[Federal Register Volume 88, Number 38 (Monday, February 27, 2023)]
[Notices]
[Pages 12384-12385]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-03947]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2022-P-1013]


Determination That CHANTIX (Varenicline Tartrate) Tablets, 0.5 
Milligram and 1 Milligram, Has Not Been Withdrawn From Sale for Reasons 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 CHANTIX (varenicline tartrate) tablets, 0.5 milligram 
(mg) and 1 mg, has not been withdrawn from sale for reasons of safety 
or effectiveness to the extent that the drug can be manufactured or 
formulated in a manner that satisfies any applicable acceptable intake 
limit for nitrosamine impurities. This determination means that FDA 
will not begin procedures to withdraw approval of abbreviated new drug 
applications (ANDAs) that refer to this drug product, and it will allow 
FDA to continue to approve ANDAs that refer to the product as long as 
they meet relevant legal and regulatory requirements.

FOR FURTHER INFORMATION CONTACT: David Faranda, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6258, Silver Spring, MD 20993-0002, 301-
796-8767, [email protected].

SUPPLEMENTARY INFORMATION: Section 505(j) of the Federal Food, Drug, 
and Cosmetic Act (FD&C Act) (21 U.S.C. 355(j)) allows the submission of 
an ANDA to market a generic version of a previously approved drug 
product. To obtain approval, the ANDA applicant must show, among other 
things, that the generic drug product: (1) has the same active 
ingredient(s), dosage form, route of administration, strength, 
conditions of use, and (with certain exceptions) labeling as the listed 
drug, which is a version of the drug that was previously approved, and 
(2) is bioequivalent to the listed drug. ANDA applicants do not have to 
repeat the extensive clinical testing otherwise necessary to gain 
approval of a new drug application (NDA).
    Section 505(j)(7) of the FD&C Act 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 has been 
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 approval of 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.
    CHANTIX (varenicline tartrate) tablets, 0.5 mg and 1 mg, is the 
subject of NDA 021928, held by PF Prism CV (c/o Pfizer Inc.), and 
initially approved on May 10, 2006. CHANTIX is indicated for use as an 
aid to smoking cessation treatment.
    PF Prism CV has voluntarily discontinued marketing of CHANTIX 
(varenicline tartrate) tablets, 0.5 mg and 1 mg. The levels of the N-
nitroso-varenicline (NNV) impurity in Chantix exceeded FDA's acceptable 
intake limit.\1\ FDA's current understanding is

[[Page 12385]]

that the NNV impurity can be controlled within the acceptable intake 
limit by sponsors of varenicline products within the context of their 
particular applications.
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    \1\ Nitrosamine impurities in the drug supply are an important 
public health concern to which the Agency is dedicating significant 
resources. As explained in FDA's Guidance for Industry, Control of 
Nitrosamine Impurities in Human Drugs, ``Nitrosamine compounds are 
potent genotoxic agents in several animal species and some are 
classified as probable or possible human carcinogens by the 
International Agency for Research on Cancer (IARC). They are 
referred to as ``cohort of concern'' compounds in the ICH guidance 
for industry M7(R1) Assessment and Control of DNA Reactive 
(Mutagenic) Impurities in Pharmaceuticals To Limit Potential 
Carcinogenic Risk (March 2018).'' Many drug products have been found 
to contain levels of nitrosamines that are unacceptable or require 
further evaluation. FDA's current understanding is that nitrosamine 
levels in affected drug products have different causes and may be 
controlled using different strategies, including formulation design 
(i.e., adding antioxidants or adding pH adjusters that modify the 
microenvironment to base or neutral pH) and supplier qualification 
programs.
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    CHANTIX (varenicline tartrate) tablets, 0.5 mg and 1 mg, is 
currently listed in the ``Discontinued Drug Product List'' section of 
the Orange Book.
    Medley Pharmaceuticals Ltd. submitted a citizen petition dated June 
6, 2022 (Docket No. FDA-2022-P-1013), under 21 CFR 10.30, requesting 
that the Agency determine whether CHANTIX (varenicline tartrate) 
tablets, 0.5 mg and 1 mg, were withdrawn from sale for reasons of 
safety or effectiveness.
    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 CHANTIX (varenicline tartrate) tablets, 0.5 mg 
and 1 mg, has not been withdrawn for reasons of safety or effectiveness 
to the extent that the drug can be manufactured or formulated in a 
manner that satisfies any applicable acceptable intake limit for 
nitrosamine impurities.
    Accordingly, the Agency will continue to list CHANTIX (varenicline 
tartrate) tablets, 0.5 mg and 1 mg, 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. FDA will not begin procedures to withdraw approval of 
approved ANDAs that refer to this drug product. Additional ANDAs for 
this drug product may be approved by the Agency as long as they meet 
all other legal and regulatory requirements for the approval of ANDAs, 
including satisfying any applicable acceptable intake limit for 
nitrosamine impurities. If FDA determines that labeling for this drug 
product should be revised to meet current standards, the Agency will 
advise ANDA applicants to submit such labeling.

    Dated: February 22, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-03947 Filed 2-24-23; 8:45 am]
BILLING CODE 4164-01-P