Identifying the Correct FDA Guidance Documents and Standards
Clients who engage us for FDA 510(k) submission consulting often ask what testing is required by the FDA to clear their device. While testing requirements are easy to determine for some devices, other devices require intensive research.
It is very important to identify the correct testing requirements. Failure to do so could result in a longer 501(k) review time if the FDA sends an Additional Information (AI) request, asking for test data that was not anticipated or budgeted. If you cannot provide the requested test data in a timely manner, you might even have to withdraw your 510(k) submission.
This article does not cover how the FDA uses recognized consensus standards to make substantial equivalence determinations in 510(k) submissions. To better understand this process and other matters related to the use of standards, consult the following FDA guidance documents:
- CDRH Standard Operating Procedures for the Identification and Evaluation of Candidate Consensus Standards for Recognition
- Guidance for Industry and for FDA Staff: Use of Standards in Substantial Equivalence Determinations
- Frequently Asked Questions on Recognition of Consensus Standards
We will discuss how to identify the correct testing requirements and performance standards for your device using FDA databases, as well as other methods to determine relevant testing information for predicate devices outside normal FDA databases.
Classifying Your Medical Device under the U.S. FDA
Before a device sponsor can determine the testing requirements for their device, they must correctly classify their device according to the FDA’s Product Classification database. They must also complete all design and development activities as defined in 21 CFR Part 820.30, Design Controls, as any test data submitted in a 510(k) should be conducted on a finished device, or a device that fully represents the final design.
The FDA has three classes for medical devices (Class I, Class II, and Class III) based on the level of risk the device poses to the user. Class I devices pose the least risk to the user, while Class III devices pose the highest risk. All medical devices have a certain degree of risk associated with their use, as no device is considered perfectly safe. The entity named on the device’s label is responsible for managing those risks, and demonstrating that their device is both safe and effective for its intended use. One way to accomplish this for moderate to high-risk devices is to test the device against a known standard(s) that subjects it to simulated use conditions. Many devices are actually tested to worst case conditions to assess the risk of extreme use situations.
Most Class I devices are exempt from the 510(k) process, while most Class III devices require Premarket Approval (PMA), which is a more rigorous regulatory pathway than a 510(k). A PMA requires clinical data, as well as performance data, to prove safety and effectiveness. To help manage the risk a device poses to a patient or user, the FDA imposes their regulatory controls on the manufacturer of the device, which vary by classification.
Home-use devices often present hazardous situations for the layperson. Devices sold over-the-counter (OTC) or by prescription are usually self-administered by a layperson in a home setting. A popular example of such a product is a hand-held, light-based laser device to treat full-face wrinkles.
The FDA requires extensive testing for electrical safety, electromagnetic compatibility and biocompatibility, as well as other specialized tests that may be applicable, for home-use devices. The test data obtained from these different tests is included in the 510(k) submission. The FDA critically assesses the test data during their review to determine if the subject device is substantially equivalent to the predicate device.
Methods for Finding Applicable Testing Requirements
With the product classification out of the way and assumed to be correct, I will demonstrate methods for finding the applicable testing requirements and standards. These examples highlight some of the techniques and pitfalls you might encounter when dealing with testing requirements. Two of the most important special controls are the FDA’s guidance documents (aka guidelines) and recognized consensus standards (aka performance standards).
Vertical vs. Horizontal Standards
Many FDA guidance documents and performance standards are product code specific (“vertical”) because they apply to a specific type of device (e.g., dental implant; product code DZE). However, other guidance documents and performance standards are not product code specific (“horizontal”) and cover many different types of devices across various device classification panels.
Vertical guidance documents are particularly important when making a 510(k) submission. In addition to the testing requirements for that specific device, vertical guidance documents contain other valuable information required to clear the device, such as special product labeling requirements, identified risks and hazards that need to be considered, if clinical data will be required in the submission, etc.
Each device sponsor should approach their testing strategy with a master test plan, so that all known tests can be identified and budgeted. Manufacturers are encouraged to discuss their test strategy with the FDA prior to starting any testing, via a pre-submission meeting. This is especially important if any testing is unique to your device and not covered under any known performance standard, whether it’s an FDA recognized consensus standard or not.
How to Use and Understand FDA Databases—Example 1
Let’s look at some specific examples of how to identify the testing requirements for
different devices. For our first example, let’s search for “endosseous dental implant” (product code DZE).
Using the FDA’s product classification database, insert “DZE” into the “Product Code” field and click on the “Search” button in the lower right of the screen, as shown in Figure 1. All of the relevant FDA regulatory information for this device is shown in Figure 2. We suggest using the product classification database as the starting point when searching for product code specific guidance documents and performance standards, as these should come up in the search if they exist.
This is a good example of when the FDA’s product classification database yields a lot of valuable information on a device: ten standards and one guidance document are listed. Two of those standards (ADA/ANSI Specification No.38, and ISO 14801) are vertical and unique to dental implants, dental abutments and a few other dental devices. The other eight standards are horizontal, and may or may not be applicable to a particular dental implant depending on the specific characteristics of the device (e.g., the material, surface finish, etc.).
However, this list does not include horizontal standards that could also apply to dental implants, such as sterilization and packaging. Finding those horizontal standards requires a separate search.
Using Guidance Documents to Your Advantage
Also shown in Figure 2 is the FDA’s guidance document specific to endosseous dental implants: Guidance for Industry and FDA Staff – Class II Special Controls Guidance Document: Root-form Endosseous Dental Implants and Endosseous Dental Abutments. This guidance document also covers dental abutments (product code NHA; regulated within 872.3630 as a Class II device) as shown in Figure 3. Dental abutments are often sold with dental implants as a system, and cleared under the same 510(k). Or, they can be cleared and sold separately.
A product code specific guidance document is a big advantage when making a 510(k) submission. The FDA is essentially telling the device sponsor what they expect to see in their 510(k). Assuming the device sponsor has read the guidance document, understands what is being requested, and presents that information (and test data) in their submission, there should (theoretically) be no unexpected questions from the FDA.
The guidance document for dental implants (and abutments) listed above is a good example of the level of detailed information, including specific test data, the FDA expects to see in a 510(k) submission for those devices. If the device sponsor fails to address these key areas, it could significantly increase the 510(k) review time or force the device sponsor to withdraw their submission if they cannot supply the requested additional information in a timely manner. This FDA guidance document references the potential need to submit clinical data (see Section 12, Clinical Studies) if the implants are within a certain size range, are made from novel materials or manufacturing methods, among other things.
All the standards for dental implants obtained from the product classification database search shown in Figure 2 can also be found by searching in the FDA’s recognized consensus standards database. Again, inserting “DZE” into the “Product Code” field and clicking on the “Search” button, as seen in Figures 4 and 5, extracts the same results shown in Figure 2. However, this method alone will not find the FDA’s guidance document for dental implants, which requires a separate search using the FDA’s guidance document database, shown in Figure 6.
How to Use and Understand FDA Databases—Example 2
In example 2, we’ll search for Product Code NFO (Transcutaneous Electrical Stimulator for Aesthetic Purposes). Figure 7 shows the relevant regulatory information for a transcutaneous electrical stimulator for aesthetic purposes extracted from the FDA’s product classification database (product code NFO; regulated within 882.5890 as a Class II device). These are typically hand-held OTC devices used by laypersons in a home setting, and cleared for “facial stimulation and cosmetic use.”
In Figure 7, no FDA guidance documents or performance standards are referenced, as in Example 1 for dental implants. Additionally, no relevant performance standards were extracted when searching in the FDA’s standards database under product code “NFO.” Searching the FDA’s guidance document database using key search terms (i.e., “aesthetic,” “transcutaneous,” “electrical,” and “stimulator”) does not return a relevant guidance document for this type of device (these terms identified guidance documents for several unrelated devices). However, an unsuccessful search does not
mean that extensive device testing is not required to clear such a device.
Product Codes with No Linked Guidances or Standards
Many product codes have no vertical guidance documents or performance standards linked to them. Unless you know how to look further in other FDA databases (or elsewhere), or have experience clearing similar devices, you may not find them and assume testing is not required. However, it’s important to remember that the FDA has not issued guidance documents for many product codes.
In situations where the FDA’s product classification, guidance document, and recognized consensus standards databases do not reveal the testing requirements for a particular device, use the FDA’s 510(k) Premarket Notification database. This database contains information about testing completed for previously cleared devices under the same product code. The FDA will likely require similar testing for the subject device. If the device sponsor has already selected a predicate device for their 510(k) submission, reviewing the 510(k) summary in the FDA database is a good place to start the search.
Using product code NFO and performing this type of search shows twenty devices cleared from 2001-2016, as seen in Figures 8 and 9.
Read the 510(k) summary for a few devices for any relevant information about the testing performed on them. We recommend looking at 510(k) summaries for the most recently cleared devices for relevant technical information, as opposed to devices cleared longer than five years ago.
The substantial equivalence table in the 510(k) summary for Product A, which was cleared in 2016, references a number of tests (highlighted in yellow) performed to clear this device.
From the table, the performance testing conducted was: electrical safety (per IEC 60601-1), EMC (per 60601-1-2), performance of nerve and muscle stimulators (per IEC 60601-2-10), and requirements for medical electrical equipment and medical electrical systems used in the home healthcare environment (per IEC 60601-1-11). Biocompatibility testing was also conducted: cytotoxicity (per ISO 10993-5), and sensitization and irritation (per ISO 10993-10).
Other Valuable Information in a 510(k) Summary
Additional information is available in various sections of the 510(k) summary. For example, in Section 7 (Clinical Performance Data) of the 510(k) summary for Product A, the device manufacturer references an 80-person usability and product self-selection study. These types of studies are typically required by the FDA for many home-use devices.
A 510(k) summary may not identify all tests conducted on the device. 510(k) summaries for different predicate devices might only reference IEC 60601-1 and IEC 60601-1-2. However, this does not mean additional tests, as well as usability and self-selection studies, were not performed.
If the device contains operating system software that controls program settings and the amount of current administered to the user, risk analysis and software verification and validation are required under product code NFO. Below is a list of related guidance documents that should be evaluated for relevance:
- ISO 14971, Medical devices – application of risk management to medical devices
- IEC 62304, Medical device software – software life cycle processes
- Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices – Guidance for Industry and FDA Staff
- General Principles of Software Validation; Final Guidance for Industry and FDA Staff
- Guidance for Industry, FDA Reviewers and Compliance on Off-The-Shelf Software Use in
- Applying Human Factors and Usability Engineering to Medical Devices
- Design Considerations for Devices Intended for Home Use
This list includes the FDA’s guidance documents on human factors and usability engineering, and design considerations for home-use devices. These important design related topics for home use devices must be addressed in the 510(k) submission with supporting data and documentation (i.e., usability and self-selection studies, and user manual) to comply with 21 CFR Part 820.30, Design Controls and 21 CFR Part 801 Labeling.
These extensive testing requirements and other verification and validation activities are often overlooked by many first-time device sponsors. They often lack experience searching FDA databases, making 510(k) submissions, or are not aware of the different types of testing, verification, and validation activities. It is not until the device sponsor receives an Additional Information request from the FDA that they realize it may take much longer than 90 days to clear their device. Also, the process might cost more than they anticipated.
The Difference Between a 510(k) Summary and a 510(k) Statement
The 510(k) summary is written by the manufacturer of the device, not the FDA. However, the FDA is stricter than it used to be regarding required information for the 510(k) summary of a cleared device. Recently, FDA started to require more detailed technical information in their 510(k) summaries as a way to help new device sponsors identify those relevant features – including references to performance testing – about the predicate device they chose. This is why 510(k) summary information for older device clearances may include very little technical information.
For a predicate device with a published 510(k) statement, rather than a 510(k) summary, the only information in a 510(k) statement is the Indications for Use. This is allowed by the FDA, although it carries limitations and conditions. We do not recommend using a predicate device cleared with a 510(k) statement unless it is the only option available. There will be no other relevant information on that device in the FDA’s 510(k) database, which can make it very difficult to demonstrate substantial equivalence, unless one does side-by-side performance testing against the predicate device.
How to Use and Understand FDA Databases—Example 3
There are other ways to search for a standard in addition to searching by product and regulation number. These different search fields available in the database are shown in Figure 11; these include the following options:
- Standards Organization (e.g., ISO, IEC, ASTM, etc.)
- Standards Designation Number (e.g., 14971, 10993, etc.)
- Standards Title or Keywords
- Specialty Task Groups (e.g., sterility, biocompatibility, materials, etc.)
- Type of Standard (e.g., vertical, national, horizontal, etc.)
- Publication Date
Using these search fields can narrow the list of relevant standards for testing your device.
For example, the FDA may recognize more than one testing standard version, issued by different standards organizations, for the same test. The FDA might impose a transition period for a certain standard, after which they will no longer recognize it. Always check a standard’s FDA status before starting expensive testing.
Two common tests in this category address electrical safety and electromagnetic compatibility (EMC). These tests apply to a wide range of medical devices that require a source of electrical power to function.
Entering “electromagnetic” in the “Standards Title or Keywords” field of the FDA’s standards database and clicking on the “Search” function in the lower right of the screen extracts the titles of nine different standards as seen in Figure 12.
Five of the standards listed are actually for specific devices (e.g., pacemakers, defibrillators, wheelchairs and scooters). One standard is related to the measurement of electromagnetic immunity of medical devices to radiated radio-frequency emissions from RF transmitters. Therefore, none of these standards are the relevant general standard for EMC testing.
This leaves four different FDA-recognized versions of the relevant horizontal standard for measuring EMC in medical devices. That standard is 60601-1-2 as seen in Figure 13. Clicking on the hyperlink of the versions in Figure 13 shows an FDA information page related to each standard, as seen for the IEC 60601-1-2 Edition 4.0 version. This link contains all of the related information on that standard, including its FDA recognition number and transition period. To obtain the actual standard, the user must purchase it directly from the issuing standards organization. They are copyrighted by the issuer, and the FDA does not make any standards available to the public.
For example, even if a device sponsor has been selling an electrical-based medical device in Europe for the last 10 years, the FDA may not accept their EMC testing to the second edition of IEC 60601-1-2. For further clarification about how to address a situation like this, see the previously referenced FDA guidance document: Frequently Asked Questions on Recognition of Consensus Standards
Even after looking at all the different FDA databases, you may need to search the predicate manufacturer’s website, or those of similar devices, to determine applicable testing requirements. This search method may lead to other valuable information, as some manufacturers place the user manual and/or service manual on their website for the device, which often contains references to conformance standards.
Determining Testing Requirements for Novel Devices
For some novel devices, there will be no standardized tests referenced in the FDA databases that adequately test the subject device for its intended use. In these cases, the device sponsor may need to develop their own internal test procedure. The test protocol and report must be included in the 510(k) submission.
Note that the FDA wants data supporting the subject device’s safety and effectiveness (SE). Sometimes the only way to demonstrate SE is in the form of comparison or side-by-side testing to the predicate. It is the device sponsor’s responsibility to ensure they do the appropriate testing.
However, it may be prudent to discuss any specialized tests with the FDA prior to conducting them, as the FDA may have comments/concerns about the proposed testing. The FDA’s pre-submission process is the best method for approaching the agency to discuss proposed testing requirements. Other topics related to the pending 510(k) submission can be addressed through the FDA’s pre-submission process (see guidance document linked above).
Commonly Referenced FDA Guidance Documents and Recognized Consensus Standards
Table 1 lists some of the common FDA guidance documents and recognized (horizontal) consensus standards that may apply to devices currently under design and development. This table is by no means complete, as other FDA guidance documents and performance standards may apply to your device. Selecting the appropriate FDA guidance documents and performance standards is the device sponsor’s responsibility. If in doubt, contact the FDA directly or engage a reputable advisory firm for assistance.
|Guidance Document||Consensus Standard|
|Use of International Standard ISO-10993-1, Biological Evaluation of Medical Devices Part 1: Evaluation and Testing Within a Risk Management Process Web Link||ISO 10993-1:2009, Biological Evaluation of Medical devices – Part 1: Evaluation and Testing Within a Risk Management Process|
|Submission and Review
of Sterility Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile Guidance for Industry and Food and Drug Administration Staff Web Link
|ISO 11607-1:2006, Packaging for Terminally Sterilized Medical Devices – Part 1: Requirements for Materials, Sterile Barrier Systems and Packaging Systems|
|ISO 11607-2:2006, Packaging for Terminally Sterilized Medical Devices — Part 2: Validation Requirements for Forming, Sealing and Assembly Processes|
|ISO 17665-1:2006, Sterilization of Health Care Products – Moist Heat – Part 1: Requirements for the Development, Validation and Routine Control of a Sterilization Process for Medical Devices|
|ISO 11135:2014, Sterilization of Health-Care Products – Ethylene Oxide – Requirements for the Development, Validation and Routine Control of a Sterilization Process for Medical Devices|
|ISO 11137-1:2006, Sterilization of Health Care Products – Radiation – Part 1: Requirements for Development, Validation and Routine Control of a Sterilization Process for Medical Devices|
|–||ASTM F1980 – 07:2011, Standard Guide for Accelerated Aging of Sterile Barrier
Systems for Medical Devices
|–||AAMI / ANSI ES 60601-1:2005, Medical Electrical Equipment – Part 1: General
Requirements for Basic Safety and Essential Performance
|Information to Support a Claim of Electromagnetic Compatibility (EMC) of Electrically-Powered Medical Devices Guidance for Industry and Food and Drug Administration Staff Web Link||IEC 60601-1-2 Ed 4.0, Medical Electrical Equipment – Part 1-2: General Requirements for Basic Safety and Essential Performance – Collateral Standard: Electromagnetic Compatibility – Requirements and Tests|
|Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices Web Link||IEC 62304:2006, Medical Device Software – Software Life Cycle Processes|
|General Principles of Software Validation; Final Guidance for Industry and FDA Staff Web Link|
|Guidance for Industry, FDA Reviewers and Compliance on Off–The-Shelf Software Use in Medical Devices Web Link|
|Draft Guidance for Industry and Food and Drug Administration Staff – Applying Human Factors and Usability Engineering to Optimize Medical Device Design Web Link||ISO 14971, Medical Devices – Application of Risk Management to Medical Devices|
|Design Considerations for Devices Intended for Home Use Web Link|
Table 1: Commonly referenced FDA guidance documents and standards
Final Thoughts on Testing Requirements for 510(k) Submissions
Obtaining FDA clearance through the 510(k) process in the 21st century requires some form of device testing, likely to a known standard. It might also require other types of verification and validation activities related to the device’s design and performance. These critical items prove the safety and efficacy of the device and, in so doing, demonstrate substantial equivalence to the predicate device. There is simply no way around this. Many companies complain about the FDA’s burdensome 510(k) and PMA requirements for medical devices. However, there are very good reasons for them, which are well documented in the news and on the FDA’s warning letter database.
When bringing a new product to market – especially a medical device, where the stakes are much higher – the chances of achieving commercial success increase when you put more thought into the early stages of planning, design, and development. If you take the time to research all of the testing requirements, FDA guidance documents, and performance standards that apply to your device, your 510(k) submission should move through the FDA’s review process with fewer questions.
Two devices submitted under the same product code can have dramatically different 510(k) clearance times if one company understood the FDA testing requirements and the other does not. Understanding the FDA’s testing requirements and identifying all the required performance standards, as well as compliance with their applicable guidance requirements, can help you achieve an efficient clearance.
In summary, the key steps to determining the correct FDA guidance documents and performance testing requirements that apply to your device are:
- Understand the intended use and fundamental scientific technology of your device;
- Accurately classify your device under the FDA’s product classification system;
- Identify all FDA guidance documents and performance standards, both vertical and horizontal, that apply to the intended use and fundamental scientific technology of your device;
- Perform an appropriate risk analysis on your device in accordance with ISO 14971 based on the device’s product classification, intended use, and fundamental scientific technology;
- Give early consideration to any potential predicate devices used in your 510(k) submission so you can thoroughly review the testing performed on those devices;
- Design, develop, and manufacture your device in accordance with 21 CFR Part 820, Quality System Regulation, with particular attention to Part 820.30, Design Controls;
- Perform all identified testing used in your 510(k) submission on a finished device design, or an accurate prototype of the device that will be placed on the market, and not on a device that is still under development and subject to design changes.
Stuart Goldman is a Senior Consultant at Emergo with 25 years of experience in the medical device industry. Before joining Emergo in 2006, he spent the first 15 years of his career involved in various quality functions for a leading manufacturer of high-risk cardiovascular implants and instrumentation. He now focuses on medical device regulations for the U.S. and Europe. Stuart’s areas of expertise include medical device classification and regulatory strategies and submissions; medical device testing requirements and FDA Warning Letter responses; and QMS audits. Stuart has worked on FDA submissions for a wide range of devices, with a focus on dental, orthopedic, radiological, electrosurgical, general surgical and personal use products. He has a Bachelor of Science in Materials Science and Engineering from North Carolina State University. Stuart can be reached at firstname.lastname@example.org.