More Clarifications on Some Significant Changes re: Generic Stability Program Implementation

In the Press Briefing Call this morning on the newly revised Q&A document on ANDA stability, three important and significant issues were clarified by the Office of Generic Drugs’ (OGD) Radhika Rajagopalan, Ph.D. that will have important implications for the generic industry.

1)     As noted in my blog post of yesterday (here), there was some uncertainty regarding the issue of the use of multiple lots of API for the primary stability batches.  Dr. Rajagopalan clarified that the operative sentence in C.Q4 A4 is that a minimum of two lots of API must be used in the three primary stability batches.  The first sentence is being rewritten to clarify this fact.

2)     Relative to E.Q1 and the response – OGD has listened to the industry and removed the absolute requirement for a fourth time point on accelerated conditions.  Dr. Rajagopalan indicated that the 6-month intermediate time point should obviate the need for the fourth time point if the product undergoes significant change at the 3-month or 6-month time station.  She also indicated if there appears that there will be a significant change based on the results of the 3-month time point; the firm can always add an additional accelerated testing point.

3)     The biggest change that may have really gone unnoticed based on the long history relative to the packaging of solid oral dosage forms is that OGD will accept the 100,000 dosage form minimum for packaging from the three primary stability batches – so it could be 40,000 from batch 1, 30,000 from batch 2 and 30,000 from batch 3 to satisfy the 100,000 requirement.  Previously it was thought that at least one primary batch would need to have at least 100,000 dosage units packaged.  But that is not the case now.  This is a huge change from past practice.  Just be certain you take into account all container closure systems, cGMP under 21 CFR 211, and the need for reserve samples outlined in the regulations when deciding on your stability packaging needs.