[Federal Register: December 14, 1998 (Volume 63, Number 239)]
[Proposed Rules]
[Page 68710-68712]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr14de98-21]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 312
[Docket No. 98N-0979]
Investigational New Drug Applications; Clinical Holds; Companion
Document to Direct Final Rule
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is proposing to amend
its regulations governing investigational new drug applications (IND's)
for human drug and biological products. This proposed action would
amend the IND clinical hold requirements to state that the agency will
respond in writing to a sponsor's request that a clinical hold be
removed from an investigation within 30-calendar days of the agency's
receipt of the request and the sponsor's complete response to the
issue(s) that led to the clinical hold. This proposed action is being
taken in accordance with provisions of the Food and Drug Administration
Modernization Act of 1997 (the Modernization Act). This proposed rule
is a companion document to a direct final rule published elsewhere in
this issue of the Federal Register. If FDA receives any significant
adverse comment, the direct final rule will be withdrawn, and the
comments will be considered in the development of a final rule using
usual notice-and-comment rulemaking based on this proposed rule.
[[Page 68711]]
DATES: Comments must be received on or before March 1, 1999.
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT:
Murray M. Lumpkin, Center for Drug Evaluation and Research (HFD-2),
Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857,
301-594-5417, or
Rebecca A. Devine, Center for Biologics Evaluation and Research
(HFM-10), Food and Drug Administration, 1401 Rockville Pike, Rockville,
MD 20852, 301-827-0373.
SUPPLEMENTARY INFORMATION:
I. Background
On November 21, 1997, President Clinton signed into law the
Modernization Act (Pub. L. 105-115). Section 117 of the Modernization
Act amends the Federal Food, Drug, and Cosmetic Act (the act) by
codifying in section 505(i) (21 U.S.C. 355(i)) several of the
procedures and requirements governing the use of investigational new
drugs that are already set forth in FDA regulations (parts 50 and 312
(21 CFR parts 50 and 312)).
Section 505(i)(2) of the act, as amended by the Modernization Act,
provides that if a sponsor of an IND that has been placed on clinical
hold requests in writing that the clinical hold be removed and submits
a complete response to the issue(s) identified in the clinical hold
order, FDA is required to respond in writing to the sponsor within 30-
calendar days of receipt of the complete response. This proposed rule
would amend Sec. 312.42(e) to reflect this new statutory requirement
and to clarify when a sponsor may resume an investigation after FDA
issues a clinical hold order.
II. Additional Information
This proposed rule is a companion to the direct final rule
published elsewhere in this issue of the Federal Register. The
companion proposed rule and the direct final rule are identical. This
companion proposed rule will provide the procedural framework to
finalize the rule in the event 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
for the direct final rule. Any comments received under the companion
proposed rule will be treated as comments regarding the direct final
rule.
The amendments in this proposed rule are a direct result of the new
provisions in section 505(i)(2) of the act. 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,
FDA will publish a confirmation document within 30 days after the
comment period ends confirming that the direct final rule will go into
effect on April 28, 1999. If FDA receives significant adverse comments,
the agency will withdraw the direct final rule. FDA will proceed to
respond to comments received regarding the rule and, if appropriate,
the rule will be finalized under this companion proposed rule using
usual notice-and-comment procedures.
For additional information, see the corresponding direct final rule
published elsewhere in this issue of the Federal Register. All persons
who wish to comment should review the detailed 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.
III. Environmental Impact
The agency has determined under 21 CFR 25.30(h) that 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.
IV. Analysis of Impact
FDA has examined the impacts of this companion proposed rule under
Executive Order 12866, the Regulatory Flexibility Act (5 U.S.C. 601-
612), and 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). Executive Order 12866
classifies a rule as significant if it meets any one of a number of
specified conditions, including having an annual effect on the economy
of $100 million or adversely affecting in a material way a sector of
the economy, competition, or jobs, or if it raises novel legal or
policy issues. The agency believes that this proposed rule is
consistent with the regulatory philosophy and principles identified in
the Executive Order. In addition, the proposed rule is not a
significant regulatory action as defined by the Executive Order and so
is not subject to review under the Executive Order.
The Regulatory Flexibility Act requires agencies to analyze
regulatory options to minimize any significant impact on small
entities. The agency has considered the effect that this rule will have
on small entities, including small businesses, and certifies that the
proposed rule will not have a significant economic impact on a
substantial number of small entities. Therefore, under the Regulatory
Flexibility Act, no further analysis is required.
The Unfunded Mandates Reform Act requires an agency to prepare a
budgetary impact statement before issuing any rule likely to result in
a Federal mandate that may result in expenditures by State, local, and
tribal governments or the private sector of $100 million (adjusted
annually for inflation) in any 1 year. This proposed rule will not
result in an expenditure of $100 million or more on any governmental
entity or the private sector, so no budgetary impact statement is
required.
V. Paperwork Reduction Act of 1995
FDA tentatively concludes that this proposed rule contains no
collections of information. Therefore, clearance by the Office of
Management and Budget under the Paperwork Reduction Act of 1995 is not
required.
VI. Request for Comments
Interested persons may, on or before March 1, 1999, submit to the
Dockets Management Branch (address above) written comments regarding
this proposal. Two copies of any comments are to be submitted, except
that individuals may submit one 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 office above between 9
a.m. and 4 p.m., Monday through Friday.
List of Subjects in 21 CFR Part 312
Drugs, Exports, Imports, Investigations, Labeling, Medical
research, Reporting and recordkeeping requirements, Safety.
[[Page 68712]]
Therefore, under the Federal Food, Drug, and Cosmetic Act, the
Public Health Service Act, and under authority delegated to the
Commissioner of Food and Drugs, it is proposed that 21 CFR part 312 be
amended to read as follows:
PART 312--INVESTIGATIONAL NEW DRUG APPLICATION
1. The authority citation for 21 CFR part 312 is revised to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 371; 42
U.S.C. 262.
2. Section 312.42 is amended by revising paragraph (e) to read as
follows:
Sec. 312.42 Clinical holds and requests for modification.
* * * * *
(e) Resumption of clinical investigations. An investigation may
only resume after FDA (usually the Division Director, or the Director's
designee, with responsibility for review of the IND) has notified the
sponsor that the investigation may proceed. Resumption of the affected
investigation(s) will be authorized when the sponsor corrects the
deficiency(ies) previously cited or otherwise satisfies the agency that
the investigation(s) can proceed. FDA may notify a sponsor of its
determination regarding the clinical hold by telephone or other means
of rapid communication. If a sponsor of an IND that has been placed on
clinical hold requests in writing that the clinical hold be removed and
submits a complete response to the issue(s) identified in the clinical
hold order, FDA shall respond in writing to the sponsor within 30-
calendar days of receipt of the request and the complete response.
FDA's response will either remove or maintain the clinical hold, and
will state the reasons for such determination. Notwithstanding the 30-
calendar day response time, a sponsor may not proceed with a clinical
trial on which a clinical hold has been imposed until the sponsor has
been notified by FDA that the hold has been lifted.
* * * * *
Dated: December 4, 1998.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 98-33030 Filed 12-11-98; 8:45 am]
BILLING CODE 4160-01-F