15934 Federal Register / Vol. 60, No. 59 / Tuesday, March 28, 1995 / Notices

ADDRESSES: Submit written requests for

single copies of the guideline entitled,

‘‘Protocol Development Guideline for

Clinical Effectiveness and Target

Animal Safety Trials’’ to the

Communications and Education Branch

(HFV–12), Center for Veterinary

Medicine, Food and Drug

Administration, 7500 Standish Pl.,

Rockville, MD 20855, 301–594–1755.

Send two self-addressed adhesive labels

to assist that office in processing your

requests. Submit written comments on

the guideline to the Dockets

Management Branch (HFA–305), Food

and Drug Administration, rm. 1–23,

12420 Parklawn Dr., Rockville, MD

20857. Requests and comments should

be identified with the docket number

found in brackets in the heading of this

document. A copy of the guideline and

received comments are available for

public examination in the Dockets

Management Branch between 9 a.m. and

4 p.m., Monday through Friday.

FOR FURTHER INFORMATION CONTACT:

Larry Ventura, Center for Veterinary

Medicine (HFV–130), Food and Drug

Administration, 7500 Standish Pl.,

Rockville, MD 20855, 301–594–1647.

SUPPLEMENTARY INFORMATION: FDA is

announcing the availability of the

guideline entitled, ‘‘Protocol

Development Guideline for Clinical

Effectiveness and Target Animal Safety

Trials’’ prepared by CVM. The guideline

is intended to be used by clinical

investigators, study monitors, and

sponsors, when designing investigations

of effectiveness and target animal safety

for animal drug approval and may be

used when submitting the final reports

of these trials. This guideline was

written in response to a request by the

animal health industry for guidance on

facilitating protocol development and

expediting CVM’s review of the

submitted protocols, and it should help

sponsors to include all essential

components of the study in the protocol.

More uniform reports should allow a

systematic, orderly review of the data by

CVM. The goals of the protocol

development guideline are to:

1. Suggest a uniform system for

writing study protocols,

2. Provide a reference of essential

items that should be considered for

inclusion in a study protocol,

3. Facilitate the development of

complete study protocol(s) by the

author(s),

4. Design more user friendly protocols

for investigator(s),

5. Enable FDA reviewers to evaluate

study protocols more quickly and

convey their comments in terms more

easily understood by the sponsor, and

6. Reduce the number of essential

revisions of study protocols.

The guideline offers a complete

outline of the components necessary for

a well-designed study so that CVM and

industry have a common reference

point. This uniform approach will

facilitate the drafting of study reports by

the sponsor and their subsequent review

by CVM. The contents of this guideline

are neither all inclusive nor will all

items listed be applicable to all study

protocols. It is the responsibility of the

sponsor to ensure that the essential

components of a study are included in

their protocol. Guidelines state

procedures or practices that may be

useful to the persons to whom they are

directed, but are not legal requirements.

A person may follow the guideline or

may choose to follow alternate

procedures or practices. If a person

chooses to use alternate procedures or

practices, that person may wish to

discuss the matter further with the

agency to prevent an expenditure of

money and effort on activities that may

later be determined to be unacceptable

to FDA.

Guidelines are generally issued under

§§ 10.85(a) and 10.90(b)(21 CFR 10.85(a)

and 10.90(b)). The agency is now in the

process of revising §§ 10.85(a) and

10.90(b). Therefore, this guideline is not

being issued under the authority of

§§ 10.85(a) and 10.90(b). A guideline

does not bind the agency, and it does

not create or confer any rights,

privileges, or benefits for or on any

person. When a guideline states a

requirement imposed by statute or

regulation, however, the requirement is

law and its force and effect are not

changed in any way by virtue of its

inclusion in the guideline.

Interested persons may, at any time,

submit written comments on the

guideline to the Dockets Management

Branch (address above). FDA will

consider these comments in

determining whether further

amendments to, or revisions of, the

document are warranted. Two copies of

any comments should be submitted,

except that individuals may submit one

copy, identified with the docket number

found in brackets in the heading of this

document. The guideline and received

comments may be seen in the Dockets

Management Branch between 9 a.m. and

4 p.m., Monday through Friday, at the

Dockets Management Branch.

Dated: March 16, 1995.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 95–7513 Filed 3–27–95; 8:45 am]

BILLING CODE 4160–01–F

Industry and Consumer Exchange

Meeting Concerning FDA and APHIS

Activities on a Potential Agreement

With the European Union Related to

Human and Animal Drug and

Biological Product Information; Notice

of Public Meeting

AGENCIES: Food and Drug

Administration, HHS.

ACTION: Notice of public meeting.

SUMMARY: The Food and Drug

Administration (FDA) and Animal and

Plant Health Inspection Service (APHIS)

are cosponsoring a public meeting with

all persons interested in a potential

agreement with the European Union

that would facilitate the harmonization

of good manufacturing practices

(GMP’s) and quality controls for human

and animal drug and biological products

and associated compliance and

enforcement activities, and provide for

the exchange and use of such

information by the respective regulatory

authorities. Such an agreement would

enhance the goals of harmonizing the

monitoring and enforcement standards

of the GMP’s and would facilitate

international trade.

DATES: The industry and consumer

exchange meeting will be held on

Friday, March 31, 1995, 9 a.m. to 12 m.

ADDRESSES: The industry and consumer

exchange meeting will be held at the

Hubert H. Humphrey Bldg., Humphrey

Auditorium, 200 Independence Ave.

SW., Washington, DC.

FOR FURTHER INFORMATION CONTACT:

Walter M. Batts, Office of Health Affairs

(HFY–50), Food and Drug

Administration, 5600 Fishers Lane,

Rockville, MD 20857, 301–443–4480

(Fax 301–443–0235).

Those persons interested in attending

this meeting should Fax their

registration, including name, firm, or

organization name, address, and

telephone number to Nathaniel L.

Geary, Office of External Affairs, Food

and Drug Administration (301–443–

5153) or telephone 301–443–6776.

There is no registration fee, but advance

registration is requested. Additionally, if

there are any individuals that wish to

make a presentation at this meeting,

advance notice is required.

SUPPLEMENTARY INFORMATION: The

purpose of the public meeting is to

provide information concerning FDA

and APHIS activities with the European

Union related to human and animal

drug and biological product GMP’s and

quality controls, as well as to provide an

opportunity to hear and address

concerns from persons involved in these

industries and persons representing

consumer and other interests.
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