Qualification of Medical Device Development Tools

Guidance for Industry, Tool Developers, and Food and Drug

Administration Staff

Moshe Ben Yitzhak, MBA, MScCGMP Solutions, Ltd.

What is the MDDT Program?• The FDA’s Medical Device Development Tools (MDDT)

program is a way for the Center for Devices and Radiological Health (CDRH) to qualify tools that medical device sponsors can use in the development and evaluation of medical devices.

• The goal of the voluntary MDDT program is to assess and refine the qualification process for tools used to develop and evaluate medical devices

– The program aims to provide MDDT developers and medical device manufacturers with a mechanism for discussing early concepts about a tool, fostering collaboration on tool development, and potentially increasing adoption and use of the qualified tools.

• https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM374432.pdf

What is an MDDT?

• An MDDT is a method, material, or measurement used to assess the effectiveness, safety, or performance of a medical device.

• An MDDT is scientifically validated and can be qualified for use in device evaluation and to support regulatory decision-making.

– Examples of MDDTs are clinical outcome assessments, assessments of biomarkers, and nonclinical assessment methods or models.

• The use of a qualified MDDT by a product sponsor is voluntary.

What does Qualification Mean?

• Qualification reflects CDRH’s expectation that, within a specified context of use (the conditions and boundaries within which the MDDT has been qualified for use), the results of an assessment that uses an MDDT can be relied upon in device evaluation and to support regulatory decision-making.

• Qualification is a voluntary process to establish the scientific rigor associated with an MDDT for a specific use in supporting regulatory decision-making.

• The existence of a qualified MDDT does not obligate a sponsor to use that particular tool; other scientifically valid tools or approaches may also be used.

Who initiates development of an MDDT?

• The process for MDDT qualification can be initiated

in one of three ways:

– 1) FDA identifies an area of need and/or calls for

development activity in a specific area;

– 2) Need and interest in an area is determined by

individual or consortia of stakeholders (may include

academia, industry, medical societies, patient groups); or

– 3) MDDT developer pursues qualification to foster broad

use of the tool, potentially across multiple device

development programs.

Limitations• Once an MDDT is qualified for a specific context of use, CDRH

encourages developers to make their qualified MDDTs publicly available, which can include under a licensing arrangement, so that they can be used by any medical device sponsor for that context of use.– CDRH reviewers should accept the MDDT for the qualified context of use without

the need to reconfirm the suitability and utility of the MDDT when used in a CDRH regulatory submission.

• FDA will not place limitations on MDDT licensing or fees, or the degree of access to intellectual property associated with an MDDT that a tool developer may give to a device sponsor.

• The FDA will publicly list MDDTs once they are qualified, along with a summary of evidence and basis of qualification for the tool.

How can MDDTs be used in device evaluation and regulatory decision-making?

• MDDTs can be used to demonstrate safety, effectiveness, or device performance and to support regulatory decision-making, by facilitating the efficient provision of supporting evidence in non-clinical or clinical settings.

• MDDTs may have a variety of roles in a device clinical study such as:

– patient selection,

– study population enrichment,

– monitoring treatment response,

– predicting or identifying safety problems related to treatment with a medical device, or

– identifying patients who are or are not candidates for certain forms of therapy.

How can MDDTs be used in device evaluation and regulatory decision-making?

• In addition, MDDTs may be used in a variety of ways to collect, evaluate, and/or predict bench or in vivo performance.

• Appropriate use of qualified MDDTs may increase the efficiency of the device development and evaluation process by providing reliable predictions about device performance or identifying patients more likely to respond to treatment or experience disease progression in the near future.

MDDT Program Categories

The FDA has defined three categories of MDDT:

1. Clinical Outcome Assessment (COA): measures of how a patient feels or functions. These could be patient-reported or clinician-reported rating scales like the NIH stroke scale, measures based on clinical decision-making, observer-reported outcomes such as from a parent or caregiver, or performance outcome measures, such as measures of gait speed or memory recall.

– Examples include: patient reported outcome rating scales, such as those used to measure pain, improved mobility, symptom relief, function, or health status and heart failure-related hospitalization.

Clinical Outcome Assessment

• The four common types of COAs are:

– Patient-reported outcome (PRO) measures,

– Clinician-reported outcome (ClinRO) measures,

– Observer-reported outcome (ObsRO) measures, and

– Performance outcome (PerfO) measures.

• Other COAs used as a measure of patient benefit or safety may be qualified as MDDTs.

MDDT Program Categories2. Biomarker test: a lab test or instrument used to detect or

measure an indicator of biologic processes or pharmacologicresponses to a treatment (biomarker).

A biomarker is a defined characteristic that is objectivelymeasured and evaluated as an indicator of normal biologicalprocesses, pathogenic processes, or responses to a therapeuticintervention. Molecular, histologic, radiographic, or physiologiccharacteristics are types of biomarkers. A biomarker is not anassessment of how an individual feels, functions, or survives.

– Examples include:

• Tests used as an aid in diagnosis, for patient selection, or as clinical study endpoints, such as instruments or methods for measuring blood pressure; or

• Instruments or methods for measuring certain concentrations of serum proteins, such as an assay to detect the level of a specific hormone in a patient in order to determine enrollment eligibility for study population in a clinical trial.

MDDT Program Categories

3. Non-clinical Assessment Model (NAM): a nonclinical test

method or model (e.g. in vitro “bench,” animal or

computational model) that measures or predicts device

function or performance in a living organism.

– Examples include:

• Models used 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 to evaluate a device instead of collecting

data from human subjects;

• Use of tissue and other material phantoms to evaluate imaging

devices; or In vitro models to replace animal testing.

MDDT Qualification Process

Proposal

Phase

Incubator

Phase

Pre-

qualification

Phase

Qualification

Phase

Qualification

Decision

MDDT Qualification Process

Proposal

Phase

Incubator

Phase

Pre-

qualification

Phase

Qualification

Phase

Qualification

Decision

The goal of the proposal phase is to determine if the MDDT is suitable for qualification through the program.

Firms interested in seeking qualification should submit a complete proposal package, including a description of the MDDT, and a justification for how the MDDT will help address a public health need.

MDDT Qualification Process

Proposal

Phase

Incubator

Phase

Pre-

qualification

Phase

Qualification

Phase

Qualification

Decision

In certain instances CDRH may accept MDDTs with a high potential public health impact that are not fully developed.

The goal of the incubator phase is for CDRH to work with firms to foster the development of tools that have potential to significantly improve public health.

This is an optional phase, determined by CDRH.

MDDT Qualification Process

Proposal

Phase

Incubator

Phase

Pre-

qualification

Phase

Qualification

Phase

Qualification

Decision

During the pre-qualification phase, CDRH can provide feedback to submitters on their plan to collect evidence to support qualification of the tool.

Depending on the quality of the original proposal, this phase may not be necessary.

CDRH will make the determination.

MDDT Qualification Process

Proposal

Phase

Incubator

Phase

Pre-

qualification

Phase

Qualification

Phase

Qualification

Decision

The goal of the qualification phase is to determine whether, for a specific context of use, the tool is qualified based on the evidence and justifications provided.

MDDT Qualification Process

Proposal

Phase

Incubator

Phase

Pre-

qualification

Phase

Qualification

Phase

Qualification

Decision

CDRH considers the following when determining whether to qualify a proposed MDDT:

MDDT description. Is it adequately described?

Context of use. Is the proposed use context adequate and well-defined?

Public health impact. Would the scope and use of the tool have a broad public health impact?

Strength of evidence. Does the available scientific evidence demonstrate that the tool reliably and accurate?

Assessment of advantages and disadvantages. Do the advantages outweigh potential disadvantages of making decisions based on measurements obtained using the tool?

Is there a template?

• In the appendix to the Guidance, FDA has suggested a template for submitting MDDTs for the CDRH qualification process.

– Sponsors are not under any legal obligation to use this template.

– Sponsors may need to revise or otherwise add sections to or delete sections from the template, depending on the Context of Use (COA) stated in the MDDT’s proposal.