Medical devices have been regulated by the Food & Drug Administration (FDA) since 1976. The FDA recognized that there is wide variation in device complexity along with the potential for a device to cause harm, so it developed a risk-based classification system for devices in order to regulate them based on a device’s inherent risks and benefits.
The risk classification of a device is defined in Title 21 of the Code of Federal Regulations (21 C.F.R.) by three levels of risk that range from low risk as Class I, medium risk as Class II and high risk as Class III. The FDA also established classifications for more than 1,700 generic devices within 16 medical specialties (known as panels) and defined these classification rules within 21 C.F.R., Parts 862–892.
Device classification is required to determine the type of regulatory submission that is filed with the FDA. For example, most medium risk Class II devices are required to file a premarket notification (known as a 510(k) submission) with the FDA prior to marketing a device. A 510(k) submission includes information and data to demonstrate that a device is substantially equivalent to another device that was previously cleared by the FDA through 510(k) (the “predicate device”). The 510(k) submission requirements are specified in the federal regulations under 21 C.F.R. 807.87. The necessary 20 elements of a 510(k) submission are defined below:
- Medical Device User Fee (MDUFA) coversheet is printed when a company pays its user fee to the FDA and should be included in the submission to confirm payment has been made. The user fee for Fiscal Year 2020 is $11,594. The fee for a company that has received a small business designation (SBD) is $2,899.
- CDRH Premarket Review Submission coversheet is the form providing the basic information about the type of submission and the reason for the submission, including details such as the device name, the trade or proprietary name, device classification, the establishment registration number of the owner, and contact information for the correspondent manufacturing facility and sterilization facility if the device is sterile. The final section is a list of performance standards, as applicable to the device.
- The 510(k) Cover Letter is an introduction to the submission that describes the type of 510(k) and provides a summary of the information included in the submission.
- The Indications for Use Statement is included on a template provided by the FDA. The Indications for Use is information publicly available on the FDA website.
- The 510(k) Summary is a condensed version of the entire submission that will also be publicly available on the FDA website. The idea is to document how the device meets the FDA requirements of substantial equivalence without providing specific proprietary details of the new or modified device.
- A Truthful and Accuracy Statement certifies that all of the information included is correct and that nothing has been omitted. The FDA provides exact wording for this statement.
- The Class III Summary and Certification is, in most cases for 510(k) submissions, simply a statement that “this device is not a Class III device.” If the device is a Class III device, the FDA provides a draft statement to use. The sponsor must provide a summary of all safety and effectiveness issues with the device along with data to support that statement.
- A Financial Certification or Disclosure Statement requires the sponsor to provide a statement such as: “No clinical studies were performed to test this device.” If a human clinical study was conducted, there is a Financial Certification form to complete if clinical investigators were not compensated or a Disclosure Statement to complete if clinical investigators were compensated.
- Declaration(s) of Conformity and Summary Report(s) is required if there are any specific standards that apply to a device. This includes a Declaration of Conformity identifying which standards were used and whether the standards were followed as-is or had any deviations.
- Device Description is an expansion of the brief description that has been used previously in the submission. It includes copies of the detailed specifications and/or drawings complete with dimensions and tolerances for each device, accessory and component. If a device is patient-contacting, it must list such components and their material specifications. For any applicable device-specific guidance documents, the submission should include all of the requirements in the device description. The device description section should provide sufficient detail to ensure the reviewer has a complete and thorough understanding of the device under review.
- The Executive Summary and Predicate Comparison is a description of the medical device with a concise comparison to the predicate device. This will include a summary of all the testing performed on the device.
- The Substantial Equivalence Discussion is the core element for the 510(k) submission and demonstrates that a new device is safe and effective because of its similarity or substantial equivalence to another device that has already been reviewed and cleared by the FDA. It is a stepwise comparison of both devices to demonstrate how the indications for use, technology, safety and performance are the same or no worse than the chosen predicate or reference device. It is commonly provided in a table format to make it easy for the FDA reviewer to locate the relevant information.
- Cleaning, Disinfection and Sterilization provides information related to the device sterility. A non-sterile device should be clearly identified as non-sterile in the submission and labeling. Cleaning procedures for reprocessed devices can be outlined in this section. A sterile device requires the sterilization validation summary and testing.
- Packaging and Shelf Life is another critical section of a 510(k), especially if the submission includes a sterile device. Shelf life of the device must be provided demonstrating the device is sterile at the end of the proposed shelf life and that the device still performs as expected. Packaging validation must support that the device packaging is effective in keeping the device sterile and undamaged during distribution and for the labeled shelf life of the device.
- Biocompatibility and Chemical Compatibility is addressed through an evaluation of biocompatibility, which is required when there are direct or indirect patient-contacting devices. This is typically presented with test data but, upon occasion, may be evaluated through scientific literature. The only exception for not evaluating biocompatibility is if the device material and manufacturing processes can be demonstrated to be identical to a predicate device that has previously been cleared.
The remaining five sections (16-20) may consist of a simple justification statement about why the section is not applicable to the device.
- Software: Many new medical devices contain software, and there are several FDA software guidance documents to consider during the design and development process and when completing the 510(k).
- Electrical Safety and Electromagnetic Compatibility: A device containing electrically powered components, regardless of whether those components are in patient contact or not, must be evaluated for its electrical safety and electromagnetic compatibility (EMC). The sponsor needs to know if a device interferes with other devices (either deliberately or accidentally) or can be interfered with by other devices.
- Performance Testing—Bench: The majority of design verification and validation testing is included in this section. Depending on the type of submission, this section could be a summary of the bench testing, or it may require providing all test protocols and reports. Test results and conclusions are included in this section.
- Performance Testing—Animal: This section is completed if any animal studies were conducted to support the safety or effectiveness of a device.
- Performance Testing—Clinical: This section is necessary if human clinical trials were conducted to support device safety and effectiveness but is usually not required for most 510(k) submissions.
In addition to the required elements, the FDA recently introduced a Refuse to Accept (RTA) checklist. The RTA is used by the FDA to facilitate an administrative review of 510(k) submissions prior to starting the review clock for the presence of all required elements in the submission.
All 510(k) submissions require a user fee to be paid to the FDA and require the submission to be sent to the FDA in an electronic format following the eCopy guidelines. The 510(k) submission is mailed with a hard copy of the cover letter to the appropriate Document Control Center (DCC). The DCC acknowledges receipt of the file, typically within 1 to 2 days, and then a unique identification number (K#) is assigned to the file. The K# corresponds with the current year and the order in which the file is received. The administrative review is conducted against the RTA checklist and is typically completed within 15 calendar days.
The FDA reviews approximately 3,000 submissions per year and publishes annual goals for their target review times, which, beginning in Fiscal Year 2020, is 116 days. The FDA also publishes quarterly performance reports to track progress to their goals. On average, a 510(k) submission is cleared in approximately 140–180 days, based on the performance metrics over the past five years. Most delays occur during the administrative/RTA review or result from additional information requests from the agency. Preventing delays in review times requires that all the elements submitted in a premarket notification and the supporting documentation present a clear and complete summary of the device. Concise comparison to its predicate allows the FDA reviewer to decide about the device’s substantial equivalence more quickly when the supporting information is complete and easily accessible within the submission.
Although the three types of 510(k) submissions require all the elements described above, the submissions will differ in the level of detail provided for each element depending on the type of submission:
- Traditional 510(k) is probably the most common type of submission and is required for most new devices. The target review clock for a traditional 510(k) is 90 days; however, it typically takes 4–6 months total for the original submission review and to review the sponsor’s response to deficiencies issued by the FDA. The submission includes all 20 elements as well as the full validation test protocols and reports that were conducted on the device.
- Special 510(k) submissions may only be used by companies making device modifications on their own devices. It contains summary information for any validation testing conducted on the device. A Declaration of Conformity for Design Controls and a risk analysis specific to the changes that are the scope of the submissions must be included in a special 510(k). The target review clock for a special 510(k) is 30 days; however, it typically takes 2–3 months total for a submission to be reviewed by the FDA.
- Abbreviated 510(k) is an alternative approach if there are device-specific guidance documents, special controls or voluntary performance standards that may be applicable to a device. Summary reports are provided describing how the guidance document was used to support substantial equivalence and how the device complies with any special controls or FDA consensus standards for device performance. The target review clock for an abbreviated 510(k) is 90 days. Abbreviated 510(k)s are not commonly used by the industry.