 would contain the general procedural

information now found in current Secs. 25.20 and 25.22.

The proposed rule would create new Sec. 25.l6 Public health and

safety emergencies using revised language now contained in current

Sec. 25.40(b).

Actions requiring preparation of an EA (proposed Sec. 25.20) would

remain essentially the same as current Sec. 25.22, except that: (1)

Current Sec. 25.22(a)(13), promulgation and enforcement of FDA

regulations relating to the control of communicable disease and to

interstate conveyance sanitation, has been deleted and is covered by

proposed Sec. 25.20(g); and (2) actions relating to approval of new

drug applications (NDA's) and abbreviated applications, actions on

investigational new drug applications (IND's) (current

Sec. 25.22(a)(14)), issuance of licenses for biologic products (current

Sec. 25.22(a)(16)), and approval of supplements to existing approvals

of FDA-regulated articles (Sec. 25.22(a)(8)) have been combined into

one provision (proposed Sec. 25.20(l)) and revised to reflect current

terminology.

The proposed regulations include new Sec. 25.21 Extraordinary

circumstances, which addresses circumstances under which categories of

actions that would ordinarily be categorically excluded would require

preparation of environmental documents. Proposed Sec. 25.21

incorporates current Sec. 25.23(b) and includes two examples of

circumstances under which an action would require the preparation of

environmental documents because it might have the potential to

significantly affect the environment. The examples of circumstances

that will cause an action not to qualify for categorical exclusion are:

(1) Actions for which data available establish that, at the expected

level of exposure, there is the potential for serious harm to the

environment (proposed Sec. 25.21(a)); and (2) actions that adversely

affect a species or the critical habitat of a species determined under

the Endangered Species Act or the Convention on International Trade in

Endangered Species of Wild Flora and Fauna to be endangered or

threatened, or wild flora or fauna that are entitled to special

protection under some other Federal law (proposed Sec. 25.21(b)). In

addition, the proposed rule references the CEQ regulations at 40 CFR

1508.27, which provide examples of circumstances in which significant

effects may occur. Extraordinary circumstances may be shown by either

data available to the agency or data available to the applicant or

petitioner and may be based on production, use, or disposal from use.

The two examples of extraordinary circumstances in proposed

Sec. 25.21 reflect Are they really disqualification criteria? If the

criteria are met, the exclusion is warranted. See 25.24(c)(1). Gail

concurs with this.criteria that appear in some of the categorical

exclusions listed in current Sec. 25.24. The language in the first

example, proposed Sec. 25.21(a), is derived from but differs slightly

from current Sec. 25.24 language relating to toxicity (see, e.g.,

Sec. 25.24(a)(10), (b)(2), and (c)(6)). The extraordinary circumstance

example in proposed Sec. 25.21(a) would revise the language in current

Sec. 25.24, ``the substance may be toxic to organisms in the

environment'' to read ``there may be harm to the environment.'' FDA is

revising this language to reflect that possible adverse environmental

effects other than toxicity should be considered. For example, some

biological agents that may be released may not be toxic to indigenous

organisms, but could have lasting effects on ecological community

dynamics.

FDA considers a substance to be toxic if it is harmful to some

biological mechanism or system. Although FDA recognizes that any

substance may produce damage to biological mechanisms or systems under

specific conditions, for the purposes of these regulations, FDA

considers a substance to be toxic if it is harmful to appropriate test

organisms at the expected level of exposure even though it may be

without effect in humans or other organisms at these concentrations,

and may even be used by humans because of its toxic properties.

As a result of the new language in proposed Sec. 25.21(a), the

words ``toxic'' and ``toxic substance'' are no longer used in the

proposed regulation. Therefore, FDA is proposing to remove the

definition of ``toxic substance'' at current Sec. 25.15(b)(6).

Furthermore, FDA no longer believes that the second part of the current

definition relating to toxicity of a substance is appropriate for the

following reasons: (1) Evaluation of the toxicity of a substance based

only on the concentration at the point of entry or point of highest

concentration ignores factors such as instantaneous dispersion that

typically takes place as a result of processes such as river flow and

wind, and that not all substances bioaccumulate. Consideration of such

dilution processes may be reasonable and scientifically sound in

estimating environmental concentrations for certain purposes; and (2)

the use of a factor of 1/100 of the concentration that causes 50-

percent mortality in a test organism to assess the toxicity of a

substance is not appropriate in all cases. The factors used to assess

toxicity should be directly related to the amount of valid ecotoxicity

data available. Although a factor of 1/100 may be appropriate in some

instances, it may be too much or too little in others. In evaluating

whether extraordinary circumstances exist, FDA will take into account

any ecotoxicity data relevant to the issue.

[[Page 14924]]

The second example of extraordinary circumstances relates to

instances in which the proposed action could adversely affect an

endangered or threatened species, or a species entitled to protection

under some other Federal law. FDA intends to closely examine proposed

actions that involve FDA-regulated articles obtained from wild flora

and fauna and will use the extraordinary circumstances provision to

require at least an EA in any instance in which it appears from an

examination of the proposed action that the action may cause a species

to become endangered or threatened.

In addition, the agency notes that the language in proposed

Sec. 25.21(a) includes the indirect effects as well as direct effects

of agency actions. For example, when the agency takes action to

prohibit or restrict the use of an FDA-regulated product, the agency

may consider whether the increased use of substitutes for the

prohibited or restricted product might, at the expected level of

exposure, result in harm to the environment.

FDA is proposing to remove current Sec. 25.25 (Retroactive

environmental consideration), because any request by FDA to an

applicant to submit additional information to an existing FDA approval

will be made under authority granted to FDA by the Federal Food, Drug,

and Cosmetic Act (the act) or the Public Health Service Act (the PHS

Act).

C. Categorical Exclusions

1. General

The proposed rule would increase the number of categorical

exclusions and reorganize the categorical exclusions into the following

five sections in proposed subpart C of part 25: Section 25.30 General;

Sec. 25.31 Human drugs and biologics; Sec. 25.32 Foods, food additives,

and color additives; Sec. 25.33 Animal drugs, and Sec. 25.34 Devices

and electronic products. The agency is also proposing to delete the

general introductory language from current Sec. 25.24 because it is

unnecessary to include this information in the regulation.-

The agency is proposing to retain most of the general categorical

exclusions listed in current Sec. 25.24(a) (proposed Sec. 25.30) and to

make certain revisions described below:

Current Sec. 25.24(a)(4) categorically excludes destruction or

disposition of any FDA-regulated article condemned after seizure,

following detention or recall at agency request, or the distribution or

use of which has been enjoined. In proposed Sec. 25.30(d), FDA is

proposing to revise the criteria for the categorical exclusion from

``if the method of destruction or disposition of the article, including

packaging material, will not result in the release of a toxic substance

into the environment'' to ``if the waste is disposed of in compliance

with all Federal, State, and local requirements.'' The agency is

proposing this revision to reflect current agency practice and because

the previous criterion is covered under paragraph (a) of proposed

Sec. 25.21 Extraordinary circumstances.

The agency is proposing to revise the categorical exclusion for

current good manufacturing practice (CGMP) regulations

(Sec. 25.24(a)(10), proposed Sec. 25.30(j)) to include regulations

based on the hazard analysis critical control points (HACCP)

principles. The HACCP concept is a systematic approach to the

identification, assessment of risk, and control of the biological,

chemical, and physical food safety hazards associated with a particular

food production process. The HACCP system is based upon the

implementation of a control plan developed by a food producer that

analyzes significant food safety hazards, identifies the points in the

production process where a hazard can be prevented, and determines the

preventive measures that are necessary for proper control.

The agency has recently issued regulations (60 FR 65096, December

18, 1995) that use HACCP principles to ensure the safe processing and

importing of seafood. The agency is also considering developing HACCP

regulations for other regulated food industries (59 FR 39888, August 4,

1994). FDA has found that the environmental considerations based on

HACCP principles are essentially identical to the environmental

considerations of regulations based on CGMP's. Neither type of

regulation is likely to have significant environmental impacts.

Therefore, the agency believes that it is appropriate to incorporate

into the categorical exclusion for CGMP regulations an exclusion of the

HACCP regulations.

FDA also is proposing to add a categorical exclusion (proposed

Sec. 25.30(m)) for actions relating to the disposal of the hazardous

laboratory waste materials generated in FDA laboratories (low-level

radioactive waste and chemical waste). Today, all of this hazardous

waste is disposed of under contract with a hazardous waste management

firm.We don't mention what the waste is--even though it is in the

codified part. The contractor is responsible for the collection,

handling, storage, packing, and ultimate disposal of the waste

materials at facilities permitted by the U.S. Environmental Protection

Agency (EPA) and/or facilities licensed by the Nuclear Regulatory

Commission (NRC). In awarding contracts, FDA takes into consideration

whether a prospective contractor has all applicable licenses, permits,

and insurance necessary to perform the work and transport the waste as

required under the contract. The contractor and all disposal facilities

must certify that they are in full compliance with all applicable

Federal, State, and local requirements, before FDA will award the

contract. Further, FDA requires the contractor to present a

comprehensive operational plan. FDA reviews this plan to determine if

the contractor's approach is complete, safe, appropriate, and

responsive to, among other things, FDA's requirements for waste

disposal. Further, the contractor must operate in full compliance with

appropriate regulations issued by EPA (Title 40), the Department of

Transportation (Title 49), the Department of Labor (Title 29), NRC

(Title 10), and with relevant State and local regulations governing the

disposal of hazardous and nonhazardous waste. Therefore, FDA is

proposing in Sec. 25.30(m) to categorically exclude disposal of low-

level radioactive waste materials and chemical waste materials

generated in laboratories serviced by FDA-administered contracts.

2. Human Drugs and Biologics

In the National Performance Report, ``Reinventing Drug and Medical

Device Regulations,'' April 1995, the President announced FDA's

proposal to reduce the number of EA's submitted by industry under NEPA

by increasing the number of categorical exclusions for those actions

relating to drugs and biologics that, as a class, have no individual or

cumulative significant effect on the environment. As described below,

in fulfillment of this commitment, FDA is proposing additional

categorical exclusions for classes of actions on drugs and biologic

products that, based on experience in reviewing these types of actions,

the Center for Drug Evaluation and Research (CDER) and the Center for

Biologics Evaluation and Research (CBER) have concluded do not have

significant effects on the human environment. All of the environmental

reviews of these categories of actions performed under the current

regulations have resulted in FONSI's.

The proposed new categorical exclusions in Sec. 25.31(a) and (b)

apply to actions on an NDA, abbreviated application or a supplement to

such

[[Page 14925]]

applications, or action on an over-the-counter (OTC) monograph. They

are divided into two sections: (1) Proposed Sec. 25.31(a), which

applies if FDA's action does not increase the use and disposal of the

drug; and (2) proposed Sec. 25.31(b), which applies if FDA's action

does increase the use and disposal of the drug. This is similar to the

distinction drawn in the existing regulations between actions that

increase use and actions that do not. Proposed Sec. 25.31(a) and (b)

use the term ``active moiety'' rather than substance, drug product, or

other terminology to clarify the exact focus of the environmental

review.

The categorical exclusion in proposed Sec. 25.31(a) is based on the

categorical exclusions in current Sec. 25.24(c)(1) and (c)(2) and the

fact that, if the action does not increase the use of a drug, there is

no change in the level of the substance in the environment. FDA has

defined ``increased use'' of a drug to include those circumstances

currently listed in Sec. 25.24(c)(1) and (c)(2). Because the

environmental effects, if any, associated with the use and disposal of

the drug were incurred when it was first approved, actions to approve

additional products may be categorically excluded if they do not

increase the use of the drug. Among the actions covered under this

categorical exclusion may be approvals of new dosage forms, prodrugs,

generic drug products, and manufacturing supplements that may change

the method or site of manufacture of a drug but not its use.

Actions under proposed Sec. 25.31(b) that may increase the use or

disposal of a drug product may be categorically excluded if the

concentration of the substance in the environment will be below 1 part

per billion (ppb), the level that FDA has found, based on past

experience, will not significantly affect the aquatic environment. This

reflects a change from current regulations that require an

environmental assessment in any case in which an action may increase

the use of a drug. The basis for this change is described below.

CDER performed a retrospective review of available toxicity

information from EA's that were previously submitted in support of

NDA's and NDA supplements. This information, which includes data from

each review division that are representative of pharmacological drug

classifications, has routinely demonstrated that there are no

significant observed effects on relevant standard test organisms in the

aquatic environment at concentrations below 1 ppb.

Based on the method of entry into the environment from use and

their physical and chemical characteristics (e.g., water solubility),

human drugs would be expected predominantly to enter the aquatic

environment, and the data submitted in EA's reviewed by CDER have

routinely supported this hypothesis. Human drugs and their metabolites

enter the environment from use by excretion from patients. The majority

of hospitals, clinics, and homes in the United States are serviced by a

wastewater treatment facility where compounds are subjected to some

form of aerobic and anaerobic decomposition. Drug and/or metabolites

that are not degraded in the wastewater treatment facility may be

discharged into surface water or removed from the wastewater treatment

plant in sludge.

The data also have routinely shown that in those cases in which an

applicant has provided toxicity results for terrestrial organisms in

addition to acute toxicity results for aquatic organisms, the drugs are

toxic to aquatic organisms at lower levels than they are to terrestrial

organisms, suggesting that the use of aquatic organisms is a

conservative approach.

CDER evaluates the potential for significant environmental effects

by relating the concentrations determined to have toxic effects on

relevant standard test organisms to the level of the substance expected

in the environment. CDER's retrospective review shows that drugs at

concentrations less than 1 ppb in the aquatic environment have no

significant effect on relevant standard test organisms and, therefore,

are unlikely to have a significant effect on the environment. The vast

majority of actions taken by CDER result in the substance being in the

aquatic environment at concentrations less than 1 ppb because the

majority of drugs are produced and used at low levels, and the use of

drugs is not typically localized but rather is spread throughout the

United States.

One of the criteria for determining that a drug is safe for human

use is consideration of its potential to bioaccumulate. The vast

majority of drugs do not have the physical or chemical characteristics

that would allow them to bioaccumulate in tissue because this would

raise safety concerns for use in humans. If a drug does have the

physical or chemical characteristics that would allow it to

bioaccumulate, there has to be a mechanism for the human body to

metabolize the compound to a substance that has lower bioaccumulation

potential so that it is cleared from the body. In the environmental

assessments that CDER reviewed, bioaccumulation has not been an issue.

Thus, FDA has determined that actions that may increase the use or

disposal of a drug should be categorically excluded if the

concentration of the substance in the environment from use will be less

than 1 ppb and no extraordinary circumstances exist. For example, even

under conditions in which an action would increase the use of a drug,

such as an efficacy supplement adding a new indication, the proposed

action may be categorically excluded under this proposal if the

substance in the environment will be below 1 ppb. CDER has provided

guidance on appropriate calculations for estimating environmental

concentrations (Guidance for Industry for the Submission of an

Environmental Assessment in Human Drug Applications and Supplements,

November 1995).

CDER will continue to critically review the environmental toxicity

information submitted for those actions requiring an EA. As additional

data become available to CDER, the agency may propose to modify the 1

ppb environmental concentration cut-off through notice and comment

rulemaking.

Proposed Sec. 25.31(a) and (b) include actions on NDA's. Under the

current regulations (Sec. 25.24(c)(1) and (c)(2)), abbreviated new drug

applications (ANDA's) and supplements may be categorically excluded,

but NDA's for the same type of action may not. Sometimes an applicant

has a choice whether to submit a proposed action as an NDA or ANDA

(e.g., a new dosage form may be submitted as an ANDA with a suitability

petition or as an NDA). Thus, the applicant's choice of submission

would determine whether an EA would need to be submitted. Proposed

Sec. 25.31(a) and (b) would permit FDA to treat NDA's, abbreviated

applications, and supplements alike based on the type of action being

affected by the application.

Current Sec. 25.24(c)(6) categorically excludes actions on OTC

monographs if the product is already marketed for the proposed use. FDA

is proposing to add OTC monographs to proposed Sec. 25.31(a) and (b)

because, by action on an OTC monograph, FDA permits the manufacture and

marketing of OTC drugs that meet the monograph. It should be noted that

actions to switch drugs from prescription to OTC use that are submitted

in an NDA or supplement would also be covered under these provisions.

Proposed Sec. 25.31(a) and (b) would also delete any reference to

``actions on amendments'' to clarify that the agency

[[Page 14926]]

does not take actions on amendments. Amendments are merely changes to a

pending application that are incorporated into the application. The

action the agency takes is on the application as a whole, not on the

amendment.

Proposed Sec. 25.31(a) and (b) applies to drugs regulated by CDER.

FDA is proposing a new categorical exclusion in Sec. 25.31(c) for

substances that occur naturally in the environment, that would apply to

both drugs and biologics. Proposed Sec. 25.31(b) would apply to actions

on an NDA, abbreviated application, application for marketing approval

of a biologic product, a supplement to such applications, or action on

an OTC monograph when the action is not expected to alter significantly

the concentration or distribution of the substance, its metabolites, or

degradation products in the environment. Under the current regulations,

FDA requires an abbreviated EA for a drug that occurs naturally in the

environment. These abbreviated EA's require information about the

production site and about whether the use of the product will

significantly alter the concentration, distribution, and effect of the

natural substance in the environment.

Since the publication of the NEPA regulations in 1985, FDA has

reviewed abbreviated EA's for substances that are naturally occurring.

FDA has found that actions on submissions for these substances will not

affect the environment if the action will not significantly alter the

concentration or distribution of the natural substance in the

environment. Under these circumstances, the agency has prepared

FONSI's. Both CDER and CBER routinely include in safety evaluations

evidence that a product and/or living system used to produce the

product are inactivated following production and prior to release into

the environment, if there is a reasonable possibility that the product

or living system may be harmful to the environment. Therefore, there

are not likely to be any environmental effects. The proposed

regulations would categorically exclude an action for a substance that

occurs naturally in the environment when the action will not alter

significantly the concentration or distribution of the substance in the

environment. FDA has access to information regarding metabolites and

degradation products to aid in determining if the categorical exclusion

request is appropriate.

When an action does alter significantly the concentration or

distribution of a naturally occurring substance, its metabolites, or

degradation products in the environment, e.g., when the use and

disposal will occur in a geographic area where the substance is not

naturally occurring, an EA may be required.

FDA is proposing in Sec. 25.31(d) to expand the categorical

exclusion provision for the withdrawal of approval of an NDA or

abbreviated application. The agency is proposing that all types of

withdrawals of approval, whether requested by industry or initiated by

the agency, be categorically excluded because, based on CDER's

experience, these types of actions will not result in the production or

distribution of any substances and, therefore, will not result in the

introduction of any substance into the environment.There would be no

increase in use of substitutes? See line 21 on page 38 (of 1/26 draft).

EIS considered increase of hydrocarbon propellants in anti-perspirant

aerosols.

Proposed Sec. 25.31(e) would revise the categorical exclusions for

actions on an IND. Current Sec. 25.24(c)(4) categorically excludes

actions on IND's if the drug shipped under such notice is intended to

be used for clinical studies or research in which waste will be

controlled or the amount of waste expected to enter the environment may

reasonably be expected to be nontoxic. Under proposed Sec. 25.31(e),

FDA would categorically exclude all IND's. In many cases, FDA's actions

on IND's do not significantly increase the use of the drug or the

amount of drug introduced into the environment because the drug is

being tested in few patients or is already being marketed for another

use. Therefore, no changes in environmental effects will occur. In

those cases in which an increase in the use of the drug may occur as a

result of an investigation under an IND, CDER's experience in reviewing

actions on IND's indicates that significant environmental effects will

not occur because the use of such drugs is limited and controlled.

The agency is proposing to delete the language ``if the drug

shipped * * * may reasonably be expected to be nontoxic'' because an

action that results in waste that is expected to be toxic would require

an EA under proposed Sec. 25.21 Extraordinary circumstances.Is that

what 25.21(a) means--that if waste is toxic, there may be harm and an

EA will be required?

Proposed Sec. 25.31(g) would add a categorical exclusion for the

testing and release by CBER of lots or batches of a licensed biologic

product. The effects on the environment of licensed biologic products

are evaluated during the safety evaluation and approval of the license

application. Therefore, conducting a separate NEPA review for the

testing and release by CBER of individual lots or batches is

unnecessary.

Proposed Sec. 25.31(i) would permit a categorical exclusion for the

establishment of a comparability determination for a biologic product

subject to licensing. Establishment of a comparability determination

does not result in introduction of a substance into the environment. A

substance will be introduced into the environment only when CBER has

made a comparability determination and subsequently approves a license

application for a specific biologic product. The environmental

considerations will be made in connection with the review of individual

license applications that meet the comparability criteria.

Proposed Sec. 25.31(j) incorporates current Sec. 25.24(c)(10), the

categorical exclusion for promulgation, amendment, or revocation of a

standard for a licensed biologic product, and would eliminate the

current requirement that there be no increased use of the product. The

standards normally explain how the product is to be manufactured and

any additional requirements for approval and marketing. Therefore, the

increased use criterion is unnecessary.

Proposed Sec. 25.31(k), regarding revocation of a biologic product,

would eliminate the current criteria in Sec. 25.24(c)(9) that the

biological product ``is no longer being marketed'' or that the action

is ``at the request of the license holder. The agency is proposing to

delete these criteria as unnecessary because revocation of a license

for a biologic product means that the product can no longer be

marketed. Marketing of the product after license revocation must cease

regardless of whether the revocation was at the request of the license

holder or initiated by the agency. Revocation of a license for a

biologic product under any circumstances will not result in the

introduction of any substance into the environment and, therefore, will

not significantly affect the environment.

The agency is also proposing other minor, nonsubstantive amendments

to delete unnecessary language, improve the accuracy and clarity of the

categorical exclusions, and reflect current terminology.

3. Foods, Food Additives, and Color Additives

In the President's National Performance Report, ``Reinventing Food

Regulations,'' January 1996, the President announced that FDA proposed

to reduce the number of EA's

[[Page 14927]]

submitted by industry under NEPA by increasing the number of

categorical exclusions for food and color additives and generally

recognized as safe (GRAS) substances based on little or no impact on

the environment from the use and disposal of these products. As

described below, in fulfillment of this commitment, FDA is proposing

additional categorical exclusions for actions on foods, food additives,

color additives, and GRAS substances which, based on experience in

reviewing these types of actions, the Center for Food Safety and

Applied Nutrition (CFSAN) has concluded will not significantly affect

the human environment.

As was explained previously, FDA is proposing to remove criteria

from certain exclusions in current Sec. 25.24. For actions involving

foods, food additives, color additives, and GRAS substances, the

criteria for the exclusions in current Sec. 25.24(a)(10), (b)(2),

(b)(3), (b)(7), (b)(8), and (b)(9) have been removed. These exclusions

can be located in proposed Secs. 25.30(j), and 25.32(b), (c), (f), (g),

and (h). This change is being made because the provisions in proposed

Sec. 25.21 Extraordinary circumstances could apply to any of the

agency's exclusions, making certain criteria for individual exclusions

unnecessary.

In addition, to reflect current FDA policy, the agency is removing

from part 25 the environmental review requirements for the

establishment of action levels for unavoidable poisonous or deleterious

substances in food or food packaging, and for natural or unavoidable

defects in food that present no health hazard. This change is discussed

below.

For the classes of actions proposed for categorical exclusion in

Sec. 25.32(i), (j), (k), (l), (o), (q), and (r), FDA has traditionally

required certain information to assess the potential environmental

impact of the production of the food additive, color additive, or GRAS

substance. In all cases, FDA has found in its reviews that the

production of these substances did not significantly affect the

environment. The agency has determined that FDA ordinarily will not

consider potential impacts at sites of production of FDA-regulated

products, as discussed in section III.D of this document.

a. Proposed Sec. 25.32(f). Currently, FDA's NEPA procedures in

Sec. 25.24(b)(7) provide for a categorical exclusion for actions

relating to the affirmation of a food substance as GRAS if the

substance is already marketed for the use for which affirmation is

sought. FDA is proposing to expand this categorical exclusion in

proposed Sec. 25.32(f) to include actions to establish and amend

regulations under part 181 (21 CFR part 181) for prior-sanctioned

ingredients that are already marketed in the United States. Actions

involving prior-sanctioned ingredients are similar to certain GRAS

affirmation actions in that the food substance is likely to be already

marketed in the United States for the proposed use at the time the

action is being considered and will continue to be marketed after the

regulation is published. As defined in Sec. 170.3(l) (21 CFR 170.3(l))

and Sec. 181.5(a), a prior sanction shall exist only for a specific use

of a substance for which there was explicit approval by FDA or the U.S.

Department of Agriculture (USDA) before September 6, 1958. Actions to

affirm substances as GRAS or prior-sanctioned for the specific uses for

which they were already marketed in the United States create little or

no change in the introduction of the substance into the environment.

Therefore, such actions have no significant effect on the environment.

b. Proposed Sec. 25.32(i). FDA is proposing to amend its NEPA

procedures to categorically exclude from the requirement to prepare an

EA actions to approve a food additive petition or grant a request for

exemption from regulation as a food additive under Sec. 170.39 (21 CFR

170.39) (threshold of regulation) when a food additive is a functional

component of finished food-packaging materials present at not greater

than 5 percent-by-weight. FDA based this proposed exclusion on its

review of 95 petitions for food additives in this class, all of which

resulted in FONSI's, and on the evaluation of the potential for future

petitions in this class to have significant environmental effects. FDA

has had limited experience in considering the environmental impact of

threshold of regulation submissions because the regulations

establishing a threshold of regulation policy were recently issued (60

FR 36582, July 17, 1995). However, because the information currently

required for such submissions is identical to the information required

for the food-packaging class of indirect food additives discussed in

this section, the agency believes that its experience with the 95 food

additive petitions is relevant to these threshold of regulation

submissions and that these submissions also warrant a categorical

exclusion.

The agency's evaluation of functional components of food-packaging

materials present at not greater than 5 percent-by-weight has

traditionally included consideration of potential impacts relating to

the disposal of food-packaging materials containing the additive and

the use of natural resources and energy.

To determine the potential for significant introductions of

substances into the environment at the site of disposal of food-

packaging materials, i.e., municipal solid waste landfill or combustion

sites, the agency currently requires an estimate of the maximum yearly

market volume for the proposed use of the food additive and the percent

of that amount that will become a component of the finished food-

packaging material. To determine the potential for significant

introductions at landfill sites, FDA estimated the concentration of the

additive that could be present in landfill leachate for each of the 95

petitions it reviewed for additives used as functional components of

food-packaging materials. FDA found that in virtually all cases, the

concentration of the additives in landfill leachate was less than 50

ppb. The concentration of the additives in surface or ground water

receiving landfill leachate was expected to be substantially less,

taking into consideration the mobility and degradation of the additives

in landfills and their dilution in receiving waters.

Consequently, FDA determined in all cases that these extremely low

levels would not have significant environmental impacts at landfill

sites. The agency believes that approvals of future petitions in this

class are even less likely to result in significant introductions of

substances at landfill sites because EPA published new landfill

regulations in the Federal Register of October 9, 1991 (56 FR 50978),

that require new and expanded landfills to have leachate collection

systems and liners to prevent leachate from entering surface or

groundwater. Although operators of existing landfills are not required

to retrofit liner systems, they are required to monitor groundwater

adjacent to existing landfills and to take corrective action as

appropriate.

The agency's evaluation of petitions for additives used as

functional components of food-packaging materials has also shown that

there is little potential for significant introductions from the

combustion of packaging materials containing the additives. These types

of additives are used at low levels in the packaging materials, <5

percent by weight, and, therefore, the additional amounts of combustion

products emitted were found to be insignificant compared to the levels

already being generated during municipal solid waste combustion.

Because FDA's experience shows that the use levels for additives used

as

[[Page 14928]]

functional components of food-packaging materials are low, the agency

believes that future approvals will also result in insignificant

introductions into the environment at municipal solid waste combustor

sites.

Under current part 25, FDA requires no documentation to assess

potential impact on energy and resource use if the proposed additive is

intended for the same use as another additive already in use and will

not materially change the potential uses of the packaging materials to

which it is added. The agency has required sponsors to provide

information in an abbreviated EA showing that these criteria are met.

Based on FDA's experience in reviewing petitions for functional

components of food-packaging materials, the agency has found that

petitioners generally were able to demonstrate that a proposed additive

would compete with and replace other, already regulated additives and

that approval would not change the uses of the packaging materials to

which they were added. In cases where a proposed additive did not

compete with and replace an already regulated additive, the agency was

still able to conclude that there would not be a significant impact on

energy and natural resource use largely because use of the additive in

food-contact articles represented a very small fraction of total usage.

Thus, based on the low levels of use of these functional components

of food-packaging materials and on FDA's experience reviewing

abbreviated EA's for these functional components, the agency believes

that approvals of future submissions for such additives are highly

unlikely to have significant effects on the environment. Therefore,

under proposed Sec. 25.32(i) a requestor need not ordinarily submit an

EA.

c. Proposed Sec. 25.32(j). FDA is proposing to categorically

exclude actions to approve a food additive and to grant a request for

exemption from regulation as a food additive under Sec. 170.39 when the

additive is a component of food-contact surfaces of permanent or

semipermanent equipment or of other food-contact articles intended for

repeated use (proposed Sec. 25.32(j)). This proposed exclusion is based

on FDA's experience with 43 petitions for additives used as components

of repeat-use food-contact articles, all of which resulted in a FONSI.

FDA has had limited experience in considering the environmental impact

of threshold of regulation submissions for components of repeat-use,

food-contact articles because the regulations establishing a threshold

of regulation policy were recently issued. However, because the

information currently required for such submissions is identical to the

information required for food additive petitions for these types of

indirect food additives used in repeat-use, food-contact articles, the

agency believes that its experience with the 43 food additive petitions

is relevant to these threshold of regulation submissions and that

approval of these submissions warrants a categorical exclusion.

In reviewing the petitions for components of repeat-use, food-

contact articles, the agency's evaluation of environmental impact has

traditionally included consideration of potential impacts relating to

the disposal of the food-contact articles containing the additive. To

determine the potential for significant introductions of substances

into the environment at the sites of disposal of food additives that

are used as components of the food-contact surfaces of permanent or

semipermanent equipment, or of other repeat-use articles, the agency

currently requires an estimate of the maximum yearly market volume for

the proposed use of the additive. In reviewing abbreviated EA's for

these additives, FDA found that these additives ordinarily have limited

potential for causing significant environmental effects as a result of

their use and disposal. The potential for significant introductions of

substances to the environment due to disposal is, in fact, very low

because of the long service life of the food-contact equipment or other

repeat-use articles, of which additives in this class are components,

and the limited market volumes of the additives as estimated by the

petitioners. Because its actions on these petitions and requests will

not significantly affect the environment, FDA will not ordinarily

require the preparation of an EA.

d. Proposed Sec. 25.32(k). FDA is proposing to categorically

exclude actions to approve food additive, color additive, and GRAS

affirmation petitions for substances added directly to food that are

intended to remain in food through ingestion by consumers and that are

not intended to replace macronutrients in food. This proposed exclusion

is based on FDA's experience reviewing 21 petitions in this class, all

of which resulted in a FONSI. Examples of the types of additives and

GRAS substances that belong to this class are the color additives added

to foods listed in 21 CFR parts 73 and 74, most of the direct food

additives listed in part 172 (21 CFR part 172), and certain GRAS

substances listed in part 184 (21 CFR part 184). Examples of substances

that are not included in the class for which this categorical exclusion

is being proposed are the substances intended to replace macronutrients

in food (such as sweetening agents intended to replace sugar, e.g., see

Secs. 172.800 and 172.804, and fat substitutes, e.g., Sec. 184.1498).

The agency's evaluation of the environmental effects of substances

added directly to food has included consideration of the potential for

impacts from the disposal of human waste products containing the

petitioned substance and/or its products of digestion and metabolism,

and from the use of natural resources and energy.

The substances added directly to food considered here will be

ingested by consumers as components of food containing these

substances. After ingestion, these substances are either digested and/

or metabolized to other substances or excreted largely intact. In all

cases, the agency's review of past actions on substances added directly

to food resulted in decisions to issue FONSI's. To address the

potential for environmental impacts from disposal of this class of

substances, the agency's FONSI's relied on one or more of the following

scenarios: (1) The agency's approval of the petition resulted in very

low levels (in the low ppb range or lower) of the substances in either

effluents and/or sewage sludge from publicly owned wastewater treatment

plants and these levels were determined not to be toxic to organisms in

the environment; (2) the petitioned substance was digested and/or

metabolized bypara.humans such that only products of digestion and

metabolism were expected to be excreted and these products were the

same as (or very similar to) the products of digestion and metabolism

resulting from human food; such products should have no potential for

significant environmental effects because wastewater treatment

facilities are already designed to handle them; or (3) the petitioned

substance was excreted largely intact but was rapidly degraded into

nontoxic products either in wastewater treatment plants or in the

environment.

FDA's experience shows that substances added directly to food and

intended to remain with food through ingestion that are the subject of

new petitions will have use and disposal patterns similar to those

described above and will not be toxic to organisms in the environment

at the expected levels of exposure. Thus, use and disposal of such

substances are not expected to result in significant environmental

effects.

The agency has also found, as a result of its review of petitions

for substances in the class being considered here, that

[[Page 14929]]

in no case was there potential for significant impacts on energy and

natural resources. These findings relied on one or more of the

following scenarios: (1) The substances were expected to compete with

and replace other already regulated substances with no significant

change in the overall use of natural resources or energy, (2) the

substances are also used in nonfood contact situations and the food-

contact usage represented a small increase in the overall production

and usage of the substance such that the small increase in the uses of

natural resources and energy was not significant, or (3) the predicted

market volumes for the petitioned substances were very small so that

the use of natural resources and energy for the petitioned substances

was very limited. In no case did the agency find that there would be

any effects on threatened or endangered species. Because the use and

disposal of substances added directly to foods and intended to remain

with foods through ingestion has no significant effect on the

environment and has very limited potential for significant effects on

energy and natural resources, EA's for these substances will not

ordinarily be required.

e. Proposed Sec. 25.32(l). FDA is proposing to categorically

exclude actions to approve color additives used in contact lenses,

sutures, polymethylmethacrylate filaments used in supporting haptics

for intraocular lenses, bone cement, and in other FDA-regulated

products that involve similar low levels of use. The agency reviewed

EA's for 20 color additive petitions for these types of uses and found

that all proposed uses involve small amounts of color additives.

Because of the nature of these uses, the highest annual market volume

encountered for any of these color additives was 12 kilograms (kg),

while most of the petitioned uses involved considerably less than 5 kg.

Consequently, the environmental introduction levels of the color

additives from manufacture, use, and disposal would be exceedingly

small. FDA's experience shows that petitions for color additives in

these types of applications will have very low market volumes such that

only extremely low levels of substances will be introduced into the

environment and will not cause significant environmental effects.

Therefore, FDA is proposing to categorically exclude actions on such

petitions from the requirement to prepare an EA.

f. Proposed Sec. 25.32(m). FDA is proposing to categorically

exclude actions to prohibit or otherwise restrict or reduce the use of

a substance in food, food packaging, or cosmetics, e.g., the withdrawal

of approval for the use of a food or color additive, removal of the use

of a substance from a GRAS list (21 CFR parts 182, 184, and 186), or

prohibition of the use of a prior-sanctioned substance (defined under

Secs. 170.3(l) and 181.5(a)). The agency has prepared EA's for 12

actions to withdraw approval for the use of a food or color additive or

to prohibit the use of a substance in food. The agency has prepared

only one EIS for the withdrawal of approval of a food additive. In

1978, the agency prepared an EIS for its action to prohibit the use of

certain chlorofluorocarbons in food, food additive, drug, animal food,

animal drug, cosmetic, and medical device products as propellants in

self-pressurized containers (43 FR 11301, March 17, 1978). The

specified chlorofluorocarbons were prohibited because their continued

use was predicted to result in the depletion of the stratospheric ozone

layer. FDA prepared the EIS as part of an interagency effort to address

this problem. CEQ determined that an EIS was necessary for this

particular action because of the controversy surrounding the scientific

issues associated with the potential effects of these chemicals on

stratospheric ozone. The agency considers its action on

chlorofluorocarbons to be an exception. It is the only action of this

type that involved potentially significant effects on the environment.

The effect of withdrawing approval or prohibiting the use of a

substance is to reduce or eliminate environmental exposure to that

substance. Thus, no potential exists for direct adverse environmental

effects from the agency's prohibition of the use of a substance. It may

sometimes be necessary, however, to consider the potential indirect

environmental effects that would result from increased use of

substitutes for the prohibited substance. Since the agency began

considering the environmental impact of its actions under NEPA, it has

not found that significant adverse environmental effects would result

from the increased use of a substitute for a food or color additive or

other food substance that was being restricted. In the agency's

evaluation of past actions in this class, the agency has found that

there are frequently a number of substitutes for the prohibited

substance. Thus, the increase in production, use, or disposal of

substitutes is spread among a number of substances. Further,

environmental exposure to any one substitute is minimal. In some cases,

the agency has found that substitutes have been previously subjected to

environmental review under NEPA by the agency, and that this review

encompassed the use of the substitute as a replacement for the

prohibited substance and resulted in an EA and FONSI being prepared.

Any new food or color additive that may be developed to replace a

prohibited one would undergo environmental review during the premarket

approval process.

g. Proposed Sec. 25.32(n). FDA is proposing to categorically

exclude actions to issue, amend, or revoke regulations pertaining to

infant formulas. FDA is proposing to exclude actions on infant formulas

because they have little or no potential for adverse environmental

effects. The preparation, distribution, and directions for use of

infant formulas are carefully controlled by regulations in 21 CFR parts

106 and 107 and, along with other foods, by the CGMP regulations in 21

CFR part 110. In addition, the nature of this product, a food designed

for infants, means that the product itself is very unlikely to cause

adverse environmental impacts. Infant formulas are expected to be used

and disposed of in a manner similar to other human food, but infant

formulas form only a small fraction of the total human food supply

since they are used only in the first year or 2 of human life.

Therefore, it is unlikely that future actions on infant formulas will

have potential for significant environmental effects, and thus, FDA is

proposing to exclude them from the requirement to prepare an EA.

h. Proposed Sec. 25.32(o). FDA is proposing to exclude actions to

approve a food additive petition when an additive is the intended

expression product(s) present in food derived from new plant varieties.

The proposed exclusion is based on our determination that the USDA

Animal and Plant Health Inspection Service (APHIS) has lead

responsibility, under the Federal Plant Pest Act (7 U.S.C. 150aa et

seq.), to prevent the movement and dissemination in the United States

of plant pests. Under that authority, USDA APHIS addresses the

potential of new plant varieties to pose a plant pest risk in

accordance with the requirements mandated under NEPA. USDA considers

the potential for risk in a very broad context, so that not only is

direct disease or damage to plants and plant materials considered as a

component of plant pest risk, but indirect effects on beneficial or

other organisms in the agronomic context are also addressed. Before

issuing a determination of nonregulated status for an organism that has

been subject to USDA oversight because it was considered to present a

[[Page 14930]]

potential risk of being a plant pest, USDA conducts an environmental

analysis in compliance with its NEPA requirements that addresses plant

pest risk characteristics, disease and pest susceptibilities,

expression of any introduced gene products and effects thereof, new

enzymes, or changes to plant metabolism, weediness of the plant, impact

on the weediness of any other plant with which it can interbreed,

agricultural or cultivation practices, effects of the plant on

nontarget organisms, indirect plant pest effects on other agricultural

products, transfer of genetic information to organisms with which it

cannot interbreed, and any other information believed to be relevant to

a determination. The issues considered by FDA are the same or a subset

of the issues that USDA addresses as part of its NEPA review.

Therefore, a NEPA review by FDA would be redundant.

i. Proposed Sec. 25.32(p). FDA is proposing to categorically

exclude actions under part 101 (21 CFR part 101) to issue, amend, or

revoke a regulation in response to a reference amount petition

(Sec. 101.12(h)), a nutrient content claim petition (Sec. 101.69), a

health claim petition (Sec. 101.70), or a petition pertaining to the

label declaration of ingredients (Sec. 101.103). The agency has

regulations pertaining to various aspects of food labeling in part 101.

These regulations include provisions that enable interested persons to

petition the agency to issue regulations on several subjects related to

labeling, listed above. These petitions must include, under current

regulations, either a claim for categorical exclusion under current

Sec. 25.24 or an EA under current Sec. 25.31.

Current Sec. 25.24(a)(11) contains an exclusion for the

establishment or repeal by regulation of labeling requirements for

marketing articles, ``if there will be no increase in the existing

levels of use or change in the intended uses of the product or its

substitutes.`` The criteria are intended to ensure that the excluded

labeling actions will not cause significant environmental effects. This

exclusion can be used with petitions of the type listed above, if

petitioners demonstrate that the criteria are met. For those actions

that would not qualify for exclusion under current Sec. 25.24(a)(11)

because there will be an increase in the use of the product, FDA now

believes that this increased use will not have significant

environmental effects. Thus, the agency has determined that a specific

unqualified categorical exclusion for petitions related to food

labeling is appropriate.

When changes in the labeling on food products are allowed, there is

a potential for changes in the levels of use, and in the intended uses,

of such products or their substitutes. In fact, nutrient content claims

and health claims are generally intended to increase the use of the

labeled product. However, the changes that will result from FDA's

actions on the types of petitions listed above will be modifications of

the purchasing and consumption habits of consumers. A food labeled in

the newly allowed manner will be purchased and consumed instead of

another food that, for a variety of reasons, will not be labeled in

this new manner. The net result will be the substitution of one food

for a similar food. Thus, no significant adverse effects on the

environment will result. Therefore, the agency is proposing that its

future actions on petitions for the issuance, amendment, or revocation

of regulations on reference amounts customarily consumed per eating

occasion (Sec. 101.12(h)), on nutrient content claims (Sec. 101.69), on

health claims (Sec. 101.70), and on the label declaration of

ingredients (Sec. 101.103) be categorically excluded from the

preparation of an environmental assessment.

j. Proposed Sec. 25.32(q). FDA is proposing in Sec. 25.32(q) to

categorically exclude from the requirement to submit an EA actions to

approve food additive petitions for substances registered by EPA under

the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) (7

U.S.C. 136 et seq.) for the same use requested in the petition. FDA has

had limited experience in considering the environmental impact of

threshold of regulation submissions for substances registered by EPA

under FIFRA because the regulations establishing threshold of

regulation policy were recently issued. However, because the

information currently required for such submissions is identical to the

information required for food additive petitions for these types of

substances, the agency believes that its experience with food additive

petitions is revelant. This proposed exclusion is based on FDA's

experience reviewing 12 petitions in this class, all of which resulted

in a FONSI. All of these petitions were for antimicrobial substances

used either in the processing of food or in food-packaging materials.

FDA's evaluation of the potential environmental effects of

antimicrobial substances has included consideration of potential

impacts at the site of use and disposal of the antimicrobial substance,

and from the use of natural resources and energy. Currently, for the

use sites of antimicrobial substances, petitioners are directed to rely

on information in studies submitted to EPA for registration of the

product under FIFRA, and to describe any potential adverse

environmental effects determined by EPA. Petitioners may submit a brief

description and summary of results of EPA studies in lieu of the

complete test reports. For use sites, FDA has based its environmental

decision on a prediction of exposure levels, using introduction and

fate information, that is compared with relevant toxicological data to

determine the potential for significant environmental effects.

The agency's experience with antimicrobial petitions has been that,

before an antimicrobial product can be used in food-contact situations,

EPA will have already examined the environmental risks and benefits of

registering the product under FIFRA. The parallel between EPA's review

and FDA's environmental review is illustrated by FDA's finding that it

has not had to require environmental testing for antimicrobial products

because such tests were already conducted as part of EPA's review. In

addition, antimicrobial substances that are used and discharged at

point sources within the United States are subject to the requirements

of National Pollution Discharge Elimination System (NPDES) permits

under the Clean Water Act (33 U.S.C. 1251 et seq.). In registering a

product under FIFRA, EPA requires the label to state that: (1) The

product is not to be discharged into lakes, streams, ponds, estuaries,

oceans, or other waters unless in accordance with the requirements of

an NPDES permit and unless the permitting authority has been notified

in writing prior to discharge; and (2) the product is not to be

discharged to sewer systems without previously notifying the local

sewage treatment plant authority. EPA also requires, if necessary, that

labels contain information such as a warning of toxicity to fish and/or

wildlife, as specified in 40 CFR 156.10(h)(2)(ii). Thus, FDA has found

that its assessment of the fate and effects of antimicrobial substances

essentially duplicates the review by EPA under FIFRA and, to some

extent, the review by NPDES permitting authorities under the Clean

Water Act.

Currently, petitioners must address the potential for impact on the

use of natural resources and energy as required in an EA by specifying

the natural resources and energy required to produce, transport, use,

and/or dispose of a given amount of the product that is the subject of

the action. FDA's experience with this area of potential impacts is

that these types of substances almost always compete with and replace

other similar substances so that there is

[[Page 14931]]

little or no change in the use of natural resources and energy. Thus,

FDA believes that future food additive petitions for the same use as

pesticides approved by EPA under FIFRA will have little or no potential

for significant environmental impacts and that FDA's actions on these

petitions warrant exclusion from the requirement to prepare an EA.

k. Removal of action levels. At the time the current environmental

regulations were issued, the agency believed that the establishment of

an action level required environmental review. Thus, the agency

included a paragraph for the establishment of action levels in current

Sec. 25.22(a)(11) and specified an EA format in current Sec. 25.31d.

FDA also provided a categorical exclusion in current Sec. 25.24(b)(6)

for action levels for natural or unavoidable defects in food for humans

or animals if these defects presented no health hazard.

In 1987, in a limited holding, the Court of Appeals for the D.C.

Circuit in Community Nutrition Institute v. Young, 818 F.2d 943 (D.C.

Cir. 1987), found that FDA was treating its action levels as

substantive, legislative rules and, thus, action levels were subject to

the notice-and-comment requirements of the Administrative Procedure Act

(5 U.S.C. 551 et seq.). The court recognized, however, that FDA could

proceed by action levels that are not binding rules. Since the court's

holding, FDA has followed this approach. Under its statutory authority

under 21 U.S.C. 342(a)(1), (a)(2)(A), and 346 to limit the amount of

poisonous or deleterious substances in food, FDA establishes ``action

levels'' to inform food producers of the level of contaminants in food

that may result in regulatory action. Action levels are not intended to

bind the public, or FDA, or to create or confer any rights, privileges,

immunities, or benefits on or for any private person, but are intended

merely for internal FDA guidance for deciding whether to bring an

enforcement action. The establishment of an action level is not agency

action and is not subject to NEPA.

Moreover, under CEQ regulations (40 CFR 1508.18(a)), bringing

judicial, administrative, civil, or criminal enforcement actions is not

major Federal action. Because establishment of action levels is

intended merely for internal guidance for deciding whether to bring an

enforcement action, establishment of an action level is not major

Federal action.

Therefore, FDA is proposing to remove all references to action

levels from part 25. The agency will continue to apply these

regulations to the establishment of tolerances for poisonous or

deleterious substances in food for human or animal consumption or in

packaging materials intended for use with human food and animal feeds.

l. Proposed Sec. 25.32(r). FDA is proposing to categorically

exclude actions to approve a food additive, a color additive, or a GRAS

affirmation petition for a substance that occurs naturally in the

environment, when the action is not expected to alter significantly the

concentration or distribution of the substance, its metabolites, or

degradation products. This proposed exclusion is based on FDA's review

of 19 petitions for substances in this class, all of which resulted in

a finding of no significant impact.

The agency currently requires limited information for substances

that occur naturally in the environment, as specified in the

abbreviated EA format in current Sec. 25.31a(b)(5). This format focuses

on whether the use of the substance can reasonably be expected, on the

basis of all available evidence, to alter significantly the

concentration and distribution of the substance, its metabolites, or

degradation products in the environment and on information about the

environmental effects of substances expected to be emitted into the

environment. From its review of 19 petitions, the agency has found that

the use of naturally occurring substances as food additives, color

additives, or GRAS substances did not alter significantly the

concentration and distribution of the substance, its metabolites or

degradation products in the environment, and therefore, substances

emitted into the environment did not have adverse environmental

effects.

Among the 19 petitions for naturally occurring substances reviewed

by the agency were several petitions for substances intended to replace

macronutrients in food. In Sec. 25.32(k), FDA is not proposing to

exclude from the requirement to prepare an EA petitions for substances

intended to replace macronutrients. However, when a macronutrient

replacement is also a substance that occurs naturally in the

environment, the categorical exclusion proposed here will apply, unless

the agency finds that extraordinary circumstances exist, as delineated

in proposed Sec. 25.21.

4. Veterinary Drugs and Feed Additives

The National Performance Report, ``Reinventing Food Regulations,''

January 1996, announced FDA's proposal to reduce the number of EA's

submitted by industry under NEPA by increasing the number of

categorical exclusions for actions relating to animal drugs, animal

feeds, and food and color additives, which as a class have no

individual or cumulative significant effects on the environment. As

described below, in fulfillment of this commitment, FDA is proposing

additional categorical exclusions for actions on animal drugs and feed

additives that, based upon its experience in reviewing these types of

actions, the Center for Veterinary Medicine (CVM) has concluded will

not significantly affect the human environment.

Under proposed Sec. 25.33(a), actions relating to new animal drug

applications (NADA's), abbreviated applications, and supplements to

such applications that do not increase the use and disposal of the

substances are categorically excluded.

Proposed Sec. 25.33(a) includes the categorical exclusions listed

in current Sec. 25.24(d)(1) and (d)(2), and broadens the categorical

exclusion to allow FDA to categorically exclude other actions that do

not result in increased use of a drug and, consequently, do not result

in an increase in the expected level of environmental exposure. For

example, the approval of a supplement for a new manufacturing site is

not specifically listed but may be categorically excluded if it is not

expected to result in increased use of the substance for which the

supplement was submitted. Proposed Sec. 25.33(a)(7) for animal drugs

used in feeds is the same as current Sec. 25.24(d)(2) but has been

revised for clarity because FDA approves animal drugs for use in animal

feeds.What about 512(m) and proposed 25.24(e)?

The categorical exclusions in proposed Sec. 25.33(a) include

actions relating to abbreviated new animal drug applications (ANADA's)

in recognition of the creation of ANADA's under the 1988 Generic Animal

Drug and Patent Term Restoration Act (GADPTRA) (21 U.S.C. 301 note). An

ANADA is merely an abbreviated form of an NADA and seeks to effectuate

the same action, approval of an animal drug. Therefore, the nature of

environmental considerations is similar. For animal drugs not otherwise

excluded in Sec. 25.33(a), the agency is reserving Sec. 25.33(b) to

provide for a categorical exclusion analogous to that contained in

proposed Sec. 25.31(b) for human drugs. The categorical exclusion would

be for actions that increase the use of an animal drug in the instance

that the agency determines a level at or below which the concentration

of the substance in the environment does not significantly affect the

environment.

[[Page 14932]]

FDA recognizes that proposed Sec. 25.31(b) for human drugs allows

for a categorical exclusion for increased uses of human drugs if the

concentration of the substance in the aquatic environment will be at or

below 1 ppb. At this time, FDA is not adopting a specific environmental

concentration from use of animal drugs because the agency is still

conducting a retrospective review of environmental assessments for

these products and a review of revelant environmental science. The

Animal Health Institute and FDA/CVM held an Environmental Risk

Assessment Workshop on February 20 and 21, 1996, to establish a

comprehensive ecological risk assessment process for the evaluation of

animal health products. Following this opportunity for public debate,

and for drugs not otherwise excluded, FDA will adopt a risk assessment

paradigm for determining environmental introductions for animal drugs

and an environmental concentration at or below which no meaningful

environmental effects are expected to occur.

Proposed 25.33(c) would categorically exclude any action on an

NADA, abbreviated application, or a supplement to such actions for

substances that occur naturally in the environment, when the action is

not expected to alter significantly the concentration or distribution

of the substance, its metabolites, or degradation products in the

environment. Currently, FDA's regulations require an abbreviated EA for

an animal drug substance that occurs naturally in the environment.

These abbreviated EA's require information about the production site

and about whether the use of the product will significantly alter the

concentration, distribution, and effect of the natural substance in the

environment.

Since the publication of the NEPA regulations in 1985, FDA has

reviewed abbreviated EA's for substances that are naturally occurring.

FDA has found that actions on submissions for these substances will not

affect the environment if the action will not significantly alter the

concentration or distribution of the natural substance in the

environment. Under these circumstances, the agency has prepared

FONSI's.

Therefore, the proposed regulations would categorically exclude

actions on an NADA, abbreviated application, or a supplement to such

applications for substances that occur naturally in the environment

when the action is not expected to alter significantly the

concentration or distribution of the substance, its metabolites, or

degradation products in the environment. FDA has access to information

regarding metabolites and degradation products to aid in determining if

the categorical exclusion request is appropriate. Neither an EA nor an

EIS would be required for such actions. When an action does alter

significantly the concentration or distribution of the products, its

metabolites, or degradation products in the environment, e.g., when the

use and disposal will occur in a geographic area where the substance is

not naturally occurring, an environmental assessment may be required.

Proposed Sec. 25.33(d) includes categorical exclusions for actions

relating to approval of applications for animal drugs intended for use

in nonfood animals, for local or general anesthesia, for ophthalmic or

topical applications, for the treatment of a disease occurring in minor

species animals, as defined in Sec. 514.1(d)(1)(i) (21 CFR

514.1(d)(1)(i)), and for use under prescription or veterinarian's

order. Under current Sec. 25.31a(b)(4), FDA requires abbreviated EA's

to be submitted as part of any request for such approvals. These

abbreviated EA's require environmental information for production

sites. Since the publication of the NEPA regulation in 1985, CVM has

reviewed many abbreviated EA's for these types of products. In every

instance, the agency has prepared a FONSI because the manufacturing was

determined to be in compliance and would remain in compliance with the

Federal, State, and local environmental requirements that apply to the

site of manufacturing, and the market volume for such products was so

low that FDA found, based on its experience, the drugs would not

significantly affect the environment. Furthermore, as the agency

explains in section III.D. of this document, the agency has determined

that ordinarily FDA will not consider potential impacts at the site of

production.

The categorical exclusion for local and general anesthetic products

applies only to those products that are administered individually. Some

anesthetic products may be intended to be administered to many animals

or in significant quantities. In these instances, potential

environmental effects exist that require environmental analysis. The

exclusion for ophthalmic and topical products is limited to those

products intended for nonsystemic use. Products used systemically could

result in greater environmental introductions that could potentially

affect the environment and, therefore, require further environmental

analysis. Furthermore, FDA is clarifying that the categorical exclusion

for drugs for minor species applies only to those animal drugs that

have been previously approved for use in another or the same species

when similar animal management practices are used. When management

practices are different, environmental introductions and impacts may

also be different and require environmental analyses. Minor species

include wildlife and endangered species (Sec. 514.1(d)(1)(ii)).

The categorial exclusion for animal drugs used under prescription

or veterinarian's order applies only to animal drugs for therapeutic

uses as defined in section 201(g)(1)(B) of the act (21 U.S.C.

321(g)(1)(B)). Based on its experience in reviewing EA's for these

products, FDA has found that prescription products are generally

administered individually to a limited number of animals for a limited

amount of time. Therefore, there are no significant environmental

effects. However, FDA may require an EA if the agency determines that

there are extraordinary circumstances associated with the use of such a

product.

Current Sec. 25.24(d)(4) categorically excludes actions on an

investigational new animal drug application (INAD) if the drug to be

shipped under such notice is intended to be used for clinical studies

or research in which wastes will be controlled or the amount of wastes

expected to enter the environment may reasonably be expected to be

nontoxic. Under proposed Sec. 25.33(e), FDA would categorically exclude

all actions on INAD's. In many cases, FDA's actions on INAD's do not

significantly increase the use of the drug and, thus, the amount of

drug introduced into the environment. Therefore, no changes in

environmental effects will occur. In those cases where an increase in

use of a drug may occur as a result of an investigation under an INAD,

FDA's experience from reviewing many actions on INAD's shows that

significant environmental effects will not occur because the use of

such drugs is limited and controlled.

Proposed Sec. 25.33(f) would categorically exclude actions on

applications submitted under section 512(m) of the act (21 U.S.C.

360b(m)). FDA is proposing to exclude actions on such applications

because they permit feed manufacturers to manufacture animal feed

bearing or containing new animal drugs previously approved for use in

feeds. The potential for environmental effects to occur is considered

at the time the new animal drug is approved for use in feed. Therefore,

there is no need to require an

[[Page 14933]]

additional EA each time the agency considers approval of an application

submitted under section 512(m) of the act.

Current Sec. 25.24(d)(3) categorically excludes withdrawals of

approval of NADA's when the drug is no longer marketed or at the

request of the application holder. Under proposed Sec. 25.33(g), FDA

would categorically exclude withdrawals of approval of ANADA's, as well

as withdrawals of approval of NADA's, without conditions. FDA has

determined that withdrawal of an NADA or ANADA approval does not

significantly affect the environment because any change in introduction

of the drug will generally be a decrease.

Under proposed Sec. 25.33(h), FDA would categorically exclude

actions to withdraw the approval for uses of food additives in animal

feeds or to remove substances for use in animal feeds from the GRAS

list or to remove substances from the GRAS list (parts 182, 184, or

186). Withdrawal or removal of a food additive substance that reduces

or eliminates animal feed use will not significantly affect the

environment because any change in introduction of the substance to the

environment will generally be a decrease.

In those cases where the withdrawal of the NADA, ANADA, or FAP, or

GRAS substance has resulted in the use of a substitute product, the

agency has found in all instances that the increased use of the

substitutes will not significantly affect the environment.

FDA is proposing to eliminate the categorical exclusions under

current Sec. 25.24(d)(5) and (d)(6) because FDA does not do testing and

certification of batches of antibiotics for animal use, and FDA does

not use monographs for animal drugs. FDA is proposing to eliminate

current Sec. 25.24(d)(7). This action takes place under an INAD, and

its effect is to set the standard for approving ANADA's. FDA will

determine whether it needs to consider environmental effects when it

approves individual ANADA's.

5. Devices and Electronic Products

The agency is proposing to redesignate current Sec. 25.24(e) as

proposed Sec. 25.34 and to remove criteria in Sec. 25.24(e)(4) and

(e)(7), now incorporated in proposed Sec. 25.21 Extraordinary

circumstances.

D. Subpart D--Preparation of Environmental Documents

The proposed rule would reorganize current subpart C of part 25 to

improve the usefulness and readability of the current regulations.

Proposed Sec. 25.40(b) would eliminate the EA and abbreviated EA

formats and delete any reference to formats. After consultation with

CEQ, the agency has decided to remove the standard formats from part

25, and to provide appropriate formats in guidance documents. Guidance

documents, which do not bind the agency or the public, are more easily

revised. Use of such documents will give FDA greater flexibility to

tailor environmental documents to reflect state-of-the-art developments

in environmental analysis and to assist companies in focusing on

important environmental issues. Information/guidance concerning the

nature and scope of information that an applicant or petitioner should

submit in an EA may be obtained from the center responsible for the

action subject to environmental evaluation (proposed Sec. 25.40(c)).

In the Federal Register of January 11, 1996, FDA announced the

availability of a guidance document entitled, ``Guidance for Industry

for the Submission of an Environmental Assessment in Human Drug

Applications and Supplements'' (61 FR 1031). The guidance, prepared by

CDER, is intended to assist industry by providing guidance on how to

prepare EA's for submission to CDER as part of NDA's, antibiotic

applications, ANDA's, abbreviated antibiotic applications, and IND's.

This guidance will be amended to reflect the final regulations and

categorical exclusions and to include biologic products subject to

licensure under the PHS Act. The guidance document employs a tiered

approach to testing and accepts the use of test methods recognized and

recommended by competent authorities such as FDA (see e.g., FDA's EA

Technical Assistance Handbook), EPA (see 40 CFR parts 796 and 797) and

the Organization for Economic Co-operation and Development. Under the

proposed rule, this approach will continue to be acceptable.

The current formats in part 25 focus the environmental analysis on

the use and disposal from use of FDA-regulated articles but also

address production impacts. FDA proposes to maintain this focus in the

proposed revised regulations, but, for the following reasons, is

proposing to change the way it addresses production impacts. To address

the potential environmental impacts from production of FDA-regulated

articles, FDA currently requires a limited amount of information to

make sure that the article will be produced in compliance with

applicable emissions requirements. Specifically, the agency requires

that the following information be included in an EA: A list of the

substances expected to be emitted, the controls exercised, a citation

of applicable emissions requirements and statement of compliance with

these requirements, and a discussion of the effect the approval of the

petition will have on compliance with these requirements.

FDA recognizes, however, that Federal, State, and local

environmental protection agencies have the responsibility for issuing

regulations, permitting and licensing facilities, and enforcing

compliance with the requirements that these agencies have determined

are necessary to ensure adequate protection of the environment from

emissions from production operations. Regulating emissions from

production sites requires balancing between air, water, and solid waste

emissions for all production operations carried out at a production

site and in the region with consideration of the costs of compliance

and available technology that requires expertise found primarily in

Federal, State, and local environmental agencies. As required by

environmental regulations and/or as conditions of retaining licenses

and permits, manufacturers must obtain or modify permits and provide

information to these agencies when production operations are initiated

or changed. The information required to be provided to FDA regarding

production impacts and compliance with emission requirements is

information that is generally required to be provided to or is known by

other agencies whose responsibility is to monitor compliance.

FDA has reviewed hundreds of EA's in which information regarding

the manufacturing site, such as emitted substances and emission

controls, was provided. As a result of this review, FDA has found that

FDA-regulated articles produced in compliance with all applicable

emission requirements (e.g., Clean Air Act, Clean Water Act,

Occupational Safety and Health Act) will not significantly affect the

environment. Based on these findings, FDA has determined that it is no

longer necessary to review a company's compliance with Federal, State,

and local environmental laws and FDA is proposing to delete the

requirements for the submission of emission information for production

sites. Accordingly, under the proposed regulations, FDA will continue

to focus its environmental reviews on the use and disposal from use of

FDA-regulated articles, and FDA will no longer routinely require

submission of information regarding manufacturing sites or a

certification of compliance with Federal, State, and

[[Page 14934]]

local emission requirements. However, if information available to the

agency or the applicant establishes that the general or specific

emission requirements promulgated by Federal, State, or local

environmental protection agencies do not address unique emission

circumstances and the emissions may harm the environment, this would be

sufficient grounds for requesting manufacturing information in an EA.

FDA generally requires manufacturing information to be submitted as

part of applications or petitions for FDA-regulated articles. This

information will aid FDA in determining if a categorical exclusion

request is appropriate.

Proposed Sec. 25.40(a) includes additional information found in the

CEQ regulations to clarify that the EA shall include brief discussions

of the need for the proposal, alternatives, environmental impacts of

the proposed action, and a listing of agencies and persons consulted,

and include additional information to clarify the scope and focus of an

EA. Environmental documents shall concentrate on timely and significant

issues, not amass needless detail. To that end, the agency has included

some general information regarding the acceptability of using a tiered

testing scheme. A tiered testing scheme results in test termination

when sufficient data are available to assess the potential

environmental fate and effects of an FDA-regulated article in the

environment. Specific information regarding tiered testing will be

provided in guidance documents. Although the number of pages for any EA

may vary in relation to the complexity of the issues, generally they

should not exceed 30 pages, not including test reports and data.

The agency is proposing to add Sec. 25.40(b) to clarify that CEQ

regulations (40 CFR 1506.5(b)) place ultimate responsibility on FDA for

the scope and content of environmental analyses. Thus, FDA may require

additional information from applicants or may itself include additional

information in environmental documents (EA's, FONSI's, or EIS's) when

warranted. Proposed Sec. 25.40(c) would include information found in

current Sec. 25.30(a) and encourages applicants or petitioners who

submit EA's to FDA to consult with FDA regarding the appropriate scope

and content for EA's for the requested action. Proposed Sec. 25.40(d)

discusses incorporation of information in an EA by reference.

Proposed Sec. 25.41 would include information on FONSI's that is

found in current Sec. 25.32(a) and (c). The agency is proposing to

delete the language on notices of intent and draft, final, and

supplemental EIS's, found in current Secs. 25.33 and 25.34, because the

CEQ regulations describe the process for determining the scope of an

EIS and provide detailed requirements for the preparation of draft and

final EIS's. Thus, this information is duplicative and unnecessary in

FDA regulations (40 CFR 1501.7 and part 1502).

Proposed Sec. 25.42 would describe the subject matter that needs to

be discussed in an EIS and references the CEQ regulations governing the

requirements for preparation of an EIS. Proposed Sec. 25.42(c) fulfills

the CEQ requirement under 40 CFR 1502.9(c) that FDA adopt procedures

for introducing a supplement into its administrative record.

The agency is proposing to add new Sec. 25.43 to clarify the

agency's existing responsibility under the CEQ regulations to prepare a

concise public record of decision for cases requiring EIS's (40 CFR

1505.2).

Proposed Sec. 25.44 would include information found in current

Sec. 25.10(b), describing the responsibilities of lead and cooperating

agencies. The agency is proposing to delete duplicative and unnecessary

information on lead and cooperating agencies that is already found in

the CEQ regulations, and to delete the first sentence in current

Sec. 25.10(b) because it is self-evident that FDA will be the lead

agency for programs administered by FDA.

Proposed Sec. 25.45 would include information from current

Sec. 25.42, describing who the responsible agency official will be and

his or her responsibilities. The agency is proposing to remove

information in current Sec. 25.42 that is duplicative of requirements

already found in CEQ regulations.

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

Documents-

The proposed rule would improve the usefulness and readability of

the regulations by reorganizing current subpart D of part 25, ``agency

decisionmaking'' (now proposed ``Public Participation and Notification

of Environmental Documents'') by deleting unnecessary information that

is duplicative of requirements found in the CEQ regulations, and, as

discussed above, moving information to other relevant sections.

Proposed subpart E would now address public participation in the NEPA

process and clarify circumstances under which environmental documents

will publicly be disclosed. These revisions are consistent with our

responsibilities under the CEQ regulations and under Executive Order

12898, Federal Actions to Address Environmental Justice in Minority

Populations and Low Income Populations, February 11, 1994.

CEQ regulations require that agency procedures ensure full

compliance with NEPA to the extent possible, unless existing law

applicable to the agency's operations expressly prohibits or makes

compliance impossible (40 CFR 1500.6). Proposed Sec. 25.50 clarifies

that laws governing public disclosure may limit FDA's ability to comply

with NEPA and CEQ regulations.

Proposed Sec. 25.51(a) and (b), public disclosure of FONSI's and

EA's, would include the public disclosure information found in current

Sec. 25.30(b) and 25.41(b). The proposed rule would move the

information relating to statutory time frames from current

Sec. 25.40(c) to proposed Sec. 25.51(b)(1).

Proposed Sec. 25.52 would add new information relating to the

public disclosure of EIS's.

F. Subpart F--Other Requirements

Current subpart E will be renumbered as subpart F. The agency is

not proposing to amend this subpart.

IV. Environmental Impact Considerations

The agency has determined under current 21 CFR 25.24(a)(8) that

this action is of a type that does not individually or cumulatively

have a significant effect on the human environment. Therefore, neither

an EA nor an EIS is required.

V. Analysis of Impacts

FDA has examined the impacts of the proposed rule under Executive

Order 12866, under the Regulatory Flexibility Act (Pub. L. 96-354), and

under the Unfunded Mandates Reform Act (Pub. L. 104-4). Executive Order

12866 directs agencies to assess all costs and benefits of available

regulatory alternatives and, when regulation is necessary, to select

regulatory approaches that maximize net benefits (including potential

economic, environmental, public health and safety, and other

advantages; distributive impacts and equity). The Regulatory

Flexibility Act requires agencies to analyze regulatory options that

would minimize any significant impact of a rule on small entities. The

Unfunded Mandates Reform Act requires (in section 202) that agencies

prepare an assessment of anticipated costs and benefits before

proposing any rule that may result in an annual expenditure by State,

local, and tribal governments, in

[[Page 14935]]

the aggregate, or by the private sector, of $100,000,000 (adjusted

annually for inflation). That act also requires (in section 205) that

the agency identify and consider a reasonable number of regulatory

alternatives and from those alternatives select the least costly, most

cost effective, or least burdensome alternative that achieves the

objective of the rule. The following analysis demonstrates that this

proposed rule is consistent with the principles set forth in the

Executive Order and in these two statutes. The proposed rule is not an

economically significant regulatory action under Executive Order 12866.

Based on the approximate number of EA's that FDA currently receives

each year and the resources needed to prepare them, the agency

estimates that the proposed reduced requirements for submitting EA's

will result in an annual cost savings to industry of approximately

$15.7 million. The basis for this estimate is as follows:

Human pharmaceuticals: Approximately 125 EA's related to human

pharmaceuticals would be eliminated annually under the proposal. About

one-half of these are abbreviated EA's; the remainder are full

assessments. FDA assumes that the average cost of preparing an

abbreviated assessment was approximately $40,000, while the average

cost of a full assessment was approximately $200,000. These assumptions

yield a cost savings of about $2.5 million for abbreviated EA's and

$12.5 million for full EA's, for a total savings to industry from the

reduced requirements of EA's relating to human pharmaceuticals of

approximately $15 million per year.

Veterinary products: The proposed changes would eliminate

approximately 37 abbreviated EA's for veterinary products each year, at

an average cost of approximately $5,000 each. About 77 brief

submissions, which currently require categorical exclusion criteria

review, would also be eliminated; these cost an estimated $300 each to

prepare. Total cost savings to the veterinary products industry under

the proposal would thus be approximately $208,000 per year.

Food products: About 36 EA's per year received by CFSAN would be

eliminated under the proposal. Approximately 28 of these would have

been abbreviated EA's and 8 would have been full assessments under

current rules. FDA estimates that the cost of producing most

abbreviated EA's for CFSAN is approximately $2,500 and the average cost

of producing a full EA is approximately $50,000. These assumptions

imply an annual cost savings of approximately $70,000 for abbreviated

EA's and $400,000 for full EA's, for a total annual savings to the

foods industry of approximately $470,000.

In addition to these savings to industry, the proposed changes

would improve FDA efficiency by eliminating agency review costs of

approximately $1 million per year.

The Regulatory Flexibility Act requires agencies to analyze

regulatory options that would minimize any significant impact of a rule

of small entities. Because these regulations will not impose

significant new costs on any firms, the agency certifies that the

proposed rule will not have a significant economic impact on a

substantial number of small entities. Therefore, under the Regulatory

Flexibility Act, no further analysis is required.

VI. Paperwork Reduction Act of 1995

This proposed rule contains reporting requirements that are subject

to public comment and review by the Office of Management and Budget

(OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3506 and

3507). Therefore, in accordance with 5 CFR part 1320, a description of

reporting requirements with an estimate of the annual collection of

information burden is given below by cross reference to existing FDA

clearance submissions previously approved by OMB which this proposed

rule affects.

FDA is soliciting comments to: (1) Evaluate whether the proposed

collection of information is necessary for the proper performance of

the functions of the agency, including whether the information will

have practical utility; (2) evaluate the accuracy of the agency's

estimate of the proposed collection of information; (3) evaluate the

quality, utility, and clarity of the information to be collected; and

(4) minimize the burden of the collection of information on those who

are to respond.

Title: National Environmental Policy Act; Policies and Procedures.

Description: FDA has previously issued regulations that implement

NEPA (part 25). The proposed rule would reduce the number of NEPA

evaluations by providing for categorical exclusions for additional

classes of actions that do not individually or cumulatively have a

significant effect on the human environment and for which, therefore,

neither an EIS nor an EA is required. FDA is also proposing to amend

these regulations to ensure that the NEPA procedures are more concise

and understandable to the public and to reflect current FDA policy with

respect to environmental considerations. This proposed rule is in

response to initiatives announced in the President's National

Performance Reports, ``Reinventing Drug and Medical Device

Regulations,'' April 1995, and ``Reinventing Food Regulations,''

January 1996.

Description of Respondents: Persons and businesses, including small

businesses.

Estimated Annual Reporting and Recordkeeping Burden. The estimated

burden associated with the information collection requirements for this

proposed rule will be recognized in the individual FDA clearances where

NEPA considerations apply. Listed below are those clearances affected

by this regulation, including the section of title 21 CFR, the title,

and the OMB approval number:

Section 10.30, Citizen Petitions, 0910-0183; Sec. 71.1, Color

Additive Petitions, 0910-0185; Sec. 170.35, Affirmation of Generally

Recognized As Safe (GRAS) Status, 0910-0132; Sec. 101.12, Reference

amounts customarily consumed per eating occasion, 0910-0286;

Sec. 101.69, Petitions for nutrient content claims, 0910-0288;

Sec. 101.70, Petitions for health claims, 0910-0287; Sec. 170.39,

Threshold of regulation for substances used in food-contact articles,

0910-0298; Sec. 171.1, Food Additive Petitions, 0910-0016; Sec. 312.23,

Conditions for Exemption of New Drugs for Investigational Use, 0910-

0014; Sec. 511.1, New Animal Drugs for Investigational Use Exempt From

Section 512(a) of the Act, 0910-0117; Sec. 514.1, New Animal Drug

Applications, 0910-0032; Sec. 514.8, Supplemental New Animal Drug

Applications, 0910-0032; Sec. 571.1, Food Additive Petitions, 0910-

0016; Sec. 601.2 Product Licenses-Procedures for Filing, 0910-0124;

Sec. 812.20, Investigational Device Exemptions Application, 0910-0078.

The proposed rule would reduce these information collections that

have already been reviewed and approved by the OMB.-Reporting burdens

imposed by current part 25 are approved by OMB through December 31,

1997 (see OMB control number 0910-0190, ``National Environmental Policy

Act; Policy and Procedures--21 CFR Part 25'').

The agency has submitted copies of the proposed rule to OMB for its

review of these reporting requirements. Interested persons are

requested to send comments regarding information collection by May 3,

1996, to the Office of Information and Regulatory Affairs, OMB (address

above).

[[Page 14936]]

List of Subjects in 21 CFR Part 25

Environmental impact statements, Foreign relations, Reporting and

recordkeeping requirements.

Therefore, under the Federal Food, Drug, and Cosmetic Act, the

Public Health Service Act, and authority delegated to the Commissioner

of Food and Drugs, it is proposed that 21 CFR part 25 be revised to

read as follows:

PART 25--ENVIRONMENTAL IMPACT CONSIDERATIONS

Subpart A--General Provisions

Sec.

25.1 Purpose.

25.5 Terminology.

25.10 Policies and NEPA planning.

Subpart B--Agency Actions Requiring Environmental Consideration

25.15 General procedures.

25.16 Public health and safety emergencies.

25.20 Actions requiring preparation of an environmental

assessment.

25.21 Extraordinary circumstances.

25.22 Actions requiring preparation of an environmental impact

statement.

Subpart C--Categorical Exclusions

25.30 General.

25.31 Human drugs and biologics.

25.32 Foods, food additives, and color additives.

25.33 Animal drugs.

25.34 Devices and electronic products.--

Subpart D--Preparation of Environmental Documents

25.40 Environmental assessments.-

25.41 Findings of no significant impact.

25.42 Environmental impact statements.

25.43 Records of decision.-

25.44 Lead and cooperating agencies.

25.45 Responsible agency official

Subpart E--Public Participation and Notification of Environmental

Documents---

25.50 General information.

25.51 Environmental assessments and findings of no significant -

impact.

25.52 Environmental impact statements.-

Subpart F--Other Requirements

25.60 Environmental effects abroad of major agency actions.

Authority: Secs. 201-903 of the Federal Food, Drug, and Cosmetic

Act (21 U.S.C. 321-393); secs. 351, 354-361 of the Public Health

Service Act (42 U.S.C. 262, 263b-264); 42 U.S.C. 4321, 4332; 40 CFR

parts 1500-1508; E.O. 11514, 3 CFR, 1966-1970 Comp., p. 902, as

amended by E.O. 11991, 3 CFR, 1977 Comp., p. 123; E.O. 12114, 3 CFR,

1979 Comp., p. 356.

Subpart A--General Provisions

Sec. 25.1 Purpose.

The National Environmental Policy Act of 1969 (NEPA), as amended,

directs that, to the fullest extent possible, the policies,

regulations, and public laws of the United States shall be interpreted

and administered in accordance with the policies set forth in NEPA. All

agencies of the Federal Government shall comply with the procedures in

section 102(2) of NEPA except where compliance would be inconsistent

with other statutory requirements. The regulations in this part

implement section 102(2) of NEPA in a manner that is consistent with

FDA's authority under the Federal Food, Drug, and Cosmetic Act and the

Public Health Service Act. This part also supplements the regulations

for implementing the procedural provisions of NEPA that were published

by the Council on Environmental Quality (CEQ) in 40 CFR Parts 1500

through 1508 and the procedures included in the ``HHS General

Administration Manual, Part 30: Environmental Protection'' (45 FR 76519

to 76534, November 19, 1980).Sec. 25.5 Terminology.

(a) Definitions that apply to the terms used in this part are set

forth in the CEQ regulations under 40 CFR part 1508. The terms and the

sections of 40 CFR part 1508 in which they are defined follow:

(1) Categorical exclusion (40 CFR 1508.4).

(2) Cooperating agency (40 CFR 1508.5).

(3) Cumulative impact (40 CFR 1508.7).

(4) Effects (40 CFR 1508.8).

(5) Environmental assessment (EA) (40 CFR 1508.9).

(6) Environmental document (40 CFR 1508.10).

(7) Environmental impact statement (EIS) (40 CFR 1508.11).

(8) Federal agency (40 CFR 1508.12).

(9) Finding of no significant impact (40 CFR 1508.13).

(10) Human environment (40 CFR 1508.14).

(11) Lead agency (40 CFR 1508.16).

(12) Legislation (40 CFR 1508.17).

(13) Major Federal action (40 CFR 1508.18).

(14) Mitigation (40 CFR 1508.20).

(15) NEPA process (40 CFR 1508.21).

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

(17) Proposal (40 CFR 1508.23).

(18) Scope (40 CFR 1508.25).

(19) Significantly (40 CFR 1508.27).

(b) The following terms are defined solely for the purpose of

implementing the supplemental procedures provided by this part and are

not necessarily applicable to any other statutory or regulatory

requirements:-

(1) Abbreviated application applies to an abbreviated new drug

application, an abbreviated antibiotic application, and an abbreviated

new animal drug application.

(2) Active moiety means the molecule or ion, excluding those

appended portions of the molecule that cause the drug to be an ester,

salt (including a salt with hydrogen or coordination bonds), or other

noncovalent derivative (such as a complex chelate or clathrate) of the

molecule responsible for the physiological or pharmacological action of

the drug substance.

(3) Agency means the Food and Drug Administration (FDA).

(4) Increased use of a drug or biologic product may occur if the

drug will be administered at higher dosage levels, for longer duration

or for different indications than were previously in effect, or if the

drug is a new molecular entity. New molecular entity means a drug for

which the active moiety (present as the unmodified (parent) compound,

or an ester or a salt, clathrate, or other noncovalent derivative of

the base (parent) compound) has not been previously approved or

marketed in the United States for use in a drug product, either as a

single ingredient or as part of a combination product or as part of a

mixture of stereoisomers. The term ``use'' also encompasses disposal of

FDA-regulated articles by consumers.

(5) Responsible agency official means the agency decisionmaker

designated in part 5 of this chapter.

(c) The following acronyms are used in this part:

(1) CEQ--Council on Environmental Quality.

(2) CGMP--Current good manufacturing practice.

(3) EA--Environmental assessment.

(4) EIS--Environmental impact statement.

(5) The act--Federal Food, Drug, and Cosmetic Act.

(6) FIFRA--Federal Insecticide, Fungicide, and Rodenticide Act.

(7) FONSI--Finding of no significant impact.

(8) GLP--Good laboratory practice.

(9) GRAS--Generally recognized as safe.

(10) HACCP--Hazard analysis critical control point.

(11) IDE--Investigational device exemption.

(12) IND--Investigational new drug application.

(13) INAD--Investigational new animal drug application.

(14) NADA--New animal drug application.

(15) NDA--New drug application.

(16) NEPA--National Environmental Policy Act of 1969.-

(17) PDP--Product development protocol.

(18) PMA--Premarket approval application.-

[[Page 14937]]

Sec. 25.10 Policies and NEPA planning.

(a) All FDA's policies and programs will be planned, developed, and

implemented to achieve the policies declared by NEPA and required by

CEQ's regulations to ensure responsible stewardship of the environment

for present and future generations.

(b) Assessment of environmental factors continues throughout

planning and is integrated with other program planning at the earliest

possible time to ensure that planning and decisions reflect

environmental values, to avoid delays later in the process, and to

avoid potential conflicts.

(c) For actions initiated by the agency, the NEPA process will

begin when the agency action under consideration is first identified.

For actions initiated by applicants or petitioners, NEPA planning

begins when FDA receives a submission from an applicant or petitioner

seeking action by FDA. FDA may issue a public call for environmental

data or otherwise consult with affected individuals or groups when a

contemplated action in which it is or may be involved poses potential

significant environmental effects.

(d) Environmental documents shall concentrate on timely and

significant issues, not amass needless detail.

(e) If a proposed action for which an EIS will be prepared involves

possible environmental effects that are required to be considered under

statutes or Executive Orders other than those referred to under

``AUTHORITY'' in this part, these effects shall be considered in the

NEPA review, consistent with 40 CFR 1502.25 and the Department of

Health and Human Services' General Administration Manual, part 30.

Subpart B--Agency Actions Requiring Environmental Consideration

Sec. 25.15 General procedures.

(a) All applications or petitions requesting agency action require

the submission of an EA or a claim of categorical exclusion. A claim of

categorical exclusion shall include a certification of compliance with

the categorical exclusion criteria and shall certify that to the

applicant's knowledge, no extraordinary circumstances exist. Failure to

submit an adequate EA for an application or petition requesting action

by the agency of a type specified in Sec. 25.20, unless the agency can

determine that the action qualifies for exclusion under Secs. 25.30,

25.31, 25.32, 25.33, or 25.34, is sufficient grounds for FDA to refuse

to file or approve the application or petition.

(b) The responsible agency officials will evaluate the information

contained in the EA to determine whether it is accurate and objective,

whether the proposed action may significantly affect the quality of the

human environment, and whether an EIS will be prepared. If significant

effects requiring the preparation of an EIS are identified, FDA will

prepare an EIS for the action in accordance with the procedures in

subparts D and E of this part. If significant effects requiring the

preparation of an EIS are not identified, resulting in a decision not

to prepare an EIS, the responsible agency official will prepare a FONSI

in accordance with Sec. 25.41.

(c) Classes of actions that individually or cumulatively do not

significantly affect the quality of the human environment ordinarily

are excluded from the requirement to prepare an EA or an EIS. The

classes of actions that qualify as categorical exclusions are set forth

in Secs. 25.30, 25.31, 25.32, 25.33, or 25.34.

(d) A person submitting an application or petition of a type

subject to categorical exclusion under Secs. 25.30, 25.31, 25.32,

25.33, or 25.34, or proposing to dispose of an article as provided in

Secs. 25.30(d) or 25.32(h), is not required to submit an EA if the

person certifies that the action requested qualifies for a categorical

exclusion, citing the particular categorical exclusion that is claimed,

and certifies that to the applicant's knowledge, no extraordinary

circumstances exist.

Sec. 25.16 Public health and safety emergencies.

There are certain regulatory actions that, because of their

immediate importance to the public health or safety, may make adherence

to the procedural provisions of NEPA and CEQ's regulations impossible.

For such actions, the responsible agency official shall consult with

CEQ about alternative arrangements before the action is taken, or after

the action is taken, if time does not permit prior consultation with

CEQ.

Sec. 25.20 Actions requiring preparation of an environmental

assessment.

Any proposed action of a type specified in this section ordinarily

requires at least the preparation of an EA, unless it is an action in a

specific class that qualifies for exclusion under Secs. 25.30, 25.31,

25.32, 25.33, or 25.34:

(a) Major recommendations or reports made to Congress on proposals

for legislation in instances where the agency has primary

responsibility for the subject matter involved.

(b) Destruction or other disposition of articles condemned after

seizure or whose distribution or use has been enjoined, unless

categorically excluded in Secs. 25.30(d) or 25.32(h).

(c) Destruction or other disposition of articles following

detention or recall at agency request, unless categorically excluded in

Secs. 25.30(d) or 25.32(h).

(d) Disposition of FDA laboratory waste materials, unless

categorically excluded in Sec. 25.30(m).

(e) Intramural and extramural research supported in whole or in

part through contracts, other agreements, or grants, unless

categorically excluded in Sec. 25.30(e) or (f).

(f) Establishment by regulation of labeling requirements, a

standard, or a monograph, unless categorically excluded in

Secs. 25.30(k) or 25.31(a), (b), (c), (h), (i), or (j), or 25.32(a) or

(p).

(g) Issuance, amendment, and enforcement of FDA regulations, or an

exemption or variance from FDA regulations, unless categorically

excluded in Secs. 25.30(h), (i), or (j), or 25.32(e), (g), (n), or (p).

(h) Withdrawal of existing approvals of FDA-approved articles,

unless categorically excluded in Secs. 25.31(d) or (k), 25.32(m), or

25.33(g) or (h).

(i) Approval of food additive petitions and color additive

petitions, approval of requests for exemptions for investigational use

of food additives, and granting of requests for exemption from

regulation as a food additive, unless categorically excluded in

Sec. 25.32(b), (c), (i), (j), (k), (l), (o), (q), or (r).

(j) Establishment of a tolerance for unavoidable poisonous or

deleterious substances in food or in packaging materials to be used for

food.--

(k) Affirmation of a food substance as GRAS for humans or animals,

on FDA's initiative or in response to a petition, under part 182, 184,

186, or 582 of this chapter and establishment or amendment of a

regulation for a prior-sanctioned food ingredient, as defined in

Secs. 170.3(l) and 181.5(a) of this chapter, unless categorically

excluded in Sec. 25.32(f), (k), or (r).

(l) Approval of NDA's, abbreviated applications, applications for

marketing approval for marketing of a biologic product, supplements to

such applications, and actions on IND's, unless categorically excluded

in Sec. 25.31(a), (b), (c), (e), or (l).

(m) Approval of NADA's, abbreviated applications, supplements, and

actions on INAD's, unless categorically excluded under Sec. 25.33(a),

(c), (d), or (e).

(n) Approval of PMA's for medical devices, notices of completion of

PDP's for medical devices, authorizations to commence clinical

investigation under an approved PDP, or applications for an

[[Page 14938]]

IDE, unless categorically excluded in Sec. 25.34.

Sec. 25.21 Extraordinary circumstances.

As required under 40 CFR 1508.4, FDA will require at least an EA

for any specific action that ordinarily would be excluded if

extraordinary circumstances indicate that the specific proposed action

may significantly affect the quality of the human environment (see 40

CFR 1508.27 for examples of significant impacts). Examples of such

extraordinary circumstances include:

(a) Actions for which available data establish that, at the

expected level of exposure, there is the potential for serious harm to

the environment; and

(b) Actions that adversely affect a species or the critical habitat

of a species determined under the Endangered Species Act or the

Convention on International Trade in Endangered Species of Wild Flora

and Fauna to be endangered or threatened or wild flora or fauna that

are entitled to special protection under some other Federal law.

Sec. 25.22 Actions requiring the preparation of an environmental

impact statement.

(a) There are no categories of agency actions that routinely

significantly affect the quality of the human environment and that

therefore ordinarily require the preparation of an EIS.

(b) EIS's are prepared for agency actions when evaluation of data

or information in an EA or otherwise available to the agency leads to a

finding by the responsible agency official that a proposed action may

significantly affect the quality of the human environment.

Subpart C--Categorical Exclusions

Sec. 25.30 General.

The classes of actions listed in this section and Secs. 25.31

through 25.34 are categorically excluded and, therefore, ordinarily do

not require the preparation of an EA or an EIS:

(a) Routine administrative and management activities, including

inspections, and issuance of field compliance programs, program

circulars, or field investigative assignments.

(b) Recommendation for an enforcement action to be initiated in a

Federal court.

(c) Agency requests for initiation of recalls.

(d) Destruction or disposition of any FDA-regulated article

condemned after seizure or the distribution or use of which has been

enjoined or following detention or recall at agency request if the

method of destruction or disposition of the article, including

packaging material, is in compliance with all Federal, State, and local

requirements.

(e) Extramural contracts, other agreements, or grants for

statistical and epidemiological studies, surveys and inventories,

literature searches, and report and manual preparation, or any other

studies that will not result in the production or distribution of any

substance and, therefore, will not result in the introduction of any

substance into the environment.

(f) Extramural contracts, other agreements, and grants for research

for such purposes as to develop analytical methods or other test

methodologies.

(g) Activities of voluntary Federal-State cooperative programs,

including issuance of model regulations proposed for State adoption.

(h) Issuance, amendment, or revocation of procedural or

administrative regulations and guidelines, including procedures for

submission of applications for product development, testing and

investigational use, and approval.

(i) Corrections and technical changes in regulations.

(j) Issuance of CGMP regulations, HACCP regulations, establishment

standards, emergency permit control regulations, GLP regulations, and

issuance or denial of permits, exemptions, variances, or stays under

these regulations.

(k) Establishment or repeal by regulation of labeling requirements

for marketed articles if there will be no increase in the existing

levels of use or change in the intended uses of the product or its

substitutes.

(l) Routine maintenance and minor construction activities such as:

(1) Repair to or replacement of equipment or structural components

(e.g., door, roof, or window) of facilities controlled by FDA;

(2) Lease extensions, renewals, or succeeding leases;

(3) Construction or lease construction of 10,000 square feet or

less of occupiable space;

(4) Relocation of employees into existing owned or currently leased

space;

(5) Acquisition of 20,000 square feet or less of occupiable space

in a structure that was substantially completed before the issuance of

solicitation for offers; and

(6) Acquisition of between 20,000 square feet and 40,000 square

feet of occupiable space if it constitutes less than 40 percent of the

occupiable space in a structure that was substantially completed before

the solicitation for offers.

(m) Disposal of low-level radioactive waste materials (as defined

in the Nuclear Regulatory Commission regulations at 10 CFR 61.2) and

chemical waste materials generated in the laboratories serviced by the

contracts administered by FDA, if the waste is disposed of in

compliance with all applicable Federal, State, and local requirements.

Sec. 25.31 Human drugs and biologics.

The classes of actions listed in this section are categorically

excluded and, therefore, ordinarily do not require the preparation of

an EA or an EIS:

(a) Action on an NDA, abbreviated application, or a supplement to

such application, or action on an OTC monograph, if the action does not

increase the use of the active moiety.

(b) Action on an NDA, abbreviated application, or a supplement to

such application, or action on an OTC monograph, if the action

increases the use of the active moiety, but the concentration of the

substance in the environment will be below 1 part per billion.

(c) Action on an NDA, abbreviated application, application for

marketing approval of a biologic product, or a supplement to such

application, or action on an OTC monograph, for substances that occur

naturally in the environment when the action does not alter

significantly the concentration or distribution of the substance, its

metabolites, or degradation products in the environment.

(d) Withdrawal of approval of an NDA or an abbreviated application.

(e) Action on an IND.

(f) Testing and certification of batches of an antibiotic or

insulin.

(g) Testing and release by the Center for Biologics Evaluation and

Research of lots or batches of a licensed biologic product.

(h) Issuance, revocation, or amendment of a monograph for an

antibiotic drug.

(i) Establishment of bioequivalence requirements for a human drug

or a comparability determination for a biologic product subject to

licensing.

(j) Issuance, revocation, or amendment of a standard for a biologic

product.

(k) Revocation of a license for a biologic product.

(l) Action on an application for marketing approval for marketing

of a biologic product for transfusable human blood or blood components

and plasma.

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

The classes of actions listed in this section are categorically

excluded and,

[[Page 14939]]

therefore, ordinarily do not require the preparation of an EA or an

EIS:

(a) Issuance, amendment, or repeal of a food standard.

(b) Action on a request for exemption for investigational use of a

food additive if the food additive to be shipped under the request is

intended to be used for clinical studies or research.

(c) Approval of a color additive petition to change a provisionally

listed color additive to permanent listing for use in food, drugs,

devices, or cosmetics.

(d) Testing and certification of batches of a color additive.

(e) Issuance of an interim food additive regulation.

(f) Affirmation of a food substance as GRAS for humans or animals

on FDA's initiative or in response to a petition, under parts 182, 184,

186, or 582 of this chapter, and establishment or amendment of a

regulation for a prior-sanctioned food ingredient, as defined in

Secs. 170.3(l) and 181.5(a) of this chapter, if the substance or food

ingredient is already marketed in the United States for the proposed

use.

(g) Issuance and enforcement of regulations relating to the control

of communicable diseases or to interstate conveyance sanitation under

parts 1240 and 1250 of this chapter.

(h) Approval of a request for diversion of adulterated or

misbranded food for humans or animals to use as animal feeds.

(i) Approval of a food additive petition or the granting of a

request for exemption from regulation as a food additive under

Sec. 170.39 of this chapter when the additive is present in finished

food-packaging material at not greater than 5 percent-by-weight and is

also a functional component of the finished packaging material.

(j) Approval of a food additive petition or the granting of a

request for exemption from regulation as a food additive under

Sec. 170.39 of this chapter when the additive is to be used as a

component of a food-contact surface of permanent or semipermanent

equipment or of another food-contact article intended for repeated use.

(k) Approval of a food additive, color additive, or GRAS petition

for substances added directly to food that are intended to remain in

food through ingestion by consumers and that are not intended to

replace macronutrients in food.

(l) Approval of a petition for color additives used in contact

lenses, sutures, filaments used as supporting haptics in intraocular

lenses, bone cement, and in other FDA-regulated products having

similarly low levels of use.

(m) Action to prohibit or otherwise restrict or reduce the use of a

substance in food, food packaging, or cosmetics.

(n) Issuance, amendment, or revocation of a regulation pertaining

to infant formulas.

(o) Approval of a food additive petition for the intended

expression product(s) present in food derived from new plant varieties.

(p) Issuance, amendment, or revocation of a regulation in response

to a reference amount petition as described in Sec. 101.12(h) of this

chapter, a nutrient content claim petition as described in Sec. 101.69

of this chapter, a health claim petition as described in Sec. 101.70 of

this chapter, or a petition pertaining to the label declaration of

ingredients as described in Sec. 101.103 of this chapter.

(q) Approval of a food additive petition or the granting of a

request for an exemption from regulation as a food additive under

Sec. 170.39 of this chapter for a substance registered by the

Environmental Protection Agency under FIFRA for the same use requested

in the petition.

(r) Approval of a food additive, color additive, or GRAS

affirmation petition for a substance that occurs naturally in the

environment, when the action does not alter significantly the

concentration or distribution of the substance, its metabolites, or

degradation products in the environment.

Sec. 25.33 Animal drugs.

The classes of actions listed in this section are categorically

excluded and, therefore, ordinarily do not require the preparation of

an EA or an EIS:

(a) Action on an NADA, abbreviated application, or supplement to

such applications, if the action does not increase the use of the drug.

Actions to which this categorical exclusion applies include:

(1) An animal drug to be marketed under the same conditions of

approval as a previously approved animal drug;

(2) A combination of previously approved animal drugs;

(3) A new premix or other formulation of a previously approved

animal drug;

(4) Changes specified in Sec. 514.8(a)(5), (a)(6), or (d) of this

chapter;

(5) A change of sponsor;

(6) A previously approved animal drug to be contained in medicated

feed blocks under Sec. 510.455 of this chapter or as a liquid feed

supplement under Sec. 558.5 of this chapter; or

(7) Approval of a drug for use in animal feeds if such drug has

been approved under Sec. 514.2 or 514.9 of this chapter for other uses.

(b) [Reserved]

(c) Action on an NADA, abbreviated application, or a supplement for

substances that occur naturally in the environment when the action does

not alter significantly the concentration or distribution of the

substance, its metabolites, or degradation products in the environment.

(d) Action on an NADA, abbreviated application, or a supplement to

such applications, for:

(1) Drugs intended for use in nonfood animals;

(2) Anesthetics, both local and general, that are individually

administered;

(3) Nonsystemic topical and ophthalmic animal drugs;

(4) Drugs for minor species, including wildlife and endangered

species, when the drug has been previously approved for use in another

or the same species where similar animal management practices are used;

and

(5) Drugs intended for use under prescription or veterinarian's

order for therapeutic use.

(e) Action on an INAD.

(f) Action on an application submitted under section 512(m) of the

act.

(g) Withdrawal of approval of an NADA or an abbreviated NADA.

(h) Withdrawal of approval of a food additive petition that reduces

or eliminates animal feed uses of a food additive.

Sec. 25.34 Devices and electronic products.

The classes of actions listed in this section are categorically

excluded and, therefore, ordinarily do not require the preparation of

an EA or an EIS:

(a) Action on a device premarket notification submission under

subpart E of part 807 of this chapter.

(b) Classification or reclassification of a device under part 860

of this chapter.

(c) Issuance, amendment, or repeal of a standard for a class II

medical device or an electronic product, and issuance of exemptions or

variances from such a standard.

(d) Approval of a PMA or a notice of completion of a PDP or amended

or supplemental applications or notices for a class III medical device

if the device is of the same type and for the same use as a previously

approved device.

(e) Changes in the PMA or a notice of completion of a PDP for a

class III medical device that do not require submission of an amended

or supplemental application or notice.

(f) Issuance of a restricted device regulation if it will not

result in increases in the existing levels of use or changes in the

intended uses of the product or its substitutes.

[[Page 14940]]

(g) Action on an application for an IDE or an authorization to

commence a clinical investigation under an approved PDP.

(h) Issuance of a regulation exempting from preemption a

requirement of a State or political subdivision concerning a device, or

a denial of an application for such exemption.

Subpart D--Preparation of Environmental Documents

Sec. 25.40 Environmental assessments.-

(a) As defined by CEQ in 40 CFR 1508.9, an EA is a concise public

document that serves to provide sufficient evidence and analysis for an

agency to determine whether to prepare an EIS or a FONSI. The EA shall

include brief discussions of the need for the proposal, of alternatives

as required by section 102(2)(E) of NEPA, of the environmental impacts

of the proposed action and alternatives, and a listing of agencies and

persons consulted. An EA shall be prepared for each action not

categorically excluded in Secs. 25.30, 25.31, 25.32, 25.33, or 25.34.

The EA shall focus on relevant environmental issues and shall be a

concise, objective, and well-balanced document that allows the public

to understand the agency's decision. If potentially adverse

environmental impacts are identified for an action or group of related

actions, the EA shall discuss any reasonable alternative course of

action that offers less environmental risk or that is environmentally

preferable to the proposed action. The use of a scientifically

justified tiered testing approach, in which testing may be stopped when

the results suggest that no significant impact will occur, is an

acceptable approach.

(b) Generally, FDA requires an applicant to prepare an EA and make

necessary corrections to it. Ultimately, FDA is responsible for the

scope and content of EA's and may include additional information in

environmental documents when warranted.

(c) Information concerning the nature and scope of information that

an applicant or petitioner shall submit in an EA may be obtained from

the center or other office of the agency having responsibility for the

action that is the subject of the environmental evaluation. Applicants

and petitioners are encouraged to submit proposed protocols for

environmental studies for technical review by agency staff. Applicants

and petitioners also are encouraged to consult applicable FDA EA

guidance documents, which provide additional advice on how to comply

with FDA regulations.

(d) Consistent with 40 CFR 1500.4(j) and 1502.21, EA's may

incorporate by reference information presented in other documents that

are available to FDA and to the public.

(e) The agency evaluates the information contained in an EA and any

public input to determine whether it is accurate and objective, whether

the proposed action may significantly affect the quality of the human

environment, and whether an EIS or FONSI will be prepared. The

responsible agency official designated in part 5 of this chapter as

responsible for the underlying action examines the environmental risks

of the proposed action and the alternative courses of action, selects a

course of action, and ensures that any necessary mitigating measures

are implemented as a condition for approving the selected course of

action.

Sec. 25.41 Findings of no significant impact.

(a) As defined by the CEQ regulations (40 CFR 1508.13), a FONSI is

a document prepared by a Federal agency stating briefly why an action,

not otherwise excluded, will not significantly affect the human

environment and for which, therefore, an EIS will not be prepared. A

FONSI includes the EA or a summary of it and a reference to any other

related environmental documents.

(b) The agency official(s) responsible for approving the FONSI will

sign the document, thereby establishing that the official(s) approve(s)

the conclusion not to prepare an EIS for the action under

consideration.

Sec. 25.42 Environmental impact statements.

(a) As defined by CEQ regulations (40 CFR 1508.11) and section

102(2)(C) of NEPA, an EIS should be a clear, concise, and detailed

written statement describing:

(1) The environmental impacts of a proposed action;

(2) Any adverse effects that cannot be avoided if the action is

implemented;

(3) Alternatives to the action;

(4) The relationship between local short-term uses of the

environment and the maintenance and enhancement of long-term

productivity; and

(5) Any irreversible and irretrievable commitments of resources

that would be involved in the proposed action should it be implemented.

(b) The CEQ regulations (40 CFR 1501.7 and part 1502) describe the

process for determining the scope of an EIS and provide detailed

requirements for the preparation of draft and final EIS's. CEQ format

and procedures for preparing EIS shall be followed.

(c) Under the conditions prescribed in 40 CFR 1502.9, the agency

will prepare a supplement for a draft or final EIS and introduce the

supplement into the administrative record.

Sec. 25.43 Records of decisions.

(a) In cases requiring environmental impact statements, at the time

of its decision, the agency shall prepare a concise public record of

decision.

(b) The record of decision shall:

(1) State what the decision was;

(2) Identify and discuss alternatives considered by the agency in

reaching its decision;

(3) State whether all practicable means to avoid or minimize

environmental harm have been adopted, and if not, why not; and

(4) Discuss and implement any monitoring and enforcement program

necessary to affect mitigation.

Sec. 25.44 Lead and cooperating agencies.--

For actions requiring the preparation of an EIS, FDA and other

affected Federal agencies will agree which will be the lead agency and

which will be the cooperating agencies. The responsibilities of lead

agencies and cooperating agencies are described in the CEQ regulations

(40 CFR 1501.5 and 1501.6, respectively). If an action affects more

than one center within FDA, the Commissioner of Food and Drugs will

designate one of these units to be responsible for coordinating the

preparation of any required environmental documentation.

Sec. 25.45 Responsible agency official.

(a) The person designated in part 5 of this chapter as the

responsible agency official for the underlying action is responsible

for preparing environmental documents or ensuring that they are

prepared.

(b) The responsible agency official will weigh any environmental

impacts of each alternative course of action, including possible

mitigation measures, and will balance environmental impacts with the

agency's objectives in choosing an appropriate course of action. The

weighing of any environmental impacts of alternatives in selecting a

final course of action will be reflected in the agency's record of

formal decisionmaking as required by 40 CFR 1505.2.

Subpart E--Public Participation and Notification of Environmental

Documents

Sec. 25.50 General information.

(a) To the extent actions are not protected from disclosure by

existing law applicable to the agency's operation, FDA will involve the

public

[[Page 14941]]

in preparing and implementing its NEPA procedures and will provide

public notice of NEPA-related hearings, public meetings, and the

availability of environmental documents.

(b) Many FDA actions involving investigations, review, and approval

of applications, and premarket notifications for human drugs, animal

drugs, biologic products, and devices are protected from disclosure

under the Trade Secret Act, 18 U.S.C. 1905, and 301(j) of the act.

These actions are also protected from disclosure under FDA's

regulations including part 20, Secs. 312.130(a), 314.430(b), 514.11(b),

514.12(a), 601.50(a), 601.51(a), 807.95(b), 812.38(a), and 814.9(b) of

this chapter. Even the existence of applications for human drugs,

animal drugs, biologic products, and devices is protected from

disclosure under these regulations. Therefore, unless the existence of

applications for human drugs, animal drugs, biologic products, or

premarket notification for devices has been made publicly available,

the release of the environmental document before approval of human

drugs, animal drugs, biologic products, and devices is inconsistent

with statutory requirements imposed on FDA. Appropriate environmental

documents, comments, and responses will be included in the

administrative record to the extent allowed by applicable laws.

Sec. 25.51 Environmental assessments and findings of no significant -

impact.

(a) Data and information that are protected from disclosure by 18

U.S.C. 1905 or 21 U.S.C. 331(j) or 360j(c) shall not be included in the

portion of environmental documents that is made public. When such data

and information are pertinent to the environmental review of a proposed

action, an applicant or petitioner shall submit such data and

information separately in a confidential section We have spend 20 years

trying to keep confidential information out of Eas. I suggest the

preceding revision. Gail said she prefers confidential appendix to the

EA.and shall summarize the confidential data and information in the EA

to the extent possible.

(b) FONSI's and EA's will be available to the public in accordance

with 40 CFR 1506.6 as follows:

(1) When the proposed action is the subject of a notice of proposed

rulemaking or a notice of filing published in the Federal Register, the

notice shall state that no EIS is necessary and that the FONSI and the

EA are available for public inspection at FDA's Dockets Management

Branch. If the responsible agency official is unable to complete

environmental consideration of the proposed action before a notice of

filing of a food or color additive petition is required to be published

under the act, and if the subsequent environmental analysis leads to

the conclusion that no EIS is necessary, the Federal Register document

publishing the final regulation rather than the notice of filing shall

state that no EIS is necessary and that the FONSI and the EA are

available upon request and filed in FDA's Dockets Management Branch.

(2) For actions for which notice is not published in the Federal

Register, the FONSI and the EA shall be made available to the public

upon request according to the procedures in 40 CFR 1506.6.

(3) For a limited number of actions, the agency may make the FONSI

and EA available for public review (including review by State and

areawide information clearinghouses) for 30 days before the agency

makes its final determination whether to prepare an EIS and before the

action may begin, as described in 40 CFR 1501.4(e). This procedure will

be followed when the proposed action is, or is closely similar to, one

that normally requires an EIS or when the proposed action is one

without precedent.

Sec. 25.52 Environmental impact statements.

(a) If FDA determines that an EIS is necessary for an action

involving investigations or approvals for drugs, animal drugs, biologic

products, or devices, an EIS will be prepared but will become available

only at the time of the approval of the product. Disclosure will be

made in accordance with 40 CFR 1506.6 and part 20 of this chapter. The

EIS will in all other respects conform to the requirements for EIS's as

specified in 40 CFR part 1502 and 1506.6(f).

(b) Comments on the EIS may be submitted after the approvalof the

drug, animal drug, biologic product, and device. Those comments can

form the basis for the agency to consider beginning an action to

withdraw the approval of applications for a drug, animal drug, biologic

product, or to withdraw premarket notifications or premarket approval

applications for devices.

(c) In those cases where the existence of applications and

premarket notifications for drugs, animal drugs, biologic products, or

devices has already been disclosed before the agency approves the

action, the agency will make diligent effort (40 CFR 1506.6) to involve

the public in preparing and implementing the NEPA procedures for EIS's

while following its own disclosure requirements including those listed

in part 20, Secs. 312.130(b), 314.430(d), 514.11(d), 514.12(b),

601.51(d), 807.95(e), 812.38(b), and 814.9(d) of this chapter.

(d) Draft and final EIS's, comments, and responses will be included

in the administrative record and will be available from the Dockets

Management Branch (HFA-305), Food and Drug Administration, 12420

Parklawn Dr., rm. 1-23, Rockville, MD 20857.

Subpart F--Other Requirements

Sec. 25.60 Environmental effects abroad of major agency actions.

(a) In accordance with Executive Order 12114, ``Environmental

Effects Abroad of Major Federal Actions'' of January 4, 1979 (44 FR

1957, January 9, 1977), the responsible agency official, in analyzing

actions under his or her program, shall consider the environmental

effects abroad, including whether the actions involve:

(1) Potential environmental effects on the global commons and areas

outside the jurisdiction of any nation, e.g., oceans and the upper

atmosphere.

(2) Potential environmental effects on a foreign nation not

participating with or otherwise involved in an FDA activity.

(3) The export of products (or emissions) that in the United States

are prohibited or strictly regulated because their effects on the

environment create a serious public health risk.

(4) Potential environmental effects on natural and ecological

resources of global importance designated under the Executive Order.

(b) Before deciding on any action falling into the categories

specified in paragraph (a) of this section, the responsible agency

official shall determine in accordance with section 2-3 of the

Executive Order whether such actions may have a significant

environmental effect abroad.

(c) If the responsible agency official determines that an action

may have a significant environmental effect abroad, the responsible

agency official shall determine in accordance with section 2-4(a) and

(b) of the Executive Order, whether the subject action calls for:

(1) An EIS;

(2) A bilateral or multilateral environmental study; or

(3) A concise environmental review.

(d) In preparing environmental documents under this subpart, the

responsible official shall:

(1) Determine, as provided in section 2-5 of the Executive Order,

whether proposed actions are subject to the exemptions, exclusions, and

[[Page 14942]]

modification in contents, timing, and availability of documents.

(2) Coordinate all communications with foreign governments

concerning environmental agreements and other arrangements in

implementing the Executive Order.

Dated: March 19, 1996.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 96-8090 Filed 4-2-96; 8:45 am]

BILLING CODE 4160-01-F