
[Federal Register Volume 78, Number 150 (Monday, August 5, 2013)]
[Notices]
[Pages 47321-47322]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-18731]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-P-0241]


Determination That CYTOXAN (Cyclophosphamide) 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Not Withdrawn From Sale for Reasons of Safety or Effectiveness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) has determined that 
CYTOXAN (cyclophosphamide) for Injection (lyophilized formulations), 
100 milligrams (mg)/vial, 200 mg/vial, 500 mg/vial, 1 gram (g)/vial, 
and 2 g/vial, and CYTOXAN (cyclophosphamide) for Injection (non-
lyophilized formulations), 100 mg/vial and 200 mg/vial, were not 
withdrawn from sale for reasons of safety or effectiveness. This 
determination will allow FDA to approve abbreviated new drug 
applications (ANDAs) for these products, if all other legal and 
regulatory requirements are met.

FOR FURTHER INFORMATION CONTACT: Christine Kirk, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6280, Silver Spring, MD 20993-0002, 301-
796-2465.

SUPPLEMENTARY INFORMATION: In 1984, Congress enacted the Drug Price 
Competition and Patent Term Restoration Act of 1984 (Pub. L. 98-417) 
(the 1984 amendments), which authorized the approval of duplicate 
versions of drug products 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. ANDA applicants do not have to 
repeat the extensive clinical testing otherwise necessary to gain 
approval of a new drug application (NDA).
    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 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).
    A person may petition the Agency to determine, or the Agency may 
determine on its own initiative, whether a listed drug was withdrawn 
from sale for reasons of safety or effectiveness. This determination 
may be made at any time after the drug has been withdrawn from sale, 
but must be made prior to approving an ANDA that refers to the listed 
drug (Sec.  314.161 (21 CFR 314.161)). FDA may not approve an ANDA that 
does not refer to a listed drug.
    CYTOXAN (cyclophosphamide) for Injection (lyophilized 
formulations), 100 mg/vial, 200 mg/vial, 500 mg/vial, 1 g/vial, and 2 
g/vial, and CYTOXAN (cyclophosphamide) for Injection, 100 mg/vial and 
200 mg/vial, are the subject of NDA 012142, held by Baxter Healthcare, 
and initially approved on November 16, 1959. CYTOXAN for Injection is 
an alkylating drug product indicated for treatment of malignant 
lymphomas, Hodgkin's disease, lymphocytic lymphoma, mixed-cell type 
lymphoma, histiocytic lymphoma, Burkitt's lymphoma, multiple myeloma, 
leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, 
retinoblastoma, breast carcinoma, and minimal change nephrotic syndrome 
in pediatric patients.
    CYTOXAN (cyclophosphamide) for Injection (lyophilized 
formulations), 100 mg/vial, 200 mg/vial, 500 mg/vial, 1 g/vial, and 2 
g/vial, and CYTOXAN (cyclophosphamide) for Injection, 100 mg/vial and 
200 mg/vial, are currently listed in the ``Discontinued Drug Product 
List'' section of the Orange Book.
    Foley & Lardner LLP submitted a citizen petition dated February 26, 
2013 (Docket No. FDA-2013-P-0241), under 21 CFR 10.30, requesting that 
the Agency determine whether CYTOXAN (cyclophosphamide) for Injection 
(lyophilized formulations), 100 mg/vial, 200 mg/vial, 500 mg/vial, 1 g/
vial, and 2 g/vial, were voluntarily withdrawn or withheld from sale 
for reasons of safety or effectiveness. Although the citizen petition 
did not address the non-lyophilized 100 mg/vial and 200 mg/vial 
formulations, those strengths have also been discontinued. On our own 
initiative, we have also determined whether those strengths were 
withdrawn for safety or effectiveness reasons.
    After considering the citizen petition and reviewing Agency records 
and based on the information we have at this time, FDA has determined 
under Sec.  314.161 that CYTOXAN (cyclophosphamide) for Injection 
(lyophilized formulations), 100mg/vial, 200mg/vial, 500 mg/vial, 1 g/
vial, and 2 g/vial, and CYTOXAN (cyclophosphamide) for Injection, 100 
mg/vial and 200 mg/vial, were not withdrawn for reasons of safety or 
effectiveness. The petitioner has identified no data or other 
information suggesting that CYTOXAN (cyclophosphamide) for Injection 
(lyophilized formulations), 100 mg/vial, 200 mg/vial, 500 mg/vial, 1 g/
vial, and 2 g/vial, or CYTOXAN (cyclophosphamide) for Injection, 100 
mg/vial and 200 mg/vial, were withdrawn for reasons of safety or 
effectiveness. We have carefully reviewed our files for records 
concerning the withdrawal of CYTOXAN (cyclophosphamide) for Injection 
(lyophilized formulations), 100 mg/vial, 200 mg/vial, 500 mg/vial, 1 g/
vial, and 2 g/vial, and CYTOXAN (cyclophosphamide) for Injection, 100 
mg/vial and 200 mg/vial, from sale. We have also independently 
evaluated relevant literature and data for possible postmarketing 
adverse events. We have found no information that would indicate that 
these products were withdrawn from sale for reasons of safety or 
effectiveness.
    Accordingly, the Agency will continue to list CYTOXAN 
(cyclophosphamide) for Injection (lyophilized formulations), 100 mg/
vial, 200 mg/vial, 500 mg/vial, 1 g/vial, and 2 g/vial, and CYTOXAN 
(cyclophosphamide) for Injection, 100 mg/vial and 200 mg/vial, 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 CYTOXAN 
(cyclophosphamide) for Injection (lyophilized formulations), 100 mg/
vial, 200 mg/vial, 500 mg/vial, 1 g/vial, and 2 g/vial, or CYTOXAN 
(cyclophosphamide) for Injection, 100 mg/vial and 200 mg/vial, may be 
approved by the Agency as long as they meet all other 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.



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    Dated: July 30, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-18731 Filed 8-2-13; 8:45 am]
BILLING CODE 4160-01-P


