[Federal Register Volume 62, Number 145 (Tuesday, July 29, 1997)]
[Rules and Regulations]
[Pages 40570-40600]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-19566]
[[Page 40569]]
_______________________________________________________________________
Part II
Department of Health and Human Services
_______________________________________________________________________
Food and Drug Administration
_______________________________________________________________________
21 CFR Part 10, et al.
National Environmental Policy Act; Revision of Policies and Procedures;
Final Rule
Federal Register / Vol. 62, No. 145 / Tuesday July, 29, 1997 / Rules
and Regulations
[[Page 40570]]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 10, 20, 25, 71, 101, 170, 171, 312, 314, 511, 514,
570, 571, 601, 812, and 814
[Docket No. 96N-0057]
National Environmental Policy Act; Revision of Policies and
Procedures
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is amending 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 final rule is
to increase the efficiency of FDA's implementation of NEPA and to
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 amending
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. The amendments to FDA's
regulations governing compliance with NEPA reflect FDA's continuing
review of its policies and procedures to determine whether revisions
are necessary to ensure full compliance with the purpose and provisions
of NEPA and implement the President's reinventing Government
initiatives announced in ``Reinventing Drug and Medical Device
Regulations,'' April 1995, and ``Reinventing Food Regulations,''
January 1996.
DATES: The regulations are effective on August 28, 1997. For
applications or petitions pending before the agency on August 28, 1997,
for which the agency has not signed a finding of no significant impact
(FONSI) on or before August 28, 1997, the applicant or petitioner may
submit an amendment to the application or petition under 21 CFR
10.30(g), 71.6(b), 171.6, 314.60, 514.6, 571.6, 601.2 or 814.37
claiming a categorical exclusion in accordance with Sec. 25.15(d) of
this final rule. The applicant or petitioner should state in the
amendment that the applicant or petitioner waives the claim for
categorical exclusion if a FONSI has been signed on or before August
28, 1997.
FURTHER INFORMATION CONTACT:
For information regarding human drugs:
Nancy B. Sager, Center for Drug Evaluation and Research (HFD-357),
Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857,
301-594-5629
For information regarding biologics:
Daniel C. Kearns, Center for Biologics Evaluation and Research
(HFM-208), 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 O. 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
In the Federal Register of April 3, 1996 (61 FR 14922) (republished
May 1, 1996 (61 FR 19476)), FDA proposed to amend its regulations in
part 25 (21 CFR part 25) governing compliance with NEPA as implemented
by the regulations of CEQ. FDA provided 90 days for public comment on
the proposed rule. In addition, in the Federal Register of October 22,
1996 (61 FR 54746), FDA announced the placement in the administrative
record of additional information and underlying data concerning the
proposed rule, and granted a 30-day comment period permitting
interested parties to submit comments relating to those categorical
exclusions for which additional information was provided. The agency
has revised portions of the final regulations in response to comments
received on the proposal.
This final rule amending FDA's NEPA procedures increases the
efficiency of the agency's implementation of NEPA by substantially
reducing the number of EA's required to be submitted by industry and
reviewed by FDA and by providing for categorical exclusions for
additional classes of actions that do not individually or cumulatively
have a significant impact on the human environment. This final rule
also makes the regulations more concise and useful to the public and
regulated industry.
II. Comments on the Proposed Rule
FDA received 17 letters, including letters from manufacturers,
trade associations, environmental groups, academics, environmental
consultants, and the U.S. Environmental Protection Agency (EPA),
commenting on the proposed rule. In general, the comments supported
FDA's proposed revisions to more efficiently implement NEPA. One
manufacturer of human and veterinary pharmaceuticals projected that the
final rule would reduce by 75 percent the number of its products that
will require EA's, and a pharmaceutical industry trade association
estimated that the rule will reduce by 90 percent the amount of
environmental information submitted to the agency. FDA's analysis of
the impacts of this final rule is included in section III of this
document, ``Analysis of Impacts.''
A. Subpart A--General Provisions
1. One comment stressed the need to have more interaction and
greater alignment among the agencies involved in implementing NEPA in
order to develop more consistent policies.
CEQ regulations direct agencies with similar programs to consult
with each other and with CEQ to coordinate their procedures (40 CFR
1507.3). However, differences in Federal agencies' policies and
procedures to implement NEPA are inevitable because each agency has its
own distinct statutory mandates. Each agency needs to evaluate and
prioritize different environmental risks based on the nature of the
agency's actions. CEQ reviews the procedures of all agencies to ensure
their conformity with NEPA and CEQ regulations. FDA consults and
coordinates with other Federal agencies regarding the protection of the
environment to the fullest extent possible.
2. Proposed Sec. 25.5(b)(4) states that increased use of a drug or
biologic product may occur if the drug may 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.
This section further defines new molecular entity as, ``a drug for
which the active moiety * * * has not been previously approved or
marketed in the
[[Page 40571]]
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.'' FDA has decided not to include the definition of new
molecular entity in Sec. 25.5(b)(4). The term is currently defined in
guidance documents issued by the Center for Drug Evaluation and
Research (CDER). The agency does not find it necessary to include the
definition in its regulations. Parties interested in the definition of
new molecular entity should consult the information available from
CDER.
3. Proposed Sec. 25.10(c) describes when the environmental planning
process begins under NEPA: ``For actions initiated by applicants or
petitioners, NEPA planning begins when FDA receives a submission from
an applicant or petitioner seeking action by FDA.'' Proposed
Sec. 25.10(c) differs from current Sec. 25.10(a), which states that:
For actions initiated by applicants or petitioners, the process
begins when FDA receives from an applicant or petitioner an
environmental assessment (EA) or a claim that a categorical
exclusion applies, or when FDA personnel consult with applicants or
petitioners on the NEPA-related aspects of their requested actions.
One comment indicated that current Sec. 25.10(a) is consistent with
NEPA and CEQ regulations because it provides for consultation between
the agency and applicants or petitioners prior to Federal action.
However, the comment contended that proposed Sec. 25.10(c), as it
amends current Sec. 25.10(a), is inconsistent with NEPA and CEQ
regulations. The comment specifically cites an inconsistency between
proposed Sec. 25.10(c) and 40 CFR 1501.2(d), which states that in
``cases where actions are planned by private applicants or other non-
Federal entities before Federal involvement,'' agencies shall provide
policies or designated staff members ``to advise potential applicants
of studies or other information foreseeably required for later Federal
action,'' and shall begin the NEPA process ``at the earliest time
possible.''
FDA agrees with the comment. As explained in the preamble to the
proposal (61 FR 14922 at 14923, 61 FR 19476 at 19477), FDA intended to
eliminate unnecessary language by combining Sec. 25.5 (Policies) and
Sec. 25.10 (NEPA planning) into proposed Sec. 25.10 (Policies and NEPA
planning). FDA did not intend to change the timing of the initiation of
the agency's environmental planning process or to preclude early
consultation with FDA prior to Federal action when it proposed the
language in Sec. 25.10(c). Thus, because the proposed section does not
clearly express the agency's policy, the agency will incorporate the
current Sec. 25.10(a) language, and Sec. 25.10(c) will provide, in
relevant part:
For actions initiated by applicants or petitioners, NEPA
planning begins when FDA receives from an applicant or petitioner an
environmental assessment (EA) or a claim that a categorical
exclusion applies, or when FDA personnel consult with applicants or
petitioners on the NEPA-related aspects of their requested actions.
4. One comment stated that under CEQ regulations (40 CFR
1501.2(d)), FDA is required to ensure that potential applicants or
petitioners prepare an EA prior to the harvest of natural resources,
such as the Pacific yew tree, regardless of whether the drug sponsor
has filed an application or petition with the agency. The comment
requested that the proposed regulations be revised to specifically
address the issue of ``stockpiling'' harvested material prior to
submitting an application or petition.
The requirements and procedures of NEPA are triggered by a major
Federal action. Until FDA reviews an application or petition, initiates
an action, or is consulted regarding potential agency action, no action
exists to set the NEPA process in motion, and there is no regulatory
requirement for applicants or petitioners to inform FDA of their use of
natural resources prior to the submission of an application or petition
to FDA. Therefore, FDA cannot ensure that applicants or petitioners
prepare an EA prior to the harvest of natural resources. In accordance
with 40 CFR 1501.2(d), the agency makes staff available to advise
potential applicants or petitioners of studies or other information
foreseeably required for later Federal action and commences its NEPA
process at the earliest possible time (see Sec. 25.10(c) of this final
rule). FDA will request information about stockpiling and harvesting
once the NEPA process is triggered by a proposed action.
With regard to the comment's specific concerns about the Pacific
yew, the agency published a notice in the Federal Register of November
18, 1996 (61 FR 58694), clarifying the environmental information that
must be submitted to the agency with a new drug application (NDA),
abbreviated new drug application (ANDA), or investigational new drug
application (IND) involving paclitaxel derived from or otherwise
involving the Pacific yew.
5. One comment requested that proposed Sec. 25.10, which states
FDA's overall policy in implementing the NEPA requirements, be modified
to indicate that applicants should be involved in the development of
agency policies, procedures, and guidance documents that are designed
to interpret, clarify, or elaborate on the requirements placed on
applicants to satisfy FDA's statutory obligations under NEPA.
In a notice in the Federal Register of February 27, 1997 (62 FR
8961), FDA announced its ``Good Guidance Practices'' (GGP's), which
represents the agency's policy regarding the development and use of
guidance documents (hereinafter referred to as the GGP's notice). The
GGP's address public participation in the guidance document development
process generally. FDA does not believe that it is necessary or
appropriate to address public participation in the NEPA guidance
document development process specifically. Interested individuals are
encouraged to review the Federal Register notice and related comments
(Docket No. 95P-0110).
6. One comment requested that Sec. 25.10 be revised to provide that
a single center official be responsible for addressing and resolving
questions raised by reviewers and for mediating conflicts arising
between reviewers and sponsors regarding interpretations of the
regulatory requirements. The comment also requested that a provision be
included that establishes an appeal from the center's responsible
official to the Center Director, in the event that the center official
is unable to resolve questions raised by reviewers.
FDA does not believe it is necessary to revise proposed Sec. 25.10
as suggested by the comment. Individuals in each center with
specialized training and expertise oversee the NEPA review process,
resolve questions raised by reviewers, and mediate conflicts between
reviewers and sponsors. Actions by reviewers or other center officials
may be appealed through the appeals mechanisms already in place in each
center to the Center Director and, ultimately, to the Commissioner of
Food and Drugs (the Commissioner). Individuals who are interested in
obtaining copies of the appeals procedures established in each center
may contact the relevant center for such information.
B. Subpart B--Agency Actions Requiring Environmental Consideration
7. Proposed Sec. 25.15(a) states that the failure of an applicant
or petitioner to submit an ``adequate EA'' for a requested action that
is not categorically excluded is sufficient grounds for FDA to refuse
to file or approve the application or petition. One comment noted that
while FDA requires an ``adequate'' EA, the definition of that
[[Page 40572]]
term found in current Sec. 25.22(b) is not included in the proposed
regulations. The comment requested that the agency retain the
definition of adequate EA in its regulations.
The agency agrees that clarification of when an EA is adequate for
filing or approval is appropriate. Consequently, proposed Sec. 25.15(a)
has been revised to include the clarifying statements currently found
in Sec. 25.22(b):
An EA adequate for filing is one that addresses the relevant
environmental issues. An EA adequate for approval is one that
contains sufficient information to enable the agency to determine
whether the proposed action may significantly affect the quality of
the human environment.
8. Proposed Sec. 25.15(a) and (d) requires that applicants and
petitioners who claim that a categorical exclusion applies to a
proposed action certify that the action qualifies for a categorical
exclusion, citing the particular exclusion that is claimed, and certify
that to their knowledge no extraordinary circumstances exist. One
comment specifically welcomed and believed important to the success of
FDA's proposals the certification of compliance with the categorical
exclusion criteria required in Sec. 25.15(a) and (d). Another comment
requested clarification of the certification requirement in
Sec. 25.15(a) and (d), questioning whether the categorical exclusion
document needs to contain a separate certification indicating the
truthfulness and accuracy of the information provided in the
certification, or whether the categorical exclusion document alone is
sufficient.
Applications and petitions that are filed with the agency are
signed by a responsible agent or official of the sponsor, who attests
to the truth and accuracy of the information within the application or
petition. A separate, signed categorical exclusion document is not
needed. Under Sec. 25.15(a) and (d), FDA requires that an applicant or
petitioner requesting a categorical exclusion identify the categorical
exclusion being claimed, state that the action complies with the
categorical exclusion criteria, and state that to the applicant's
knowledge no extraordinary circumstances exist. For clarification,
Sec. 25.15(a) and (d) have been modified to indicate that a statement,
not a certification, is needed.
9. One comment contended that proposed Sec. 25.15(a) and (d) is
inconsistent with CEQ regulations in that the CEQ regulations require
that the agency use specific criteria to judge whether an action fits
within a categorical exclusion (40 CFR 1507.3(b)(2)(ii)) and
independently evaluate the information submitted and be responsible for
the accuracy of the information (40 CFR 1506.5). The comment also
asserted that proposed Sec. 25.15(a) and (d) departs from existing FDA
regulations, which require that applicants claiming a categorical
exclusion provide supporting information that the action meets the
criteria for the applicable exclusion.
Under current Sec. 25.23(c), a person who claims a categorical
exclusion provides information when appropriate that establishes to the
agency's satisfaction that the action meets the criteria for the
applicable exclusion (emphasis added). Proposed Sec. 25.15(a) and (d)
does not reflect a departure from current FDA regulations. In revising
its NEPA procedures, FDA has formulated its categorical exclusions to
include specific criteria, as required by CEQ's regulations (40 CFR
1507.3(b)(2)(ii)) that in most instances can either be facially
determined or confirmed by review of other information submitted as
part of the request for action. This approach is consistent with CEQ's
view that in most cases additional information should not be required.
In the limited instances when it may be necessary, FDA will request
additional information as needed to establish to the agency's
satisfaction that the criteria for a categorical exclusion have been
met.
10. One comment objected to the absence of information in the
proposal concerning the actions FDA may take in response to a
petitioner or applicant filing a false certification with the agency.
It is a violation of the criminal code (18 U.S.C. 1001) for anyone,
in any matter within the jurisdiction of any department or agency of
the United States, to knowingly and willfully make any false,
fictitious, or fraudulent statement or representation to such
department or agency. Enforcement decisions are generally a matter of
an agency's discretion. FDA will exercise its enforcement discretion
consistent with its statutory responsibilities under all applicable
statutes, including NEPA.
11. One comment recommended that the basic physical/chemical
characterization of a potential product be included in all EA documents
including claims for categorical exclusion.
In the event FDA determines that basic physical/chemical
characterization information is relevant to its environmental
consideration of a specific proposed action, FDA will request that such
information be provided in an EA. FDA intends to issue guidance
documents that will provide applicants with information about the
nature and scope of information that should be included in an EA. A
claim for categorical exclusion shall comply with Sec. 25.15(a) and (d)
and, as discussed in the response to comment 9, should not normally
include additional information.
12. Proposed Sec. 25.20 lists broad categories of agency actions
that require the preparation of an EA, unless the action qualifies for
exclusion. One comment noted that although FDA stated in the preamble
to the proposal that the types of actions requiring an EA remain
essentially the same as in current Sec. 25.22, the proposal did not
include the ``catch-all action'' in current Sec. 25.22(a)(19): ``Action
other than one listed in this subsection, unless subject to exclusion
under Secs. 25.23 and 25.24, that may significantly affect the quality
of the human environment.'' The comment recommended that a clause be
retained in new Sec. 25.20 providing that an ``EA must be prepared for
an action other than one listed in (Sec. 25.20) that may significantly
affect the quality of the human environment.''
The list of actions requiring preparation of an EA was not intended
to be all-inclusive. The list includes broad classes of actions that
require preparation of at least an EA, unless categorically excluded in
subpart C of part 25. Under NEPA and CEQ's implementing regulations,
FDA is required to consider the environmental impact of each of its
proposals for major Federal action that is not categorically excluded.
Therefore, it is not necessary for FDA to include the described catch-
all clause in the final rule.
13. Another comment noted that proposed Sec. 25.20(i) requires an
EA for actions on requests for exemptions for investigational use of
food additives, unless categorically excluded under proposed
Sec. 25.32(b), and questioned whether the agency expects a claim for
exclusion to be submitted for actions involving investigational food
additives. The comment asked FDA to clarify its intent.
The intent of the provision in proposed Sec. 25.20(i) is to
identify actions involving food additives that ordinarily require an
EA, unless the actions are in a specific class that qualifies for a
categorical exclusion. Similar to the agency's experience with actions
on investigational human and animal drugs, FDA expects that if action
were taken on an investigational food additive, such action would
qualify for the exclusion under Sec. 25.32(b) of the final rule.
14. Proposed Sec. 25.21 addresses ``extraordinary circumstances''
under which categories of actions that would
[[Page 40573]]
ordinarily be categorically excluded would require preparation of an
EA. One comment contended that this exception to categorical exclusions
will result in the potential for ``regulatory creep,'' that is, the
potential for FDA to implement the exception in a manner that results
in an expansion of the degree of FDA review, a lengthening of time for
review, and an increased cost of review. The comment expressed
particular concern about the opportunity for regulatory creep in
relation to applying the exception to categorical exclusions for
actions on new animal drug applications (NADA's). The comment suggested
that a primary safeguard against misuse of the extraordinary
circumstances exception is to ensure that decisions on exceptions are
reserved and delegated in part 5 (21 CFR part 5) to a truly responsible
official; in the case of actions on animal drugs, to the Director of
the Center for Veterinary Medicine.
As the comment recognizes, under CEQ regulations at 40 CFR 1508.4,
FDA is required to provide for extraordinary circumstances in which a
normally excluded action may have a significant effect on the
environment. Under proposed Sec. 25.21 (current Sec. 25.23(b)), FDA
requires 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. CEQ regulations, in 40 CFR 1508.27, define
``significantly'' to require consideration of both the context and
intensity of an agency action. Proposed Sec. 25.21 cites Sec. 1508.27
to emphasize that, in implementing its regulations, FDA will rely on
the principles established by CEQ for determining whether an
extraordinary circumstance exists such that an action, ordinarily
excluded, may significantly affect the environment. By definition, a
categorical exclusion means a category of actions that has been found
not to have a significant effect on the human environment, therefore
application of the extraordinary circumstances provision should be
limited. Since 1985, in implementing its NEPA procedures, FDA has
invoked the extraordinary circumstance exception to categorical
exclusions in limited instances and in a manner consistent with CEQ
regulations. Section 25.21 lists two examples of extraordinary
circumstances where FDA may apply the exception.
FDA declines to modify part 5 to reflect that the authority to
determine the existence of extraordinary circumstances related to
animal drugs is reserved to the Director of the Center of Veterinary
Medicine. The agency's decision is described in the response to comment
60 below, which discusses the revision of part 5 with respect to all
FDA Center Directors.
15. One comment asserted that the extraordinary circumstances
provision will not result in the preparation of EA's for applications
involving paclitaxel that otherwise meet the criteria for categorical
exclusion. The comment stated that the Pacific yew is not classified as
an endangered or threatened species under the Endangered Species Act
(ESA), nor is the species currently listed in any of the appendices to
the Convention on International Trade in Endangered Species of Fauna
and Flora (CITES) and expressed concern that agency actions regarding
products containing paclitaxel would escape environmental consideration
because they do not fall within FDA's examples of extraordinary
circumstances. The comment also questioned the standard that the agency
has proposed to use in determining whether an action involving wild
flora and fauna falls within FDA's second example of extraordinary
circumstances, citing FDA's statement in the preamble that the agency:
(I)ntends 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.
Finally, the comment asserted that unlike the ESA, CITES does not speak
in terms of endangered or threatened species.
The examples provided by the agency in proposed Sec. 25.21 are
illustrative of the types of action that would require an EA despite
the fact that the action otherwise qualifies for a categorical
exclusion. The two examples are not intended to be an exhaustive list
of those actions.
FDA's extraordinary circumstances provision requires that an EA be
prepared if a normally excluded action may significantly affect the
quality of the human environment. FDA has specifically determined that
actions relating to applications involving paclitaxel derived from or
otherwise involving the Pacific yew tree fall within the CEQ definition
of ``significantly'' (40 CFR 1508.27) and has documented, in the
agreement filed in the U.S. District Court for the District of Columbia
in Oregon Natural Resources Council Action v. Shalala, No. 96-1449 PLF
(D.C.D.C. Oct. 4, 1996), its intent to require EA's for all actions on
applications, except some actions on IND's, involving paclitaxel
derived from or otherwise involving the Pacific yew tree. FDA also
published a notice in the Federal Register clarifying the environmental
information that must be submitted to the agency in marketing
applications for drug products containing paclitaxel (61 FR 58694).
FDA is clarifying that it will require an EA for an action,
including one involving wild flora and fauna, that is ordinarily
excluded if the action may have a significant effect on the
environment. Where a species of wild flora or fauna may become
endangered or threatened, the action may have a significant effect.
The comment is inaccurate in stating that CITES does not speak in
terms of endangered or threatened species. The regulations implementing
CITES (50 CFR 23.2) note that the appendices include endangered and
threatened species and a ``Facts'' sheet published by the Fish and
Wildlife Service explains that Appendix I includes species presently
threatened with extinction.
16. One comment expressed concern about the environmental effects
of synthetic estrogens in the aquatic environment, specifically those
synthetic estrogens in oral contraceptives and estrogenic replacement
therapy prescribed for post-menopausal women. The comment requested
that until research is available to determine a more accurate critical
concentration, FDA consider the use of synthetic estrogens in human
drugs to be an extraordinary circumstance so that actions involving
estrogen use would require an EA. The authors of the comment state that
they have observed significant alterations of gender ratios when
developing larval medaka (a fish) were exposed to 0.1 part per billion
(ppb) of 17-estradiol (naturally occurring) for 4 weeks.
Additionally, they cite from a published article that male rainbow
trout exposed to 0.002 ppb ethinyl estradiol (used in oral
contraceptives) for 3 weeks showed significantly elevated vitellogenin
levels and decreased testes weight and compromised spermatogenesis.
Concern was also expressed about the potential for higher
concentrations of these compounds in certain local areas.
FDA will require an EA for any specific action that ordinarily
would be excluded if available evidence establishes that, at the
expected level of exposure, a potential exists for a significant effect
on the environment.
[[Page 40574]]
The agency has considered the request that the use of synthetic
estrogens in human drugs be considered an extraordinary circumstance,
but has concluded that the available evidence does not support that, at
the expected level of exposure, a potential exists for significant
effect on the environment. FDA has considered many factors in arriving
at this conclusion including normal prescribing patterns for the drugs,
medical uses, pharmacological properties, waste water treatment
practices and expected introduction and environmental concentrations of
the substances. FDA provided its analysis to the EPA for review and EPA
agreed with FDA's position on this issue. Therefore, FDA will not
generally apply the extraordinary circumstances exception to actions
involving synthetic estrogens used in oral contraceptives and hormone
replacement therapy that otherwise meet the criteria for categorical
exclusion. A report explaining the basis of the agency's decision has
been placed in Docket No. 96N-0057. FDA will continue to investigate
this issue in general and assess each action on an individual basis to
determine whether an extraordinary circumstance exists.
17. Proposed Sec. 25.22 provides for the preparation of an EIS when
the responsible agency official finds, as a result of evaluating
relevant data and information, that a proposed action may significantly
affect the quality of the human environment. One comment recommended
that FDA establish specific criteria to determine the need to prepare
an EIS. The comment suggested that the agency base the criteria on the
number of potentially affected parties or on the formula used by the
European Union (EU) to trigger the EU equivalent of an EIS. The EU
criteria are based on annual tonnage.
An EIS is prepared when evaluation of data or information in an EA
or otherwise available to the agency leads to a finding that a proposed
action may significantly affect the quality of the human environment.
FDA does not believe it is necessary to further identify criteria for
preparing an EIS. CEQ regulations (40 CFR 1508.27) define
``significantly'' and provide guidance to FDA in its determination of
whether an action significantly affects the environment. Furthermore,
it is difficult to develop criteria that are more specific and that may
be applied with great frequency. Criteria relating to the amount of
material produced are not appropriate criteria for determining when an
EIS must be prepared. For example, an EIS may not be necessary for FDA-
regulated articles produced in large quantities if environmental
depletion mechanisms are identified and/or the material is relatively
nontoxic to environmental organisms at expected environmental
concentrations.
18. In the preamble to the proposal, FDA stated that it 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). One comment
contended that this proposed action is inconsistent with both CEQ
regulations and case law governing implementation of NEPA. The comment
stated that FDA was suggesting it could not comply with 40 CFR
1502.9(c)(1)(ii) because its authority to require additional
environmental information from applicants only stems from the act or
the PHS Act. The comment stated that the Federal court, in
Environmental Defense Fund v. Mathews, 410 F.Supp. 336, 338 (D.C.D.C.
1976), rejected similar claims when FDA issued its NEPA regulations in
the 1970's.
Because the comment misunderstands the agency's stated reasons for
proposing to remove current Sec. 25.25, FDA is clarifying them here.
Current Sec. 25.25 applies to agency consideration of the need to
prepare an EIS after the agency has already taken an action, e.g.,
promulgation of a regulation or action relating to an approval. NEPA
and CEQ regulations both require an agency to consider the
environmental impact of its actions before decisions are made and
before actions are taken. Thus, the agency must prepare an EIS for an
action it has found may significantly affect the environment before it
takes the action. NEPA does not apply retroactively; instead, however,
if an ongoing project undergoes changes which themselves amount to
``major Federal actions,'' the agency must then prepare an EIS (Upper
Snake River Chapter of Trout Unlimited v. Hodel, 921 F.2d 232, 234 (9th
Cir. 1990)). FDA is removing Sec. 25.25, which concerned retroactive
environmental consideration.
The comment cites Environmental Defense Fund v. Mathews, 410
F.Supp. 336, 338 (D.C.D.C. 1976), which relates to FDA's 1973
regulations implementing its obligations under NEPA. The case held
that, in addition to its other statutory mandates, FDA has a
nondiscretionary responsibility under NEPA to take environmental
considerations into account in its process of decisionmaking. For the
reasons stated above, elimination of current Sec. 25.25 does not affect
this responsibility and is not inconsistent with CEQ regulations or
case law.
The agency specifically acknowledges its responsibility to prepare
supplements in accord with Sec. 1502.9 in the new regulations (see
Sec. 25.42(c)). FDA's discussion in the preamble to the proposed rule
was intended to point out that CEQ regulations only discuss when a
supplement to a draft or final EIS is needed. CEQ regulations do not
specifically address or grant any authority to an agency to request
additional information under other circumstances. FDA also wanted to
make it clear that once FDA has taken an action, the agency has
authority under the act and the PHS Act to request that an applicant
submit additional information to an existing approval.
C. Subpart C--Categorical Exclusions
19. One comment found no major issues or problems with the policy
and procedure revisions, but expressed concern whether FDA had made
adequate analyses to substantiate the proposed categorical exclusions.
Another comment stated that the commenter was unable to evaluate the
proposed categorical exclusions, specifically the exclusion provided in
Sec. 25.31(b), because FDA had not made the information upon which it
based its conclusions available to the public.
To provide additional substantiation for its proposed categorical
exclusions, FDA supplemented the administrative record for the proposed
regulations with additional information. On October 22, 1996, the
agency published a notice in the Federal Register (61 FR 54746)
announcing the availability of specific information, including
underlying data, that along with the information in the preamble to the
proposed rule supports the categorical exclusions. FDA also reopened
the comment period for 30 days for the sole purpose of inviting public
comment on those categorical exclusions for which information had been
added to the administrative record. The agency received four comments
during this extended comment period, three of which addressed
categorical exclusions for drug and biologic products. FDA, therefore,
believes that it has provided adequate explanation of the categorical
exclusions and has provided adequate opportunity for comment on the
categorical exclusions by interested parties.
20. Proposed Sec. 25.30(j) revised the categorical exclusion for
issuance of certain types of regulations, including current good
manufacturing practice
[[Page 40575]]
(CGMP) regulations, to categorically exclude regulations based on the
hazard analysis critical control points (HACCP) principles. One comment
agreed with this change but recommended that HACCP programs incorporate
mandatory self audits and independent audits into their requirements.
This recommendation is outside the scope of this rulemaking.
1. Human Drugs and Biologics
21. Proposed Sec. 25.31(a) would categorically exclude FDA action
on an NDA, abbreviated application, or a supplement to such
applications, or action on an over-the-counter (OTC) monograph, if the
action does not increase the use of the active moiety of the drug. FDA
intended to include in this categorical exclusion applications for
marketing approval of a biologic product. As discussed in the preamble
to the proposed rule with regard to NDA's, abbreviated applications,
supplements, and OTC monographs, if an action, including action on a
marketing application for a biologic product, does not increase the use
of the product, there is no change in the level of substance in the
environment and, consequently, no increase in any environmental effects
associated with the use and disposal from use of the product.
Therefore, proposed Sec. 25.31(a) has been modified as follows:
Action on an NDA, abbreviated application, application for
marketing approval of a biologic product, or a supplement to such
applications, or action on an OTC monograph, if the action does not
increase the use of the active moiety.
22. Proposed Sec. 25.31(b) would categorically exclude FDA action
on a marketing application for a human drug, or 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 ppb. Several comments generally supported
the 1 ppb criterion, but sought minor revisions to or clarifications of
the criterion.
One comment suggested that the 1 ppb criterion be changed to 0.1
ppb using the predicted environmental concentration (PEC). PEC is
defined as the introduction concentration, corrected based on
metabolism/excretion data, on wastewater treatment facility fate
information, and on the use of an appropriate stream dilution factor of
10. Two comments suggested that proposed Sec. 25.31(b) be clarified to
indicate that the relevant concentration is at the point of entry into
the aquatic environment. One of these comments agreed that substances
entering the environment at less than or equal to 1 ppb will have an
insignificant environmental impact, but suggested that the standard be
an expected introduction concentration because this would give more
consideration to potential exposure to primary human receptors which
may come in contact with the substance before it degrades or enters a
wastewater treatment facility. Another comment suggested that because 1
ppb computes to a production rate of 40,700 kilograms (kg) per year
using the calculation method provided in FDA guidance, FDA should add
an exclusion for actions relating to human drugs for which the
production rate of the active moiety is less than 40,700 kg per year.
FDA agrees to clarify that the 1 ppb requirement is relevant at the
point of entry into the aquatic environment, that is, the environmental
introduction concentration (EIC). Under current part 25, FDA requires
EA's to initially provide an estimate of the quantity and concentration
of the substance that is expected to enter the environment. The
calculation method suggested by CDER is explained in its ``Guidance for
Industry for the Submission of an Environmental Assessment in Human
Drug Applications and Supplements'' (FDA, November 1995). If
environmental fate and effects information for a substance is required
in an EA, spatial and temporal concentration and depletion mechanisms
will, as appropriate, be used to adjust the EIC to estimate the
expected environmental concentration (EEC)/exposure concentration of
the product. PEC, as defined by the comment, is the same as the EEC/
exposure concentration. The comment's suggested use of a criterion of
0.1 ppb, calculated using a dilution factor of 10, is equivalent to the
agency's proposed criterion of 1 ppb calculated without using a
dilution factor, in that the same amount of the substance entering the
environment would qualify for categorical exclusion under each
proposal. It may be appropriate for FDA to consider a dilution factor
when estimating a substance's EEC/exposure concentration, based on
information provided in an EA, to evaluate the fate and effects of the
substance. For the purposes of a categorical exclusion criterion,
however, a conservative estimate of the concentration, EIC, will be
used.
As explained in the preamble to the proposed rule (61 FR 14922 at
14925, 61 FR 19476 at 19479), based on their 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. The data submitted in EA's reviewed
by CDER have routinely supported this hypothesis. 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. Proposed Sec. 25.31(b) has been revised to clarify that the
relevant concentration is at the point of entry into the aquatic
environment.
CEQ regulations require that localized (i.e., site-specific)
effects of a substance on the environment be considered, where
appropriate (40 CFR 1508.27(a)). Typically, the use of a drug product
is spread throughout the United States. However, in the rare instance
in which the use of a drug will be localized in one geographic area, a
categorical exclusion based on the concentration of a substance at the
point of entry into the aquatic environment, such as 1 ppb, provides
for an evaluation of the local environmental effect of that drug. The
suggestion to add a categorical exclusion based on a set quantity of
the drug product, such as 40,700 kg, ignores the possibility of
localized use that the agency is required to consider. Therefore, FDA
is not adding a categorical exclusion based on production rates.
Concerning potential exposure to primary human receptors, as
discussed in Calorie Control Council, Inc. v. U.S. Department of
Health, Education, and Welfare, No. 77-0776 (D.C.D.C. 1977), the
primary concern of NEPA is the impact of agency actions on physical
environmental resources, not the public health consequences of a
proposed action. Furthermore, NEPA authority is intended to supplement
other statutory responsibilities of a Federal agency. FDA already
addresses primary receptor issues as public health issues under the act
rather than through NEPA evaluation.
As a result of this discussion, proposed Sec. 25.31(b) has been
revised to state:
Action on a NDA, abbreviated application, or a supplement to
such applications, or action on an OTC monograph, if the action
increases the use of the active moiety, but the estimated
concentration of the substance at the point of entry into the
aquatic environment will be below 1 part per billion.
CDER's document, ``Guidance for Industry for the Submission of an
[[Page 40576]]
Environmental Assessment in Human Drug Applications and Supplements,''
provides a method for calculating the estimated concentration of the
substance at the point of entry into the aquatic environment. Other
calculation methods may be appropriate. However, such alternative
calculations will be reviewed by the agency on a case-by-case basis to
determine whether they are appropriate for determining whether the
categorical exclusion applies.
23. One comment reiterated a comment made during the initial
comment period that the agency needs to broaden ``extraordinary
circumstances,'' especially as the provision relates to paclitaxel, and
further noted ``troubling defects'' in the Toxicity Report the agency
provided in the administrative record to support the 1 ppb categorical
exclusion criterion in Sec. 25.31(b). The defects cited in the comment
include: (1) The report is grounded in an evaluation of ecotoxicity in
a few select laboratory species, not in wild organisms that may already
be stressed by other pollutants; (2) the report appears to be based on
EA's submitted by applicants to the agency, and no information is given
about how the toxicity figures were obtained and whether certain
assumptions were made in the studies; (3) the report does not consider
cumulative impacts associated with disposal of the products in the
environment, including the potential for bioaccumulation of pollutants
over time; and (4) the report provides no scientific explanation, other
than citing one article, for dividing the median effective
concentration (EC50) or median lethal concentration (LC50) values by
1,000 to arrive at a predicted no observed effect concentration (NOEC).
The comment also stated that the Toxicity Report is based on toxicity
tests that may be considered antiquated in light of recent efforts by
the Organization for Economic Cooperation and Development (OECD) and
EPA to revise such evaluations. The comment did not suggest any changes
to the proposed regulations.
FDA's extraordinary circumstances provision requires that at least
an EA be prepared if a normally excluded action may significantly
affect the quality of the human environment. The agency has
specifically determined that most actions relating to paclitaxel
derived from or otherwise involving the Pacific yew require the
preparation of EA's, irrespective of the expected concentration of
paclitaxel at its point of entry into the aquatic environment. (See the
response to comment 15, above.)
With respect to the alleged defects of the Toxicity Report,
environmental risk assessment initially involves determining the toxic
effect of a compound on a few select laboratory species. The test
organisms used by the applicants to generate the data in the Toxicity
Report are typically the same as those suggested by EPA (see 40 CFR
797) and OECD for this initial screening. CDER evaluates the potential
for significant environmental effects by relating the concentrations
determined to have toxic effects on these test organisms to the level
of the substance expected in the environment. Field studies (i.e.,
evaluation in actual environmental settings) are generally conducted
only when initial evaluation and subsequent intermediate evaluations
indicate that the potential for significant environmental harm may
exist.
FDA based the proposed 1 ppb categorical exclusion on toxicity data
submitted to the agency in EA's. The agency's analysis of the toxicity
data is explained in the Toxicity Report. Under 40 CFR 1506.5, the
agency asks applicants to prepare an EA and FDA independently evaluates
the information in the EA to determine its acceptability. The Toxicity
Report provides summary information from the EA's, identifying the
location of the detailed EA reports and FONSI's in the public docket.
FDA reviewed the test reports provided in EA's and determined that the
methodologies, assumptions, and conclusions of the reports were
acceptable. Any interested party may obtain additional information
regarding the test methods used for each EA from those reports in the
public docket.
Impacts on the environment which result from the incremental impact
of an action when added to other past, present, and reasonably
foreseeable future actions are known as cumulative impacts.
Consideration of cumulative impacts is included in the proposed
categorical exclusions for human drugs and biologics. Under
Sec. 25.31(a), action on a marketing application for a human drug or
biologic or action on an OTC monograph may be categorically excluded if
the action does not increase the use of the active moiety. However, if
an action increases the use of the active moiety, the impacts of that
increased use will require environmental analysis unless the action
meets other specific categorical exclusion criteria established in
Sec. 25.31(b) and (c). The potential for cumulative effects is also
considered in the calculation of the EIC of an active moiety of a drug
because the applicant bases these estimates on the expected quantities
that will be used 5 years in the future, including the use quantities
associated with related FDA applications (see, e.g., Guidance for
Industry for the Submission of an Environmental Assessment in Human
Drug Applications and Supplements, Section III.D.6.e, November 1995).
As stated in the preamble to the proposed rule (61 FR 14922 at
14925, 61 FR 19476 at 19479), one of the criteria for determining that
a drug is safe for human use is consideration of its potential to
bioaccumulate in body tissue. The vast majority of drugs do not
bioaccumulate because that characteristic would raise safety concerns
for use of the drugs in humans. If a drug has characteristics that
would allow it to bioaccumulate in tissue, the body must have a
mechanism to metabolize the compound into a substance that has lower
bioaccumulation potential so that it may be cleared from the body. In
the EA's that the agency reviewed, bioaccumulation was not an issue.
The practice of using assessment factors in environmental risk
assessments is well established. FDA's use of an assessment factor of
1,000 is consistent with EPA's approach (e.g., Zeeman, M., and J.
Gilford, ``Ecological Hazard Evaluation and Risk Assessment Under EPA's
Toxic Substances Control Act (TSCA): An Introduction,'' in
Environmental Toxicology and Risk Assessment, ASTM STP 1179, edited by
W. Landis, J. Hughes, and M. Lewis, pp. 7-21, American Society for
Testing and Materials, Philadelphia, 1993.).
The toxicity tests performed by FDA applicants and described in the
Toxicity Report are consistent with contemporary practice and are based
on current scientific thinking. Potential future revision of test
methods does not render invalid current testing, data obtained as a
result of that testing, or conclusions based on that data.
24. One comment stated that under Sec. 25.31(b), FDA will now
apparently permit companies seeking approval of metered dose inhalers
to forgo preparation of EA's in connection with their marketing
applications. The comment asked that the agency make clear in its final
regulations that FDA will require EA's with all applications involving
metered dose inhalers that release chlorofluorocarbons (CFC's) and that
such EA's must thoroughly evaluate the cumulative impacts of CFC's on
the Antarctic environment and alternatives that avoid such impacts.
In 1978, FDA finalized a programmatic EIS regarding the use of
fluorocarbons in products subject to regulation by the agency under the
act (Final Environmental Impact Statement;
[[Page 40577]]
Fluorocarbons: Environmental and Health Implications, February, 1978,
Docket No. 76N-0640) and announced the availability of the final EIS in
the Federal Register (43 FR 11316, March 17, 1978). This EIS was used
as the basis for prohibiting use of CFC's as propellants in self-
pressurized containers if the use of the CFC was not deemed to be
essential. As stated in the EIS:
The Commissioner of Food and Drugs has concluded that the
continued use of chlorofluorocarbon propellants in self-pressurized
containers in products subject to the Federal Food, Drug, and
Cosmetic Act (FFD&C) poses an unreasonable risk of long-term
biological and climatic impacts.
Accordingly, the Food and Drug Administration is finalizing a
prohibition of the nonessential use of chlorofluorocarbons as
propellants in self-pressurized (aerosolized) containers in products
subject to the FFD&C Act. The products to which the regulation
applies are human food, food additives, human drugs, including
biological products, animal food, animal drugs, cosmetics, and
medical devices. (p. iii)
The EIS further stated:
The selection of fluorocarbon use(s) to be regulated requires a
determination of whether or not a particular fluorocarbon use is
essential. The Commissioner of Food and Drugs has defined
essentiality to mean that there are no technically feasible aerosol
or non-aerosol alternatives to using a fluorocarbon in a product and
that a product provides a substantial public benefit such as a
therapeutic medical benefit. The product need not be indispensable
to life, but the benefit must be important and consist of more than
added convenience. (p. 89)
A copy of the programmatic EIS has been placed in the administrative
record for this rule (Docket No. 96N-0057).
FDA regulations pertaining to the use of CFC propellants in self-
pressurized containers are described in Sec. 2.125. CFC's may be used
as propellants in a self-pressurized container only if the drug is
approved, a petition has been filed as described in Sec. 2.125(f), and
Sec. 2.125(e) has been amended to specify the use as essential. The
petition requesting an essential use designation must be supported by
an adequate showing that: (1) No technically feasible alternatives
exist to the use of a CFC in the product; (2) the product provides a
substantial health benefit, environmental benefit, or other public
benefit that would not be obtainable without the use of the CFC; and
(3) the use does not involve a significant release of CFC's into the
atmosphere or, in the alternative, the release is warranted in view of
the consequences of the use not being permitted. The petition is a
public document about which any interested party may comment before a
final determination is made by the agency.
FDA is in the process of establishing a policy for determining when
uses of CFC's currently designated essential will no longer be deemed
essential under the Clean Air Act due to the availability of safe and
effective medical product technology that does not use CFC's. (See
Docket No. 97N-0023.)
The agency has, in the programmatic EIS, evaluated the individual
and cumulative effects, including the effects on human health,
stratospheric ozone, biological systems (nonhuman), and climate, of
approvals of marketing applications that result in the release of
CFC's. FDA has fulfilled its responsibilities and has adequately
considered the environmental issues regarding CFC's. Therefore, a
requirement that individual marketing applications for metered dose
inhalers that release CFC's must include EA's is not necessary because
the environmental information would already be under consideration by
the agency in its decision whether to designate an essential use under
Sec. 2.125(e). Resubmission of this information to the agency would not
be consistent with CEQ goals of reducing excessive paperwork. NEPA
supplements, but does not supersede, other statutory responsibilities.
NEPA establishes requirements to ensure that an agency considers
environmental information in its decisionmaking process. Thus, after a
review of the relevant environmental information, FDA may, but is not
required to, decline to take an action that may have a significant
effect on the environment.
25. Proposed Sec. 25.31 lists the general classes of agency actions
relating to human drugs and biologics that are categorically excluded
and, therefore, ordinarily do not require the preparation of EA's or
EIS's. One comment requested that a categorical exclusion be added to
the regulations for ``[a]ction on an NDA, abbreviated application, or a
supplement to such application, or action on an OTC monograph, if the
active moiety has been previously approved by FDA and the concentration
in the environment will be above 1 part per billion.''
The agency believes that providing a categorical exclusion in
Sec. 25.31 for an active moiety that has been previously approved by
the agency is inappropriate. FDA does not have any evidence that
actions relating to the approval of a drug or biologic for which the
active moiety has been previously approved do not individually or
cumulatively have a significant effect on the environment. In some
cases, the approval of a new indication or dosage form of a previously
approved active moiety could substantially increase the use of the
product. In such cases, an EA must be prepared unless the action meets
one of the other criteria for a categorical exclusion.
26. One comment requested that proposed Sec. 25.31 be revised to
add a categorical exclusion for actions relating to drugs that involve
substances that have an environmental concentration greater than 1 ppb
(i.e., do not meet the criteria for categorical exclusion under
Sec. 25.31(b)) but have a PEC to a predicted no effects concentration
(PNEC) ratio equaling less than one.
The agency declines to amend Sec. 25.31 as requested. A PEC/PNEC
ratio is one of several commonly used approaches for evaluating
environmental effects. To calculate the PEC/PNEC ratio, ecotoxicity
studies are performed, results are compared to expected environmental
concentrations, and a conclusion is drawn. The calculation also
requires use of an assessment factor that will vary depending on the
type of ecotoxicity data generated. The PEC/PNEC ratio constitutes an
environmental analysis and, therefore, is not an appropriate criterion
for a categorical exclusion. If FDA were to use a PEC/PNEC ratio as a
criterion for categorical exclusion, FDA would need to review the
underlying data that supports the PEC/PNEC ratio, including the
assessment factor, and would, in essence, be requiring an EA. Thus, FDA
will not add a categorical exclusion for actions relating to drugs
based on the calculation of a PEC/PNEC ratio. An applicant is not
precluded, however, from using a PEC/PNEC ratio to assess environmental
effects in an EA or to aid in determining whether extraordinary
circumstances exist such that a proposed action, which is normally
excluded, may have an environmental effect.
27. One comment recommended that the categorical exclusion
described in proposed Sec. 25.31(c) for naturally occurring substances
not include new steroid or hormone modulating drugs.
As explained in the preamble to the proposal (61 FR 14922 at 14926,
61 FR 19476 at 19480), FDA based the categorical exclusion in
Sec. 25.31(c) on its finding, after reviewing abbreviated EA's for
substances that are naturally occurring, 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. No information was provided in
the comment to support the need for this change. The available
[[Page 40578]]
evidence does not support a finding that new steroid or hormone
modulating drugs, at the expected level of exposure, have the potential
to significantly affect the environment. Therefore FDA will not modify
Sec. 25.31(c). The agency specifically addressed concerns regarding
synthetic estrogens used in human drugs in comment 16 of this document.
The agency will evaluate each proposed action on an individual basis to
determine if extraordinary circumstances exist such that further
environmental documentation is needed.
28. One comment requested clarification regarding the definition of
``substances that occur naturally in the environment'' as that phrase
is used in proposed Sec. 25.31(c). The comment suggested that the
categorical exclusion be revised to read ``substances that either occur
naturally in the environment, or are derived from biological systems''
or, alternatively, that FDA provide a definition in the regulation.
The agency declines to adopt the language suggested in the comment
because the term ``or derived from biological systems'' is too broad.
Not all substances produced by a biological system may be substances
that occur naturally in the environment. The biological system, or the
substance itself, may be modified such that the substance does not
occur naturally in the environment. The comment provided no rationale
as to why biologically-derived substances not occurring naturally in
the environment should be subject to the categorical exclusion.
FDA intends to clarify which type of actions would fall under this
categorical exclusion in guidance documents prepared by each center.
FDA-regulated articles may be considered for categorical exclusion
under this provision whether they are obtained from natural sources,
biological systems, or are chemically synthesized. The agency will
consider the form in which the FDA-regulated article will exist in the
environment when determining if an action will be eligible for this
categorical exclusion. For example, a modified active moiety (e.g.,
salt) which does not occur naturally may be considered a naturally
occurring substance if it is established that, in vivo and in the
environment, the active moiety exists in a form that is found
naturally. Biological and biotechnological products will be similarly
evaluated. For example, a protein or DNA comprised of naturally
occurring amino acids or nucleosides, but with a sequence different
from that of a naturally occurring substance, will normally qualify for
this categorical exclusion after consideration of metabolism. The same
principle will apply to synthetic peptides and oligonucleotides. Living
and dead cells and organisms regulated by the agency may also be
considered for categorical exclusion under this provision if the action
does not alter significantly the concentration or distribution of the
substance, its metabolites, or degradation products in the environment.
The agency will rely on the significant amount of information submitted
by an applicant in support of a requested action (for example
information about metabolism, excretion, and stability; viability (if
applicable); and physical/chemical characteristics of the product) in
determining whether categorical exclusion under Sec. 25.31(c) is
appropriate.
29. One comment requested that the phrase ``action on an OTC
monograph,'' which is included in the categorical exclusions in
Sec. 25.31 (a), (b), and (c), be changed to ``OTC activity'' and that
the regulation define ``OTC activity'' as ``an action on an OTC
monograph or a switch of a drug from prescription to OTC use that is
submitted in an NDA or supplement, if the product is already marketed
for the proposed use.'' The comment expressed a belief that the
preamble to the proposed rule ``is clear on the intent for a
prescription to an OTC switch to be considered as a categorical
exclusion.''
FDA does not believe it is necessary or appropriate to substitute
``OTC activity'' for ``action on an OTC monograph'' in Sec. 25.31 (a),
(b), and (c). Agency action on any request to switch a drug from
prescription to OTC use is already covered in Sec. 25.31 (a), (b), and
(c) by the language ``action on an NDA, abbreviated application, or a
supplement to such application, or action on an OTC monograph.''
Depending on the circumstances and the applicant's preference, a
prescription to OTC switch may be requested using any of these
administrative filing mechanisms. As discussed in the preamble (61 FR
14922 at 14925, 61 FR 19476 at 19479), the agency will not elevate form
over substance and will treat like actions alike, regardless of the
avenue through which the actions are requested. Thus, the same
categorical exclusion criteria will apply to NDA's, abbreviated
applications, supplements, and ``actions on OTC monographs.''
Prescription to OTC switches have generally been, and will continue
to be, considered by CDER to be actions that increase use because the
potential patient population expands from only those persons who seek
treatment under a physician's care to any person who enters a retail
establishment that sells OTC products. Therefore, agency action on an
OTC switch will be categorically excluded if the criteria of Sec. 25.31
(b) or (c) apply to the action, specifically if the concentration of
the substance at the point of entry into the aquatic environment will
be below 1 ppb (Sec. 25.31(b)), or if it is a substance that occurs
naturally in the environment and the action will not significantly
alter the concentration of the substance in the environment
(Sec. 25.31(c)).
30. Proposed Sec. 25.31(e) would categorically exclude action on an
IND from the requirement to prepare an EA. One comment suggested that
this exclusion be limited by specifying in the exclusion a ceiling on
the quantity (number of doses) to be released into the environment.
As stated in the preamble to the proposed rule (61 FR 14922 at
14926, 61 FR 19476 at 19480), FDA action on an IND in many cases does
not significantly increase the use of the drug or the amount of the
drug introduced into the environment because the drug is being
administered to few patients or is already being marketed for another
use. Consequently, no changes in the effect on the environment will
occur due to agency action on the IND. In the event FDA action on an
IND would increase the use of a drug, the agency's experience has
demonstrated that significant environmental effects would not occur
because the investigational use is limited and controlled. The dosing
regimen for investigational drugs that would result in an environmental
introduction concentration of 1 ppb (the concentration below which FDA
has found no significant effect on the environment) is not expected for
clinical trials held under an IND. Very large clinical trials are rare,
but, cumulatively, they enroll approximately 8,000 patients. Those
subjects would need to use 14 grams of the active moiety every day for
an entire year to result in an environmental introduction concentration
of approximately 1 ppb, the concentration below which CDER has
routinely observed no significant effects on relevant standard test
organisms in the aquatic environment. The level and duration of this
dosing regimen, as described, are greater than is expected under
clinical trials, thus the addition of a criterion limiting the number
of doses is unnecessary.
The preamble to the proposed rule (61 FR 14922 at 14923, 61 FR
19476 at 19477) noted that categorical exclusion
[[Page 40579]]
criteria relating to toxicity, which includes current Sec. 25.24(c)(4),
``if * * * waste will be controlled or the amount of waste expected to
enter the environment may reasonably be expected to be nontoxic,'' have
been incorporated into the extraordinary circumstances provision of
Sec. 25.21(a). Therefore, the categorical exclusion for IND's remains
essentially unchanged. In the event FDA has reason to believe its
action on an IND may significantly affect the environment, FDA will
invoke the provision relating to ``extraordinary circumstances'' and
require an EA. Therefore, the agency declines the suggestion to modify
the categorical exclusion in Sec. 25.31(e).
2. Foods, Food Additives, and Color Additives
31. Proposed Sec. 25.32(b) provides for a categorical exclusion for
FDA action on a request for exemption for investigational use of a food
additive, if the food additive is intended to be used for clinical
studies or research. One comment noted the absence of a discussion
concerning the potential impact of the investigational use of food
additives in the preamble to the proposal, despite the discussion about
the potential environmental impact of investigational and clinical
research for drugs. The comment recommended that FDA establish a
maximum annual quantity for investigational uses of food additives
allowed to be released to the environment.
The agency declines to establish additional criteria for the
application of the categorical exclusion of the investigational use of
food additives. FDA has not required that a formal application be
submitted to the agency for the investigational use of a food additive.
The investigational use of food additives is expected to be limited to
small amounts needed in studies with laboratory animals under 21 CFR
170.17. Occasionally additives are tested in limited clinical trials
under the control of institutional review boards. The program has
functioned for 40 years with little investigational activity under 21
U.S.C. 348(i). Thus, the agency is not aware of any need to revise this
exclusion to include a ceiling on the yearly amount of a substance that
may be released into the environment. Furthermore, the comment provided
no information on which to conclude that such a ceiling is justified.
32. One comment specifically supported the categorical exclusions
in the proposed rule for food and color additives and generally
recognized as safe (GRAS) substances. Another comment specifically
supported the categorical exclusions set forth in proposed Sec. 25.32
(i), (k), and (r), but raised issues regarding the need for reform of
the review process for food additive and GRAS petitions.
Reform of the review process for food additive and GRAS petitions
is outside the scope of this rulemaking and will not be addressed here.
33. One comment, while generally supporting the categorical
exclusions in proposed Sec. 25.32 (i) and (j), requested that they be
expanded to include all actions on components of food-contact
materials, including actions on GRAS petitions, except where
extraordinary circumstances exist. The comment asserted that compiling
the information needed for EA's for food-packaging materials is
unnecessary and unduly burdensome, that the costs of preparing EA's for
these materials are significant, and that routine preparation of EA's
for these actions results in an unnecessary expenditure of industry and
agency resources. The comment requested that the agency not require
EA's for actions on nonfunctional components of food-packaging
materials because Federal, State, and local laws and regulations
adequately control emissions to the environment at sites where these
substances are used in the manufacture of food-packaging materials. The
comment pointed out that the agency is proposing not to require
information on the production of FDA-regulated substances based on its
recognition that Federal, State, and local environmental laws and
regulations adequately protect the environment at the production sites
for those substances. The comment requested that the agency apply the
same reasoning to conclude that EA's are no longer needed to assess the
environmental impact of nonfunctional components of food-packaging
materials that are used and enter the environment at the production
sites of the packaging material. The comment also requested that EA's
not be required for actions involving components of finished food-
packaging material present at greater than 5 percent-by-weight because:
(1) Most of these additives will replace other similar, already
regulated additives and will not have any meaningful impact on the
potential uses of the finished food-packaging material; and (2)
adequate Federal, State, and local laws and regulations are in place to
protect environments that may be affected by disposal of food-packaging
material. The comment pointed out that ``in certain rare situations,
for example, in instances where the use of a new material may affect
recycling streams, disposal of food-packaging materials prepared from a
newly regulated polymer could potentially have some effect on the
environment.'' The comment suggested that in these instances it may be
appropriate for the agency to require an EA and that proposed
Sec. 25.21 (Extraordinary circumstances) will provide the agency with
the means to require EA's for these few situations.
FDA agrees that the new categorical exclusions in proposed
Sec. 25.32 (i) and (j) should be revised to include GRAS petitions. The
agency also acknowledges that there are certain classes of
nonfunctional components of food-packaging materials and certain
classes of components of food-packaging material present at greater
than 5 percent-by-weight of the finished food-packaging material that
should be included under Sec. 25.32(i). However, FDA does not agree
that all classes of actions on substances intended for use as
components of food-contact materials warrant categorical exclusion. Nor
does the agency agree that compiling the information needed for EA's
for food-packaging materials is unnecessary, unduly burdensome, and
costly. The basis for the agency's decision on these classes of actions
is explained below.
GRAS petitions: None of the petitions that the agency has reviewed
while developing the categorical exclusions in Sec. 25.32 (i) and (j)
(including those it has reviewed since the proposal issued) were GRAS
affirmation petitions for components of food-packaging material or
components of food-contact surfaces of equipment or other repeat use
food-contact articles. But, because the environmental information that
would be needed under part 25 for a GRAS petition for these types of
food-contact substances is identical to the information required for a
food additive petition, the agency believes that its experience with
food additive petitions is relevant to GRAS affirmation petitions and
that any future GRAS affirmation petitions for these classes of actions
can also be excluded. Therefore, FDA has revised proposed Sec. 25.32(i)
and (j) to include actions on GRAS affirmation petitions.
Nonfunctional components of food-packaging material: The agency
does not believe it is appropriate to categorically exclude all actions
on nonfunctional components of food-packaging material, as requested by
the comment. To evaluate the request that FDA revise Sec. 25.32(i) to
further exclude from the requirements for EA actions on nonfunctional
components of food-packaging materials, the agency reviewed 44
petitions for nonfunctional components of food-packaging
[[Page 40580]]
materials.1 As a result of this review, the agency found
that a number of these petitions warranted exclusion from the need for
an EA, while others did not. The agency found that 13 of the petitions
were for additives that remained with food-packaging materials used by
consumers despite the fact that these additives did not function in the
finished food-packaging material. As they pertained to use and disposal
of nonfunctional components of food-packaging materials, the FONSI's
for the agency's actions on these petitions were based on the following
factors: (1) Only very small quantities, if any, of these additives
were expected to enter the environment at sites where the additives
were used in the manufacture of food-packaging materials; (2) only
extremely low levels of substances, if any, could be expected to enter
the environment as a result of disposal of food-packaging materials;
and (3) virtually no change in the use of natural resources and energy
would be expected because the additives would be replacing other,
currently regulated, additives and would not affect the uses of the
packaging materials to which they were added. These factors are the
same as those upon which the agency bases its exclusion for actions on
functional components of finished food-packaging materials. Therefore,
the agency has decided that it is appropriate to revise proposed
Sec. 25.32(i) to include all components of food-packaging materials
that remain with finished packaging through use by consumers and are
present at less than 5 percent-by-weight, regardless of whether they
perform a function in the finished package.
---------------------------------------------------------------------------
\1\ ``Index of Petitions for Nonfunctional Components of Food-
packaging Materials,'' (Docket No. 96N-0057).
---------------------------------------------------------------------------
In its review of the remaining 31 petitions involving nonfunctional
components of finished food-packaging material, the agency found that 5
petitions were for antimicrobial substances that are also regulated by
EPA under the Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA) as pesticides. In Sec. 25.32(q) of the proposed rule, actions
to approve a food additive petition or grant a request for exemption
from regulation as a food additive under Sec. 170.39 are categorically
excluded when the substance that is the subject of the petition or
request is registered by EPA under FIFRA for the same use requested in
the petition or in the request for exemption.
Also among these 31 petitions were 6 petitions for substances that
occur naturally in the environment. These petitions would be excluded
from the requirement to prepare an EA under the categorical exclusion
in Sec. 25.32(r) of the final rule.
The 20 remaining petitions involving nonfunctional components of
finished food-packaging material were for additives that were not
expected to remain with the finished article, but instead were expected
to enter the environment at sites where they were used as processing
aids in the manufacture of food-packaging materials and were neither
antimicrobial substances nor naturally occurring substances. These
types of additives are not intended to remain with the finished food-
packaging materials which are used and disposed of by consumers
throughout the United States. The results of environmental toxicity
tests presented in some of these petitions showed that the additives
had the potential to harm organisms in the environment present at or
adjacent to the use sites. For 17 of these 20 petitions, FDA conducted
an analysis of the environmental exposure levels of the additives at
the use sites and compared these exposure levels to environmental
toxicity information on the additives to determine the potential for
significant impact. In some cases, the margin between environmental
exposure levels and levels found to be toxic to organisms present in
the receiving environment was very narrow. For the remaining three
petitions, FDA relied upon adequate regulation of potential discharges
to reach its environmental decision.
Under current part 25, FDA has required specific information about
Federal, State, and local laws and regulations that are applicable to
emissions at the site of production of the subject substances where the
manufacturing operations are designed to provide maximum yield of the
FDA-regulated article for commercial sale. FDA reviewed hundreds of
submissions with this information before deciding to eliminate the
requirements for its inclusion. However, the formats for EA's in
current Sec. 25.31a do not require information on emissions
requirements at the sites where nonfunctional components of food-
packaging materials are used to produce the finished article. A review
of FDA's experience with EA's for most nonfunctional components of
finished food-packaging materials that are expected to enter the
localized use site environment (i.e., the finished food-packaging
manufacturing facility) has revealed that analysis of exposure and
environmental toxicity is necessary to determine the potential for
significant impact. Based on this experience, therefore, the agency
does not agree with the comment that it can rely on other Federal,
State, and local laws for protecting the environment to exclude actions
on petitions for these nonfunctional components of food-packaging
materials as was done to eliminate requirements for information on the
sites of production of FDA-regulated articles.
Thus, the agency cannot establish an additional categorical
exclusion for petitions for nonfunctional components of food-packaging
that do not remain with food-packaging through use by consumers. The
agency will provide specific guidance to petitioners for preparing EA's
for those categories of petitions that will require EA preparation. The
guidance for EA's involving nonfunctional components of food-packaging
materials will focus on the relevant issues surrounding a proposed
action and will take into consideration whether other laws and
regulations adequately control potential environmental impacts or
whether an action may threaten a violation of such laws and regulations
as required by CEQ regulations (40 CFR 1508.27(b)(10)).
Components of Finished Food-packaging Material Present at Greater
than 5 Percent-by-Weight: The comment requested a categorical exclusion
for actions involving components of finished food-packaging material
present at greater than 5 percent-by-weight, but did not provide any
specific information showing that actions on petitions in this category
do not individually or cumulatively have significant environmental
effects. To evaluate this request, FDA reviewed 30 petitions for
components of food-packaging materials present at greater than 5
percent.2 The agency found that five of these petitions were
for coatings or components of coatings for food-packaging materials.
The FONSI's for the agency's actions on these petitions were based on
the following factors: (1) Only extremely low levels of substances, if
any, could be expected to enter the environment as a result of use and
disposal of these coated food-packaging materials; and (2) virtually no
change in the use of natural resources and energy would occur because
the additives would be replacing other, currently regulated, additives
and would not affect either the uses of the packaging materials to
which they were added or the disposal technologies used for these
materials. These factors are the same as those upon which the exclusion
for actions on functional components of
[[Page 40581]]
finished food-packaging materials present at less than 5 percent are
based even though the components of the coatings may be present in the
finished food-packaging material at greater than 5 percent-by-weight.
Therefore, the agency is revising the exclusion in proposed
Sec. 25.32(i) to include actions on the components of coatings of
finished food-packaging materials.
---------------------------------------------------------------------------
\2\ ``Index of Petitions for Components of Food-packaging
Materials Present at Greater than 5%,'' (Docket No. 96N-0057).
---------------------------------------------------------------------------
The agency's findings for the remaining 25 petitions support FDA's
position that significant environmental effects may result from agency
actions on components of finished food-packaging material present at
greater than 5 percent-by-weight. Examples of petitions that required
extensive analysis to determine the potential impact of food-packaging
materials on solid waste management strategies include food additive
petition (FAP) 6B3948 (Docket No. 86F-0341); FAP 7B3979 (Docket No.
86F-0508); FAP 8B4107 (Docket No. 88F-0404); FAP 1B4236 (Docket No.
91F-0198); and FAP 8B4110 (Docket No. 88F-0339). In some cases, the
agency and the petitioners decided to include mitigating measures in
the food additive regulations to avoid potentially significant
environmental effects. In addition, the agency has not acted on FAP
7B3994, because it needs to consider further whether significant
effects on solid waste management strategies may result (53 FR 47264 at
47267, November 22, 1988). Evaluation of these potential effects is
being conducted along with an evaluation of the agency's proposed
action to provide for the safe use of vinyl chloride polymers (51 FR
4177, February 3, 1986). The agency announced on November 22, 1988 (53
FR 47264), its intent to prepare an EIS on its actions on vinyl
chloride and other chlorinated polymers. FDA continues to work on this
statement.
This comment asserted that EA's are not needed for petitions for
components of food-packaging materials because the effects of disposal
of food-packaging materials by incineration or landfilling are subject
to the control of laws, regulations, and government authorities
directly concerned with the environment. FDA, based on its experience,
agrees that the extremely low levels of substances that may leach from
food-packaging materials disposed of in landfills are adequately
controlled by EPA regulations in 40 CFR part 258. FDA is aware of laws
and regulations governing the incineration of municipal solid waste,
which include the incineration of food-packaging materials. However,
there is potential for incineration of food-packaging materials to
threaten a violation of these laws and regulations. FDA will consider
this potential effect under 40 CFR 1508.27(b)(10). For example, in its
decision to prepare an EIS on its actions on vinyl chloride and other
chlorinated polymers (53 FR 47264 at 47265, November 22, 1988), the
agency found that the expected increase in hydrogen chloride emissions
from incinerators may affect the ability of incinerator operators to
comply with existing and anticipated emissions standards. This issue is
still under agency review.
A number of the agency's actions on components of food-packaging
materials present at greater than 5 percent-by-weight had potential for
significant effects on the environment. The agency is unable, without
specific information such as that provided in an EA, to distinguish
which petitions for these actions may have potential for significant
impact. Therefore, the agency will continue to require EA's for this
category of petitions, with the exception of those petitions pertaining
to components of coatings. The agency will develop and provide to
petitioners specific guidance for preparing EA's for those categories
of petitions that will require the preparation of EA's. The guidance
for EA's involving components of packaging present at greater than 5
percent-by-weight will focus on the relevant issues surrounding a
proposed action, and will take into consideration the extent to which
other laws and regulations adequately control potential environmental
impacts.
As a result of this analysis, proposed Sec. 25.32, categorical
exclusions for foods, food additives, and color additives, will be
revised at paragraphs (i) and (j) to read as follows:
(i) Approval of a food additive petition, GRAS affirmation
petition, or the granting of a request for exemption from regulation
as a food additive under Sec. 170.39 of this chapter, when the
substance is present in finished food-packaging material at not
greater than 5 percent-by-weight and is expected to remain with
finished food-packaging material through use by consumers or when
the substance is a component of a coating of a finished food-
packaging material.
(j) Approval of a food additive petition, GRAS affirmation
petition, or the granting of a request for exemption from regulation
as a food additive under Sec. 170.39 of this chapter, when the
substance 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.
Burden of compiling the information for EA's for food-packaging
materials: As discussed above, for certain actions involving food-
packaging materials, FDA will continue to require petitioners to submit
an EA. FDA does not agree that the information it requires the
petitioner to submit in these EA's is unnecessary, nor does the agency
believe the effort to provide such information is unduly burdensome. As
FDA has stated above, it will provide guidance to industry regarding
the focus of environmental documents. In addition, FDA has limited in
the past and will continue to limit its requests for information to
only the amount needed to assess the potential environmental impact of
its actions. FDA recognizes that in some cases the information needed
for EA's is not readily available or is not yet known to a petitioner.
In such cases, the agency in the past has asked the petitioner to
provide a best possible forecast or to use a conservative approach to
analyze environmental effects. FDA will continue this approach,
recognizing that in some cases there may be uncertainty about the
potential for significant environmental impact of food-packaging
materials.
In the preamble to the proposal (61 FR 14922 at 14935, 61 FR 19476
at 19489), FDA noted its calculation that the proposed changes in the
environmental regulations would reduce the costs for both the regulated
industry and for the agency. These reduced costs will result from,
among other things, providing for categorical exclusions for additional
classes of actions. To this end, the agency proposed and is now making
final two exclusions that will apply to actions on food-packaging
materials (Sec. 25.32 (i) and (j)). As explained above, these
exclusions have been expanded in the final rule to include additional
classes of actions. These changes are expected to further reduce the
costs of preparing and reviewing environmental documents for food-
packaging materials. The agency believes that the remaining actions on
food-packaging materials that require EA's have the potential to result
in significant environmental effects, and information in an EA is
necessary for the agency to make decisions on these potential effects.
34. Proposed Sec. 25.32(k) would 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 foods. One comment claimed that FDA was
proposing a 1 ppb environmental exposure threshold below which the
exclusion applied, as was done for human drugs in proposed
Sec. 25.31(b). The comment requested that FDA establish a maximum
annual quantity of
[[Page 40582]]
the food additive allowed to be released to the environment under this
exclusion.
The agency declines to establish additional criteria for the
exclusion under Sec. 25.32(k) covering substances that are intended to
remain in food through ingestion by consumers and are not intended to
replace macronutrients in food. As explained in the preamble to the
proposal (61 FR 14922 at 14928, 61 FR 19476 at 19482), the basis for
this exclusion is FDA's experience reviewing 21 petitions in this
class, all of which resulted in a FONSI. The FONSI's relied on one or
more of the following scenarios: (1) The approval of the petition
resulted in very low levels of the substances in either effluents and/
or sewage sludge; (2) the substance was digested and/or metabolized by
humans such that only the products of digestion and metabolism were
expected to be excreted and those products were the same as (or very
similar to) other products of digestion and metabolism resulting from
human food; or (3) the substance was excreted largely intact but was
rapidly degraded into nontoxic products. Based upon this review of
petitions in this class, the agency found that it was not necessary to
establish either an exposure threshold concentration or a maximum
annual quantity of substances allowed to be released. Even in the three
instances where it was necessary to compare the environmental exposure
level of the substance with environmental toxicity data, there was a
wide margin of safety. No information to support the establishment of
either of these qualifying thresholds is provided in the comment.
Therefore, the agency has no basis on which to revise Sec. 25.32(k) to
incorporate either an exposure threshold concentration or a maximum
annual quantity that may be released.
35. An additional comment about the exclusion in proposed
Sec. 25.32(k) expressed concern about the potential for significant
impacts on energy and natural resources resulting from the use and
disposal of nonnutritive oils. This comment recommended that the
proposed exclusion be withdrawn or that a ceiling be added that would
require an EA where such substances enter the environment above a
certain annual level.
The agency declines to amend the proposed exclusion as recommended.
Actions on food additive petitions for nonnutritive oils or fat
substitutes would not qualify for the categorical exclusion in
Sec. 25.32(k), because such substances are considered to be
replacements for macronutrients. An EA submitted for a fat substitute
would include consideration of the impact on energy and natural
resources resulting from the production (if appropriate), use, and
disposal of such substances. Such considerations were part of FDA's
action to approve the use of the fat substitute olestra (Docket No.
87F-0179).
36. Proposed Sec. 25.32(m) would categorically exclude actions to
prohibit or otherwise restrict or reduce the use of asubstance in food,
food packaging, or cosmetics. One comment supported this exclusion, but
requested clarification regarding how FDA will consider under this
exclusion impacts on the environment (to human well-being and on the
environment itself) that are controversial.
As discussed in the preamble to the proposal (61 FR 14922 at 14929,
61 FR 19476 at 19483), the agency has found that this class of actions
has not involved controversial issues with respect to potential impact
on the physical environment. FDA's action to prohibit the use of CFC's
is the only exception to this principle to date.
In most instances, the purpose of actions to restrict or withdraw
approval of foods, food packaging, or cosmetics is to protect the
public health. Potential impacts on human health, and any controversy
surrounding such impacts, are fully considered in Federal Register
documents (e.g., a preamble to a proposed or final rule restricting or
withdrawing approval) supporting the action. See the response to
comment 22, above. The appropriateness of an exclusion for a proposed
action to restrict or eliminate the use of a substance in food, food-
packaging, or cosmetics will depend on whether the action may involve
extraordinary circumstances that would require evaluation through an EA
or an EIS. Under proposed Sec. 25.21, extraordinary circumstances
include the degree to which the possible effects on the human
environment are likely to be highly controversial, as provided in 40
CFR 1508.27(b)(4).
37. Proposed Sec. 25.32(o) would categorically exclude actions to
approve a food additive petition for the intended expression product(s)
present in food derived from new plant varieties. One comment
recommended that compounds that may be ``hormone modulators'' should
not be included in this categorical exclusion.
FDA is not aware of any specific substances derived from new plant
varieties that could potentially affect the endocrine system of other
organisms. It is unlikely that FDA would receive a food additive
petition for a substance derived from new plant varieties that was
intended to have a physiological effect on the human endocrine system.
A substance derived from new plant varieties that is intended to have
such an effect on the human endocrine system would be regulated by FDA
as a drug. Thus, it is unlikely that a claim for categorical exclusion
for a hormone modulator would be made under Sec. 25.32(o) and FDA
declines to modify Sec. 25.32(o) to reflect such a scenario.
In the event FDA receives a food additive petition for a substance
derived from new plant varieties that is known or suspected to have
potential for affecting the endocrine system in humans, aquatic life,
and/or wildlife, agency action on such a petition would generally be
excluded under Sec. 25.32(o). As described in the preamble to the
proposed rule (61 FR 14922 at 14929-14930, 61 FR 19476 at 19483-19484),
under Sec. 25.32(o) environmental review of new plant varieties would
be performed by the United States Department of Agriculture (USDA).
Therefore, if USDA has granted a categorical exclusion or conducted an
environmental review, NEPA review by FDA would be redundant and
therefore, unnecessary.
38. In proposed Sec. 25.32(q), actions to approve a food additive
petition or grant a request for exemption from regulation as a food
additive under Sec. 170.39 are categorically excluded when the
substance that is the subject of the petition or request is registered
by EPA under FIFRA for the same use requested in the petition or in the
request for exemption. One comment stated that the same information
submitted to EPA for registration of pesticides under FIFRA should be
encouraged for FDA submissions. The comment expressed concern about the
lack of policy alignment between agencies regarding the level of risk
and about the ability of FDA to meet deadlines due to its reliance on
the review of data by another agency that may have different review
priorities. The comment suggested that FDA ``handle this proposed
exclusion as a guideline policy rather than a categorical exclusion,''
or align interagency risk determination policies before allowing this
exclusion.
FDA does not agree with the suggestion that the exclusion be
handled as a guideline policy. As discussed in the preamble to the
proposal (61 FR 14922 at 14930, 61 FR 19476 at 19484), FDA has found
that the scope of EPA's review of the environmental risk of
antimicrobial substances subject to pesticide registration under FIFRA
encompasses FDA's review of the environmental risk
[[Page 40583]]
of these substances for food additive use under NEPA. In evaluating
whether a food additive petition or request for exemption meets the
categorical exclusion in Sec. 25.32(q), FDA will ensure that the
substance for which a petitioner seeks approval is identical to the
substance that is registered as a pesticide under FIFRA. If the
substance is registered as part of a formulation under FIFRA, FDA will
ensure that it is approving the substance for use as part of that
formulation registered under FIFRA. By ``same use'' the agency means
that in a comparison of the food additive use to the pesticide use, the
purpose of the use, any components used with the substance for the
petitioned use, and the amount of the substance and the amounts of any
components used with it are substantially identical. FDA has found
that, when these antimicrobial substances are intended for the same
use, its assessment of the environmental risk of antimicrobial
substances is the same as EPA's assessment of the environmental risk of
pesticides and, therefore, the food additive use will be subsumed under
EPA's environmental review of the substance as a pesticide registered
under FIFRA.
In addition to ensuring that the substance is identical to and for
the same use as the registered pesticide, FDA will ensure that the
label for the use of the substance as a food additive includes
information related to the environmental effects, such as precautionary
statements on environmental hazards, that is required on the label for
the use of the substance as a registered pesticide under FIFRA. This
will provide assurance that any adverse environmental effects from the
use of the substance as a food additive have been addressed and are
mitigated, as needed, to the same extent as any adverse environmental
effects from the use of the substance as a pesticide registered under
FIFRA.
In response to the comment that FDA may not be able to meet its
deadlines because of its reliance on review of data by another agency,
nothing in this final rule precludes a petitioner or requester from
submitting an environmental assessment to FDA for review, despite the
fact that the action may be eligible for a categorical exclusion under
Sec. 25.32(q). Moreover, establishing a categorical exclusion for an
antimicrobial substance that is registered as a pesticide with EPA
under FIFRA should not affect FDA's ability to meet its statutory
deadlines for completing the review of food additive petitions that are
eligible for an exclusion under Sec. 25.32(q). In order for a substance
to be eligible for a Sec. 25.32(q) categorical exclusion, the substance
must be registered by EPA as a pesticide under FIFRA for the same use
requested in the petition at the time the food additive petition is
submitted to FDA. Antimicrobial substances that are not registered by
EPA under FIFRA for the same use at the time the food additive petition
is submitted to FDA would not be eligible for a categorical exclusion
under Sec. 25.32(q). Without the pesticide registration, FDA would not
be able to determine whether the use is the same as that in the food
additive petition or request for exemption and therefore eligible for a
categorical exclusion.
As previously mentioned, the scope of environmental review for a
pesticide registration, based on the agency's review of previous
petitions, encompasses FDA's environmental review for the use of the
substance as a food additive. Therefore, the agency does not anticipate
that any additional environmental review would be required for a
petitioned food additive use of a substance that is registered as a
pesticide under FIFRA. However, if the substance is not registered as a
pesticide under FIFRA or the environmental impacts resulting from the
petitioned food additive use or request for exemption are not within
the scope of EPA's environmental assessment performed for the pesticide
registration, FDA's action on the substance would not warrant
categorical exclusion under Sec. 25.32(q), and instead, would require
at least an EA under Sec. 25.20.
3. Veterinary Drugs and Feed Additives
39. Proposed Sec. 25.33(a) would categorically exclude action on an
NADA, abbreviated application, or supplement to such applications, if
the action does not increase the use of the drug. One comment pointed
out that, in its categorical exclusion relating to actions that do not
increase use, FDA uses the term ``active moiety'' when referring to
human drugs in proposed Sec. 25.31(a) and ``drug'' when referring to
animal drugs in proposed Sec. 25.33(a). The comment stated that the
reason for the use of different terms was not apparent, and recommended
that the term active moiety also be used when referring both to human
drugs and animal drugs.
The agency does not agree that the term ``active moiety'' should be
used in Sec. 25.33(a) to describe the actions on animal drugs that are
categorically excluded because for many animal drugs an explicit active
moiety cannot be defined. For example, an animal drug may consist of
biomass which is the purified broth from fermentation manufacturing. In
that case, the animal drug consists of a variety of components but an
``active moiety'' is not explicitly defined. If there is no increase in
the use of an animal drug, it follows that there is no increase in the
level of the substance in the environment and, consequently, no
increase in any associated environmental effects.
40. One comment requested that proposed Sec. 25.33(a) be revised to
categorically exclude actions that do not increase the use and the
concentration of the drug. The comment reasoned that when an animal
drug is administered, the concentration of that drug in the
environment, rather than the fact of ``use,'' has the potential to
raise environmental concerns.
The agency agrees that an increase in concentration has the
potential to raise environmental concern but does not agree that the
addition of the term ``increase concentration'' to the exclusion is
necessary. The primary purpose of the categorical exclusion is to
provide a simple method to identify for drug sponsors which actions
obviously have no significant environmental impacts. An increase in
use, such as an increase in dosage level, an increase in the duration
of use, or the addition of a new indication obviously results in an
increase in the environmental concentration. To help clarify what
actions are categorically excluded under proposed Sec. 25.33(a), the
agency has defined in proposed Sec. 25.5(b)(4) that ``increased use''
may occur if the drug is administered at higher dosage levels, for
longer duration, or for different indications than were previously in
effect, and if the drug is a new molecular entity. The term ``use'' is
further defined to encompass disposal of FDA-related articles. Section
25.33(a) also lists specific examples of the actions that are excluded.
Therefore, the agency believes that the use of the term ``increased
use,'' as defined in Sec. 25.5(b)(4), along with the examples provided,
best describes the criteria for categorical exclusion under proposed
Sec. 25.33(a).
41. In proposed Sec. 25.33(a), change in sponsor is included as one
of the types of actions covered by the categorical exclusion
(Sec. 25.33(a)(5)). One comment requested that FDA reconsider the
inclusion of actions relating to changes in drug sponsors in this
categorical exclusion because such a change may result in manufacturing
or process changes that could cause a difference in end product
chemical profiles. The comment argued that differences in manufacturing
practices may warrant further environmental evaluation.
[[Page 40584]]
The agency reconsidered the proposed categorical exclusion for
changes in drug sponsor but decided to retain the exclusion in the
final rule. A change in sponsor does not necessarily involve a change
in the manufacturing or processing of a drug. In the event that a
change in sponsor results in manufacturing or process changes, it is
not likely that there will be a change in the end product that will
affect the environmental impacts of the drug because a new sponsor must
maintain the same quality, composition, and purity of the drug to
assure that its safety and effectiveness are the same as the product
approved for manufacture by a previous sponsor. Any change that would
result in a change in the chemical profile of the end product would
require a supplement to be filed with the agency. The need for
environmental information would be evaluated by FDA in conjunction with
agency action on that supplement. The exclusion in Sec. 25.33(a) has
been changed to clarify that actions listed ``may'' be excluded if the
actions meet the criteria in the categorical exclusion.
42. In the preamble to FDA's proposed regulations (61 FR 14922 at
14931, 61 FR 19476 at 19485), FDA stated that proposed Sec. 25.33(b) is
being reserved for animal drugs ``not otherwise excluded in
Sec. 25.33(a).'' One comment expressed concern that this statement
regarding Sec. 25.33(b) may inadvertently create confusion about the
actions on animal drugs exclusions in other paragraphs of proposed
Sec. 25.33, especially in proposed Sec. 25.33(d)(5).
FDA can understand how the wording in the preamble (61 FR 14922 at
14931 and 14932, 61 FR 19476 at 19485 and 19486) could be confusing,
but the regulations are explicit about what actions are categorically
excluded. Actions that do not meet the criteria of Sec. 25.33(a) may
still be categorically excluded under Sec. 25.33 (c) or (d), including
Sec. 25.33(d)(5). If the agency adopts criteria for excluding actions
under Sec. 25.33(b) as discussed in the preamble, this will add
additional criteria for excluding actions, it will not restrict the
application of other criteria to exclude actions.
43. One comment suggested that reserved Sec. 25.33(b) should
categorically exclude any action on an NADA, abbreviated application,
or a supplement to such applications, that increases the use of a drug
if the PEC in soil is less than the PNEC, based on a scientifically
valid environmental test conducted with a representative soil organism.
The comment noted that a relatively simple scientific explanation or
calculation would be needed to determine whether an action qualifies
for such an exclusion. The comment defended the use of a scientific
threshold or screening test for a categorical exclusion as appropriate,
citing regulations issued by the Bureau of Indian Affairs (BIA), EPA,
and the Federal Highway Administration (FHWA).
The agency declines to revise the proposed regulations as
suggested. As explained above, the agency stated in the preamble to the
proposal that it was reserving Sec. 25.33(b) to provide for actions
that increase the use of an animal drug when the agency determines a
level at or below which the concentration of the substance in the
environment does not significantly affect the environment. Criteria for
this categorical exclusion would require a relatively simple
calculation using limited available information. The proposed PEC to
PNEC comparison represents more than a simple calculation or
explanation. Ecotoxicity studies are performed, results are compared to
expected environmental concentrations, and a conclusion is drawn (see
the response to comment 26). The agency considers this activity to be
an environmental risk assessment that is more appropriately provided as
part of an EA.
The agency reviewed the BIA, EPA, and FHWA regulations cited in the
comment. The BIA categorical exclusion refers to standards that are
required by the Bureau of Land Management (BLM). To qualify for this
categorical exclusion, an applicant merely states that it is in
compliance with the BLM requirements. No scientific threshold or
screening test is required. The EPA and FHWA citations refer to EPA and
FHWA general categorical exclusion processes and do not include
scientific explanations or calculations.
44. One comment addressed its statements to FDA's description, in
the preamble to the proposal (61 FR 14922 at 14931, 61 FR 19476 at
19485), of the categorical exclusions established in proposed
Sec. 25.33 (a) and (b). The comment stated that the EIC, rather than
the EEC, should be used to determine potential environmental impacts of
veterinary drugs and feed additives. The comment argued that this will
give more weight in determining potential exposures to ``primary
receptors'' before environmental degradation or waste treatment. The
comment also recommended that the evaluation should include potential
human exposure, such as the potential exposure to children assisting in
animal care or living in close proximity to family farm feedlots, at
the EIC.
As explained above in response to comment 43 and in the preamble to
the proposed rule (61 FR 14922 at 14931, 61 FR 19476 at 19485),
Sec. 25.33(a) categorically excludes action on an NADA, abbreviated
application, or supplement to such applications, if the action does not
increase the use of the drug. Proposed Sec. 25.33(b) is reserved and
would be for actions that increase the use of an animal drug if the
agency determines a level at or below which the concentration of the
substance in the environment does not significantly affect the
environment.
The EEC is an appropriate measure to use in evaluating information
in an EA to determine whether an environmental impact is expected. The
EEC provides the most accurate means of determining the concentration
of a substance to which organisms may be exposed. Due to various
factors in the environment, e.g., dilution, binding to particulate
matter, and volatility, the concentration of an introduced compound may
change significantly before it comes into contact with organisms that
may be harmed.
FDA addresses primary receptor issues, such as a child assisting in
animal care or living in proximity to family farm animals, as public
health issues under the act rather than through NEPA evaluation. See
the response to comment 22, above.
45. Proposed Sec. 25.33(d)(5) states that an action on a marketing
application or supplement for an animal drug intended for therapeutic
use under a prescription or veterinary order is categorically excluded
and, therefore, ordinarily does not require an EA or an EIS. One
comment contended that prescription animal drugs that are categorically
excluded under proposed Sec. 25.33(d)(5) could subsequently require an
EA if they become available OTC. The comment assumes this is an
unintended result and that grandfathering would be appropriate. The
comment recommended that proposed Sec. 25.33(d)(5) be revised to
include a statement indicating that an animal drug that was once
categorically excluded should not subsequently require an EA if it
becomes available OTC.
The comment is correct in its assertion that a categorically
excluded prescription animal drug could require an EA when the agency
acts on an application to switch the drug to OTC availability. However,
the comment incorrectly concludes that such a result is anomalous and
unintended. As discussed in the preamble to the proposal (61 FR 14922
at 14932, 61 FR 19476 at 19486), the therapeutic use of an animal drug
under a prescription by a veterinarian results in the drug being
[[Page 40585]]
administered to a limited number of animals for a limited amount of
time. The agency's experience in reviewing EA's for these types of
veterinary products indicates that this limited use results in no
significant environmental impact. The limitations inherent in
prescription use are not found in OTC use. Broader use and greater
introduction of the drug into the environment may occur with OTC
availability. Therefore, the agency believes that prescription to OTC
switches of animal drugs warrant consideration through an EA.
Grandfathering is not appropriate.
46. One comment stressed the importance of interpreting the term
``therapeutic use'' as it is used in the categorical exclusion for
prescription veterinary drugs in proposed Sec. 25.33(d)(5) independent
of the percentage of the herd treated. The comment indicated that if
prescription use were limited to single animal treatment, the section
would cease to be an important measure to reduce the number of EA's.
Prescription animal drugs, by definition under the act, are limited
to use under the professional supervision of a licensed veterinarian
and, thus, are expected to be administered to a limited number of
animals for a limited amount of time. Specifically, products intended
for use by prescription require a veterinarian diagnosis of the disease
or condition to be treated. The nature of this process limits the use
of the prescription product and its introduction into the environment.
Further, administration of the drug product by a veterinarian affords
an added level of control over the use and disposal of the drug
product. All veterinarians are trained on appropriate drug use
procedures. Therefore, allowing a categorical exclusion under these
circumstances is appropriate and the agency does not intend to
interpret therapeutic use, as it pertains to proposed Sec. 25.33(d)(5),
based on the number or percentage of animals treated.
It is important to note that the agency's decision to propose this
categorical exclusion of prescription animal drug products is primarily
based upon its experience in reviewing EA's for these products. The
EA's that comprise the bulk of agency experience in this area are for
products used in terrestrial species. The agency has limited experience
with reviewing drugs that will be used for the treatment of diseases in
fish and other aquatic species. For this reason, the agency is revising
proposed Sec. 25.33(d)(5) to clarify that it applies only to
terrestrial species. The section has been revised to state, ``Drugs
intended for use under prescription or veterinarian's order for
therapeutic use in terrestrial species.''
47. One comment noted that the same experience that led the agency
to categorically exclude prescription animal drugs under
Sec. 25.33(d)(5) could ultimately result in all animal drug products
being excluded regardless of whether they are prescription or over the
counter (OTC), subject to extraordinary circumstances.
FDA will not speculate on future categorical exclusions. The agency
based its decision to categorically exclude prescription animal drugs
intended for therapeutic use on its extensive experience in reviewing
EA's for those products. As the agency gains experience in reviewing
other classes of drug products, additional categorical exclusions may
be proposed. In all instances, FDA will require an EA to be prepared
for products that would ordinarily be categorically excluded if there
are extraordinary circumstances, see Sec. 25.21.
48. Proposed Sec. 25.33(h) would categorically exclude the
withdrawal of approval of a food additive petition that reduces or
eliminates animal feed uses of a food additive. One comment questioned
whether the disposal of nonnutritive oil in animal feed requires a food
additive petition.
The inclusion of nonnutritive oils in animal feeds requires the
submission of a food additive petition and the preparation of an EA.
(See the response to comment 35, above.) The categorical exclusion for
the withdrawal of approval of a food additive petition has no bearing
on whether a food additive petition, and corresponding EA for the
petition, would be required for the nonnutritive oil.
D. Subpart D--Preparation of Environmental Documents
49. Proposed part 25 regulations focus on the use and disposal from
use of FDA-regulated articles, and do not routinely require submission
of information regarding manufacturing sites or a certification of
compliance with Federal, State, and local emission requirements. One
comment recommended that manufacturing and production considerations
continue to be included in the environmental evaluation process and
suggested that FDA consider potential occupational exposures and worker
safety. The comment also expressed concern that by basing some
categorical exclusions, specifically Sec. 25.31(b), on presumed
toxicity of a substance disposed of after use, the agency ``ignores the
very substantial environmental impacts that may arise from
manufacture'' of the product.
Another comment by the same author expressed particular concern
about secondary and tertiary manufacturing processes involving food
additives that may result in uncontrolled end products. The comment
cited as an example a nonnutritive food grade oil that may be
synthesized by a primary producer who then sells it to a secondary
manufacturer for ingredient use in food product processing. The comment
recommended that production of food additives, color additives, and
GRAS substances not be included as a categorical exclusion and that the
environmental impact of secondary or tertiary manufacturing be
considered in an EA. Several related comments recommended that the
production, processing, and disposal of nonnutritive oils, including
the impact of liquid and solid oil components, the effect of processing
on the form of the food additive entering the environment, and the
potential nutritional impact of nonnutritive oils on microorganisms and
invertebrates be included in EA's.
The agency has determined that its environmental evaluation process
need not generally include a review of information on the manufacturing
and production of FDA-regulated products, including food additives,
color additives, and GRAS substances. This determination forms part of
the basis for FDA's establishment of additional categorical exclusions
for certain actions that currently require consideration of production
sites in EA's and is the basis for FDA's decision that, for those
actions requiring an EA, the EA will generally focus on potential
impacts resulting from product use and disposal. Federal, State, and
local environmental protection agencies are responsible for issuing
regulations, permitting and licensing facilities, and enforcing
compliance with those requirements that are necessary to ensure
adequate protection of the environment from emissions resulting from
production operations. Emergency response training and worker safety/
training are under the purview of these agencies and/or the
Occupational Safety and Health Administration (OSHA).
As discussed in the preamble to the proposed rule (61 FR 14922 at
14933, 61 FR 19476 at 19487), after reviewing hundreds of EA's that
contained information regarding manufacturing sites, the agency found
that FDA-regulated articles produced in compliance with applicable
emission and occupational safety requirements will not significantly
affect the
[[Page 40586]]
environment. However, if information available to the agency or the
applicant establishes that a general or specific emission requirement
issued by Federal, State, or local environmental agencies does not
adequately address unique emission circumstances, and the emission may
harm the environment, there would be sufficient grounds for FDA to
request manufacturing information in an EA. Likewise, in accordance
with CEQ regulations (40 CFR 1508.27(b)(10)), any action that threatens
to violate a Federal, State, or local law or other requirement imposed
for the protection of the environment would fall under Sec. 25.21
(Extraordinary circumstances), and an EA would be required for the
proposed action. Thus, although manufacturing site information will not
routinely be requested, there may be specific circumstances that would
require the submission of such information.
Concerning the comment about secondary and tertiary food additive
production sites, FDA usually considers these facilities to be sites of
use. The agency has found, with certain exceptions, that environmental
introductions of food additives, color additives, and GRAS substances
at secondary and tertiary production sites are minimal because these
substances are typically meant to be incorporated into and function in
food, food packaging, or food-contact equipment. Secondary direct food
additives and nonfunctional components of food-packaging materials may,
however, enter the environment at use sites because these additives are
used as processing aids in the production of food and food-packaging
materials, and are not intended to be present in the food or the
finished packaging material. The agency did not propose a new
categorical exclusion specifically for secondary direct additives,
therefore, actions on these types of additives will generally require
an EA. However, the agency notes that actions on certain secondary
direct additives may qualify for exclusion under Sec. 25.32 (j), (q),
or (r), as revised, because they are used as components of the food-
contact surface of permanent or semipermanent equipment or of another
food-contact article intended for repeated use, are pesticides
registered by EPA under FIFRA and subject to FDA's regulatory authority
as food additives for the same use, or are substances that occur
naturally in the environment. As discussed above in response to comment
33, the agency will continue to require EA's for certain actions
involving nonfunctional components of food-packaging materials. The
agency will also require EA's for any normally excluded action if there
are extraordinary circumstances suggesting that the action may have
significant effects at use sites.
Regarding the example in the comment of a nonnutritive food oil,
these actions do not qualify for exclusion under Sec. 25.32(k), as
revised, and require an EA because actions on these types of substances
have the potential for significant environmental effects (see the
responses to comments 35 and 48, above). The EA will take into
consideration the potential effects raised in the comment, including
introductions at all use and disposal sites (see, for example, the EA
and FONSI for FDA's action on the fat substitute olestra (Docket No.
87F0179)).
50. Several comments suggested revisions to proposed Sec. 25.40(a),
which states: ``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.'' Two comments
recommended the inclusion of a statement that the focus of the
environmental review would be on the use and disposal of FDA-regulated
articles, but not the manufacturing. One comment recommended
substituting the following sentence: ``The EA shall focus on relevant
environmental issues relating to the use and disposal from use of FDA
regulated articles and shall be a concise, objective, and well balanced
document,'' thus eliminating the phrase that the EA shall be ``a
document that allows the public to understand the agency's decision.''
One comment requested additional language stating that manufacturing
site information, including emission information, would not be
required.
The EA formats in current part 25, which have been eliminated in
the proposed rule, focus on an analysis of the use and disposal of FDA-
regulated articles. To clarify the focus of EA's under the proposed
regulations, FDA agrees with the suggestion to amend proposed
Sec. 25.40(a) to state that ``The EA shall focus on relevant
environmental issues relating to the use and disposal from use of FDA-
regulated articles * * * * '' Inclusion in the final regulation of a
statement to the effect that emission information from production sites
is not required in EA's would be contrary to FDA's position, as stated
in the preamble to the proposed rule (61 FR 14922 at 14934, 61 FR 19476
at 19487 and 19488), that when information establishes that emission
requirements promulgated by Federal, State, or local environmental
protection agencies do not address unique emission circumstances and
the emissions may harm the environment, FDA will request manufacturing
information in an EA.
The phrase included in the proposed regulations that an EA should
be ``a document that allows the public to understand the agency's
decision'' is consistent with CEQ environmental policies and objectives
and will not be deleted. NEPA procedures must ensure that environmental
information is available to public officials and citizens (40 CFR
1500.1(b)). Thus, among other things, environmental documents need to
be written in plain language so that the public can readily understand
them (see, e.g., Sec. 1502.8).
51. Proposed Sec. 25.40(a) states that EA's shall include a brief
discussion of alternatives to the proposed action as described by
section 102(2)(E) of NEPA. Proposed Sec. 25.40(a) also states that if
potentially adverse impacts on the environment are identified in the
EA, the EA shall discuss any reasonable alternative course of action
that offers less environmental risk or that is environmentally
preferable to the proposed action. One comment stated that this
requirement ``would only require applicants or petitioners to discuss
`reasonable' alternatives where `potentially adverse environmental
impacts are identified,' '' and, therefore, is inconsistent with 40 CFR
1508.9.
FDA does not believe there is an inconsistency between proposed
Secs. 25.40(a) and 1508.9. EA's are to be concise public documents to
determine whether a more detailed analysis, an EIS, is required
(Sec. 1508.9). A discussion of alternatives other than those which are
``reasonable'' is inconsistent with this overriding principle.
Therefore, FDA is not amending Sec. 25.40(a) in response to this
comment.
52. One comment requested that proposed Sec. 25.40(a) include a
maximum page limit for EA documents.
Because the number or pages for any EA will vary in relation to the
complexity of relevant environmental issues, and such flexibility
should be permitted by the regulations, FDA declines to include in its
regulation a page limit for EA's. CEQ regulations do not specify any
limit on the number of pages in EA's. FDA suggested in the preamble (61
FR 14922 at 14934, 61 FR 19476 at 19488) that, as a general rule, an EA
should normally be no more than 30 pages, not including test reports
and data.
53. The last sentence of proposed Sec. 25.40(a) allows for a tiered
environmental testing scheme that would result in test termination when
[[Page 40587]]
sufficient data are available to suggest that no significant
environmental impact will occur as a result of the potential agency
action. One comment suggested that this sentence be changed to state
that when results of the initial tier of testing indicate that testing
may be stopped, the EA need only contain a certification which states
that a PEC/PNEC calculation has been completed and the ratio of the PEC
to PNEC is less than one.
The agency declines to include the suggested revision. Proposed
Sec. 25.40(a) describes general EA requirements for all FDA-regulated
articles. While a tiered testing approach may be adopted by applicants
and petitioners of all products regulated by the agency, the language
recommended in the comment is limited to human drugs, biologics, and
animal drugs. Thus, the inclusion of the suggested language in
Sec. 25.40(a) is not appropriate. Additionally, as discussed earlier in
response to comment 26, if a PEC/PNEC ratio is used, FDA would need to
review the underlying data that supports the PEC/PNEC ratio.
54. FDA has proposed to remove the EA and abbreviated EA formats
and any reference to the formats currently found in Sec. 25.31a and to
provide appropriate formats in guidance documents. One comment
emphasized that to the extent such guidance documents amend or revise
informational requirements under NEPA, such requirements are
impermissible unless the guidance documents are issued through notice
and comment rulemaking under the Administrative Procedure Act (the APA)
(5 U.S.C. 553), and the agency consults with CEQ to ensure that the FDA
guidance is consistent with NEPA and CEQ requirements.
The APA (5 U.S.C. 553) does not require notice of interpretive
rules, general statements of policy, or rules of agency organization,
procedure, or practice except when notice is required by other statute.
Guidance documents are issued by FDA to provide assistance to the
regulated industry and interested parties by interpreting and
clarifying requirements that have been imposed by statute or
regulation. They reflect the agency's current thinking on the
implementation of its regulatory scheme, and because they are not
binding on industry or on the agency, they do not create requirements.
Consequently, guidance documents are not subject to the notice and
comment rulemaking provisions of the APA.
CEQ regulations (40 CFR 1507.3) encourage agencies to publish
explanatory guidance for their own procedures and to revise them as
necessary to ensure full compliance with the purposes and provisions of
NEPA. Use of guidances provides the agency with greater flexibility to
interpret requirements under its NEPA procedures in a manner that
responds to the evolving nature of environmental science and the needs
of industry and interested parties. In the Federal Register of February
27, 1997, FDA announced its adoption of GGP's, which describes the
agency's policies and procedures for the development, issuance, and use
of guidance documents, including public input in the development of
guidance and publication of a notice of availability. Any further
development of guidance related to FDA's implementation of NEPA will be
developed in accordance with these GGP's. Thus, although guidance
documents that clarify the submission of environmental information to
FDA are not required to undergo the notice and comment rulemaking
procedures of the APA, such guidance documents are subject to public
comment and input under the agency's GGP's. Until guidance documents
are issued in accordance with the GGP's, applicants that need to submit
an EA may follow the EA formats previously published by the agency or
may contact the appropriate center for specific guidance on preparing
the EA.
In the Federal Register of January 11, 1996 (61 FR 1031), 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.'' That guidance was intended to
assist industry by providing guidance on how to prepare EA's for
submission to CDER under current part 25 as part of NDA's, antibiotic
applications, abbreviated applications, and IND's. In preparing the
``Guidance for Industry for the Submission of an Environmental
Assessment in Human Drug Applications and Supplements,'' CDER consulted
with CEQ and gave CEQ an opportunity to review and comment on the
guidance prior to its issuance. This guidance will be revised, as
necessary, to ensure that the guidance is consistent with this final
rule when it becomes effective. The agency intends to continue its
working relationship with the CEQ in issuing additional guidance
documents under the final rule.
55. Two comments requested that a general format for EA's be
incorporated into proposed Sec. 25.40(a). Both comments expressed
concern that removal of the general format from part 25 may invite
regulatory expansion, i.e., the opportunity for FDA to request more
information.
As explained above and in the preamble to the proposal (61 FR 14922
at 14933, 61 FR 19476 at 19487), the agency, in consultation with CEQ,
has decided that to the extent that EA formats are helpful, they are
more appropriately placed in guidance documents. The formats included
in former part 25 were developed to be applicable to all FDA-regulated
articles. Due to the diverse nature of the products regulated by FDA,
not all format items were relevant to each action. Consequently, some
EA's contained unnecessary information and, in some instances,
information needed to assess the environmental effects of an action was
not initially submitted to the agency. Thus, the formats may be more
appropriately included in guidance documents prepared by each center.
Guidance documents will allow FDA to suggest EA formats that focus on
important environmental issues relating to each type of product
regulated by FDA and will assist the preparer in tailoring individual
EA's to focus on environmental issues specific to the particular
action.
56. Current Sec. 25.31a establishes EA formats for proposed actions
to approve food or color additives, drugs, biological products, animal
drugs, and some medical devices, to affirm food substances as GRAS, and
to grant requests for exemption from regulation as a food additive. One
comment noted that in the prescribed EA format, an applicant or
petitioner is required to identify the natural resources needed to
produce, transport, use and/or dispose of a given amount of any product
which is the subject of the action; to describe measures taken to avoid
or mitigate potential adverse environmental impacts associated with the
proposed action; and to describe in detail the environmental impact of
all reasonable alternatives to the proposed action, including those
that will enhance the quality of the environment and avoid some or all
of the adverse environmental impacts of the proposed action
(Sec. 25.31a(a)). The comment expressed concern that the proposed rule
``completely eliminates'' those obligations as they apply to marketing
applications for paclitaxel derived from the Pacific yew.
Proposed Sec. 25.21 will require an EA for any action, including
one involving natural resources, that is ordinarily excluded if the
action may have a significant effect on the environment. Proposed
Sec. 25.40(a) establishes that an EA shall include a brief discussion
of the need for the proposed action,
[[Page 40588]]
alternatives to it, and environmental impacts of the proposed action
and alternatives. If potentially adverse impacts on the environment are
identified in the EA, the EA shall also discuss any alternative course
of action that offers less environmental risk or that is
environmentally preferable to the proposed action. The agency has
determined that more specific information regarding the nature and
scope of information that should be included in an EA will be provided
in guidance documents rather than through regulatory requirements. Use
of guidance documents will provide the agency with greater flexibility
to implement NEPA in a manner that responds to the evolving nature of
environmental science and the needs of industry and other interested
parties. See the response to comment 54, above. As a result of this
decision, topics to be analyzed in each EA will be discussed and
clarified in guidance documents that will be issued by the center
responsible for the underlying action. Such topics will include the use
of natural resources in the proposed action (if relevant), and a
description of measures that have been taken to avoid or mitigate
adverse environmental impacts that may result from the proposed action.
With regard to marketing applications for drugs involving
paclitaxel derived from the Pacific yew, FDA published a notice in the
Federal Register (61 FR 58694), explaining the extent of environmental
documentation that needs to be submitted to the agency for drug
products containing paclitaxel. See the response to comment 15, above.
Persons interested in the agency's application of NEPA requirements
with regard to paclitaxel and the Pacific yew are encouraged to review
that notice.
57. Proposed Sec. 25.40(d) states that EA's may incorporate by
reference information presented in other documents that are available
to FDA and to the public. One comment recommended that this section be
revised to clarify that other EA's for approved FDA-regulated articles
may be incorporated by reference into an EA.
EA's that are available under the Freedom of Information Act are
public information and therefore may be incorporated by reference into
an EA to the extent that they are relevant to the action addressed in
the EA. Information that is not publicly available but to which an
applicant or petitioner has a right of reference or ownership may also
be incorporated by that applicant or petitioner into an EA. In
accordance with proposed Sec. 25.51(a), however, such confidential
information shall be summarized in the EA to the extent possible. The
agency does not find it necessary to revise the proposed regulation to
further clarify this point.
58. Proposed Sec. 25.40(e) states that the agency evaluates the
information contained in an EA, along with 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 the agency should prepare a FONSI or EIS. One comment
requested that this section be revised to define and restrict specific
procedures in manufacturing and disposal to effectively prevent
opportunities for some types of environmental release.
Defining and restricting specific procedures in manufacturing and
disposal to prevent pollution are more appropriately handled by
Federal, State, or local environmental protection agencies that have
regulatory authority and more expertise in those matters. However, as
part of FDA's NEPA review process, alternatives and mitigation measures
are considered by FDA.
59. Proposed Sec. 25.43 states that in cases where EIS's are
required, the agency will prepare, at the time of its decision, a
concise public record of decision. One comment asserted that this
section should explicitly address the CEQ provisions governing
limitations on actions during the NEPA process. CEQ regulations (40 CFR
1506.1(b)) require an agency to take appropriate action to ensure that
the objectives and procedures of NEPA are achieved if the agency is
aware that an applicant is about to take an action within the
jurisdiction of the agency that will have adverse environmental impacts
or will limit the choice of reasonable alternatives.
FDA is not required under 40 CFR 1507.3(b), and does not see any
need, to explicitly include in its procedures specific language to
implement 40 CFR 1506.1(b). Because an agency's procedures must
supplement CEQ regulations, all CEQ regulations in 40 CFR parts 1500
through 1508 are incorporated by reference into FDA's policies and
procedures implementing NEPA.
60. Proposed Sec. 25.45 (Responsible agency official) states that
the agency official identified in part 5 as being responsible for the
underlying application or petition is responsible for preparing
environmental documents. One comment suggested that Sec. 25.45 be
revised to require the responsible agency official to be available to
review any questions arising from the preparation of an EA. Two
comments recommended that part 5 be amended to include a provision that
establishes the Center Directors as the responsible officials for
deciding the existence of extraordinary circumstances under proposed
Sec. 25.21 and prohibits redelegation of such authority. One of these
comments also requested revisions to make it clear that any decision by
the Center Director on the question of extraordinary circumstances
constitutes final agency action.
FDA does not find it necessary to revise proposed Sec. 25.45 to
require the responsible agency official to be available to review
questions arising from the preparation of an EA. The FDA official
responsible for preparing environmental documents is available to
review questions concerning environmental issues and to meet with
interested parties (see, e.g., Sec. 10.65 (21 CFR 10.65)). In proposed
Sec. 25.40, FDA specifically encourages interaction between the
responsible agency official and those submitting EA's during the
preparation of the environmental documents.
FDA also declines to amend part 5. Part 5 delegates to specific
agency officials responsibility for taking particular actions on behalf
of the agency. Responsibility for actions on petitions and applications
is generally delegated to the Director or Deputy Director(s) of the
center responsible for reviewing submissions relating to the FDA-
regulated product for which an action is requested. Consistent with
CEQ's policy that the disciplines of those who prepare environmental
documents be appropriate to the scope and issues of the document, see
e.g., 40 CFR 1502.6, the Center Directors delegate responsibility
(e.g., authority to determine extraordinary circumstances and to
mediate conflicts between reviewers and sponsors) to individuals within
their organization who have specialized training and expertise to
evaluate all relevant issues. Individuals in each center who have
training and experience in environmental science and in implementing
environmental statutes are responsible for determining the adequacy of
EA's and claims for categorical exclusion and the existence of
extraordinary circumstances. These individuals are expected to consult
with their supervisors and other management officials as needed.
Specific delegations of responsibility are available to the public
through each center office.
Furthermore, each center has appeals procedures by which decisions
of center personnel can be appealed to the Center Director. The Center
Director's decision does not necessarily, however, constitute final
agency action. A procedure for internal review of agency
[[Page 40589]]
decisions is established in Sec. 10.75(a) (21 CFR 10.75(a)), which
states that a decision of any FDA employee, other than the
Commissioner, is subject to review by the employee's supervisor. Thus,
the proposal that a Center Director's decision necessarily constitutes
final agency action is contrary to FDA regulations and FDA does not
believe that its regulations should be modified.
E. Subpart E--Public Participation and Notification of Environmental
Documents
61. Proposed Sec. 25.50(b) states that many actions performed by
FDA are protected from disclosure by the act, the Trade Secret Act (the
TSA) (18 U.S.C. 1905), and FDA regulations and ``unless the existence
of an application for human drugs * * * has been made publicly
available, the release of the environmental document before approval of
human drugs * * * is inconsistent with statutory requirements imposed
on FDA.'' One comment stated that this provision conflicts with the
requirements of NEPA and CEQ that mandate public involvement at the
earliest possible time. The comment stated that FDA may not completely
abandon NEPA's public participation provisions by broadly invoking
protection under the TSA. The comment stated that at least for NDA's
and ANDA's, FDA clearly has authority to release environmental
documents following issuance of an approvable letter to the applicant.
The comment cited two Federal court cases, Flint Ridge Development Co.
v. Scenic Rivers Association of Oklahoma et al., 426 U.S. 776 (1976)
and Concerned About Trident v. Rumsfeld, 555 F.2d 817 (D.C. Cir. 1977),
to support the proposition that exceptions to NEPA's requirements have
been construed narrowly.
Proposed Sec. 25.50(b) is consistent with NEPA and CEQ regulations.
Section 102 of NEPA (42 U.S.C. 4332)
(D)irects that, to the fullest extent possible: (1) The
policies, regulations, and public laws of the United States shall be
interpreted and administered in accordance with the policies set
forth in [NEPA], and (2) all agencies of the Federal government
shall-- * * * (C) include in every recommendation * * * for * * *
major Federal action significantly affecting the quality of the
human environment, a detailed statement by the responsible official
on--(i) the environmental impact of the proposed action (emphasis
added).
Section 102 of NEPA further requires copies of any such detailed
statement and the comments and views of the appropriate Federal, State,
and local agencies, which are authorized to develop and enforce
environmental standards, to be made available to the President, CEQ,
and to the public as provided in 5 U.S.C. 552. CEQ regulations (40 CFR
1500.6) state that ``the phrase `to the fullest extent possible' in
section 102 means that each agency of the Federal Government shall
comply with that section unless existing law applicable to the agency's
operations expressly prohibits or makes compliance impossible.''
The TSA expressly prohibits any officer or employee of the United
States from publishing, divulging, disclosing, or making known in any
manner or to any extent not authorized by law any information which
concerns or relates to trade secrets, processes, operations, styles of
work, or apparatus, or to the identity, confidential statistical data,
amount or source of any income, profits, losses, or expenditures of any
person, firm, partnership, corporation, or association. The TSA covers
trade secrets as well as confidential commercial or financial
information. Therefore, FDA is prohibited from disclosing trade secrets
and confidential commercial information except to the extent authorized
by law.
Under section 301(j) of the act (21 U.S.C. 331(j)), FDA is
authorized to disclose trade secret information only to the Secretary
of the Department of Health and Human Services or officers or employees
of the Department, courts when relevant in any judicial proceeding
under the act, either House of Congress, or, to the extent of matter
within its jurisdiction, any committee or its subcommittee or any joint
committee of Congress or its subcommittee. FDA is not authorized to
disclose trade secrets to any other parties.
The comment cited two cases. Flint Ridge stands for the proposition
that the only time that a Federal agency can avoid compliance with NEPA
under the ``to the fullest extent possible'' caveat is when a clear and
unavoidable conflict in statutory authority exists, in which case NEPA
must give way. In Concerned about Trident, the Court rejected the
Department of Defense-Navy's attempt to exempt from the mandate of NEPA
strategic military decisions made by the Department of Defense-Navy
because the Navy pointed to no existing specific statutory authority
prohibiting compliance with NEPA in that case or making such compliance
impossible.
Proposed Sec. 25.50(b) is consistent with NEPA's direction to
implement its policies ``to the fullest extent possible,'' as the case
law has interpreted that phrase. In those instances in which the TSA
and section 301(j) of the act prohibit FDA from disclosing
environmental information to the public, compliance with NEPA is
impossible and NEPA must give way. FDA cannot disclose to the public
environmental information prior to taking action to approve certain
marketing applications. Thus, FDA does not contravene NEPA when it
refuses to disclose information in such circumstances.
Furthermore, FDA's procedures comply with NEPA's requirements to
implement NEPA to the fullest extent possible because the procedures
require FDA to review and/or prepare environmental documentation for
any major Federal action before taking the action unless the action
meets criteria for categorical exclusion. Moreover, FDA's procedures
specifically provide that information will be released to the public in
accordance with NEPA when, and to the extent, permitted by the TSA and
other laws governing FDA's operations. Clearly, FDA is not completely
abandoning NEPA's public participation provisions. If FDA is not
prohibited under the TSA and the act from disclosing specific
environmental information before FDA takes action, FDA will disclose
that environmental information at the earliest possible time before
action is taken. To the extent that compliance with the TSA and the act
make impossible disclosure of environmental information before action
is taken, FDA will disclose environmental information after the action
is taken to the extent permitted under the TSA and the act.
Finally, Sec. 25.50 is also consistent with the requirement that
environmental information be made available to the public as provided
in the Freedom of Information Act (the FOIA) (5 U.S.C. 552). Although
the FOIA requires an agency to make available to the public most
information available to the agency, certain matters are exempt from
disclosure. Specifically, the FOIA exempts from disclosure trade
secrets and commercial or financial information that is obtained from a
person and is privileged or confidential.
62. Proposed Sec. 25.52(a) states that if an EIS is prepared for a
drug, animal drug, biologic product, or device, it will become
available to the public only at the time of the approval of the
product. One comment asserted that this provision ``cuts back
significantly on one of the most fundamental requirements of NEPA and
the CEQ regulations--the ability of the public to review and comment on
proposed agency decisions.'' The comment stated that the proposal
``constitutes a complete repeal of the agency's current NEPA
regulations providing for public
[[Page 40590]]
involvement in the EIS process and, as such, it must be rejected.''
The agency disagrees. Proposed Sec. 25.52 does not repeal the
agency's regulations providing for public involvement in the EIS
process but merely clarifies that when there is a clear and unavoidable
conflict between NEPA's public disclosure goals and other laws
governing FDA's disclosure of information, FDA must follow the
disclosure laws that govern its operations. As discussed in response 61
above, the agency is limited in its ability to disclose to the public
information contained within certain marketing applications. The agency
will generally make an EIS available to the public at the time of
approval of the relevant drug, animal drug, biological product, or
device (Sec. 25.52(a)) but, in instances where disclosure of an
application has occurred, the agency will abide by its responsibility
to make a diligent effort to involve the public while concurrently
complying with its own disclosure requirements (Sec. 25.52(c)).
F. Subpart F--Other Requirements
63. Section 25.60 states that in accordance with Executive Order
12114, ``Environmental Effects Abroad of Major Federal Actions,''
January 4, 1979, FDA will consider the environmental effects abroad of
its potential actions. One comment claimed that under this provision,
Executive Order 12114, not NEPA, would govern environmental impacts
that may occur abroad as a result of FDA action. The comment stated
that as a result, FDA's proposal would not govern environmental impacts
associated with harvest of Pacific yew trees in Canada for paclitaxel
marketed in the United States. The comment cited Environmental Defense
Fund v. Massey, 986 F.2d 528 (D.C. Cir. 1993), stating that the Court
of Appeals for the D.C. Circuit rejected the notion that NEPA only
governs activities within the United States.
Executive Order 12114 and proposed Sec. 25.60 (current Sec. 25.50)
have not changed since 1985. Executive Order 12114, ``Environmental
Effects Abroad of Major Federal Actions,'' represents the U.S.
Government's ``exclusive and complete determination of * * * actions to
be taken by Federal agencies to further the purpose of the National
Environmental Policy Act with respect to the environment outside the
United States, its territories, and possessions.'' The agency issued
current Sec. 25.50 to implement this executive order. FDA requirements
include the consideration of potential environmental effects of an
action on a foreign nation, current Sec. 25.50(a)(2) (proposed
Sec. 25.60(a)(2)). In the event the agency action would have a
significant environmental effect on the foreign nation, the agency
official will require additional environmental documentation, current
Sec. 25.50(c) (proposed Sec. 25.60(c)).
In the case cited in the comment, Environmental Defense Fund v.
Massey, 986 F.2d 528, 532 (D.C. Cir. 1993), the court held that the
National Science Foundation must comply with NEPA before going forward
with plans to incinerate food waste in Antarctica. The court expressly
limited its decision to the unique circumstances of Antarctica,
stating, ``we do not decide today how NEPA might apply to actions in a
case involving an actual sovereign.'' (Massey, at 537.) The court did
not rule on the applicability of Executive Order 12114.
The comment's allegation that FDA's proposal would not govern the
environmental impacts associated with the harvest of the Pacific yew in
Canada for paclitaxel marketed in the United States is without basis.
FDA is required to consider the environmental impacts of its actions
either under NEPA or the Executive Order. Executive Order 12114 states
if the responsible official determines that an action may have a
significant environmental effect abroad, the responsible official shall
prepare appropriate environmental documents. Additionally, as discussed
in the response to comment 15, above, FDA issued a notice in the
November 18, 1996, Federal Register explaining the environmental
information to be submitted with marketing applications for drug
products containing paclitaxel.
III. Conforming Amendments
The environmental regulations in part 25 are cited throughout FDA's
regulations. Because FDA is revising part 25, the agency is taking this
opportunity to make conforming amendments to 21 CFR parts 10, 20, 71,
101,170, 171, 312, 314, 315, 511, 514, 570, 571, 601, 812, 813, and 814
to reflect revised part 25. These conforming amendments will ensure the
accuracy and consistency of the regulations.
IV. Analysis of Impacts
FDA has examined the impacts of the final rule under Executive
Order 12866, under the Regulatory Flexibility Act (5 U.S.C. 601-612),
and under the Unfunded Mandates Reform Act of 1995 (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
unless the rule is not expected to have a significant economic impact
on a substantial number of small entities. The Unfunded Mandates Reform
Act (Pub. L. 104-4) requires that agencies prepare an assessment of
anticipated costs and benefits before proposing any rule that may
result in an annual expenditure by State, local, and tribal
governments, in the aggregate, or by the private sector, of
$100,000,000 or more (adjusted annually for inflation). The following
analysis demonstrates that this final rule is consistent with the
principles set forth in the Executive Order and in these two statutes.
The final rule is a significant but not an economically significant
regulatory action under Executive Order 12866 and the rule does not
impose any mandates on State, local, or tribal governments, or the
private sector, that will result in an annual expenditure of
$100,000,000 or more.
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 reduced requirements for submitting EA's will result
in an annual cost savings to industry of approximately $15.7 million.
Two letters received by FDA in response to the proposed rule commented
that the rule would eliminate a majority of EA's that the respondents,
or their members, have been required to submit in the past. These
comments are consistent with the estimate presented here. The basis for
this estimate is as follows:
Human Pharmaceuticals
Approximately 125 EA's related to human pharmaceuticals will be
eliminated annually under the final rule. About one-half of these are
abbreviated EA's; the remainder are full assessments. Based on industry
estimates, 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.
[[Page 40591]]
Veterinary Products
The changes eliminate approximately 37 abbreviated EA's for
veterinary products each year, at an industry-estimated average cost of
approximately $5,000 each. About 77 brief submissions, which currently
require categorical exclusion criteria review, are also eliminated;
these cost an industry-estimated $300 each to prepare. Total cost
savings to the veterinary products industry under the proposal are thus
approximately $208,000 per year.
Food Products
About 39 EA's per year received by the Center for Food Safety and
Applied Nutrition (CFSAN) will be eliminated under the final rule.
Approximately 30 of these would have been abbreviated EA's and 9 would
have been full assessments under current rules. Based on industry
estimates, FDA projects 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 $75,000 for abbreviated EA's
and $450,000 for full EA's, for a total annual savings to the foods
industry of approximately $525,000.
In addition to these savings to industry, the final rule will
improve FDA efficiency by eliminating agency review costs of
approximately $1 million per year.
As these regulations will not impose significant new costs on any
firms, under the Regulatory Flexibility Act, 5 U.S.C. 605(b), the
Commissioner certifies that the final 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.
V. The Paperwork Reduction Act of 1995
This final rule contains information collection provisions that are
subject to review by the Office of Management and Budget (OMB) under
the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). A
description of these provisions is given below with an estimate of the
annual reporting burden. Included in the estimate is the time for
reviewing instructions, searching existing data sources, gathering and
maintaining the data needed, and completing and reviewing each
collection of information.
Title: National Environmental Policy Act; Reporting Provisions.
Description: FDA has previously issued regulations that implement
NEPA (part 25). This final rule calls for applicants and petitioners to
submit environmental information to FDA, in the form of EIS's, EA's, or
claims for categorical exclusion, where appropriate. NEPA requires such
reporting to enable FDA to take into account in its decisionmaking
process the potential impact of agency actions on the environment.
This final rule will 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 amending 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.
Individuals and organizations may submit comments on these burden
estimates or on any other aspect of these information collection
provisions, including suggestions for reducing the burden, and should
direct them to the appropriate contact person listed at the beginning
of this document.
Description of Respondents: Persons and businesses, including small
businesses.
Estimated Annual Reporting Burden
----------------------------------------------------------------------------------------------------------------
Annual
No. of frequency Total Hours per
CFR section respondents per annual Responses Total hours
response responses
----------------------------------------------------------------------------------------------------------------
25.15(a), (d).................................. 455 11.82 5,376 7.94 42,685
25.40(a), (c).................................. 455 .13 58 2832.93 164,310
----------------------------------------------------------------
Total...................................... ........... ........... ........... ........... 206,995
----------------------------------------------------------------------------------------------------------------
This estimate represents the total reporting burden for the amended
regulations. The total reporting burden for the regulations in part 25
before the amendments was 710,987 hours; thus, the amended regulations
will result in an estimated net decrease in burden of 503,992 hours, a
reduction of more than 70 percent.
The information collection provisions in this final rule have been
approved under OMB Control No. 0910-0332. This approval expires June
30, 1999. An agency may not conduct or sponsor, and a person is not
required to respond to, a collection of information unless it displays
a currently valid OMB control number.
List of Subjects
21 CFR Part 10
Administrative practice and procedure, News media.
21 CFR Part 20
Confidential business information, Courts, Freedom of information,
Government employees.
21 CFR Part 25
Environmental impact statements, Foreign relations, Reporting and
recordkeeping requirements.
21 CFR Part 71
Administrative practice and procedure, Color additives,
Confidential business information, Cosmetics, Drugs, Reporting and
recordkeeping requirements.
21 CFR Part 101
Food labeling, Nutrition, Reporting and recordkeeping requirements.
21 CFR Part 170
Administrative practice and procedure, Food additives, Reporting
and recordkeeping requirements.
21 CFR Part 171
Administrative practice and procedure, Food additives.
21 CFR Part 312
Drugs, Exports, Imports, Investigations, Labeling, Medical
research, Reporting and recordkeeping requirements, Safety.
21 CFR Part 314
Administrative practice and procedure, Confidential business
[[Page 40592]]
information, Drugs, Reporting and recordkeeping requirements.
21 CFR Part 511
Animal drugs, Medical research, Reporting and recordkeeping
requirements.
21 CFR Part 514
Administrative practice and procedure, Animal drugs, Confidential
business information, Reporting and recordkeeping requirements.
21 CFR Part 570
Animal feeds, Animal foods, Food additives.
21 CFR Part 571
Administrative practice and procedure, Animal feeds, Animal foods,
Food additives.
21 CFR Part 601
Administrative practice and procedure, Biologics, Confidential
business information.
21 CFR Part 812
Health records, Medical devices, Medical research, Reporting and
recordkeeping requirements.
21 CFR Part 814
Administrative practice and procedure, Confidential business
information, Medical devices, Medical research, 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, 21 CFR parts 10, 20, 25, 71, 101, 170, 171, 312,
314, 511, 514, 570, 571, 601, 812, and 814 are amended as follows:
PART 10--ADMINISTRATIVE PRACTICES AND PROCEDURES
1. The authority citation for 21 CFR part 10 continues to read as
follows:
Authority: Secs. 201-903 of the Federal Food, Drug, and Cosmetic
Act (21 U.S.C. 321-394); 21 U.S.C. 41-50, 141-149, 467f, 679, 821,
1034; secs. 2, 351, 354, 361 of the Public Health Service Act (42
U.S.C. 201, 262, 263b, 264); secs. 2-12 of the Fair Packaging and
Labeling Act (15 U.S.C. 1451-1461); 5 U.S.C. 551-558, 701-721; 28
U.S.C. 2112.
2. Section 10.30 is amended in paragraph (b) by revising item C to
read as follows:
Sec. 10.30 Citizen petition.
* * * * *
(b) * * *
C. Environmental impact.
(A) claim for categorical exclusion under Secs. 25.30, 25.31,
25.32, 25.33, or Sec. 25.34 of this chapter or an environmental
assessment under Sec. 25.40 of this chapter.)
* * * * *
3. Section 10.40 is amended by revising paragraph (b)(1)(ix) to
read as follows:
Sec. 10.40 Promulgation of regulations for the efficient enforcement
of the law.
* * * * *
(b) * * *
(1) * * *
(ix) a reference to the existence or lack of need for an
environmental impact statement under Sec. 25.52 of this chapter; and
* * * * *
PART 20--PUBLIC INFORMATION
4. The authority citation for 21 CFR part 20 continues to read as
follows:
Authority: Secs. 201-903 of the Federal Food, Drug, and Cosmetic
Act (21 U.S.C. 321-393); secs. 301, 302, 303, 307, 310, 311, 351,
352, 354-360F, 361, 362, 1701-1706, 2101 of the Public Health
Service Act (42 U.S.C. 241, 242, 242a, 242l, 242n, 243, 262, 263,
263b-263n, 264, 265, 300u-5, 300aa-1); 5 U.S.C. 552; 18 U.S.C. 190;
19 U.S.C. 2531-2582; 21 U.S.C. 1401-1403.
5. Section 20.100 is amended by revising paragraph (c)(3) to read
as follows:
Sec. 20.100 Applicability; cross-reference to other regulations.
* * * * *
(c) * * *
(3) Environmental assessments; finding of no significant impact, in
Sec. 25.51 of this chapter, or draft and final environmental impact
statements, in Sec. 25.52 of this chapter.
6. Part 25 is 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 the 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, 4331-4335; 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
1977 Comp., p. 123.
PART 25--ENVIRONMENTAL IMPACT CONSIDERATIONS
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:
[[Page 40593]]
(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. 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) OTC--Over-the-counter.
(18) PDP--Product development protocol.
(19) PMA--Premarket approval application.
Sec. 25.10 Policies and NEPA planning.
(a) All FDA's policies and programs will be planned, developed, and
implemented to achieve the policies declared by NEPA and required by
CEQ's regulations to ensure responsible 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 from an applicant or petitioner an EA or a
claim that a categorical exclusion applies, or when FDA personnel
consult with applicants or petitioners on the NEPA-related aspects of
their requested actions. 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 HHS General
Administration Manual, part 30: Environmental Protection.
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 statement of compliance with the
categorical exclusion criteria and shall state 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. An EA adequate for
filing is one that addresses the relevant environmental issues. An EA
adequate for approval is one that contains sufficient information to
enable the agency to determine whether the proposed action may
significantly affect the quality of the human environment.
(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,
[[Page 40594]]
25.31, 25.32, 25.33, or 25.34, or proposing to dispose of an article as
provided in Sec. 25.30(d) or 25.32(h), is not required to submit an EA
if the person states that the action requested qualifies for a
categorical exclusion, citing the particular categorical exclusion that
is claimed, and states 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 full
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 Sec. 25.30 (h), (i), or (j), or Sec. 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 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, unless categorically
excluded in Sec. 25.32 (f), (k), or (r).
(l) Approval of NDA's, abbreviated applications, applications for
marketing approval of a biologic product, supplements to such
applications, and actions on IND's, unless categorically excluded in
Sec. 25.31 (a), (b), (c), (e), or (l).
(m) Approval of NADA's, abbreviated applications, supplements, and
actions on INAD's, unless categorically excluded under Sec. 25.33 (a),
(c), (d), or (e).
(n) Approval of PMA's for medical devices, notices of completion of
PDP's for medical devices, authorizations to commence clinical
investigation under an approved PDP, or applications for an IDE, unless
categorically excluded in Sec. 25.34.
Sec. 25.21 Extraordinary circumstances.
As required under 40 CFR 1508.4, FDA will require at least an EA
for any specific action that ordinarily would be 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.
[[Page 40595]]
(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, application for
marketing approval of a biologic product, or a supplement to such
applications, 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 applications, or action on an OTC monograph, if the action
increases the use of the active moiety, but the estimated concentration
of the substance at the point of entry into the aquatic 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
applications, or action on an OTC monograph, for substances that occur
naturally in the environment when the action does not alter
significantly the concentration or distribution of the substance, its
metabolites, or degradation products in the environment.
(d) Withdrawal of approval of an NDA or an abbreviated application.
(e) Action on an IND.
(f) Testing and certification of batches of an antibiotic or
insulin.
(g) Testing and release by the Center for Biologics Evaluation and
Research of lots or batches of a licensed biologic product.
(h) Issuance, revocation, or amendment of a monograph for an
antibiotic drug.
(i) Establishment of bioequivalence requirements for a human drug
or a comparability determination for a biologic product subject to
licensing.
(j) Issuance, revocation, or amendment of a standard for a biologic
product.
(k) Revocation of a license for a biologic product.
(l) Action on an application for marketing approval for marketing
of a biologic product for transfusable human blood or blood components
and plasma.
Sec. 25.32 Foods, food additives, and color additives.
The classes of actions listed in this section are categorically
excluded and, therefore, ordinarily do not require the preparation of
an EA or an EIS:
(a) Issuance, amendment, or repeal of a food standard.
(b) Action on a request for exemption for investigational use of a
food additive if the food additive to be shipped under 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, GRAS affirmation
petition, or the granting of a request for exemption from regulation as
a food additive under Sec. 170.39 of this chapter, when the substance
is present in finished food-packaging material at not greater than 5
percent-by-weight and is expected to remain with finished food-
packaging material through use by consumers or when the substance is a
component of a coating of a finished food-packaging material.
(j) Approval of a food additive petition, GRAS affirmation
petition, or the granting of a request for exemption from regulation as
a food additive under Sec. 170.39 of this chapter, when the substance
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.
[[Page 40596]]
(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 a supplement to
such applications, if the action does not increase the use of the drug.
Actions to which this categorical exclusion applies may 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 to
such applications, 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 in terrestrial species.
(e) Action on an INAD.
(f) Action on an application submitted under section 512(m) of the
act.
(g) Withdrawal of approval of an NADA or an abbreviated NADA.
(h) Withdrawal of approval of a food additive petition that reduces
or eliminates animal feed uses of a food additive.
Sec. 25.34 Devices and electronic products.
The classes of actions listed in this section are categorically
excluded and, therefore, ordinarily do not require the preparation of
an EA or an EIS:
(a) Action on a device premarket notification submission under
subpart E of part 807 of this chapter.
(b) Classification or reclassification of a device under part 860
of this chapter.
(c) Issuance, amendment, or repeal of a standard for a class II
medical device or an electronic product, and issuance of exemptions or
variances from such a standard.
(d) Approval of a PMA or a notice of completion of a PDP or amended
or supplemental applications or notices for a class III medical device
if the device is of the same type and for the same use as a previously
approved device.
(e) Changes in the PMA or a notice of completion of a PDP for a
class III medical device that do not require submission of an amended
or supplemental application or notice.
(f) Issuance of a restricted device regulation if it will not
result in increases in the existing levels of use or changes in the
intended uses of the product or its substitutes.
(g) Action on an application for an IDE or an authorization to
commence a clinical investigation under an approved PDP.
(h) Issuance of a regulation exempting from preemption a
requirement of a State or political subdivision concerning a device, or
a denial of an application for such exemption.
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 relating to the use
and disposal from use of FDA-regulated articles 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 a 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 a 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
[[Page 40597]]
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 decision.
(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) Summarize the program for monitoring and enforcing the
practicable means adopted to avoid or minimize the environmental harm.
Sec. 25.44 Lead and cooperating agencies.
For actions requiring the preparation of an EIS, FDA and other
affected Federal agencies will agree which will be the lead agency and
which will be the cooperating agencies. The responsibilities of lead
agencies and cooperating agencies are described in the CEQ regulations
(40 CFR 1501.5 and 1501.6, respectively). If an action affects more
than one center within FDA, the Commissioner of Food and Drugs will
designate one of these units to be responsible for coordinating the
preparation of any required environmental documentation.
Sec. 25.45 Responsible agency official.
(a) The person designated in part 5 of this chapter as the
responsible agency official for the underlying action is responsible
for preparing environmental documents or ensuring that they are
prepared.
(b) The responsible agency official will weigh any environmental
impacts of each alternative course of action, including possible
mitigation measures, and will balance environmental impacts with the
agency's objectives in choosing an appropriate course of action. The
weighing of any environmental impacts of alternatives in selecting a
final course of action will be reflected in the agency's record of
formal decisionmaking as required by 40 CFR 1505.2.
Subpart E--Public Participation and Notification of Environmental
Documents
Sec. 25.50 General information.
(a) To the extent actions are not protected from disclosure by
existing law applicable to the agency's operation, FDA will involve the
public in preparing and implementing its NEPA procedures and will
provide public notice of NEPA-related hearings, public meetings, and
the availability of environmental documents.
(b) Many FDA actions involving investigations, review, and approval
of applications, and premarket notifications for human drugs, animal
drugs, biologic products, and devices are protected from disclosure
under the Trade Secret Act, 18 U.S.C. 1905, and 301(j) of the act.
These actions are also protected from disclosure under FDA's
regulations including part 20, Secs. 312.130(a), 314.430(b), 514.11(b),
514.12(a), 601.50(a), 601.51(a), 807.95(b), 812.38(a), and 814.9(b) of
this chapter. Even the existence of applications for human drugs,
animal drugs, biologic products, and devices is protected from
disclosure under these regulations. Therefore, unless the existence of
applications for human drugs, animal drugs, biologic products, or
premarket notification for devices has been made publicly available,
the release of the environmental document before approval of human
drugs, animal drugs, biologic products, and devices is inconsistent
with statutory requirements imposed on FDA. Appropriate environmental
documents, comments, and responses will be included in the
administrative record to the extent allowed by applicable laws.
Sec. 25.51 Environmental assessments and findings of no significant
impact.
(a) Data and information that are protected from disclosure by 18
U.S.C. 1905 or 21 U.S.C. 331(j) or 360j(c) shall not be included in the
portion of environmental documents that is made public. When such data
and information are pertinent to the environmental review of a proposed
action, an applicant or petitioner shall submit such data and
information separately in a confidential section and shall summarize
the confidential data and information in the EA to the extent possible.
(b) FONSI's and EA's will be available to the public in accordance
with 40 CFR 1506.6 as follows:
(1) When the proposed action is the subject of a notice of proposed
rulemaking or a notice of filing published in the Federal Register, the
notice shall state that no EIS is necessary and that the FONSI and the
EA are available for public inspection at FDA's Dockets Management
Branch. If the responsible agency official is unable to complete
environmental consideration of the proposed action before a notice of
filing of a food or color additive petition is required to be published
under the act, and if the subsequent environmental analysis leads to
the conclusion that no EIS is necessary, the 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
[[Page 40598]]
available for public review (including review by State and areawide
information clearinghouses) for 30 days before the agency makes its
final determination whether to prepare an EIS and before the action may
begin, as described in 40 CFR 1501.4(e). This procedure will be
followed when the proposed action is, or is closely similar to, one
that normally requires an EIS or when the proposed action is one
without precedent.
Sec. 25.52 Environmental impact statements.
(a) If FDA determines that an EIS is necessary for an action
involving investigations or approvals for drugs, animal drugs, biologic
products, or devices, an EIS will be prepared but will become available
only at the time of the approval of the product. Disclosure will be
made in accordance with 40 CFR 1506.6 and part 20 of this chapter. The
EIS will in all other respects conform to the requirements for EIS's as
specified in 40 CFR part 1502 and 1506.6(f).
(b) Comments on the EIS may be submitted after the approval of the
drug, animal drug, biologic product, or 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, or 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, 1979), the responsible agency official, in analyzing
actions under his or her program, shall consider the environmental
effects abroad, including whether the actions involve:
(1) Potential environmental effects on the global commons and areas
outside the jurisdiction of any nation, e.g., oceans and the upper
atmosphere.
(2) Potential environmental effects on a foreign nation not
participating with or otherwise involved in an FDA activity.
(3) The export of products (or emissions) that in the United States
are prohibited or strictly regulated because their effects on the
environment create a serious public health risk.
(4) Potential environmental effects on natural and ecological
resources of global importance designated under the Executive Order.
(b) Before deciding on any action falling into the categories
specified in paragraph (a) of this section, the responsible agency
official shall determine, in accordance with section 2-3 of the
Executive Order, whether such actions may have a significant
environmental effect abroad.
(c) If the responsible agency official determines that an action
may have a significant environmental effect abroad, the responsible
agency official shall determine, in accordance with section 2-4(a) and
(b) of the Executive Order, whether the subject action calls for:
(1) An EIS;
(2) A bilateral or multilateral environmental study; or
(3) A concise environmental review.
(d) In preparing environmental documents under this subpart, the
responsible official shall:
(1) Determine, as provided in section 2-5 of the Executive Order,
whether proposed actions are subject to the exemptions, exclusions, and
modification in contents, timing, and availability of documents.
(2) Coordinate all communications with foreign governments
concerning environmental agreements and other arrangements in
implementing the Executive Order.
PART 71--COLOR ADDITIVE PETITIONS
7. The authority citation for 21 CFR part 71 continues to read as
follows:
Authority: Secs. 201, 402, 409, 501, 505, 506, 507, 510, 512-
516, 518-520, 601, 701, 721, 801 of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 321, 342, 348, 351, 355, 356, 357, 360,
360b-360f, 360h-360j, 361, 371, 379e, 381); secs. 215, 351 of the
Public Health Service Act (42 U.S.C. 216, 262).
8. Section 71.1 is amended in paragraph (c) by revising item J to
read as follows:
Sec. 71.1 Petitions.
* * * * *
(c) * * *
J. The petitioner is required to submit either a claim for
categorical exclusion under Sec. 25.30 or 25.32 of this chapter or an
environmental assessment under Sec. 25.40 of this chapter.
* * * * *
PART 101--FOOD LABELING
9. The authority citation for 21 CFR part 101 continues to read as
follows:
Authority: Secs. 4, 5, 6 of the Fair Packaging and Labeling Act
(15 U.S.C. 1453, 1454, 1455); secs. 201, 301, 402, 403, 409, 701 of
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 342,
343, 348, 371).
10. Section 101.12 is amended by revising paragraph (h)(12) to read
as follows:
Sec. 101.12 Reference amounts customarily consumed per eating
occasion.
* * * * *
(h) * * *
(12) A claim for categorical exclusion under Sec. 25.30 or 25.32 of
this chapter or an environmental assessment under Sec. 25.40 of this
chapter; and
* * * * *
11. Section 101.69 is amended by revising paragraph (h), item E of
paragraph (m)(1), item C of paragraph (n)(1), and item C of paragraph
(o)(1) to read as follows:
Sec. 101.69 Petitions for nutrient content claims.
* * * * *
(h) All petitions submitted under this section shall include either
a claim for a categorical exclusion under Sec. 25.30 or 25.32 of this
chapter or an environmental assessment under Sec. 25.40 of this
chapter.
* * * * *
(m) * * *
(1) * * *
E. The petitioner is required to submit either a claim for
categorical exclusion under Sec. 25.30 or Sec. 25.32 of this chapter
or an environmental assessment under Sec. 25.40 of this chapter.
* * * * *
(n) * * *
(1) * * *
C. The petitioner is required to submit either a claim for
categorical exclusion under Sec. 25.30 or Sec. 25.32 of this chapter
or an environmental assessment under Sec. 25.40 of this chapter.
* * * * *
(o) * * *
[[Page 40599]]
(1) * * *
C. The petitioner is required to submit either a claim for
categorical exclusion under Sec. 25.30 or Sec. 25.32 of this chapter
or an environmental assessment under Sec. 25.40 of this chapter.
* * * * *
12. Section 101.70 is amended in paragraph (f) by revising item F
to read as follows:
Sec. 101.70 Petitions for health claims.
* * * * *
(f) * * *
F. The petitioner is required to submit either a claim for
categorical exclusion under Sec. 25.30 or Sec. 25.32 of this chapter
or an environmental assessment under Sec. 25.40 of this chapter.
* * * * *
PART 170--FOOD ADDITIVES
13. The authority citation for 21 CFR part 170 continues to read as
follows:
Authority: Secs. 201, 401, 402, 408, 409, 701 of the Federal
Food, Drug, and Cosmetic Act (21 U.S.C. 321, 341, 342, 346a, 348,
371).
14. Section 170.35 is amended by revising paragraph (c)(1)(viii) to
read as follows:
Sec. 170.35 Affirmation of generally recognized as safe (GRAS) status.
* * * * *
(c) * * *
(1) * * *
(viii) A claim for categorical exclusion under Sec. 25.30 or
Sec. 25.32 of this chapter or an environmental assessment under
Sec. 25.40 of this chapter.
* * * * *
15. Section 170.39 is amended by revising the second sentence in
paragraph (c)(6) and the seventh sentence in paragraph (e) to read as
follows:
Sec. 170.39 Threshold of regulation for substances used in food-
contact articles.
* * * * *
(c) * * *
(6) * * * The request should contain either a claim for categorical
exclusion as specified in Sec. 25.32 of this chapter or an
environmental assessment as specified in Sec. 25.40 of this chapter.
* * * * *
(e) * * * For actions requiring an environmental assessment, the
agency's finding of no significant impact and the evidence supporting
that finding, contained in the petitioner's environmental assessment,
also will be available for public inspection at the Dockets Management
Branch in accordance with Sec. 25.51(b)(2) of this chapter. * * *
* * * * *
PART 171--FOOD ADDITIVE PETITIONS
16. The authority citation for 21 CFR part 171 continues to read as
follows:
Authority: Secs. 201, 402, 409, 701 of the Federal Food, Drug,
and Cosmetic Act (21 U.S.C. 321, 342, 348, 371).
17. Section 171.1 is amended in paragraph (c) by revising item H to
read as follows:
Sec. 171.1 Petitions.
* * * * *
(c) * * *
H. The petitioner is required to submit either a claim for
categorical exclusion under Sec. 25.30 or 25.32 of this chapter or
an environmental assessment under Sec. 25.40 of this chapter.
* * * * *
PART 312--INVESTIGATIONAL NEW DRUG APPLICATION
18. The authority citation for 21 CFR part 312 continues to read as
follows:
Authority: Secs. 201, 301, 501, 502, 503, 505, 506, 507, 701 of
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 351,
352, 353, 355, 356, 357, 371); sec. 351 of the Public Health Service
Act (42 U.S.C. 262).
19. Section 312.23 is amended by revising paragraph (a)(7)(iv)(e)
to read as follows:
Sec. 312.23 IND content and format.
(a) * * *
(7) * * *
(iv) * * *
(E) Environmental analysis requirements. A claim for categorical
exclusion under Sec. 25.30 or 25.31 or an environmental assessment
under Sec. 25.40.
* * * * *
PART 314--APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG OR AN
ANTIBIOTIC DRUG
20. The authority citation for 21 CFR part 314 continues to read as
follows:
Authority: Secs. 201, 301, 501, 502, 503, 505, 506, 507, 701,
704, 721 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321,
331, 351, 352, 353, 355, 356, 357, 371, 374, 379e).
21. Section 314.50 is amended by revising paragraph (d)(1)(iii) to
read as follows:
Sec. 314.50 Content and format of an application.
* * * * *
(d) * * *
(1) * * *
(iii) Environmental impact. The application is required to contain
either a claim for categorical exclusion under Sec. 25.30 or 25.31 of
this chapter or an environmental assessment under Sec. 25.40 of this
chapter.
22. Section 314.101 is amended by revising paragraph (d)(4) to read
as follows:
Sec. 314.101 Filing an application and an abbreviated antibiotic
application and receiving an abbreviated new drug application.
* * * * *
(d) * * *
(4) The applicant fails to submit a complete environmental
assessment, which addresses each of the items specified in the
applicable format under Sec. 25.40 of this chapter or fails to provide
sufficient information to establish that the requested action is
subject to categorical exclusion under Sec. 25.30 or Sec. 25.31 of this
chapter.
* * * * *
PART 511--NEW ANIMAL DRUGS FOR INVESTIGATIONAL USE
23. The authority citation for 21 CFR part 511 continues to read as
follows:
Authority: Secs. 201, 501, 502, 503, 512, 701 of the Federal
Food, Drug, and Cosmetic Act (21 U.S.C. 321, 351, 352, 353, 360b,
371).
24. Section 511.1 is amended by revising paragraph (b)(10) to read
as follows:
Sec. 511.1 New animal drugs for investigational use exempt from
section 512(a) of the act.
* * * * *
(b) * * *
(10) The sponsor shall submit either a claim for categorical
exclusion under Sec. 25.30 or Sec. 25.33 of this chapter or an
environmental assessment under Sec. 25.40 of this chapter.
* * * * *
PART 514--NEW ANIMAL DRUG APPLICATIONS
25. The authority citation for 21 CFR part 514 continues to read as
follows:
Authority: Secs. 501, 502, 512, 701, 721, 801 of the Federal
Food, Drug, and Cosmetic Act (21 U.S.C. 351, 352, 360b, 371, 379e,
381).
26. Section 514.1 is amended by revising paragraph (b)(14) to read
as follows:
Sec. 514.1 Applications.
* * * * *
(b) * * *
(14) Environmental assessment. The applicant is required to submit
either a claim for categorical exclusion under Sec. 25.30 or Sec. 25.33
of this chapter or an
[[Page 40600]]
environmental assessment under Sec. 25.40 of this chapter.
* * * * *
27. Section 514.8 is amended by revising the fourth sentence of
paragraph (a)(1) to read as follows:
Sec. 514.8 Supplemental new animal drug applications.
(a)(1) * * * A supplemental application shall be accompanied by
either a claim for categorical exclusion under Sec. 25.30 or Sec. 25.33
of this chapter or an environmental assessment under Sec. 25.40 of this
chapter.
* * * * *
28. Section 514.110 is amended by revising paragraph (b)(10) to
read as follows:
Sec. 514.110 Reasons for refusing to file applications.
* * * * *
(b) * * *
(10) The applicant fails to submit a complete environmental
assessment under Sec. 25.40 of this chapter or fails to provide
sufficient information to establish that the requested action is
subject to categorical exclusion under Sec. 25.30 or Sec. 25.33 of this
chapter.
* * * * *
29. Section 514.111 is amended by revising paragraph (a)(9) to read
as follows:
Sec. 514.111 Refusal to approve an application.
(a) * * *
(9) The applicant fails to submit an adequate environmental
assessment under Sec. 25.40 of this chapter or fails to provide
sufficient information to establish that the requested action is
subject to categorical exclusion under Sec. 25.30 or Sec. 25.33 of this
chapter.
* * * * *
PART 570--FOOD ADDITIVES
30. The authority citation for 21 CFR part 570 continues to read as
follows:
Authority: Secs. 201, 401, 402, 408, 409, 701 of the Federal
Food, Drug, and Cosmetic Act (21 U.S.C. 321, 341, 342, 346a, 348,
371).
31. Section 570.35 is amended by revising paragraph (c)(1)(viii) to
read as follows:
Sec. 570.35 Affirmation of generally recognized as safe (GRAS) status.
* * * * *
(c) * * *
(viii) A claim for categorical exclusion under Sec. 25.30 or 25.32
of this chapter or an environmental assessment under Sec. 25.40 of this
chapter.
* * * * *
PART 571--FOOD ADDITIVE PETITIONS
32. The authority citation for 21 CFR part 571 continues to read as
follows:
Authority: Secs. 201, 402, 409, 701 of the Federal Food, Drug,
and Cosmetic Act (21 U.S.C. 321, 342, 348, 371); sec. 301 of the
Public Health Service Act (42 U.S.C. 241).
33. Section 571.1 is amended in paragraph (c) by revising item H to
read as follows:
Sec. 571.1 Petitions.
* * * * *
(c) * * *
H. The petitioner is required to submit either a claim for
categorical exclusion under Sec. 25.30 or Sec. 25.32 of this chapter
or an environmental assessment under Sec. 25.40 of this chapter.
* * * * *
PART 601--LICENSING
34. The authority citation for 21 CFR part 601 continues to read as
follows:
Authority: Secs. 201, 501, 502, 503, 505, 510, 513-516, 518-520,
701, 704, 721, 801 of the Federal Food, Drug, and Cosmetic Act (21
U.S.C. 321, 351, 352, 353, 355, 360, 360c-360f, 360h-360j, 371, 374,
379e, 381); secs. 215, 301, 351, 352 of the Public Health Service
Act (42 U.S.C. 216, 241, 262, 263); secs. 2-12 of the Fair Packaging
and Labeling Act (15 U.S.C. 1451-1461).
35. Section 601.2 is amended by revising the third sentence in
paragraph (a) and the second sentence in paragraph (c)(2) to read as
follows:
Sec. 601.2 Applications for establishment and product licenses;
procedures for filing.
(a) * * * The applicant shall also include either a claim for
categorical exclusion under Sec. 25.30 or 25.31 of this chapter or an
environmental assessment under Sec. 25.40 of this chapter.
* * * * *
(c) * * *
(2) * * * The applicant shall also include either a claim for
categorical exclusion under Sec. 25.30 or 25.31 of this chapter or an
environmental assessment under Sec. 25.40 of this chapter.
* * * * *
PART 812--INVESTIGATIONAL DEVICE EXEMPTIONS
36. The authority citation for 21 CFR part 812 continues to read as
follows:
Authority: Secs. 301, 501, 502, 503, 505, 506, 507, 510, 513-
516, 518-520, 701, 702, 704, 721, 801 of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 331, 351, 352, 353, 355, 356, 357, 360,
360c-360f, 360h-360j, 371, 372, 374, 379e, 381); secs. 215, 301,
351, 354-360F of the Public Health Service Act (42 U.S.C. 216, 241,
262, 263b-263n).
37. Section 812.20 is amended by revising paragraph (b)(9) to read
as follows:
Sec. 812.20 Application.
* * * * *
(b) * * *
(9) A claim for categorical exclusion under Sec. 25.30 or 25.34 or
an environmental assessment under Sec. 25.40.
* * * * *
PART 814--PREMARKET APPROVAL OF MEDICAL DEVICES
38. The authority citation for 21 CFR part 814 continues to read as
follows:
Authority: Secs. 501, 502, 503, 510, 513-520, 701, 702, 703,
704, 705, 721, 708, 801 of the Federal Food, Drug, and Cosmetic Act
(21 U.S.C. 351, 352, 353, 360, 360c-360j, 371, 372, 373, 374, 375,
379e, 381).
39. Section 814.20 is amended by revising paragraph (b)(11) to read
as follows:
Sec. 814.20 Application.
* * * * *
(b) * * *
(11) An environmental assessment under Sec. 25.20(n) prepared in
the applicable format in Sec. 25.40, unless the action qualifies for
exclusion under Sec. 25.30 or Sec. 25.34. If the applicant believes
that the action qualifies for exclusion, the PMA shall under
Sec. 25.15(a) and (d) provide information that establishes to FDA's
satisfaction that the action requested is included within the excluded
category and meets the criteria for the applicable exclusion.
* * * * *
Dated: May 9, 1997.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 97-19566 Filed 7-28-97; 8:45 am]
BILLING CODE 4160-01-P
