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

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
Background
CBER minimum potency standards
SPECIFICITY
LOT
Anti-A
Anti-B
Anti-D (for IgG products)
Anti-D (for IgM products)
6A
7A-1
4a-1
9
Background (cont)
Anti-C (rapid tube)
Anti-C (saline tube)
Anti-c (rapid tube)
Anti-E (rapid tube)
Anti-E (saline tube)
Anti-e (rapid tube)
Anti-Human Globulin (Anti-IgG)
Anti-Human Globulin (Anti-C3d)
10
14
13
11a
15
12a
16A
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
Anti-B standard 03/164
• Use a 1:8 dilution
• Use a 1:4 dilution
• Replaces FDA Anti-A, 6A
• 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