Teleconference Follow-up, October 23, 2013 - Eloctate

From: Suzanne Stella <suzanne.stella@biogenidec.com>
Sent: Friday, October 25, 2013 6:11 PM
To: Kirschbaum, Nancy
Cc: Elijah Tan; Pracht, Leigh
Subject: RE: BLA 125487 - 23Oct teleconference follow-up
Attachments: Batch Disposition Table.doc

Hi Nancy,

Attached is the completed table. Any batches selected for DP validation will be placed on stability.

For next week’s communication of decisions, will that be by email or should we block of time for quick teleconference on Thursday? Let me know and I can send call in information,

Have a great weekend,
Sue

From: Kirschbaum, Nancy [mailto:Nancy.Kirschbaum@fda.hhs.gov]
Sent: Friday, October 25, 2013 7:46 AM
To: Suzanne Stella
Cc: Elijah Tan; Pracht, Leigh
Subject: RE: BLA 125487 - 23Oct teleconference follow-up

Hi Sue,

Thank you for the additional information. As mentioned during our teleconference, the Agency is committed to working with Biogen Idec to facilitate the development of a scientifically sound, regulatory compliant and irrefutable data set to support approval of BL STN 125487. Could you please fill in the attached table? Also, please feel free to add any information you feel is pertinent. Finally, please be advised that any drug substance batches used to support process validation should be put into the formal stability program.

Thank you and Kind Regards,

Nancy

From: Suzanne Stella [mailto:suzanne.stella@biogenidec.com]
Sent: Thursday, October 24, 2013 7:37 PM
To: Kirschbaum, Nancy
Cc: Elijah Tan
Subject: BLA 125487 - 23Oct teleconference follow-up

Hi Nancy,

In follow-up to yesterday’s conversation, I wanted to clarify the data we would have to support the use of rFVIIIFc drug substance already manufactured using the validated manufacturing process for the requested drug product validation of intermediate strengths. The Company understands the Agency position regarding prospective validation but is confident that the use of validated commercial processes results in uniform and consistent starting material suitable for subsequent prospective drug product validation. In addition, Biogen Idec believes that the proposal to use already manufactured drug substance with additional prospective testing is scientifically sound based upon the following items:

1. Each batch of drug substance produced is extensively monitored and tested through normal batch operations. Provided in Table 1 (attached), is a comparison of the monitoring and testing performed for prospective process validation vs monitoring and testing performed for routine commercial manufacturing. As shown in Table 1, there are very few parameters not monitored during routine manufacturing. The parameters not monitored are primarily in the cell culture steps. These parameters are –b(4)-------------------- for some but not all stages of cell culture process; however, -b(4)---- is continuously monitored on-line for all process –b(4)------ and multivariate trends are available to confirm the consistency and acceptability of the –b(4)---- operations. The –b(4)---------------------- measurements not routinely performed during the cell culture states are intermediate values bracketed by –b(4)--------------------------- measurements which occur either at the –b(4)---- of the specific cell culture –b(4)------------------- of stage confirmation.

2. On-going prospective protocols for column lifetime studies are currently in execution. These protocols monitor the chromatographic columns with respect to performance and consistency of potential in-process impurities. A summary of the impurities monitored during process validation and chromatographic column life time is provided in Table 2. As shown, all of the potential impurities are monitored periodically by these protocols under pre-defined acceptance criteria.

3. The Company will develop a prospective characterization protocol for the drug substance to further confirm the material is consistent with the previous process validation.This protocol will eliminate any concerns around inadvertent bias within a validated process. The protocol will contain predefined acceptance criteria for the attributes to be tested and will be approved prior to the execution of any additional testing. This testing is designed to supplement the already executed routine release tests. Table 3 provides a comparison of testing performed in the original PVR, release testing, and the proposed additional characterization to be performed. As shown through release and additional characterization all attributes examined in the original PVR’s will be examined and confirmed comparable.

The company realizes full prospective validation is not being performed as you requested, but all information that would have been evaluated from that exercise would be assessed. In addition, to execute such a prospective protocol at this time would result in significant delay to approval. A typical process validation of WCB thaw followed by end on end DS and DP manufacture, testing, and assessment in validation reports typically takes –b(4)------------- to execute. The company estimates through expedited testing and manufacture the earliest availability of such an exercise would be –b(4)---------- time frame.It is standard practice to schedule plant time many months in advance due to use of the lines for other licensed and approved processes. This, along with the time required to source raw materials and the serial nature of many of the studies, results in a delay of –b(4)----- These expedited activities assumes appropriate and timely manufacturing capacity for both DS and DP operations.

We really appreciate the Agency’s support for Biogen Idec and the approval of our products. We hope you find this additional information valuable in helping to determine the Agency’s opinion of the use of this material

Sue

 

Suzanne Stella
Biogen Idec
Director, Regulatory CMC
5000 Davis Drive
Research Triangle Park, NC 27709
P: 919-993-1121
--b(6)------------------

2 Pages determined to be not releasable: b(4)