[Federal Register Volume 79, Number 15 (Thursday, January 23, 2014)]
[Notices]
[Pages 3828-3829]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-01309]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-N-0032]


Improving the Quality of Abbreviated New Drug Application 
Submissions to the Food and Drug Administration; Establishment of a 
Public Docket

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; establishment of docket; request for comments.

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SUMMARY: The Food and Drug Administration (FDA) is establishing a 
public docket to receive input and suggestions from the public on ways 
to improve the quality of abbreviated new drug applications (ANDAs) and 
associated amendments and supplements to FDA's Office of Generic Drugs 
(OGD). Specifically, FDA is interested in hearing about any 
difficulties sponsors are having developing and preparing their ANDA 
submissions that FDA could help address, for example by providing more 
or better information to industry. This action is intended to solicit 
suggestions that will improve the completeness and quality of ANDA 
submissions to FDA. FDA is also seeking input on how to best share 
suggestions for improving the quality of ANDAs with the generic drug 
industry. More complete, higher quality ANDA submissions will 
positively affect the availability of low-cost, high-quality generic 
drugs to the public.

DATES: Although FDA welcomes comments at any time, to help FDA address 
issues related to ANDA submission quality in a timely fashion, we 
encourage submission of electronic or written comments by March 24, 
2014.

ADDRESSES: Submit electronic comments 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. All comments should be identified with the docket 
number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Elizabeth Giaquinto, Center for Drug 
Evaluation and Research (HFD-600), Food and Drug Administration, 7519

[[Page 3829]]

Standish Pl., Rockville, MD 20885, 240-276-8607, 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    On July 9, 2012, the President signed the Generic Drug User Fee 
Amendments (GDUFA) (Pub. L. 112-144, Title III) into law. With the 
enactment of GDUFA, OGD committed to expedite the availability of high-
quality, lower cost generic drugs by bringing greater predictability to 
the review times for ANDAs and associated amendments and supplements. 
OGD agreed to specific performance review metrics to reduce the time 
needed to bring a generic drug to market compared to typical pre-GDUFA 
review times. However, OGD's review is often hindered by the quality of 
the ANDA submissions.
    As part of efforts to fulfill its GDUFA commitments, OGD is 
soliciting input and suggestions from all interested stakeholders on 
how to improve the completeness and quality of ANDA submissions to OGD. 
FDA is interested in hearing about any difficulties sponsors are having 
developing and preparing their applications for submission that FDA 
could help address (please see specific questions for comment listed in 
this section of the document). FDA is also seeking input on how to best 
share suggestions for improving the quality of ANDA submissions with 
industry. To receive comments and suggestions from the public, FDA is 
establishing a public docket. Improving the quality of ANDA submissions 
will result in more submissions accepted for filing, fewer amendments, 
and easily correctable deficiencies, and ultimately, more generic drug 
approvals.
    FDA review staff routinely note common, recurring deficiencies 
found in ANDA submissions to OGD and try to communicate these 
deficiencies to industry in guidance documents and during 
presentations. Common, recurring deficiencies include, but are not 
limited to:
     Filing: Failure to provide a completed Form FDA 356h; 
unjustified inactive ingredient levels; inadequate dissolution data; 
packaging less than the recommended threshold amount without 
justification; inadequate or insufficient stability data; submissions 
of non-qualitative and non-quantitative (not Q/Q) same formulations; 
electronic submission and formatting deficiencies; applications 
containing an incorrect or unfounded basis of submission.
     Chemistry: Poor or inadequate justification of impurities 
limits; failure to provide a list of potential impurities and their 
origins; failure to provide adequate verification of analytical 
procedures for active pharmaceutical ingredient and finished dosage 
forms, where appropriate; failure to identify the critical 
manufacturing process parameters or to link in-process controls to 
development studies; failure to provide appropriate acceptance criteria 
of manufacturing yields for the critical steps, or providing yield 
values varying without adequate rationale or explanation.
     Sterility assurance for sterile drug product applications 
manufactured by aseptic processing: Failure to describe sterilization 
and/or depyrogenation of relevant equipment and components that may 
come in contact with the sterile drug; failure to provide relevant 
validation data for sterilization and/or depyrogenation of relevant 
equipment and components that may come in contact with the sterile 
drug; failure to provide validation data for sterilizing grade filters, 
if needed; failure to provide process simulation data for the proposed 
aseptic filling process/line/room.
     Bioequivalence: Inaccurate and/or incomplete information 
contained in electronic tables; submission of pharmacokinetic repeats; 
inaccurate and/or incomplete biowaiver requests (e.g., inappropriate 
method of solubility determination, lack of dissolution data for all 
strengths, missing standard operating procedures for analytical 
methods).
     Fatal flaws: Significant flaws in the design of a drug 
product such that the proposed product will not be able to meet all 
conditions of use of the reference listed drug.
     Drug master files: Submission contains more than a single 
drug substance or more than a single drug manufacturing process; 
failure to update the drug master file following a large number of 
amendments or time lapse since the original submission; failure to 
provide a complete description of manufacturing process and controls; 
failure to justify appropriate starting materials.
    As noted previously, this list provides examples of common, 
recurring deficiencies FDA has identified. FDA is particularly 
interested to learn what steps it can take to help reduce these 
deficiencies and enhance the completeness and quality of ANDA 
submissions. Comments submitted to this docket are encouraged to 
address one or more of the following points, as well as any others that 
the commenter thinks are important:
    1. What aspects of the ANDA application process are confusing or 
not well defined?
    2. What problems do ANDA applicants encounter when developing a 
submission that FDA could help address?
    3. Prior to GDUFA, were ANDA submissions consistently slowed or 
stalled at certain recurring review points post-filing? If so, why?
    4. How should FDA share suggestions for improving ANDA submissions 
with industry, beyond issuing regulatory guidance?

II. Comments

    Interested persons may submit either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). 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, and will be posted to the docket at http://www.regulations.gov.

    Dated: January 16, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-01309 Filed 1-22-14; 8:45 am]
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