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
24558 Federal Register / Vol. 63, No. 85 / Monday, May 4, 1998 / Notices

phase. These periods of time were

derived from the following dates:

1. The date a clinical investigation

involving this device was begun: April

18, 1986. FDA has verified the

applicant’s claim that the date the

investigational device exemption (IDE)

required under section 520(g) of the

Federal Food, Drug, and Cosmetic Act

(21 U.S.C. 360j(g)) for human tests to

begin became effective April 18, 1996,

the date that the IDE for a similar,

related product, LIPOSORBER LA–40

System, was approved.

Although the device was

subsequently modified, the results of

the initial clinical investigations on the

earlier model, LIPOSORBER LA–40

System were included in FDA’s analysis

of the approved product’s safety and

effectiveness. The test on the earlier

model is, therefore, part of the testing

phase.

Additionally, the product is of a type

which, under present regulations,

would require IDE approval prior to the

start of clinical investigations, and

normally the initiation of the testing

phase for a medical device is

determined by reference to the approval

phase of the relevant IDE.

2. The date an application was

initially submitted with respect to the

device under section 515 of the Federal

Food, Drug, and Cosmetic Act (21 U.S.C.

360e): October 3, 1991. The applicant

claims March 24, 1988, as the date the

premarket approval application (PMA)

for the LIPOSORBER LA–40 System

(PMA 880019) was initially submitted,

which applicant argues should be used

in place of the PMA for LIPOSORBER

LA–15 System (PMA 910018). FDA

records indicate that PMA 880019 was

received by the agnecy on March 25,

1998, but this PMA was never filed, and

it was withdrawn by the applicant on

April 3, 1996. The applicant claims that

PMA 910018 was submitted on March

26, 1991, but FDA records indicate that

it was submitted on October 3, 1991.

The applicant argues that the PMA for

the LA–40 device should be used as the

start of the approval phase for the LA–

15 device, because its liposorber

technology and adsorbent are identical

to those described in the patent for

which applicant is requesting extension,

U.S. Patent No. 4,637,994. The LA–15

device contains additional components

of a plasma separator, the tubing system

for plasmaphereses and the apheresis

unit.

However, the patent term restoration

regulations define the approval phase of

medical device in terms of the actual

approved product, not an earlier tested

product. For example, while the patent

term restoration statute does define drug

product as the active ingredient of a

new drug, ‘‘product’’ for ‘‘medical

devices’’ has been defined as ‘‘[a]ny

medical device * * * subject to

regulation under the Federal Food,

Drug, and Cosmetic Act’’ (35 U.S.C.

156(f)). Given that the LA–40 device

was withdrawn by applicant from

further regulatory consideration, the

LA–15 device is the only applicable

medical device subject to FDA

regulations.

Regarding the definition of regulatory

review period for the start of the

approval phase of a medical device, the

regulations state ‘‘* * * the period

beginning on the date the application

was initially submitted with respect to

the device under section 515 and ending

on the date such application was

approved under such Act * * *’’ 35

U.S.C. 156(g)(3)(B); see also 21 CFR

60.22(c)(2)(i). In this case, the only PMA

which submitted, filed, and approved

under section 515 of the Federal Food,

Drug, and Cosmetic Act was PMA

P910018, which was submitted on

October 3, 1991, and is, therefore, the

appropriate date the approval

application was initially submitted for

LIPOSORBER LA–15 System.

3. The date the application was

approved: February 21, 1996. FDA has

verified the applicant’s claim that PMA

P9910018 was approved on February 21,

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 1,825 days of patent

term extension.

Anyone with knowledge that any of

the dates as published is incorrect may,

on or before July 6, 1998, 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 November 2, 1998, 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 31, 1998.

Thomas J. McGinnis,

Deputy Associate Commissioner for Health

Affairs.

[FR Doc. 98–11682 Filed 5–1–98; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

Dental Plaque Subcommittee of the

Nonprescription Drugs Advisory

Committee; Notice of Meeting

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

This notice announces a forthcoming

meeting of a public advisory committee

of the Food and Drug Administration

(FDA). The meeting will be open to the

public.

Name of Committee: Dental Plaque

Subcommittee of the Nonprescription

Drugs Advisory Committee.

General Function of the Committee:

To provide advice and

recommendations to the agency on

FDA’s regulatory issues.

Date and Time: The meeting will be

held on May 27, 28, and 29, 1998, 8:30

a.m. to 5 p.m.

Location: Holiday Inn, Two

Montgomery Village Ave., Gaithersburg,

MD.

Contact Person: Robert L. Sherman or

Stephanie A. Mason, Center for Drug

Evaluation and Research (HFD–560),

Food and Drug Administration, 5600

Fishers Lane, Rockville, MD, 301–827–

5191, or FDA Advisory Committee

Information Line, 1–800–741–8138

(301–443–0572 in the Washington, DC

area), code 12541. Please call the

Information Line for up-to-date

information on this meeting.

Agenda: On May 27, 1998, the

subcommittee will discuss: (1) The

safety and effectiveness of the

combination of stannous pyrophosphate

and zinc citrate; (2) the effectiveness of

the combination of hydrogen peroxide,

sodium lauryl sulfate, sodium citrate

and zinc chloride; (3) the safety and

effectiveness of hexetidine, soluble

pyrophosphate, nonsaponifiable fraction

of corn oil, bromchlorophene and

chlorhexidine digluconate; and (4) final

formulation testing. On May 28, 1998,

the subcommittee will discuss labeling