Safety of plant-made pharmaceuticals: product development and regulatory considerations based on case studies of two autologous human cancer vaccines.

Guidelines issued by regulatory agencies for the development of plant-made pharmaceutical (PMP) products provide criteria for product manufacturing and characterization, safety determination, containment and mitigation of environmental risks. Features of plant-made products do not always enable an easy fit within the criteria subscribed to by regulators. The unconventional nature of plant-based manufacturing processes and peculiarities of plant biology relative to that of traditional biological production systems have led to special considerations in the regulatory scrutiny of PMP. Presented in this review are case studies of two plant-made autologous (patient-specific) cancer vaccines, the nature of which introduced challenges to conventional and standardized development and preclinical evaluation routes. The rationale presented to FDA by the sponsors of each vaccine to build consensus and obtain variances to existing guidelines is discussed. While development of many plant-made biologics can be accomplished within the existing regulatory framework, the development of specialized products can be defended with rational arguments based on strong science.