8/2/2007 Email - XYNTHA
 
From: Kearns, Daniel 

Sent: Thursday, August 02, 2007 2:29 PM 

To: Renshaw, Carolyn; Lee, Timothy 

Cc: Cottrell, Pauline; Stephenson, Franklin; Trout, Deborah 

Subject: Wyeth 125264-0 telecon re: inspection, adjustments 

MEMO of TELECON

DATE: Thursday, August 2, 2007 1:35 to 2:05 pm
 FROM: Daniel Kearns, HFM-675
 TO: Andrew Papas, Wyeth representative
 SUBJECT: STN 125264/0 - - inspections, endotoxin, and adjustments

I returned a call from Andrew Papas, who said that he had been given the task to answer my questions (see July 26, 2007 telecon below this telecon).

We first discussed the ----------------------------------------------------------------------------------------------------------------------------
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I reiterated my questions about bioburden and endotoxin (see telecon below) and what I needed to answer my concerns.

I also raised a point I noted from today's review of Wyeth's BLA - section 3.2.P.3.5, page 58 for lot 66518. There had been a deviation in the shelf temperature. I stated that the short duration of the deviation led me to believe that it was inconsequential, but as there was no further detail about how high the temperature deviation was, what phase of the lyophilization process the deviation happened in, and if any more substantial investigation occurred other than the fact that release tests were met, it was difficult for me to reach a conclusion with regards to Wyeth's assessment of the deviation. Mr. Papas said he would get the information about the circumstances of that deviation and Wyeth's assessment of it to me.

Mr. Papas asked if the response should be an amendment. I said that I intended to merely receive the information over the phone and write it up as a telecon, as I anticipated, based on my experience with Wyeth's --------- submission, that Wyeth's responses would be typical and satisfactory (i.e., -----------------------------------------------------------------
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Mr. Papas said it would take about a week to get back to me - - I stated there was no rush, and that 1 week was fine.

The conversation concluded.

Prepared by D.Kearns on Thursday, August 2, 2007 at about 2:20 pm.


MEMO of TELECON

DATE: Thursday, July 26, 2007 10:35 to 10:45 am
 FROM: Daniel Kearns, HFM-675
 TO: Joyce Schwenk, Wyeth representative
 SUBJECT: STN 125264/0 - - Master file, inspections, and adjustments

I (DK) called and spoke to Joyce Schwenk, a Wyeth manager and representative for Wyeth STN 125264/0.

First, I told her the situation with regard to whether a Master File for -------- was resolved - --------- did not have to have or submit a master file.

Second, I said that some more background on the ------------------------ inspection history would be helpful. Particularly, has the Refacto ------------------ been inspected, ----------------------------------------------.

Third, I asked for some clarification on the "adjustments" (table 4-1 in section 2.3 Drug product 2.3.P.3 Manufacture) that could be made with regard to endotoxin and bioburden (pH and integrity test filter were not a problem). I explained that I hadn't looked up the final amount of endotoxin permitted, but if the endotoxin limit was at or near the release amount, dilution of the bulk drug substance was not permitted to meet endotoxin release specifications. If the limit was set lower, and the limit was set to spot trends and take corrective actions, it was OK.

With bioburden, I said I needed to make sure that the contaminant were speciated, and this was taken into consideration in the investigation, as well as determining if the high bioburden affected endotoxin limits.

Ms. Schwenk said that Marina Derfal would get back to me ASAP - I mentioned that this was not time critical and they could take their time.

The conversation concluded.

Prepared by D.Kearns on Thursday, July 26, 2007 at about 11:15 am
