[Federal Register Volume 79, Number 163 (Friday, August 22, 2014)]
[Notices]
[Pages 49780-49781]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-19961]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket Nos. FDA-2014-P-0637, FDA-2014-P-0315]


Determination That FUSILEV (Levoleucovorin Calcium), Injection, 
175 Milligrams/17.5 Milliliters and 250 Milligrams/25 Milliliters, 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Not Withdrawn From Sale for Reasons of Safety or Effectiveness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) has determined that 
FUSILEV (levoleucovorin calcium), Injection, 175 milligrams (mg)/17.5 
milliliters (mL) and 250 mg/25 mL, were not withdrawn from sale for 
reasons of safety or effectiveness. This determination will allow FDA 
to approve abbreviated new drug applications (ANDAs) for levoleucovorin 
calcium, injection, 175 mg/17.5 mL and 250 mg/25 mL, if all other legal 
and regulatory requirements are met.

FOR FURTHER INFORMATION CONTACT: Darren Eicken, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6206, Silver Spring, MD 20993-0002, 240-
402-0978.

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 
(Sec.  314.162 (21 CFR 314.162)).
    A person may petition the Agency to determine, or the Agency may

[[Page 49781]]

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)). FDA may not approve an ANDA that does not refer 
to a listed drug.
    FUSILEV (levoleucovorin calcium), Injection, 175 mg/17.5 mL and 250 
mg/25 mL, are the subjects of NDA 020140, held by Spectrum 
Pharmaceuticals, and were initially approved on April 29, 2011 
(supplemental approval). FUSILEV is indicated for rescue after high-
dose methotrexate therapy in osteosarcoma, to diminish the toxicity and 
counteract the effects of impaired methotrexate elimination and of 
inadvertent overdosage of folic acid antagonists, and for use in 
combination chemotherapy with 5-fluorouracil in the palliative 
treatment of patients with advanced metastatic colorectal cancer.
    FUSILEV (levoleucovorin calcium), Injection, 175 mg/17.5 mL and 250 
mg/25 mL, are currently listed in the ``Discontinued Drug Product 
List'' section of the Orange Book. Spectrum Pharmaceuticals has never 
marketed FUSILEV (levoleucovorin calcium), Injection, 175 mg/17.5 mL. 
In previous instances (see, e.g., 72 FR 9763 and 61 FR 25497), 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.
    Lachman Consultant Services, Inc. (Lachman), submitted two citizen 
petitions, dated March 18, 2014, and May 14, 2014 (Docket Nos. FDA-
2014-P-0315 and FDA-2014-P-0637, respectively), under 21 CFR 10.30, 
requesting that the Agency determine whether FUSILEV (levoleucovorin 
calcium), Injection, 175 mg/17.5 mL and 250 mg/25 mL, were withdrawn 
from sale for reasons of safety or effectiveness.
    After considering the Lachman citizen petitions and reviewing 
Agency records and based on the information we have at this time, FDA 
has determined under Sec.  314.161 that FUSILEV (levoleucovorin 
calcium), Injection, 175 mg/17.5 mL and 250 mg/25 mL, were not 
withdrawn from sale for reasons of safety or effectiveness. Lachman has 
identified no data or other information suggesting that FUSILEV 
(levoleucovorin calcium), Injection, 175 mg/17.5 mL and 250 mg/25 mL, 
were withdrawn for reasons of safety or effectiveness. We have 
carefully reviewed our files for records concerning the withdrawal from 
sale of FUSILEV (levoleucovorin calcium), Injection, 175 mg/17.5 mL and 
250 mg/25 mL. We have also independently evaluated relevant literature 
and data for possible postmarketing adverse events. We have reviewed 
the available evidence and determined that these products were not 
withdrawn from sale for reasons of safety or effectiveness.
    Accordingly, the Agency will continue to list FUSILEV 
(levoleucovorin calcium), Injection, 175 mg/17.5 mL and 250 mg/25 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 FUSILEV 
(levoleucovorin calcium), Injection, 175 mg/17.5 mL and 250 mg/25 mL, 
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.

    Dated: August 19, 2014.
Peter Lurie,
Associate Commissioner for Policy and Planning.
[FR Doc. 2014-19961 Filed 8-21-14; 8:45 am]
BILLING CODE 4164-01-P