GUIDANCE FOR INDUSTRY There are six important issues to consider when filing an Investigational New Drug (IND) Application for a PMB. We will examine them here.
Agency Overlap. FDA and USDA issued "Draft Guidance for Industry: Drugs, Biologics, and Medical Devices Derived from Bioengineered Plants for Use in Humans and Animals," in September 2002.34 This guidance resulted from collaboration between FDA and USDA and outlines the regulatory expectations for products derived from bioengineered plants. It describes the division of authority between the two agencies and also provides technical guidance on the use and characterization of the plants and the products produced from them. The document is still in draft form but provides an idea of FDA and USDA concerns. Issues addressed in the guidance are shown in Table 2. (Table 1 is in Part 1). Note the high degree of overlap between FDA and USDA issues.
Seed Banking. The fundamental requirements for preparing and maintaining a master seed bank (MSB) and a working seed bank (WSB) are applied to PMB products. Characterization data will be specific to each MSB or WSB and will include parameters such as uniformity, bioburden, storage conditions, gene content and stability, phenotype or genotype stability, and viability data.
A difference between an MSB for cultured cells and one for plants is that seed cannot be frozen in liquid nitrogen vials. Seed must be stored at a temperature and humidity that will maintain viability. Depending on the type of plant, viability may be reduced over time (4-10 years, depending upon the seed) below production specifications. Therefore, new MSBs must be generated and characterized on a regular basis. Another difference is the ability to generate starting material for PMB purification from one generation of the host, compared to multiple generations for cell culture and fermentation. Again, the type of data needed to characterize and verify consistency of the MSBs and WSBs for plants should be appropriate for the system and ensure the consistency and safety of the final PMB product.