Perspectives on the New Stability Guidance Shine at GPhA Fall Tech Conference

Kiran Krishnan (Vice President, Regulatory Affairs, Apotex) presented an overview of the new stability requirements and the implications on the Generic Industry. He noted that

  • Cost of generic drug development increased at a minimum 1.5-fold, but based on API costs could be much higher
  • Timelines of development increased by 2-fold
  • It is projected that the workload in stability labs for the enhanced stability testing will increase by 45% over 3 years
  • Firms stability study budget will increase by 40% over 5 years

This also means additional capital expenses, personnel hiring issues, and analytical work.  The problem that firms may run into is pushing back their R&D program to be able to meet filing date requirements.

Other concerns relate to bracketing and matrixing under the ICH guidelines.  The generic industry has great angst over use of this Guidance because, in the past, OGD has not accepted other than routine bracketing for solid oral dosage forms.  Other requests for bracketing or matrixing scenarios were almost always rejected by OGD.

Kiran requested on behalf of GPhA that:

  • The FDA reconsider the adoption of the fourth time point where ICH requirements only requires 3 points. (It appeared from the FDA comments during the Q&A session that FDA will likely revise the data point requirements to be consistent with ICH [3 time points – but don’t take this to the bank until FDA revises its Q&A guidance].)
  • GPhA proposes for Agency’s consideration on a pathway to addition of alternate manufacturing site. GPhA proposes a pathway for addition of alternate manufacturing site by manufacturing one of the pilot scale batches at the alternate site.
  • The Generic Industry requests the Agency to keep this Q&A document as dynamic and to be updated periodically as Agency becomes aware of new issues
  • GPhA believes there is an opportunity to discuss on Prior Approval Supplement relief due to additional data provided in the ANDA in combination with QbD information

Susan Rosencrance, Ph.D., Acting Deputy Director for Chemistry at OGD, went over the stability requirements under the new Guidance document on this topic (see previous post here).   She noted that the three-batch requirement (as previously reported) would be required for all products, but notes that certain exceptions with justification may be considered for the following extreme situations:

  • A drug shortage ANDA
  • ANDAs that meet a specific U.S. Government need
  • ANDAs where the RLD has an orphan drug exemption
  • ANDAs that fall under the PEPFAR program or PET guidance recommendations
  • ANDAs using a controlled drug substance with certain limitations where quotas may be impacted

There appears to be a hint that OGD may be reconsidering the requirements for 4 specific time points where the ICH only requires 3 time points.  One of the FDA staff said, basically, we heard you loud and clear at the CMC workshop, but we need to sift through the comments and then see where we are.  As you know, one of the reasons FDA chose to revise the ANDA stability requirements was to be consistent with the ICH Stability guidance.  So we will have to wait to see where this zeros out.  Stay tuned to the blog for further details.