Biomarkers for Drug Development: The Emerging Regulatory Landscape

Why Should You Attend:

Biomarkers have long been advocated by the FDA as a way of making development more efficient. However, detailed guidances are only now being issued. Over the last eighteen months the FDA has explained its current thinking on biomarkers in a series of final and draft guidances. Though not formally labeled as a series by the Agency, it is useful to consider a number of recent guidances as a group.

This session will cover the emerging regulatory aspects for all classes of biomarkers: biomarkers of (1) efficacy, (2) toxicity, (3) dose-selection, & (4) patient-selection. The utility of each of these four classes of biomarkers varies according to the degree of validation, the business model of the company using them, and the terms under which regulatory approval is sought.

This training will enable industrial scientists and clinicians to understand the recent guidances on biomarkers and companion diagnostics and allow them to prepare detailed roadmaps ensuring proper qualification and implementation of biomarkers to a standard that will be accepted by the FDA in registration packages for either small molecule drugs or biologicals.

Learning Objectives:

An up-to-date understanding of regulatory requirements for the development and implementation of biomarkers in drug development programs, as well as highlights of the most recent FDA sources on general, imaging (Including PET) and pharmacogenomic biomarkers.

Areas Covered in the Seminar:

• Types of  biomarkers and their regulatory implications.
• Overviews of emerging regulatory aspects for all classes of biomarkers.
• Specific  guidances for biochemical, genomic and imaging biomarkers.
• Elements constituting context of use for a biomarker.
• The qualification process for biomarkers.
• Context, structure and format of regulatory submissions for qualification of biomarkers.
• Definition and use of a Companion Diagnostic Device.
• Applicable standards when imaging is used to  assess a primary endpoint.
• Definition of clinical, investigative and research use in the context of PET drugs.
• Clinical evaluation of pharmacogenomics.

Who Will Benefit:

This webinar will provide valuable assistance to pharmaceutical and biotechnology personnel with responsibility for the implementation of biomarkers in clinical development programs and registration packages, including:

• Translational Medicine scientists developing biomarkers
• Clinical Scientists designing Phase 2 and Phase 3 trials
• Preclinical scientists developing biomarker assays
• Administrative managers in charge of Clinical Research
• Regulatory Compliance Associates and Managers

Instructor Profile:

Orest Hurko, is a Senior Clinical Consultant with the Biologics Consulting Group, Inc. in Alexandria Virginia. He was the founding director of Investigative Medicine for the Neurology CEDD in GSK and Discovery/Translational Medicine in Wyeth, responsible for biomarker development in oncology, neuroscience, inflammation, cardiovascular and bone disease as well as women’s health. He has published extensively on the application of biomarkers in drug development, most recently in Nature Reviews Drug Discovery. He currently serves on the Data and Publications Committee of the Alzheimer Disease Neuroimaging Initiative, and the faculties of the Pharmaceutical Education & Research Institute, Inc., the University of Dundee and the annual International Conference on Drug Development sponsored by the University of Texas in Austin.

Topic Background:

In 2006, the FDA’s Critical Path Opportunities Report reported “Our outreach efforts uncovered a remarkable consensus that the two most important areas for improving medical product development are biomarker development and streamlining clinical trials.” The pharmaceutical and biotech industries responded to this and earlier encouragement from the FDA with significant investments in biomarker development. However, only a handful of these efforts have been successful, in large part because of a lack of clarity surrounding the optimal use of biomarkers in drug development. This complex subject is only now being defined at the level required for cost-effective implementation.

Unraveling this complexity requires recognition of several types of biomarkers, each with distinct regulatory implications: biomarkers of (1) efficacy, (2) toxicity, (3) dose-selection, & (4) patient-selection. The utility of each of these four classes of biomarkers varies according to the degree of validation, the business model of the company using them, and the terms under which regulatory approval is sought.

Only a small handful of efficacy biomarkers have been validated as “surrogates” that the FDA approves as primary endpoints in traditional pivotal trials. However, the FDA’s Accelerated Approval process allows use of surrogates for certain serious diseases, even if they have not been validated sufficiently for a traditional approval process. The Government Accountability Office tabulated 64 NDA’s and BLA’s that had been approved on the basis of surrogate biomarkers. This policy is not uniform across all reviewing divisions. Biomarkers predicting side effects or frank toxicity are as difficult to validate as surrogates as are efficacy biomarkers.

Although biomarkers of efficacy and toxicity have attracted the most attention, more cost-effective have been two other kinds of biomarkers: those that guide dose-selection and selection of responsive patients for clinical trials. FDA senior staff repeatedly cites dosing as a root cause of many regulatory problems. Dose-selection biomarkers do not require recognition as surrogates by the FDA, inasmuch as sponsors are given considerable latitude in the choice of dosing regimens, bounded only by the need for acceptable safety margins defined by preclinical and Phase 1 studies. Similarly, patient–selection biomarkers do not require designation as surrogates. Trial sponsors may define entry criteria as narrowly as they like. However, they do so with the responsibility to provide a companion diagnostic, which itself must meet regulatory standards for reliability.

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