Federal Register / Vol. 60, No. 59 / Tuesday, March 28, 1995 / Notices 15935

FDA and APHIS have been

participating in bilateral Mutual

Recognition Agreement talks. These

talks are being led by the Office of the

U.S. Trade Representative and the

Department of Commerce and by

representatives of the European Union.

FDA and APHIS will meet with

representatives from the European

Union and its Member States from April

3 to April 5, 1995, in Brussels, Belgium

to exchange information on their

respective programs. During the

Brussels meeting, U.S. industry will

have the opportunity to present its

experience with U.S. and European

GMP and quality control programs.

Dated: March 24, 1995.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 95–7740 Filed 3–24–95; 3:14 pm]

BILLING CODE 4160–01–F

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.

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

October 1994. 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 will be held in June

1995. Drug companies may submit

review requests for the June meeting

before April 27, 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,

301–443–1306.

FOR FURTHER INFORMATION CONTACT:

Deborah A. Wolf, Center for Drug

Evaluation and Research (HFD–362),

Food and Drug Administration, 7500

Standish Pl., Rockville, MD 20855, 301–

594–1046.

SUPPLEMENTARY INFORMATION: FDA

regulations at 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 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

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 21 CFR 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 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 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 30 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

30 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 21 CFR 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, 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. First, CDER

completed a center-wide review of

clinical holds recorded in the

management information system. While

some differences in practice and

procedure were discerned among

divisions, it appeared that the

procedures specified in the regulations

were, in general, being followed, and

that 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
15936 Federal Register / Vol. 60, No. 59 / Tuesday, March 28, 1995 / Notices

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 matter 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 FDA’s Chief Mediator and

Ombudsman. The committee now meets

semiannually. The committee last met

in October 1994.

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

FDA’s Chief Mediator and Ombudsman,

who is responsible for selecting clinical

holds for review. The committee and

CDER staff, with the exception of the

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 from the 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 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 April

27, 1995, to Amanda B. Pedersen, FDA

Chief Mediator and Ombudsman

(address above).

Dated: March 18, 1995.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 95–7575 Filed 3–27–95; 8:45 am]

BILLING CODE 4160–01–F

National Institutes of Health

Division of Research Grants; Notice of

Closed Meetings

Pursuant to Section 10(d) of the

Federal Advisory Committee Act, as

amended (5 U.S.C. Appendix 2), notice

is hereby given of the following Division

of Research Grants Special Emphasis

Panel (SEP) meetings:

Purpose/Agenda

To review individual grant applications.

Name of SEP: Behavioral and

Neurosciences.

Date: April 12, 1995.

Time: 2 p.m.

Place: NIH, Westwood Building, Room

303, Telephone Conference.

Contact Person: Dr. Joe Marwah, Scientific

Review Administrator, 5333 Westbard Ave.,

Room 303, Bethesda, MD 20892, (301) 594–

7158.

Name of SEP: Biological and Physiological

Sciences.

Date: April 18, 1995.

Time: 12:30 p.m.

Place: NIH, Westwood Building, Room

417B, Telephone Conference.

Contact Person: Dr. Gerald Greenhouse,

Scientific Review Admin., 5333 Westbard

Ave., Room 417B, Bethesda, MD 20892, (301)

594–7385.

Name of SEP: Multidisciplinary Sciences.

Date: April 26, 1995.

Time: 10 a.m.

Place: NIH, Westwood Building, Room

2A15, Telephone Conference.

Contact Person: Dr. Houston Baker,

Scientific Review Administrator, 5333

Westbard Ave., Room 2A15, Bethesda, MD

20892, (301) 594–7374.

The meetings will be closed in accordance

with the provisions set forth in secs.

552b(c)(4) and 552b(c)(6), Title 5, U.S.C.

Applications and/or proposals and the

discussions could reveal confidential trade

secrets or commercial property such as

patentable material and personal information

concerning individuals associated with the

applications and/or proposals, the disclosure

of which would constitute a clearly

unwarranted invasion of personal privacy.

This notice is being published less than 15

days prior to the meeting due to the urgent

need to meet timing limitations imposed by

the grant review cycle.

(Catalog of Federal Domestic Assistance

Program Nos. 93.306, 93.333, 93.337, 93.393–

93.396, 93.837–93.844, 93.846–93.878,

83.892, 93.893, National Institutes of Health,

HHS)

Dated: March 21, 1995.

Susan K. Feldman,

Committee Management Officer, NIH.

[FR Doc. 95–7515 Filed 3–27–95; 8:45 am]

BILLING CODE 4140–01–M

Public Health Service

National Institutes of Health; Statement

of Organization, Functions, and

Delegations of Authority

Part H, Chapter HN (National

Institutes of Health) of the Statement of

Organization, Functions, and

Delegations of Authority for the

Department of Health and Human

Services (40 FR 22859, May 27, 1975, as

amended most recently at 59 FR 60997–

8, November 29, 1994) is amended to

reflect the reorganization of the Office of

the Director, National Institute of

Allergy and Infectious Diseases (OD/

NIAID). The reorganization consists of

the following: (1) Retitle the (a) Office

of Administrative Management

(HNM17) to the Office of Administrative

Services (HNM17); (b) Financial

Management and Information Systems

Branch (HNM173) to the Office of

Financial Management (HNMI2); and (c)

Personnel Management Branch

(HNMI74) to the Office of Human

Resources Management (HNM14); (2)

establish the Office of Technology

Information Systems (HNM15); and (3)

transfer the functions of the Office of

Tropical Medicine and International

Research (OTMIR) (HNM19) to the

Division of Microbiology and Infectious

Diseases (HNM5) and abolish the

OTMIR. This reorganization will enable

the NIAID to better fulfill its mission by

restructuring the OD/NIAID to better

integrate related program areas and

streamline operations.

Section HN–B, Organization and

Functions is amended as follow: (1)

Under the heading Office of the Director

(HNM1), National Institute of Allergy

and Infectious Diseases (HNM), insert

the following:

Office of Financial Management

(HNM12). (1) Serves as principal advisor

to the Institute Director, Deputy Director

for Management and Operations, and

Division Directors in the financial

management aspects of the planning,

formulation, execution, and evaluation

of the Institute’s research grant, training,

and intramural research programs; (2)

collaborates with program planning staff

in the development and coordination of

the Institute programs with the budget

process; (3) formulates and monitors the

Institute’s financial management

program and establishes a system of

effective control of funds utilized