Vaccines are a group of pharmaceuticals that include some of the oldest biologically-made compounds. The Smallpox vaccine was introduced by Edward Jenner as early as in 1796 and Louis Pasteur created the first live attenuated bacterial (Chicken Cholera) and viral (Rabies) vaccines at the end of the 19th century.
A vaccine contains an antigen that is capable of inducing an immune response in a living organism and as such, typically enhances the organism’s ability to fight off or minimize disease. These antigens can be live attenuated (weakened) microorganisms such as in the MMR (Measles, Mumps, Rubella) virus vaccine, inactivated microbes (bacteria, virus) or parts thereof (proteins, polysaccharides) such as the DTaP (Diphtheria, Tetanus, acellular Pertussis) vaccine.
Vaccines are biologically active products designed to stimulate the immune system against future invasion of a pathogen by inducing memory to specific antigens. Vaccines may be produced from viral pathogens such as those causing polio, influenza and Lyme Disease, or from bacterial pathogens such as pertussis, tetanus, diphtheria and anthrax. Recombinant fermentation techniques such as those used for hepatitis vaccine, produce highly purified antigen-specific sub units that stimulate immunity without concern of pathogen infection. Vaccine production typically uses several filtration and purification steps.
To obtain a purified vaccine the selected microorganism must first be grown then the selected antigen must be separated, purified, formulated and sterilized prior to delivery.
The way a vaccine is manufactured, depends on the type of antigen that makes up the vaccine. As there are many different types of antigens, there are correspondingly many different vaccine manufacturing processes. Especially in human vaccines, manufacturing processes have been customized and often are carried out in dedicated facilities. Standardization of the processes and technologies in a way that makes maximum use of existing facilities and equipment, and of a regulatory track record, could, however, bring many benefits in term of cost reduction and speed-to-market. Animal vaccine manufacturing has typically worked according to this platform approach, with manufacturing in multi-product facilities.
Vaccines can be classified into general antigen groups and manufacturing methods, in which some element of process standardization may exist:
- Viral vaccines and viral vectors (ex. Polio, MMR, Adenoviral vectors)
- Microbial vaccines and toxoids (ex. DTaP)
- Recombinant Protein vaccines (ex. Hepatitis B and HPV)
- Polysaccharide vaccines and conjugates (ex. Hib and Pneumococcal vaccines)
- DNA vaccines & gene therapy (some animal vaccines, vaccines in development)
Vaccine manufacturing platform standardization is increasingly applicable to new vaccines and vaccine concepts in the large developments pipeline. Possible standardized unit operation steps include:
- Upstream, producing the vaccine antigen in a well-characterized host cell line or recombinant system, adapted for high cell densities in bioreactors, leading to high yields
- Downstream, by using modular, flexible and robust purification technologies
- Antigen presentation & formulation, involving conjugation, folding in virus-like-particles or virosomes, or making use of adjuvants and adjuvant systems like emulsions and liposomes
Furthermore, buffer & media preparations, inactivation, and other process steps can be standardized. To maximally take advantage of these capabilities, single-use manufacturing technologies are recommended, allowing for increased flexibility in the process, low cross-contamination risk with multi-products, maximum containment and aseptic control, allowing manufacturing in lower cost Grade C environments.