Vaccine producers share many development and manufacturing problems with colleagues who commercialize other types of biopharmaceuticals. Smooth progress through R&D and clinical trials, plus cost-effective production and quick time-to-market are much sought-after. The nature and use of vaccines nevertheless presents some special issues with which producers must contend, particularly regarding scale, affordability, change-of-pace, and safety.The urgent need to increase stocks of the influenza vaccine means that producers face scale challenges that are somewhat different from those seen with other therapeutics. In the advent of a pandemic, currently existing global manufacturing capacity would only suffice to vaccinate the US population.1 This scenario has stimulated the mobilization of billions of dollars of public money and grants, and has motivated influenza vaccine-producing companies to invest in a shift in technology from eggs to cells, and to build additional manufacturing capacity.
A second issue confronting manufacturers is cost. In developing countries, the mortality rate for children as a result of infectious diseases such as pneumonia, malaria, and HIV is extremely high, but even the most basic immunizations cannot be afforded by those who need it most.
Thirdly, new vaccines for cancer or other therapeutic vaccines will open a new, highly competitive, and probably high-price market, where the leader will shape the market so that time-to-clinic and time-to-market will become a very important issue.
Finally, from a technical perspective, vaccine production is much like any other biopharmaceutical production workflow in that it generally requires about six steps: fermentation, clarification, purification, sterilization, formulation, and final filling. All of the steps need to be robust and reproducible, which is a particular challenge in biopharmaceutical manufacture because of the complexities and natural variability of biological systems. One important difference between the production of vaccines and other biopharmaceuticals, however, is the risk and safety considerations related to working with pathogens and pathogenic antigens.
The development of vaccines and manufacturing capability must therefore follow four ground rules:
In the light of these pressures, it is increasingly important to make use of the latest technologies to simplify vaccine development and manufacturing. The following sections offer insight into technology solutions that will address the needs of vaccine manufacturers.
Analytical Method Development That Drives Time-Savings
Process development should always start by defining the required target purity goals and selecting analytical methods with appropriate detection limit that are sufficiently accurate and time-efficient. As with all biomolecules purified from crude biological material, the removal of contaminants, e.g., derivatives from the host cell such as DNA, host cell protein, or leachables, must be documented. The removal or inactivation of adventitious viruses is a special challenge.
Of the in vitro and in vivo assays currently applied to vaccine production processes, some take weeks to run, although the accuracy of others, such as the single radial immunodiffusion (SRID) test used for batch-release, is limited.2