[Federal Register Volume 67, Number 88 (Tuesday, May 7, 2002)]
[Notices]
[Pages 30716-30717]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-11206]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 01P-0315]


Determination That Acetaminophen and Codeine Phosphate Tablets, 
500 Milligrams (mg)/15 mg, 500 mg/30 mg, and 500 mg/60 mg, 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Withdrawn From Sale for Reasons of Safety or Effectiveness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) is announcing its 
determination that acetaminophen and codeine phosphate tablets, 500 mg/
15 mg, 500 mg/30 mg, and 500 mg/60 mg, were not withdrawn from sale for 
reasons of safety or effectiveness. This determination will allow FDA 
to approve abbreviated new drug applications (ANDAs) for acetaminophen 
and codeine phosphate

[[Page 30717]]

tablets, 500 mg/15 mg, 500 mg/30 mg, and 500 mg/60 mg.

FOR FURTHER INFORMATION CONTACT: Carol E. Drew, 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 under a 
new drug application (NDA). Sponsors of ANDAs do not have to repeat the 
extensive clinical testing otherwise necessary to gain approval of an 
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 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 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.
    There are no NDAs for acetaminophen and codeine phosphate tablets. 
The initial acetaminophen/codeine combination drug product was accepted 
as an ANDA based on a Federal Register notice finding TRIGESIC with 
codeine to be effective for the relief of mild to moderate pain. (See 
38 FR 3210, February 2, 1973.) FDA made this effectiveness 
determination under the 1962 amendments to the act, which required a 
demonstration of the effectiveness of new drugs, including those 
approved prior to 1962. FDA contracted with the National Academy of 
Science/National Research Council to carry out the Drug Efficacy Study 
assessing the evidence of effectiveness available for new drugs 
approved prior to 1962. TRIGESIC with codeine contained codeine, 
acetaminophen, aspirin, and caffeine. The initial ANDA for 
acetaminophen and codeine tablets was considered to be similar and 
related to TRIGESIC with codeine tablets, and therefore was accepted as 
an ANDA.
    Roxane Laboratories (Roxane) filed a suitability petition (86P-
0161/CP) on April 14, 1986, requesting permission to file ANDAs for 
three different strengths of acetaminophen and codeine phosphate 
tablets. Its suitability petition was approved on May 8, 1986. Roxane's 
acetaminophen and codeine phosphate tablets, 500 mg/15 mg, 500 mg/30 
mg, and 500 mg/60 mg, are the subject of ANDAs 89-511, 89-512, and 89-
513, respectively. FDA approved ANDAs 89-511, 89-512, and 89-513, held 
by Roxane, on April 24, 1989, at which time they became ``listed 
drugs'' within the meaning of 21 CFR 314.3. On October 23, 1997, Roxane 
requested withdrawal of approval of ANDAs 89-511, 89-512, and 89-513. 
FDA withdrew approval of these ANDAs on June 11, 1998.
    On July 23, 2001, Aspire Pharmaceuticals, Inc., submitted a citizen 
petition (Docket No. 01P-0315/CP1) under 21 CFR 10.30 to FDA requesting 
that the agency determine whether Roxane's acetaminophen and codeine 
phosphate tablets, 500 mg/15 mg, 500 mg/30 mg, and 500 mg/60 mg, were 
withdrawn from sale for reasons of safety or effectiveness.
    The agency has determined that Roxane's acetaminophen and codeine 
phosphate tablets, 500 mg/15 mg, 500 mg/30 mg, and 500 mg/60 mg, were 
not withdrawn from sale for reasons of safety or effectiveness. Two 
grounds support the agency's finding. First, there are drug products 
with a combination of acetaminophen and codeine phosphate being 
marketed today with greater than 500 mg of acetaminophen. Second, when 
FDA's Center for Drug Evaluation and Research Suitability Petition 
Committee first considered Roxane's suitability petition for its 
acetaminophen and codeine phosphate drug products, it concluded that 
the drug products did not need any safety or efficacy studies to 
support their approval because the proposed change in strength of the 
acetaminophen component fell within acceptable limits established by 
the Monograph for Over-the-Counter Internal Analgesic, Antipyretic, and 
Antirheumatic Drug Products.
    After considering the citizen petition and reviewing its records, 
FDA determines that, for the reasons outlined previously in this 
document, Roxane's acetaminophen and codeine phosphate tablets, 500 mg/
15 mg, 500 mg/30 mg, and 500 mg/60 mg, were not withdrawn from sale for 
reasons of safety or effectiveness. Accordingly, the agency will 
continue to list acetaminophen and codeine phosphate tablets, 500 mg/15 
mg, 500 mg/30 mg, and 500 mg/60 mg 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 
withdrawn from marketing for reasons other than safety or 
effectiveness. ANDAs that refer to acetaminophen and codeine phosphate 
tablets, 500 mg/15 mg, 500 mg/30 mg, and 500 mg/60 mg, may be approved 
by the agency .

    Dated: April 29, 2002.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 02-11206 Filed 5-6-02; 8:45 am]
BILLING CODE 4160-01-S