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Vaccines, Blood & Biologics
Meeting Date: October 6, 2009
Meeting Time: 3:30 –4:30 PM
Meeting Location: Woodmont Office Complex, Conference Room 2
File: BLA 125285
Product Name: Flublok
Sponsor: Protein Science Corporation (PSC)
Maryna Eichelberger, Cynthia Nolletti, Matthew Sandbulte, Jerry Weir, Katherine Matrakas, Rakesh Pandey, Lewis Schrager, Wellington Sun, Loris McVittie, Timothy Fritz
Purpose of Meeting:
To determine whether OVRR had remaining concerns regarding PSC’s clinical lot consistency study and hemagglutinin inhibition (HAI) assay.
Cynthia Nolletti provided a summary of her analysis of the efficacy data and indicated that immune response and non-inferiority endpoints were met for the H1 and H3 strains in each of the studies (PSC04, PSC01, PSC03 and PSC06) but that the B strain failed to meet the seroconversion criterion in 3 of the 4 studies (the B strain met both immunogenicity endpoints in the pivotal study PSC04). Concurrence was reached that the clinical efficacy study data (from study PSC04, adults 18 – 49 years old) seemed to support Flublok efficacy in this age group. Efficacy in subjects older than 49 years (PSC03 and PSC06) was not demonstrated due to strain mismatch and very low attack rates so that licensure in people > 49 years old would need to be based on GMT and seroconversion surrogates.
It was noted that the clinical lot consistency study (PSC04) failed with regard to the H3 antigen. However, this study was conducted in 2007, prior to the validation of the manufacture of the H1, H3 or B antigens. The sponsor had provided a reasonable explanation for the failure of the lot consistency study: that Lot A of the H3 antigen contained twice as much antigen as Lots B and C. It was noted that the sponsor had taken corrective actions to improve manufacturing consistency since study PSC04 and the Product Reviewer (Maryna Eichelberger) indicated that these actions had, to a great extent, addressed CBER’s concerns regarding manufacturing consistency.
It was noted that the Statistical Reviewer (Barbara Krasnicka) had concerns regarding the validation of PSC’s HAI assay in which recombinant hemagglutinin was used in place of the more typical egg-derived antigen. Since licensure in people > 49 years old would be based on the GMT and seroconversion surrogates as measured by PSC’s HAI assay, concurrence was reached that the topic of HAI assay validation should be discussed at the meeting between OVRR and OBE scheduled for October 7, 2009.