The advisory committee had two topics for discussion: 1) review of FDA’s risk assessment for potential exposure to vCJD in human plasma-derived antihemophilic (FVIII) products and communications materials; and 2) the levels of TSE clearance in the manufacture of plasma-derived Factor VIII (FVIII).
FDA presented a risk assessment to the committee to seek its advice on key message points in both the risk assessment itself and appropriate ways to communicate this information to physicians, patients and the general public.
In response to the risk assessment — which found that the potential to transmit vCJD from plasma-derived FVIII products used by some patients with hemophilia A and von Willebrand disease is highly uncertain, but appears likely to be very low — the advisory committee voiced concerns about how the FDA was going to account for underreporting since reporting is not mandatory, and what objective evidence FDA used in making its assumption that there is a four-log reduction in the final product. The committee also expressed its support for the use of spiking experiments as a step in the right direction for determining the clearance of the infectious agent.
A lengthy discussion was held on the proposed risk communication plan, with the committee concluding that the concept was sound but there was some room for improvement. The advisory committee agreed that there cannot be a “one size fits all” philosophy. The key points for a physician would be different from those for a patient. For example, the message to physicians should be that infected patients need to receive the same standard of care as noninfected patients, not treated differently as they were when HIV was first an issue during the 1980s. For patients, there should be a focus on the positive aspects of the therapy, i.e., the benefits of taking the product.
The committee also addressed the safety and efficacy of plasma-derived FVIII products. In response to an FDA request for advice on the efficacy of a minimum TSE agent reduction factor — which has been demonstrated in laboratory-based experimental models to enhance vCJD safety of the products — the chair of the Plasma Protein Therapeutics Association (PPTA) Pathogen Safety Steering Committee presented data on the level of the prions removed by the manufacturing process, a value that ranged from 3.9 to >9.05 logs, depending on the company. The presentations prompted questions on subjects ranging from the methodology of preparing the samples to how the log reduction was determined for the overall process, ultimately leading to a nonunanimous decision that, based on the scientific evidence, exogenous studies are a means of assuring the safety of plasma-derived FVIII products. However, the advisory committee was unable to make a recommendation to FDA for what would be an appropriate log reduction factor.