The 510(k) Application - 5 Best Practices Medical Device Companies Must Follow for Successful Submissions

    Improve compliance with 510(k) application requirements and procedures, ensuring faster clearance for marketing of medical devices..

    A successful 510(k) application is important for medical device companies to reduce burdens of cost, time, multiple inspections and faster regulatory clearance. This article provides information about classification of medical devices, important sections of the application, content not to be missed in documentation and other best practices to be followed to compile and submit a 510(k) for successful approval.

    US FDA's Plan for Modernizing the 510(k) Pathway - Meet the New Expectations

    What are the different types of device classes?

    According to the Federal Food, Drug and Cosmetic Act, medical devices are classified into three categories based on the level of risk, intended use and also upon indications for use. The class to which a device belongs determines the type of premarketing submission required for FDA approval.

    Class I: Simple devices (General Controls - the cGMPs) with minimal risk and safe to the end-user are included under this group and are exempt from FDA clearance / 510(k) requirements.

    Class II: Devices which pose a moderate level of risk to the end-user (General Controls and Special Controls) are included in this group. They require a regulatory submission (premarket notification - 510 (k)) before commercial distribution, unless the device is a pre-amendments device or substantially equivalent to such a device. Sterile products are classified under Class II even if they are simple products that normally would be considered as Class I.

    Class III: Devices which pose a serious risk (devices like implants or those used to sustain life) to the end-user are included in this group and they require a regulatory submission (510 (k) / PMA (Premarket Approval) submission) before commercial distribution.

    What is a 510 k and to which device does it apply?

    A 510 (k) is a premarket notification with 21 sections included that is a standard regulatory path which applies to all devices except those exempt under the FD&C Act.

    • It has to be submitted by all registrants (at least 90 days before) in order to introduce a new device into market or upgrade characteristics (like safety, efficacy and manufacturing process, intended use) of an existing device.
    • Manufacturers should first consider if their product does require a 510(k) or if it is a Class I, II or a Class III device.
    • The Federal Agency evaluates whether or not the device meets requirements for market clearance and this whole process aims to promote device innovation, establish a more predictable regulatory environment and make safe, effective devices available to patients in a timely manner.

    A 510(k) application is required for Class II (those which pose moderate risk to the user) before commercial distribution. For Class III devices, a PMA will be required (a more complicated and time-consuming process) for commercial distribution in U.S market; unless the device is a pre-amendments device (in such a case, a 510k will be the route to market)

    A pre-market approval is required under the following conditions:

    • To introduce a device into the U.S. market for commercial distribution, irrespective of the location or origin of the manufacturer.
    • Specification developer (the person whose name appears on the label) introducing a device to the U.S. market, even if they do not manufacture that device at all, they need to submit a 510(k).
    • 510(k) is required the first time a device is introduced into the commercial distribution, for a different intended use, devices for which repackaging or relabeling changes are being made as a part of re-processing or when changes are made which could significantly affect the device's safety or effectiveness.

    510(k) is not required

    • For devices not marketed in U.S or commercially distributed (like clinical trials)
    • When modifications are made to a device which do not significantly affect its safety or effectiveness
    • When re-packagers have not made any significant changes to labelling
    • For a device that is exempted from 510(k) by regulation etc.

    Why is it important to have a foolproof 510(k) submission?

    The FDA has become more stringent yet transparent, consistent in its approach and criteria (by implementing internal reforms and intense scrutiny, tightening evaluation of some parameters); as a result many 510(k) applications for approval of medical products are being rejected.

    The Agency has become more predictable in its approach and is adhering to its action plan against deficiencies cited in applications. More limitations are imposed on the ability to use multiple predicates. There are more chances of the new device being categorized as 'Not Substantially Equivalent (NSE)'. There are also restrictions on the use of the Special 510(k) application.

    Applicants must establish 'Substantial Equivalence' of their device to the predicate device to avoid being questioned for discrepancies and rejection. The Agency clarifies that it will now consider only one main and one secondary predicate device to evaluate 'Substantial Equivalence'.

    The FDA has of late provided more detailed guidelines, information on decision-making process of FDA for determining 'Substantial Equivalence' and has also provided additional details about the regulations, strategies, and norms. It expects applicants to go through every point relevant to their device before submission.

    A 510(k) application being a standard and widely employed regulatory path for moderate risk devices, it is essential to have tested, fool-proof 510(k) submissions.

    Best Practices for Successful 510(k) Submissions

    Manufacturers should provide complete, quality and timely responses to reviewers and must be aware of deadlines to provide additional information which is requested. The Agency expects applicants to respond within 30 days unless they submit an extension request (upon approval they will have 180 days to respond) to provide the requested information. The 510(k) will be considered withdrawn and a new 510(k) will need to be submitted if they fail to submit after this granted period.

    The below mentioned best practices can be followed to ensure that 510(k) submission is foolproof and clearance granted for commercial distribution.

    1. Determine classification of the device accurately

    A device has to be classified accurately in order to prove in a 510(k) that the new product is basically the same as the predicate device or legally marketed device in terms of safety, efficacy and other issues and there are no added safety concerns.

    The manufacturer should focus on the classifications as listed in 21 CFR the 800 Series.

    It is important to ensure that the device classification is according to the definition laid by the FDA (even though there are a lot of similarities in terms of risks in those set in other rules like those of the European Union, but they are different), if the device is intended to be marketed in U.S.

    According to the FDA's definition of classification, all the device classes require that the companies manufacture the product under the cGMP with some additional requirements, as per 21 CFR 820. FDA's Quality Management System under these GMPs is considered to be more stringent than other systems requiring documentation, so companies can follow those spelled out in guidance documents that are on the FDA's website.

    Companies should also follow FDA's classification which is a scheme based on two things - one is the Intended Use and the other is proving 'Substantial Equivalence' of product to the legally marketed device. This is considered as a major issue which applicants face as they are not always aware of what the 510(k) has said for specific medical products.

    2. Decide What Type of 510(k) is Necessary for Your Device

    • A Traditional 510(k) can be filed for an original 510(k) or when modifications are made to a previously cleared device.
    • An Abbreviated 510(k) is submitted to leverage the accepted information regarding various aspects of the 510(k) which the Agency has already cleared and is quicker as it relies on standards. It can be submitted when guidance documents exist, a special control has been established and a standard has been identified. Sections within an Abbreviated 510(k) are same as Traditional 510(k) but with the benefit of 'Expedited Review'.
    • A Special 510(k) submission is aimed for review and clearance of a modification to a manufacturer's device which has been already cleared for commercial distribution. This can be an addition to existing 510(k) of a company for changes made to the device in terms of its Intended Use or fundamental scientific technology. The Agency usually processes this type of application within a month.

    The FDA exercises the right to change a Special 510(k) or an Abbreviated 510(k) into a Traditional 510(k) (the same is communicated within 30 days by the Agency) if it finds that the level of evidence or documentation does not meet the requirements of the specific program. Manufacturers can either allow it to be converted into a traditional 510(k) after completing the requirements or withdraw the submission.

    A new 510(k) has to be submitted with required information that addresses the outstanding deficiencies if:

    • The manufacturer fails to respond to the Agency's requests for additional information or
    • If they wish to delete a contradiction or
    • Use a fundamental scientific technology or device specifications that affect the safety, performance or effectiveness of the device.

    Applicants can also opt for so called 'Expedited Review' for devices or products intended to treat or diagnose a life threatening, or irreversibly debilitating disease or condition with clinically meaningful results.

    3. Provide Proof of Substantial Equivalence of Device

    The basis for clearance of a 510(k) is Substantial Equivalence (SE) which means that the new product is as safe and effective as a predicate device. Applicants should first identify their predicate device and compare their new product in order to support its SE.

    • A 510(k) summary should include all necessary evidence, supporting documents to support SE determination. The application should also include any clinical/animal data in cases where in performance data is inadequate to support SE of the new device.
    • A finding of SE indicates that the new device's indications for use fall within the intended use of the legally marketed device. All new indications for use should be properly evaluated to determine whether they reflect a new intended use. Intended use is the primary characteristic, it is essential for manufacturers to clearly communicate that the intended use of their product is same as the predicate device.
    • FDA stipulates that intended use, technological characteristics, safety, effectiveness of the new device should match with the predicate.

    The Agency adopts a flexible approach to determine SE, keeping in view evolving technology, thus maintaining predictability and consistency in its review.

    FDA will review all information in the new device's proposed labeling, its indications for use in order to evaluate its intended use and that the product does not raise any additional risks before approval for commercial distribution.

    4. Provide the Indications of Use Statement

    Indication for Use Statement' is the fourth section of 510(k) to be made on a separate page in the prescribed format / form and should include specific indications, clinical settings, target population etc. This statement is the basis for all subsequent FDA submission, review actions, getting 510(k) cleared and establishes marketing claims / limitations. Any further changes to the device or expansion of Intended Use would require a new 510(k).

    • Applicants should ensure that information written on this statement is uniform and identical in words throughout the application in the labeling, advertising, instructions for use, service statement and other sections also.
    • There are several other places where Indications for Use statement is used, applicants should keep in mind that it can't be changed from one paragraph to another or one tab to another.
    • Environmental specifications, performance characteristics, patient /user interface, dimensional specifications or software do affect indications for use.

    The key purpose and the key ingredient of the 510(k) is to show that the new product is substantially equivalent to predicate and that it doesn't raise new issues of safety and efficacy; it is essential to restate this through the Indications for Use Statement.

    5. Ensure the 510(k) Summary is Airtight

    The FDA will always look at the 510(k) summary first to understand the contents of the application - therefore it is vital to get this part right.

    A 510(k) summary in 510(k) application must include:

    • description of device's attributes,
    • list of all device components such as model numbers,
    • device characteristics
    • the level of evidence required to support a Substantial Equivalence (SE),
    • new intended use of the new device
    • data in tabular form about the technical characteristics of the new device as well as the predicate device
    • information about special controls applicable to a particular device

    Applicants should cross-check the relevance of the test program used for the device, the intended use, lay more emphasis on the safety of the product and provide proof that new product does not raise any new safety and efficacy issues.

    Supporting clinical data can be submitted when:

    • Other forms of performance data is inadequate to confirm SE
    • various questions on safety and effectiveness of the new device arise
    • issues cannot be addressed using non-clinical methods

    It is important for registrants to ensure that 510 (k) has relevant information about clinical data to eliminate concerns about safety and efficacy and avoid radical changes (not included in the rationale).

    New devices need not be identical to the predicate, features can be upgraded and as long as new safety issues do not arise and additional testing can be carried out as a part of the regulatory strategy.

    510(k) - A Key Step in Marketing New Medical Devices in the US

    As discussed in this article, the importance of the 510(k) in the device approval process cannot be underestimated. Any company introducing a new device into U.S market has to file a new 510(k).

    Applicants should ensure that data submitted is logical, scientifically sound, meets the content and format requirements to avoid negative outcomes. A final 510(k) submission should be a completed comprehensive document including all 21 sections and other information needed for approval by the FDA.

    How can medical device regulatory compliance training help?

    The areas highlighted above are just a small part of the wide range of practices and processes for medical device regulatory compliance . Subjects such as device compliance are multi-faceted and complex and can be better understood after attending a training course such as the ones offered by ComplianceOnline. Our courses are available as live webinars, training recordings and in-person seminars. We also offer customized training courses developed in conjunction with organizations that wish to train large groups of their employees.

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