1. 1 U.S. vCJD Donor Screening: Human Cells, Tissues, and Cellular and Tissue- Based Products (HCT/Ps) Melissa A Greenwald, MD CAPT, U.S. Public Health Service Chief, Human Tissues and Reproduction Branch Division of Human Tissues OCTGT/ CBER/ FDA TSE Advisory Committee 1 August 2011

2. 2 Scope Regulatory Background Donor screening for vCJD in the US ComparisonsConclusion

3. 3 What is an HCT/P? Human cells, tissues and cellular and tissue-based products Regulatory definition: Articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient Encompass a wide variety of products Regulated by OCTGT

4. 4 Examples of HCT/Ps From deceased (cadaveric) donors: Musculoskeletal tissues Skin Dura mater Cardiovascular tissues Ocular tissues Tissue/device and other combined products From living donors: Hematopoietic stem/progenitor cells from peripheral and cord blood Other cell therapy products –pancreatic islets –mesenchymal stem/ stromal cells –fibroblasts Cells transduced with gene therapy vectors Reproductive cells and tissues

5. 5 Not HCT/Ps Vascularized human organs for transplantation (HRSA oversight) Whole blood or blood components; blood derivative products Secreted or extracted human products, e.g. oMilk oCollagen oCell Factors In vitro diagnostic products Minimally manipulated bone marrow for homologous use and not combined with another article Ancillary products used in the manufacture of HCT/Ps Cells, tissues, and organs derived from animals other than humans

6. 6 21 CFR Part 1271 Regulation Issues Addressed Establishment Registration and Listing Applicability: types and uses of products that will be regulated by these rules, requirements for registering and listing products Donor Eligibility Requirements for donor screening and testing for “relevant communicable disease agents and diseases” Current Good Tissue Practice (CGTP) Manufacturing to ensure that HCT/Ps do not contain communicable disease agents, are not contaminated, and do not become contaminated

7. 7 Goal of 21 CFR 1271 Regulations HCT/Ps carry a potential risk of communicable disease transmission from the donor to the recipient 1271 regulations are designed to minimize the risk of communicable disease transmission –Donor screening –Donor testing –Ensure cells or tissues are not contaminated during recovery, processing, storage or distribution Donor screening and testing only for relevant communicable disease agents or diseases (RCDADs)

8. 8 Current RCDADs Agent Required for ScreeningTesting HIV-1 and -2 AllXX Hepatitis B AllXX Hepatitis C AllXX SyphilisAllXX TSEAllX WNVAllX SepsisAllX Vaccinia (recent smallpox vaccination) AllX

9. 9 Current RCDADs Agent Required for ScreeningTesting HTLV-I and II Viable, Leukocyte- rich XX CMV* X Chlamydia tracomatis ReproductiveXX Neisseria gonorrhoeae ReproductiveXX *CMV is not a RCDAD; donors of viable leukocyte-rich HCT/Ps must be tested for CMV and positive test results must be communicated to the responsible physician

10. 10 vCJD Donor Screening Recommendations

11. 11 HCT/P Donor Screening (vCJD) Donor Screening Criteria (donor ineligible if they meet any of the following criteria) – Persons diagnosed with any form of CJD, including vCJD –Persons who have spent more than 3 months cumulatively in the United Kingdom from the beginning of 1980 to the end of 1996

12. 12 HCT/P Donor Screening (vCJD) Persons who are current or former U.S. military members, civilian military employees, or dependants of a military member or civilian employee who resided at U.S. military bases in Northern Europe (Germany, Belgium, and the Netherlands) for 6 months or more cumulatively from 1980 through 1990, or elsewhere in Europe (Greece, Turkey, Spain, Portugal, and Italy) for 6 months or more cumulatively from 1980 through 1996

13. 13 HCT/P Donor Screening (vCJD) Persons who have spent 5 years or more cumulatively in Europe from 1980 until the present This criterion includes time spent in the U.K. from 1980- 1996 –Albania, Austria, Belgium, Bosnia-Herzegovina, Bulgaria, Croatia, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Liechtenstein, Luxembourg, Macedonia, Netherlands, Norway, Poland, Portugal, Romania, Slovak Republic, Slovenia, Spain, Sweden, Switzerland, United Kingdom, and Yugoslavia. –The United Kingdom should include all of the following: England, Northern Ireland, Scotland, Wales, the Isle of Man, the Channel Islands, Gibraltar, and the Falkland Islands.

14. 14 HCT/P Donor Screening (vCJD) –Persons who received any transfusion of blood or blood components in the U.K. or France between 1980 and the present No current donor screening recommendations regarding Saudi Arabia

15. 15 Major difference between HCT/P and blood donor screening criteria HCT/P donor screening recommendations –Do not exclude donors for exposure to injected bovine insulin –Do not distinguish between France and the rest of Europe Donor medical history interview for deceased donors is performed by questioning someone other than the donor, and this information would be difficult to obtain reliably

16. 16 Health Canada Cell and Tissue Donor Screening Health Canada requires that travel information be collected, and requires some donor screening for vCJD risk factors However, for cell and tissue donors, there are no exclusion criteria based upon risk factors associated with residence or travel history to specific geographic areas

17. 17 Summary Geography-based screening for vCJD risk is based on evaluating the donor’s risk of exposure to the BSE agent Screening criteria are consistent for all HCT/Ps; they are not product-specific Today’s discussion regarding risk of exposure to the BSE agent in Saudi Arabia applies to HCT/P donor screening

18. 18 Additional Information 21 CFR 1271 www.accessdata.fda.gov/scripts/cdrh/cfdocs /cfcfr/CFRSearch.cfm?CFRPart=1271 www.accessdata.fda.gov/scripts/cdrh/cfdocs /cfcfr/CFRSearch.cfm?CFRPart=1271 Donor Eligibility Guidance www.fda.gov/BiologicsBloodVaccines/Guida nceComplianceRegulatoryInformation/Guida nces/Tissue/ucm073964.htm www.fda.gov/BiologicsBloodVaccines/Guida nceComplianceRegulatoryInformation/Guida nces/Tissue/ucm073964.htm

19. 19 Questions?

20. 20 Contact Information: Melissa.Greenwald@fda.hhs.gov General inquiries: 301-827-1800 Consumer inquiries: ocod@fda.hhs.gov ocod@fda.hhs.gov Manufacturer inquiries: matt@fda.hhs.gov matt@fda.hhs.gov www.fda.gov/BiologicsBloodVaccines/default/htm