The ABCs of BPDs

1. Presented by Karen Dosanjh Quality Director Blood Systems The ABCs of BPDs

2. Disclosure I have no relevant financial relationships to disclose.

3. Learning Objectives • Describe a scenarios that would be reportable as a BPD. • Recognize when patient lookback is required. • Apply root cause analysis tools to process improvement.

4. FDA Guidance: BPD Reporting for Blood and Plasma Establishments • Who Must Report? All establishments involved in the manufacture of blood and blood components, including: -licensed manufacturers, -unlicensed registered establishments, -transfusion services.

5. FDA Guidance: BPD Reporting for Blood and Plasma Establishments • Who Must Report? Per 21 CFR 606.171,  the manufacturer that had control over the product when the deviation from current good manufacturing practice, applicable regulations, applicable standards, or established specifications or an unexpected or unforeseeable event that may affect the safety, purity, or potency…

6. FDA Guidance: BPD Reporting for Blood and Plasma Establishments • Who Must Report? Contract Manufacturing: Viral Marker or Compatibility Testing Irradiation Blood Collection Storage Distribution

7. FDA Guidance: BPD Reporting for Blood and Plasma Establishments • What Must Be Reported? • Event • Represents a deviation from current good manufacturing practice, applicable regulations, applicable standards, or established specifications that may affect the safety, purity, or potency of that product; or • Represents an unexpected or unforeseeable event that may affect the safety, purity, or potency of that product; • Occurs in your facility or a facility under contract with you; • Involves a distributed blood or blood component.

8. FDA Guidance: BPD Reporting for Blood and Plasma Establishments • Flow Chart Questions (1) Was the event associated with “manufacturing” or holding or distribution as they are described in the regulation? (2a) Was there a deviation that may affect the safety, purity, or potency of a product? (2b) Was there an unexpected or unforeseeable event that may affect the safety, purity, or potency of a product? (3) Did it occur in your facility or in a facility under contract with you? (4) Did you have control over the product when the event occurred? (5) Was the product distributed?

9. FDA Guidance: BPD Reporting for Blood and Plasma Establishments • Items of significance in the guidance (PDI): • Report post donation information if you would have deferred the donor had you known the information at the time of donation and the safety, purity, or potency of the product could be affected. • PDI is also reportable if the medical evaluation reasonably suggests that the safety, purity, or potency of the product could be affected , or the information is insufficient to conclude that the safety, purity, or potency of the product is not affected.

10. FDA Guidance: BPD Reporting for Blood and Plasma Establishments • What Is NOT Reported? • When you did not distribute potentially affected products, regardless of the event. • When you determined, prior to distributing the product, that the event did not actually affect the safety, purity, or potency of the product. • When you detected the event and prior to distribution, made the appropriate corrections. • When the event was related to donor safety only and did not have the potential to affect the safety, purity, or potency of the product. • If your report would simply state that you were late in reporting the event to us.

11. Error Examples – Reportable or Not Reportable?

12. Error Examples – Reportable or Not Reportable?

13. PDI Examples – Reportable or Not Reportable?

14. PDI Examples – Reportable or Not Reportable?

15. PDI Examples – Reportable or Not Reportable?

16. PDI Examples – Reportable or Not Reportable?

17. Lookback per 21 CFR 610 • Initially reactive viral marker test results require donor lookback. (NR) • Confirmed positive viral marker test results for HCV and HIV also require patient lookback. (RE) • NAT reactive test results for HCV and HIV require donor and patient lookback. (RE) • NAT reactive test results for other infectious diseases may require donor and patient lookback. (RE)

18. FDA Guidance: BPD Reporting for Blood and Plasma Establishments • What Must Be Reported? • Facility information • Date of Discovery • BPD Reporting Code • Description of the event • Investigation/RCA findings and Corrective Actions • Only distributed components from the impacted or affected donation(s).

19. FDA Guidance: BPD Reporting for Blood and Plasma Establishments • BPD Reporting Codes • Donor Suitability – PDI • Donor Suitability – Donor Screening and Deferral • Collection • Component Preparation • Testing • Labeling • Quality Control & Distribution

20. BPD Reporting Codes – Which Code Fits Best? • On a subsequent visit, a donor reported using needles to take drugs not prescribed by their physician 3 years ago. During the same visit, the donor reported having had a tattoo prior to his last donation. • PD-12-16 IV Drug Use Not Prescribed by a Doctor • PD-12-53 Multiple High Risk Behaviors/Contact

21. BPD Reporting Codes – Which Code Fits Best? • An underweight FFP product was received in the manufacturing lab for quarantine and subsequently discarded. During the investigation, it was determined that the apheresis kit may have been prematurely raised resulting in a changed collection status from a closed system to an open system. Companion platelet products had shipped prior to discovery of the information with a 5 day expiration date, and not the 24 hour open system expiration date. • QC-94-12 Product identified as unsuitable due to a collection deviation or unexpected event • LA-81-06 Expiration date or time extended or missing

22. BPD Reporting Codes – Which Code Fits Best? • A red blood cell product was returned by a consignee because the product was labeled as A negative and the consignee typed the product as A positive. Reference Laboratory testing resulted in a typing of A positive, supporting a partial D antigen. This is a known limitation of the commercial reagents currently available. • LA-81-02 ABO and/or Rh incorrect or missing • RT-61-04 Testing performed, interpreted, or documented incorrectly – ABO and/or Rh

23. BPD Reporting Codes – Which Code Fits Best? • On a subsequent visit, Collection staff discovered that a male donor who presented and donated at 3 prior visits had the incorrect sex identified in the donor identification profile in the BECS. As a result, the electronic donor questionnaire launched to the donor on each of these previous visits excluded the male gender questions (unanswered). • DS-22-02 Donor record incomplete or incorrect – Donor identification • DS-22-03 Donor record incomplete or incorrect - Donor history questions

24. Investigation/Root Cause Analysis and Corrective Action • Investigation and root cause analysis of an unexplained discrepancy or failure of a lot of unit to meet specification must be robust. • Determination of the root cause may be achieved through the use of a root cause analysis tool.

25. Root Cause • The root cause of an event is the most basic cause from which the event, desirable or undesirable, originates from.

26. Root Cause Analysis Tools • 5 Whys • Cause and Effect Diagram • Ishikawa (Fishbone) Diagram • Flowcharts • Pareto Charts • Histograms

27. Root Cause Analysis Do’s and Don’ts • Don’t use judgments. • Don’t state your opinion. • Don’t state your emotions. • DO visualize the problem using tools. • DO consider the data you will need to collect. • DO think about the past: • Has this happened before? • What was done in the past? • DO analyze the data objectively. • DO implement process improvement & prevention.

28. Questions? Kdosanjh@bloodsystems.org Reference: FDA Guidance for Industry: Biological Product Deviation Reporting for Blood and Plasma Establishments, dated October 2006