How to justify using multiple predicate devices in a 510k submission?

# How to Justify Using Multiple Predicate Devices in a 510(k) Submission Navigating the FDA 510(k) process requires a clear demonstration of Substantial Equivalence (SE) to a legally marketed device, known as a predicate. In most cases, sponsors identify a single predicate device that shares the same intended use and similar technological characteristics. However, for innovative devices that combine features from different existing products, finding a single predicate can be impossible. In these situations, sponsors may consider a "split predicate" approach, using multiple predicate devices to support their SE argument. This strategy is appropriate when a new device integrates technologies from more than one device type, and no single product on the market has the same combination of features. The key challenge is to provide a robust scientific justification demonstrating that the combination of features does not raise new questions of safety or effectiveness. Without a compelling rationale, the FDA may reject the 510(k) and issue a Not Substantially Equivalent (NSE) determination. ### Key Points * **When It's Appropriate:** A split predicate strategy should only be used when no single predicate device can be identified that has the same intended use and combination of technological characteristics as the new device. * **Primary Predicate is Crucial:** The sponsor must identify a primary predicate that most closely matches the new device's fundamental intended use and core technology. Secondary predicates are used to support equivalence for additional, distinct features. * **Justification is Paramount:** The 510(k) submission must include a detailed scientific rationale explaining why the combination of features from multiple predicates is as safe and effective as the individual components and does not create a new intended use. * **Focus on Integration Risks:** The justification must specifically address the risks associated with integrating the different features. This requires testing that evaluates potential negative interactions, such as electrical interference, software conflicts, or material incompatibility. * **Early FDA Engagement is Recommended:** Due to the complexity of this approach, sponsors should strongly consider discussing their split predicate strategy with the FDA through the Q-Submission program before investing in a full 510(k) submission. ## Understanding the "Split Predicate" Approach The 510(k) regulatory framework, outlined in 21 CFR Part 807, is built on the principle of comparing a new device to a predicate. A split predicate strategy is an extension of this principle, allowing a sponsor to piece together an argument for substantial equivalence using more than one legally marketed device. ### The Role of Primary and Secondary Predicates In a split predicate submission, the devices serve distinct roles: 1. **Primary Predicate:** This is the most important predicate. It must be the device that most closely resembles the new device’s overall intended use and core technology. For example, for a surgical device that adds a new sensor, the primary predicate would be a similar surgical device without the sensor. It establishes the foundational basis for the 510(k). 2. **Secondary Predicate(s):** These are used to demonstrate substantial equivalence for the specific features or technological characteristics that are not present in the primary predicate. For instance, the secondary predicate for the surgical device example might be a standalone medical sensor that uses the same technology. The sponsor’s goal is to demonstrate that their new device is simply a combination of established, legally marketed technologies and that this combination performs as safely and effectively as its constituent parts. ## Building a Robust Justification A successful split predicate argument hinges on a clear, comprehensive, and scientifically sound justification. The FDA will closely scrutinize these submissions to ensure that the integration of features does not introduce new risks. ### What FDA Will Scrutinize * **The Rationale for the Split:** The submission must first clearly explain why a single predicate could not be used. * **The Safety of the Combination:** The core of the justification is addressing the question: "Is the integrated device as safe and effective as using the predicate devices separately?" The sponsor must analyze potential failure modes, performance trade-offs, and interaction effects. * **Intended Use:** The sponsor must demonstrate that the combination of features does not create a new intended use that falls outside the scope of the predicate devices. ### Critical Performance Data to Provide To support the justification, sponsors must provide robust performance data that specifically addresses the risks of integration. This often goes beyond the standard testing required for the individual features and may include: * **Integration Testing:** Specialized bench tests designed to assess negative interactions between the combined features (e.g., electrical interference, thermal transfer, fluidic disruption). * **Comprehensive Risk Analysis:** An updated risk analysis that identifies hazards unique to the integrated system. * **Software Validation (if applicable):** If software controls the integrated features, validation must demonstrate that the software safely and effectively manages all functions and potential interactions. ## Scenario: An Orthopedic Implant with a Novel Surface Technology To illustrate the concept, consider the following generic scenario. ### The Situation A manufacturer develops a new orthopedic screw (e.g., for spinal fusion) that is identical in material, dimensions, and intended use to an existing, legally marketed screw. However, the new screw features a unique, micro-textured surface designed to encourage bone in-growth, a technology borrowed from a legally marketed dental implant. No single orthopedic screw on the market has this specific surface technology. ### The Split Predicate Strategy * **Primary Predicate:** A legally marketed orthopedic screw of the same material, size, and intended surgical use. This establishes equivalence for the core mechanical function and surgical application. * **Secondary Predicate:** A legally marketed dental implant that uses the same micro-texturing surface technology. This is used to support the safety and performance of the surface technology itself. ### What FDA Will Scrutinize FDA will focus on whether the combination of the screw's form factor and the new surface technology raises new questions. For example, does the surface texturing compromise the mechanical strength or insertion properties of the screw? Does the manufacturing process for creating the texture introduce new material contaminants or alter the biocompatibility of the base material? ### Critical Performance Data to Provide * **Mechanical Testing:** Full mechanical testing (e.g., torque, pull-out strength) on the final, surface-textured screw, compared directly against the primary predicate. * **Biocompatibility Testing:** A full suite of biocompatibility tests on the final finished device to ensure the surface texturing process did not introduce any toxic residues. * **Surface Characterization:** Detailed analysis confirming that the micro-texture on the screw is identical to that on the secondary (dental implant) predicate. ## Strategic Considerations and the Role of Q-Submission A split predicate approach is a complex regulatory strategy that carries a higher risk of an NSE determination compared to a standard 510(k) submission. The burden is on the sponsor to proactively identify and mitigate all risks associated with feature integration and to present a clear, logical argument to the FDA. Given these complexities, engaging the FDA early through the Q-Submission program is a critical strategic step. A Pre-Submission meeting allows a sponsor to present their proposed device, the identified primary and secondary predicates, and their testing plan. This provides an opportunity to receive direct FDA feedback on the appropriateness of the strategy and to align on the evidence needed to support a future 510(k) submission. As of 2024, early communication remains one of the most effective tools for de-risking complex regulatory submissions. ### Key FDA References - FDA Guidance: general 510(k) Program guidance on evaluating substantial equivalence. - FDA Guidance: Q-Submission Program – process for requesting feedback and meetings for medical device submissions. - 21 CFR Part 807, Subpart E – Premarket Notification Procedures (overall framework for 510(k) submissions). ## How tools like Cruxi can help Managing a split predicate justification involves detailed comparison tables, extensive testing evidence, and a well-structured narrative. Tools like Cruxi can help regulatory teams organize these complex elements, link evidence to claims, and build a clear, traceable submission file to present a compelling argument to the FDA. This article is for general educational purposes only and is not legal, medical, or regulatory advice. For device-specific questions, sponsors should consult qualified experts and consider engaging FDA via the Q-Submission program.