[Federal Register: November 6, 2003 (Volume 68, Number 215)]
[Notices]               
[Page 62810-62811]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr06no03-57]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket Nos. 2002P-0506 and 2003P-0021]

 
Determination That Hyaluronidase For Injection Was Not Withdrawn 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 hyaluronidase for injection (Wydase) was not 
withdrawn from sale for reasons of safety or effectiveness. While this 
determination will allow FDA to approve abbreviated new drug 
applications (ANDAs) for hyaluronidase for injection, in considering 
whether to file an ANDA for this product, future applicants are advised 
that such an application raises complex issues regarding the 
characterization of the active ingredient.

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 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,

[[Page 62811]]

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). 
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.
    Lachman Consultant Services, Inc., submitted a citizen petition 
dated December 5, 2002 (Docket No. 02P-0506/CP1), under 21 CFR 10.30 to 
FDA requesting that the agency determine whether hyaluronidase for 
injection was withdrawn from sale for reasons of safety or 
effectiveness. On January 8, 2003, Amphastar Pharmaceuticals, Inc., 
submitted a citizen petition (Docket No. 03P-0021/CP1) requesting the 
same action. On July 15, 2003, Merchant-Taylor International, Inc. 
(MTI), on behalf of Hyalozyme Therapeutics, Inc., filed a comment to 
both citizen petitions requesting that FDA determine that hyaluronidase 
for injection was withdrawn from sale for reasons of safety and 
effectiveness. Hyaluronidase for injection is the subject of approved 
NDA 6-343, formerly held by Wyeth Pharmaceuticals, Inc. (Wyeth), now 
held by Baxter Healthcare Corp. Hyaluronidase for injection is a 
protein enzyme and is a preparation of highly purified bovine 
testicular hyaluronidase used to increase the absorption and dispersion 
of other injected drugs. Wyeth ceased manufacture of hyaluronidase for 
injection in December 2001, and it was moved from the prescription drug 
product list to the ``Discontinued Drug Product List'' section of the 
Orange Book.
    FDA has reviewed its records and the comment filed by MTI and, 
under Sec.  314.161, has determined that hyaluronidase for injection 
was not withdrawn from sale for reasons of safety or effectiveness. 
Accordingly, the agency will continue to list hyaluronidase for 
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 
hyaluronidase for injection may be approved by the agency; however, FDA 
recommends that in considering whether to file an ANDA for this drug 
product, future applicants be advised that such an application is 
likely to raise complex issues regarding the characterization of the 
active ingredient under section 505(j) of the act (see docket on 
conjugated estrogen drug products, Docket No. 98P-0311).

    Dated: October 24, 2003.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 03-27880 Filed 11-5-03; 8:45 am]

BILLING CODE 4160-01-S