Determination of Regulatory Review Period for Purposes of Patent Extension; LIPOSORBERRegister LA-15 System

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.

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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

[[Page 24558]]

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]

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