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Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications: Guidance for Industry and Food and Drug Administration Staff

FinalCenter for Devices and Radiological Health Center for Biologics Evaluation and Research08/30/2019

Description

FDA has developed thisguidance documentto provide greater clarity for FDA reviewers and industry regarding the principal factors FDA considers when making benefit-risk determinations during the premarket review process for certain medical devices. FDA believes that the uniform application of the factors listed in this guidance document will improve the predictability, consistency, and transparency of the premarket review process.

Scope & Applicability

Product Classes

9
Medical Device

FDA intends to assess device cybersecurity based on a number of factors; demonstrate or maintain its safety and effectiveness; ensuring cybersecurity has become essential to FDA’s ability to protect the public health; Cyber-resiliency capabilities for medical devices

In vitro diagnostic

Used for patient management or selection in a clinical trial

Permanent, implantable devices

Category of device associated with specific known risks

In vitro diagnostic device

Specific labeling and performance testing requirements for IVDs

Novel device

replaces a patient's memory to treat Alzheimer's disease

Breakthrough Technologies

Devices addressing unmet medical needs

Class I

General manual surgical instruments exempt from 510(k)

Class II

The devices that are the subject of this guidance are Class II non-spinal metallic bone screws and washers

Class III Device

Generally recommended for Enhanced Documentation; Regulatory classification mentioned for implantable sensors and HPV tests; Mentioned in the context of an in vitro nucleic acid test for CMV DNA.

Stakeholders

7
Sponsor

Entity responsible for submitting applications under section 524B

Caregivers

Individuals providing information for medical product development; Participants in facilitated discussions and observational studies

Healthcare professional

User population that might train lay users or perform specific tasks.

Care-partner

Perspectives considered when PPI is not feasible; care-partner perspectives may be considered in circumstances where it is not feasible to obtain PPI; care-partner perspectives may be considered in circumstances where it is not feasible to obtain PPI.

Manufacturer

Entity responsible for submitting NDINs

Neurosurgeons

specially trained professionals required for implantation

Specially trained surgeon

Risk mitigation by requiring implantation by specialized personnel

Regulatory Context

Attributes

10
Unreasonable Risk

Risk that no set of reasonable patients would be willing to endure; Assessment of whether benefits outweigh the risks.

Unmet medical need

Requirement for eligibility for the accelerated approval pathway.

Health-related quality of life

Factor taken into consideration for meaningful clinical assessment

Minimally important clinical difference

A favorable change in clinical assessment meeting this threshold; favorable change in at least 1 clinical assessment that meets or surpasses a minimally important clinical difference

Clinical benefit

Assessment of whether a clinical benefit is demonstrated for the device; assessment of the clinical benefit; Is there any evidence of clinical benefit for a modified Indications for Use?; Tipping point and/or worst-case sensitivity analysis continuing to show clinical benefit.

Benefit-Risk Profile

The overall evaluation of a product's benefits versus its risks

Uncertainty

Uncertainty should be included in the performance specifications for all quantitative imaging functions

Safety and effectiveness

Level demonstrated for the cleared device; Core regulatory standard for assay performance

Specificity

Ability to detect intended mechanism of action without interference; Performance characteristic to be validated

Sensitivity

Analysis by sex of clinical performance measures such as sensitivity

Identified Hazards

Hazards

8
False-positive results

Risk for diagnostics leading to unnecessary treatment

Adverse biological response

Risk associated with permanent implantable devices

Mechanical failure

Risk associated with permanent implantable devices

Harmful event

lower the probability of a harmful event occurring

Adverse events

Unexpected safety issues identified postmarket

Device fracture

the possibility of device fracture (which was not predicted in any of the bench and animal testing).; Risk associated with permanent implantable devices

Serious adverse events

8% risk from surgery alone; Serious adverse events include partial paralysis, loss of vision, loss of motor skills, vertigo, and insomnia.; requiring the labeling to prominently address the 8% serious adverse event rate; Risks such as device-related fractures or complications

False-negative results

Risk for diagnostics leading to missed treatment

Related CFR Sections (3)

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See Also (8)