Current Good Manufacturing Practice Regulation and Investigational New Drugs; Companion Document to Direct Final Rule, 2494-2496 [06-350]
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2494
Federal Register / Vol. 71, No. 10 / Tuesday, January 17, 2006 / Proposed Rules
oversight of IRBs. One recommendation
was that sponsors and clinical
investigators be required to notify IRBs
of any prior review (see OIG,
Department of Health and Human
Services, ‘‘Institutional Review Boards:
A Time for Reform,’’ p. 14, June 1998;
https://oig.hhs.gov/oei/reports/oei–01–
97–00193.pdf). The OIG report stated
that the OIG had:
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* * * heard of a few situations where
sponsors and/or research investigators who
were unhappy with one IRB’s reviews
switched to another without the new IRB
being aware of the other’s prior involvement.
This kind of IRB shopping deprives the new
IRB of information that it should have and
that can be important in protecting human
subjects. The ground rules should be changed
so that sponsors and investigators have the
clear obligation to inform an IRB of any prior
reviews (footnote omitted). The obligation
should be applied to all those conducting
research funded by HHS or carried out on
FDA-regulated products. It will have
particular importance for those sponsors and
investigators working with independent
IRBs.
Id.
After reviewing the OIG’s
recommendation, FDA published an
ANPRM on March 6, 2002 (67 FR
10115) (see https://www.fda.gov/
OHRMS/DOCKETS/98fr/030602a.pdf)
announcing it was considering whether
to amend its IRB regulations to require
sponsors and investigators to inform
IRBs about any prior IRB review
decisions. We invited public comments
on: (1) The frequency of IRB shopping
and under what circumstances IRB
shopping has occurred; (2) what
information about prior IRB review
should be disclosed, where should it be
disclosed, and who should disclose it;
and (3) what methods, other than
disclosure of prior IRB reviews, might
prove to be valuable for dealing with
IRB shopping.
In response to this ANPRM, FDA
received 55 comments. The majority of
the comments reported they had little or
no first hand knowledge of instances of
IRB shopping, and did not believe IRB
shopping presented a significant
problem. Many comments expressed
concern about the logistics of
maintaining a system that would enable
the exchange of information among
IRBs, especially when studies involved
multiple study sites. There was concern
that maintaining such a system would
substantially increase the IRBs’
workload and not provide any
additional human subject protection.
There was also concern that waiting for
information from other IRBs prior to the
review of research proposals within a
particular institution might contribute
to delays in the review of these
proposals.
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The Office for Human Research
Protections (OHRP) also informed FDA
that it considered the OIG’s
recommendation to require sponsors
and investigators to notify IRBs of any
prior IRB review of a research plan.
OHRP concluded that it had no reason
to believe that IRB shopping was
occurring with any regularity in the
review of HHS conducted or supported
human subjects research.
Based on these reasons, FDA
concluded that IRB shopping either
does not occur or does not present a
problem to an extent that would warrant
rulemaking at this time.
In a letter dated February 26, 2005,
FDA advised the OIG of these findings
and conclusions. FDA is now
withdrawing this ANPRM. A
withdrawal does not prevent the agency
from taking action in the future. Should
FDA decide to undertake rulemaking
sometime in the future, the agency will
provide new opportunities for comment.
industry entitled ‘‘INDs—Approaches to
Complying With CGMP During Phase 1’’
to provide further guidance on the
subject.
DATES: Submit written or electronic
comments by April 3, 2006.
ADDRESSES: Submit written comments
to the Division of Dockets Management
(HFA–305), Food and Drug
Administration, 5630 Fishers Lane, rm.
1061, Rockville, MD 20852. Submit
electronic comments to https://
www.fda.gov/dockets/comments.
FOR FURTHER INFORMATION CONTACT:
Monica Caphart, Center for Drug
Evaluation and Research (HFD–320),
Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857,
301–827–9047; or Christopher Joneckis,
Center for Biologics Evaluation and
Research (HFM–1), Food and Drug
Administration, 1401 Rockville Pike,
Rockville, MD 20852, 301–435–5681.
SUPPLEMENTARY INFORMATION:
Dated: January 4, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E6–357 Filed 1–13–06; 8:45 am]
I. Background
As described more fully in the related
direct final rule, a Phase 1 clinical trial
includes the initial introduction of an
investigational new drug into humans.
Such studies are aimed at establishing
basic safety and are designed to
determine the metabolism and
pharmacologic actions of the drug in
humans. The total number of subjects in
a Phase 1 study is limited—generally no
more than 80 subjects. This is in
contrast to Phase 2 and Phase 3 trials,
which may involve substantially greater
numbers of subjects, exposing more
subjects to the drug product, and which
aim to test the effectiveness of the drug
product.
For several reasons, we believe that
production of human drug products,
including biological drug products,
intended for use in Phase 1 clinical
trials should be exempted from
complying with the specific regulatory
requirements set forth in parts 210 and
211 (21 CFR parts 210 and 211). First,
even if exempted from the requirements
of our CGMP regulations in parts 210
and 211, investigational drugs remain
subject to the statutory provisions that
deem a drug adulterated for failure to
comply with CGMPs (21 U.S.C.
351(a)(2)(B)).
Second, we oversee drugs for use in
Phase 1 trials through our existing IND
authority. Every IND must contain,
among other things, a section on
chemistry, manufacturing, and control
information that describes the
composition, manufacture, and control
of the investigational drug product (21
CFR 312.23(a)(7)). This information
should suffice to enable us to
BILLING CODE 4160–01–S
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
21 CFR Part 210
[Docket No. 2005N–0285]
Current Good Manufacturing Practice
Regulation and Investigational New
Drugs; Companion Document to Direct
Final Rule
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Proposed rule.
SUMMARY: The Food and Drug
Administration (FDA) is publishing this
companion proposed rule to the direct
final rule, published elsewhere in this
issue of the Federal Register, which is
intended to amend our current good
manufacturing practice (CGMP)
regulations for human drugs, including
biological products, to exempt most
investigational ‘‘Phase 1’’ drugs from
complying with the regulatory
requirements. We will instead exercise
oversight of production of these drugs
under the agency’s general statutory
CGMP authority and investigational
new drug application (IND) authority.
Elsewhere in this issue of the Federal
Register, FDA is announcing the
availability of a draft guidance for
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Federal Register / Vol. 71, No. 10 / Tuesday, January 17, 2006 / Proposed Rules
adequately protect subjects in early
Phase 1 trials.
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II. Additional Information
This proposed rule is a companion to
the direct final rule published in the
final rules section of this issue of the
Federal Register. The proposed rule and
the direct final rule are identical. This
companion proposed rule provides the
procedural framework to proceed with
standard notice-and-comment
rulemaking if the direct final rule
receives significant adverse comment
and is withdrawn. The comment period
for the companion proposed rule runs
concurrently with the comment period
of the direct final rule. Any comments
received on this companion proposed
rule will also be treated as comments on
the direct final rule and vice versa.
For additional information, see the
corresponding direct final rule
published in the final rules section of
this issue of the Federal Register. All
persons who may wish to comment
should review the rationale for these
amendments set out in the preamble
discussion of the direct final rule. A
significant adverse comment is one that
explains why the rule would be
inappropriate, including challenges to
the rule’s underlying premise or
approach, or would be ineffective or
unacceptable without a change. A
comment recommending a rule change
in addition to this rule will not be
considered a significant adverse
comment, unless the comment states
why this rule would be ineffective
without the additional change. If no
significant adverse comment is received
in response to the direct final rule, no
further action will be taken related to
this companion proposed rule. Instead,
we will publish a confirmation notice
within 30 days after the comment
period ends, and we intend the direct
final rule to become effective 30 days
after publication of the confirmation
notice. If we receive significant adverse
comments, we will withdraw the direct
final rule. We will proceed to respond
to all of the comments received
regarding the direct final rule, treating
those comments as comments to this
proposed rule. The agency will address
the comments in a subsequent final rule.
We will not provide additional
opportunity for comment.
III. Legal Authority
Under section 501(a)(2)(B) of the
Federal Food, Drug, and Cosmetic Act
(the act) (21 U.S.C. 201 et seq.) a drug
is deemed adulterated if the methods
used in, or the facilities, or controls
used for, its manufacture, processing,
packing, or holding do not conform to
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Jkt 208001
or are not operated in conformity with
CGMPs to ensure that such drug meets
the requirements of the act as to safety,
and has the identity and strength, and
meets the quality and purity
characteristics, which it purports or is
represented to possess. The rulemaking
authority conferred on FDA by Congress
under the act permits the agency to
amend its regulations as contemplated
by this direct final rule. Section 701(a)
of the act (21 U.S.C. 371) gives FDA
general rulemaking authority to issue
regulations for the efficient enforcement
of the act. We refer readers to the legal
authority section of the preamble of the
1978 CGMP regulations for a fuller
discussion (43 FR 45014 at 45020–
45026, September 29, 1978).
IV. Environmental Impact
The agency has determined that under
21 CFR 25.30(h) this action is of a type
that does not individually or
cumulatively have a significant effect on
the human environment. Therefore,
neither an environmental assessment
nor an environmental impact statement
is required.
V. Analysis of Impacts
FDA examined the impacts of this
proposed rule under Executive Order
12866 and the Regulatory Flexibility Act
(5 U.S.C. 601–612), and the Unfunded
Mandates Reform Act of 1995 (Public
Law 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 agency
believes that this proposed rule is not a
significant regulatory action as defined
by the Executive order.
Under the Regulatory Flexibility Act,
if a rule has a significant impact on a
substantial number of small entities, an
agency must analyze regulatory options
that would minimize any significant
impact of the rule on small entities. The
agency has considered the effect that
this rule would have on small entities.
Because exempting production of drugs
for use in Phase 1 studies from
compliance with specific regulatory
requirements does not add any burden,
the agency certifies that the 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.
Section 202(a) of the Unfunded
Mandates Reform Act of 1995 requires
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2495
that agencies prepare a written
statement, which includes an
assessment of anticipated costs and
benefits, before proposing ‘‘any rule that
includes any Federal mandate that may
result in the 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)
in any one year.’’ The current threshold
after adjustment for inflation is $115
million using the most current (2003)
Implicit Price Deflator for the Gross
Domestic Product. FDA does not expect
this proposed rule to result in any 1year expenditure that would meet or
exceed this amount.
For a further discussion of the
impacts of this rulemaking, see the
Analysis of Impacts section in the
corresponding direct final rule
published in the final rules section of
this issue of the Federal Register.
VI. Paperwork Reduction Act of 1995
This proposed rule contains no new
information collection requirements 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). Under the
proposed rule, the production of human
drug products, including biological drug
products, intended for use in Phase 1
clinical trials would be exempted from
complying with the specific regulatory
requirements set forth in parts 210 and
211. Parts 210 and 211 contain
information collection requirements that
have been approved by OMB under
control number 0910–0139. As
explained in the following paragraph,
the information collection requirements
in parts 210 and 211 would be reduced
under this proposed rule.
The OMB-approved hourly burden to
comply with the information collection
requirements in parts 210 and 211
(control number 0910–0139) is 848,625
hours. FDA estimates that, under the
proposed rule, approximately 7,315
drugs would be exempted from
complying with the specific regulatory
requirements set forth in parts 210 and
211. Based on this number and the total
number of drugs that are subject to parts
210 and 211, FDA estimates that the
burden hours approved under control
number 0910–0139 would be reduced
by approximately 50,493 hours. Thus, as
a result of the proposed rule, the
amended burden hours in control
number 0910–0139 would be
approximately 798,132 hours.
VII. Federalism
FDA has analyzed this proposed rule
in accordance with the principles set
forth in Executive Order 13132. FDA
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Federal Register / Vol. 71, No. 10 / Tuesday, January 17, 2006 / Proposed Rules
has determined that the rule does not
contain policies that have substantial
direct effects on the States, on the
relationship between the National
Government and the States, or on the
distribution of power and
responsibilities among the various
levels of government. Accordingly, the
agency has concluded that the rule does
not contain policies that have
federalism implications as defined in
the Executive order and, consequently,
a federalism summary impact statement
is not required. We invite comments on
the federalism implications of this
proposed rule.
VIII. Request for Comments
Interested persons may submit to the
Division of Dockets Management (see
ADDRESSES) written or electronic
comments regarding this document.
This comment period runs concurrently
with the comment period for the direct
final rule; any comments received will
be considered as comments regarding
the direct final rule. Submit a single
copy of electronic comments or two
paper copies of any mailed comments,
except that individuals may submit one
paper copy. Comments are to be
identified with the docket number
found in brackets in the heading of this
document. Received comments may be
seen in the Division of Dockets
Management between 9 a.m. and 4 p.m.,
Monday through Friday.
List of Subjects in 21 CFR Part 210
Drugs, Packaging and containers.
Therefore, under the Federal Food,
Drug, and Cosmetic Act and under
authority delegated to the Commissioner
of Food and Drugs it is proposed that 21
CFR part 210 be amended as follows:
PART 210—CURRENT GOOD
MANUFACTURING PRACTICE IN
MANUFACTURING, PROCESSING,
PACKING, OR HOLDING OF DRUGS;
GENERAL
1. The authority citation for 21 CFR
part 210 continues to read as follows:
Authority: 21 U.S.C. 321, 351, 352, 355,
360b, 371, 374; 42 U.S.C. 216, 262, 263a, 264.
2. Section 210.2 is revised by adding
paragraph (c) to read as follows:
§ 210.2 Applicability of current good
manufacturing practice regulations.
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*
*
*
*
*
(c) An investigational drug for use in
a Phase 1 study, as defined in
§ 312.21(a) of this chapter, is subject to
the statutory requirements set forth at 21
U.S.C. 351(a)(2)(B). The production of
such drug is exempt from compliance
with the regulations in part 211 of this
chapter. However, this exemption does
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13:49 Jan 13, 2006
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not apply to an investigational drug for
use in a Phase 1 study once the
investigational drug has been made
available for use by or for the sponsor
in a Phase 2 or Phase 3 study, as defined
in § 312.21(b) and (c) of this chapter, or
the drug has been lawfully marketed. If
the investigational drug has been made
available in a Phase 2 or 3 study or the
drug has been lawfully marketed, the
drug for use in the Phase 1 study must
comply with part 211 of this chapter.
Dated: January 9, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 06–350 Filed 1–12–06; 8:45 am]
BILLING CODE 4160–01–S
DEPARTMENT OF THE TREASURY
Internal Revenue Service
158080–04) that was the subject of FR
Doc. 05–19379, is corrected as follows:
On page 57930, column 1, in the
preamble, under the paragraph heading
FOR FURTHER INFORMATION CONTACT:
lines 4 thru 8, the language ‘‘concerning
submissions of comments, the hearing,
and/or to be placed on the building
access list to attend the hearing, Richard
A. Hurst at (202) 622–7116 (not toll-free
numbers).’’ is corrected to read
‘‘concerning submission of comments,
the hearing, and/or to be placed on the
building access list to attend the
hearing, Richard A. Hurst at (202) 622–
7180 (not toll-free numbers).’’.
Guy R. Traynor,
Acting Chief, Publications and Regulations
Branch, Legal Processing Division, Associate
Chief Counsel (Procedure and
Administration).
[FR Doc. 06–395 Filed 1–12–06; 8:45 am]
BILLING CODE 4830–01–U
26 CFR Part 1
[REG–158080–04]
DEPARTMENT OF THE TREASURY
RIN–1545–BE79
Internal Revenue Service
Application of Section 409A to
Nonqualified Deferred Compensation
Plans; Correction
26 CFR Part 1
Internal Revenue Service (IRS),
Treasury.
ACTION: Correction to notice of proposed
rulemaking.
AGENCY:
SUMMARY: This document corrects a
notice of proposed rulemaking that was
published in the Federal Register on
Tuesday, October 4, 2005 (70 FR 57930),
regarding the application of section
409A to nonqualified deferred
compensation plans. The regulations
affect service providers receiving
amounts of deferred compensation, and
the service recipients for whom the
service providers provide services.
FOR FURTHER INFORMATION CONTACT:
Stephen Tackney, (202) 927–9639 (not a
toll-free number).
SUPPLEMENTARY INFORMATION:
Background
The notice of proposed rulemaking
(REG–158080–04) that is the subject of
this correction is under section 409A of
the Internal Revenue Code.
Need for Correction
As published, REG–158080–04
contains an error that may prove to be
misleading and is in need of
clarification.
Correction of Publication
Accordingly, the publication of the
notice of proposed rulemaking (REG–
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[REG–106418–05]
RIN 1545–BE34
Guidance Under Subpart F Relating to
Partnerships
Internal Revenue Service (IRS),
Treasury.
ACTION: Notice of proposed rulemaking
by cross-reference to temporary
regulations.
AGENCY:
SUMMARY: In the Rule and Regulations
section of this issue of the Federal
Register, the IRS is issuing temporary
regulations that provide rules for
determining whether a controlled
foreign corporation’s (CFC’s)
distributive share of partnership income
is excluded from foreign personal
holding company income under the
exception contained in section 954(i).
The regulations will affect CFCs that are
qualified insurance companies, as
defined in section 953(e)(3), that have
an interest in a partnership and U.S.
shareholders of such CFCs. The text of
those temporary regulations also serves
as the text of these proposed
regulations.
Written or electronic comments
and requests for a public hearing must
be received by April 17, 2006.
ADDRESSES: Send submissions to:
CC:PA:LPD:PR (REG–106418–05), room
5203, Internal Revenue Service, PO Box
7604, Ben Franklin Station, Washington,
DATES:
E:\FR\FM\17JAP1.SGM
17JAP1
]]>Agencies
[Federal Register Volume 71, Number 10 (Tuesday, January 17, 2006)]
[Proposed Rules]
[Pages 2494-2496]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 06-350]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 210
[Docket No. 2005N-0285]
Current Good Manufacturing Practice Regulation and
Investigational New Drugs; Companion Document to Direct Final Rule
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is publishing this
companion proposed rule to the direct final rule, published elsewhere
in this issue of the Federal Register, which is intended to amend our
current good manufacturing practice (CGMP) regulations for human drugs,
including biological products, to exempt most investigational ``Phase
1'' drugs from complying with the regulatory requirements. We will
instead exercise oversight of production of these drugs under the
agency's general statutory CGMP authority and investigational new drug
application (IND) authority. Elsewhere in this issue of the Federal
Register, FDA is announcing the availability of a draft guidance for
industry entitled ``INDs--Approaches to Complying With CGMP During
Phase 1'' to provide further guidance on the subject.
DATES: Submit written or electronic comments by April 3, 2006.
ADDRESSES: Submit written comments to the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
rm. 1061, Rockville, MD 20852. Submit electronic comments to https://
www.fda.gov/dockets/comments.
FOR FURTHER INFORMATION CONTACT: Monica Caphart, Center for Drug
Evaluation and Research (HFD-320), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-827-9047; or Christopher
Joneckis, Center for Biologics Evaluation and Research (HFM-1), Food
and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852, 301-
435-5681.
SUPPLEMENTARY INFORMATION:
I. Background
As described more fully in the related direct final rule, a Phase 1
clinical trial includes the initial introduction of an investigational
new drug into humans. Such studies are aimed at establishing basic
safety and are designed to determine the metabolism and pharmacologic
actions of the drug in humans. The total number of subjects in a Phase
1 study is limited--generally no more than 80 subjects. This is in
contrast to Phase 2 and Phase 3 trials, which may involve substantially
greater numbers of subjects, exposing more subjects to the drug
product, and which aim to test the effectiveness of the drug product.
For several reasons, we believe that production of human drug
products, including biological drug products, intended for use in Phase
1 clinical trials should be exempted from complying with the specific
regulatory requirements set forth in parts 210 and 211 (21 CFR parts
210 and 211). First, even if exempted from the requirements of our CGMP
regulations in parts 210 and 211, investigational drugs remain subject
to the statutory provisions that deem a drug adulterated for failure to
comply with CGMPs (21 U.S.C. 351(a)(2)(B)).
Second, we oversee drugs for use in Phase 1 trials through our
existing IND authority. Every IND must contain, among other things, a
section on chemistry, manufacturing, and control information that
describes the composition, manufacture, and control of the
investigational drug product (21 CFR 312.23(a)(7)). This information
should suffice to enable us to
[[Page 2495]]
adequately protect subjects in early Phase 1 trials.
II. Additional Information
This proposed rule is a companion to the direct final rule
published in the final rules section of this issue of the Federal
Register. The proposed rule and the direct final rule are identical.
This companion proposed rule provides the procedural framework to
proceed with standard notice-and-comment rulemaking if the direct final
rule receives significant adverse comment and is withdrawn. The comment
period for the companion proposed rule runs concurrently with the
comment period of the direct final rule. Any comments received on this
companion proposed rule will also be treated as comments on the direct
final rule and vice versa.
For additional information, see the corresponding direct final rule
published in the final rules section of this issue of the Federal
Register. All persons who may wish to comment should review the
rationale for these amendments set out in the preamble discussion of
the direct final rule. A significant adverse comment is one that
explains why the rule would be inappropriate, including challenges to
the rule's underlying premise or approach, or would be ineffective or
unacceptable without a change. A comment recommending a rule change in
addition to this rule will not be considered a significant adverse
comment, unless the comment states why this rule would be ineffective
without the additional change. If no significant adverse comment is
received in response to the direct final rule, no further action will
be taken related to this companion proposed rule. Instead, we will
publish a confirmation notice within 30 days after the comment period
ends, and we intend the direct final rule to become effective 30 days
after publication of the confirmation notice. If we receive significant
adverse comments, we will withdraw the direct final rule. We will
proceed to respond to all of the comments received regarding the direct
final rule, treating those comments as comments to this proposed rule.
The agency will address the comments in a subsequent final rule. We
will not provide additional opportunity for comment.
III. Legal Authority
Under section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic
Act (the act) (21 U.S.C. 201 et seq.) a drug is deemed adulterated if
the methods used in, or the facilities, or controls used for, its
manufacture, processing, packing, or holding do not conform to or are
not operated in conformity with CGMPs to ensure that such drug meets
the requirements of the act as to safety, and has the identity and
strength, and meets the quality and purity characteristics, which it
purports or is represented to possess. The rulemaking authority
conferred on FDA by Congress under the act permits the agency to amend
its regulations as contemplated by this direct final rule. Section
701(a) of the act (21 U.S.C. 371) gives FDA general rulemaking
authority to issue regulations for the efficient enforcement of the
act. We refer readers to the legal authority section of the preamble of
the 1978 CGMP regulations for a fuller discussion (43 FR 45014 at
45020-45026, September 29, 1978).
IV. Environmental Impact
The agency has determined that under 21 CFR 25.30(h) this action is
of a type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
V. Analysis of Impacts
FDA examined the impacts of this proposed rule under Executive
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and
the Unfunded Mandates Reform Act of 1995 (Public Law 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 agency believes that
this proposed rule is not a significant regulatory action as defined by
the Executive order.
Under the Regulatory Flexibility Act, if a rule has a significant
impact on a substantial number of small entities, an agency must
analyze regulatory options that would minimize any significant impact
of the rule on small entities. The agency has considered the effect
that this rule would have on small entities. Because exempting
production of drugs for use in Phase 1 studies from compliance with
specific regulatory requirements does not add any burden, the agency
certifies that the 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.
Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires
that agencies prepare a written statement, which includes an assessment
of anticipated costs and benefits, before proposing ``any rule that
includes any Federal mandate that may result in the 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) in any one year.'' The current threshold after adjustment
for inflation is $115 million using the most current (2003) Implicit
Price Deflator for the Gross Domestic Product. FDA does not expect this
proposed rule to result in any 1-year expenditure that would meet or
exceed this amount.
For a further discussion of the impacts of this rulemaking, see the
Analysis of Impacts section in the corresponding direct final rule
published in the final rules section of this issue of the Federal
Register.
VI. Paperwork Reduction Act of 1995
This proposed rule contains no new information collection
requirements 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). Under the proposed rule, the production of human drug products,
including biological drug products, intended for use in Phase 1
clinical trials would be exempted from complying with the specific
regulatory requirements set forth in parts 210 and 211. Parts 210 and
211 contain information collection requirements that have been approved
by OMB under control number 0910-0139. As explained in the following
paragraph, the information collection requirements in parts 210 and 211
would be reduced under this proposed rule.
The OMB-approved hourly burden to comply with the information
collection requirements in parts 210 and 211 (control number 0910-0139)
is 848,625 hours. FDA estimates that, under the proposed rule,
approximately 7,315 drugs would be exempted from complying with the
specific regulatory requirements set forth in parts 210 and 211. Based
on this number and the total number of drugs that are subject to parts
210 and 211, FDA estimates that the burden hours approved under control
number 0910-0139 would be reduced by approximately 50,493 hours. Thus,
as a result of the proposed rule, the amended burden hours in control
number 0910-0139 would be approximately 798,132 hours.
VII. Federalism
FDA has analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. FDA
[[Page 2496]]
has determined that the rule does not contain policies that have
substantial direct effects on the States, on the relationship between
the National Government and the States, or on the distribution of power
and responsibilities among the various levels of government.
Accordingly, the agency has concluded that the rule does not contain
policies that have federalism implications as defined in the Executive
order and, consequently, a federalism summary impact statement is not
required. We invite comments on the federalism implications of this
proposed rule.
VIII. Request for Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this document.
This comment period runs concurrently with the comment period for the
direct final rule; any comments received will be considered as comments
regarding the direct final rule. Submit a single copy of electronic
comments or two paper copies of any mailed comments, except that
individuals may submit one paper copy. Comments are to be identified
with the docket number found in brackets in the heading of this
document. Received comments may be seen in the Division of Dockets
Management between 9 a.m. and 4 p.m., Monday through Friday.
List of Subjects in 21 CFR Part 210
Drugs, Packaging and containers.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs it is
proposed that 21 CFR part 210 be amended as follows:
PART 210--CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING,
PROCESSING, PACKING, OR HOLDING OF DRUGS; GENERAL
1. The authority citation for 21 CFR part 210 continues to read as
follows:
Authority: 21 U.S.C. 321, 351, 352, 355, 360b, 371, 374; 42
U.S.C. 216, 262, 263a, 264.
2. Section 210.2 is revised by adding paragraph (c) to read as
follows:
Sec. 210.2 Applicability of current good manufacturing practice
regulations.
* * * * *
(c) An investigational drug for use in a Phase 1 study, as defined
in Sec. 312.21(a) of this chapter, is subject to the statutory
requirements set forth at 21 U.S.C. 351(a)(2)(B). The production of
such drug is exempt from compliance with the regulations in part 211 of
this chapter. However, this exemption does not apply to an
investigational drug for use in a Phase 1 study once the
investigational drug has been made available for use by or for the
sponsor in a Phase 2 or Phase 3 study, as defined in Sec. 312.21(b)
and (c) of this chapter, or the drug has been lawfully marketed. If the
investigational drug has been made available in a Phase 2 or 3 study or
the drug has been lawfully marketed, the drug for use in the Phase 1
study must comply with part 211 of this chapter.
Dated: January 9, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 06-350 Filed 1-12-06; 8:45 am]
BILLING CODE 4160-01-S
