I submitted a Citizen Petition to the FDA on October 1, 2018, requesting the withdrawal of its guidance documents and related recommendations concerning assessments of drug dissolution characteristics of pharmaceutical products such as tablets and capsules (link).
On April 1, 2019, the FDA responded on an interim basis, stating that the FDA has been unable to reach a decision on the petition because it raises complex issues requiring extensive review and analysis by Agency officials (see here) or @ the FDA site (link).
I believe that a decision has already been made in support of the Petition (i.e., withdrawal of the guidance documents); however, the FDA requires time for its implementation. My reasoning is as follows:
The Petition has two parts; Part 1 (Rationale) – requires the use of currently recommended dissolution testers (USP Paddle/Basket) which have never been validated and/or qualified for the intended purposes, i.e., relevance to the assessment of products dissolution in humans. Further, if a (blinded) product sample is given to an analyst, he/she would not be able to determine its dissolution characteristics, making the test scientifically invalid and practically useless. Part 2 – (Guidance withdrawal) considering the lack of validity of the apparatuses and testing as described in Part 1, the guidance documents become null and void as these depend on the use of non-validated apparatuses. Hence their withdrawal was requested.
To dismiss the Petition, all the FDA had to do was provide evidence (link, reference and/or laboratory document) demonstrating that apparatuses are validated/qualified for the intended use. This should have required practically no time. Secondly, if an example was not available already for the analysis of a blinded sample, then it would have taken the Agency couple of days (maximum) to run an experiment to establish the dissolution characteristics of the product. As the testers are not qualified or validated, obviously, testing of a (blinded) sample is not possible. Thus, the Petition could not be dismissed.
Therefore, in my view, FDA is considering withdrawing the guidance documents. This should not require an extended period as well. However, considering the issue’s complexity (as noted in the response), such as meeting procedural formalities and associated adjustments may require extra time, which is understandable. This may easily take many months.
If my interpretation is correct, it becomes important to promptly inform the scientific and manufacturing communities about the situation so that they should be cautious and avoid using the non-validated dissolution testers and methods. In addition, it will provide an opportunity to explore other options for addressing the issues, perhaps submitting ideas to the authorities as well for moving forward. Noting that no one is determining, or can determine, valid or useful dissolution results of any product (1, 2).
I look forward to promptly resolving the issue by removing the non-validated/non-qualified (thus non-GMP) dissolution testers and tests and the associated guidance documents from the regulatory system. It will lead to simpler, efficient, and science-based approaches to assessing and monitoring the quality of pharmaceutical products.