Consideration of Labeling Claims for TSE Agent Clearance in Plasma Derivatives

1. Consideration of Labeling Claims for TSE Agent Clearance in Plasma Derivatives TSE Advisory Committee February 20, 2003 Dorothy Scott, M.D. DH/OBRR/CBER/FDA

2. Reduction of possible risk of CJD and vCJD in Plasma Derivatives: FDA Recommendations • Donor deferrals: vCJD, vCJD risk • > 3 months travel/residence U.K. (1980- 1996) • > 5 years travel/residence France (1980- present) • > 6 months U.S. military bases in Europe (1980-1990 or 1996; location-dependent) • Transfusion in the U.K. 1980- present • U.K.-sourced bovine insulin 1980- present • Donor deferrals: CJD, CJD risk (hGH, dura, FH) • Quarantine/retrieval plasma unit from donor with CJD, vCJD • Withdrawal plasma derivatives with vCJD donor

3. Current Recommendation: Donors of Source Plasma are not deferred for travel/residence BSE countries (except France and the U.K.) • Model TSE agents partitioned/removed during plasma fractionation in published studies • European risk of vCJD (except France, U.K.) low because of smaller BSE epidemic relative to U.K. • Effects of European donor deferral on nationwide/worldwide plasma supplies uncertain, but potentially severe

4. vCJD: Ongoing Concerns • TSE transmission by blood in animals • Rodents • Lemurs • Experimental BSE in sheep • Natural scrapie in sheep • Insufficient epidemiologic information • Epidemic size unknown (prevalence incubating donors) • Likelihood of transmission by blood products unknown • Lymphoid tissue expression abnormal protein • Implies but does not prove lymphoid tissue more infectious than for CJD • Suggests unusual tissue distribution infectious agent

5. Risk Reduction Measures for Infectious Agents in Plasma Derivatives Virus CJD Donor Deferral Donor Testing Clearance by Processing + + + - + Possible

6. Labeling and Transmissible Agents in Plasma Derivatives • Labeling • Provides estimate of risk of transmission of infectious agents • Discusses measures taken to reduce risks • Allows the public to make a more informed decision on risk/benefit • Labeling claims typically undergo thorough scientific/regulatory review prior to implementation • Labeling claims for pathogen removal in the past have been based upon rigorous and specific scientific evidence

7. Current FDA Recommendation: Labeling for Risk of CJD in Plasma Derivatives: “Because [this product] is made from human blood, it carries a risk of transmitting infectious agents, e.g. viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.”

8. Questions to the Committee • Should FDA consider labeling claims for TSE clearance in plasma derivatives, based upon specific demonstration of TSE removal during manufacturing?* • Assumes adequacy of decontamination procedures • in product manufacturing

9. Questions to the Committee • If so, please comment on whether such data would support the following draft wording for labeling: “Because this product is made from human plasma, it carries a risk of transmitting infectious agents, e.g. viruses, and, theoretically the vCJD agent. It has been demonstrated that [the manufacturer’s] manufacturing process provides substantial clearance of agents similar to those causing CJD and vCJD. Thus the theoretical risk of transmission of CJD or vCJD is extremely remote.”

10. Speakers • Virus Removal from Blood Products: Validation, Label Claims, and Possible Paradigm for Removal of TSE Agents • Mahmood Farshid, Ph.D., OBRR/FDA • TSE Agent Clearance Issues • Dorothy Scott, M.D., OBRR/FDA • Risk Analysis for TSE’s in Plasma Derivatives • Steve Anderson, Ph.D., OBE/FDA • European Perspective on TSE Agent Clearance in Plasma Derivatives • Sol Ruiz, Ph.D., Spanish Medicines Agency • TSE Clearance Studies by Plasma Manufacturers • Henry Baron, M.D., Aventis Behring, speaking for Plasma Protein Therapeutics Association