In the Federal Register (FR) Pre-Publication listing this morning (here), FDA is announcing the issuance of a Draft Guidance entitled, Abbreviated New Drug Applications: Content and Format of Abbreviated New Drug Applications. The FDA says in the FR notice that “[I]n an effort to increase the number of original ANDAs that the Agency can receive upon initial submission and to decrease the number of review cycles required to approve an application for marketing, FDA prepared this Guidance on improving the quality of original ANDA submissions. FDA is committed to providing comprehensive assistance in the early stages of the application process to ensure that an original ANDA contains all information necessary for FDA to complete its review in one review cycle.“
The FR notice goes on to state:
“The guidance document is intended to assist applicants in preparing complete and high-quality original abbreviated new drug applications (ANDAs) for submission to FDA under the Federal Food, Drug, and Cosmetic Act. The guidance summarizes the statutory and regulatory requirements for ANDAs, references existing guidance documents, and incorporates additional recommendations on the content and format of ANDA submissions. This guidance describes the Common Technical Document format for human pharmaceutical product applications and specifies the information to be submitted in each section of the application.”
The Guidance actually issues today and was posted on the FDA website this morning. The 32 page document (here) outlines the Office of Generic Drugs (OGD) expectations and requirements for submission in a Module-by-Module and section-by section approach used in the CTD format. FDA states that “[T]his guidance identifies the information an applicant should include to ensure that a complete, high-quality application is submitted to FDA. FDA has previously published guidance on the filing process, including the refuse-to-receive standards, which should be reviewed thoroughly to avoid common deficiencies found in ANDA submissions.”
The Guidance Document goes into exquisite detail relative to the submission expectations, standards and requirements and brings together information in one place that has been previously scattered throughout many Guidance documents, FR publications, FDA presentations and some general knowledge issues that may not actually be written down in any one place like they are in this document. It also provides reference to numerous other Guidance and regulations and statutes where appropriate.
The Document also provides an Appendix A listing all references relative to the citations in the Guidance and an Appendix B that provides a cover letter template that outlines a minimum of 17 specific paragraphs that should be used to provide appropriate information to include in the cover letter.
Even with the specificity of this outstanding document (and there is really not a lot new here), but there are a couple of issues that may have been muddied by this Draft Guidance document.
- While there is reference to the need to submit executed batch records and blank batch records, there is not a specific statement that batch records for all of the exhibit / primary stability batches to support the ANDA must be included.
- In the stability section this Guidance states “For liquid or semisolid products, applicants should submit accelerated stability data reflecting the worst-case storage conditions (related to orientation), at minimum.” This seems to contradict the Q&A stability guidance where upright and inverted/horizontal storage orientations are recommended. Does this mean OGD wants only worst case for accelerated but both orientations for room temperature studies? This needs to be clarified in the final guidance.
OGD recognizes it needs to review to approval more applications in the first review cycle if it hopes to get a good handle on the still huge backlog of pending applications, and is working hard to issue guidance and recommendations to help ANDA sponsors submit more complete and higher quality applications to meet that end. OGD must also remember that many applications are already in the queue and that many more are on the way into OGD as we speak. Improvement in submissions under this guidance may not be evident for at least a year since it is not expected that most ANDAs submitted taking this Guidance into consideration won’t be picked up until then. Let’s hope that OGD means what it says about application requirements and that is an applicant does submit the appropriate and necessary information there will be an increasing number of first cycle ANDA approvals. If history is an indicator and given that there is really nothing that new in the Guidance, I still have some doubts.