Email - Lyophilization Scale Up, March 4, 2009 - Adenovirus

Hithe, Darlene

From: Miller, Daryll L 
Sent: Wednesday, March 04, 2009 11:56 AM 
To: 'Pakulski, John' Cc: Hithe, Darlene 
Subject: Request for more information regarding lyophilization scale-up

Hi John,

Instead of having a telecon, I have been asked to forward the following comments to you regarding the lyophilization -----------(b)(4)--------------.  Dr. Wang and I would appreciate if you would answer these questions at least one week prior to our arrival for the inspection of your Forest, VA facility on April 20.
1.What data do you have to support the bioburden control during the lyophilization? Have you performed bioburden test on the drug substance before and after lyophilization? Have you performed a media fill study to support the bioburden control for lyophilization?
2.Please justify why you did not use thermocouples to monitor the real-time temperature in your lyophilized product (or placebo) during the validation study?
3.Please justify your sampling plan for the lyophilization validation study. How many trays in each shelf were tested for moisture? Please justify why you did not sample all --(b)(4)-- in each shelf during the validation study (i.e., every representative location in each shelf)? How many spots and where exactly are the sampling spots in each tray that were taken for the moisture test?
4.Please describe how you perform the cake appearance test for each lyophilized tray?
5.Please justify the discrepancy of moisture specifications between Wyeth and Barr Labs ----(b)(4)--------------

 

Please consider this e-mail as a formal request for information.  No fax or letter will be sent separately.

Best regards

Daryll Regulatory Project Manager
FDA\CBER\OVRR\DVRPA 1401 
Rockville Pike, Suite 370 N 
Rockville, MD 20852 Phone: 
301-827-3070 Fax:      301-827-3532
