[Federal Register Volume 80, Number 111 (Wednesday, June 10, 2015)]
[Notices]
[Page 32962]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-14145]



[[Page 32962]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-N-1663]


Determination That Ondansetron (Ondansetron Hydrochloride) 
Injection, USP in PL 2408 Plastic Container, 32 Milligrams in 50 
Milliliters, Was Withdrawn From Sale for Reasons of Safety or 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 
Ondansetron (ondansetron hydrochloride (HCl)) Injection, USP in PL 2408 
Plastic Container, 32 milligrams (mg) in 50 milliliters (mL), single 
intravenous (IV) dose, was withdrawn from sale for reasons of safety or 
effectiveness. The Agency will not accept or approve abbreviated new 
drug applications (ANDAs) for Ondansetron (ondansetron HCl) Injection, 
USP in PL 2408 Plastic Container, 32 mg/50 mL, single IV dose.

FOR FURTHER INFORMATION CONTACT: Emily Helms Williams, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6280, Silver Spring, MD 20993-0002, 301-
796-3381.

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 among other things 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 
(21 CFR 314.161). FDA may not approve an ANDA that does not refer to a 
listed drug.
    Ondansetron (ondansetron HCl) Injection, USP in PL 2408 Plastic 
Container, 32 mg/50 mL, single IV dose, is the subject of NDA 021915, 
held by Baxter Healthcare Corporation (Baxter), and initially approved 
on December 27, 2006. The product is indicated for prevention of nausea 
and vomiting associated with initial and repeat courses of emetogenic 
cancer chemotherapy in adult patients. It was approved under the 
pathway described by section 505(b)(2) of the Federal Food, Drug, and 
Cosmetic Act (21 U.S.C. 355(b)(2)). Baxter's application relied in part 
on FDA's finding of safety and effectiveness for ZOFRAN, NDA 020007, 
held by GlaxoSmithKline (GSK).
    In September 2011, FDA issued a Drug Safety Communication noting 
concerns that the 32 mg single IV dose of ZOFRAN, NDA 020007, and 
generic versions of that product could increase the risk of abnormal 
changes in the electrical activity of the heart, which could result in 
a potentially fatal abnormal heart rhythm. Specifically, the Agency 
noted that the 32 mg single IV dose of ondansetron could cause QT 
prolongation, which can lead to a serious and sometimes fatal heart 
rhythm called Torsades de Pointes. At FDA's request, GSK conducted a 
study to assess that risk. That study identified a significant QT 
prolongation effect in connection with the 32 mg single IV dose of 
Ondansetron. Based on this data, FDA approved GSK's supplemental 
application to remove the 32 mg single IV dose information from the 
labeling for ZOFRAN and has worked with manufacturers of all 32 mg, 
single IV dose ondansetron products to have them removed from the 
market.
    In a letter dated September 5, 2012, Baxter notified FDA that 
Ondansetron (ondansetron HCl) Injection, USP in PL 2408 Plastic 
Container, 32 mg/50 mL, single IV dose, was being discontinued, and FDA 
moved the drug product to the ``Discontinued Drug Product List'' 
section of the Orange Book. In a letter dated November 27, 2012, Baxter 
requested withdrawal of NDA 021915 for Ondansetron (ondansetron HCl) 
Injection, USP in PL 2408 Plastic Container, 32 mg/50 mL, single IV 
dose. In a contemporaneous notice, FDA is announcing that it is 
withdrawing approval of NDA 021915.
    We have carefully reviewed our files for records concerning the 
withdrawal of Ondansetron (ondansetron HCl) Injection, USP in PL 2408 
Plastic Container, 32 mg/50 mL, single IV dose, from sale. We have also 
evaluated relevant literature and data. FDA has determined under 
Sec. Sec.  314.161 and 314.162(a)(2), that Ondansetron (ondansetron 
HCl) Injection, USP in PL 2408 Plastic Container, 32 mg/50 mL, single 
IV dose, was withdrawn from sale for reasons of safety.
    Accordingly, the Agency will remove Ondansetron (ondansetron HCl) 
Injection, USP in PL 2408 Plastic Container, 32 mg/50 mL, single IV 
dose, from the list of drug products published in the Orange Book. FDA 
will not accept or approve ANDAs that refer to this drug product.

    Dated: June 4, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-14145 Filed 6-9-15; 8:45 am]
BILLING CODE 4164-01-P