1. Rapid Microbiology Methods Industry Concerns Jeanne Moldenhauer Vectech Pharmaceutical Consultants, Inc.

2. Business Objectives  Laboratory Compliance to FDA requirements  Low cost provider of high quality products  Reduce overhead  Just-in-time production  Reduce inventory hold times  Expedite product approvals  State of the art technology usage

3. Concerns Over Use of Rapid Methods  Regulatory review and approval expectations are not clear  Cost of equipment is high and perceived regulatory risk is high  Most types of equipment for rapid methods cannot be validated to be equivalent, due to superior technology  Compliance issues vs. Submission issues  Scientific Issues

4. Case Study 1: Water Testing  Reviewing division indicated “unofficially” it was a compliance issue  Local District consulted and issues were discussed, e.g., equivalence and number of tests  Advised that: –When approved technology would raise the bar. –Compliance is not likely to move on this issue very very slowly. –ROI was dependent upon using testing method during validation and validation could not be held for an indefinite time period.

5. Case Study 2: Biological Indicator Enumeration  Regulatory Strategy: Develop method, validate and submit with a drug where a known deficiency would occur. Have parallel testing, in case new method was not approved.  USP Stimuli to Revision indicated method was suitable for bacteria, fungi and spores.  Started to develop method

6. Case Study 2: Biological Indicators cont.  Counts were erratic and went to the vendor  Modified test several times, with some counts being lower than traditional method.  Modified test and control counts were good but stressed organism test counts were up to 4 logs higher  What does that say about the sterilization model?

7. Case Study 2: Biological Indicators cont.  Studies done and showed that indicator organism was dying in expected log fashion, with good approximation of D- value  Supposed that counts still were not true  Eventually, was able to find out scientifically that clumping was an issue  Final method yielded counts approximately one-half log higher for stressed organisms