What is a MDDT? Clinical Outcome Assessments MDDT Types Biomarker Tests Nonclinical Assessment Models A Medical Device Development Tool is a scientifically validated tool that aids device development and regulatory evaluation

What is a MDDT? A Medical Device Development Tool is a scientifically validated tool that aids device development and regulatory evaluation MDDT Types Clinical Outcome Assessments Biomarker Tests Nonclinical Assessment Models

MDDT Types Clinical Outcome Assessments MDDT Types Biomarker Tests Nonclinical Assessment Models Patient selection Clinical study outcomes Objective measure of biologic process or response to an intervention Patient selection Predict or identify outcomes New method to measure or predict a parameter of interest Replace/ reduce animal testing

What does FDA Qualification of a MDDT mean? The results of an assessment from a qualified MDDT, within a specified context of use, can be relied upon by the medical device industry in support of their device submissions 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

Why are we qualifying tools? TODAY: Tools considered and evaluated on a case-by-case basis TOMORROW: Tools qualified for regulatory purposes, within defined context of use Crossing the Potomac White’s Ferry Point of Rocks bridge BENEFITS: Allow for new methods to be assessed outside of the medical device application Minimize uncertainty in the review process Promote innovation in medical device development and regulatory science to help bridge the gap between research and the delivery of devices to patients

Benefits of MDDT Qualification For device industry: More predictable and efficient product evaluation / reduced regulatory risk For FDA product evaluators: More efficient process / reduced review time spent arguing about endpoints and other methods of measuring. 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. For FDA regulatory scientists: Standing program to bridge advances in regulatory science into regulatory practice For tool developers: Foster adoption of tools, facilitate collaboration in a pre-competitive setting to amplify evidence collection and reduce individual resource expenditure For patients: Increased adoption of outcome assessments with patient-centered treatment benefit, effective and safe medical devices coming to market more quickly

What is a MDDT Context of Use? Device or Product Area Specific Role of the MDDT Stage of Development Regulatory Evaluation Context of use defines the boundaries within which evidence & justification supports tool use

What is a MDDT Context of Use? Device or Product Area Specific Role of the MDDT Stage of Development Regulatory Evaluation Context of use defines the boundaries within which evidence & justification supports tool use

What is a MDDT Context of Use? Device or Product Area Specific Role of the MDDT Stage of Development Regulatory Evaluation Context of use defines the boundaries within which evidence & justification supports tool use

What is a MDDT Context of Use? Device or Product Area Specific Role of the MDDT Stage of Development Regulatory Evaluation Context of use defines the boundaries within which evidence & justification supports tool use

PRE-QUALIFICATION (PQP) MDDT Process Overview PROPOSAL PRE-QUALIFICATION (PQP) QUALIFICATION

Proposal  Pre-Qualification PQP  Qualification Prioritization/acceptance to the MDDT Program will depend on the following factors: Tool readiness: Does the tool exist in prototype or final form? Proposed context of use: Does available information support acceptance of the tool principle/method of measurement for the proposed context of use, or for any use? Timeline: What is the expected timeline to submission of a qualification package? Potential for Public Health Impact: What type of impact will MDDT have on product development? Will the tool facilitate development of devices that will address unmet public health need? Proposal is sent as an email to MDDT@fda.hhs.gov

Proposal  Pre-Qualification PQP  Qualification Opportunity to work interactively with FDA to develop the Qualification Plan. The Pre-Qualification Phase is Optional. Sent as an “informational meeting” request, pre-Submission (Q-submission), based on FDA guidance document: Requests for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with Food and Drug Administration Staff If evidence supporting an MDDT COU is not yet available, the Pre-Qualification Phase is highly recommended. Otherwise, it’s utility will depend on the stage of MDDT development.

Proposal  Pre-Qualification PQP  Qualification Validation, verification and uncertainty quantification Evidence that supports the validity of the MDDT for the COU Justification and evidence to describe the limitations and domain in which the MDDT is validated Context of use defines the boundaries within which evidence & justification supports tool use

What are the process stages for MDDT Qualification? Proposal & Prioritization Planning & Consultation Evidence Development/Gathering Assessment & Qualification Determination Incubator Proposal Pre-Qualification Qualification Tool developer proposes tool and FDA determines eligibility for program FDA engages submitter as qualification protocols and plans are evaluated FDA makes qualification decision and works with submitter to make tool public

MDDT Pilot Goals The proposed MDDT qualification voluntary process is intended to support the development of MDDTs Pressure test the process Develop needed organizational procedures and resources Identify challenges, barriers to adoption Best practices and training Qualify a variety of tools

Current status of MDDT Pilot Proposals, N = 31 Common reasons for not advancing to next stage Broad, poorly defined context of use Low public health impact Not used in device evaluation Pre-Qualification, N = 19 Unclear qualification plan Protocols don’t support context of use This slide contains time sensitive text. Please contact the MDDT WG at mddt@fda.hhs.gov for current status. Qualification, N = 4 Data doesn’t support context of use Disadvantages outweigh advantages Qualified, N = TBD as of 1/31/2017

Standards and Guidance vs. MDDT Standards describe technical methods or minimal performance criteria for which there is community consensus. Medical devices and MDDTs often use standards in their development and to support regulatory decision-making. Guidance provides the current thinking for a topic; e.g., the expected assessments for a particular medical device or product. Consensus standards mddt guidance MDDTs do not replace standards or guidance, it’s an alternate route for tools. Standards MDDTs are not one or the other. Standards typically prepare technical methods for approaches that are “standardized” in the community. Sometimes consensus standards are more appropriate but if the tool is a commercial product, then MDDT is the more appropriate route. Also, if we do not know enough about the methodology or technology to qualify it, then the tool might be more appropriate for consensus standard. Also, it’s important to note that we have the ability to pull in outside experts to help review the tool. Guidance MDDT is different than guidance say for one product, you’re thinking about all the different types of assessments for that product whereas the MDDT is to address one particular aspect of assessment for a medical device – it’s more focused. Ultimately, the final decision of the MDDT is reported in a technical guidance appendix. MDDTs can be medical devices that have a tool-like “indication”. For example, explain the canary system MDDTs are methods, materials, or measurements used to assess a medical device. FDA will qualify scientifically validated MDDTs for use in device evaluation and to support regulatory decision-making.

Standards and Guidance vs. MDDT Standards describe technical methods or minimal performance criteria for which there is community consensus. Medical devices and MDDTs often use standards in their development and to support regulatory decision-making. Guidance provides the current thinking for a topic; e.g., the expected assessments for a particular medical device or product. Consensus standards MDDTs do not replace Standards and Guidance. Each may have some overlapping aspects with the others. Each will have some of the same and new stakeholders. mddt guidance MDDTs are methods, materials, or measurements used to assess a medical device. FDA will qualify scientifically validated MDDTs for use in device evaluation and to support regulatory decision-making.

Premarket Submission vs. MDDT   Premarket Submission MDDT Who Sponsor Medical Device Manufacturer Submitter Tool Developer What Device Tool Boundaries Indication for Use Context of Use Decision Framework Benefit-Risk Advantages & Disadvantages Threshold 510(k) PMA Substantial Equivalence Safety and Effectiveness Strength of Evidence Tool validity Plausibility Extent of prediction Public Health Impact Decision Clearance or Approval Within boundaries of Indication for Use Qualification Within boundaries of Context of Use FDA transparency SSED or Sponsor 510(k) Summary MDDT qualification summary, a technical guidance appendix This slide is sometimes nice to include in an Extra Slides section of a presentation; i.e. to be shared when sharing a copy of the slide deck, but not necessarily shared in the oral presentation.

Resources Federal Register (FR) notice announcing the MDDT Pilot Program: https://www.federalregister.gov/articles/2014/08/15/2014-19360/pilot-program-for-qualification-of-medical-device-development-tools FDA MDDT Guidance Document (Draft): http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM374432.pdf FDA MDDT Webpage: http://www.fda.gov/MedicalDevices/ScienceandResearch/MedicalDeviceDevelopmentToolsMDDT/default.htm

FAQs Who may submit an MDDT? Any individual or group may submit an MDDT. The intent of this voluntary CDRH MDDT program is to promote the development and use of tools to streamline device development and regulatory evaluation. Once an MDDT is qualified for a specific context of use, CDRH encourages developers to make their qualified tools available to the public, so that the tools can be used by any medical device sponsor for that Context of Use. How can an MDDT be submitted for qualification? An MDDT Proposal can be submitted by emailing the CDRH MDDT Working Group at MDDT@fda.hhs.gov. Tool developers should follow the recommendations in the MDDT Draft Guidance Document and the FR notice announcing the MDDT Pilot Program. If you have questions or would like to preliminarily discuss the value of your tool to this program, please email the MDDT Working Group. Is there a fee associated with submission? No, at this time there are no fees associated with the MDDT program. This slide contains time sensitive text. Tool developers should follow the recommendations in the MDDT Draft Guidance Document and the FR notice announcing the MDDT Pilot Program.

FAQs Are there qualified MDDT already available? No. The MDDT qualification process described in the draft guidance is a draft policy that the pilot program is designed to test and evaluate. What information about the tools will the FDA make accessible to the public? When the FDA has qualified an MDDT for a context of use, the FDA’s decision and a summary basis of the decision will be provided to the public. Information that is proprietary to the tool developer will not be disclosed. Once qualified, is the MDDT required to be made available for public use for free and is the tool required to be open source? The tool developer determines the conditions of use of a tool such as licensing, cost, or degree of access to Intellectual Property associated with the tool. For example, if the tool includes software, the software may be open or closed source, free or licensed. The Program intends to qualify tools that the developer will make available to the public, rather than tools that are offered only to certain parties. This slide contains time sensitive text. No. The MDDT qualification process described in the draft guidance is a draft policy that the pilot program is designed to test and evaluate.

Jay Vaishnav Christine Cezar Mary Beth O’Brien Ronald Schuchard Micro, Immunology, Genetics, Rad Health Division Directors Medical Officers Division Directors OIR POCs OSEL POCs ODE POCs OIR Lead OSEL Lead ODE Lead Dan Krainak (BIO) Donna Lochner (NAM) Andrew Yeatts (COA) Jean Cooper Jay Vaishnav Christine Cezar Mary Beth O’Brien Ronald Schuchard OSEL Co-leads OIR Co-lead ODE Co-leads Hilda Scharen-Guivel MDDT Program Lead Joan Adams-White Project Manager Katie O’Callaghan Center Lead Monica Pagan Motta Communication Madhu Nambiar Policy Hina Pinto Policy CDRH Policy Support and Outreach