At the Center for Drug Evaluation & Research (CDER) Small Business Industry Assistance (SBIA) meeting held on April 25th, titled “Facilitating Generic Product Availability Through Product-Specific Guidances (PSGs) for 2024,” the FDA presented some updates regarding the FDA Dissolution Database. Dr. Leah Falade, Senior Pharmacologist in the Office of Pharmaceutical Quality, CDER, was the presenter in Session 6. This presentation, along with other presentations on hot topics that were discussed during the webinar, will be posted on the FDA CDER website soon. Look for the posts and enjoy the gems they may present to you and your firm.
The dissolution methods database currently includes 1,518 dissolution methods. Dr. Falade pointed out that these methods should be used as a starting point for method development; however, the final method should be optimized for your formulation and justified. The FDA discussed this additionally on the Q&A page (here), where it provides recommendations on what it expects to see related to dissolution for a specific ANDA submission.
Did you know that, just like PSG batch postings, dissolution database updates are posted on a quarterly basis? (On occasion, updates may be posted outside the normal scheduled quarterly updates if a special case arises, and an urgent correction is needed.) Updates can come from multiple sources, but primarily emanate from Prior Approval Supplements (PASs) to the NDA product which may inform the FDA of a change in formulation or test method that gives FDA reason to reconsider the current method listed. Alternatively, the FDA stated that when it receives requests or comments from applicants via other methods, they are tracked via an internal system (ECO) and may be used as a basis for updates to the dissolution database.
One other resource that was mentioned is the final FDA Guidance for Industry “Dissolution Testing and Acceptance Criteria for Immediate-Release Solid Oral Dosage Form Drug Products Containing High Solubility Drug Substances“ (August 2018). This document outlines two potential methods to use for highly soluble drug substances in immediate-release solid oral dosage products, provided that certain criteria are met. The Guidance offers some variations (e.g., speed, etc.) on these two methods and states where additional justification should be provided.
Additionally, beginning in September 2023, methods using USP Purified Water (water) as the media were revised as water is not physiologically relevant and lacks buffering capacity. There were additional questions asked during the Q&A session such as “What do we use if the USP monograph has a dissolution method that uses water as a media?” and the response was a little unclear as Dr. Falade stated that the methods in the database are recommendations and the FDA recommends that you try different media to see how your product behaves. It was understood by me and others in the audience of this webinar that the FDA will no longer be accepting dissolution methods that use USP Purified Water only (i.e., with no buffering capacity) as the media even if they are the current USP methods. However, the expectation remains that you will need to demonstrate that your method is equivalent to or better than the USP method as well as demonstrate that it is discriminatory for the proposed dosage form and sensitive to possible changes in the quality of the drug product.
It will be interesting to see how the FDA plans to implement the change from USP Purified Water to other media in the USP and for approved products. Meanwhile, industry is surely wondering what the impact will be and how soon it needs to react.
If you have any questions about your dissolution methods or planning for changes to them, Lachman can help! Please reach out to us at LCS@LachmanConsultants.com for a consultation.
