12832 Federal Register / Vol. 62, No. 52 / Tuesday, March 18, 1997 / Notices

regulatory review period may count

toward the actual amount of extension

that the Commissioner of Patents and

Trademarks may award (for example,

half the testing phase must be

subtracted as well as any time that may

have occurred before the patent was

issued), FDA’s determination of the

length of a regulatory review period for

an animal drug product will include all

of the testing phase and approval phase

as specified in 35 U.S.C. 156(g)(4)(B).

FDA recently approved for marketing

the animal drug product BAYTRIL

(enrofloxacin). BAYTRIL is indicated

for chickens to control mortality

associated with Escherichia coli

susceptible to enrofloxacin, and for

turkeys to control mortality associated

with E. coli and Pasturella multocida

(fowl cholera) susceptible to

enrofloxacin. Subsequent to this

approval, the Patent and Trademark

Office received a patent term restoration

application for BAYTRIL (U.S. Patent

No. 4,670,444) from Bayer

Aktiengesellschaft and requested FDA’s

assistance in determining the patent’s

eligibility for patent term restoration. In

a letter dated January 21, 1997, FDA

advised the Patent and Trademark

Office that this animal drug product had

undergone a regulatory review period

and that the approval of BAYTRIL

represented the first commercial

marketing of the product. Shortly

thereafter, the Patent and Trademark

Office requested that FDA determine the

product’s regulatory review period.

FDA has determined that the

applicable regulatory review period for

BAYTRIL is 4,334 days. Of this time,

648 days occurred during the testing

phase of the regulatory review period,

while 3,686 days occurred during the

approval phase. These periods of time

were derived from the following dates:

1. The date an exemption under

section 512(j) of the Federal Food, Drug,

and Cosmetic Act became effective:

November 24, 1984. The applicant

claims November 20, 1984, as the date

the investigational new animal drug

application (INAD) became effective.

However, FDA records indicate that the

date of FDA’s official acknowledgment

letter assigning a number to the INAD

was November 24, 1984, which is

considered to be the effective date for

the INAD.

2. The date the application was

initially submitted with respect to the

human drug product under section

512(b) of the Federal Food, Drug, and

Cosmetic Act: September 2, 1986. The

applicant claims August 26, 1986, as the

date the new animal drug application

(NADA) for BAYTRIL (NADA 140–

828) was initially submitted. However,

a review of FDA records reveals that the

date of FDA’s official acknowledgment

letter assigning a number to the NADA

was September 2, 1986, which is

considered to be the initially submitted

date for the NADA.

3. The date the animal drug was

approved: October 4, 1996. FDA has

verified the applicant’s claim that

NADA 140–828 was approved on

October 4, 1996.

This determination of the regulatory

review period establishes the maximum

potential length of a patent extension.

However, the U.S. Patent and

Trademark Office applies several

statutory limitations in its calculations

of the actual period for patent extension.

In its application for patent extension,

this applicant seeks 1,827 days of patent

term extension.

Anyone with knowledge that any of

the dates as published is incorrect may,

on or before May 19, 1997, submit to the

Dockets Management Branch (address

above) written comments and ask for a

redetermination. Furthermore, any

interested person may petition FDA, on

or before September 15, 1997, for a

determination regarding whether the

applicant for extension acted with due

diligence during the regulatory review

period. To meet its burden, the petition

must contain sufficient facts to merit an

FDA investigation. (See H. Rept. 857,

part 1, 98th Cong., 2d sess., pp. 41–42,

1984.) Petitions should be in the format

specified in 21 CFR 10.30.

Comments and petitions should be

submitted to the Dockets Management

Branch (address above) in three copies

(except that individuals may submit

single copies) and identified with the

docket number found in brackets in the

heading of this document. Comments

and petitions may be seen in the

Dockets Management Branch between 9

a.m. and 4 p.m., Monday through

Friday.

Dated: March 6, 1997.

Stuart L. Nightingale,

Associate Commissioner for Health Affairs.

[FR Doc. 97–6719 Filed 3–17–97; 8:45 am]

BILLING CODE 4160–01–F

[Docket No. 97D–0024]

Medical Devices; Immunotoxicity

Testing Framework; Draft Guidance;

Availability

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing the

availability of a draft guidance entitled

‘‘Immunotoxicity Testing Framework.’’

This guidance will provide reviewers

and manufacturers with a coherent

strategy for assessing whether testing for

potential adverse effects involving

medical devices or constituent materials

and the immune system is needed. The

draft guidance will also aid in

developing a systematic approach to

such testing.

DATES: Written comments by June 16,

1997.

ADDRESSES: Submit written requests for

single copies of the draft guidance

entitled ‘‘Immunotoxicity Testing

Framework’’ to the Division of Small

Manufacturers Assistance, Center for

Devices and Radiological Health (HFZ–

220), Food and Drug Administration,

5600 Fishers Lane, Rockville, MD

20857, 301–443–0806 (toll free outside

of MD 1–800–638–2041). Send two self

addressed adhesive labels to assist that

office in processing your requests. The

draft guidance is also available via the

World Wide Web at http://

www.fda.gov/cdrh/draftgui.html. A text

only version is also available from a

VT–100 compatible terminal via the

FDA bulletin board by dialing 800–

222–0185 (terminal settings are 8/1/N).

Submit written comments on the draft

guidance to the Dockets Management

Branch (HFA–305), Food and Drug

Administration, 12420 Parklawn Dr.,

rm. 1–23, 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 draft guidance and received

comments are available for public

examination in the Dockets

Management Branch (address above)

between 9 a.m. and 4 p.m., Monday

through Friday.

FOR FURTHER INFORMATION CONTACT: John

J. Langone, Center for Devices and

Radiological Health (HFZ–113), Food

and Drug Administration, 12709

Twinbrook Pkwy., Rockville, MD 20852,

301–443–7132.

SUPPLEMENTARY INFORMATION:

I. Background

In May 1995, FDA adopted the

General Program Memorandum G95–1,

an FDA-modified version of

International Standard ISO–10993,

entitled ‘‘Biological Evaluation of

Medical Devices-Part 1: Evaluation and

Testing.’’ It was pointed out that in

addition to the general guidance for

toxicity testing contained in that

document, additional guidance might be

needed for evaluation of specific organ

or system toxicity. As a result, the Office

of Device Evaluation, Center for Devices

and Radiological Health, developed the
Federal Register / Vol. 62, No. 52 / Tuesday, March 18, 1997 / Notices 12833

draft ‘‘Immunotoxicity Testing

Framework’’ to deal specifically with

testing for adverse effects of medical

devices or constituent materials on the

immune system. The draft guidance will

provide medical device manufacturers

with FDA’s current thinking on

immunotoxicity testing, and it will help

to ensure a consistent and scientifically

sound approach to the overall

evaluation of product safety.

The draft guidance also contains a

flow chart to determine if

immunotoxicity testing is

recommended, and three tables that lead

sequentially from potential

immunological effects, to potential

responses commonly associated with

those effects, to examples of testing that

might be considered as part of the

overall safety evaluation of finished

devices or constituent materials.

In the past, guidances generally have

been issued under § 10.90(b) (21 CFR

10.90(b)), which provides for the use of

guidances to state procedures or

standards of general applicability that

are not legal requirements, but that are

acceptable to FDA. This guidance

represents FDA’s current thinking on

the issue of immunotoxicity testing for

medical devices and constituent

materials. It does not create or confer

any rights for or on any person and does

not operate to bind FDA or the public.

An alternative approach may be used if

such approach satisfies the

requirements of the applicable statute,

regulations, or both.

II. Request for Comments

Interested persons may, on or before

June 16, 1997, submit to the Dockets

Management Branch (address above)

written comments regarding the draft

guidance. Two copies of any comments

are to be submitted, except that

individuals may submit one copy.

Comments are to be identified with the

docket number found in brackets in the

heading of this document. The draft

guidance and received comments may

be seen in the office above between 9

a.m. and 4 p.m., Monday through

Friday.

Received comments will be

considered in determining whether to

amend the current draft guidance

document.

Dated: March 6, 1997.

Joseph A. Levitt,

Deputy Director for Regulations Policy, Center

for Devices and Radiological Health.

[FR Doc. 97–6715 Filed 3–17–97; 8:45 am]

BILLING CODE 4160–01–F

Investigational Biological Product

Trials; Procedure to Monitor Clinical

Hold Process; Meeting of Oversight

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 its clinical hold oversight

committee, which reviews the clinical

hold orders 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 meeting will be held on May

13, 1997. Biological product companies

may submit review requests for the May

meeting by April 4, 1997.

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: Joy

A. Cavagnaro, Center for Biologics

Evaluation and Research (HFM–5), 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. 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 § 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 a

review committee to review clinical

holds (see 61 FR 1033, January 11,

1996). CBER held its first clinical hold

oversight committee meeting on May 17,

1995, and plans to conduct further

quality assurance oversight of the IND

process. The committee last met in

February 1997. 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,