24556 Federal Register / Vol. 63, No. 85 / Monday, May 4, 1998 / Notices

VII. Submission Requirements

The original and five copies of the

completed Grant Application Form PHS

398 (Rev. 5/95) or the original and two

copies of the PHS 5161 (Rev. 7/92) for

State and local governments, with

copies of the appendices for each of the

copies, should be delivered to Robert L.

Robins (address above). State and local

governments may choose to use the PHS

398 application form in lieu of the PHS

5161. The application receipt date is

June 18, 1998. If the receipt date falls on

a weekend, it will be extended to

Monday; if the date falls on a holiday,

it will be extended to the following

workday. No supplemental or

addendum material will be accepted

after the receipt date.

The outside of the mailing package

and item 2 of the application face page

should be labeled ‘‘Response to RFA–

FDA–CFSAN–98–1.’’

VIII. Method of Application

A. Submission Instructions

Applications will be accepted during

working hours, 8 a.m. to 4:30 p.m.,

Monday through Friday, on or before

the established receipt date.

Applications will be considered

received on time if sent or mailed on or

before the receipt date as evidenced by

a legible U.S. Postal Service dated

postmark or a legible date receipt from

a commercial carrier, unless they arrive

too late for orderly processing. Private

metered postmarks shall not be

acceptable as proof of timely mailing.

Applications not received on time will

not be considered for review and will be

returned to the applicant. Applicants

should note that the U.S. Postal Service

does not uniformly provide dated

postmarks. Before relying on this

method, applicants should check with

their local post office.

Do not send applications to the Center

for Scientific Research (CSR), NIH. Any

application that is sent to NIH, that is

then forwarded to FDA and not received

in time for orderly processing, will be

deemed unresponsive and returned to

the applicant. Instructions for

completing the application forms can be

found on the NIH home page on the

Internet (address: http://www.nih.gov/

grants/funding/phs398/phs398.html; the

forms can be found at http://

www.nih.gov/grants/funding/phs398/

formsltoc.html). However, as noted

previously, applications are not to be

mailed to NIH. Applications must be

submitted via mail delivery as stated

previously. FDA is unable to receive

applications via Internet.

B. Format for Application

Submission of the application must be

on Grant Application Form PHS 398

(Rev. 5/95). All ‘‘General Instructions’’

and ‘‘Specific Instructions’’ in the

application kit should be followed with

the exception of the receipt dates and

the mailing label address. Applicants

are also advised that FDA does not

adhere to the page limitations or the

type size and line spacing requirements

imposed by NIH on its applications. Do

not send applications to CSR, NIH.

Applications from State and local

governments may be submitted on Form

PHS 5161 (Rev. 7/92) or Form PHS 398

(Rev. 5/95).

The face page of the application

should reflect RFA’s number RFA–

FDA–CFSAN–98–1.

Data included in the application, if

restricted with the legend specified

below, may be entitled to confidential

treatment as trade secret or confidential

commercial information within the

meaning of the Freedom of Information

Act (FOIA) (5 U.S.C. 552(b)(4)) and

FDA’s implementing regulations (21

CFR 20.61).

Information collection requirements

requested on Form PHS 398 and the

instructions have been submitted by

PHS to the Office of Management and

Budget (OMB) and were approved and

assigned OMB control number 0925–

0001.

C. Legend

Unless disclosure is required by FOIA

as amended (5 U.S.C. 552), as

determined by the freedom of

information officials of DHHS or by a

court, data contained in the portions of

this application which have been

specifically identified by page number,

paragraph, etc., by the applicant as

containing restricted and/or proprietary

information shall not be used or

disclosed except for evaluation

purposes.

Dated: April 3, 1998.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 98–11743 Filed 5–1–98; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 96P–0090]

Determination That Testosterone

Propionate 2% Ointment Was Not

Withdrawn From Sale for Reasons of

Safety or Effectiveness; Amendment

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is amending a

previous determination regarding the

fact that testosterone propionate 2%

ointment (Perandren Ointment) was not

withdrawn from sale for reasons of

safety or effectiveness. FDA has

determined that it is not appropriate at

this time to accept abbreviated new drug

applications (ANDA’s) for testosterone

propionate 2% ointment.

FOR FURTHER INFORMATION CONTACT:

David T. Read, Center for Drug

Evaluation and Research (HFD–7), Food

and Drug Administration, 5600 Fishers

Lane, Rockville, MD 20855, 301–594–

2041.

SUPPLEMENTARY INFORMATION: ANDA

sponsors must, with certain exceptions,

show that the drug for which they are

seeking approval contains the same

active ingredient in the same strength

and dosage form as a ‘‘listed drug.’’ A

listed drug is one that has an effective

approval, either under section 505(c) of

the Federal Food, Drug, and Cosmetic

Act (the act) (21 U.S.C. 355(c)) for safety

and effectiveness or under section 505(j)

of the act, which has not been

withdrawn for reasons of safety or

effectiveness (21 CFR 314.3, see also 21

U.S.C. 355(j)(6)). Neither at the time of

ANDA submission nor at the time of

ANDA approval is it essential that a

listed drug be currently marketed.

FDA’s ‘‘Approved Drug Products with

Therapeutic Equivalence Evaluations’’

(popularly referred to as the ‘‘Orange

Book’’) contains the official register of

listed drugs, and a drug is removed from

this register in either of two ways. First,

a listed drug is removed if the agency

withdraws or suspends approval of the

drug’s new drug application (NDA) or

ANDA for reasons of safety or

effectiveness. Second, in the case of a

listed drug that was discontinued from

sale but did not have its approval

withdrawn or had its approval

withdrawn for reasons other than safety

or effectiveness, the drug is removed if

FDA determines that it was

discontinued from sale for reasons of
Federal Register / Vol. 63, No. 85 / Monday, May 4, 1998 / Notices 24557

safety or effectiveness (21 CFR 314.162).

FDA may be called upon to make such

a finding when petitioned by a potential

ANDA applicant (§ 314.161 (21 CFR

314.161)).

On March 19, 1996, Richard Hamer

Associates, Inc., submitted a citizen

petition (Docket No. 96P–0090/CP1),

under 21 CFR 10.25(a), 10.30, and

314.161(b), requesting that the agency

determine whether testosterone

propionate 2% ointment was

discontinued from sale for reasons of

safety or effectiveness and, if the agency

determines that the drug was not

discontinued from sale for reasons of

safety or effectiveness, to relist the drug

in the Orange Book. Testosterone

propionate 2% ointment (Perandren

Ointment) was the subject of NDA 0–

0499 held by Ciba Pharmaceutical Co.

This NDA was submitted to FDA on

January 24, 1939, and under the

procedures of the act at that time, the

NDA ‘‘became effective’’ (the statutory

equivalent of ‘‘approval’’ under the act

as it appears now) on March 7, 1939, 23

years before passage of the 1962

amendments to the act. The significance

of these dates is that from 1938 through

1962, FDA reviewed drugs only to pass

upon their safety. The 1962

amendments to the act (Pub. L. 87–781

(October 10, 1962)) required FDA to

review drugs not only for safety, but

also for effectiveness. The effectiveness

standard applied both prospectively to

new drugs entering the market and

retrospectively to drugs whose

applications became effective between

1938 and 1962.

In the Federal Register of September

23, 1971 (36 FR 18885), FDA withdrew

approval of NDA 0–0499 for Perandren

Ointment based on the applicant’s

failure to submit required annual

reports (section 505(e) of the act and 21

CFR 314.80 and 314.81).

In the Federal Register of December 6,

1996 (61 FR 64754), FDA in responding

to the Hamer petition, announced its

determination that testosterone

propionate 2% ointment (Perandren

Ointment) was not discontinued from

sale for reasons of safety or

effectiveness. In that same notice, FDA

announced that this determination will

allow FDA to approve ANDA’s for

testosterone propionate 2% ointment.

Upon further investigation, however,

FDA has determined that NDA 0–0499

for Perandren Ointment was never

approved as effective for any of its

labeled indications and, therefore, was

never a ‘‘listed drug’’ such that it could

be ‘‘relisted.’’ As discussed previously,

for a drug approved under section

505(c) of the act to be a ‘‘listed drug,’’

it must have been approved for

effectiveness as well as safety. No

information was ever submitted on the

effectiveness of this product prior to its

withdrawal of approval in 1971. So,

while it remains true that NDA 0–0499

was not discontinued from sale for

reasons of safety or effectiveness, it is

not appropriate at this time to accept

ANDA’s for testosterone propionate 2%

ointment.

The Federal Register notice of

December 6, 1996, is amended insofar as

it is inconsistent with the findings of

this notice.

Dated: April 27, 1998.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 98–11684 Filed 5–1–98; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 96E–0189]

Determination of Regulatory Review

Period for Purposes of Patent

Extension; LIPOSORBER LA–15

System

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) has determined

the regulatory review period for

LIPOSORBER LA–15 System and is

publishing this notice of that

determination as required by law. FDA

has made the determination because of

the submission of an application to the

Commissioner of Patents and

Trademarks, Department of Commerce,

for the extension of a patent which

claims that medical device.

ADDRESSES: Written comments and

petitions should be directed to the

Dockets Management Branch (HFA–

305), Food and Drug Administration,

12420 Parklawn Dr., rm. 1–23,

Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT:

Brian J. Malkin, Office of Health Affairs

(HFY–20), Food and Drug

Administration, 5600 Fishers Lane,

Rockville, MD 20857, 301–827–6620.

SUPPLEMENTARY INFORMATION: The Drug

Price Competition and Patent Term

Restoration Act of 1984 (Pub. L. 98–417)

and the Generic Animal Drug and Patent

Term Restoration Act (Pub. L. 100–670)

generally provide that a patent may be

extended for a period of up to 5 years

so long as the patented item (human

drug product, animal drug product,

medical device, food additive, or color

additive) was subject to regulatory

review by FDA before the item was

marketed. Under these acts, a product’s

regulatory review period forms the basis

for determining the amount of extension

an applicant may receive.

A regulatory review period consists of

two periods of time: A testing phase and

an approval phase. For medical devices,

the testing phase begins with a clinical

investigation of the device and runs

until the approval phase begins. The

approval phase starts with the initial

submission of an application to market

the device and continues until

permission to market the device is

granted. Although only a portion of a

regulatory review period may count

toward the actual amount of extension

that the Commissioner of Patents and

Trademarks may award (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 a medical device will include

all of the testing phase and approval

phase as specified in 35 U.S.C.

156(g)(3)(B).

FDA recently approved for marketing

the medical device LIPOSORBER LA–

15 System. LIPOSORBER LA–15

System is indicated for use in

performing low density lipoprotein

cholesterol (LDL–C) apheresis to acutely

remove LDL–C from the plasma of high

risk patient populations for whom diet

has been ineffective and maximum drug

therapy has either been ineffective or

not tolerated. Subsequent to this

approval, the Patent and Trademark

Office received a patent term restoration

application for LIPOSORBER LA–15

System (U.S. Patent No. 4,637,994) from

Kanegafuchi Kagaku Kogyo Kabushiki

Kaisha, and the Patent and Trademark

Office requested FDA’s assistance in

determining this patent’s eligibility for

patent term restoration. In a letter dated

August 7, 1996, FDA advised the Patent

and Trademark Office that this medical

device had undergone a regulatory

review period and that the approval of

LIPOSORBER LA–15 System

represented the first permitted

commercial marketing or use 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

LIPOSORBER LA–15 System is 3,598

days. Of this time, 1,995 days occurred

during the testing phase of the

regulatory review period, while 1,603

days occurred during the approval