Drug Regulators, EMEA, publish ICH guidance on Genomic Biomarkers Related to Drug Response – For Comment

The EMEA has published “ICH Topic E16 Genomic Biomarkers Related to Drug Response: Context, Structure and Format of Qualification Submissions”

Objective of Guideline

The guideline describes recommendations regarding context, structure, and format of regulatory submissions for qualification of genomic biomarkers, as defined in ICH E15. Biomarker qualification has not been covered in any ICH guideline. Qualification is a conclusion that the biomarker data submitted support use of the biomarker in drug discovery, development or post-approval and, where appropriate, in regulatory decision-making. The objective of the guideline is to create a harmonized structure for the qualification of genomic biomarkers that will foster consistency of applications across regions and facilitate joint discussions with and among regulatory authorities.

Background

The use of biomarkers in drug discovery, development and post-approval has the potential to facilitate development of safer and more effective medicines, to guide dose selection and to enhance the benefit-risk profile of approved medicines.

Scope

The scope of this guideline is the context, structure, and format of qualification submissions for clinical and non-clinical genomic biomarkers related to drug response including translational medicine approaches, pharmacokinetics, pharmacodynamics, efficacy and safety aspects. This guideline covers genomic biomarkers used singly or in combination with other genomic biomarkers or in combination with non-genomic biomarkers. It does not cover non-genomic biomarkers; however, it is anticipated that many of the principles described in this document might be applicable to other biomarker categories (e.g., proteomics) and other qualification contexts not associated with drug response.

General Principles

The proposed context of use (hereinafter referred to as “context”) of a genomic biomarker should determine the data supporting its qualification. Therefore, the relevant context should be clearly detailed in the submission package. Reference should be made to the specific use of the genomic biomarker in drug development. The format of the data for qualifying a genomic biomarker can vary significantly depending on the context. It is therefore only possible to provide general guidelines on data format for a genomic biomarker qualification submission.

Structure of Genomic Biomarker Qualification Submissions

Section 1: Regional Administrative Information

This section should contain documents specific to each region, for example, application forms and/or cover letter. The content and format of this section can be specified by the relevant regulatory authorities.

Section 2: Summaries

Introduction:

This section should be concise. It can include a description of the disease and/or experimental setting, the nature of the genomic biomarker (e.g., Single Nucleotide Polymorphisms (SNPs) and Copy Number Variation (CNV)) and provide a rationale for its use in drug discovery, development or post-approval studies.

Context

The elements describing the context for a biomarker should include (i) the general area, (ii) the specific biomarker use, and (iii) the critical parameters which define when and how the biomarker should be used.

• General Are (including, but not limited to)
  • Non-Clinical
    • Pharmacology
    • Safety and Toxicology
  • Clinical
    • Pharmacology
    • Safety
    • Efficacy
• Specific Biomarker Use (including, but not limited to)
  • Patient selection
    • Inclusion/Exclusion
    • Trial enrichment or stratification
  • Assessment of mechanism of action
    • Mechanism of drug action
    • Mechanism of therapetuic effect
    • Mechanism of toxicity/adverse reaction
  • Dose optimization
    • No observed effect level (NOEL) in animal models
    • No observed adverse effect level (NOAEL) in animal models
    • Algorithm-based dose determination (qualititative algorithmic dosing)
    • Determination of likley dose range
  • Response Monitoring
    • Monitoring drug safety
    • Monitoring drug efficacy
  • Toxicity/Adverse reactions/Risk minimization
    • Indicating/predicting toxicity/adverse reactions
• Critical Parameters of Context Description (including, but not limited to)
  • Drug-secofo9c use
  • Disease diagnosis, prognosis, or stage
  • Assay specifications
  • Tissue or physiological.pathological process addressed
  • Species
  • Demographics including ancestry and/or geographic origin
  • Use in clinical trials

A biomarker could have more than one context, including the general area and/or specific use within a single submission (e.g., non-clinical and clinical predictive biomarker(s)).

Non-clinical safety

biomarkers for tox/safety examples given

Clinical Pharmacology/Drug Metabolism

biomarkers for clinical pharmacology/drug metabolism examples given.

Clinical Safety

Biomarker use in clinical safety examples given.

Methodology and results

This section should include a summary of nonclinical or clinical studies, including integrated analysis of the genomic biomarker qualification studies and individual study synopses.

Section 3: Quality

Drug quality and manufacturing data would in general not be included in a biomarker ualification submission independent from an NDA or MAA.

Sections 4: (Nonclinical) and 5 (clinical): Study Reports

In this section, full study reports for biomarker qualification should be provided, and raw data could be made available to the regulatory agency upon request. Information on compliance with Good Laboratory Practices (GLP) or Good Clinical Practices (GCP) can be included in these sections. This guideline suggests that, where appropriate, the study reports can follow relevant ICH guidelines (e.g., E3, M4E, M4S) for their preparation.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

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