[Federal Register Volume 83, Number 176 (Tuesday, September 11, 2018)]
[Notices]
[Pages 45940-45941]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-19663]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-N-3262]


Determination That CEFZIL (Cefprozil) Tablets, 250 Milligrams and 
500 Milligrams, and for Oral Suspension, 125 Milligrams/5 Milliliters 
and 250 Milligrams/5 Milliliters, Were Not Withdrawn From Sale for 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 or Agency) has 
determined that CEFZIL (cefprozil) tablets, 250 milligrams (mg) and 500 
mg and CEFZIL (cefprozil) for oral suspension, 125 mg/5 milliliters 
(mL) and 250 mg/5 mL were not withdrawn from sale for reasons of safety 
or effectiveness. This determination will allow FDA to continue to 
approve abbreviated new drug applications (ANDAs) that refer to these 
drugs as long as they meet relevant legal and regulatory requirements.

FOR FURTHER INFORMATION CONTACT: Diana J. Pomeranz, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6288, Silver Spring, MD 20993-0002, 240-
402-4654.

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 (FD&C 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.
    Under Sec.  314.161(a)(2), the Agency must also determine whether a 
listed drug was withdrawn from sale for reasons of safety or 
effectiveness if ANDAs that referred to the listed drug have already 
been approved prior to its market withdrawal. If the Agency determines 
that a listed drug was withdrawn from sale for reasons of safety or 
effectiveness, and there are approved ANDAs that reference that listed 
drug, FDA will initiate a proceeding to determine whether the 
suspension of the ANDAs is also required (21 CFR 314.153(b)).
    CEFZIL (cefprozil) tablets, 250 mg and 500 mg, are the subject of 
NDA 050664 held by Corden Pharma Latina S.p.A., and initially approved 
on December 23, 1991. CEFZIL (cefprozil) for oral suspension, 125 mg/5 
mL and 250 mg/5 mL, is the subject of NDA 050665 held by Corden Pharma 
Latina S.p.A., and initially approved on December 23, 1991. CEFZIL is 
indicated for the treatment of patients with mild to moderate 
infections caused by susceptible strains of the designated 
microorganisms in the conditions listed below:
    <bullet> Upper respiratory tract: Pharyngitis/tonsillitis caused by 
Streptococcus pyogenes; otitis media caused by Streptococcus 
pneumoniae, Haemophilus influenzae (including [beta]-lactamase-
producing strains), and Moraxella (Branhamella) catarrhalis (including 
[beta]-lactamase-producing strains); and acute sinusitis caused by 
Streptococcus pneumoniae, Haemophilus influenzae (including [beta]-
lactamase-producing strains), and Moraxella (Branhamella) catarrhalis 
(including [beta]-lactamase-producing strains);
    <bullet> Lower respiratory tract: Acute bacterial exacerbation of 
chronic bronchitis caused by Streptococcus pneumoniae, Haemophilus 
influenzae (including [beta]-lactamase-producing strains), and 
Moraxella (Branhamella) catarrhalis (including [beta]-lactamase-
producing strains); and
    <bullet> Skin and skin structure: Uncomplicated skin and skin-
structure infections caused by Staphylococcus aureus (including 
penicillinase-producing strains) and Streptococcus pyogenes. Abscesses 
usually require surgical drainage.
    In a letter dated September 7, 2010, Bristol-Myers Squibb \1\ 
notified FDA that CEFZIL (cefprozil) tablets, 250 mg and 500 mg and 
CEFZIL (cefprozil) for oral suspension, 125 mg/5 mL and 250 mg/5 mL, 
were discontinued from sale, and FDA moved the drug products to the 
``Discontinued Drug Product List'' section of the Orange Book. Later, 
Corden Pharma Latina S.p.A. notified the Agency in writing that these 
drug products were no longer marketed and requested that the approval 
of the applications be withdrawn. In the Federal Register of June 21, 
2017 (82 FR 28322 at 28326), the Agency issued a notice withdrawing 
approval of the applications, effective July 21, 2017.
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    \1\ On May 26, 2011, Bristol-Myers Squibb transferred ownership 
of NDA 050664 and NDA 050665 to Corden Pharma Latina S.p.A.
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    After reviewing Agency records and based on the information we have 
at this time, FDA has determined under Sec.  314.161 that CEFZIL 
(cefprozil) tablets, 250 mg and 500 mg, and CEFZIL (cefprozil) for oral 
suspension, 125 mg/5 mL and 250 mg/5 mL, were not withdrawn from sale 
for reasons of safety or effectiveness.
    We note that CEFZIL (cefprozil) tablets, 250 mg and 500 mg, and 
CEFZIL (cefprozil) for oral suspension, 125 mg/5 mL and 250 mg/5 mL, 
previously were approved with an indication for secondary bacterial 
infection of acute bronchitis (SBIAB). On October 3, 2016, FDA sent 
Corden Pharma Latina S.p.A. a Prior Approval Supplement Request letter 
seeking removal of the SBIAB indication from the labeling of these drug 
products. In response, on October 28, 2016, Corden Pharma Latina S.p.A. 
submitted supplements proposing to remove the indication. On November 
22, 2016, FDA approved these supplements and the indication was

[[Page 45941]]

removed. The ANDA applicants referencing these NDAs subsequently 
followed suit and submitted supplements proposing to remove the SBIAB 
indication from their labeling. The Agency approved these supplements.
    Further, based on a review of relevant information, FDA concluded 
that the SBIAB indication is not appropriate because most cases of 
SBIAB are considered to be viral or non-infectious. As an antibacterial 
drug, CEFZIL (cefprozil) is not considered to be effective to treat 
SBIAB. Such use of CEFZIL (cefprozil) would likely result in 
inappropriate antibacterial drug use. Accordingly, the risk benefit 
balance for the treatment of SBIAB with CEFZIL (cefprozil) is 
unfavorable and does not support approval of these products (or ANDAs 
referencing them) for this indication.
    The Agency will continue to list CEFZIL (cefprozil) tablets, 250 mg 
and 500 mg, and CEFZIL (cefprozil) for oral suspension, 125 mg/5 mL and 
250 mg/5 mL, in the ``Discontinued Drug Product List'' section of the 
Orange Book. FDA will continue to accept and, where appropriate, 
approve ANDAs that refer to these drug products, but does not intend to 
do so if they propose to include the SBIAB indication (see, e.g., 
section 505(j)(2)(A)(v) and (j)(4)G) of the FD&C Act and 21 CFR 
314.94(a)(8)(iv) and 314.127(a)(7)). If FDA determines that labeling 
for this drug product should be revised, the Agency will advise ANDA 
applicants to submit such labeling.

    Dated: September 4, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-19663 Filed 9-10-18; 8:45 am]
 BILLING CODE 4164-01-P