[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Draft Guidance for Industry on Bioequivalence Recommendation for 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access to the draft guidance documents.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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