General Laboratory: Managing Reagent Lot to Lot Changes Online Training

Welcome to the General Laboratory: Managing Reagent Lot to Lot Changes Online Training course.  This course will explore how to deal with changes in Quality Control that sometimes occur when a new reagent lot is started. Select Next to continue. This course was created by: Nils B. Person, Ph.D., FACB Senior Scientist Global Product Education. Upon successful completion of this course, you will be able to:   State how the QC sample matrix may impact QC results   Outline a protocol to verify a new reagent lot does not change patient results   Identify a process for determining acceptable limits for reagent lot to lot performance shifts   Select Next to continue. “True” Concentration in QC material   Measured  Concentration in QC material   Patient Results   Measured  Concentration in QC material   Basic assumption: QC samples are “surrogates” for patient samples and respond in the same way patient samples do   Limitations: QC samples are NOT identical to patient samples QC material is modified during manufacture Manufacturing process affects sample matrix Matrix:  everything in the sample except what we are measuring QC sample matrix differs from patient samples Matrix proteins in particular Matrix modified in manufacture Proteins may denature QC results may shift with a new reagent lot   QC target mean may need to be updated   New reagent lots should be evaluated using patient results   Immunoassays and enzyme activity assays are the methods most commonly affected Once lack of change in patient results confirmed Update is necessary to keep QC rules performing effectively Need to establish clinically significant difference Significant difference will not be the same for all methods Pool Serum Remove selected analytes   Add analytes back at target concentrations   Stabilize for storage   Ca+2 Glucose LDH TSH Recombinant TSH   Porcine LDH   Ca+2 Glucose Methods sensitive to sample protein matrix   Immunoassays Enzyme activity assays Performance impacted by altered sample protein matrix   Matrix effects may change with new reagent lot   Impact on QC results varies by   Reagents contain multiple biologic components One or more components may be a new lot in a new reagent lot   Method Lot QC material   QC brand A - Lot 123 QC brand C QC brand A IA control QC brand A - Lot 125 New Reagent Lot Enough Data Over Enough Time From Enough Systems Note: If expected QC results are updated, QC material IFU values and historical peer group data will no longer be useful as reference points   Updated QC Information Lot 1 Mean:  97.4 SD: 7.8 CV: 8.0% Lot 2 Mean:  109.6 SD:  6.10 CV:  5.6% Actual concentration QC target mean Patient Results Measured Concentration Updated QC target mean Possible reasons for a shift may include: Instrument problem Reagent problem       Usually see a shift in QC mean Possible reasons for a shift may include: Instrument problem Reagent problem Real Problems: Need to rule out or fix     Possible reasons for a shift may include: Instrument problem Reagent problem Real Problems: Need to rule out or fix Changes in QC material New Reagent lot   Possible reasons for a shift may include: Instrument problem Reagent problem Real Problems: Need to rule out or fix Changes in QC material New Reagent lot Do not indicate system problem May require updates to QC targets Reagent lot to lot QC shifts are fairly common.  One lab monitoring reagents on a general chemistry system had QC shifts with ~20% of the new reagent lots1.   Most Likely 1Martindale, et al., Validating New Reagents: Roadmaps through the Wilderness, LabMed, 37, 2006, 347-351   Demonstrate lack of impact using patient samples   CAP requires validation before using new lot. Note: Good clinical laboratory science includes patient based comparisons when possible   Test patient samples with old and new reagent lots Does not require large numbers of samples (<10 will do) Can evaluate based on clinical judgment Decide if lot to lot difference is significant What is an acceptable lot to lot difference for patient results?   Will not be the same for every method “less than 10%” – will not work for all methods Must take into account method imprecision   Especially when comparing single results for each lot Should be based on clinical significance   Possible ways to determine: Clinical outcomes Medical recommendations Biologic variability Professional recommendations EQA limits Method capability For additional information on this process, the CLSI document EP26-A can be helpful.   Significant Not Significant Conclusion: Lot to Lot Difference New Lot Acceptable   New Lot Acceptable Update QC targets   Hold use of New Lot Confirm study Contact manufacturer