System Info - 97170 SMITH, MICHAEL J 19-Jun-2009 12:12:07 SMITHM
RECORD OF TELEPHONE CONVERSATION
Submission Type: Original Application Submission ID: 125324/0 Office: OVRR
Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein)
Wyeth Pharmaceuticals Inc.
Telecon Date/Time: 18-JUN-2009 02:56 AM Initiated by FDA? Yes
Author: MICHAEL SMITH
Drug product and Drug substance validation questions stemming from the review of SOPPs that Dr. Gupta requested
FDA Participants: Michael Smith, Julie Vaillancourt and Colleen Sweeney
Non-FDA Participants: Jack Love and Carmel Devlin
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
From: Smith, Michael (CBER)
Sent: Thursday, June 18, 2009 2:56 PM
To: 'Jack Love'; 'Carmel Devlin'
Cc: Vaillancourt, Julienne; Sweeney, Colleen
Subject: RE: Talking points for June 19 teleconference to discuss drug product and drug substance issues
Jack and Carmel,
The talking points that Dr. Willie Vann generated regarding the drug product and drug substance issues are included in this email (see below). These talking points should help facilitate the discussion at the teleconference tomorrow.
We would like to discuss the following issues and how you plan to address them.
There are several issues that have become apparent after review of SOPs and validation reports for the analytical methods for the 13-valent vaccine.
- Which assay does the firm consider as proof of conjugation or quantitation of the amount of conjugate?
- We have concerns regarding the use of -------(b)(4)---------in raising antibodies to certain serotypes for the -------(b)(4)--------- method. Antibodies used for the ----(b)(4)--- method should be raised against a conjugate prepared with a -------------------(b)(4)---, preferably using a different chemistry, if possible.
- The validations should be performed according to ICH guidelines. For example linearity, accuracy and precision of the methods for most validations reviewed thus far do not contain data on entire range of method, accuracy and precision not evaluated on reportable results, linearity not evaluated with samples.
- Free saccharide is not included as a parameter in stability studies.
- It is known that bacterial polysaccharides are stable at higher temperatures and conjugates are not. There is no data to show that stability of ----------------(b)(4)---- at higher temperatures correlates with stability of the conjugate.
- You have not demonstrated that free saccharide is accurately separated from conjugated polysaccharide.
- The matrix used in the validation studies is not consistent with the matrix used in the drug product.
We look forward to discussing these talking points with you at the 1:00 PM teleconference on Friday, June 19, 2009.
Mike Smith, Ph.D.
Lieutenant Commander (LCDR), U.S. Public Health Service
Division of Vaccines and Related Products Applications
Office of Vaccines Research and Review
Center for Biologics Evaluation and Research
US Food and Drug Administration
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