1. Exploring the Risks of Contaminated Medical Products MODERATOR: Susan R. Chmieleski, APRN, CPHRM, FASHRM, JD, Senior Vice President, Healthcare Product Manager & Risk Management Lead, Darwin Allied World PANELISTS: Clay Anselmo, President & Chief Executive Officer, Reglera Scott Brubaker, CTBS, Chief Policy Officer, American Association of Tissue Banks Robert E. Jurgel, Jr., MBA, RPLU, Senior Vice President & Head of Healthcare Underwriting, ROCKHILL Underwriting Management Anthony Vale, Esq., Partner, Pepper Hamilton, LLP

2. Chicago, Illinois ~ March 24 & 25, 2009 Industry Overview / Case Study Rob Jurgel, RPLU Senior Vice President - Healthcare ROCKHILL Underwriting Management

3. What is an allograft? A graft of tissue or an organ taken from one individual (donor) and given to another individual (recipient).

4. Organ Bank Industry 58 federally chartered banks (non profit) Matching Network – UNOS via Unet (1999) 25,628 Transplants, 12,934 Donors 6 Products – Kidney, Heart, Lung, Liver, Pancreas, Intestines Procurement - Transplant Centers – 253 Regulation – HRSA, AOPO - voluntary Morphing into Tissue

5. Tissue Bank Industry 200+ Banks, 100 AATB Accredited 1.5 million grafts annually Hundreds of products Procurement– Hospitals, Universities, Funeral Homes, Morgues Regulation – FDA, AATB – accreditation is VOLUNTARY New Regulations- May 2005

6. Tissue Processing & Distribution Identify & Screen Donors Obtain Informed Consent Recover Tissue Test, Process, Sterilize & Store Tissue Distribute Record Keeping

7. Case Study - Video You’ll never look at Healthcare the same!

8. Claims Fallout 1077 bodies harvested illegally 13,000 people have received tissue harvested illegally Recipient Cases: “Disease” “Disease Phobia” Donor Cases - Estate Multiple parties

9. Chicago, Illinois ~ March 24 & 25, 2009 Laws, Regulations, and Litigation Anthony Vale, Esq. Partner, Pepper Hamilton, LLP

10. Allograft Basics Human bone, ligaments, valves, skin  Each donor may provide 50-100 allografts  Over 1 million musculoskeletal per year Obtained by “recovery agency” “Tissue bank” processes bone/tissue Distributor supplies to hospital/surgeon

11. Three statutes: NOTA, “Blood Shield” and UAGA National Organ Transplant Act: human tissue may not be sold  Tissue banks may charge “reasonable fees” for services Blood shield laws Anatomical Gift Act: who may give consent? May rely on facially valid documents

12. Federal, some state regulations and AATB Federal regulations  Require testing of donor for infectious disease and medical history  No equivalent of FDA 510k State regulations  May require inspection of facility AATB standards

13. Tissue Processors Few major players Role: increase donations; use donations to maximize value; ensure safety Redundant safety measures: screening by recovery agency; blood test; sterilization or other processing

14. Litigation Risks Widespread use of allograft High demand for donations Supply chain extended Processing practically eliminates risks of disease transmission  Fear of disease? Potential claims by donors’ families

15. Chicago, Illinois ~ March 24 & 25, 2009 Are Practices Safe? Scott Brubaker, CTBS Chief Policy Officer

16. How many Tissue Banks are there? Depends on what your definition is-  FDA’s eHCTERs database for registered “Tissue Establishments” Query capabilities are flawed in some ways but it can be useful….depends what you need  Expectations probably include Tissue Banks involved in the chain (consent/recovery, processing, distribution) leading to the most commonly distributed tissues

18. Examples of Who Must Register - by Function Recover HCT/Ps, Screen HCT/P Donors Test Donors Process Package, Label, Store Distribute

20. FDA’s HCT/P List* Bone (including demineralized bone), cartilage Ligaments, tendons, fascia, pericardium, dura mater Skin, amniotic membrane (when used alone, not for ocular repair) Arteries and veins (except umbilical cord veins, etc.) Heart valve allografts Semen, oocytes, embryos Ocular tissue (corneas and sclera) Hematopoietic stem/progenitor cells derived from cord blood *grouped by me

22. Recover Recover (active registrations, query 4-17-08) eHCTERs Query Result Actual (minus search flaws and satellites) Accredited by AATB Bone1409850 Skin13610349

23. Process Process (active registrations, query 4-17-08) eHCTERs Query Result Actual (minus search flaws and those w/limited processing activities, satellites) Accredited by AATB Bone933223 Skin712617

24. Process Process (active registrations, query 4-17-08) eHCTERs Query Result Actual (minus search flaws and those w/limited activities, satellites) Accredited by AATB Heart Valves 4544 Vascular4554

25. Distribute Distribute (active registrations, query 4-17-08) eHCTERs Query Result Actual (minus search flaws and satellites) Accredited by AATB Bone37828346

26. 2007 AATB Survey of Accredited Tissue Banks - Distribution Graft Type# of Grafts Musculoskeletal1,281,259 Tissue Devices419,418 Soft Tissue (tendons, ligaments) 160,800 Skin88,249 (21,825 sq ft) Cardiac5,399 Vascular3,814 Dura331 1,959,270

27. State Requirements for Tissue Banks (Data circa 2007) New York State Department of Health  811 TBs licensed;191 located outside of NY Florida Agency for Health Care Administration  76 TBs licensed; 56 located outside of FL California Health and Safety Code  496 TBs licensed; 118 hold outside of licenses Other permit, licensing, certification, programs  DE, DC, GA, IL, LA, MD, MI, OK, OR

28. AATB Bulletin No. 08-55 13 States listed & requirements differ http://www.aatb.org/files/staterequirementsforlicensure.pdf

29. AATB & State Laws AATB accreditation or certification of personnel is referenced in statutes/laws in >20 states

30. Recommendations & AATB Accreditation American Academy of Orthopaedic Surgeons  Policy: use tissue only from banks accredited by AATB. American Burn Association  Require compliance with all federal, state, and JCAHO requirements, and recommend standards of the AATB. Philadelphia Grand Jury Report (BTS investigation)  Recommendation requires all tissue agencies to be licensed by the state and accredited by the AATB should be required for a license FDA’s Inspection Program  Tiered approach; use professional accreditation as a factor when stratifying TEs to inspect

31. AATB’s Standards 1st published in 1984 AATB’s Standards have served as a model for:  FDA’s CGTP regulations  Health Canada’s Safety of Cells, Tissues and Organs Regulations & draft Guidance  New York DOH’s Tissue & Cell Standards  European Union Commission Directives  European Association of Tissue Banks Standards  British Association for Tissue Banking Standards  Spanish Association of Tissue Banks’ Standards  (ALaBaT) Latin American Association for Tissue Banks Standards (in development)

32. AATB’s Standards are More Detailed than FDA Regulations Standards require :  Medical Director makes all donor suitability (eligibility) determinations  Detailed consent requirements  Donor screening for risk/quality  Specific “quality” screening requirements  Detailed tissue recovery requirements time limitations for recovery technical recovery methods

33. AATB’s Standards- More Detailed than FDA Regulations Standards:  Donor reconstruction requirements  Archiving of a serum or plasma sample from every donor if any remains after testing  Process control endpoints related to quality  Specific tissue release criteria  More labeling & package insert controls, content  More personnel-related safety concerns  Must establish recipient follow-up data collection protocols

34. 3rd Party Inspections In general, state licensing & voluntary accreditation offers an enhanced level of satisfaction and safety since there exists 3rd-party scrutiny of the tissue and/or eye bank’s operations. AATBEBAA New York California Florida

35. Standards for End Users “Tissue Services” The Joint Commission  Transplant Safety Chapter - Transplanting Tissues Hospitals, Critical Access Hospitals, Ambulatory Care, Office- based Surgery, Laboratory AABB  Standards for Blood Banks & Transfusion Services College of American Pathologists  Transfusion Medicine Checklist American Association of Tissue Banks  Section L - Tissue Dispensing Services Tissue handling oversight unknown if not under these umbrellas

36. Disease Transmission by Tissue Since 2000 2000 (2002) HCV Frozen tendons, cryo vein Inadequate Infectious Disease Test Methodology (HCV NAT not in use) AATB required NAT in 2005; FDA required NAT in 2008 2001Clostridium Fresh bone/cartilage Violated Standards; Inadequate microbial detection methods; a death occurred 2002Clostridium Fresh/frozen tendon, meniscus Inadequate microbial detection methods 2003Strep. pyogenes Frozen tendons Inadequate microbial detection methods; lack of sharing of records 2006 Chryseobacterium meningosepticum Frozen tendons Contamination from processing environment CDC in 2005: Estimated incidence = 0.0004% per 900,000 implants/yr

37. Largest Recalls 2005-2006  BTS-related  ≈ 28,000 allografts from 6 tissue banks made available TBs verified where all grafts were sent ≈ 700 tissue grafts unaccounted for by end users  500 US + 200 International ≈ 1,300 tissue devices unaccounted for by distributors & end users ≈ 8,000 returned or destroyed by end users ≈ 15,800 implanted The rest were not distributed and quarantined at TBs No disease transmission proven 7.1%

38. Largest Recalls 2006  Chryseobacterium meningosepticum  2 infections reported; resolved, grafts remain in place and functional  ≈ 4,800 frozen tendons/ligaments recalled TB verified where all grafts were sent Disposition of 99% of the grafts known within 30 days  Will some help from FDA, 100% reached ≈ 750 hospitals in Canada, Mexico, and the US  ≈ 1,000 grafts returned by end users  ≈ 3,800 grafts implanted

39. A Sentinel Event Recovery agency and tissue processor were not accredited by AATB AATB Standards were violated (body not cooled within 12 hrs of death for recovery up to 24 hrs after death; not until 19 hrs) Death event should not have occurred Processor has since attained AATB accreditation but recovery agency has not ?

40. “That men do not learn very much from the lessons of history is the most important of all the lessons of history.” A., Matthew. "Photo Cited" somaweb.org. 1995-2008; photographer unknown Aldous Huxley 1894-1963 Thank you!

41. Chicago, Illinois ~ March 24 & 25, 2009 ENSURING PATIENT SAFETY THROUGH APPLICATION OF QUALITY ASSURANCE SYSTEMS IN TISSUE BANKING Presented by Clay Anselmo, RAC President and CEO Reglera LLC Denver, CO

42. Key Risk Elements Donors Tissue Handling Processing Storage and Distribution Regulatory

43. Quality Management Systems (QMS) PURPOSE  FDA/Regulatory – Prevent Disease Transmission  General – Ensure Safety of Tissue Products GENERAL CONCEPT- Procedure-Based Controls to Detect, Correct, Prevent Sources of Product Problems Systematic Self-Correcting Continuously Improving Addressing Each Risk Area Provide Structure for Regulatory / Standards Compliance Operational Stability

44. Quality Management Systems (QMS) Diagram

45. Tissue Regulations, Standards and Guidance Important Regulations  21 CFR 1271  State Specific Regulations Important Standards  AATB Standards For Tissue Banking  EBAA Medical Standards What Are These and Why Are They Important?  Establish SPECIFIC Requirements for Tissue Banking  Provide QMS Implementation Framework  Establish Inspectional / Certification Criteria

46. Important Risk Reduction Activities Donor Eligibility Determination Processing, Storage & Handling Controls Audits Post Market Monitoring Activities Overall QMS Adoption

47. Measuring Performance Accreditation Regulatory History Assessment Post-Market Monitoring

48. Thank You