
CMC Review Memo, April 21, 2010 - MenHibrix

  
 
DEPARTMENT OF HEALTH & HUMAN SERVICES

FDA, Center for Biologics Evaluation and Research



MEMORANDUM
                                                                                                                             
Date:               April 21, 2010                        

From:               Michael P. Schmitt, Ph. D.
Laboratory Of Respiratory and Special Pathogens, Division of Bacterial, Parasitic, and Allergenic Products, HFM-437

Through:          Drusilla Burns, Ph.D. 
Chief, Laboratory of Respiratory and Special Pathogens, Division of Bacterial, Parasitic, and Allergenic Products, HFM-434

To:                   File, BLA 125363/0

Product:          MenHibrix (Meningococcal Group C and Y and Haemophilus b Tetanus Toxoid Conjugate Vaccine)

Subject:           CMC Review Memo – Tetanus Toxoid Manufacturing and ---(b)(4)---- Serology

                           
SUBMISSIONS REVIEWED
STN 125363/0 Original BLA  
STN 125363/0.1 (amendment received 8/27/2009)
STN 125363/0.3 (amendment received 2/12/2010)

This review memo covers Tetanus Toxoid manufacturing and testing, and ---(b)(4)----  serology validation studies. Areas covered by this review include all information in Sections 2 and 3 that are relevant to the manufacturing and testing of the Tetanus Toxin and Tetanus Toxoid.  Additionally, ---(b)(4)----  serology validation studies and (b)(4) protocols in section 5.3.5.4 are reviewed. 

Background:

On August 12, 2009 GlaxoSmithKline Biologicals submitted a BLA for Meningococcal Group C and Y and Haemophilus b Tetanus Toxoid Conjugate Vaccine, which has the proposed proprietary name MenHibrix.  Clinical development of this vaccine was conducted under IND (b)(4).  The vaccine contains N. meningitidis serogroup C and Y polysaccharides (PSC and PSY, respectively) and H. influenzae type b capsular polysaccharide (PRP), with each covalently attached to tetanus toxoid.  The final vaccine product is lyophilized and provided in (b)(4) glass vials, and is reconstituted prior to injection with a saline diluent in –b(4)--------.  The final vaccine contains 2.5 mg PRP-TT, 5 mg PSC-TT and 5 mg PSY-TT in a 0.5 ml dose.  The vaccine is indicated for immunization of toddlers 6 weeks through 15 months for the prevention of invasive disease caused by N. meningitidis serogroup C and Y and H. influenzae type b.

Overview of Tetanus Toxoid Manufacturing at the -----(b)(4)-------- location, GSK Biologicals     b(4)--

 

Review:   

The material covered by this review includes the following areas:
1.Manufacturing of tetanus toxoid (TT) at the –(b)(4)-- site, from ---------------(b)(4)----------------------------------------- of the purified tetanus toxoid
2.Purification and --(b)(4)-------of the TT performed at Rixensart, Belgium
3.TT process development to include manufacturing history at –(b)(4)--  as well as TT lot development in support of MenHibrix
4.Process Validation of the TT manufacturing process
5.C. tetani (b)(4) system
6.Tetanus Toxoid Specifications
7.Stability studies
8.---(b)(4)--   serology review (sections 5.3.5.4; -----(b)(4)-----)

1.         Manufacture of TT at -(b)(4)--  facility (3.2.S.2.2):

  

17 pages redacted do to (b)(4)

 

 specifications.  Although we understand that these specifications were initially determined for manufacturing in building -(b)(4)-, we recommend that you establish updated Alert and Action limits for monitoring tests throughout the manufacturing process for the purified TT produced in -(b)(4)-.  Please provide updated Alert and Action limits for the TT manufacturing process or provide a proposal on how you will revise these specifications in the future.  Please specify the number of lots you will use in establishing updated specifications.

4.         Please specify the exact date when TT manufacturing was initiated in building -(b)(4)-.

5.         We note that the initial -(b)(4)- testing done at Rixensart on the purified TT is for monitoring purposes only (Table 99, m3.2.S.2.4-section 3.2).  In order to maintain manufacturing process consistency, we request that you develop a specification ----------(b)(4)------ for the -(b)(4)- analysis on TT prior to ------(b)(4)------------ at Rixensart.  In addition, we request that you revise the -(b)(4)- test currently performed on the purified TT----(b)(4)----- to a “quality decision test” instead of a monitoring purposes only test.  Please comment.
