The Bumpy Road Toward Vaccine Registration: How to Overcome Regulatory Hurdles
Vaccines belong to the steadily growing group of biological medicinal products, also specified as biologics, indicating that the active substance, i.e., the vaccine antigen, consists of or is extracted from biological starting materials such as microbial organisms or viruses. In addition, for viral vaccines, growth substrates such as embryonated eggs and primary and permanent cell lines are biological systems essential for vaccine production. Furthermore, a wide range of raw materials and excipients of both biological and nonbiological origin are indispensable for vaccine manufacturing and formulation. Consequently, numerous regulations are in place imposing stringent control over any substance entering manufacturing processes for vaccines. Likewise, vaccine production itself is meticulously controlled by specifying many critical process parameters and critical quality attributes, ensuring batch-to-batch consistency of production. Additional obligations regarding nonclinical and clinical investigations, pediatric investigation plans, and postmarketing requirements are considered as significant hurdles which must be successfully overcome before licensing and market launch can ever be envisaged.
Vaccine production originally performed in small production entities followed by a switch to an industrial scale about 3 decades ago was consistently accompanied by minor and major incidents and accidents which ultimately resulted in the legal framework as well as scientific guidance governing vaccines, all of which should be adhered to nowadays. Individually and collectively, these rules and procedures are aimed at reducing risks to an unavoidable minimum for populations to be vaccinated. Strict compliance to these principles appears to be cumbersome and is certainly extremely cost intensive and can, apparently, only be consistently ensured by big pharmaceutical companies. Without professional regulatory support, small- and medium-sized enterprises usually experience major difficulties on their way from lab to license. However, in order to avoid that regulatory principles and huge economic burden associated to it will hamper scientific progress prohibiting access to better or novel vaccines, the existing regulatory system in the western world offers broad scientific advice to any institution focused on vaccine research and development. From that perspective, only awareness is needed that a regulatory and scientific framework specific for vaccines exists and that advice from competent authorities should be sought already at very early stages of vaccine development in order to ensure compliance with relevant principles. Keeping this in mind will ensure that particularly academic institutions as well as smaller enterprises will be able to efficiently bridge the wide gap between brilliant ideas and successful market introduction.