Food and Drug Administration, HHS.
Notice; establishment of docket; request for comments.
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.
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.
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.
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FOR FURTHER INFORMATION CONTACT:
Elizabeth Giaquinto, Center for Drug Evaluation and Research (HFD-600), Food and Drug Administration, 7519 Start Printed Page 3829Standish Pl., Rockville, MD 20885, 240-276-8607, email@example.com.
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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?
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.
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Dated: January 16, 2014.
Assistant Commissioner for Policy.
[FR Doc. 2014-01309 Filed 1-22-14; 8:45 am]
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