The FDA Exemptions, Variances, and Alternative Forms of Adverse Event Reporting for Medical Devices program may benefit manufacturers in reducing the burden of medical device reporting (21 CFR Part 803, under 21 CFR 80.309(b) where real world data/evidence is being collected, such as in post-market clinical follow-up (PMCF) studies. Our aim is to encourage participation in this dynamic, collaborative process with the Agency by serving as a liaison on behalf of manufacturers.

RQM+ PMCF Studies As a Source of Aggregate Data

In the course of developing a PMCF data collection study, our team at RQM+ gathers and analyzes aggregate real world evidence provided from healthcare providers (HCPs) based on patient medical records / charts. We conduct PMCF studies by deploying anonymous questionnaires to HCPs through a GDPR compliant vendor. The most common type of PMCF activity we conduct is a retrospective patient-level medical record / chart review which often involves surveying HCPs in the United States, the European Union, and rest of world.

Today, the main regulatory driver for PMCF studies is the collection of safety and performance data for compliance with Medical Device Regulation (EU) 2017/745 (MDR), as well as the FDA 522 Postmarket Surveillance Studies Program. Collecting real world data from HCP data allows us to collect safety and performance data from medical devices on a global scale to provide valuable clinical evidence across markets.

Safety Data Generated in PMCF Studies

As an input to a PMCF study plan, the manufacturer provides a list of potential AEs associated with the medical device based on labelling, risk management and complaint information. We ask HCPs to review patient charts, typically regarding a specific case or procedure, and report whether any of these AEs were observed, to adjudicate the relationship of the event to the device (possible, probable, or causal), the severity of the AE and the outcome to the patient. The collected PMCF data is used to support the benefit-risk profile of the device as well as identify and monitor any unknown or emergent issues. The PMCF process is only one aspect of a robust risk management, complaint handling, and quality management system. What makes our PMCF studies unique, strategic, and valuable to manufacturers is that we can verify use of a device in real-world clinical practice using patient level real world evidence.

Depending on the sample size, it is common for PMCF data to generate dozens of device-related AEs usually ranging from mild (such as redness, tingling) to moderate (headache, pain) with varying degrees of device-relatedness. The AE data is considered in the PMCF Evaluation Report, which feeds into the benefit-risk assessment for the device. This data is processed by the company’s complaint handling system, which will determine if the events identified are reportable to regulatory authorities, as well as trend the complaints to identify emerging risks.

At the conclusion of the PMCF study, manufacturers have the cumbersome responsibility  of complying with reporting requirements for the AE data collected even though the data may have been proactively solicited. What is the best way to report 50 possibly device-related cases of headache using anonymized patient data where the only personal information known is the country, age, and sex of the patients? What do regulatory bodies require in the reporting submission?

The Exemptions And Variances Process

If a sponsor's applications is approved, the Exemptions process simplifies many of these concerns around conducting PMCF studies that collect potential negative feedback that must be triaged and analyzed for reportability. The aim is to reduce the burden of reporting individual AEs by granting an exemption or variance, which permits certain deviations from reporting requirements, when associated with a planned PMCF study on a case-by-case basis. Once an exemption is granted, the Agency will communicate to the manufacturer what, how, and when the collected AE data can be reported in lieu of submitting typically burdensome Medical Device Reports. The advantage to the manufacturer is that this permits abbreviated summary AE reporting. Similarly, the benefit to the FDA is reduced review time while continuing to monitor the safety of medical devices, protect patients, and foster the development and availability of cutting-edge medical tech.

To submit an Exemption Request, the manufacturer (sponsor) must request the exemption. This is an area where RQM+ could be authorized to liaise on behalf of the manufacturing sponsor to initiate the request. The Exemption Request is submitted during the early planning stages of the PMCF activity with an established list of proposed AEs, device information, description of the PMCF study, and a proposed timeframe for deployment.

The FDA is highly engaged in encouraging participation in the Exemptions and Variances process to support collection of real-world evidence from EHRs including PMCF studies, in addition to registries and medical claims databases. At RQM+, we have been impressed with the transparency and collaborative nature of the team at the Office of Product Evaluation and Quality and their commitment to providing a collaborative, iterative, informal review process. There are no set templates or guidelines, and each Exemption Request will be evaluated individually. The FDA will review requests for exemptions and variances case-by-case and may provide specific requirements when granting an application. The manufacturer can expect the Agency to provide tailored information on what information will be required in an abbreviated Summary Medical Device Report and how quickly this is expected after closure of PMCF data collection. See more information regarding this process at: Exemptions, Variances, and Alternative Forms of Adverse Event Reporting for Medical Devices | FDA.


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