FDA Guidance Seeks More Effective Postapproval Change Strategies

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FDA recently issued a much-anticipated draft guidance on how to define and report established conditions in market applications.


As part of its efforts to promote lifecycle management of drugs and biologics and to encourage continual improvement in manufacturing processes, FDA recently issued a much-anticipated draft guidance on how to define and report “established conditions” in market applications. In the process, the advisory clarifies when certain postapproval changes don’t always have to be reported in a supplement, an approach that aims to help the agency and industry adopt more flexible and effective postapproval change strategies.

The importance of refining reporting requirements for post-approval changes was emphasized at the April CMC Workshop sponsored by the Drug Information Association (DIA) and is discussed in more detail in the June 2015 issue of BioPharm International. FDA’s guidance on Established Conditions: Reportable CMC Changes for Approved Drug and Biologic Products was posted on the FDA website on May 29, 2015. It describes which factors in products, manufacturing processes, facilities and equipment, and elements of a control strategy “assure process performance and quality of an approved product;” changes in those conditions following product approval thus should be reported to FDA in a manner that reflects the severity and importance of the change.


Changes in those parameters determined not to be established conditions by FDA, however, often may be implemented within the manufacturer’s pharmaceutical quality system, without submitting a supplement. These include batch records, development data, characterization data, validation data, and batch analysis data. FDA notes, however, that such information should be made available if requested during an inspection or other review.

The main substance of the guidance identifies those sections of the common technical document (CTD) application that contain established conditions to assist companies and the agency in identifying those items. FDA hopes to help define gray areas, such as when a change in process controls may be considered an “established condition.” The expectation is that a better understanding of which elements of CMC information are established conditions and where they should be described in an application will support “a more effective postapproval submission strategy” that incorporates risk management principles; it also should enable FDA to utilize “more flexibility and risk-based principles” in regulating postapproval changes. FDA is looking for comments from industry on the proposal and related issues.