July 2018

New Guidance on Bioanalytical Services

Author:  Seema Muranjan, Scott Hickman
Posted:  06 July 2018

Sekisui XenoTech offers bioanalytical services to support both internal groups and external clients. We have validated LC-MS/MS methods for human CYP markers, UDP glucuronosyltransferase (UGT) activity, monoamine oxidase (MAO), aldehyde oxidase (AO), animal P450s, and drug transporters (MDR1, BCRP).
 
Bioanalytical Method Validation:
Sekisui XenoTech’s approach to bioanalytical method validation is based on guidance from regulatory agencies:

  • Bioanalytical Method Validation Guidance for Industry (FDA, May 2018)
  • Guideline on bioanalytical method validation (EMA, 21 July 2011)
 
A brief outline of the procedure and deliverables is listed below (full procedures available upon request):

A full method validation study involves preparation and analysis of three batches of samples prepared in the appropriate stopped incubation matrix. Each batch will contain two replicates of six calibration standards and six replicates of quality control (QC) samples at four test article concentration levels (lower limit of quantitation, low, mid and high QC samples). The batches are analyzed and assessed for accuracy, precision and carryover as detailed in Sekisui XenoTech’s SOP for method validation. The curve range is selected based on anticipated analyte levels in sample incubations planned as part of the supported study. Calibration curve parameters will be generated using the simplest appropriate regression or weighting algorithm that best describes the concentration-response relationship.

Partial method validation is performed as necessary for each additional matrix based on the scope of the affiliated study. The partial validation consists of a single batch of samples prepared in appropriate stopped incubation matrix. The batch will contain two replicates of six calibration standards and six replicates of QC samples at three test article concentration levels.

Reinjection reproducibility, intra-batch (batch size) and stability of analyte in an applicable solvent is evaluated as part of method validation.

Long-term analyte stability in incubation matrix is not applicable to in vitro studies.
 
Method Qualification
A method qualification study involves preparation and analysis of one batch of sample prepared in the appropriate stopped incubation matrix. The batch will contain two replicates of six calibration standards and six replicates of quality control (QC) samples at three test article concentration levels (low, mid and high QC samples). The batches are analyzed and assessed for accuracy, precision and carryover. The curve range is selected based on anticipated analyte levels in sample incubations planned as part of the supported study. Calibration curve parameters will be generated using the simplest appropriate regression or weighting algorithm that best describes the concentration-response relationship.

Additional method qualification is performed as necessary for each additional matrix based on the scope of the affiliated study.
 
Deliverables:
A draft report will be prepared and submitted to sponsor for review. The report will consist of sample preparation procedures, method validation/qualification procedures, and statistical validation/qualification results. Analytical method information is presented in the appendix of the report. Performance of calibration standards and quality control samples for each method is presented as tables. Results for stability, reinjection reproducibility data and intra-batch analysis (applicable for method validation) is also presented as tables. Representative chromatograms for method validation batches will be included in the report.

References for method validation:
  • [EMA] European Medicines Agency (2011) Guideline on bioanalytical method validation, Science Medicines Health, Committee for Medicinal Products for Human Use (CHMP). 23 p.
  • [FDA] Food and Drug Administration (2018) Guidance for industry: Bioanalytical method validation, Center for Drug Evaluations and Research, Center for Veterinary Medicine, U.S. Department of Health and Human Services, Rockville, MD. 44 p.

Learn more about our Analytical Services
Read the new FDA Bioanalytical Method Validation Guidance for Industry
View other Regulatory Resources
 

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