[Federal Register Volume 77, Number 29 (Monday, February 13, 2012)]
[Notices]
[Pages 7586-7587]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-3233]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2007-D-0369]
Draft Guidance for Industry on Bioequivalence Recommendation for
Nitroglycerin Metered Spray/Sublingual Products and Metered Aerosol/
Sublingual Products; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of two draft guidances for industry entitled
``Bioequivalence Recommendations for Nitroglycerin,'' one for
nitroglycerin metered spray/sublingual products and one for
nitroglycerin metered aerosol/sublingual products. The recommendations
provide specific guidance on the design of bioequivalence (BE) studies
to support abbreviated new drug applications (ANDAs) for these
products. The draft guidances are revised versions of previously
published draft guidances on the subject.
DATES: Although you can comment on any guidance at any time (see 21 CFR
10.115(g)(5)), to ensure that the Agency considers your comment on the
draft guidances before it begins work on the final versions of the
guidances, submit either electronic or written comments on the draft
guidances by April 13, 2012.
ADDRESSES: Submit written requests for single copies of the draft
guidances to the Division of Drug Information, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD 20993-0002. Send
one self-addressed adhesive label to assist that office in processing
your requests. See the SUPPLEMENTARY INFORMATION section for electronic
access to the draft guidance documents.
Submit electronic comments on the draft guidances to http://www.regulations.gov. Submit written comments to the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Doan T. Nguyen, Center for Drug
Evaluation and Research (HFD-600), Food and Drug Administration, 7519
Standish Pl., Rockville, MD 20855, 240-276-8608.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register sof June 11, 2010 (75 FR 33311), FDA
announced the availability of a guidance for industry, ``Bioequivalence
Recommendations for Specific Products,'' which explained the process
that would be used to make product-specific BE recommendations
available to the public on FDA's Web site at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. As
described in that guidance, FDA adopted this process as a means to
develop and disseminate product-specific BE recommendations and provide
a meaningful opportunity for the public to consider and comment on
those recommendations. This document announces the availability of two
revised draft BE recommendations, one for nitroglycerin metered spray/
sublingual products and one for nitroglycerin metered aerosol/
sublingual products.
Nitrolingual Pumpspray (nitroglycerin lingual spray), approved by
FDA in October 1985, is a metered dose spray indicated for acute relief
of an attack or prophylaxis of angina pectoris due to coronary artery
disease. Nitromist (nitroglycerin lingual aerosol), approved by FDA in
November 2006, is another metered dose spray indicated for acute relief
of an attack or acute prophylaxis of angina pectoris due to coronary
artery disease. Nitrolingual Pumpspray and Nitromist are designated as
reference listed drugs (RLDs), and therefore any ANDAs for generic
nitroglycerin lingual spray or generic nitroglycerin lingual aerosol
must demonstrate BE to the relevant RLD prior to approval. There are no
approved ANDAs for these products.
In February 2010, FDA posted on its Web site a draft guidance for
industry on the Agency's recommendations for BE studies to support
ANDAs for nitroglycerin metered spray/sublingual products (Draft
Nitroglycerin Spray BE Recommendations of February 2010). In that draft
guidance, FDA recommended three studies to demonstrate BE of generic
nitroglycerin metered spray/sublingual products: An in vivo fasting
study, an in vitro study of unit dose and uniformity of unit dose, and
an in vitro study of priming and tail off.
In March 2010, FDA posted on its Web site a draft guidance for
industry on the Agency's recommendations for BE studies to support
ANDAs for nitroglycerin metered aerosol/sublingual products (Draft
Nitroglycerin Aerosol BE Recommendations of March 2010). In that draft
guidance, FDA recommended three studies to demonstrate BE of generic
nitroglycerin metered aerosol/sublingual products: An in vivo fasting
study, an in vitro study of unit dose and uniformity of unit dose, and
an in vitro study of priming and tail off.
FDA has reconsidered the recommendations for both of these draft
guidances and has decided to revise them. In November 2011, FDA
withdrew the Draft Nitroglycerin Spray BE Recommendations of February
2010 and the Draft Nitroglycerin Aerosol BE Recommendations of March
2010. FDA is now issuing revised draft guidances for industry on BE
recommendations for nitroglycerin metered spray/sublingual products
(Revised Draft Nitroglycerin Spray BE Recommendations) and
nitroglycerin metered aerosol/sublingual products (Revised Draft
Nitroglycerin Aerosol BE Recommendations). In these revised draft
guidances, FDA recommends one
[[Page 7587]]
study (an in vivo fasting study) to demonstrate BE of generic
nitroglycerin metered spray/sublingual products and generic
nitroglycerin metered aerosol/sublingual products. In both of the
revised draft guidances, FDA notes that even though we have not
requested comparative in vitro studies, in vitro studies outlined in
the 2002 guidance for industry, ``Nasal Spray and Inhalation Solution,
Suspension, and Spray Drug Products--Chemistry, Manufacturing, and
Controls Documentation,'' should still be submitted for chemistry,
manufacturing, and controls evaluation.
In December 2010, G. Pohl-Boskamp GmbH and Company KG (Pohl),
manufacturer of the RLD Nitrolingual Pumpspray, filed a citizen
petition challenging FDA's Draft Nitroglycerin Spray BE Recommendations
of February 2010 (Docket No. FDA-2010-P-0648). FDA is reviewing the
issues raised in the petition and will consider any comments on the
Revised Draft Nitroglycerin Spray BE Recommendations before responding
to Pohl's citizen petition and finalizing its BE recommendation for
nitroglycerin metered spray/sublingual products.
These draft guidances are being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). The draft guidances,
when finalized, will represent the Agency's current thinking on the
design of BE studies to support ANDAs for nitroglycerin metered spray/
sublingual products and nitroglycerin metered aerosol/sublingual
products. They do not create or confer any rights for or on any person
and do not operate to bind FDA or the public. An alternative approach
may be used if such approach satisfies the requirements of the
applicable statutes and regulations.
II. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) either electronic or written comments regarding this
document. It is only necessary to send one set of comments. Identify
comments with the docket number found in brackets in the heading of
this document. Received comments may be seen in the Division of Dockets
Management between 9 a.m. and 4 p.m., Monday through Friday.
III. Electronic Access
Persons with access to the Internet may obtain the documents at
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or http://www.regulations.gov.
Dated: February 7, 2012.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2012-3233 Filed 2-10-12; 8:45 am]
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