apma 2008 cber reference/sera candidacy testing
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APMA 2008 CBER Reference/Sera Candidacy Testing. September 2008. James King. Agenda. Review of last years commitment to CBER Proposal for standardizing the optimization process for reference or sera replacement Proposal for summarizing reference replacement and unknown ERP data - PowerPoint PPT PresentationTRANSCRIPT
APMA 2008CBER Reference/Sera
Candidacy Testing
September 2008
James King
9/04/03
Agenda
Review of last years commitment to CBER Proposal for standardizing the optimization
process for reference or sera replacement Proposal for summarizing reference
replacement and unknown ERP data Discuss minimum aliquots required for
proposed testing of reference or sera replacements
9/04/03
APMA meeting October 2007
Industry accepted the need to partner with CBER to provide quick and useful data for reference and sera replacement
Industry committed to have reference review to CBER in 30 days
Per the meeting minutes, CBER was going to supply industry with a standard method to supply results
CBER or Industry to standardize method for communicating reference/sera review
9/04/03
To facilitate a unified collaboration between industry and CBER, HollisterStier Laboratories would like to propose:
A systematic approach to review new reference or sera
A means to report the data in a standardized format
Sharing data between industry and CBER
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Approach for replacement review
Optimization of assay parameters
Side by side testing of approved and proposed system
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Optimization
Goals:– Perform checkerboard optimization to achieve
desired signal to noise.– Minimize consumption of CBER reference
and sera.– Formalize a standard practice to communicate
results to CBER.
9/04/03
Optimization Proposal
Product Name = Mite D. Farinae Coating Dilutions
1:750 1:100 1:250 1:500 1:750 1:1000 1:750 1:100 1:250 1:500 1:750 1:10001 (Blank) 2 3 4 5 6 7 (Blank) 8 9 10 11 12
Sera 1:5 ADilution 1:10 B High Control High Control
1:20 C Anti-IgE 1:1000 Anti-IgE 1:20001:25 D
HSA 1:5 EDilution 1:10 F Low Control Low Control
1:25 G Anti-IgE 1:1000 Anti-IgE 1:20001:50 H
Exsisting coating dilution no sera added Exsisting coating dilution no sera added
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Example Checkerboard
Product Name = Mite D. pteronyssinus Sera Optimization
BLANK 1:100 1:250 1:500 1:750 1:1000 BLANK 1:100 1:250 1:500 1:750 1:1000A 0.221 1.389 1.220 1.051 0.882 0.713 0.198 1.220 1.051 0.882 0.713 0.544B 0.200 0.987 0.890 0.793 0.696 0.599 0.190 0.890 0.793 0.696 0.599 0.502C 0.198 0.560 0.401 0.242 0.242 0.231 0.179 0.560 0.535 0.510 0.485 0.460D 0.210 0.301 0.270 0.239 0.208 0.177 0.182 0.230 0.277 0.324 0.371 0.418E 0.201 0.289 0.287 0.285 0.283 0.281 0.176 0.289 0.287 0.285 0.283 0.281F 0.189 0.270 0.267 0.264 0.261 0.258 0.198 0.270 0.267 0.264 0.261 0.258G 0.220 0.200 0.225 0.250 0.275 0.300 0.189 0.200 0.225 0.250 0.275 0.300H 0.225 0.198 0.210 0.222 0.234 0.246 0.190 0.198 0.210 0.222 0.234 0.246
Selected Conditions:Sera Dilution 1:20Coating Dilution 1:1000Anti IgE dilutuion 1:1000
Low Control (Anti IgE 1:2000)High control (Anti IgE 1:1000) Low Control (Anti IgE 1:1000)
High control (Anti IgE 1:2000)
9/04/03
Performing CBER side by side testing
CBER distributes new reference – Two unknown samples are included– Third sample reserved for reference
comparison– Samples tested on current system – Samples are tested on new optimized
system
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Example of Results for submission to CBER and Industry
Test 1logRP RP logRP RP logRP RP logRP RP
Plate 1 0.0866 1.2207 -0.0321 0.9288 -0.0380 0.9163 0.1302 1.3494Plate 2 -0.0048 0.9861 -0.0707 0.8498 -0.0748 0.8418 -0.0629 0.8652Plate 3 0.1112 1.2919 -0.0410 0.9099 -0.0495 0.8922 -0.0399 0.9122Mean 0.0643 1.1597 -0.0479 0.8955 -0.0541 0.8829 0.0091 1.0213
Test 2logRP RP logRP RP logRP RP logRP RP
Plate 1 0.0289 1.0689 0.0079 1.0183 0.0172 1.0404 -0.0367 0.9189Plate 2 0.0858 1.2184 0.0321 1.0767 0.0494 1.1206 -0.0090 0.9795Plate 3 0.0938 1.2412 0.0171 1.0402 0.0429 1.1039 -0.0466 0.8982Mean 0.0695 1.1735 0.0190 1.0448 0.0365 1.0877 -0.0308 0.9316
Percent Difference 1% 15% 20% 9%
E9-Df as Ref Std and Coating Extract (1:500)CBER Sample #1 CBER Sample #2 E9-Df QC RefE8-Df
E8-Df QC RefE9-DfE8-Df as Ref Std and Coating Extract (1:500)
CBER Sample #1 CBER Sample #2
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HollisterStier will provide to those interested:
Spreadsheet for checkerboard optimization– Including fields for identifying selected
conditions Spreadsheet for side by side comparisons
– Including automated calculation for percent difference or other statistical method as discussed by CBER and industry
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Needs from CBER
Provide enough of the proposed reference or sera to perform the testing as outlined in this slide show.
– Approximately 500µL reference needed– Approximately 2 or 3 vials of sera
Provide unknown test samples for comparative testing
Communicate with industry when references are low so we can better adjust production
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In summary
This process is intended to:– expedite testing of proposed CBER
reference or sera replacements– minimize impact to industry– summarize and share test results with
industry in a standardized format– provide justification for accepting or
rejecting reference or serum replacement– most importantly, allow us to work
together
9/04/03
Thank you for your time
Remember to submit your yearly forecast of CBER reference and sera consumption to
CBER by January 2009