Federal Register / Vol. 72, No. 99 / Wednesday, May 23, 2007 / Notices 28981 

Patent Term Restoration Act (Public 

Law 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 human 

biological products, the testing phase 

begins when the exemption to permit 

the clinical investigations of the human 

biological product becomes effective 

and runs until the approval phase 

begins. The approval phase starts with 

the initial submission of an application 

to market the human biological product 

and continues until FDA grants 

permission to market the biological 

product. Although only a portion of a 

regulatory review period may count 

toward the actual amount of extension 

that the Director 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 

a human biological product will include 

all of the testing phase and approval 

phase as specified in 35 U.S.C. 

156(g)(1)(B). 

FDA recently approved for marketing 

the human biological product 

ELAPRASE (idursulfase). ELAPRASE is 

indicated for patients with Hunter 

Syndrome (Mucopolysaccharidosis II). 

Subsequent to this approval, the Patent 

and Trademark Office received a patent 

term restoration application for 

ELAPRASE (U.S. Patent No. 5,932,211) 

from Women’s and Children’s Hospital, 

and the Patent and Trademark Office 

requested FDA’s assistance in 

determining this patent’s eligibility for 

patent term restoration. In a letter dated 

February 6, 2007, FDA advised the 

Patent and Trademark Office that this 

human biological product had 

undergone a regulatory review period 

and that the approval of ELAPRASE 

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 

ELAPRASE is 2,008 days. Of this time, 

1,764 days occurred during the testing 

phase of the regulatory review period, 

while 244 days occurred during the 

approval phase. These periods of time 

were derived from the following dates: 

1. The date an exemption under 

section 505(i) of the Federal Food, Drug, 

and Cosmetic Act (the act) (21 U.S.C. 

355(i)) became effective: January 25, 

2001. The applicant claims March 12, 

2001, as the date the investigational new 

drug application (IND) became effective. 

However, FDA records indicate that the 

IND effective date was January 25, 2001, 

which was 30 days after FDA receipt of 

the IND. 

2. The date the application was 

initially submitted with respect to the 

human biological product under section 

351 of the Public Health Service Act (42 

U.S.C. 262): November 23, 2005. FDA 

has verified the applicant’s claim that 

the biologics license application (BLA) 

for ELAPRASE (BLA 125151) was 

initially submitted on November 23, 

2005. 

3. The date the application was 

approved: July 24, 2006. FDA has 

verified the applicant’s claim that BLA 

125151 was approved on July 24, 2006. 

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 1,103 days of patent 

term extension. 

Anyone with knowledge that any of 

the dates as published are incorrect may 

submit to the Division of Dockets 

Management (see ADDRESSES) written or 

electronic comments and ask for a 

redetermination by July 23, 2007. 

Furthermore, any interested person may 

petition FDA for a determination 

regarding whether the applicant for 

extension acted with due diligence 

during the regulatory review period by 

November 19, 2007. 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 Division of Dockets 

Management. Three copies of any 

mailed information 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. Comments and petitions may 

be seen in the Division of Dockets 

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

Monday through Friday. 

Dated: May 7, 2007. 

Jane A. Axelrad, 

Associate Director for Policy, Center for Drug 

Evaluation and Research. 

[FR Doc. E7–9951 Filed 5–22–07; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. 2002P–0399] 

Determination That ESTROSTEP 21 

(Ethinyl Estradiol and Norethindrone 

Acetate) Tablets Were Not Withdrawn 

From Sale for Reasons of Safety or 

Effectiveness 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) has determined 

that ESTROSTEP 21 (ethinyl estradiol 

and norethindrone acetate) tablets were 

not withdrawn from sale for reasons of 

safety or effectiveness. This 

determination will allow FDA to 

approve abbreviated new drug 

applications (ANDAs) for the 

combination drug ethinyl estradiol and 

norethindrone acetate tablets, 0.02 

milligram (mg)/1 mg, 0.03 mg/1 mg, and 

0.035 mg/1 mg. 

FOR FURTHER INFORMATION CONTACT: 

Mary Catchings, Center for Drug 

Evaluation and Research (HFD–7), Food 

and Drug Administration, 5600 Fishers 

Lane, Rockville, MD 20857, 301–594–

2041. 

SUPPLEMENTARY INFORMATION: In 1984, 

Congress enacted the Drug Price 

Competition and Patent Term 

Restoration Act of 1984 (Public Law 98–

417) (the 1984 amendments), which 

authorized the approval of duplicate 

versions of drug products approved 

under an ANDA procedure. 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 the ‘‘listed drug,’’

which is typically a version of the drug 

that was previously approved. Sponsors 

of ANDAs do not have to repeat the 

extensive clinical testing otherwise 

necessary to gain approval of a new 

drug application (NDA). The only 

clinical data required in an ANDA are 

data to show that the drug that is the 

subject of the ANDA is bioequivalent to 

the listed drug. 

The 1984 amendments include what 

is now section 505(j)(7) of the Federal 


pwalker on PROD1PC71 with NOTICES
28982 Federal Register / Vol. 72, No. 99 / Wednesday, May 23, 2007 / Notices 

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

355(j)(7)), which requires FDA to 

publish a list of all approved drugs. 

FDA publishes this list as part of the 

‘‘Approved Drug Products With 

Therapeutic Equivalence Evaluations,’’

which is generally known as the 

‘‘Orange Book.’’ Under FDA regulations, 

drugs are removed from the list if the 

agency withdraws or suspends approval 

of the drug’s NDA or ANDA for reasons 

of safety or effectiveness, or if FDA 

determines that the listed drug was 

withdrawn from sale for reasons of 

safety or effectiveness (§ 314.162)(21 

CFR 314.162)). 

Under § 314.161(a)(1)(21 CFR 

314.161(a)(1)), the agency must 

determine whether a listed drug was 

withdrawn from sale for reasons of 

safety or effectiveness before an ANDA 

that refers to that listed drug may be 

approved. FDA may not approve an 

ANDA that does not refer to a listed 

drug. 

ESTROSTEP 21 (ethinyl estradiol and 

norethindrone acetate) tablets, 0.02 mg/ 

1 mg, 0.03 mg/1 mg, and 0.035 mg/1 mg, 

are the subject of approved NDA 20–130 

held by Warner Chilcott. ESTROSTEP 

21 tablets, 0.02 mg/1 mg, 0.03 mg/1 mg, 

and 0.035 mg/1 mg, were approved on 

October 9, 1996, as oral contraceptives 

indicated for the prevention of 

pregnancy in women who elect to use 

these products as a method of 

contraception. FDA also approved 

ESTROSTEP FE under NDA 20–130 on 

October 9, 1996, for the same indication. 

On July 1, 2001, FDA approved 

ESTROSTEP 21 and ESTROSTEP FE for 

the treatment of moderate acne vulgaris 

under NDA 21–276. Both ESTROSTEP 

21 and ESTROSTEP FE provide a 

gradually increasing estrogen dose with 

a constant dose of progestin. Both drugs 

provide the same dosage regimen of oral 

contraceptive tablets for the first 21 days 

of a 28–day cycle. ESTROSTEP FE 

provides an additional seven ferrous 

fumarate tablets. The ferrous fumarate 

tablets, which are nonhormonal and 

serve no therapeutic purpose, are added 

to facilitate patient compliance by the 

use of a 28-day regimen where the 

patient takes a pill every day. Except for 

the nontherapeutic ferrous fumarate 

tablets, ESTROSTEP 21 and 

ESTROSTEP FE have the same 

therapeutic regimen. 

ESTROSTEP 21 is listed in the Orange 

Book as a discontinued product. 

ESTROSTEP FE, currently named 

ESTROSTEP, remains on the list of 

currently marketed drug products. 

Barr Laboratories, Inc., submitted a 

citizen petition dated September 4, 2002 

(Docket No. 2002P–0399/CP1), under 21 

CFR 10.30 and § 314.161, requesting 

that FDA determine whether 

ESTROSTEP 21 tablets had been 

discontinued from sale for reasons of 

safety or effectiveness. In a letter dated 

December 1, 2004, Warner Chilcott 

confirmed to the agency that the firm 

never commercially marketed 

ESTROSTEP 21 in the United States. In 

previous instances (see the Federal 

Register of December 30, 2002 (67 FR 

79640 at 79641) (addressing a relisting 

request for Diazepam Autoinjector)), 

FDA has concluded that, for purposes of 

§§ 314.161 and 314.162, never 

marketing an approved drug product is 

equivalent to withdrawing the drug 

from sale. 

The agency has determined that 

ESTROSTEP 21 tablets, 0.02 mg/1 mg, 

0.03 mg/1 mg, and 0.035 mg/1 mg, were 

not withdrawn from sale for reasons of 

safety or effectiveness. In support of this 

finding, we note that Warner Chilcott 

continues to market ESTROSTEP FE, 

which contains the same therapeutic 

dosage regimen as ESTROSTEP 21. The 

petitioner identified no data or other 

information suggesting that ESTROSTEP 

21 was withdrawn from sale as a result 

of safety or effectiveness concerns. FDA 

has independently evaluated relevant 

literature and data for possible 

postmarketing adverse event reports 

associated with this combination drug 

product and has found no information 

that would indicate this product was 

withdrawn from sale for reasons of 

safety or effectiveness. 

After considering the citizen petition 

and reviewing agency records, FDA 

determines that for the reasons outlined 

in this document, ESTROSTEP 21 

tablets, 0.02 mg/1 mg, 0.03 mg/1 mg, 

and 0.035 mg/1 mg, were not withdrawn 

from sale for reasons of safety or 

effectiveness. Accordingly, the agency 

will continue to list ESTROSTEP 21 in 

the ‘‘Discontinued Drug Product List’’

section of the Orange Book. The 

‘‘Discontinued Drug Product List’’

delineates, among other items, drug 

products that have been discontinued 

from marketing for reasons other than 

safety or effectiveness. ANDAs that refer 

to ESTROSTEP 21 may be approved by 

the agency as long as they meet all 

relevant legal and regulatory 

requirements for approval of ANDAs. If 

FDA determines that labeling for these 

drugs products should be revised to 

meet current standards, the agency will 

advise ANDA applicants to submit such 

labeling. 

Dated: May 15, 2007. 

Jeffrey Shuren, 

Assistant Commissioner for Policy. 

[FR Doc. E7–9949 Filed 5–22–07; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. 2007N–0191] 

Determination That Protamine Sulfate 

Injection and 26 Other Drug Products 

Were Not Withdrawn From Sale for 

Reasons of Safety or Effectiveness 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) has determined 

that the 27 drug products listed in this 

document were not withdrawn from 

sale for reasons of safety or 

effectiveness.This determination means 

that FDA will not begin procedures to 

withdraw approval of abbreviated new 

drug applications (ANDAs) for the drug 

products, and it will allow FDA to 

continue to approve ANDAs for the 

products. 

FOR FURTHER INFORMATION CONTACT: 

Mary Catchings, Center for Drug 

Evaluation and Research (HFD–7), Food 

and Drug Administration, 5600 Fishers 

Lane, Rockville, MD 20855, 301–594–

2041. 

SUPPLEMENTARY INFORMATION: In 1984, 

Congress enacted the Drug Price 

Competition and Patent Term 

Restoration Act of 1984 (Public Law 98–

417) (the 1984 amendments), which 

authorized the approval of duplicate 

versions of drug products approved 

under an ANDA procedure. 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 the ‘‘listed drug,’’

which is a version of the drug that was 

previously approved. Sponsors of 

ANDAs do not have to repeat the 

extensive clinical testing otherwise 

necessary to gain approval of a new 

drug application (NDA). The only 

clinical data required in an ANDA are 

data to show that the drug that is the 

subject of the ANDA is bioequivalent to 

the listed drug. 

The 1984 amendments include what 

is now section 505(j)(7) of the Federal 

Food, Drug, and Cosmetic Act (the act) 

(21 U.S.C. 355(j)(7)), which requires 

FDA to publish a list of all approved 

drugs. FDA publishes this list as part of 

the ‘‘Approved Drug Products With 

Therapeutic Equivalence Evaluations,’’

which is generally known as the 

‘‘Orange Book.’’ Under FDA regulations, 

drugs are withdrawn from the list if the 

agency withdraws or suspends approval 


pwalker on PROD1PC71 with NOTICES