[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Milligram and 1 Milligram, Has Not Been Withdrawn From Sale for Reasons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(mg) and 1 mg, has not been withdrawn from sale for reasons of safety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