Preparing a US FDA Medical Device 510(K) Submission

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1 Preparing a US FDA Medical Device 510(K) Submission If you want to introduce your medical device to the US market, you need to obtain clearance from the FDA. This clearance is obtained from the FDA via a 510(k) submission, also known as Pre-Market Notification. Below are the steps that will be explained in details later on; Step (1): Medical device confirmation and Classification Step (5): Clearance and Registration Step (2): Predicate device finding Step (4): Preparation and Submission of 510(k) application Step (3): Application standard/guidanc e Documents Identification The New 510(k): Recent changes to the process: The 510(k) process became more complicated and time consuming due to the following reasons; The FDA obligated and approved a more structured approach to 510(k) submissions, which includes submission of both paper and electronic copies. The submission must pass the ecopy test before the FDA will accept the submission. The FDA placed the Refuse-to-Accept process, which is intended to assure that the requested data and documents of a 510(k) submission are present and correctly submitted.180 days will be given to correct faults and complete missing data identified in a RTA letter. The FDA reviewers typically subdivide the submission to various sub-reviewers. These sub-reviewers are evaluating the 510(k) submission much more closely than in the past. Before, simply stating that this work was done or providing a high-level summary was

2 sufficient. Now, the FDA is carefully reviewing the actual data and check the details of how it is done. The agency also uses the Additional Information Required (AI) process to request more information. However, the agency recently adopted a one-response requirement for AIs, in which sponsors receive one opportunity to address the FDA s concerns or requests for additional information. Should that response be inadequate or incomplete, the submission may be deleted. Now, we will go through the steps of the 510(k) process in details. Also, we will review the most common mistakes that may delay the 510(k) registration. Step (1): Medical Device Confirmation and Clarification: The first step to obtaining FDA 510(k) clearance is to make sure your product qualifies as a medical device. The definition of a medical device from the Federal Food, Drug, and Cosmetic Act (FD&C) is a product that: 1) Is recognized in the national formulary as a device (rare). 2) Is intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals. 3) Is intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purpose through mechanical action within or on the body. Items 2 and 3 are usually the most relevant. If a product meets the legal definition of a device, then you must determine its classification by searching the device type on the FDA classification database. The FDA s Classification System Divides Medical Devices into Three Classes: Class I: devices posing the lowest risk to patients or users Class II: devices that could harm patients or users if used improperly or malfunction Class III: devices that could severely injure or kill patients or users if used improperly or malfunction. For the most part, Class I devices do not require FDA pre-market clearance or approval for sale in the US. Yet, Class I device manufacturers must still register their products with the agency. Most Class II devices, however, must go through the FDA 510(k) process, while nearly all highrisk Class III devices go through the more rigorous premarket approval (PMA) process. Step (2): Predicate device finding: Market approval in the US is based on establishing substantial equivalence with another cleared device. This requires manufacturers to identify another device already on the market that shares the same intended use and is technologically similar to the device they wish to market. Once the product code is identified, the FDA s 510(k) database can be searched for products that have been cleared under that code. After you find devices that might be useful as predicates, download the 510(k) Summary for each potential predicate (available through the 510(k) database). This document provides the exact indications for use, a summary of the technological features, and sometimes even a list of the testing that was conducted.

3 Key Points: 1. Select the predicate device with identical indications for use (or as close as you can find). 2. Select the predicate device that employs similar technology to yours. 3. Newer clearances are usually better choices than older clearances. Step (3): Application Standard/Guidance Documents Identification: This is one of the more difficult tasks when mapping out a 510(k) submission. Unfortunately, the FDA does not provide a complete and comprehensive list of what may be required. However, there are several sources you should consult: 1. Product code information: By searching the product code identified in FDA production classification, this will return a lot of useful information, including specific standards, FDA Guidance Documents for this device, the risk class (Class II etc.), and confirmation of the CFR reference for the product code. 2. Special guidance and international standards: Determine if any special regulatory guidance documents or international standards apply to your device using the 510(k) clearance letter. These may include software validation, electrical safety, or other standards. 3. Biocompatibility testing: It is often required for devices or parts of devices to determine the potential toxicity resulting from contact with the user. FDA recognizes the series of ISO standards for biological evaluation of medical devices, which provides guidance for selecting the necessary tests 4. Guidance documents: Search the FDA website for applicable guidance documents. Carefully follow the recommendations set forth in guidance documents to ensure a successful submission to the FDA. 5. Software or firmware: The FDA recently changed the validation requirements for software or firmware that may be used with the device. The validation requirement is not new, but its application to simple firmware is a new requirement. Unless your firmware is very basic, expect to validate the software to the moderate level of concern. 6. Clinical data: The agency may require a clinical study in cases where the agency does not feel the technology of the subject device is close enough to the predicate device. Clinical research has its own requirements and failure to follow these can invalidate your study or lead to significant penalties. 7. Usability studies: It demonstrates that the user can read and understand the directions and use the device correctly. For products intended to be sold over-the-counter, the FDA also wants a demonstration that the expected user can correctly select the product.

4 Step (4):Preparation and Submission of 510K application: There is some flexibility on how a 510(k) may be assembled for submission to the FDA. However, the FDA is fairly strict about how the application is organized. A common process utilizes 20 individual sections, each addressing a specific 510(k) requirement. Most 510(k)s are well over 100 pages and must also meet the FDA s ecopy submission requirements to be accepted for review. Once you have identified your predicate device and finalized all safety and performance Testing for your product in comparison to your predicate, you must begin preparing your 510(k) application for submission to the FDA for review. The FDA timeframe for 510(k) review is 90 working days. The 90-day review clock stops in the event of a Refuse-to-Accept (RTA) letter or an Additional Information Required (AI) letter. Sponsors have 180 days to resolve RTA issues. Note that if responses are not received during the 180-day time frame, the FDA will delete the submission without refunding the user fee. Generally, you should plan for the 510(k) submission to take no less than 4-6 months. Common mistakes that can delay FDA 510(k) reviews: As discussed, there are two places where the 510(k) process can come to a halt. The first is the RTA process which is used when a submission does not contain all of the required information. This can result in a significant delay. The other major impact to the successful clearance of your 510(k) is the AI Letter. Common Issues that can result an AI Common Issues Details All 510(k) submissions must include accurate descriptions of how the device is intended to function. An incomplete or inaccurate description will prevent FDA reviewers from determining if your device has been properly evaluated; Inadequate Device description reviewers will also be unable to determine if your documentation supports your device s intended use. You must include a thorough and accurate description of your device to ensure a substantive FDA review of your 510(k) submission. 510(k) submissions are highly redundant the same information appears in multiple sections throughout the document. Repeating this information Discrepancies throughout submission may assist the FDA when they divide the submission among various sub-reviewers. Nonetheless, it is important to be consistent in these redundant sections.

5 Product Name Failure to follow guidance documents Missing performance testing data Usability Report Risk Management Missing clinical data The product name is likely to occur a hundred times throughout the submission, so ensure it is consistent throughout the documentation. In order to help medical device manufacturers determine what to include in their 510(k) applications, the FDA issues guidance documents or defers to national or international standards. All traditional 510(k) submissions must include performance testing data. FDA reviewers cannot determine substantial equivalence between your device and its predicate device without performance testing. Usability reports are an issue when the testing was not conducted as described in the guidance document. The consensus standard for risk management in the US is ISO 14971:2007. It requires a Risk Management Plan, a Risk Management Analysis, and a Risk Management Summary Report. The analysis is frequently a Failure Modes and Effect Analysis (FMEA) but other tools are also acceptable and must be submitted with the 510(k). Risk Analysis is a complex, time-consuming team activity. Allow plenty of time to complete this process and documentation before finalizing the 510(k) submission. For some device types, 510(k) submissions must include clinical performance data in order to evaluate substantial equivalence. If clinical data is submitted, there are forms that document if the investigator had any financial relationship with the sponsor, as well as the ClinicalTrials.gov form, which are required. Note that if clinical data is not submitted, these forms are no longer required.

6 Step (5): Clearance and Registration: Upon successful review of your 510(k) application, the FDA will send you a 510(k) clearance letter with your unique 510(k) number. In this letter they will note that your device is substantially equivalent to the predicate device outlined in your application. Keep in mind that the FDA does not approve medical devices through the 510(k) process - they clear them for sale. The only devices the FDA officially approves for sale are those that go through the PMA process. FDA 510(k) clearance requires you to implement and maintain a quality management system that complies with FDA Quality System Regulation (QSR). Once you receive your 510(k) clearance letter, you are subject to random inspection by the US FDA. Therefore, you must be in compliance with the QSR the day you receive FDA 510(k) clearance. If the FDA does inspect you and finds major deficiencies in compliance, they can issue a Warning Letter. This letter is made public on the FDA website in perpetuity, which is not optimal to those searching for your company name. The FDA 510(k) process is considerably more complex than it was previously. While it is significantly less burdensome than a Pre-Market Approval (PMA), the 510(k) is now more complex and comprehensive. Still, careful document preparation, following a known successful pathway, and clear communication with personnel preparing the submission will help ensure a more efficient clearance process for your device.

510(k) submissions. Getting US FDA clearance for your device: Improving

510(k) submissions. Getting US FDA clearance for your device: Improving Getting US FDA clearance for your device: Improving 510(k) submissions Audrey Swearingen, RAC Director, Regulatory Affairs Telephone: +1 512.222.0263 Email: aswearingen@emergogroup.com Download this white