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New Guidance on Bioanalytical Services

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:

About the Authors

Scott Hickman has managed the customer experience for innovative life science companies for over 25 years and currently serves as the Director of Global Marketing for SEKISUI XenoTech, joining in 2018. Scott received a BA from Randolph-Macon College and his MBA from George Washington University.
Seema Muranjan serves as Director of the Analytical Services group, managing scientists within the department, leads analytical support for contract services, and is responsible for study design and protocol preparation for LC-MS/MS method development and validation, bioanalysis and metabolite characterization (in vitro and in vivo) studies. She has worked in the Analytical Services department at SEKISUI XenoTech since 2007. Seema has a Masters of Science degree in Chemistry from Tulane University, and a Masters of Science degree in Organic Chemistry from Bombay University

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