1. 1 The role of competent authorities in Bio Vigilance M. Jesus Felix (mjfelix@catsalut.cat) Medical Coordinator of Tissues and Cells Catalan Transplant Organization on behalf of Catalan Health Services. Health Department. Government of Catalonia

2. 2 SURVEILLANCE (BIO VIGILANCE)

3. 3 Catalonian reporting circuit Urgent events: before 24 h Non urgent events: before 36 h

4. 4 Reporting Circuit Catalonian Hospitals Other Spanish Hospitals European Hospitals

5. 5

6. 6 SAR in recipients

7. 7 SAR in living donor

8. 8 Incident

9. 9 SAE

10. 10 Serious adverse effect: affects the product and /or the process Serious adverse reaction: affects the person (the donor or the recipient) DEFINITIONS

11. 11 Evaluation of the event Case investigation Risk evaluation Notification: Clinical Report Corrective implementing measures if required Solving the case to prevent and register it

12. 12 The role of Competent authorities (CA) Clinical notification report sent to CA Analyzing and investigating Ask for more /new data (if necessary) To TETo Transplant Responsible Donor data Tissue data Contralateral cornea :  Transplanted and results  or not transplanted. Wy? - SAE/SAR explanation - Intervention data - First measures applied -Recipient status - Consequences for recipient

13. 13 Implementing Measures With all data and documents available, it becomes:  An evaluation of possible damage is made  Appropriate measures are taken  Disseminating information to all involved areas and responsible  Close the case  And introduced SAE/SAR in BV Register  An evaluation of possible damage is made  Appropriate measures are taken  Disseminating information to all involved areas and responsible  Close the case  And introduced SAE/SAR in BV Register

14. 14 CLINICAL CASES

15. 15 Avaluation of an Event Every event should be analyzed in: –Severity. –Imputability. –Impact.

16. 16 Severity

17. 17 Imputability

18. 18 Impact Assessment Step 1: assessing likelihood of occurrence/ recurrence of SAR/E:

19. 19 Impact Assessment Step 2: assessing Impact /Consequences of SAR/E should it recur.

20. 20 Impact Assessment Step 3: Applying the Impact Matrix.

21. 21 Impact Assessment Step 4: The response of a tissue or cell bank or a health authority to a specific SAE/SAR should be proportionate to the potential impact as assessed by the matrix described. GREEN: The tissue or cell bank to manage the corrective and preventive actions and the health authority to file the report and keep a ‘watching brief’. YELLOW: Requires interaction between the tissue or cell bank and the health authority which may request an inspection that focuses on the SAE/SAR and corrective and preventive actions to be followed up, including evidence of effective recall, where necessary. Written communication to professionals working in the field might be appropriate. RED: Health authority will generally designate representatives to participate in developing or approving the corrective and preventive action plan, possibly a task force to address broader implications. Inspection, follow up and written comm

22. 22 MADE-UP EXAMPLE

23. 23 A cornea recipient from United Kingdom developed vCJD symptoms five years after the graft. SAE or SAR?? Do you need to measure severity and imputability? And the impact assessment tool?

24. 24 A cornea recipient from United Kingdom developed CJD symtomes five years after the graft. SAE or SAR?? SAR Do you need to measure severity and imputabilily? YES And the impact assessment tool? YES

25. 25 Severity

26. 26 Imputability

27. 27 Impact Assessment Step 1: assessing likelihood of occurrence/ recurrence of SAR/E:

28. 28 Impact Assessment Step 2: assessing Impact /Consequences of SAR/E should it recur.

29. 29 Impact Assessment Step 3: Applying the Impact Matrix.

30. 30 CASE 1

31. 31 A piece of bone identified as distal femur was sent to a hospital to be grafted. When the professionals opened the graft they discovered it was a proximal femur. What would you do? Is it a SAE or SAR?

32. 32 The tissue was grafted without any complication for the recipient. The label and package procedure of the tissue establishment was revised.

33. 33 CASE 2

34. 34 Donor of heart valves and corneas. The first determination RPR was negative. But in a second determination, it was TPHA + (IgG +, IgM-). One cornea was already grafted. What would you do? SAE or SAR?

35. 35 Another analysis was performed, and it was also positive. It was a past infection.

36. 36 The corneas were kept in Optisol® No complication in the recipient.

37. 37 CASE 3

38. 38 An haematologist reported a neumothorax while setting a central catheter in the subclavian for obtaining peripheral blood for an autologous HSCT. What would you do? SAE or SAR? Can the event be imputed to the procedure?

39. 39 The patient stayed in hospital where he received medical treatment and he recovered completely. The transplant was performed.

40. 40 CASE 4

41. 41 Two tissue recipients presented a positive culture to Enterobacter cloacae in the exudate of the surgical wound. What would you do?

42. 42 In both cases the antiobiogramme was the same, and it was sensible to Gentamicina (an antibiotic used for cleaning the bones at the tissue bank). In one recipient the tissue culture was negative but the site culture wasn’t performed. In the other recipient no culture was performed. What else would you do?? SAE or SAR?

43. 43 They contacted the other professionals that had grafted tissues from the same donor. The cultures in all cases were negative. A bone piece stayed at the tissue establishment and it was sent to be analyzed. The result was also negative. They concluded that it was a surgery contamination.

44. 44 They concluded that it was a surgery contamination. Both recipients got antibiotic treatment and they recovered completely.

45. 45 CASE 5

46. 46 The results of the anatomical pathology informed that a tissue donor had an adenocarcinoma. It was a heart valve and ocular donor. One cornea was grafted, the other was discarded due to quality reasons. Heart valves were stored at the bank. What would you do? SAE or SAR?

47. 47 Follow up of the recipient. He hasn’t developed any reaction.

48. 48 CLINICAL CASES