FDA biomarker qualification program Paul Hockings, Imaging Director - - PowerPoint PPT Presentation

FDA biomarker qualification program

Paul Hockings, Imaging Director Antaros Medical

• An externalized R&D function - Design and Delivery of Decision enabling

studies in cardiometabolic drug development

Objectives

• Overview of regulatory framework for biomarkers
• Concept of Use
• Next steps

The primary efficacy endpoint should be the prevention or slowing of decline in the level of renal function, defined as “Clinically meaningful and stable GFR loss rate” with or without:

• Prevention of proteinuria/albuminuria or
• Time to occurrence of CKD 3 or
• Incidence rate of CKD 3 or higher

NKF workshop March 15-16 on validation of novel surrogate endpoints in early CKD

Guidelines for prevention of CKD

Biomarkers in Drug Development /Clinical Practice

Objective: Establish the biomarker for use in multiple development programs

Biomarkers as a diagnostic tool

EMA/US Acceptance through stand alone studies Responsible parties: Anybody FDA Process: CDRH process – 90 days/PMA 120 days EU notified body: Devices except IVD IVDs self registration

Biomarker Information

Stand alone IFU E.g.: Troponin Acceptance through Drug Approval

FDA/EMA

Responsible parties: Sponsors FDA Process: Review division EMA Process: Discuss CHMP working party

EMA

Day -60: letter of intent

• Public consultation

Day 190: CHMP adoption

FDA

• Review Team: BQRT
• Consultation and advice
• Review and comments
• Approval
• Public comments

Biomarker Information

Embedded in drug labels E.g.: Immune cancer therapy

Biomarker Information

Qualified biomarkers announced as draft guidance

Biomarkers in Drug Development

EMA/US Biomarker Qualification Letter of intent US Responsible: Generally Consortia EU Responsible: Anybody

Concept of Use

Drug Development Tool

Diagnostic/Enrichment e.g. fast progressors

Exploratory Biomarker

Understanding disease biology/treatment action Acceleration of development timelines

Surrogate Endpoint

A biomarker to evaluate Drug safety/mode of action

Drug Metabolism Target Engagement

Assessment of drug/target engagement

Repeat Measurements Monitoring Patient Stratification

Use of a prognostic biomarker

Patient Selection

Diagnostic/Prognostic e.g. hyperfilterers Pharmacodynamic Biomarker

FDA 21st Century Cures Act

• 21st Century Cures Act enacted December 2016
• Qualification of Drug Development Tools (DDT) was added
• Formally establishes an updated, multi-step process for DDT qualification
• Qualification of a DDT is for a specific context of use (COU)
• The qualification process includes three submissions:
• Letter of Intent (LOI)
• Qualification Plan (QP)
• Full Qualification Package (FQP)

To receive early indication of regulatory feasibility

FDA: Biomarker Qualification Program

• Deputy Director

Critical Path Institute

• Director

National Kidney Foundation PARENCHIMA Consortium FDA: DCaRP*

• Deputy Director
• Medical division lead
• Medical Reviewer

FDA: In Vitro Diagnostics and Radiological Health

• Biomarker engineer
• Need of alignment between consortiums and diagnostic companies
• Concept of Use is key for the LOI process

* Division of Cardiovascular and Renal Products (DCaRP)

Initial FDA interaction - Critical Path Innovation Meeting

Qualification of Biomarker and/or Diagnostic tool

Qualification of Biomarker

• Craft letter of intent – one letter to both FDA and EMA
• Information included
• Proposed Context of Use (COU) (limited to 500 characters)
• Describe PARENCHIMA program – emphasizing current knowledge

EMA will give feedback first time 90 days after submission

• 150 days after submission we will be asked to come back with clinical evidence and get

recommendations

• After supplying data we might have approval after an additional 100 days

FDA no specific timelines

• 2-4 months after submission we will be asked for briefing document or suggested to go to CPIM

Diagnostic tool

• DeNovo 510 K – define Pro/Con – Timing
• CE marking – define Pro/Con – Timing

EMA Procedures for Qualification of Biomarker

Abbreviations:

QT: Qualification team SAWP: Scientific advice working party CHMP: Committee for Medicinal Products for Human Use

Qualification of novel methodologies for drug development: guidance to applicants EMA/CHMP/SAWP/72894/2008

FDA Biomarker Qualification Process

Note:

The timeline based on our experience to date and may vary. This timeline does not capture the time needed by submitters to generate the data and submit the necessary documents (Letter of Intent (LOI), Briefing document, and Final Qualification Package) or requested additional information.

Amur et al, Clin. Pharm. Ther. 98 (1) 34-46, 2015

Conclusion

• Need to decide Diagnostic Tool vs Drug Development Tool
• Need to decide Concept of Use
• FDA, EMA or both
• Need to establish links to the National Kidney Foundation and other advisory

bodies

• Method qualification is stronger if broad
• many sites, many countries can replicate findings
• deliver data with multiple different drugs
• open platforms create better penetration
• Big Pharma have Regulatory Departments with expertise in interactions with

authorities

Questions?