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withdrawn from sale for reasons of 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withdrawn from sale for reasons of 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
Federal Register / Vol. 72, No. 99 / Wednesday, May 23, 2007 / Notices 28983 

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 (21 CFR 314.162). 

Under § 314.161(a) (21 CFR 

314.161(a)), the agency must determine 

whether a listed drug was withdrawn 

from sale for reasons of safety or 

effectiveness: (1) Before an ANDA that 

refers to that listed drug may be 

approved or (2) whenever a listed drug 

is voluntarily withdrawn from sale, and 

ANDAs that refer to the listed drug have 

been approved. Section 314.161(d) 

provides that if FDA determines that a 

listed drug was removed from sale for 

safety or effectiveness reasons, the 

agency will initiate proceedings that 

could result in the withdrawal of 

approval of the ANDAs that refer to the 

listed drug. 

FDA has become aware that the drug 

products listed in the table in this 

document are no longer being marketed. 

(As requested by the applicants, FDA 

withdrew approval of NDA 6–460 for 

Protamine Sulfate Injection, NDA 18–

675 for TAVIST Syrup, NDA 19–243 for 

PROVENTIL Inhalation Solution, NDA 

19–471 for CARDIZEM SR Capsules, 

and NDA 19–817 for PERSANTINE 

Injection in the Federal Register of 

March 4, 2005 (70 FR 10651), NDA 8–

857 for PHENERGAN Injection in the 

Federal Register of May 5, 2004 (69 FR 

25124), and NDA 13–400 for ALDOMET 

Tablets and NDA 13–401 for ALDOMET 

Injection in the Federal Register of June 

16, 2006 (71 FR 34940)). 

Application 

No. Drug Applicant 

NDA 6–460 Protamine Sulfate Injection, 10 milligrams (mg)/milliliter (mL) 

in a 25-mL vial 

Eli Lilly and Co., Lilly Corporate Center, Indianapolis, IN 

46285 

NDA 6–773 ARTANE (trihexyphenidyl hydrochloride (HCl)) Tablets, 2 mg 

and 5 mg 

Lederle, c/o Wyeth Pharmaceuticals, P.O. Box 8299, Philadelphia, PA 19101–8299 

NDA 8–857 PHENERGAN (promethazine HCl) Injection, 25 mg/mL and 

50 mg/mL in 1-mL vials 

Wyeth Pharmaceuticals, P.O. Box 8299, Philadelphia, PA 

19101–8299 

NDA 9–149 THORAZINE (chlorpromazine HCl) Tablets, 10, 25, 50, 100, 

and 200 mg 

GlaxoSmithKline, 2301 Renaissance Blvd., King of Prussia, 

PA 19406 

NDA 11–145 DIURIL (chlorothiazide) Tablets, 250 mg and 500 mg Merck & Co., Inc., Sumneytown Pike, BLA–20, P.O. Box 4, 

West Point, PA 19486 

NDA 11–664 DECADRON (dexamethasone) Tablets, 0.25, 4, and 6 mg Do. 

NDA 11–808 MELLARIL (thioridazine HCl) Tablets, 10, 15, 25, 50, 100, 

150, and 200 mg 

Novartis Pharmaceuticals Corp., One Health Plaza, East 

Hanover, NJ 07936 

NDA 11–870 DIURIL (chlorothiazide) Suspension, 250 mg/5 mL Merck & Co., Inc. 

NDA 13–400 ALDOMET (methyldopa) Tablets, 125, 250, and 500 mg Do. 

NDA 13–401 ALDOMET (methyldopate HCl) Injection, 50 mg/mL Do. 

NDA 16–363 LASIX (furosemide) Injection, 10 mg/mL Aventis Pharmaceuticals, Inc., 200 Crossing Blvd., Bridgewater, NJ 08807–0890 

NDA 17–391 IMURAN (azathioprine) Injection, 100 mg base/vial Prometheus Laboratories, 5739 Pacific Center Blvd., San 

Diego, CA 92121–4203 

NDA 17–939 TAGAMET (cimetidine HCl) Injection, 300 mg/2 mL GlaxoSmithKline 

NDA 18–513 CHENIX (chenodiol) Tablets, 250 mg Axcan Scandipharm, Inc., 22 Inverness Center Parkway, Birmingham, AL 35242–4814 

NDA 18–675 TAVIST (clemastine fumarate) Oral Syrup, 0.5 mg/5 mL Novartis Consumer Health, Inc., 200 Kimball Dr., Parsippany, 

NJ 07054–0622 

NDA 18–922 LODINE (etodolac) Capsules, 200 mg; LODINE Tablets, 400 

mg and 500 mg 

Wyeth Pharmaceuticals, Inc. 

NDA 19–201 VOLTAREN (diclofenac sodium) Delayed-Release Tablets, 

25 mg and 50 mg 

Novartis Pharmaceuticals, Inc. 

NDA 19–243 PROVENTIL (albuterol sulfate) Inhalation Solution, 0.5% and 

0.083% 

Schering-Plough Corporation, 2000 Galloping Hill Rd., Kenilworth, NJ 07033 

NDA 19–434 TAGAMET HCl (cimetidine HCl) in Sodium Chloride 0.9% in 

Plastic Container, EQ 6 mg/mL 

GlaxoSmithKline 

NDA 19–471 CARDIZEM SR (diltiazem HCl) Capsules, 60, 90, 120, and 

180 mg 

Biovail Laboratories, Inc., c/o Bioavail Technologies Ltd., 700 

Route 202/206 North, Bridgewater, NJ 08807–0980 

NDA 19–817 PERSANTINE (dipyridamole) Injection, 5 mg/mL Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury 

Rd., P.O. Box 368, Ridgefield, CT 06877–0368 


pwalker on PROD1PC71 with NOTICES
28984 Federal Register / Vol. 72, No. 99 / Wednesday, May 23, 2007 / Notices 

Application 

No. Drug Applicant 

NDA 20–144 TRANSDERM–NITRO (nitroglycerin), 0.1 mg/hour (hr), 0.2 

mg/hr, 

0.4 mg/hr, 0.6 mg/hr, 0.8 mg/hr 

Novartis Pharmaceuticals Corp. 

NDA 20–584 LODINE (etodolac) XL Tablets, 600 mg Wyeth Pharmaceuticals, Inc. 

NDA 21–110 RAPAMUNE (sirolimus) Tablets, 5 mg Wyeth Pharmaceuticals, Inc. 

NDA 50–477 NEBCIN (tobramycin sulfate) Injection, 10 mg/mL Eli Lilly and Co. 

NDA 50–519 NEBCIN (tobramycin sulfate) Injection, 1.2 grams/vial Do. 

ANDA 62–008 NEBCIN (tobramycin sulfate) Injection, 40 mg/mL Do. 

FDA has reviewed its records and, 

under § 314.161, has determined that 

the drug products listed in this 

document were not withdrawn from 

sale for reasons of safety or 

effectiveness. Accordingly, the agency 

will continue to list the drug products 

listed in this document in the 

‘‘Discontinued Drug Product List’’

section of the Orange Book. The 

‘‘Discontinued Drug Product List’’

identifies, among other items, drug 

products that have been discontinued 

from marketing for reasons other than 

safety or effectiveness. Approved 

ANDAs that refer to the NDAs and 

ANDA listed in this document are 

unaffected by the discontinued 

marketing of the products subject to 

those NDAs and ANDA. Additional 

ANDAs for the products may also be 

approved by the agency if they comply 

with relevant legal and regulatory 

requirements. If FDA determines that 

labeling for these drug 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. E7–9962 Filed 5–22–07; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. 2004E–0319] 

Determination of Regulatory Review 

Period for Purposes of Patent 

Extension; BEXTRA 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) has determined 

the regulatory review period for 

BEXTRA 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 Director of Patents 

and Trademarks, Department of 

Commerce, for the extension of a patent 

which claims that human drug product. 

ADDRESSES: Submit written comments 

and petitions to the Division of Dockets 

Management (HFA–305), Food and Drug 

Administration, 5630 Fishers Lane, rm. 

1061, Rockville, MD 20852. Submit 

electronic comments to http:// 

www.fda.gov/dockets/ecomments. 

FOR FURTHER INFORMATION CONTACT: 

Beverly Friedman, Office of Regulatory 

Policy (HFD–007), Food and Drug 

Administration, 5600 Fishers Lane, 

Rockville, MD 20857, 301–594–2041. 

SUPPLEMENTARY INFORMATION: The Drug 

Price Competition and Patent Term 

Restoration Act of 1984 (Public Law 98–

417) and the Generic Animal Drug and 

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 drug 

products, the testing phase begins when 

the exemption to permit the clinical 

investigations of the human drug 

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 drug product and continues 

until FDA grants permission to market 

the drug 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 drug 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 drug product BEXTRA 

(valdecoxib). BEXTRA is indicated for 

relief of the signs and symptoms of 

osteoarthritis and adult rheumatoid 

arthritis and for the treatment of 

primary dysmenorrhea. Subsequent to 

this approval, the Patent and Trademark 

Office received a patent term restoration 

application for BEXTRA (U.S. Patent 

No. 5,633,272) from G.D. Searle, LLC, 

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 31, 2004, FDA advised the 

Patent and Trademark Office that this 

human drug product had undergone a 

regulatory review period and that the 

approval of BEXTRA represented the 

first permitted commercial marketing or 

use of the product. 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 

BEXTRA is 1,767 days. Of this time, 

1,462 days occurred during the testing 

phase of the regulatory review period, 

while 305 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 16, 

1997. The applicant claims January 15, 

1997, as the date the investigational new 

drug application (IND) became effective. 

However, FDA records indicate that the 


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