Top Deficiencies Found in CDER’s Micro Review of Regulatory Submissions Include Incomplete Information on Validation of Aseptic and Terminal Processes

Incomplete media fill information for aseptic processes and an inadequate comparison between production and validation conditions for terminal sterilization are among the microbiology concerns in regulatory submissions that most frequently generate information requests and deficiency letters from FDA’s Center for Drug Evaluation and Research (CDER).

At the PDA Aseptic Processing/Sterilization Conference in mid-June in Chicago, CDER Product Quality Microbiology Reviewer Jessica Cole cited the general lack of information – in particular, regarding media fills and terminal sterilization validation – as the top problem area CDER’s microbiology staff is finding in their reviews.

Cole emphasized that media fill information provided in an application needs to show that the simulations adequately mimic the manufacturing process and are sufficient to validate it. In turn, terminal sterilization processes should not only include detail on the production and validation conditions, but also provide a comparison of the two in which the linkages between them are clear, she stressed.

FDA often does not get enough detail on microbiology “across the board” for steriles, non-steriles, container-closure integrity testing, methods, release methods, and verification studies, she said, advising that “as much as you can send us, as much as your regulatory folks are willing to have you send us, is useful.”

[CLICK HERE for the complete story.with more on Cole’s discussion of the “top ten” micro deficiencies she has seen in submissions.  Nonsubscribers can purchase the story for $195 by contacting Karen Bertani (  For subscription/license information, click here.]