[Federal Register: August 8, 2007 (Volume 72, Number 152)]
[Notices]
[Page 44559-44560]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr08au07-88]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2006P-0520]
Determination That Methotrexate Injection, USP, Preservative
Free, Equivalent to 500 Milligrams Base/20 Milliliters (25 Milligrams/
Milliliter), Was Not Withdrawn From Sale for Reasons of Safety or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) has determined that
methotrexate injection, USP, preservative free, equivalent to (Eq.) 500
milligrams (mg) base/20 milliliters (mL) (25 mg/mL), was not withdrawn
from sale for reasons of safety or effectiveness. This determination
will allow FDA to approve abbreviated new drug applications (ANDAs) for
methotrexate injection, preservative free, Eq. 500 mg base/20 mL (25
mg/mL).
FOR FURTHER INFORMATION CONTACT: Elena Cohen, 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
typically a version of the drug that was previously approved. ANDA
applicants 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 (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 (21
CFR 314.162).
Under 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.
Methotrexate injection, USP, preservative free, Eq. 500 mg base/20
mL (25 mg/mL), is the subject of approved NDA 11-719 currently held by
Mayne Pharma USA (Mayne). Although NDA 11-719 was originally approved
in 1959, this formulation and dosage was approved in April 2005 (S-
108). Methotrexate is an antifolate cytotoxic drug used in the
treatment of a variety of malignancies, including acute lymphoblastic
leukemia, osteosarcoma, advanced metastatic breast cancer, and others.
It is also used to treat some inflammatory conditions such as
rheumatoid arthritis. To date, Mayne has not marketed methotrexate
injection, USP, preservative free, Eq. 500 mg base/20 mL (25 mg/mL). At
the request of the sponsor, the product was moved to the discontinued
section of the Orange Book in June 2005. In previous instances (see,
e.g., the Federal Register document of December 30, 2002 (67 FR 79640),
addressing a relisting request for Diazepam Autoinjector), the agency
has determined 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.
SICOR Pharmaceuticals, Inc., submitted a citizen petition dated
[[Page 44560]]
December 15, 2006 (Docket No. 2006P-0520/CP1), under 21 CFR 10.30,
requesting that the agency determine whether methotrexate injection,
preservative free, Eq. 500 mg base/20 mL (25 mg/mL), was withdrawn from
sale for reasons of safety or effectiveness. The petitioner has
identified no data or other information suggesting that methotrexate
injection, preservative free, Eq. 500 mg base/20 mL (25 mg/mL), was
withdrawn from sale 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 this product was withdrawn for reasons of safety or
effectiveness.
After considering the citizen petition and reviewing agency
records, FDA has determined that, for the reasons outlined in this
document, methotrexate injection, preservative free, Eq. 500 mg base/20
mL (25 mg/mL), was not withdrawn from sale for reasons of safety or
effectiveness. Accordingly, the agency will continue to list
methotrexate injection, preservative free, Eq. 500 mg base/20 mL (25
mg/mL), 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
methotrexate injection, preservative free, Eq. 500 mg base/20 mL (25
mg/mL), may be approved by the agency as long as they meet all relevant
legal and regulatory requirements for the approval of ANDAs. 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: July 30, 2007.
Randall W. Lutter,
Deputy Commissioner for Policy.
[FR Doc. E7-15490 Filed 8-7-07; 8:45 am]
BILLING CODE 4160-01-S