Record of Telephone Conversation, September 19, 2013 - ALPROLIX

Submission Type: BLA    Submission ID: 125444/0    Office: OCBQ 
 Product:          Coagulation Factor IX (Recombinant), Fc Fusion Protein
 Applicant:       Biogen Idec Inc.
 Telecon Date/Time: 19-Sep-2013 1:00 PM        Initiated by FDA? Yes
 Communication Category:     1. Other  DMPQ Issues
 Telecon Summary:     Discuss lyophilization.
 Telephone: --------(b)(4)--------------------
 FDA Participants: 
 Jay Eltermann, Division Director, OCBQ/DMPQ
 Laurie Norwood, Deputy Division Director, OCBE/DMPQ
 Ellen Huang, Consumer Safety Officer, OCBQ/DMPQ/BII
 Jie He, M.S., Consumer Safety Officer, OCBQ/DMPQ/BII
 Qiao Bobo, Senior Regulatory Officer, Ph.D., OCBQ/DMPQ/BII

Non-FDA Participants: 
Biogen Idec Attendees:
Eliana Clark, CMC Team Director 
 Ann Dodds-Frerichs, VP, Regulatory Affairs CMC
 Tjebbe de Gruijter, Senior Manager, Contract Manufacturing
 Rohin Mhatre, VP, Technical Development
 Clive Patience, VP, Global Quality Assurance
 Denise Schultz, Associate Director, Regulatory CMC
 Suzanne Stella, Director, Regulatory Affairs CMC

-------(b)(4)--------
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Telecon Body:

FDA initiated this teleconference to discuss lyophilization. The firm had emailed background information for the telecon on 9/18/2013 and a summary of ---(b)(4)--- initial empty chamber study on 9/19/2013. The firm was requested to this information through the formal gateway.

During the call, FDA asked the firm to clarify what is driving the cycle. The firm stated --------------------------------------------------(b)(4)----------------------------------------------------------------------- drive the lyophilization cycle.

Next, the firm stated that they did have a validation strategy and their approach included:
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FDA again explained that that as per the previous telecon on 9/16/2013, the technical runs and consistency lots provided were not acceptable as the studies did not represent the final lyophilization cycle and had inadequate sampling.

To address FDAs concerns, the firm stated that they would perform the following:
1.Empty chamber temperature mapping
2.Two technical runs that would include product temperature mapping and sampling of product quality attribute. The runs would include (b)(4) vials  ----(b)(4)-with product. One run would include the minimum fill volume at the (b)(4) IU strength. The other run would include the maximum fill volume at the 3000 IU strength. These runs would be --(b)(4)--with

FDA stated that there seems to be a misunderstanding and clarified that during the telecon on 9/16/2013 we recommended that the following be performed.
1.Empty chamber shelf temperature mapping study
2.Product temperature mapping study at full scale (can be done with -------(b)(4) with product.
3.Extended sampling with actual product (testing can include items such as moisture mapping, reconstitution time, and/or potency) of the maximum and minimum load.

The firm stated that performing extended sampling on commercial loads would compromise sterility and that the vials become randomized during the capping process. Therefore, they decided to combine the product temperature mapping study with extended sampling in technical runs. The firm confirmed that the two technical runs would include vials filled with -----(b)(4)-with product. FDA communicated that the two technical runs would be acceptable.

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FDA asked when the next requalification of the lyophilizer would be performed. -(b)(4)-stated that the requalification is to be performed in October or November 2013.

FDA also asked the firm to provide the make and model of the lyophilizer.

FDA communicated that before they begin their technical runs that they need to perform adequate equipment qualification to provide confidence that they have tight control over their lyophilizer.

Biogen Idec asked if these studies could be provided as a Post Marketing Commitment. FDA stated no. There is no assurance that the lyophilization process is validated. The firm had not demonstrated that the temperature can be maintained in the lyophilizer. Additionally, the technical runs had wide variation with inadequate sampling. FDA communicated that we have proposed the minimum data set required and without this data we cannot reach a conclusion.

The call ended at 1:58 PM
