ABSTRACT
Furthermore, a balance between the timing of exposure and the risk of infection must be achieved and factored into the product profile. Dosage forms that support coitally dependent administration versus daily or continuous administration need clear rationale that supports the recommended usage in the target label. These issues are important for any microbicide product and underscore the necessary interplay between formulation development and target product profile.It is helpful to consider that all pre-clinical and clinical data generated throughout all phases of development on the product will contribute to the regulatory marketing application. With that in mind, product manufacturing changes that occur during pre-clinical and clinical stages of development may necessitate bridging studies to ensure the applicability of early formulations to the final marketed product. Depending on the type and magnitude of the manufacturing changes, the resulting differences in the manufactured product, and the importance of the specific nonclinical/clinical data generated on the earlier product to the program, the sponsor may need to perform analytical, non-clinical and/or clinical studies to demonstrate uniformity or document differences in the products and will have to discuss applicability in the final regulatory dossier. Thus, it is important to consider manufacturing changes (e.g., equipment or process changes, changes in raw material suppliers or manufacturing facilities) carefully for their potential impact on the product development timeline.This also underscores the need for thorough process docu-mentation and product characterization throughout develop-ment. Regulatory authorities recognize that process and product refinement occur during the development process and allow for less stringent processes and product specifications early in development with the expectation that specifications will tighten up and become final by dossier filing. However, it is critically important that the manufacturing process be set and scalable by Phase 3 so that the investigational product used in the pivotal trials is the same as the commercial product, thus ensuring the relevance of the primary safety and efficacy data. This is especially important in microbicide development because of the large-scale nature of pivotal trials to demonstrate effectiveness. The sponsor should bear in mind that all final product specifications will need to be scientifically justified in the dossier.
