Well here's something that doesn't happen very often, FDA asking Industry how to improve the Quality of ANDAs!!
On January 23rd FDA published a Notice in the Federal Register entitled:“Improving the Quality of Abbreviated New Drug Application Submissions to the Food and Drug Administration; Establishment of a Public Docket”
The purpose is stated as:
“The Food and Drug Administration (FDA) is establishing a public docket toi 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 is a rare opportunity indeed. Most often people working in Industry can only complain among themselves about FDA related issues that make their lives difficult. This is your opportunity to tell FDA what they should do to improve the ease of developing and submitting ANDAs. The Notice gives a list of “common recurring deficiencies” that they see in many ANDAs. This is a valuable list for any sponsor to study and to make sure that these common deficiencies do not occur in their ANDA filings. The list includes:
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.
This is a valuable checklist of common deficiencies that can be used to check that your ANDAs do not have these deficiencies before you file them.
In addition the Notice contains 4 questions that FDA thinks are important to the task of improving ANDA quality. These questions are:
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?
These questions should help in focusing sponsor thinking about how to improve the ANDA process.
So this is your opportunity to tell FDA what they should improve to help you in developing and filing ANDAs. The docket established by this notice to receive comments will remain open until March 24, 2014. Comments can be sent electronically by going to http://www.regulations.gov and following the instructions. As the saying goes “speak now or forever hold your silence!”
