New Process, Old Issues
Scaleup issues for influenza vaccine produced through the egg inoculation method were resolved decades ago. The introduction of vaccines manufactured through cell culture introduces scaleup issues that are new to this industry.
To meet these new challenges, Protein Sciences relies on a QbD approach to large-scale vaccine manufacturing that claims to produce vaccines at large scale in fewer than 50 days from identifying the target virus.
“Manufacturing a recombinant subunit protein for influenza prevention poses unique challenges, as regular modifications to the antigen are required to protect against circulating influenza viruses,” explains Robert R. Boulanger, Ph.D., manager of USP development at the company. Dr. Boulanger has developed a series of standard operating procedures based on his experience with the production and purification of dozens of recombinant human agglutinins (rHAs) through the baculovirus expression vector system (BEVS).
“This approach expedites and streamlines our response to an influenza strain change announcement,” he says.
It involves utilizing processes employed for a similar rHA, typically from the same influenza virus subtype H1, H3, or B. If the process produces an acceptable antigen, the new antigen is produced at manufacturing scale. If not, the standard operating procedure defines the process design space.
“This guides the development team through a series of systematic experiments to evaluate specific conditions and identify required process changes for manufacturing batch records. Once the new process is established, the antigen produced is evaluated to verify it meets all acceptance criteria limits,” Dr. Boulanger explains.
Implemented properly, QbD improves manufacturing efficiencies, reduces costs, and facilitates the implementation of process changes and improvements.
“The universal process we have developed for our seasonal influenza vaccine, FluBlok®, is a good example of how QbD reduced our timeline from identification of a new rHA sequence to manufacturing at the full cGMP scale,” continues Dr. Boulanger.
Protein Sciences follows this strategy for PanBlok®, the vaccine supported by the Biomedical Advanced Research and Development Authority to achieve pandemic flu preparedness. Like the FluBok program, PanBlok is based on the company’s prior experience with rHA antigens and flexibility in accommodating the physicochemical properties of new rHA antigens.
The company has also implemented a process monitoring and a continuous improvement program.
To illustrate the success of this approach, on February 28, 2012, an FDA advisory panel announced two strain changes for the 2012–2013 seasonal influenza vaccine.
“We utilized a QbD-based influenza vaccine strain change approach and completed the process from cloning of the new rHA for the A/Victoria/361/2011 sequence to completion of the first 450 L cGMP lot in 50 days,” says Dr. Boulanger.