Navigating the Regulatory Maze: Clinical Data for Medical Device Approval

In the world of medical devices, particularly those categorized as moderate to high-risk, clinical data is a critical component of the regulatory approval process. This data, presented to regulatory authorities, forms the basis for marketing authorization in most jurisdictions.

The challenge lies in determining the adequacy of the available data and crafting a persuasive justification for its suitability. Let’s explore the criteria used to assess the suitability of three different categories of data.

Literature

The existence of published literature on a subject device, even in large quantities, may not be sufficient to support a particular marketing application. Several factors come into play:

• Device and Variants: Are the articles reporting on the subject device? Is it a previous or current version of the design? Does the device have multiple variants that should be taken into consideration? Is the data stratified by variant, configuration, size?
• Indications and Intended Use: Is the indication/intended use reported in literature the same as that for which marketing authorization is sought? If there are multiple uses reported, are results stratified?
• Patient Population: Do the inclusion/exclusion criteria for the studies being reported align with the proposed device IFU? Do the patient demographics align with the demographics within the jurisdiction for which marketing authorization is sought?
• Length of Follow-up: Were the subjects followed long enough to capture the full duration of expected treatment effects or declared device lifetime, and all relevant adverse events?
• Performance Outcomes: Are the outcomes reported relevant to assessing device performance? Are they contemporary, or outdated methods? Are objective measures reported? Are any subjective assessments or scores validated?
• Safety Outcomes: Are rates of all relevant adverse events reported? Are events broken down by the timepoint at which they occurred?

Real World Evidence (RWE) and Retrospective Data

While the FDA has published guidance on the use of RWE to support marketing applications, it remains more of a theoretical option than a practical one. Similarly, Notified Bodies (NBs) will rarely find RWE such as registry data sufficient to support EU certification.

• Device Registries: Can be used as supportive data, but not the only source of evidence for safety and performance. Performance measures are rarely collected, safety data is often limited only to device failure, and no imaging data is collected (where this is relevant, e.g. orthopaedic implants).
• Standard Practice Data Collection: When looking for retrospective data to collect, it is important to understand which outcomes measures are collected as standard of care at each potentially contributing institution. Progress notes that simply state the patient is doing well are insufficient.
• Imaging and Labs: Additional testing and measures performed outside standard clinic visits pose additional challenges. For implants, regulatory authorities often require imaging reports be analyzed to ensure proper functioning and absence of specific adverse events. When these are not considered standard of care, it is unlikely that retrospective data collection will be sufficient.

Previously Conducted Prospective Studies

Data originally collected for non-regulatory purposes – publication, product development, etc. – may not meet the requirements for use as supporting evidence for a regulatory submission. Before a decision is made to rely on such data, a thorough review of sponsor and site files should be conducted to ensure documentation is available to demonstrate:

• Adherence to Good Clinical Practice (GCP) and region-specific requirements (ISO 14155, 21CFR812, etc.)
• Adequate site and sponsor documentation
• Institutional Review Board/Ethics Committee (IRB/EC) approval, continuing review, and reporting of protocol deviations and adverse events
• Informed consent was properly obtained for all subjects
• Any protocol deviations were documented and appropriately reported, and did not rise to the level of affecting the integrity of the data or study outcomes
• Data monitoring and cleaning have been performed such that the sponsor has confidence that the data reported are accurate and reflective of true subject outcomes

Positioning Your Medical Device for Regulatory Success

Navigating the regulatory landscape for medical device approval is a complex process. Understanding the criteria for assessing the suitability of available data is crucial in crafting a compelling case for regulatory approval. By considering these factors, applicants can better position themselves for a successful regulatory outcome.

For the US market, device manufacturers should consider engaging FDA via the Q-Submission (QSub) process to obtain feedback directly from reviewers regarding suitability and sufficiency of their proposed clinical data strategy.

Your Partner in Navigating Regulatory Challenges

Ensuring your clinical data meets the stringent requirements for medical device approval can be a daunting task. Whether you’re navigating the complexities of published literature, real-world evidence, or previously conducted studies, ProPharma is here to help. Our team of experts can guide you through the regulatory maze, ensuring your data is robust, compliant, and persuasive. Contact us today to learn how we can support your medical device's path to market.