[Federal Register Volume 61, Number 65 (Wednesday, April 3, 1996)]
[Notices]
[Pages 14797-14798]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-8165]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Investigational New Drugs; Procedure to Monitor Clinical Hold
Process; Meeting of Review Committee and Request for Submissions
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is announcing a meeting
of the clinical hold review committee, which reviews the clinical holds
that the Center for Drug Evaluation and Research (CDER) has placed on
certain investigational new drug trials. The committee was established
as a 1-year experiment in August 1991. The committee met quarterly
through 1992 and currently meets semiannually as a regular program. The
committee last met in November 1995. FDA is inviting any interested
drug company to use the confidential mechanism to submit to the
committee for its review the name and number of any investigational new
drug trial placed on clinical hold during the past 12 months that the
company wants the committee to review.
DATES: The meeting is currently scheduled for June 1996. Drug companies
may submit review requests for the June meeting before May 3, 1996.
ADDRESSES: Submit clinical hold review requests to Amanda B. Pedersen,
FDA Chief Mediator and Ombudsman, Office of the Commissioner (HF-7),
Food and Drug Administration, rm. 14-105, 5600 Fishers Lane, Rockville,
MD 20857, 301-827-3390.
FOR FURTHER INFORMATION CONTACT: Janet M. Jones, Center for Drug
Evaluation and Research (HFD-4), Food and Drug Administration, 5600
Fishers Lane (WOC II rm. 6020), Rockville, MD 20857, 301-594-5445.
SUPPLEMENTARY INFORMATION: FDA regulations in part 312 (21 CFR part
312) provide procedures that govern the use of investigational new
drugs in human subjects. These regulations require that the sponsor of
a clinical investigation submit an investigational new drug application
(IND) to FDA outlining the proposed use of the investigational drug.
The IND must contain the study protocol, a summary of human and animal
experience with the drug, and information about the drug's chemistry
and pharmacology. FDA reviews an IND to help ensure the safety and
rights of subjects and, in phases 2, 3, and 4 of drug development, to
help ensure that the quality of any scientific evaluation of drugs is
adequate to permit an evaluation of the drug's efficacy and safety. An
investigational new drug for which an IND is in effect is exempt from
the premarketing approval requirements that are otherwise applicable
and may be shipped lawfully for the purpose of conducting clinical
investigations of that drug.
If FDA determines that a proposed or ongoing study may pose
significant risks for human subjects or is otherwise seriously
deficient, as discussed in the investigational new drug regulations, it
may impose a clinical hold on the study. The clinical hold is one of
FDA's primary mechanisms for protecting subjects who are involved in
investigational new drug trials. A clinical hold is an order that FDA
issues to a sponsor to delay a proposed investigation or to suspend an
ongoing investigation. The clinical hold may be placed on one or more
of the investigations covered by an IND. When a proposed study is
placed on clinical hold, subjects may not be given the investigational
drug as part of that study. When an ongoing study is placed on clinical
hold, no new subjects may
[[Page 14798]]
be recruited to the study and placed on the investigational drug, and
patients already in the study should stop receiving therapy involving
the investigational drug unless FDA specifically permits it.
FDA regulations at Sec. 312.42 describe the grounds for the
imposition of a clinical hold. When FDA concludes that there is a
deficiency in a proposed or ongoing clinical trial that may be grounds
for the imposition of a hold order, ordinarily FDA will attempt to
resolve the matter through informal discussions with the sponsor. If
that attempt is unsuccessful, the agency may order a clinical hold. In
CDER, a clinical hold is ordered by the director of the new drug
division that is responsible for review of the IND. The order
identifies the studies under the IND to which the hold applies and
explains the basis for the action. The hold order may be made by
telephone or other means of rapid communication, or in writing. Within
5 working days of the imposition of the clinical hold, the division
director provides the sponsor with a written explanation of the basis
for the hold. Any sponsor who has not received a written explanation
within 5 working days should notify the division and request that it be
issued. In addition to providing a statement of reasons, this ensures
that the hold is recorded in CDER's management information system.
The clinical hold order specifies whether the sponsor may resume
the affected investigation without prior notification by FDA once the
deficiency has been corrected. If the order does not permit the
resumption, an investigation may resume only after the division
director or his or her designee has notified the sponsor that the
investigation may proceed. Resumption may be authorized by telephone or
other means of rapid communication. If all investigations covered by an
IND remain on clinical hold for 1 year or longer, FDA may place the IND
on inactive status.
FDA regulations at Sec. 312.48 and CDER's Manual of Policies and
Procedures (MAPP 6030.1) provide dispute resolution mechanisms through
which sponsors may request reconsideration of clinical hold orders. The
regulations encourage the sponsor to attempt to resolve disputes
directly with the review staff responsible for the review of the IND.
If necessary, a sponsor may request a meeting with the review staff and
management to discuss the hold.
Over the years, drug sponsors have expressed a number of concerns
about the clinical hold process, including concerns about the
scientific and procedural adequacy of some agency actions. FDA
undertook several initiatives to evaluate the consistency and fairness
of the Center's practices in imposing clinical holds.
One initiative undertaken by FDA was the establishment of a
committee in CDER to review selected clinical holds for scientific and
procedural quality. The committee held pilot meetings in 1991 and 1992.
The trial phase of the committee review process confirmed the agency's
view that the divisions in CDER impose clinical holds in a manner that
is generally consistent with FDA's procedural requirements and that
holds are imposed on scientifically supportable grounds.
The clinical hold committee review process is now a regular,
ongoing program. The review procedure of the committee is designed to
afford an opportunity for a sponsor who does not wish to seek formal
reconsideration of a pending hold to have that hold considered
``anonymously.'' The committee consists of senior managers in CDER, a
senior official from the Center for Biologics Evaluation and Research,
and the FDA Chief Mediator and Ombudsman. The committee now meets
semiannually. The committee last met in November 1995.
Clinical holds to be reviewed will be chosen randomly. In addition,
the committee will review holds proposed for review by drug sponsors.
In general, a drug sponsor should consider requesting review when it
disagrees with the agency's scientific or procedural basis for the
decision.
Requests for committee review of a clinical hold should be
submitted to the FDA Chief Mediator and Ombudsman, who is responsible
for selecting clinical holds for review. The committee and CDER staff,
with the exception of the FDA Chief Mediator and Ombudsman, are never
advised, either in the review process or thereafter, which of the holds
were randomly chosen and which were submitted by sponsors. The
committee will evaluate the selected clinical holds for scientific
content and consistency with agency regulations and CDER policy.
The meetings of the review committee are closed to the public
because committee discussions deal with confidential commercial
information. Summaries of the committee deliberations, excluding
confidential commercial information, will be available through the
Freedom of Information Staff (HFI-35), Food and Drug Administration,
5600 Fishers Lane, Rockville, MD 20857. If the status of a clinical
hold changes following the committee's review, the appropriate division
will notify the sponsor.
FDA invites drug companies to submit to the FDA Chief Mediator and
Ombudsman the name and IND number of any investigational new drug trial
that was placed on clinical hold during the past 12 months that they
want the committee to review at its June meeting. Submissions should be
made by May 3, 1996, to Amanda B. Pedersen, FDA Chief Mediator and
Ombudsman (address above).
Dated: March 28, 1996.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 96-8165 Filed 4-2-96; 8:45 am]
BILLING CODE 4160-01-F
