[Federal Register Volume 72, Number 99 (Wednesday, May 23, 2007)]
[Notices]
[Pages 28981-28982]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-9949]


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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Norethindrone Acetate) Tablets Were Not Withdrawn From Sale for Reasons 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.

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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not withdrawn from sale for reasons of safety or effectiveness.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

[[Page 28982]]

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 (Sec.  
314.162)(21 CFR 314.162)).
    Under Sec.  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 
Sec.  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 Sec. Sec.  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