CMC Postapproval Manufacturing Changes to be Documented in Annual Reports
Well, it seems to be the season for the issuance of significant new guidances. For several years now FDA has been promising guidance on a relaxed set of annually reportable CMC changes. Yesterday, without warning, it finally arrived. FDA posted a Final Guidance on Annually Reportable Manufacturing Changes. I must say I really like the new format for Guidances, especially the listing of related guidances relevant to the topic. In the past you had to remember which other guidances might also address the topic, now the guess work is gone.
For those of you who can't wait, turn straight to page 8 for a list of over 30 new examples of changes that previously required a supplemental filing that can now be filed in the Annual Report. As someone who labored to file 100's of postapproval supplements I have to say that this is a tremendous help. Not only will it eliminate the burden of preparing and making the supplemental filings, it will also enable these changes to be implemented immediately. People often overlook the damage done by having to wait sometimes years to be able to implement needed changes to solve quality problems in manufacturing. In addition starting on page 12 are a list of changes excepted from the existing guidances addressing postapproval changes.
This Guidance is notable for a number of changes permitted to sterile or aseptically filled products. Previously almost no changes to this type of product were allowed without submission of a supplement. It seems the Agency's risk tolerance for steriles is increasing, if only a little.
A few highlights of the new Annually Reportable Changes are:
Components and Composition
Change from one coating formulation to another previously used formulation for immediate-release solid dosage forms.
Change from one inactive ingredient supplier to another where the specifications remain the same. This includes inactive ingredients subject to a DMF
