FDA and American Red Cross Blood Supply Safety & Protection Geoff Withnell, CQE, CQA, CQMgr System Design Engineer

1. FDA and American Red Cross Blood Supply Safety & Protection Geoff Withnell, CQE, CQA, CQMgr System Design Engineer American Red Cross

2. Our Heritage Henri Dunant Founder of the International Red Cross and winner of the first Nobel Prize.

3. Our Heritage Clara Barton Our founder and First President

4. Our Heritage Dr. Charles Richard Drew helped organize the first Red Cross Blood Donor Center

5. American Red Cross Biomedical ServicesMISSION The American Red Cross Biomedical Services will fulfill the needs of the American people, for the safest, most reliable, most cost-effective blood, plasma, and tissue services through voluntary donations. 1

6. Blood Is Manufactured Into: • Red Blood Cells • Platelets • Plasma • Cryoprecipitate • More 1

7. Food and Drug Administration (FDA) • Represents the American public. • Works to protect and promote the health of the American people. • Enforces CGMP. • Shares goal with the Red Cross in seeking to provide safe blood products. 1

8. History of Laws & Regulations for Blood The Jungle By Upton Sinclair 2

9. History of Laws & Regulations for Blood The early years Patient Medicine The Jungle 2

10. History Of Laws & Regulations For Blood Tainted Diphtheria Antitoxin 1902 Elixir Sulfanilamide 1938 Thalidomide 1962 2

11. CGMP = Current Good Manufacturing Practice 1

12. CGMP • A standard for the whole industry • General requirements • Require interpretation • Contains words like • Adequate • Suitable 1

13. The Code of Federal Regulations (CFR) contains the CGMP requirements. 1

14. Drugs (e.g., pain pills) Parts 210 & 211Biologics (e.g., vaccines) Parts 606 & 610 (for blood) BLOOD 2

15. FDA Regulations and Guidance • CFR • Guidelines, Guidance Documents, Compliance Policy Guides, and Standard Operating Procedures and Policies (provide FDA’s current thinking on the CGMP requirements) 2

16. SQuIPP = Safety Quality Identity Potency Purity

17. CGMP Focuses On: • Processes • People • Materials and Supplies • Equipment • Work Environment/Facility. 2

18. CGMP For Our Processes • We must always follow our SOPs. They have been validated or proven to work in our process. • When followed exactly as written they will produce safe, quality products. • Always use the current version of the SOP. 2

19. CGMP for our People • KEY CGMP BEHAVIOR: Take your training seriously. • KEY CGMP BEHAVIOR: If you do not feel competent to perform a task/role, stop and speak up! 2

20. CGMP for our Materials and Supplies • KEY CGMP BEHAVIOR: Make sure your supplies are maintained properly prior to use (e.g., sterile and not expired). • KEY CGMP BEHAVIOR: Use your supplies correctly. 2

21. CGMP For Our Equipment • KEY CGMP BEHAVIOR: Follow procedures and schedules for calibrating, maintaining and cleaning equipment. • KEY CGMP BEHAVIOR: Use equipment the way it was intended. 2

22. CGMP For Work Environment And Facilities • KEY CGMP BEHAVIOR: Keep your work area clean and orderly, especially to prevent contamination of our products. 2

23. How do we know we are meeting the CGMP requirements? We have systems to monitor our effectiveness: • In Process Reviews & Checks • Records Management System • Problem Management System • Quality Assurance Group • Internal Audits/External Inspections. 3

24. In Process Reviews & Checks • During the process, we check that we have followed the SOP. • We also do quality checks on some of our products. 3

25. Records are important because they… • Show what we did • Create a manufacturing history of our products • Show whether or not we followed our SOPs. 3

26. Records… • Must be • Clear, legible • Permanent • Concurrent • Accurate • Show who, what, when and with which supplies and/or equipment. 3

27. CGMP for Record Keeping KEY CGMP BEHAVIOR: Document accurately what you do as soon as you do it. • KEY CGMP BEHAVIOR: Sign for your work and only your work. 3

28. Mistakes happen… The goal of the Problem Management System is to correct problems now and prevent their recurrence in the future. 3

29. Problem Management System • Track our mistakes. • Fix them. • Plan how not to make the mistake again. This is part of continuouslyimproving our processes. 3

30. Problem ManagementSystem • KEY CGMP BEHAVIOR: Employees must report problems. • KEY CGMP BEHAVIOR: Employees must remain compliant despite the pressures of their jobs. 3

31. FDA Expects 5 Systems In Place • Quality Assurance • Donor (Suitability) Eligibility System • Product Testing System • Quarantine/Inventory Management System • Production and Processing System

32. Quality Assurance The sum of activities planned and performed to provide confidence that all systems and their elements that influence the quality of the product are functioning as expected and relied upon. (FDA’s Guideline for Quality Assurance in Blood Establishments, July 11, 1995)

33. Donor (Suitability) Eligibility System the system that protects donor safety, determines a donor’s suitability for blood collection (including donor deferral from either history screening and/or testing), notifies donors of unsuitability for donation and donor re-entry.

34. Product Testing System the system(s) that tests for communicable diseases, blood grouping and typing, and crossmatching blood for transfusion.

35. Quarantine/Inventory Management System the system(s) pertaining to product storage, distribution and retrieval, quarantine and distribution (release for use or destruction).

36. Production and Processing System process controls in the manufacture of specific blood and blood components, and equipment quality control, calibration, and maintenance

37. Five Layers Of Safety • Donor Screening • Donor Deferral • Product Testing • Quarantining • Monitoring and Investigating Problems

38. Donor Screening procedures to identify donors who have defined risk factor(s) for communicable disease(s) or who are otherwise unsuitable to donate.

39. Donor Deferral procedures to identify unsuitable donors and prevent the distribution of blood products collected from these donors.

40. Product Testing procedures to properly test blood for required infectious diseases and antigens and antibodies that may cause a hemolytic transfusion reaction.

41. Quarantining procedures to assure that blood products are quarantined until all tests and control procedures are acceptable and unsuitable products are removed from inventory.

42. Monitoring and Investigating Problems procedures to identify system problems, biologic product deviations, and blood donor and recipient adverse reactions and to assure that adequate corrective action is implemented.

43. Audits and Inspections • Internal audit program • Inspections by • FDA • OSHA • AABB • State & Local Health Departments These all tell us how we are doing in complying with regulations. 3

44. FDA Tools of Enforcement • FDA 483’s • Warning letters • Injunction • Seizure of product • Criminal prosecution • Suspension/revocation of license • Closure 4

45. Adulterated ProductFDA Meaning A product may be deemed “adulterated” if it isn’t made according to CGMP regulations, even if it isn’t really contaminated. 4

46. FDA Inspections • Usually unannounced • Presents credentials (Badge), and a Form FDA 482 or Amended Consent Decree • May observe procedures • May examine records • May interview staff • Any observations are presented at closing meeting and in Form FDA 483. 4

47. Inspection Outcomes andFDA Actions • 483 • Warning Letters • Consent Decree • Seizure of Products • Injunction/Suspensionof Operations • Criminal Proceedings, • Suspension/revocation of license • Closure 4

48. Personal Commitments • Always place donor and patient safety first. • Always understand and follow SOPs, the CFR, and CGMP. • Always report any existing or potential problems. • Take ownership of your job, make it personal. 4

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