Information Request for BLA125478/0, April 3, 2014 - Ragwitek

From: Rivers, Katie
Sent: Thursday, April 03, 2014 2:17 PM
To: Greenfeder, Scott
Cc: Valenti, Elizabeth
Subject: Information Request - STN125478/0

Dear Scott,

We have the following comments regarding potential CMC PMCs you submitted to your BLA. If we have a clear understanding of the actions you will take and this has been specified in your BLA, then a PMC may not be needed. We understand you have to consult with your drug substance (DS) and drug product (DP) manufacturing sites to confirm; however, please respond as quickly as possible to the following CMC requests. Your proposed PMCs are listed below, followed by our responses:
1.To test –b(4) commercial batch of the DS -(b)(4)--- for stability at recommended storage. -----------------------------(b)(4)---------------------------- tests will be performed. Only -----(b)(4)------------- tests will be performed.

Please provide a clear statement from ALK-Abello that DS –b(4)-- will be initiated ---(b)(4)--.
2.To test one commercial batch of the DP ---(b)(4)-- for stability for long term storage (36 months) at 25°C ± 2°C/--b(4)-------.

As you are aware, stability testing of one commercial batch of the DP is required under the 211 cGMP regulations and such is not required as a PMC. Please provide a statement that ALK-Abello is aware of this U.S. regulatory requirement.
3.To test previous ---(b)(4)------ (Amb a ---(b)(4)--- and the current ---(b)(4)---- (Amb a ---(b)(4)---- for stability. The stability of the -----(b)(4)----- will be assessed by analysis of the ---(b)(4)----- when stored at ----(b)(4)----.

Please provide a statement that serum ---(b)(4)--- study will be performed. Please note that the status of this study will be examined during your next routine inspection.
We have the same response regarding items #4 and 5. Please see our response under #5:
4.To revise DP water content release specification post licensure if needed based on statistical analysis of additional data for water content.
5.To re-evaluate and revise if necessary the -(b)(4)- limits and corresponding (b)(4) value for ----(b)(4)------- testing after manufacture of multiple commercial lots.

The level of change and type of submission (e.g. PAS, CBE30, AR, or Product Correspondence, which are all possibilities) will be determined based on what change you actually make when data collection are complete. Please provide a statement that you will contact CBER upon completion of your studies so that we can discuss what type of regulatory submission will be required. Also, to ensure the studies are performed in a timely manner, we request a more specific number of lots for comments 4 and 5. The number of lots selected should be sufficient for you to perform a meaningful statistical analysis.

Please submit an amendment to your BLA to acknowledge the above requests. Doing so will negate the need for CMC PMCs.

Thank you,
Katie
