[Federal Register Volume 77, Number 135 (Friday, July 13, 2012)]
[Notices]
[Pages 41412-41413]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-17091]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-P-0081]


Determination That CHLOROMYCETIN (Chloramphenicol) Capsules, 250 
Milligrams, Were Withdrawn From Sale for Reasons of Safety or 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 
CHLOROMYCETIN (chloramphenicol) Capsules, 250 milligrams (mg), were 
withdrawn from sale for reasons of safety or effectiveness. The Agency 
will not accept or approve abbreviated new drug applications (ANDAs) 
for chloramphenicol capsules, 250 mg.

FOR FURTHER INFORMATION CONTACT: Nikki Mueller, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6312, Silver Spring, MD 20993-0002, 301-
796-3601.

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 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 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.
    CHLOROMYCETIN (chloramphenicol) Capsules, 250 mg, are the subject 
of ANDA 60-591, held by Parkedale Pharmaceuticals, and initially 
approved on December 8, 1950. CHLOROMYCETIN is an antibiotic indicated 
to treat only serious infections for which less potentially dangerous 
drugs are ineffective or contraindicated.
    In a letter dated October 9, 2007, Parkedale Pharmaceuticals 
requested withdrawal of ANDA 60-591 for CHLOROMYCETIN (chloramphenicol) 
Capsules, 50 mg, 100 mg and 250 mg. In the Federal Register of February 
11, 2009 (74 FR 6896), FDA announced that it was withdrawing approval 
of ANDA 60-591, effective March 13, 2009, and moved the drug to the 
``Discontinued Drug Product List'' section of the Orange Book.
    Armenpharm, Ltd., submitted a citizen petition dated February 7, 
2011 (Docket No. FDA-2011-P-0081), under 21 CFR 10.30, requesting that 
the Agency determine whether CHLOROMYCETIN (chloramphenicol) Capsules, 
250 mg, were withdrawn from sale for reasons of safety or 
effectiveness.
    After considering the citizen petition, and based on the 
information we have at this time, FDA has determined under Sec.  
314.161 that CHLOROMYCETIN (chloramphenicol) Capsules, 250 mg, were 
withdrawn for reasons of safety or effectiveness. We have carefully 
reviewed Agency records concerning the withdrawal of CHLOROMYCETIN 
(chloramphenicol) Capsules, 250 mg, from sale. We have also 
independently evaluated relevant literature and data for possible 
postmarketing adverse events. At the time of the approval of 
CHLOROMYCETIN (chloramphenicol) Capsules, 250 mg, there was significant 
unmet medical need. With the approval of additional therapies with less 
severe adverse drug effects, FDA has determined that the risks 
associated with CHLOROMYCETIN (chloramphenicol) Capsules, 250 mg, as 
currently labeled, outweigh the benefits. Most importantly, 
CHLOROMYCETIN

[[Page 41413]]

(chloramphenicol) Capsules, 250 mg, may cause a number of adverse 
reactions, the most serious being bone marrow depression (anemia, 
thrombocytopenia, and granulocytopenia temporally associated with 
treatment). A boxed warning in the prescribing information for both 
chloramphenicol sodium succinate injection and chloramphenicol capsules 
states that serious hypoplastic anemia, thrombocytopenia, and 
granulocytopenia are known to occur after administration of 
chloramphenicol. The drug product labeling recommends extensive safety 
monitoring, including baseline blood studies followed by periodic blood 
studies approximately every 2 days during therapy. The boxed warning 
also describes fatal aplastic anemia associated with administration of 
the drug and aplastic anemia attributed to chloramphenicol that later 
terminated in leukemia. There is published literature which suggests 
that the risk of fatal aplastic anemia associated with the oral 
formulation of chloramphenicol may be higher than the risk associated 
with the intravenous formation.
    FDA has also reviewed the latest approved labeling for the product 
and has determined that this labeling is inadequate and a Risk 
Evaluation and Mitigation Strategy (REMS) would be required to ensure 
that the benefits of the drug outweigh its risks. The REMS may include 
Elements to Assure Safe Use, including restricted distribution, and a 
Medication Guide could be required as part of the labeling. FDA has 
determined that additional nonclinical and possibly clinical studies of 
safety and efficacy would be necessary before CHLOROMYCETIN 
(chloramphenicol) Capsules, 250 mg, could be considered for 
reintroduction to the market.
    Accordingly, the Agency will remove CHLOROMYCETIN (chloramphenicol) 
Capsules, 250 mg, 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: July 10, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-17091 Filed 7-12-12; 8:45 am]
BILLING CODE 4160-01-P