Specialized Session M2 - Discussion Topic List
June 15, 2020, 11am to 4pm ET: Part 1
June 16, 2020, 11am to 3:30pm ET: Part 2

"BMV Guidance Day:
Interpretations & Training on ICH M10 before its Adoption; Audits Outcome using 2018 FDA; Transition from Local Guidelines to ICH M10 with Gap Analysis on Controversial Issues"

How can you be prepared for the transition from local FDA, EMA, MHLW, ANVISA Guidance/Guidelines to ICH M10? What do you need to do for the ICH M10 adoption & Global Harmonization of Bioanalytical Guidance? An in-depth gap analysis on controversial BMV issues after the public consultation of the ICH M10

View M2 Agenda

Chairs:
  • Dr. Anna Edmison, Senior Clinical Assessment Officer Division of Biopharmaceutics Evaluation, Health Canada
  • Drs. Jan Welink, Sr. Clinical Assessor, EU EMA

Understanding the Scope of new Guidance/Guidelines based on the Regulatory & Science Evolution

Recent Regulatory Findings from Different Regulators

Gap Analysis on Controversial Issues after the Public Consultation of the ICH M10

Interpretations & Training on ICH M10 before its Adoption

ASK THE REGULATORS!

  • Panel Discussion with All the Regulators:

    Address any questions you have directly to the Regulators

    • Dr. Tahseen Mirza (US FDA,)
    • Dr. Arindam Dasgupta (US FDA)
    • Dr. Mohsen Rajabiabhari (US FDA)
    • Dr. Suman Dandamudi (US FDA)
    • Dr. Diaa Shakleya (US FDA)
    • Drs. Jan Welink (EU EMA)
    • Mr. Stephen Vinter (UK MHRA)
    • Dr. Anna Edmison (Health Canada)
    • Dr. Catherine Soo (Health Canada)

 

Topic DETAILS of M2 – BMV Guidance Day

Chairs:
  • Dr. Anna Edmison, Senior Clinical Assessment Officer Division of Biopharmaceutics Evaluation, Health Canada
  • Drs. Jan Welink, Sr. Clinical Assessor, EU EMA
Understanding the Scope of new Guidance/Guidelines based on the Regulatory & Science Evolution

 

Recent Regulatory Findings from Different Regulators

 

Gap Analysis on Controversial Issues after the Public Consultation of the ICH M10
  • Topic 8
    Parallelism Evaluation in Regulated Bioanalysis for PK LBA: If "30% criterion is rubbish" what to do from a regulatory perspective?
    - Dr. Rachel Palmer, Head Biomarkers and Clinical Bioanalysis, Sanofi
    • Building on & supporting the 2019 White Paper in Bioanalysis Recommendations on ICH M10 for Parallelism for PK Assays with novel practical case studies
      • 2019 Link: https://www.future-science.com/doi/pdf/10.4155/bio-2019-0270
      • "For PK methods, parallelism should be implemented to investigate anomalous study data and should not be a routine validation assessment"
      • "The ICH M10 draft guideline states that the justification for the absence of a parallelism evaluation should be included in the Bioanalytical Report. It is recommended that the language be changed to require a justification of its applicability and an explanation of the results presented."
      • "Regarding the acceptance criteria, industry representatives questioned whether the criteria were an appropriate indication for detecting trends in parallelism. Since it is an investigative tool for PK assays, it was suggested that no a priori criteria are required."
    • Case studies
      • Use parallelism to investigate aberrant in-study PK results
      • How are anomalous data determined/identified?
      • Justification of parallelism applicability
      • Explanation of the results presented in the Bioanalytical Report
      • What are the Regulatory Expectations on the parallelism Justification & Explanation?
  •  

  • Topic 9
    Parallelism Evaluation for Endogenous Compounds: Building on WRIB recommendations, practical consideration on how to evaluate parallelism in chromatographic assays, differences from LBA, gap analysis and slope acceptance criteria
    - Dr. Allena Ji, Director Clinical Mass Spectrometry Laboratory Biomarkers and Clinical Bioanalyses, Sanofi
    • ICH M10 & Endogenous Compounds Quantification
    • Building on the 2018 White Paper in Bioanalysis Recommendations on Parallelism Evaluation for Endogenous Compounds for Chromatographic Assays with novel practical case studies
      • 2018 Link: https://www.future-science.com/doi/pdf/10.4155/bio-2018-0268
      • "When using a surrogate matrix approach, it is good practice to perform parallelism experiments in method validation, but it is not required."
      • "Dilution linearity should be tested during method development for assay characterization; it is best to use matrix from multiple individuals to test the method"
      • "Evaluation of parallelism, matrix effect and IS consistency is critical in determining whether special extraction conditions may be required to achieve equivalent recovery from both authentic and surrogate matrix"
    • Practical consideration on how to evaluate parallelism in LC-MS/MS between
      • Surrogate and authentic matrix
      • Slopes and matrix effect
    • What criteria should be established?
      • What is the reasoning behind these criteria?
      • Differences between parallelism evaluation in LBA and Chromatographic Assays for endogenous compounds
      • Slope acceptance criteria for Chromatographic Assays
  •  

  • Topic 10
    Partial & Cross Validation for PK LBA and Chromatographic Assays: Building on WRIB recommendations, understanding recent BMV Guidance/Guideline, bias and impact on clinical PK data
    - Ms. Rebecca Elliott, Sr. Scientific Manager Bioanalytical Sciences Genentech
    • What's new on Partial & Cross Validation from ICH M10?
      • Current draft ICH M10 guideline no longer proposes acceptance criteria for cross validations.
      • Statistical tools are proposed to assess comparability of 2 assays
    • Detailed recommendation on Partial & Cross Validation have already been issued in the 2011 & 2014 White Paper in Bioanalysis and used by the Global Bioanalytical Community
      • 2011 Link: https://www.future-science.com/doi/pdf/10.4155/bio.11.192
      • 2014 Link: https://www.future-science.com/doi/pdf/10.4155/bio.14.265
      • "When cross-validating methods, procedures and criteria may vary depending on the assay, the magnitude of the change and the sponsor's requirements. For example, if a single study is done at two different sites, a cross-validation using spiked QC samples and incurred samples was recommended."
      • "If the same method SOP is used at the two sites, one cross-validation run using QC samples may be sufficient."
      • "The recommendation from 2014 states that cross-validation with an existing technology is necessary only if the change of platform occurs within a program or a study; however, the presence of unique variables that could impact quality should be considered."
      • "The extent of revalidation or partial validation of a method depends on the changes.
        • For large molecules, a full validation is needed when changing detection system platforms.
        • For small molecules, a method revalidation excluding stability evaluations was suggested in 2011 when changing LCMS instrument brands or brand generations. This recommendation was reconfirmed and expanded in 2014, when it was stated that a change in detection instrument to a different platform, minimally sensitivity, precision/accuracy on at least three runs and matrix effect should be re-assessed during partial validation."
    • Case studies with both QC and incurred samples were used to evaluate comparability using fix criteria and statistical analysis
  •  

  • Topic 11
    Hybrid LBA/LCMS used for Clinical Assays: Regulatory Rigor & Acceptance Criteria while waiting for a Guidance
    - Ms. Parya Nouri, Assoc. Director Clinical Assay Group, Pfizer
    • Building on & supporting the 2019 White Paper in Bioanalysis Recommendations on ICH M10 for Hybrid LBA/LCMS used for Clinical Assays with novel practical case studies
      • 2019 Link: https://www.future-science.com/doi/pdf/10.4155/bio-2019-0270
      • …adding the minimum requirements for hybrid LBA/LCMS assays to the ICH M10 guideline as a starting point to help the industry move forward in the implementation of this bioanalytical platform in regulated bioanalysis when deemed complementary and/or alternative to traditional LBA. Experts in hybrid LBA/LCMS assays identified the following fundamentals that should be addressed in the guidance:
        • Specificity of the surrogate peptide(s);
        • Digestion efficiency;
        • LBA (20%/25%) accuracy, precision and 30% ISR criteria should be targeted until more experience with hybrid assays has accrued;
        • Dilutional linearity;
        • Capture reagent lot-to-lot variation.
    • Case studies
      • Robustness of the Hybrid LBA/LCMS for Clinical & Regulated Studies
      • Use of Hybrid LBA/LCMS for high throughput analysis
      • Ability of Hybrid LBA/LCMS to perform well overtime
      • Hybrid LBA/LCMS transferred from Pharma to CRO
      • Use of Hybrid LBA/LCMS for large studies

 

Interpretations & Training on ICH M10 before its Adoption




Final Agenda Agenda at a Glance