FDAer lists most common aseptic production slips.

FDA investigators still find recurrent problems in aseptic processing of sterile pharmaceuticals, although there is a "downward slope" in noncompliance found during preapproval inspections.

Robert Coleman, national expert investigator with FDA's Office of Regulatory Affairs, listed the following aseptic processing deficiencies during his address to the joint Parenteral Drug Association (PDA)/FDA conference in Bethesda, MD, Oct. 1:

1. Disposing of media fills that in some way did not meet the norm and not including them in evaluating a process. Sometimes the defects that led to the disposal might only be cosmetic, he said.

Asked whether strict acceptance/rejection criteria for media fills might provide a more accurate picture of the process, Coleman said that sometimes those discarded media fills might provide valuable information. Especially when results were borderline. The fills that were discarded might have provided the data needed to obtain conclusive results, he explained.

2. Over-sterilization of media. This could cause problems by diminishing the nutritive value of the media, Coleman said.

3. Failure to invert media fill units and lack of a system to identify when units were filled during the process.

Such a system can help track failures and help determine what to investigate, he said. Some companies get the incubation temperatures wrong, he continued, while others try to evaluate media fills in opaque containers. Investigators also report lack of proper investigations into media fill failures.

Training, clear SOPs stressed

4. Training. Coleman said some drug firm employees lack necessary training in such aspects of their job as proper gowning and aseptic techniques. He criticized manufacturers for hiring people with no training to perform media fill evaluation, especially temporary employees with no relevant experience.

5. SOPs being unclear about definitions. For example, when an SOP refers to "turbidity," Coleman said, asking several different people will elicit an equal number of opinions on what the word actually means.

Coleman also objected to the use of "Post-it" notes on SOPs, short notes on how to perform a procedure attached to the original procedure with adhesive note paper. He recommended that if the official procedure does not work as written, change the procedure. Coleman called the "Post-it" notes "a Readers Digest version of the SOP."