[Federal Register Volume 72, Number 138 (Thursday, July 19, 2007)]
[Notices]
[Pages 39629-39630]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-13950]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2007P-0052]


Determination That Brethine (Terbutaline Sulfate) Injection Was 
Not Withdrawn From Sale for Reasons of Safety or Effectiveness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 Brethine (Terbutaline Sulfate) Injection was not 
withdrawn from sale for reasons of safety or effectiveness. This 
determination will allow FDA to approve abbreviated new drug 
applications (ANDAs) for terbutaline sulfate injection if all other 
legal and regulatory requirements are met.

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 
applicants 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 under a new drug 
application (NDA). ANDA applicants 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

[[Page 39630]]

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 known generally 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 (21 CFR 314.162). Regulations also provide that the 
agency must make a determination as to 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 (Sec.  
314.161(a)(1) (21 CFR 314.161(a)(1))). FDA may not approve an ANDA that 
does not refer to a listed drug.
    On February 9, 2007, West-ward Pharmaceutical Corp. (West-ward), on 
behalf of Hikma Farmaceutica (Portugal), S.A., submitted a citizen 
petition (Docket No. 2007P-0052/CP1) to FDA under 21 CFR 10.30. The 
petition requests that the agency determine whether Brethine 
(terbutaline sulfate) injection (NDA 18-571), manufactured by 
AaiPharma, was withdrawn from sale for reasons of safety or 
effectiveness. AaiPharma ceased manufacture of Brethine injection and 
it was moved from the prescription drug product list to the 
``Discontinued Drug Product List'' section of the Orange Book in August 
of 2006.
    Brethine injection was first approved in 1981; this approval was 
for a glass ampoule container closure system. In 2004 AaiPharma 
received approval of a glass vial container closure system for a 
Brethine injection formulation that contained 0.055 percent disodium 
edetate. When Brethine injection was discontinued, an approved generic 
was chosen as the replacement reference listed drug. The replacement 
reference listed drug does not contain 0.055 disodium edetate and is 
based on the original glass ampoule formulation. Therefore, West-ward 
requests that the agency make a determination that the reformulated 
version of Brethine injection was not withdrawn for safety or efficacy 
reasons.
    FDA has reviewed its records and, under Sec.  314.161, has 
determined that Brethine (terbutaline sulfate) injection was not 
withdrawn from sale for reasons of safety or effectiveness. The 
petitioner identified no data or other information suggesting that 
Brethine containing 0.055 disodium edetate was withdrawn for reasons of 
safety or effectiveness. FDA has independently evaluated relevant 
literature and data for possible postmarketing adverse events and has 
found no information that would indicate that this product was 
withdrawn from sale for reasons of safety or effectiveness. Furthermore 
we have determined that the change in formulation was not for safety or 
efficacy reasons. Our files indicate that disodium edetate was added as 
a protectant against certain oxidation-derived terbutaline impurities 
and degradants when the manufacturing site and container closure system 
were changed. Accordingly, the agency will continue to list terbutaline 
sulfate injection 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 terbutaline sulfate injection may be approved by the agency if 
all other legal and regulatory requirements for the approval of ANDAs 
are met. If FDA determines that labeling for this drug product should 
be revised to meet current standards, the Agency will advise ANDA 
applicants to submit such labeling.

    Dated: July 12, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-13950 Filed 7-18-07; 8:45 am]
BILLING CODE 4160-01-S