FDA 510(k) Explained: A Basic Guide to Premarket Notification

Written by The FDA Group | March 23, 2023

Are you looking to bring a medical device to market that’s equivalent to a device currently on the market but don't know where to start with the FDA 510(k) submission process? Do you want to avoid costly and time-consuming mistakes in your premarket notification?

This brief guide provides guidance on 510(k) submissions. Knowing device manufacturers routinely seek the assistance of knowledgeable regulatory experts in preparing 510(k) submissions, this guide has been expertly crafted with the help of our regulatory affairs consultants, who have helped many firms clear their devices for the U.S. market.

Our consultants have generously shared their insights, tips, and practical advice to help you understand the key requirements, avoid common oversights, and maximize your chances of success. This guide is essential for medical device manufacturers looking to navigate the premarket notification process confidently.

Read our companion guide for a deeper dive into the 20 components of a 510(k) submission document, specifically.

Need expert help navigating the premarket notification process? Learn more about our 510(k) consulting services and contact us today to rapidly access the industry’s top regulatory talent.

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Guiding 510(k) Preparation and Submission for U.S. Medical Device Market Clearance

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The Basics of the 510(k) Regulatory Pathway

What is the 510(k)?

The 510(k) regulatory pathway is a submission process that medical device manufacturers use to get clearance from the FDA to market an eligible product in the U.S. Under the 510(k) pathway, a medical device manufacturer submits a premarket notification to the FDA, which includes information about the device's intended use, design, and performance characteristics compared to a predicate device.

The goal of the 510(k) submission is to demonstrate that the device is "substantially equivalent" to a device that has already been cleared by the FDA and is in commercial distribution. This is referred to as a "predicate device.” To make this determination, the FDA reviews the 510(k) submission to ensure that the device is equivalent to the predicate and performs as intended.

Once the FDA determines that the device is substantially equivalent to a predicate device, the agency will issue a clearance letter that allows the manufacturer to market the device in the United States. It’s important to note that clearance under the 510(k) pathway does not indicate that the FDA has approved the device but rather that the FDA has determined the device is equivalent to a similar device already on the market.

Read our other guide for more information about 510(k)s vs. PMAs.

▶️ Navigating the 510(k) Process: A Q&A with Regulatory Consultant Trey Thorsen, MS, RAC

Watch our interview with regulatory affairs consultant Trey Thorsen, MS, RAC, who answers some common questions regarding the 510(k) process:

Eligibility criteria for 510(k) clearance

To be eligible for 510(k) clearance, a medical device must meet specific criteria, which we’ve identified and briefly summarized below.

Note: The list below is not exhaustive. There may be other factors to consider depending on the regulatory environment and the specific device. To navigate these complexities, medical device companies frequently collaborate with regulatory consultants who are experienced in this process. A knowledgeable consultant can help determine if a device is eligible for 510(k) clearance and work to ensure that the submission meets all regulatory requirements.

Device Risk Level — To strike a balance between safety and efficiency, the FDA has established three levels of oversight that correspond to the risk level of each device. The first level—low risk—is for devices exempt from premarket submission. The second level—medium risk—is known as Premarket Notification or 510(k), and the third level—high risk—is Premarket Approval (PMA).
- Low-risk devices (generally exempt from premarket notification) include most Class I and select Class II devices.
- Medium-risk devices (510(k)) include mostly Class II devices, with some Class I devices.
- High-risk devices (premarket approval) include Class III devices that sustain or support life, are implanted, or present a potentially unreasonable risk of illness or injury.
Device Type — Certain types of devices are not eligible for the 510(k) clearance process. For example, devices intended for use as a component of another device, custom devices, and devices intended for investigational use are not eligible for 510(k) clearance.
Device History — The device must not have a history of being banned, withdrawn, or subject to restrictions by the FDA. The device must not have been previously rejected for 510(k) clearance or premarket approval.
Device Characteristics — The device must not pose an unreasonable risk to public health or safety and must be manufactured in accordance with the 21 CFR 820 Quality System Regulation (QSR). The device must also meet applicable performance standards, such as those established by the FDA or international standards organizations.
Substantial Equivalence — The device must be "substantially equivalent" to a legally marketed medical device, known as a "predicate device," that was already cleared by the FDA.

Key requirements for a successful 510(k) submission

A successful 510(k) is the result of several requirements being met.

Some of these are more or less obvious and flow directly from the eligibility criteria described above. Others are less obvious, underscoring the importance of seeking the guidance of a knowledgeable regulatory consultant who knows exactly what the FDA is looking for and can prepare documentation to satisfy those expectations in extreme detail from day one.

Understanding of the device classification — Medical device manufacturers must determine the correct device classification and understand the associated regulatory requirements. This information is critical in determining the appropriate type of 510(k) submission to make.
Proper documentation of the device design — Detailed documentation of the device design and how it works is a critical component of the 510(k) submission. The documentation must include drawings, schematics, and a description of the device's intended use and performance.
Selection of the most appropriate predicate device — The 510(k) submission must include a comparison of the device under consideration to a predicate device already on the market. The selected predicate device must be similar in design, intended use, and technology.
Demonstration of substantial equivalence — The 510(k) submission must include evidence demonstrating that the device is substantially equivalent to the predicate device and does not raise new questions in terms of safety and effectiveness.
Adequate labeling and instructions for use — The labeling and instructions for use must be complete and accurate and provide adequate information for the safe use of the device to the user.
Adequate testing — Adequate testing must be performed to demonstrate the device's compliance to all applicable standards. The testing must be comprehensive and appropriate for the type of device and the intended use.
Complete and accurate data — The data included in the 510(k) submission must be complete, accurate, and well-organized. The FDA will not accept submissions that are incomplete or contain false or misleading information.

The Special 510(k)

“A Special 510(k) would generally not be appropriate for devices that manufacture a biological product at the point of care, because there would likely be no well-established method to evaluate such changes and/or the performance data would not be reviewable in a summary or risk analysis format”

FDA Special 510(k) Guidance

The FDA recommends device companies consider these key questions when considering whether a device should pursue the Special 510(k) program:

Is it a change to the manufacturer’s own device? If not, a Special 510(k) is not the appropriate pathway.
Are performance data needed to evaluate the change? According to the current Special 510(k) guidance, “in cases where manufacturers determine under their design control procedures that no additional verification or validation testing is necessary to evaluate a change that otherwise requires submission and clearance of a 510(k), manufacturers may submit these changes as a Special 510(k) with a clear rationale supporting their conclusion that no performance data are necessary.”
Is there a well-established method to evaluate the change? If not, a Special 510(k) is not the appropriate pathway.
Can the data be reviewed under a summary or risk-analysis format? If not, a Special 510(k) is not the appropriate pathway.

Page 13 of the Special 510(k) guidance document also provides a number of scenarios under which the FDA believes it’s not appropriate to submit a Special 510(k).

Some of these scenarios include:

When evaluation of the change(s) to the device generally involves greater than three scientific disciplines (e.g., biocompatibility, sterility, electromagnetic compatibility).
For multiple devices with unrelated changes as described in the FDA guidance: Bundling Multiple Devices or Multiple Indications in a Single Submission.
When a recent Quality System inspection has resulted in the issuance of a violative inspection report identifying observations related to design controls that are relevant to the design changes under review in the 510(k). If a manufacturer believes such violations are unrelated to the subject 510(k), they should provide a rationale for why the 510(k) should still be appropriate for review under the Special 510(k) Program.

Appendix A of the guidance outlines the recommended content of the Special 510(k) submission. Appendix B provides examples of changes and steps through the questions excerpted above for each change, which can help determine if your device change(s) qualify for a Special 510(k).

510(k) Review Process and Timeline

Day 1	Within 7 days	By day 15
The FDA receives 510(k) application.	The FDA sends an Acknowledgement Letter or a Hold Letter if there are issues with user fees and/or eCopy.	The FDA conducts an Acceptance Review. FDA informs the applicant if 510(k) is accepted for Substantive Review or placed on RTA Hold.
By day 60	By day 90	By day 100
The FDA conducts a Substantive Review. The FDA communicates Substantive Interaction with the applicant that indicates whether the FDA will proceed with an Interactive Review or ask for Additional Information.	The FDA sends final MDUFA Decision on 510(k).	If an MDUFA Decision is not reached by day 100, the FDA provides a Missed MDUFA Decision Communication that identifies any outstanding review issues.

Common 510(k) Challenges

Before discussing best practices, it’s important to highlight the common pitfalls that lead to delays and refusals. This is by no means an exhaustive list—but rather a sample of just some of the problems that can be avoided by working with the right regulatory consultant.

Challenge #1: Not having a complete understanding of the 510(k) submission process. While this can be a problem for all companies, startups, smaller firms, and those new to medical device manufacturing sometimes don’t have a clear understanding of the important intricacies of the process. Expert guidance from an experienced regulatory professional is critical.

Challenge #2: Not successfully demonstrating substantial equivalence. As stated before, to be eligible for clearance via this regulatory pathway, a device must demonstrate substantial equivalence to a legally marketed device, known as a predicate device. This can be a common area for oversight, as some manufacturers struggle to find an appropriate predicate device.

Challenge #3: Not providing sufficient documentation. The 510(k) submission should be accompanied by complete, detailed, and well-organized documentation that supports the safety and effectiveness of the device. This includes, but is not limited to, data on device design, materials, and manufacturing processes. Often, what appears to be sufficient documentation to the company, is, in fact, not sufficient for the FDA. An experienced consultant should have the firsthand experience to read between the lines of stated guidances and understand what, specifically, the FDA expects so that knowledge can be applied when crafting the submission. Additionally, manufacturers need to have a clear understanding of relevant biocompatibility and performance testing requirements when relevant.

Challenge #4: Not proactively anticipating the FDA’s questions or concerns. The FDA will likely have questions or concerns about the device, making it important for the manufacturer to anticipate these and provide clear and convincing responses. Again, without the guidance of an experienced regulatory consultant, it can be difficult, if not impossible, to expect what these questions will be and respond to them effectively (and proactively).

Challenge #5: Failing to write for FDA reviewers. One common mistake medical device companies make when submitting a 510(k) application is not communicating effectively with the FDA reviewers. Engineers who develop the device often assume that the FDA has the same technical understanding of the device, which is rarely the case. While FDA reviewers may have a general understanding, they may not have the same level of technical expertise on your specific device as your team of engineers. Therefore, it is essential to provide a clear and concise explanation of the device that is understandable to someone who is not as familiar with your device as your team. This is one area where an experienced consultant’s assistance is critical in avoiding delays.

Challenge #6: Not clearly understanding Quality Management System (QMS) factors. Companies need to ensure that their QMS is up-to-date and covers all aspects of the product lifecycle. Design controls almost always need to be included.

Challenge #7: Not allowing sufficient time for the submission process. The 510(k) submission process can take several months, so it is important to allow sufficient time for preparation, review, and potentially additional information requests from the FDA. Too often, manufacturers interpret the timeline incorrectly and think it takes only 90 days. However, in addition to many other important milestones, the FDA has 90 calendar days to review the submission, and this time may be extended if additional information is requested (up to 180 calendar days). If your response is is not complete within the allotted time, the FDA will withdraw the submission, causing further delays and expenses.

Best Practices for 510(k) Submissions

Adhering to best practices in 510(k) submissions is crucial for maximizing the likelihood of clearance by the FDA.

Here are a few reasons why:

Compliance with FDA requirements — Adhering to best practices in 510(k) submissions helps ensure that the submission complies with the FDA's requirements and standards, increasing the likelihood of a successful outcome. The FDA has strict guidelines for the content and format of a 510(k) submission, and adhering to these guidelines can significantly improve the chances of getting a favorable review.
Efficiency — Following best practices in 510(k) submissions can improve efficiency and streamline the review process. This, in turn, can save manufacturers time and money and reduce the risk of delays or submission withdrawals.
Clarity and accuracy — Best practices in 510(k) submissions promote clear and accurate communication between the manufacturer and the FDA. This involves providing complete, accurate, and concise information in a format that is easy for FDA reviewers to comprehend and follow.
Decision-making — Following best practices in 510(k) submissions can enhance the FDA's understanding of the device and its intended use, enabling the agency's reviewers to make an informed decision. This, in turn, increases the likelihood of obtaining clearance.
Substantial equivalence — By adhering to best practices in 510(k) submissions, manufacturers can more effectively demonstrate substantial equivalence of their device to the chosen predicate.

1. Preparing for the submission process

Identifying a predicate device

When preparing a 510(k) submission to the FDA, firms need to consider the selection of a clear predicate device as one of the first steps. This is crucial because the 510(k) process requires demonstrating substantial equivalence to a predicate device that is already on the market.

The device being submitted for clearance should essentially be identical to the predicate device in terms of its indications for use, intended use, and technology. Although it may have some additional features or improvements, these differences should not raise new questions on safety or effectiveness. If firms do not choose a clear predicate device, they must invest more time and resources into finding one.

Special controls, guidance, and software considerations

In addition to selecting a predicate device, any applicable special controls and guidance documents must be considered in the context of the device in question.

These documents provide guidance on the specific tests and requirements that need to be met to demonstrate substantial equivalence to the predicate device. This information can sometimes be gleaned from the predicate device's 510(k) submission, which will provide details on the tests and studies conducted, and, therefore, what the FDA will likely expect from your device. A qualified regulatory consultant will help you navigate these intricacies, many of which may not be apparent.

If the device being submitted has software, specific guidances and risk classifications for software need to be considered. The documentation required for software will vary depending on the risk classification of the software.

Clinical data inclusion

The FDA can require the inclusion of clinical data in a 510(k) submission. This data can be essential for proving that a new device is substantially equivalent to an already existing one, or to confirm that modified uses align with the original device's intended applications.

Even though the FDA has tried to clarify this (as outlined in The 510(k) Program Guidance), there’s often a disconnect between the agency and sponsors. The contention typically arises when sponsors feel non-clinical data should suffice to establish substantial equivalence, a perspective the FDA sometimes contests.

In a bid to improve this, the FDA released a draft guidance detailing instances where clinical data is pivotal for a 510(k) submission. This isn’t just about the standard non-clinical data, like bench performance or biocompatibility testing, but also data from clinical studies.

The guidance outlines four specific scenarios where clinical data becomes a necessity:

When the new device’s indications for use differ from the predicate device.
When the technological characteristics of the new device vary from the predicate device.
When substantial equivalence can’t be established through non-clinical testing.
When newly discovered or escalated risks associated with the predicate device indicate a need for clinical data for the new device.

The draft guidance offers detailed examples for each of the four scenarios, covering both diagnostic (including in vitro) and therapeutic devices. This distinction is crucial given the varied clinical data requirements for these device categories.

The first three scenarios are clear and logical. However, the fourth, a new addition, is more complex. It outlines a case where a new device might need clinical data, even if its predicate didn’t. This can catch sponsors off guard, especially if they’ve reviewed the 510(k) summary of the predicate and found no clinical data requirement.

The guidance advises against using predicate devices associated with newly identified risks. Yet, it recognizes that in some instances, a more recent predicate without these risks might not be available. It attempts to balance the scales by requiring clinical data for new devices in such cases while existing devices might undergo postmarket surveillance or recalls.

There’s a grey area where the need for clinical data isn’t explicit, especially concerning predicate devices. The guidance doesn’t directly answer whether the predicate’s clinical data requirements influence those of the new device.

Here are three additional components of the guidance that are critical for clinical data determinations in 510(k)s:

The guidance outlines the types of clinical data supporting a 510(k), referencing the International Medical Device Regulators Forum’s recommendations (more info here). This data can stem from traditional clinical trials, scientific literature, clinical experience reports, and other sources like registries and medical records.
The guidance also emphasizes the need for adequate justification when using data from a comparable device. With the FDA’s focus on data from the final device, sponsors might benefit from engaging the FDA early to discuss data applicability, allowing time for additional clinical studies if needed. (More on that in the next section.)
Lastly, the guidance acknowledges the possibility of other, unmentioned scenarios where clinical data might be required, and that these requirements can evolve with accumulating device-type information. It can be a valuable resource for sponsors, particularly when they determine the need for clinical data and wish to discuss study designs with the FDA. However, caution is advised if the guidance implies no need for clinical data. In cases of use differences, novel technology, or potential risk profile variations, a pre-submission might be necessary to confirm the FDA’s agreement with the sponsor’s scenario application and the conclusion that clinical data isn’t required for substantial equivalence.

Given the complexity and ambiguity of these critical determinations, a skilled regulatory consultant's support can be invaluable in making sound decisions from the start.

Pre-Submission (or Q-submission)

Pre-Submission, also known as Q-Submission, is a process offered by the FDA to assist companies in identifying potential issues with their device before submitting a 510(k) application.

If a clear predicate device on the market has not been selected, or if other questions need to be addressed, a “Pre-Sub” is encouraged. This process involves the company providing the FDA with a high-level device description, indication for use, intended use, and potential predicates. The company also may want to include a substantial equivalence table with the potential predicate device.

The FDA may provide feedback on the company's strategy for demonstrating substantial equivalence and suggest additional testing or comparison testing requirements. However, the FDA will not provide specific instructions on what the company should do.

The Pre-Sub process is an important step in preparing for the 510(k) submission process, as it can help identify potential issues early on and avoid delays and additional costs. It is recommended to have a regulatory professional or consultant to assist in this process if necessary.

Using pre-sub meetings to determine if the FDA will require clinical data

The pre-sub meeting is the perfect opportunity to engage directly with the FDA to understand from the agency whether it will require clinical data in your 510(k) or not.

Demonstrating substantial equivalence

The foundation of a 510(k) submission is to demonstrate substantial equivalence between the device that is already on the market and the new device that is being submitted. Again, substantial equivalence means that the new device has the same intended use and technological characteristics as the predicate device, and that there are no significant differences between the two devices that raise new questions in terms of safety and effectiveness. A thorough search of the 510(k) database is essential in helping to identify predicate devices that are suitable for comparison.

When writing a 510(k) submission, medical device companies should focus on providing detailed information about the device's intended use, technological characteristics, and explain any differences between the new device and the predicate device.

The submission should include a comparison of the new device and the predicate device based on relevant performance and compliance with applicable performance standards. This comparison should include any bench testing, animal testing, or clinical studies that were conducted by the predciate.

Device firms should also ensure that the 510(k) submission contains all the necessary documentation the FDA expects, including device labeling, instructions for use, and a detailed summary of the device's design and sterilization/shelf life and packaging processes, if applicable. The submission should also include a comprehensive list of any applicable standards, guidelines, or regulations that the device complies with.

Writing a clear and compelling submission

Medical device companies need to communicate effectively with the FDA when submitting a 510(k) premarket notification. It’s important to remember that the FDA reviewers almost certainly will not familiar with the intricacies of your device or its technology as you are. Therefore, it’s essential to provide clear and concise explanations with all the necessary background information and context.

The language used in the submission should be easy to understand and avoid jargon or company-specific terms or acronyms that the FDA may not be familiar with. The submission should also be well-organized, with a clear structure that allows the FDA to navigate and understand its contents easily.

A well-constructed submission will provide a detailed description of the device's intended use and how it works. This description should be written in layperson's terms and include information about the device's indications for use, patient population, and any relevant safety or performance data.

Interpreting the FDA’s feedback

The FDA may provide feedback on the 510(k) submission, which can include requests for additional information or clarification on certain aspects of the submission. Interpreting FDA feedback can be challenging, as their questions and comments may not always be clear or direct. It's important to carefully review their feedback and try to understand their underlying concerns or questions. This may require asking for clarification or further explanation from the FDA reviewer.

A regulatory professional’s expertise is invaluable in helping review and interpret the FDA's feedback. This individual should have experience in working with the FDA and should be familiar with the regulatory requirements for medical devices.

It's also important to respond to the FDA's feedback in a clear and concise manner, addressing their concerns directly and providing any additional information or data that may be needed. This can help to ensure that the review process proceeds smoothly and that the FDA is satisfied with the submission.

Another important consideration when interpreting FDA feedback is to anticipate their questions or concerns ahead of time. This can help to ensure that the submission is comprehensive and addresses all potential issues, reducing the likelihood of additional questions or delays in the review process. Again, this is where an experienced regulatory professional can provide precious guidance.

3. Navigating the review process

Understanding the review process and timeline

One of the biggest blindspots in the 510(k) review process is the review timeline. Firms too often assume they can launch just three months after submitting a 510(k) application. In reality, the timeline is much longer, with a six to nine months review time, depending on how well the 510(k) application is drafted and if any questions arise during the review process.

Another aspect that companies should be aware of is the 180-calendar day period for responding to additional information requests. Failure to factor this into the timeline can lead to misunderstandings and miscommunication, especially with senior-level management expecting a shorter timeline. Setting realistic expectations and communicating them clearly with all parties involved is crucial.

Communicating with professionalism and thoughtfulness

Maintaining professionalism and thoughtfulness throughout the 510(k) review process is also important. Recognize that the FDA’s reviewers are often under time and workload pressures, too, and that their work involves complex decision-making based on a wealth of information. Being cordial and professional in all communications with reviewers is necessary to establish a positive relationship and avoid misunderstandings.

Again, this underscores the importance of clarity in submissions and all communication and being courteous and respectful when responding to reviewers' questions. Firms should avoid appearing defensive or argumentative when responding to questions or comments when disagreements arise. Instead, firms should take the time to understand the reviewer's perspective and respond thoughtfully and clearly.

In cases of a misinterpretation, requesting a phone call or email exchange can help clarify the situation. A phone call can be a more effective way to explain the problem quickly and efficiently, especially when it involves complex information. However, email communication can also be helpful, especially in cases where a record of communication is necessary.

Knowing the registration timeline

Once a device receives clearance, a company has 30 days to register the device with the FDA. If the company is new and has no devices on the market, it must also register as an establishment with the FDA, which incurs an annual fee.

Some firms are surprised to learn that additional fees are involved in this process. However, once the establishment fee is paid, the listing is free, and the company can simply update its profile in the FDA database.

This step lets the FDA know that the device is on the market. Overall, it's important for companies to be aware of these post-submission requirements to comply with FDA regulations and ensure that their devices can be legally sold on the market.

Partnering With the Right Regulatory Consultant

The FDA 510(k) submission process is complex and can be challenging for companies, especially those unfamiliar with the regulatory requirements. Over the many years we've spent helping device firms gain market clearance, we've seen companies realize they need expert help in several areas, including but not limited to the following:

Regulatory strategy — Developing a regulatory strategy that meets FDA requirements and maximizes the chances of clearance. (Success ultimately depends on the quality of the data and information provided.)
Reviewing existing regulations — Reviewing existing regulations and determining the appropriate regulatory pathway for a particular device.
Summarizing test reports — Once test reports are prepared, they must be summarized and applied to the required sections of the 510(k).
Preparation of the submission — Preparing the required 510(k) documentation involves a complex workstream that can be time-consuming and requires a deep understanding of regulatory requirements.
Interaction with the FDA — Providing guidance on preparing and submitting pre-submission documents and scheduling meetings, responding to requests for additional information, and managing other interactions with the FDA.

A qualified regulatory consultant can provide immense value throughout the 510(k) process, helping teams, among other things:

Navigate the complex regulatory landscape with an experienced guide. Regulatory consultants have in-depth knowledge of FDA regulations, guidance documents, and recent enforcement actions that can help device manufacturers understand and interpret the requirements of the FDA. They can also provide insight into FDA reviewers' expectations and preferences, which can help manufacturers avoid common pitfalls and delays in the submission process.

Identify and clear potential roadblocks before they occur. Regulatory consultants can review the device's design, labeling, indications for use, and intended use to ensure that they are consistent with FDA requirements. They can also conduct a gap analysis of existing documentation to identify areas that may require additional information. By identifying and addressing potential roadblocks early in the process, regulatory consultants help device manufacturers avoid costly and time-consuming delays in the approval process.

Maximize the likelihood of a successful submission. Regulatory consultants can provide feedback on the completeness and adequacy of the submission, ensure that all required documentation is included, and make sure that the submission meets FDA requirements. They can also provide guidance on the appropriate predicate device to use and identify potential concerns with the device's labeling or instructions for use. Regulatory consultants can help device manufacturers increase the chances of a successful outcome in the 510(k) process by ensuring that the submission is complete and meets all FDA requirements.

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