FDA’s New Draft Guidance on 510(k) Implant Devices: What You Need to KnowOctober 11, 2023
As we recently blogged, FDA released three draft guidance documents to help enhance the predictability, consistency, and transparency of the 510(k) program. One of these documents focuses on “Evidentiary Expectations for 510(k) Implant Devices.” Implant devices are used in a range of settings such as dental and orthopedic procedures. Having a clear understanding of FDA’s data expectations for 510(k) applications related to implants is crucial for successful marketing clearance. In this blog post, we highlight the distinctive data expectations recommended for implant devices in the draft guidance.
The draft guidance addresses the review considerations applicable to all implanted devices undergoing evaluation within the 510(k) program, referred to as “510(k) Implants” in the draft guidance. Implants subject to premarket approval (PMA), those eligible for the De Novo classification process, or those exempt from the 510(k) requirements fall outside the scope of this draft guidance. The objectives of the draft guidance are as follows:
- “Serve as a primary resource on expectations for all 510(k) implant devices, generally, while device-specific guidances provide further specificity for a given device type
- Assist industry in design and execution of appropriate performance testing to support 510(k) submissions for implant devices
- Provide recommendations for content and labeling to include in 510(k) submissions for implant devices, and
- Convey that the FDA considers the patient experience to be paramount in improving implant device safety, and encourages the collection, analysis, and integration of patient experience data for implants to support 510(k) submissions for those devices.”
General Considerations: What Makes Implants Unique Compared to Other Device Types?
Implant devices are unique because they are designed for continuous implantation for a period of 30 days or more, as per 21 C.F.R. § 860.3. This distinct use scenario, combined with new features of such devices, may increase the risks compared to other device types or predicate devices. For instance, FDA highlights risks associated with everyday activities (e.g., airport security screening), or surgical procedures, as well as the potential for reoperation or revision of the implant.
FDA recommends that applicants of 510(k) devices that are intended to be implanted for fewer than 30 days also consider the recommendations outlined in the draft guidance.
Performance data should be customized to the indications for use, including the specific intended patient population (adult vs. pediatric), disease state, conditions of use, and the target anatomical location. In the case of 510(k) Implants indicated for use in pediatric patients, FDA recommends consulting two other guidance documents: Pediatrics Guidance and Extrapolation Guidance.
The intended duration of implantation is another crucial factor in performance testing. Testing should be in line with the device’s intended duration of implantation, but FDA may consider whether testing results for a shorter duration can be extrapolated to provide information about long-term performance. In cases where devices are expected to be frequently replaced, testing should be guided by the aggregate patient exposure. Safety and effectiveness evaluations should encompass wear and degradation, taking into account the worst-case implantation conditions.
The draft guidance highlights non-clinical review areas that are generally relevant across 510(k) Implants and offers recommendations for performance data to include in a 510(k) submission. It is important to note that the type and amount of performance data required may vary based on the device, device type, and differences from the predicate device. If a submitter believes that certain testing described in the draft guidance does not apply to their device, they should provide a rationale in the 510(k) submission.
The draft guidance provides an overview of various standard testing areas such as biocompatibility, sterility and shelf life, reprocessing and cleaning, software and cybersecurity, electrical safety and electromagnetic compatibility (EMC), and magnetic resonance (MR) compatibility. Information about these typical non-clinical tests is generally based on previously released guidance documents for each topic, as linked above.
The draft guidance places emphasis on specific tests, such as acute systematic toxicity and material-mediated pyrogenicity for biocompatibility, pyrogenicity testing for sterility, and the applicability of ISO 14708 for the EMC of certain active implantable medical devices. For example, the draft guidance outlines a minimum five endpoints for biocompatibility testing (cytotoxicity, sensitization, irritation or intracutaneous reactivity, acute systemic toxicity, and material-mediated pyrogenicity) that should be assessed for 510(k) Implants, plus eight additional endpoints for biocompatibility (e.g., subacute/subchronic toxicity, genotoxicity, implantation, hemocompatibility, chronic toxicity, carcinogenicity, reproductive/developmental toxicity and degradation). It would be beneficial for the industry to have a clear understanding of which endpoints should be evaluated for specific types of implants and their respective implant locations.
Additionally, FDA has identified eight additional non-clinical performance testing areas unique to 510(k) Implants, as summarized in the table below. We find that this information is noteworthy for manufacturers to consider.
|Testing area||Summary of FDA’s Recommendations|
|Corrosion||“A combination of non-clinical studies on corrosion, the release of metal ions, and device-specific fatigue testing as well as animal and clinical studies, in some cases, to assess biological responses.”|
|Fatigue||Demonstration of “adequate fatigue life under conditions simulating in vivo use to mitigate the risk of device breakage and failure during the expected lifespan of the device.”|
|Degradation||“An evaluation of the degradation profile of the device should be conducted under anticipated conditions of use, including worst-case scenario conditions, to understand the degradation profile over time and any conditions that may accelerate or modulate device degradation.”|
|Particulate Characterization||Assessment of “the body’s response to any associated degradation products, including those leached from wear debris.”|
|Coating Characterization||“Information on the intended function of the coating,” “the materials used in the coating or its generation, bond method and bond strength between a coating and its substrate, and salient material or biochemical properties of the coating, including thickness, pore size, and overall volume of porous coatings.” For orthopedic implants, refer to this Guidance.|
|Imaging Compatibility and Radiotherapy Compatibility||Demonstration of whether the presence of the device impacts the image quality (e.g., image artifacts), radiopacity testing or other suitable imaging compatibility testing for localization of a device, and assessment of risks associated with exposure of the implant to other imaging exams and radiotherapy devices, as appropriate.|
|Engineering Analysis||“A combination of engineering analyses and non-clinical testing” may be sufficient to support substantial equivalence (SE) in some cases, “especially in circumstances where such analyses and testing have been validated to represent clinically-relevant failure modes.” Refer to this Guidance about computational modeling studies.|
|Bench Model Testing||“Testing using model systems with representative materials, geometries, and/or other simulated use parameters to evaluate the implant and demonstrate SE.”|
When engineering analyses and mechanical tests may not comprehensively address the complexities associated with the clinical use of an implant, the draft guidance suggests that an animal study may be necessary to support SE to the predicate device. We suggest consulting the draft guidance for a few representative examples of situations in which FDA may recommend animal testing. FDA encourages manufacturers to submit a pre-submission to discuss the animal study protocol with the Agency before submitting a 510(k) application.
Implant Device Design Considerations
Information regarding raw materials and manufacturing processes can be crucial for certain implants, such as those made of nitinol, implants with unique in vivo wear characteristics, implants composed of degradable materials or biologically-derived materials, and implants manufactured using additive manufacturing processes. In these cases, it is recommended that a 510(k) submission include details about materials, specifications, design and critical processing information, including reaction parameters and solvents used in processing or cleaning to allow FDA to better understand the final, finished form of the implant and how it compares to the predicate device in evaluating substantial equivalence.
Human Factors/Usability (HF/U) and Clinical Performance Testing
The draft guidance offers general information about HF/U and clinical performance testing. FDA acknowledges the particular importance of HF/U testing for implant devices with complex interfaces intended for implantation by healthcare practitioners (HCPs) and implants that involve post-implantation management by either the patient or HCP (e.g., programming, monitoring, maintenance).
The FDA notes that, in most 510(k) submissions, clinical data is not typically required to establish SE. However, there are specific scenarios where clinical data may become necessary to support an SE determination, as explained in another recent draft guidance on clinical data in 510(k), which we will discuss separately in a forthcoming blog post.
Patient Experience Information
As CDRH administers the Patient Science and Engagement Program, the draft guidance includes a separate section to encourage, rather than mandate, submitters to include patient experience data (such as patient preference information and patient-reported outcomes) for implants in a 510(k) submission, if it is relevant to the determination of SE. Regarding this aspect, FDA refers to three guidance documents: Patient-Reported Outcome Measures, Patient-Reported Outcome Instruments, and Patient Preference Information.
In evaluating substantial equivalence, FDA may consider patient preference information in conjunction with non-clinical and clinical testing. The totality of information helps inform FDA’s decision when it considers the overall benefit-risk profile of the implant device. Note that FDA performs a benefit-risk assessment in the 510(k) context when it determines whether the new device is “as safe and effective” as the predicate device after the Agency finds that the intended use of the new device and predicate device are the same and have different technological characteristics that do not raise different questions of safety and effectiveness if there are different technological characteristics.
Labeling and Implant ID Card
Lastly, it is critical that patients are provided with implant information as it pertains to their devices. Manufacturers should create user-friendly instructions for use that facilitate patient understanding of potential risks over the expected lifespan of the implant. FDA offers a flexible approach to achieve this goal, suggesting that some information may be suitable for inclusion on an implant ID card for the patient or caregiver, while other information may be better communicated in a different format (e.g., separate patient labeling). Concerning the implant ID card, FDA recommends including basic information such as model name and manufacturer and important details concerning patient contacting materials, including those that may be associated with allergic reactions. FDA also recommends the implant ID card provide contact information in the event of malfunctions or adverse events. Finally, for magnetic resonance (MR) conditional implants, FDA recommends identifying those conditions for safe MR use.
We encourage sponsors of implant devices to carefully review the draft guidance, participate in the FDA’s webinar scheduled for October 26, 2023, and consider submitting comments on this draft guidance by December 6, 2023, through the provided link.