Information Request for BLA125478/0, January 31, 2014 - Ragwitek

From: Valenti, Elizabeth 
Sent: Friday, January 31, 2014 12:05 PM
To: Greenfeder, Scott
Cc: Valenti, Elizabeth; Rivers, Katie
Subject: RE: FYI, correction to CMC information to be submitted

Dear Scott,
 Thank you for letting us know of your amendment with updated data. In your amendment please include the following information:
•Please provide the full investigation report and not a summary.
•Please specify all Corrective and Preventive Actions (CAPA) taken as a result of this investigation.
•It appears that you have re-calculated stability values for multiple time points. Please provide the previous values and re-calculated values for each time point where a re-calculation was performed.
•Please provide complete details regarding the method used for re-calculation of stability values, including how many times re-calculations were performed for each time point.
•Please provide complete (not summary) SOPs that were followed at any point throughout this process. For example, SOPs that cover deviations, investigations, correction/re-calculation of values (this may be in your SOP for handling of OOS results), and CAPA should be submitted in addition to any other SOPs that were used through this process.

Thank you, Betsy



From: Greenfeder, Scott [mailto:scott.greenfeder@merck.com ]
Sent: Friday, January 31, 2014 9:20 AM
To: Rivers, Katie; Valenti, Elizabeth
Subject: FYI, correction to CMC information to be submitted

Dear Katie,
 An amendment to the BLA 125.478/0 Module 3 Section 3.2.S.5 Reference Standard and Ragwitek Response to Information Requests dated Dec. 9th , 2013 and Dec. 18th, 2013 is required. Information needs to be corrected due to an investigation of the In-house Reference Standard. New values for the Radial Immunodiffusion (RID ) and --b(4)----------------------------- for the IHR provided in the BLA have been assigned.

Details of the investigation and amended Certificate of Analysis for the In-house reference standard with the new ----b(4)-------- values and corrected –b(4)-- results for the drug product stability data for Commercial scale batches (36 month timepoint only) and the drug product PPQ batches (9 and 12 month timepoints) will be submitted shortly in an amendment to the BLA 125478. The data corrections will have no impact on the conclusions of the drug product stability studies and continue to support that the Ragwitek drug product is stable at 36 months when stored at 25°C ± 2 °C/--b(4)----------

Regards,
 Scott
Scott Greenfeder, Ph.D.
Director and Liaison
 Global Regulatory Affairs
 T: +1 732-594-1021
 Fax: +1 732-594-1030
scott.greenfeder@merck.com
 Merck Research Labs
 126 East Lincoln Ave.
 MS RY33-204 
 Rahway, NJ 07065
www.merck.com

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