When Do We Accommodate Shifts in Industry Practice?
All Situation Room examples are constructed and not descriptions of actual events.
Published on: June 18, 2024
Jason Cavett
Share This Article with the Stability Community!
What is the stability situation?
In a May 2024 StabilityHub Office Hours session our QA head learned about a possible growing trend in which API (or possibly key device components) are being artificially aged prior to their inclusion in manufacture of a stability batch. This seems like a very expensive path to take that is not necessarily representative of real-world exposure. It also seems that stability characteristics of a formulated product would be independent of the API—at least in the small molecule world, so this practice would be moot. Most importantly, no agency has approached us requiring this. Still, several participants in the online conference noted that they had either performed this or had heard of it being done.
Our new small molecule tablet is (or was) within three months of filing as we now having sufficient stability data on primary batches and even have commercial scale batches scheduled for initiation in a few weeks. But QA has slammed on the brakes, claiming that we need to ensure that at least one of the commercial batches is manufactured using aged API—either aged under accelerated storage or naturally by using a pilot batch manufactured over two years ago.
How should this be resolved?
What action should we be taking regarding our filing timeline as related to this potential shift industry practice? Here are some suggestions from our end, but please elaborate more from your experience:
1. Delay the filing for at least 9 months—After three months of aging API material at accelerated conditions produce a stability-specific batch and show comparability with 6 months of long-term data. 2. Perform a risk assessment to document the anticipated risk of aged API in the given formulation—hopefully showing through historical data that current formulation is independent of the API’s impurity profile. 3. Don’t delay the filing for this potential trend when the agency has not requested this data. Just allow the randomness of the annual stability commitment batches to cover real-world aged API as production follows its normal timing.
We Want to Hear Your Thoughts!
October 5, 2024
Packaging is being changed late in development while also trying to shortcut around quality checks and balances that Stability is intended for. How does a quality representative explain to upper management the risk they are taking on?
September 7, 2024
What are some ways we could finish cooking this half-baked digitalization process and make our digitized data even more accessible and user friendly?
August 10, 2024
What career path should I take and how can I balance my work and personal life if I choose the difficult stability career path option?
Share your questions and experiences
A stabilitarian encounters new situations every day. StabilityHub’s discussion forums give Stabilitarians an opportunity to ask questions and offer solutions to specific scenarios. Join in the conversations with other Stabilitiarians and share your knowledge!
A stabilitarian encounters new situations every day. StabilityHub’s discussion forums give Stabilitarians an opportunity to ask questions and offer solutions to specific scenarios. Join in the conversations with other Stabilitiarians and share your knowledge!
