
CMC Addendum Review Memo - BEXSERO

 

 
MEMORANDUM

From: Hsiaoling Wang, Ph.D.
 CMC Reviewer
 Laboratory of Analytical Chemistry and Blood Related Products (LACBRP)
 Division of Biological Standards and Quality Control (DBSQC)
 Office of Compliance and Biologics Quality (OCBQ)
 Center for Biologics Evaluation and Research (CBER)
 Food and Drug Administration (FDA)

To: Biologics License Application Submission Tracking Number # 125546/0

Subject: Addendum Review Memo of Analytical Procedures for ---(b)(4)------- of Biologics License Application for Meningococcal Group B Vaccine 

Through: Lokesh Bhattacharyya, Ph.D., Lab Chief, LACBRP/DBSQC/OCBQ/CBER
 William M. McCormick, Ph.D., Director, DBSQC/OCBQ/CBER 

Cc:	Edward Wolfgang, MSA, Lead RPM, DVRPA/OVRR/CBER
 Margret Bash, MD. MPH, Chair, BLA Review Committee, DBPAP/OVRR/CBER

Applicant: Novartis Vaccines and Diagnostics

Product: Bexsero - Meningococcal Group B Vaccine

Biologics License Application (BLA) Submission Tracking Number (STN) #: 125546 

Submission received by CBER: July 03, 2014 

Review completed: December 29, 2014

Summary and Conclusion: 

This DBSQC reviewer found that Novartis’ ---(b)(4)--- assay for -------------------------------------------------(b)(4)---------------------------------------------------------, and appearance test, pH test, deoxycholate and sucrose determinations for ----(b)(4)------------------------ were qualified for their intended use and recommends their approval (for details see Primary Review Memo dated Nov. 17, 2014). 

Novartis committed to re-assess the specification for the ---(b)(4)---- of ----(b)(4)--------- based on the process capability. The reassessment report will be submitted in 2015. The ---(b)(4)----- specification for ---(b)(4)------ will be updated and implemented based on the outcome. 

Background

----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ The sponsor was asked to submit manufacturing scale lot data to support specification reflecting historical performance of (b)(4) in the IR sent out Oct. 08, 2014

Review

Novartis committed to re-assess the process capability and specification for the ---(b)(4)----- of ---(b)(4)------- when more data would be available. 

An information request was communicated to the sponsor on November 17, 2014 through e-mail and the response was received on November 24, 2014 in the amendment 28. 

In your “Responses to CBER’s Request for Information (dated Oct. 31, 2014)”, you stated “As such the company intends to re-assess the process capability and specification once a sufficiently dataset, including the 2014 production campaigns, becomes available. Following reassessment, the ---(b)(4)------ specification for ----(b)(4)------------------- will be updated accordingly and implemented in the next ----(b)(4)------------------- manufacturing campaign.” (page 74 of 75). Please provide the timeline for reassessment and submission of your data.

Novartis’ response

The Company acknowledges the request from CBER and would like to state that reassessment of the ---(b)(4)---- specification for -----(b)(4)--------------- which will also include all QA released ---(b)(4)----- batches from the current 2014 manufacturing campaign will be completed in Q03/2015. The data will be submitted post approval via the annual report procedure (first annual report) and the outcome of the reassessment will be implemented in the next planned manufacturing campaign in (b)(4).

Review of the response

This review considers that the timeline of the reassessment report is reasonable and concludes that the ---(b)(4)----- test can be approved as a release test for the (b)(4). 

However, the format of submission should depend upon the outcome of the sponsor’s assessment. A follow-up IR was sent to the sponsor in December 12, 2014: 

We have reviewed your response to Question 21 of our October 8, 2014 Information Request and your related response to Question 2 of our November 17, 2014 Information Request. For --(b)(4)--, you indicated that you had a relatively small data set from (b)(4) commercial lots available to evaluate the process capability and estimate specification limits precisely and you would reassess the process capability and specification once adequate number of data would be available. Please submit this report as a CBE supplement if you propose to tighten the specification, as a PAS if you propose to loosen the specification, or as Product Correspondence if you propose not to change the specifications.

The sponsor has acknowledged this request in the amendment 37 (dated December, 23, 2014). 
