[Federal Register Volume 63, Number 236 (Wednesday, December 9, 1998)]
[Notices]
[Pages 67898-67899]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-32643]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration


Investigational 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.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing the 1999 
meetings 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 biological product trials. 
FDA is inviting any interested biological product company to use this 
confidential mechanism to submit to the committee for its review the 
name and number of any investigational biological product trial placed 
on clinical hold during the past 12 months that the company wants the 
committee to review.

DATES: The meetings will be held on February 9, 1999; May 11, 1999; 
August 10, 1999; and November 9, 1999. Biological product companies may 
submit review requests for the February meeting by January 5, 1999; for 
the May meeting by March 30, 1999; for the August meeting by June 29, 
1999; and for the November meeting by September 28, 1999.

ADDRESSES: Submit clinical hold review requests to Amanda Bryce Norton, 
FDA Chief Mediator and Ombudsman, Office of the Commissioner (HF-7), 
Food and Drug Administration, 5600 Fishers Lane, rm. 14-105, Rockville, 
MD 20857, 301-827-3390.

FOR FURTHER INFORMATION CONTACT: Stephen M. Ripley, Center for 
Biologics Evaluation and Research (HFM-17), Food and Drug 
Administration, 1401 Rockville Pike, Rockville, MD 20852-1448, 301-827-
6210.

SUPPLEMENTARY INFORMATION: FDA's regulations in part 312 (21 CFR part 
312) provide procedures that govern the use of investigational new 
drugs and biologics in human subjects. 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 order 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. Section 312.42 describes the grounds for ordering a 
clinical hold.
     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 ordered on one or more of the investigations 
covered by an investigational new drug application (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.
     When FDA concludes that there is a deficiency in a proposed or 
ongoing clinical trial that may be grounds for ordering a clinical 
hold, ordinarily FDA will attempt to resolve the matter through 
informal discussions with the sponsor. If that attempt is unsuccessful, 
a clinical hold may be ordered by or on behalf of the director of the 
division that is responsible for the review of the IND.
     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.
     CBER began a process to evaluate the consistency and fairness of 
practices in ordering clinical holds by instituting an oversight 
committee to review clinical holds (see 61 FR 1033, January 11, 1996). 
CBER held its first clinical hold review committee meeting on May 17,

[[Page 67899]]

1995, and plans to conduct further quality assurance oversight of the 
IND process. 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 the Center for Drug Evaluation and 
Research, and the FDA Chief Mediator and Ombudsman.
     Clinical holds to be reviewed will be chosen randomly. In 
addition, the committee will review some of the clinical holds proposed 
for review by biological product sponsors. In general, a biological 
product sponsor should consider requesting review when it disagrees 
with FDA'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 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 FDA regulations and CBER 
policy.
     The meetings of the oversight committee are closed to the public 
because committee discussions deal with confidential commercial 
information. Summaries of the committee deliberations, excluding 
confidential commercial information, may be requested in writing from 
the Freedom of Information Office (HFI-35), Food and Drug 
Administration, 5600 Fishers Lane, rm. 12A-16, Rockville, MD 20857, 
approximately 15 working days after the meeting, at a cost of 10 cents 
per page. If the status of a clinical hold changes following the 
committee's review, the appropriate division will notify the sponsor.
     For each meeting, FDA invites biological product companies to 
submit to the FDA Chief Mediator and Ombudsman the name and IND number 
of any investigational biological product trial that was placed on 
clinical hold during the past 12 months that they want the committee to 
review. Submissions should be made by January 5, 1999, for the February 
meeting; by March 30, 1999, for the May meeting; by June 29, 1999, for 
the August meeting; and by September 28, 1999, for the November meeting 
to Amanda Bryce Norton, FDA Chief Mediator and Ombudsman (address 
above).

    Dated: December 1, 1998.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 98-32643 Filed 12-8-98; 8:45 am]
BILLING CODE 4160-01-F