Rapid Manufacture and Release of a GMP Batch of Avian Influenza A(H7N9) Virus-Like Particle Vaccine Made Using Recombinant Baculovirus-Sf9 Insect Cell Culture Technology

N ovavax reported that, in 28 days following public release of the avian influenza A/Anhui/1/2013 (H7N9) virus gene sequences, its recombinant DNA and baculovirus-Spodoptera frugiperda cell culture-based technology was used to produce a virus-like particle vaccine to avian influenza A(H7N9) virus, and murine animal challenge studies were initiated.[1] This report describes Novavax’s manufacturing process and the coordinated timing of critical activities necessary to produce and release a clinical batch of avian influenza A(H7N9) virus virus-like particle vaccine, under current good manufacturing practices, within three months from the time that the virus genomic sequences for this potential pandemic influenza virus were reported. The key enabling factors were: • A detailed, integrated project plan and daily coordination meetings • Advanced use of the baculovirus master virus seed to bypass production of the passage 3 virus stock • Successful functional testing of the master virus seed to establish process parameters • Drug substance quantitation with an alternate method prior to availability of single radial immunodiffusion assay reagents • Forward processing of intermediates prior to completion of quality control testing • A process that uses single-use manufacturing technology Introduction Since 1997, avian influenza A viruses of various subtypes, including H5N1, H9N2, H7N7, H5N2, and now H7N9 have infected humans. Unfortunately, there is no method to predict which existing, novel avian, or other influenza A subtypes—for which little or no pre-existing immunity in the human population exists—may emerge as human-tohuman transmissible and lead to the next pandemic. One of the best methods of protecting society from the health, social, and economic risks of an influenza pandemic is rapid immunization of the population with a potent vaccine prior to the major wave of infections that come with the onset of a pandemic. In the past decade, manufacturers have improved the response rate and timelines for influenza vaccine production through the use of cell culture and recombinant DNA technology— as compared to the traditional production method that uses embryonated chicken eggs with reassortant viruses adapted for high growth.[2] The industry is now preparing vaccines for avian influenza A(H7N9) virus through various novel manufacturing process technologies[3-7] in response to the recent human H7N9 infections resulting in severe respiratory symptoms, extended hospitalizations, and a high mortality rate, especially in the elderly. On March 31, 2013, the Chinese Health and Family Planning Commission noti f ied the World Health Organization (WHO) of the first confirmed human infections with avian influenza A(H7N9) virus.[8] Although the H7N9 virus is a low pathogen in avian species, three confirmed human avian influenza A(H7N9) virus-associated infections had occurred in Shanghai and Anhui.[9,10] During the first weeks of April, the incidence of confirmed cases rose rapidly, spreading to eight provinces of eastern China.[11] Patients were admitted to the hospital displaying severe Article Published Online: 29 July 2013 TRENDS & DEVELOPMENTS IN BIOPROCESS TE Article Published Online: 29 July 2013