Information request for BLA 125478/0, November 6, 2013 - RAGWITEK

(System Info - 255507 RIVERS KATIE 11/08/2013 08:35:11 RIVERSK)

From: Rivers, Katie
Sent: Wednesday, November 06, 2013 4:08 PM
To: 'Greenfeder, Scott'
Cc: Valenti, Elizabeth
Subject: Information Request for STN125478/0

Dear Scott,

We have the following information request for your BLA, STN125478/0:

In Stability Summary Section 3.2.P.8.1, your intended commercial production scale is –b(4)-. Please clarify why no clinical studies were performed with batches manufactured at the commercial production scale. Also, please clarify why product was manufactured at pilot scale for clinical safety study P05751 after product was manufactured at commercial scale for process performance qualification and stability.

Your clinical efficacy studies were conducted using pilot scale lots of –b(4)-. The data, as currently provided in your BLA, are not sufficient to assess comparability between the pilot and commercial scales. Please re-configure your data to provide direct comparability data between the pilot lots and your commercial scale demonstration lots. In your comparability data, for pilot lots and commercial demonstration lots, please provide all CMC Drug Product test results and specifications and indicate the methods used; identify the stage of process development for the lots; and indicate the associated process and equipment changes for the lots.

In addition, in Section 3.2.S.2.6, Table 1 and Section 3.2.P.2.2, Table 6, clinical trial P05751 is listed as a Phase 1 study. However, throughout other sections of your BLA it is listed as a Phase 3 study. Please clarify the phase of study P05751 and note the locations in your BLA where it should be corrected.

Please contact me if you have any questions.

Thank you, 
Katie

Katie H. Rivers, M.S.
Regulatory Project Manager, CMC1
FDA/CBER/OVRR/DVRPA
1401 Rockville Pike, HFM-481
Rockville, MD 20852

Phone 301-796-2640
Fax 301-827-3532

