Medical Device Development Tools: FDA CDRH Pilot Program MDIC M&S Summit Washington, DC June 26, 2014 Medical Device Development Tools: FDA CDRH Pilot Program Kathryn O‘Callaghan Senior Science Health Advisor Office of the Center Director FDA CDRH Tina Morrison Regulatory Advisor, Computational Modeling Office of Device Evaluation FDA CDRH

Medical Device Development The Total Product Life Cycle CMS REIMBURSEMENT POST MARKET MONITORING EVALUATION REIMBURSE DECISION REAL-WORLD PRODUCT PERFORMANCE FDA REGULATORY LAUNCH CLINICAL PRE-CLINICAL INVENTION + PROTOTYPING DISCOVERY IDEATION NEXT GENERATION DEVELOPMENT More Predictable More Efficient In the broader context of research, how does regulatory science research fit into the HoW Research Road Map? - When we refer to research we are referring to all aspects / stages of research, from discovery & ideation, innovation and prototyping, pre-clinical, clinical, through to post-market surveillance, to next generation device development

Regulatory Science Efforts Device Development & Regulatory Evaluation Animal Bench-top Human Computer

Proposed New Voluntary Program http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm374427.htm

Why is FDA CDRH developing a qualification process? TODAY: Tools considered and evaluated on a case-by-case basis TOMORROW: Qualified for regulatory purposes, within a defined context of use MDDT Case-by-case… MDDT Today: PROs, clinical rating scales, intermediate endpoints, biomarker tests, and nonclinical assessment methods or models are in use today for device development and evaluation Problem with today’s paradigm: These are accepted on a case-by-case basis, with limited or delayed benefit to other industry sponsors, contributing to development/regulatory inefficiencies. There are delays in translation of advances in regulatory science to regulatory practice. Goal/Solution: General audience - Provide a more efficient and predictable means for collecting the necessary information/evidence to make regulatory assessments. Technical audience – two-prong: More efficient development & evaluation of new devices Mechanism for leveraging advances in regulatory science MDDT MDDT

KEY CONCEPTS

Types of Tools (Categories) MDDT Qualification Clinical Outcome Assessments Biomarker Tests Nonclinical Assessment Models COA = A subjective measure of how a patient feels or functions Patient reported outcome (PRO) rating scales, such as those for pain, symptom relief, function, improved mobility, or health status (also sometimes referred to as “quality of life”) Observer-reported outcomes Clearly-defined clinical outcomes based on subjective clinical decision-making if used as a measure of treatment benefit, such as reduction in heart-failure related hospitalization. An objective clinical assessment method used to detect or measure a biomarker A lab test Medical imaging method Other objective measurement method

What is “FDA Qualification”? The results of an assessment can be relied upon for device development & evaluation, within a specified context of use Device industry need not reconfirm the suitability of a qualified MDDT Device industry users may need to demonstrate the tool is used according to the specified context of use Context of use ≈ boundaries within which evidence & justification supports tool use

Specific Role of the MDDT Context of Use Device or Product Area Specific Role of the MDDT Stage of Development

Context of Use: Clinical Roles for MDDT Clinical Study Endpoints Patient Selection Aid in Diagnosis

Context of Use: Non-Clinical Roles for MDDT Substitute for animal or human studies Minimize use of animals Reduce test duration or sample size

Strength of Evidence Needed Depends on Context of Use Stages of Product Development Invention & Prototyping Early Development Clinical / Regulatory Evaluation Clinical Care (Practice Guidelines)

Next Steps: Pilot Program Medical Device Development Tools (MDDT) July 2012 Next Steps: Pilot Program O'Callaghan/Maisel

Considerations for CDRH Qualification Tool Context of Use Strength of Evidence Advantages & Disadvantages

Threshold for CDRH Qualification Medical Device Development Tools (MDDT) July 2012 Threshold for CDRH Qualification Key Criteria: Description of MDDT. Is the MDDT adequately described? Context of use. Is the context of use adequately and appropriately defined? Strength of evidence. Tool validity, scientific plausibility, extent of prediction & capture. Advantages & disadvantages. Strength of evidence: Does the available scientific evidence demonstrate that the MDDT reliably and accurately measures what it is intended to measure, is scientifically plausible, and is reasonably likely to predict the outcome of interest? Advantages & disadvantages: Within the specified context of use and given the available strength of evidence, do the advantages of using the MDDT outweigh potential disadvantages of making decisions based on measurements obtained using the 424 MDDT? The strength of evidence needed to support qualification depends largely on the context of use. O'Callaghan/Maisel

Computational Models For computational models that are MDDTs, we will leverage the Credibility Strategy as part of the qualification process Credibility: the quality to elicit belief or trust in predictions of the CM&S within a context of use The strategy is a tool for systematic identification of ‘how much’ VVUQ is necessary to support the CM&S in a specific context of use.

Computational Models

Availability of MDDTs in the Pilot Program Transparency: For qualified MDDT, FDA will make public the context of use, and a summary of evidence and basis of the qualification determination (analogous to summaries of approved devices). FDA will keep proprietary information confidential. Accessible to public: Submitter must consent to make MDDT accessible to the public for use, and not restrict to certain private entities, such as a single manufacturer Licensing/pricing/IP: FDA and the MDDT program places no requirements on licensing/cost/degree of access to IP associated with a tool, nor does it consider restrictions related to patent claims. An MDDT submitter may include and protect proprietary methods, as long as access to the tool is not restricted to certain private entities. Available for use by the public/ public accessibility/ publicly available MDDTs are tools which are made accessible   to the public for their use , and do not include tools that are restricted to use by private entities. For example, a tool developed by a medical device company for its use only would not be included in CDRH’s MDDT program. Open source/ licensing/ cost The MDDT program places no requirements on the degree of access to the Intellectual Property associated with the tool. An MDDT may include proprietary methods, as long as the MDDT is made accessible to the public for their use. For example, if the MDDT tool includes software, the software may be open or closed source. The  conditions of use (licenses, pricing, etc.) are determined by the MDDT owner. FDA public disclosure of Qualified MDDTs When FDA has qualified an MDDT for a Context of Use, FDA’s decision and a summary related to the basis of the decision will be provided to the public, however information that is proprietary to the tool developer will not be disclosed. MDDT developer disclosure to FDA Enough information about the MDDT must be provided to FDA so that the validity, including analytical validation  , of the tool can be assessed. This includes the fundamental mechanism of operation of the tool, and detailed information that will be evaluated during the qualification   process . The amount and level of detail of the qualification of MDDTs may be similar to validation information typically provided in medical device regulatory submission  s. The MDDT pilot program will provide information about the process and content of MDDT submissions so that further guidance may be provided.

WHY PARTICIPATE?

Benefits to Medical Device Manufacturers & FDA Goal – Qualification will facilitate: More predictable product evaluation. Medical device industry can use qualified tools without the need to reconfirm validity in individual submissions to FDA, potentially reducing time and other resources needed to develop new products. More efficient regulation. FDA’s efforts to qualify one MDDT could by surpassed by the time and resources saved when the MDDT is applied to several device submissions or device development programs.

Benefits to Tool Developers Medical Device Development Tools (MDDT) July 2012 Benefits to Tool Developers Goal – Publicizing MDDT qualification determinations will foster: Adoption. Encourage adoption of tools Transparency. Allow the FDA to more quickly and clearly communicate about important advances in regulatory science Collaboration. Facilitate collaboration in a pre-competitive setting to amplify evidence collection and reduce individual resource expenditure 21 O'Callaghan/Maisel 21

Bridging Advances in Regulatory Science into Regulatory Application TODAY: Tools considered and evaluated on a case-by-case basis TOMORROW: Qualified for regulatory purposes within a defined context of use MDDT Case-by-case… MDDT Today: PROs, clinical rating scales, intermediate endpoints, biomarker tests, and nonclinical assessment methods or models are in use today for device development and evaluation Problem with today’s paradigm: These are accepted on a case-by-case basis, with limited or delayed benefit to other industry sponsors, contributing to development/regulatory inefficiencies. There are delays in translation of advances in regulatory science to regulatory practice. Goal/Solution: General audience - Provide a more efficient and predictable means for collecting the necessary information/evidence to make regulatory assessments. Technical audience – two-prong: More efficient development & evaluation of new devices Mechanism for leveraging advances in regulatory science MDDT MDDT

Upcoming Meetings ASME V&V40 Subcommittee July 29-30, 2014, FDA Campus Medical Device Special Interest Group with the Biomedical Engineering Society Annual Meeting: October 22-25, 2014, San Antonio, TX SIG Session on 10/23 BMES/FDA Modeling and Simulation Conference Formerly known as the ASME/FDA Frontiers Conference May 18-20, 2015, University of Maryland

Contact Information Tina Morrison tina.morrison@fda.hhs.gov (301) 796-6310 Katie O’Callaghan kathryn.ocallaghan@fda.hhs.gov (301) 796-6349

FAQ: Examples of Tools Eligible to be Qualified PRO rating scales, such as those for pain, symptom relief, function, improved mobility, or health status (also commonly referred to as “quality of life”) Clearly defined clinical outcomes based on subjective clinical decision-making if used as a measure of treatment benefit, such as heart-failure related hospitalization Nonclinical Assessment Models developed to measure a parameter of interest or to substitute for another generally accepted test or measurement, such as: Computer modeling to assess conditions typically evaluated through human, animal or bench testing In vitro models to replace animal testing Use of tissue and other material phantoms to evaluate imaging devices

FAQ: Proposals Proposal streams: An MDDT developer chooses to pursue qualification to allow for use of the tool across multiple device programs FDA identifies an area of need or calls for development activity in a specific area Need and interest in an area is determined by individual or consortia of stakeholders (e.g., MDIC) 26

FAQ: Factors for Prioritization Public health impact Context of use includes life-threatening AND/OR serious chronic disease/condition No/poor alternatives or unmet scientific need Benefit for innovation or efficiency Device area includes novel or innovative technology with no established regulatory paradigm Major efficiencies to be gained Scope of impact: Potential for use by multiple product development programs or sponsors From guidance Public health impact =

FAQ: Voluntary Program Opt-in policy. Medical device manufacturers may use qualified MDDT but are not required to do so* Tool developers may pursue FDA qualification but are not required to do so* Medical device manufacturers may still elect to pursue confidential use of a tool within a specific application only* *See preceding benefits slides!