# Presentation: 859147

## Joint WHO/FDA Minimum Potency Standards for Blood Grouping Reagents

**90****th**** Meeting of BPAC**
**August 17, 2007**
**Sheryl A. Kochman**
**Chief, Devices Review Branch **
**DBA/OBRR/CBER/FDA**

## Background

**CBER minimum potency standards**
***SPECIFICITY*****	****	****	****	****	*****LOT***
**Anti-A****	****	****	****	****	****	****6A**
**Anti-B****	****	****	****	****	****	****7A-1**
**Anti-D (for IgG products)****	****	****4a-1**
**Anti-D (for IgM products)****	****	****9**

## 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**

## Background (cont)

**All manufactured in the early 1970s**
**All polyclonal**
**All potentially biohazardous**

## 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.**

## 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**

## 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**

## Participants in Studies

**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**

## 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***

## *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**

## Conclusions Anti-D standard 99/836

**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**

## Conclusions

**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**

## Where to Send Requests

**Document Control Center (HFM-99) **
**Center for Biologics Evaluation and Research**
**Food and Drug Administration**
**1401 Rockville Pike, Suite 200N**
**Rockville, MD 20852-1448 **
**ATTN: HFM- 407**