[Federal Register Volume 60, Number 188 (Thursday, September 28, 1995)]
[Notices]
[Pages 50207-50208]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-24072]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
Investigational New Biological Product Trials; 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 Biologics Evaluation and Research (CBER) has placed
on certain investigational new biological product trials. CBER held its
first clinical hold review committee meeting on May 17, 1995. FDA is
inviting any interested biological company to use this confidential
mechanism to submit to the committee for its review the name and number
of any investigational new biological products trial placed on clinical
hold during the past 12 months that the company wants the committee to
review.
DATES: The meeting will be held in October 1995. Biological companies
may submit review requests for the October meeting before October 10,
1995.
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: Joy A. Cavagnaro, Center for Biologics
Evaluation and Research (HFM-2), Food and Drug Administration, 1401
Rockville Pike, Rockville, MD 20852-1448, 301-827-0379.
SUPPLEMENTARY INFORMATION: FDA regulations in part 312 (21 CFR part
312) provide procedures that govern the use of investigational new
drugs and biologics 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 product. The IND must contain the study protocol, a
summary of human and animal experience with the product, and
information on the product's characterization, chemistry and
pharmacology. FDA reviews an IND to help ensure the safety and rights
of human subjects of research and to help ensure that the quality of
any scientific evaluation of a drug is adequate to permit an evaluation
of the product's efficacy and safety.
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 or biologic 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 or biologic as part of that study. When an ongoing
study is placed on clinical hold, no new subjects may be recruited to
the study and placed on the investigational drug or biologic, and
patients already in the study should stop receiving therapy involving
the investigational drug or biologic unless FDA specifically permits
it.
FDA regulations in 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 clinical 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.
A clinical hold is ordered by or on behalf of the director of the
division that is responsible for review of the IND. The order
identifies the studies under the IND to which the clinical hold applies
and explains the basis for the action. The clinical hold order may be
made by telephone or other means of rapid communication, or in writing.
Irrespective of the 30-day time limit permitted by Sec. 312.42(d), CBER
policy provides that within 15 days of the notification of the clinical
hold by telephone or other method of rapid communication, the sponsor
will be provided with a written explanation of the basis for the
clinical hold. In addition to providing a statement of reasons, this
ensures that the clinical hold is recorded in CBER'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 without notification, 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 in Sec. 312.48 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, the sponsor may request a meeting with
the review staff and management to discuss the clinical 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 for Drug Evaluation and Research's (CDER's) practices in
imposing clinical holds. First, CDER completed a centerwide review of
clinical holds recorded in their management information system. While
some differences in practice and procedure were discerned among
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divisions in CDER, it appeared that the procedures specified in the
regulations were, in general, being followed, and that clinical holds
were scientifically supportable. Second, FDA established a committee in
CDER to review selected clinical holds for scientific and procedural
quality. The committee held pilot meetings in 1991 and met quarterly
through 1992. The committee currently meets semiannually as a regular
program. The committee last met in June 1995.
CBER has now begun a similar process to evaluate the consistency
and fairness of CBER's practices in imposing clinical holds. CBER is
beginning by instituting a review committee to review recent clinical
holds. CBER also plans to conduct further quality assurance oversight
of the IND process. CBER held its first clinical hold review committee
meeting on May 17, 1995, and intends to make the clinical hold review
process 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 clinical hold to
have that clinical hold considered ``anonymously.'' The committee
consists of senior managers of CBER, a senior official from CDER, and
FDA's Chief Mediator and Ombudsman.
Clinical holds to be reviewed will be chosen randomly. In addition,
the committee will review clinical holds proposed for review by
biological product sponsors. In general, a biological product 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 FDA's Chief Mediator and Ombudsman, who is responsible for
selecting clinical holds for review. The committee and CBER staff, with
the exception of the FDA Chief Mediator and Ombudsman, are never
advised, either in the review process or thereafter, which of the
clinical 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 CBER
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 from the FDA
Chief Mediator and Ombudsman. If the status of a clinical hold changes
following the committee's review, the appropriate division will notify
the sponsor.
FDA invites biological product companies to submit to the FDA Chief
Mediator and Ombudsman the name and IND number of any investigational
new biological product trial that was placed on clinical hold during
the past 12 months that they want the committee to review at its
October 1995 meeting. Submissions should be made by October 10, 1995,
to Amanda B. Pederson, FDA Chief Mediator and Ombudsman (address
above).
Dated: September 20, 1995.
William K. Hubbard,
Acting Deputy Commissioner for Policy.
[FR Doc. 95-24072 Filed 9-27-95; 8:45 am]
BILLING CODE 4160-01-F
