Joint WHO/FDA Minimum Potency Standards for Blood Grouping Reagents

1. Joint WHO/FDA Minimum Potency Standards for Blood Grouping Reagents 90th Meeting of BPAC August 17, 2007 Sheryl A. Kochman Chief, Devices Review Branch DBA/OBRR/CBER/FDA

2. Background CBER minimum potency standards SPECIFICITYLOT Anti-A 6A Anti-B 7A-1 Anti-D (for IgG products) 4a-1 Anti-D (for IgM products) 9

3. Background (cont) Anti-C (rapid tube) 10 Anti-C (saline tube) 14 Anti-c (rapid tube) 13 Anti-E (rapid tube) 11a Anti-E (saline tube) 15 Anti-e (rapid tube) 12a Anti-Human Globulin (Anti-IgG) 16A Anti-Human Globulin (Anti-C3d) 17A

4. Background (cont) • All manufactured in the early 1970s • All polyclonal • All potentially biohazardous

5. Why New Standards? • Questionable relevance to current reagents derived form monoclonal antibodies • Diminishing stocks • European Union In-Vitro Diagnostics Medical Device Directive, 98/79/EC, implemented • Some CBER standards found to be reactive for some tests for hepatitis.

6. Why Collaborate? • Encourage international harmonization • Elicit input from larger pool of experts • National Institute for Biological Standards and Control • International Blood Group Reference Laboratory • Sanguin CLB • CBER • WHO • Provide replacement standards for both FDA and WHO

7. Materials & Methods • Potency only • Serial two-fold dilution titrations • Hemagglutination • Manual tube test • Comparator reagents • 45 low-protein Anti-D • 10 high-protein Anti-D • 22 Anti-A • 23 Anti-B

8. Anti-D Study 20 laboratories 13 countries US Licensed American Red Cross Gamma Biologicals, Inc Immucor, Inc Medion Diagnostics, AG (formerly Medion Diagnostics GmbH) Millipore (formerly Serologicals) Ortho-Clinical Diagnostics Anti-A & Anti-B Study 17 laboratories 9 countries US Licensed American Red Cross Gamma Biologicals, Inc Immucor, Inc Medion Diagnostics, AG (formerly Medion Diagnostics GmbH) Millipore (formerly Serologicals) Ortho-Clinical Diagnostics Participants in Studies

9. Results • Wide-spread variability in end-point titer results across the laboratories for all standards and all reagents. • A few outliers • Complex analysis of the data required*

10. *References • An International Standard for specifying the minimum potency of anti-D blood-grouping reagents: evaluation of a candidate preparation in an international collaborative study, Vox Sanguinis, 2006, Vol 90, 131-139. • International standards for minimum potency of anti-A and anti-B blood grouping reagents: evaluation of candidate preparations in an international collaborative study, Vox Sanguinis, 2006 Vol 91, 336-344

11. For low-protein Anti-D reagents Use a 1:3 dilution Replaces FDA Anti-CD, 9 For high-protein Anti-D reagents Use a 1:8 dilution Replaces FDA Anti-D, 4a-1 ConclusionsAnti-D standard 99/836

12. Anti-A standard 03/188 Use a 1:8 dilution Replaces FDA Anti-A, 6A Anti-B standard 03/164 Use a 1:4 dilution Replaces FDA Anti-B, 7A-1 Conclusions

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