510(k)

If you are a third-party or hospital reprocessor, learn how to prepare an FDA eSTAR 510(k) submission for reprocessed single-use devices.

Why is there so much interest in reprocessed single-use medical devices?

With increasing pressures on the medical device industry to make healthcare more affordable, there has been a push to reprocess and reuse single-use devices. Reprocessors obtain used devices from healthcare facilities. The reprocessors clean, process, resterilize, repackage, and relabel devices. Reprocessors must obtain FDA 510(k) clearance by demonstrating that the safety and effectiveness of the reprocessed device are substantially equivalent to the single-use device produced by the original equipment manufacturer (OEM). The FDA created a FAQ document for single-use devices, and three guidance documents were published:

• Labelling recommendations for single-use-device reprocessed by third parties and hospitals (July 2001)
• Reprocessing Medical Devices in Health Care Settings – Validation Methods and Labeling
• Validation Data for 510(k) of Reprocessed Single-Use Device (September 25, 2006)

Why do reprocessors have difficulty preparing an FDA eSTAR for reprocessed single-use devices?

Obtaining 510(k) clearance for a device your company did not design can be challenging because the reprocessor doesn’t have access to all of the required design and manufacturing information. The following sections of the FDA eSTAR submission pose unique challenges for reprocessed single-use devices:

• Labeling – What should and should not be included in the reprocessed device labeling
• Biocompatibility – How to identify the materials, and determine what biocompatibility testing needs to be done
• Performance Testing – Strategies for determining appropriate performance testing

Labeling Section of the FDA eSTAR for reprocessed devices

Labeling of reprocessed devices consists of the instructions for use and the packaging label(s). Device package labeling may also direct the user to both the reprocessor’s IFU and the OEM’s IFU. If you are referencing the OEM’s IFU, it is also important to include the OEM’s model number. Instructions for use should consist of:

1. Indications for use, which must be equivalent to the OEM indications.
2. All of the necessary warnings and cautions and basic operating instructions needed to operate the device safely.
3. The instructions for use may also instruct the user to reference the OEM instructions for use for additional information.
4. Instructions on the handling of the device after use, with the likelihood that the device will be returned to the reprocessor to repeat the cycle.

Biocompatibility Section of the FDA eSTAR

Biocompatibility data is more challenging to provide if you replace or modify original components. If reprocessing does not modify the OEM device whatsoever, you can claim that the materials are identical to the OEM device. Therefore, the reprocessed device does not require biocompatibility testing. However, the reprocessor still needs to evaluate the biological risks associated with the reprocessing of the device by testing for cleaning and sterilization residuals. This involves testing for cleaning agent residuals and EO residual testing (ISO 10993-7), if applicable. If applicable, this involves testing for cleaning agent residuals and EO residual testing (ISO 10993-7)

If you replace any of the components during reprocessing with a new component that is identical in dimension and material to the OEM component, minimal biocompatibility testing will be required. If the exact material used by the OEM is unknown, reprocessors can perform material identification testing to determine the material used, and then create the replacement part out of the same material.

If you modify or replace any patient-contacting components on the device such as lubricants, insulation, etc., with components that are different from the OEM, then you will need to perform additional biocompatibility testing to prove that the new or modified material is biocompatible. This testing will depend on the duration of contact and where will the material contact the patient. The new material will also need to be listed in your device description and Section 15 of your 510(k) submission.  

Performance Testing Section of the FDA eSTAR

There are three primary sources for identifying performance testing requirements of reprocessed devices:

1. OEM Testing listed in the OEM 510(k) submission
2. Predicate Testing listed by another reprocessor of an equivalent device
3. Product Standards listed under the product classification code for the reprocessed device or the OEM device

You should reference a predicate device that has been reprocessed and the OEM device to identify performance testing. Some testing is specific to the functional performance of the device. For these tests, you need to compare performance side-by-side against the OEM. Another testing is specific to reprocessing; you will reference the predicate device. Sources of information regarding the required tests for each of these devices can be found in the 510(k) summaries of the respective devices. If possible, it’s helpful to select a predicate that has a redacted 510(k) available on the FDA’s website. If a redacted 510(K) is not readily available, you may request a redacted copy through the Freedom of Information Act online. A redacted copy of the OEM 510(k) is also helpful. It’s helpful to select a predicate with a redacted 510(k) available on the FDA’s website if possible

If testing information is not as readily available in the 510(k) summary, you will determine the essential performance functions of the device, and design tests to evaluate and compare the OEM device and the reprocessed device for those functionalities. Some devices have specific standards for their design and/or testing. To determine if the reprocessed device has any applicable standards, you should search the product code of the reprocessed device and the product code of the OEM device, if they are different, in the FDA product classification database. The search results will list recognized standards applicable to the reprocessed device.

Additional tests that may be needed to validate reprocessing include residual protein, residual carbohydrates, and the presence of hemoglobin. These tests ensure that all biological material from previous use is removed. If you are not performing biocompatibility testing on the reprocessed device, you must do a chemical test to ensure no residual detergent or cleaning residues remain on the device. You must also determine how many reprocessing cycles the device can survive before performance degradation. This can be done by repeating simulated use, reprocessing, and performance testing until a statistically relevant decrease in the performance of the device is observed.

If you have additional questions regarding preparing your 510(k) submission, please visit our Contact Us webpage to schedule a meeting with Lindsey Walker or Rob Packard.

Learn how to create a regulatory plan for combining 510k with CE marking submissions in parallel instead of doubling your workload.

My first medical device regulatory submission was for CE Marking, while my second regulatory submission was for a 510k submission of the same product. Preparing submissions for different countries in parallel is a common path for medical device regulatory submissions, but it is also an inefficient path. If you know that you will be submitting both types of documents, then you should plan for this from the start and reduce your workload by at least 35%.

The reason why you can quickly reduce your workload by more than 65% is that both submission have very similar sections. Therefore, you can write the content for those sections in such a way that the material can be used for your 510k submission and CE Marking.

Identify duplicate sections in when combining 510k with CE marking projects

Most of your testing requirements should be identical when you are combining 510k with CE Marking submissions. However, the way the testing is presented is different. For your 510k submission you will attach the full testing report and write a brief statement about how the testing supports substantial equivalence. In contrast, CE marking technical files require a summary technical document or STED. The STED is a summary of each test that was performed. If you aren’t sure what testing is required, we created a test plan webinar to address this question specifically. Most of the work will be duplicated between your two test plans, but any outliers should be identified. For example, biocompatibility will need to include a biological evaluation plan (BEP) and biological evaluation report (BER), but this is optional for a 510k submission. There are also FDA requirements that are not required for CE marking, such as material mediated pyrogenicity testing and bacterial endotoxin testing for each production lot. In general, the possible testing categories are:

1. biocompatibility
2. sterilization
3. shelf-life
4. distribution
5. reprocessing
6. software
7. cybersecurity
8. wireless coexistence
9. interoperability
10. EMC
11. electrical safety
12. non-clinical performance
13. human factors
14. animal studies
15. human clinical studies

There are a few other sections of your 510k and CE marking submissions that are nearly identical:

• device description
• labeling

How to organize your medical device files when combining 510k with CE marking

The new FDA eSTAR has a unique PDF template that must be used for organizing your submission but Patrick Axtell, the person that helped create the FDA eSTAR templates, is also the Coordinator for the IMDRF Regulated Product Submission Working Group. He has inserted links in the eSTAR sections that cross-reference to the Regulated Product Submission Table of Content (i.e., RPS ToC). Therefore, best practice is to organize your medical device file in accordance with the RPS ToC:

1. Non-In Vitro Diagnostic Device Regulatory Submission Table of Contents (nIVD ToC)

2. In Vitro Diagnostic Medical Device Regulatory Submission Table of Contents (IVD ToC)

Identify sections unique to an FDA eSTAR 510k

There are only a few sections of the FDA eSTAR 510k that are unique. The following is a list of those sections:

• Substantial Equivalence Comparison Table – only table is required with FDA eSTAR
• Truthful and Accuracy Statement – template is provided by the FDA
• 510(k) Summary – automatically generated by the FDA eSTAR
• User Fee Cover Sheet Form 3601 – generated by the FDA DFUF website when you pay the FDA user fee
• Declarations of Conformity – automatically generated by the FDA eSTAR (unless you are only partially compliant with a standard)

Technical Files for CE Marking also have a few unique sections, such as:

• GSPR Checklist
• Classification Rationale
• CE Marking Application to Notified Body
• Declaration of Conformity
• Table of Contents (i.e., TF Index)

Combining 510k with CE marking – how to construct your regulatory plan

In one of my previous blogs, I explained how the new FDA eSTAR template as a project management tool to verify that all of the section of a 510k submission are complete. Unfortunately, there is no CE Marking equivalent, but you can use your TF/MDR Index as a project management tool when you are constructing a combined plan for a 510k submission and CE Marking. The first step is to create a Index based on a recognized standard (EN standard or ISO standards). Historically we used the GHTF guidance document released by study group 1: N011:2008. When the EU MDR came into force, we added cross-references to the EU MDR in our TF/MDR Index. The GHTF guidance mirrors the format required in Annex III of the new EU MDR. I do not recommend using the NB-MED 2.5.1/rec 5 guidance document. Even though the content is similar to the GHTF guidance, the format is quite different. There is also a new IMDRF guidance document for Essential Principles of Safety and Performance that you should consider referencing.

Project and task management for your combined regulatory plan

If you are going to outsource sections of either submission, the sections should be written and reviewed by someone familiar with both types of submissions. The headers and footers will be unique to the type of submission, but I write the text in Google Docs without formatting for ease of sharing and so I can use my Chromebook.

If you have an in-house team that prepares your 510k submissions and Technical Files, you might consider training the people responsible for each section on the requirements for each type of submission. This eliminates rewriting and reformatting later. I like to assign who is writing each section in a separate column of my project management software. Then I will sort the sections by the expected date of completion. All the safety and performance testing, and any sections requiring validation, will typically be finished at the end of the project. Therefore, it is important to dedicate unique resources to those sections rather than asking one person to write several of those sections. You also will want to make sure any supporting documentation they need is completed early so that the project’s critical path doesn’t change.

Additional training for combining 510k with CE marking

We provide an on-demand  510k course series consisting of 33 FDA eSTAR webinars that you can purchase as a bundle or individually. We also have various training webinars about CE marking on our webinars page.

This article reviews the top reasons why other companies feel requesting FDA pre-sub meetings is a waste of time but you can’t afford to.

It only takes our consulting team a few hours to prepare an FDA pre-sub request using the new FDA PreSTAR. The FDA does not charge you a cent for submitting an FDA pre-sub, and a pre-sub should be part of every design plan. However, most companies are resistant to requesting FDA pre-sub meetings. In this article we review the top four reasons why companies resist submitting an FDA pre-sub request, and you will learn about the three options for the method of FDA feedback.

Our design is not finalized yet

The most common reason why people delay their request for an FDA pre-sub is that they are waiting until the design is complete. This rationale is flawed because the FDA can’t review data and the FDA can’t give you advice on the design of your device. The purpose of an FDA pre-sub is to “forge a better test plan.” The FDA prefers that you submit draft test protocols with specific questions. The ideal time to submit an FDA pre-sub request is 6-9 months before you approve your design outputs (i.e., design freeze). This timing should be shortly after you approve your design inputs (i.e., essential requirements for safety and performance, standards, and stakeholder requirements). Another reason for requesting a pre-sub early is that most companies need to submit a pre-sub supplement with a revised test plan. This is especially true for biocompatibility testing, non-clinical, benchtop performance testing plans, pre-clinical animal testing, human clinical studies, and human factors testing. The revised test plan includes protocol revisions based on the feedback from the original pre-sub.

It’s too late to request FDA pre-sub meetings

If you are less than a week away from submitting to the FDA, it is too late. The FDA target for scheduling an FDA pre-sub meeting is 70-75 days from the date your request was submitted. That’s 10-11 weeks. Most companies tell me that they plan to submit to the FDA within weeks or a couple of months, but most of the companies take nine months or longer. For example, what if your device fails EMC testing, and you have to change the design and retest for both EMC and electrical safety at an NRTL? At best, you will have an 8-week delay. If you submit a request next week, and everything goes as planned, you can always withdraw your request for the pre-sub. If you encounter a delay for any reason, suddenly, it’s not too late.

We don’t want to be bound by what the FDA says in the FDA pre-sub meeting

FDA pre-sub meetings are “non-binding.” That means that the FDA can change its mind, but it also means you don’t have to do everything the FDA says in an FDA pre-sub meeting. If you don’t ask a question about testing requirements, that doesn’t mean that the FDA does not have any testing requirements. The FDA knows what previous companies have submitted for testing better than you do, and they may be in the process of evaluating draft guidance documents. If you ask questions, you will have better insights into what the FDA expects. The most important questions are related to your rationale for why a specific testing specimen represents the “worst-case” for one of your tests. Selecting the wrong testing specimen will result in you repeating that test. Understanding FDA expectations helps you write better rationales for testing or test avoidance. You also might learn about deadlines for the implementation of new testing requirements that you might be able to avoid. Finally, you can ask the FDA about possible testing options you are considering if the FDA denies your most optimistic testing plans.

There is already a guidance document for our device

Not all device classifications have a guidance document explaining what information should be submitted in an FDA pre-market submission. However, there are almost one hundred Special Controls Guidance Documents, and for new device regulations (i.e., De Novo applications) the FDA now incorporates the special controls directly in the new regulation. Therefore, there is a good chance that the FDA published special controls as part of the regulation for your device or as a guidance document. As part of the special controls, the FDA defines what performance testing is required for your device. If you already know what testing is required, then the value in requesting FDA pre-sub meetings is diminished. But at least three other key benefits remain.

First, you can verify that the predicate you plan to use for comparative testing is not going to be a problem. Although the FDA can’t tell you which predicate to pick, the FDA can tell you if there is a problem with the predicate you have selected. This is especially important if the product is not currently registered and listed, because you may not know if the device was withdrawn from the market after it was cleared.

Second, not all testing standards are prescriptive. Many tests have testing options that require a decision. Input from the FDA may be valuable in making choices between various performance testing options. Sometimes, you forgo testing and provide a rationale instead. FDA feedback on any rationale for not doing testing is critical to prevent delays and requests for additional information later.

Third, there are many different FDA representatives who participate in FDA pre-sub meetings. The lead reviewer will invite specialists and the branch chief to the meeting. Each of these specialists can answer questions during a pre-submission meeting that they are not able to answer during the actual review process. You also have the opportunity to get feedback from the branch chief–who has insight from all the previous devices that were cleared with your product classification. Your lead reviewer is not likely to be as experienced as the branch chief, and may only have been working at the FDA for months. Your request for the 510k pre-sub meeting will help an inexperienced lead reviewer as much as it will help your company.

Which method of FDA pre-sub feedback should you request?

The FDA offers three different options for the method of feedback in pre-sub request:

1. a face-to-face meeting
2. a conference call
3. an email response

Feedback Option 1 – A Face-to-Face Meeting

Some executives believe that face-to-face meetings are critical in establishing relationships with people. However, you need to understand the culture of the people you are trying to build a relationship with. The FDA is an overworked bureaucracy, and government agencies have security concerns. When the FDA meets with visitors they must go to a different building and arrange for their guests to pass through security. This is more work and takes more time. To justify the extra work and time, you need a compelling reason why a face-to-face meeting with the FDA is necessary.

Traveling to the FDA will cost your team money and time that conference calls and emails will not. More importantly, you are limited to one hour for a pre-submission meeting. One hour is barely enough time to ask questions and listen to the answers. You only have minutes to introduce your company and your team and describe the product. There is no time for relationship building. The best way to impress the FDA is to 1) prepare thoroughly, 2) conduct an efficient meeting, and 3) ask smart questions.

There is one time when you should visit the FDA face-to-face–if you have a powerful demonstration and video just isn’t good enough.

Feedback Option 2 – Conference Call

Conference calls save you time and money, but conference calls also save the FDA time and effort. You won’t personally meet people from the agency, but you can communicate information prior to the meeting and you can provide videos of simulated use for your device. Conference calls do have the advantage of allowing you to mute the call for a moment and make a comment among your team members without the agency listening as well. Whenever you are discussing a performance testing plan or a clinical study protocol with the FDA, you will probably want a conference call to enable clarification questions. The image below is an example of a request for a teleconference as the method of feedback. The FDA will still send an email response to your questions within 70 days, and you will want to submit your presentation slide deck for the teleconference at least 48 hours before the teleconference.

Feedback option 3 – Email

Email responses from the FDA are highly underrated in value. When you specify an email response, you generally receive a response to your questions sooner. You also should receive more information, because each person from the agency is able to provide an hour of their time to write detailed feedback. In a conference call, you are speaking for part of the hour, and only one person from the FDA can speak at a time. Therefore, you almost always have less feedback during conference calls and face-to-face meetings. The primary downside to email as a feedback method is that it is not interactive. In the case of submission issue review (SIR) requests (i.e., a special type of FDA pre-sub request), the FDA will only give you the option of a teleconference or email feedback–not both. Due to the challenges of scheduling teleconference, sometimes an email response can be delivered sooner and might be your best choice for an SIR request.

Learning More about FDA Pre-sub Meetings

If you would like to learn more about how to prepare the format and contents of an FDA pre-sub request, we have a four-part webinar series that will teach you how to prepare a pre-submission meeting request using the new FDA PreSTAR template.

The FDA released a new draft 510k predicate selection guidance on September 7, but the draft guidance proposes controversial additions.

On September 7, 2023, a draft predicate selection guidance document was released by the FDA. Normally the release of a new draft of FDA guidance documents is anticipated and there is an obvious need for the draft. This new draft, however, appears to include some controversial additions that I feel should be removed from the guidance. This specific guidance was developed to help submitters use best practices in selecting a predicate. There is some useful advice regarding the need to review the FDA database for evidence of use-related and design-related safety issues associated with a potential predicate that is being considered. Unfortunately, the last section of the guidance suggests some controversial recommendations that I strongly disagree with.

Please submit comments to the FDA regarding this draft guidance

This guidance is a draft. Your comments and feedback to the FDA will have an impact on FDA policy. We are preparing a redlined draft of the guidance with specific comments and recommended changes. We will make the comments and feedback available for download from our website on our predicate selection webinar page. We are also creating a download button for the original draft in Word (.docx) format, and sharing the FDA instructions for how to respond.

Section 1 – Introduction to the guidance

The FDA indicates that this new draft predicate selection guidance document was created to provide recommendations to implement four (4) best practices when selecting a predicate device to support a 510k submission. This first objective is something that our consulting firm recommended in a training webinar. The guidance indicates that the guidance was also created by the FDA in an attempt to improve the predictability, consistency, and transparency of the 510k pre-market review process. This second objective is not accomplished by the draft guidance and needs to be modified before the guidance is released as a final guidance.

Section 2 – Background

This section of the guidance is divided into two parts: A) The 510k Process, and B) 510k Modernization.

A. The 510k Process

The FDA released a Substantial Equivalence guidance document that explains how to demonstrate substantial equivalence. The guidance document includes a new decision tree that summarizes each of the six questions that 510k reviewers are required to answer in the process of evaluating your 510k submission for substantial equivalence. The evidence of substantial equivalence must be summarized in the Predicates and Substantial Equivalence section of the FDA eSTAR template in your 510k submission, and the guidance document reviews the content that should be provided.

Substantial equivalence is evaluated against a predicate device or multiple predicates. To be considered substantially equivalent, the subject device of your 510k submission must have the same intended use AND the same technological characteristics as the predicate device. Therefore, you cannot use two different predicates if one predicate has the same intended use (but different technological characteristics), and the second predicate has the same technological characteristics (but a different intended use). That’s called a “split predicate,” and that term is defined in the guidance This does not prohibit you from using a secondary predicate, but you must meet the requirements of this guidance document to receive 510k clearance. The guidance document reviews five examples of multiple predicates being used correctly to demonstrate substantial equivalence.

B. 510k Modernization

The second part of this section refers to the FDA’s Safety Action Plan issued in April 2018. The announcement of the Safety Action Plan is connected with the FDA’s announcement of actions to modernize the 510k process as well. The goals of the FDA Safety Action Plan consist of:

1. Establish a robust medical device patient safety net in the United States
2. Explore regulatory options to streamline and modernize timely implementation of postmarket mitigations
3. Spur innovation towards safer medical devices
4. Advance medical device cybersecurity
5. Integrate the Center for Devices and Radiological Health’s (CDRH’s) premarket and postmarket offices and activities to advance the use of a TPLC approach to device safety 

Examples of modernization efforts include the following:

• Conversion of the remaining Class 3 devices that were designated for the 510k clearance pathway to the PMA approval process instead
• Use of objective performance standards when bringing new technology to the market
• Use of more modern predicate devices (i.e., < 10 years old)

In this draft predicate selection guidance, the FDA states that feedback submitted to the docket in 2019 has persuaded the FDA to acknowledge that focusing only on modern predicate devices may not result in optimal safety and effectiveness. Therefore, the FDA is now proposing the approach of encouraging best practices in predicate selection. In addition, the draft guidance proposes increased transparency by identifying the characteristics of technological characteristics used to support a 510k submission.

The FDA did not mention an increased emphasis on risk analysis or risk management in the guidance, but the FDA is modernizing the quality system regulations (i.e., 21 CFR 820) to incorporate ISO 13485:2016 by reference. Since ISO 13485:2016 requires the application of a risk-based approach to all processes, the application of a risk-based approach will also impact the 510k process in multiple ways, such as design controls, supplier controls, process validation, post-market surveillance, and corrective actions. 

Section 3 – Scope of the predicate selection guidance

The draft predicate selection guidance indicates that the scope of the guidance is to be used in conjunction with the FDA’s 510k program guidance. The scope is also not intended to change to applicable statutory or regulatory standards. 

Section 4 – How to use the FDA’s predicate selection guidance

The FDA’s intended use of the predicate selection guidance is to provide submitters with a tool to help them during the predicate selection process. This guidance suggests a specific process for predicate selection. First, the submitter should identify all of the possible legally marketed devices that also have similar indications for use. Second, the submitter should exclude any devices with different technological characteristics if the differences raise new or different issues of risk. The remaining sub-group is referred to in the guidance as “valid predicate device(s).” The third, and final, step of the selection process is to use the four (4) best practices for predicate selection proposed in the guidance. The diagram below provides a visual depiction of the terminology introduced in this guidance.

Section 5 – Best Practices (for predicate selection)

The FDA predicate selection guidance has four (4) best practices recommended for submitters to use when narrowing their list of valid predicate devices to a final potential predicate(s). Prior to using these best practices, you need to create a list of legally marketed devices that could be potential predicates. The following FDA Databases are the most common sources for generating a list of legally marketed devices:

• Registration & Listing Database
  • Trade names of similar devices (i.e., proprietary name)
  • Manufacturer(s) of similar devices (i.e., owner operator name)
• 510k Database
  • 510k number of similar devices
  • Applicant Name (i.e., owner operator name) of similar devices
  • Device Name (i.e., trade name) of similar device
• Device Classification Database
  • Device classification name of similar devices
  • Product Code of similar devices
  • Regulation Number of similar devices

Our team usually uses the Basil Systems Regulatory Database to perform our searches. Basil Systems uses data downloaded directly from the FDA, but the software gives us four advantages over the FDA public databases:

1. The search engine uses a natural-language algorithm rather than a Boolean search.
2. The database is much faster than the FDA databases.
3. The results include analytics regarding the review timelines and a “predicate tree.”
4. Basil Systems also has a post-market surveillance database that includes all of the FDA adverse events and recall data, but it also includes access to data from Health Canada and the Australian TGA.

A. Predicate devices cleared using well-established methods

Some 510k submissions use the same methods used by a predicate device that was used for their substantial equivalence comparison, while other devices use well-established methods. The reason for this may have been that the 510k submission preceded the release of an FDA product-specific, special controls guidance document. In other cases, the FDA may not have recognized an international standard for the device classification. You can search for recognized international standards associated with a specific device classification by using the FDA’s recognized consensus standards database. An example is provided below.

New 510k submissions should always use the methods identified in FDA guidance documents and refer to recognized international standards instead of copying the methods used to support older 510k submissions that predate the current FDA guidance or recognized standards. The problem with the FDA’s proposed approach is that the FDA is implying that a device that was not tested to the current FDA guidance or recognized standards is inherently not as safe or effective as another device that was tested to the current FDA guidance or recognized standards. This inference may not be true. Therefore, even though this may be a consideration, it is not appropriate to require manufacturers to include this as a predicate selection criterion. The FDA is already taking this into account by requiring companies to comply with the current FDA guidance and recognized standards for device description, labeling, non-clinical performance testing, and other performance testing. An example of how the FDA PreSTAR automatically notifies you of the appropriate FDA special controls guidance for a product classification is provided below.

B. Predicate devices meet or exceed expected safety and performance

This best practice identified in the FDA predicate selection guidance recommends that you search through three different FDA databases to identify any reported injury, deaths, or malfunctions of the predicate device. Those three databases are:

1. MAUDE Database
2. MDR Database
3. MedSun Database

All of these databases are helpful, but there are also problems associated with each database. In general, adverse events are underreported, and a more thorough review of post-market surveillance review is needed to accurately assess the safety and performance of any device. The MAUDE data represents reports of adverse events involving medical devices and it is updated weekly. The data consists of all voluntary reports since June 1993, user facility reports since 1991, distributor reports since 1993, and manufacturer reports since August 1996. The MDR Data is no longer updated, but the MDR database allows you to search the CDRH database information on medical devices that may have malfunctioned or caused a death or serious injury during the years 1992 through 1996. Medical Product Safety Network (MedSun) is an adverse event reporting program launched in 2002 by CDRH. The primary goal for MedSun is to work collaboratively with the clinical community to identify, understand, and solve problems with the use of medical devices. The FDA predicate selection guidance, however, does not mention the Total Product Life Cycle (TPLC) database which is a more efficient way to search all of the FDA databases–including the recall database and the 510k database.

The biggest problem with this best practice as a basis for selecting a predicate is that the number of adverse events depends upon the number of devices used each year. For a small manufacturer, the number of adverse events will be very small because there are very few devices in use. For a larger manufacturer, the number of adverse events will be larger–even though it may represent less than 0.1% of sales. Finally, not all companies report adverse events when they are required to, while some companies may over-report adverse events. None of these possibilities is taken into consideration in the FDA’s draft predicate selection guidance.

C. Predicate devices without unmitigated use-related or design-related safety issues

For the third best practice, the FDA predicate selection guidance recommends that submitters search the Medical Device Safety database and CBER Safety & Availability (Biologics) database to identify any “emerging signals” that may indicate a new causal association between a device and an adverse event(s). As with all of the FDA database searches, this information is useful as an input to the design process, because it helps to identify known hazards associated with similar devices. However, a more thorough review of post-market surveillance review is needed to accurately assess the safety and performance of any device–including searching databases from other countries where similar devices are marketed.

D. Predicate devices without an associated design-related recall

For the fourth best practice, the FDA predicate selection guidance recommends that submitters search the FDA recalls database. As stated above, the TPLC database includes this information for each product classification. Of the four best practices recommended by the FDA, any predicate device that was to a design-related recall is unlikely to be accepted by the FDA as a suitable predicate device. Therefore, this search should be conducted during the design planning phase or while design inputs are being identified. If you are unable to identify another predicate device that was not the subject of a design-related recall, then you should request a pre-submission meeting with the FDA and provide a justification for the use of the predicate device that was recalled. Your justification will need to include an explanation of the risk controls that were implemented to prevent a similar malfunction or use error with your device. Often recalls result from quality problems associated with a supplier that did not make a product to specifications or some other non-conformity associated with the assembly, test, packaging, or labeling of a device. None of these problems should automatically exclude the use of a predicate because they are not specific to the design.

Section 6 – Improving Transparency

This section of the FDA predicate selection guidance contains the most controversial recommendations. The FDA is proposing that the 510k summary in 510k submissions should include a narrative explaining their selection of the predicate device(s) used to support the 510k clearance. This would be a new requirement for the completion of a 510k summary because that information is not currently included in 510k summaries. The new FDA eSTAR has the ability to automatically generate a 510k summary as part of the submission (see example below), but the 510k summary generated by the eSTAR does not include a section for including a narrative explaining the reasons for predicate selection.

The FDA added this section to the draft guidance with the goals of improving the predictability, consistency, and transparency of the 510k pre-market review process. However, the proposed addition of a narrative explaining the reasons for predicate selection is not the best way to achieve those goals. Transparency is best achieved by eliminating the option of a 510k statement (i.e., 21 CFR 807.93). Currently, the 510k process allows for submitters to provide a 510k statement or a 510k summary. The 510k statement prevents the public from gaining access to any of the information that would be provided in a 510k summary. Therefore, if the narrative explaining the reasons for predicate selection is going to be required in a 510k submission, that new requirement should be added to the substantial equivalence section of the eSTAR instead of only including it in the 510k summary. If the 510k statement is eliminated as an option for submitters, then all submitters will be required to provide a 510k summary and the explanation for the predicate selection can be copied from a text box in the substantial equivalence section.

The FDA eSTAR ensures consistency of the 510k submission contents and format, and tracking of FDA performance has improved the consistency of the FDA 510k review process. Adding an explanation for predicate selection will not impact either of these goals for improving the 510k process. In addition, companies do not select predicates only for the reasons indicated in this FDA predicate selection guidance. One of the most common reasons for selecting a predicate is the cost of purchasing samples of predicate devices for side-by-side performance testing. This only relates to cost, not safety or performance, and forcing companies to purchase more expensive devices for testing would not align with the least burdensome approach. Another flaw in this proposed additional information to be included in the 510k summary is that there is a huge variation in the number of predicates that can be selected for different product classifications. For example, 319 devices were cleared in the past 10 years for the FLL product classification (i.e., clinical electronic thermometer), while 35 devices were cleared in the past 10 years for the LCX product classification (i.e., pregnancy test). Therefore, the approach to selecting a predicate for these two product classifications would be significantly different due to the number of valid predicates to choose from. This makes it very difficult to create a predictable or consistent process for predicate selection across all product classifications. There may also be confidential, strategic reasons for predicate selection that would not be appropriate for a 510k summary.

Section 7 – Examples

The FDA predicate selection guidance provides three examples. In each example, the FDA is suggesting that the submitter should provide a table that lists the valid predicate devices and compare those devices in a table using the four best practices as criteria for the final selection. The FDA is positioning this as providing more transparency to the public, but this information presented in the way the FDA is presenting it would not be useful to the public. This is creating more documentation for companies to submit to the FDA without making devices safer or improving efficacy. This approach would be a change in the required content of a 510k summary and introduce post-market data as criteria for 510k clearance. This is a significant deviation from the current FDA policy.

Example 1 from predicate selection guidance

In this example, the submitter included a table in their 510k submission, along with their rationale for selecting one of the four potential predicates as the predicate device used to support their 510k submission. This example is the most concerning because the summary doesn’t have any details regarding the volume of sales for the potential predicates being evaluated. The number of adverse events and recalls is usually correlated with the volume of sales. The proposed table doesn’t account for this information.

Example 2 from predicate selection guidance

In this example, the submitter was only able to identify one potential, valid predicate device. The submitter provided a table showing that the predicate did not present concerns for three of the four best practices, but the predicate was the subject of a design-related recall. The submitter also explained the measures taken to reduce the risk of those safety concerns in the subject device. As stated above, using the occurrence of a recall as the basis for excluding a predicate is not necessarily appropriate. Most recalls are initiated due to reasons other than the design. Therefore, you need to make sure that the reason for the recall is design-related rather than a quality system compliance issue or a vendor quality issue.

Example 3 from predicate selection guidance

In this example, the submitter identified two potential, valid predicate devices. No safety concerns were identified using any of the four best practices, but the two potential devices have different market histories. One device has 15 years of history, and the second device has three years of history. The submitter chose the device with 15 years of history because the subject device had a longer regulatory history. The problem with this approach is that years since clearance is not an indication of regulatory history. A device can be cleared in 2008, but it might not be launched commercially until several years later. In addition, the number of devices used may be quite small for a small company. In contrast, if the product with three years since the 510k clearance is distributed by a major medical device company, there may be thousands of devices in use every year. 

Medical Device Academy’s recommendations for predicate selection

The following information consists of recommendations our consulting firm provides to clients regarding predicate selection.

Try to use only one predicate (i.e., a primary predicate)

Once you have narrowed down a list of predicates, we generally recommend only using one of the options as a primary predicate and avoiding the use of a second predicate unless absolutely necessary. If you are unsure of whether a second predicate or reference device is needed, this is an excellent question to ask the FDA during a pre-submission teleconference under the topic of “regulatory strategy” (see image below). In your PreSTAR you can ask the following question, “[Your company name] is proposing to use [primary predicate] as a primary predicate. A) Does the FDA have any concerns with the predicate selection? B) Does the FDA feel that a secondary predicate or reference device is needed?”

When and how to use multiple predicates

Recently a client questioned me about the use of a secondary predicate in a 510k submission that I was preparing. They were under the impression that only one predicate was allowed for a 510k submission because the FDA considers the two predicate devices to be a “split predicate.” The video provided above explains the definition of a “split predicate,” and the definition refers to more than the use of two predicates. For many of the 510k submissions, we prepared and obtained clearance for used secondary predicates. An even more common strategy is to use a second device as a reference device. The second device may only have technological characteristics in common with the subject device, but the methods of safety and performance testing used can be adopted as objective performance standards for your 510k submission.

When you are trying to use multiple predicate devices to demonstrate substantial equivalence to your subject device in a 510k submission, you have three options for the correct use of multiple predicate devices:

1. Two predicates with different technological characteristics, but the same intended use.
2. A device with more than one intended use.
3. A device with more than one indication under the same intended use.

If you use “option 1”, then your subject device must have the technological characteristics of both predicate devices. For example, your device has Bluetooth capability, and it uses infrared technology to measure temperature, while one of the two predicates has Bluetooth but uses a thermistor, and the other predicate uses infrared measurement but does not have Bluetooth.

If you use “option 2”, you are combining the features of two different devices into one device. For example, one predicate device is used to measure temperature, and the other predicate device is used to measure blood pressure. Your device, however, can perform both functions. You might have chosen another multi-parameter monitor on the market as your predicate, however, you may not be able to do that if none of the multi-parameter monitors have the same combination of intended uses and technological characteristics. This scenario is quite common when a new technology is introduced for monitoring, and none of the multi-parameter monitors are using the new technology yet.

If you use “option 3”, you need to be careful that the ability of your subject device to be used for a second indication does not compromise the performance of the device for the first indication. For example, bone fixation plates are designed for the fixation of bone fractures. If the first indication is for long bones, and the second indication is for small bones in the wrist, the size and strength of the bone fixation plate may not be adequate for long bones, or the device may be too large for the wrist.