DEPARTMENT OF HEALTH & HUMAN SERVICES
Date: August 26, 2011
From: Meghan Ferris, M.D., M.P.H.
Medical Officer, Clinical Review Branch 1
Through: Lucia Lee, M.D.
Team Leader, Clinical Review Branch 1
Subject: Clinical Review of Biologics License Application for GlaxoSmithKline Biologicals’ Meningococcal C and Y and Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate) (proposed proprietary name: MenHibrix)
To: BLA STN# 125363
1 General Information
1.1 Medical Officer Review Identifiers and Dates
1.1.1 BLA #: 125363
1.1.2 Related INDs:
• IND –b(4)-: GSK’s Haemophilus b and Neisseria meningitides Serogroups C and Y – Conjugate
(Tetanus Toxoid Conjugate) Vaccine
• IND –b(4)-: GSK’s Neisseria meningitides Serogroups A, C, W-135, and Y – Conjugate (Tetanus
Toxoid Conjugate) Vaccine
1.1.3 Reviewer Name, Division, and Mail Code
Meghan Ferris, M.D., M.P.H
Division of Vaccines and Related Products Applications
1.1.4 Submission Received by FDA: August 12, 2009 (original); April 15, 2011 (complete response)
1.2.1 Proper Name: Meningococcal Groups C and Y and Haemophilus b Conjugate Vaccine (Tetanus Toxoid
1.2.2 Proposed Proprietary Name: MenHibrix
1.2.3 Product Formulation: MenHibrix is a lyophilized vaccine of purified polyribosyl-ribitol-phosphate capsular polysaccharide (PRP) of Haemophilus influenzae type b, Neisseria meningitidis serogroup C capsular polysaccharide (PSC), and Neisseria meningitidis serogroup Y capsular polysaccharide (PSY), each covalently bound to tetanus toxoid. Each 0.5 mL dose of MenHibrix contains 2.5 mcg of purified PRP, 5 mcg PSC, and 5 mcg PSY covalently bound to 6.25 mcg of tetanus toxoid (PRP), 5 mcg of tetanus toxoid for PSC, and 5 mcg tetanus toxoid for PSY. Each MenHibrix dose also contains 96.8 mcg of Tris (trometamol)-HCl, 12.6 mg of sucrose, and < 0.72 mcg of residual formaldehyde.
1.3 Applicant: GlaxoSmithKline Biologicals
1.4 Pharmacologic Class: Vaccine
1.5 Proposed Indication: Active immunization for the prevention of invasive disease caused by H. influenzae type b and N. meningitidis serogroups C and Y. The proposed age range for use is 6 weeks through 15 months of age.
1.6 Dosage Forms and Route of Administration: MenHibrix is a solution for intramuscular injection (0.5 mL dose) supplied as vials of lyophilized vaccine to be reconstituted with the accompanying saline diluent in prefilled syringes.
The applicant provided a Complete Response on April 15, 2011. The clinical reviewer’s information
requests were addressed sufficiently. However, based on discussions with CBER CMC and assay statistical reviewers, the applicant has not addressed a number of other issues, particularly related to the serum bactericidal assay using human complement (hSBA assay) performance. Until the applicant resolves those issues, it is not possible to evaluate the immune response to this vaccine or to recommend its approval.
The clinical reviewer defers recommendation regarding approval pending resolution of the issues related to the hSBA assay for meningococcal serogroup Y. This assay is the basis for evaluating effectiveness, as there
are no clinical efficacy data.