Concerned with a lack of specifics, Pfizer and US medical device industry group AdvaMed are calling on the US Food and Drug Administration (FDA) to amend its draft guidance on factors to consider regarding the benefits and risks for compliance and enforcement actions.

The draft guidance, released in July and known as “Factors to Consider Regarding Benefit-Risk in Medical Device Product Availability, Compliance, and Enforcement Decisions,” is meant to bring FDA’s benefit-risk framework for compliance decisions more in line with how it considers benefit and risk for marketing and investigational device exemption (IDE) application.

In particular, FDA says it considers the following factors when considering a device's benefit in light of compliance and enforcement decisions:

• Type of benefit(s)
• Magnitude of benefit(s)
• Likelihood of patients experiencing one or more benefits
• Duration of effects
• Patient preference on benefit
• Benefit factors for healthcare professionals or caregivers
• Medical necessity

Concerns

While applauding FDA’s efforts to provide clarity and transparency on how the agency intends to assess and interpret risk and benefit in its decision-making process, AdvaMed makes clear that the lack of specifics raises concerns over how the guidance can be applied.

“With so few specifics, we are concerned that this document cannot be applied consistently within FDA and throughout the industry. Effective guidance must be similarly interpreted by the majority of users in industry and FDA. The draft guidance does not provide an explanation or examples of how FDA will evaluate these benefit and risk factors to make a final decision as to whether or not to take a contemplated enforcement action,” AdvaMed said in comments released late last week.

The group representing device and diagnostic manufacturers also says it is unclear how a manufacturer can anticipate FDA’s risk tolerance.

“Manufacturers have for more than a decade been focusing on risk-based approaches (to compliance, CAPAs [corrective and preventive actions], design improvements, file remediation activities, recalls, etc.), yet FDA can always disagree with the manufacturer’s approach; this document does not provide any thresholds or specifics that would assure manufacturers that FDA would agree with a given decision,” AdvaMed says.

The group also says that it’s concerned that once the draft is finalized, FDA will find it difficult to ensure that center-based staff and field staff understand the decision-making process to mitigate and minimize subjective interpretation of FDA’s expectations for risk assessment during quality management system (QMS) inspections.

Similarly, Pfizer takes particular issue with a method to calculate the number of patients likely to be treated with a nonconforming device.

The draft says: “One method to calculate this likelihood is to take the number of patients treated with a nonconforming medical device and harmed and to divide by the total number of patients treated with nonconforming devices, over a similar time period, if reliable data exist.”

But Pfizer says: “This statement implies a method of acceptable execution. The suggested method is overly simplified and will not apply to most realistic situations. Given years of experience with such situations, it is not advisable to provide a suggested method for this likelihood factor. Each situation will have unique factors that need to be considered. Teams will need to work through the individual situations and determine the best way to assess these likelihood factors. They should then document their decisions and rationale.”

Comments on the Draft Guidance