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Decoding the 510(k) Approval Pathway: Regulatory Success in Medical Device Clearance

The 510(k) submission to the FDA is a pivotal step for marketing a medical device for human use in the United States, and unlike a premarket approval application, it offers a streamlined pathway. This submission aims to determine whether the product is substantially similar to existing ones on the market. Upon receiving 510(k) clearance, the submitter can promptly introduce the device. Crucially, modifications impacting safety or efficacy require a new 510(k) submission. Manufacturers must update the FDA on changes to intended use, design, chemical composition, or energy source. The technical dossier, known as the 510(k), is a comprehensive compilation of technical, safety, and performance details. The FDA meticulously reviews this dossier before granting clearance for legal sale or distribution in the US. In essence, the 510(k) process is integral, providing a structured approach to ensuring the safety and efficacy of medical devices and IVDs in the market.

All medical devices and IVDs must have a 510(k), which is crucial and mandated. If the product classification cannot be identified, a 513(g) request can be made.

Who Is Required To Submit A 510(K)?


The obligation to file a 510(k) is not explicitly outlined in the FD&C Act or the 510(k) regulation (21 CFR 807). Instead, specific actions, such as introducing a device to the American market, trigger the requirement for a 510(k) submission. The regulatory framework specifies situations in which manufacturers must initiate the 510(k) process, emphasizing a proactive approach to ensure compliance and the safety of medical devices available to the public. This regulatory mechanism encourages manufacturers to thoroughly assess their devices and seek clearance before market entry, contributing to a robust system of checks and balances in the medical device approval process.

Four groups of individuals or organizations must submit a 510(k) to the FDA 

  1. Domestic manufacturers introducing a device to the U.S. market
  2. Specification developers introducing a device to the U.S. market
  3. Repackers or relabelers who make labeling changes or whose operations significantly affect the device
  4. Foreign manufacturers/exporters or U.S. representatives of foreign manufacturers/exporters introducing a device to the U.S. market

Domestic manufacturers introducing a device to the U.S. market

When domestic manufacturers produce a device according to their specifications and intend to market it in the United States, they are obligated to submit a 510(k). This requirement encompasses finished devices, including any accessories made available to consumers for purchase. However, it's important to note that manufacturers of device components are not mandated to file a 510(k) unless these components are explicitly marketed for sale to end users as replacement parts. Additionally, businesses operating as contract manufacturers, producing goods under contract for another party, are exempt from the obligation to submit 510(k) applications. This nuanced regulatory approach ensures that necessary oversight is maintained while accommodating various scenarios within the medical device manufacturing landscape.

Specification developers launching a device in the U.S. market

When a specification developer defines the requirements for a final product but engages another company or organization to construct it, the responsibility of submitting the 510(k) lies with the specification developer, not the contract manufacturer. This regulatory framework ensures that the entity defining the product specifications and intending to introduce the device to the U.S. market takes on the responsibility of obtaining the necessary clearance through the 510(k) process. This distinction aligns with the objective of maintaining accountability and transparency in the regulatory oversight of medical devices.

Re-packers or re-labellers affecting the device through labelling changes or significant operations

Re-packers or re-labellers may be obligated to submit a 510(k) if their operations result in substantial alterations to the labelling or any other critical aspect of the device. Significant modifications to manuals, such as introducing a new intended use, adding or removing warnings, contraindications, etc., can be considered substantial labelling changes. Alterations to the device's state, such as changes in sterilization procedures, fall under this category. However, it's important to note that the majority of re-packagers and re-labellers are typically exempt from filing a 510(k), unless their actions result in significant impacts on the device's characteristics or performance. This exemption is in place to streamline regulatory processes while ensuring that modifications with potential implications undergo the necessary scrutiny.


Foreign manufacturers/exporters or U.S. representatives of foreign manufacturers/exporters introducing a device to the U.S. market

Foreign manufacturers/exporters or their U.S. representatives must submit a 510(k) when introducing a device to the U.S. market. Compliance with design controls (21 CFR 820.30) is mandatory for all manufacturers, including specification developers, dealing with Class II, Class III, and some Class I devices. The FDA, during a site inspection, requires access to design control documentation from the 510(k) holder. It's crucial to note that any modifications to manufacturing procedures or device specifications should align with the Quality System rule (21 CFR 820) and may necessitate a new 510(k) approval. This regulatory framework ensures that foreign manufacturers and their representatives adhere to rigorous quality and safety standards when bringing medical devices into the U.S. market.

When a 510(k) is required?

A 510(k) is required when:

  • Unless excluded, the initial release of a gadget into commercial distribution (marketing). Even though a device may have been in development or under clinical investigation prior to May 28, 1976 (the effective date of the Medical Device Amendments to the Act), anyone who wants to sell a device in the United States must submit a 510(k) application at least 90 days before offering the device for sale. A 510(k) is necessary if your company did not commercialize your product before May 28, 1976.
  • A legally marketed device has undergone a change or modification that may have a major impact on its effectiveness or safety. The onus is on the 510(k) holder to determine whether or not a modification would materially impair the device's effectiveness or safety. The Device Master Record and Change Control Records must be updated with any modifications in line with the Quality System Regulation, 21 CFR 820. It is advised that the change control records include the justification for submitting or not submitting a new 510(k).
  • If a current device is changed or modified in a way that could significantly impact its effectiveness or safety, or if the device is being marketed for a new or different intended purpose, a new 510(k) submission is necessary.

When a 510(k) is not required?

The following are examples of when a 510(k) is not required;

  • You either sell unfinished products to another company for additional processing or sell parts for other companies to assemble gadgets from. A 510(k) is necessary, nevertheless, if your parts are going to be sold directly to consumers as replacements.
  • Your device is not being advertised or sold commercially. To create, access, or test a device, you don't require a 510(k). This also covers clinical assessment. Please be aware that the Investigational Device Exemption (IDE) legislation applies if you use your device in clinical trials (21 CFR 812).
  • You distribute a product made in the United States by another company. You can sell a device to end users without submitting a 510(k) by labeling it "Distributed by ABC Firm" or "Manufactured for ABC Firm" (21 CFR 801.1).
  • Repackaging or relabeling is generally acceptable as long as the device's condition or labeling is not materially altered. The labeling should have the same warnings, precautions, and indications for use as the labeling submitted in 510(k).
  • Your device's design, components, manufacturing process, or intended purpose have not been materially altered since it was first legally distributed commercially on May 28, 1976. You have documentation demonstrating your Preamendment Status that shows these devices are "grandfathered."
  • You are the importer of the medical equipment made outside of the United States. If a 510(k) has been submitted by the foreign manufacturer and acquired marketing clearance, it is not necessary to submit another one. The foreign manufacturer may export his product to any U.S. importer after receiving 510(k) authorization for the device.
  • The regulation exempts your product from the 510(k) rule (21 CFR 862-892). In other words, some Class I or II devices can be marketed for the first time without a 510(k) submission (k). On the pages Medical Device Exemptions 510(k) and GMP Requirements, you may find a list of Class I and II exempted devices. However, if the device goes beyond the restrictions of the exemptions in Chapter.9 of the Device Classification Regulations (e.g., 21 CFR 862.9, 21 CFR 864.9), or if it is a reprocessed single-use device, or if it has a different intended use or uses a different fundamental scientific technology than a legally marketed device in that generic type of device, then a 510(k) must be submitted in order to put the new device on the market.

510(K) SUBMISSION PROCESS

1  Acknowledgement of Receipt

You can send an eSTAR or eCopy to submit your 510(k).

The FDA will give your 510(k) submission a special control number once it has been submitted to them and has been received by them. The "510(k) number" or "K number" is the name given to this number. The 510(k) number has a letter "K" at the start, then 6 digits. The last four digits represent the submission number for the year, which starts with 0001 and rises with each subsequent submission. The first two digits indicate the calendar year in which the submission was received.

For example: The first 510(k) submission for calendar year 2022 is K220001.

The FDA then conducts two verification checks to confirm that:

a)      The proper user fee payment was received for the submission.
Note: the user fee amount to be paid is based on when the 510(k) is received by the FDA and not the date on which it was sent by the submitter.

b)      A valid eSTAR or eCopy of the 510(k) submission was provided.

The FDA will email a hold letter to the 510(k) submitter if the correct user fee, a valid eSTAR, or an eCopy are not submitted, typically within seven days of receiving the 510(k) (k). Following receipt of the Hold Letter, the submitter has 180 calendar days to completely address any problems with the user fee or submission. The 510(k) is deemed to be withdrawn and deleted from our review system if the concerns are not corrected within 180 days. The submitter will then need to submit a new, complete 510(k) in order to request FDA marketing clearance.

The FDA will email an Acknowledgment Letter to the contact person listed in the 510(k) submission if the correct user fee has been paid AND a valid eSTAR or eCopy has been submitted. According to the Acknowledgement Letter, identifies:

Ø  The date of receipt (this is the date that FDA received the 510(k) submission, the proper user fee payment, and valid eSTAR or eCopy); and

The 510(k) number assigned to the submission.

2  Format and Submission Acceptance Review

eSTAR

It is not envisaged that eSTAR submissions would go through a refuse to accept (RTA) process because an electronic submission that has been properly prepared using an electronic submission template should be a full submission. For an eSTAR, however, FDA plans to use a virus scanning and technical screening method.

The 510(k) will be placed on hold until a complete replacement eSTAR is submitted to the FDA if the FDA receives an incomplete eSTAR submission. The FDA will email the submitter to alert them of the incomplete information. The FDA will consider the 510(k) to be withdrawn and the submission will be closed in the system if a new eSTAR is not received within 180 days of the date of the technical screening deficiency notification.

For eCopy

The Lead Reviewer conducts the Acceptance Review using the appropriate Acceptance Checklist in FDA's Guidance titled Refuse to Accept Policy for 510(k)s.

Based on the device type and medical specialization stated in the 510(k) submission, the FDA sends the 510(k) to the relevant OHT after sending the Acknowledgement Letter.

The Lead Reviewer decides whether the 510(k) submission satisfies the minimal standard of acceptability and should be accepted for substantive review during the acceptance review.

The submitter will get an electronic notification of the Acceptance Review outcome within 15 days of the submission's receipt, which will:

Ø  Identify the name and contact information of the FDA Lead Reviewer assigned to the 510(k);

Ø  Indicate the status of the 510(k).

The Acceptance Review result will be one of the following:

Ø  The 510(k) was accepted for substantive review; or

Ø  The 510(k) was not accepted for review (i.e., considered refused to accept or RTA); or

Ø  The 510(k) is under substantive review because FDA did not complete the acceptance review within 15 calendar days.

510(k)s that are rejected for review are put on RTA Hold. The submitter has a total of 180 calendar days to completely fix the issues listed in the RTA Hold. The 510(k) is regarded as withdrawn and removed from our review system if this is not done. A new, complete 510(k) must be submitted by the 510(k) submitter in order to request FDA marketing clearance for the device if the original 510(k) is deleted.

Once accepted, a 510(k) proceeds to the Substantive Review.

3   Substantive Review (including Substantive Interaction and Interactive Review)

The Lead Reviewer performs a thorough examination of the 510(k) submission during substantive review. The Lead Reviewer also interacts with the submitter during substantive review, which must take place within 60 days of the submission's receipt.

The Substantive Interaction communication is typically:

Ø  An email stating that FDA will proceed to resolve any outstanding deficiencies via Interactive Review; or

Ø  An Additional Information (AI) request which places the submission on hold.

Interactive Review

The submission won't be put on hold if the Lead Reviewer decides to move on with an Interactive Review and finds that any unresolved issues can be appropriately addressed within the Medical Device User Fee Amendment (MDUFA) period. During the Interactive Review, the Lead Reviewer communicates with the Submitter utilizing technologies like:

Ø  Email

Ø  Telephone Call

The submitter may transmit additional information to the Lead Reviewer directly or to the FDA in response to a request made by the Lead Reviewer during Interactive Review. The FDA must receive a valid eSTAR or eCopy with every piece of information given to them during Interactive Review.


5  Additional Information (AI) Request

Submissions are put on hold if the Lead Reviewer submits an AI Request. A full answer to the AI Request must be sent by the submitter within 180 days after the AI Request's date.

Note: The FDA must receive a complete response within 180 calendar days of the date of the AI Request. No extensions beyond 180 days are granted

The application will be deemed withdrawn and removed from our review system if FDA does not receive a thorough response to all faults in the AI Request within 180 days of the AI Request's date. The 510(k) submitter will need to file a new 510(k) in order to get FDA marketing clearance if the original 510(k) is removed.

The FDA must receive the response from the submitter together with an authorised eSTAR or eCopy. Included in the answer should be:

Ø  Submitter's name;

Ø  510(k) number;

Ø  Identification of the submission as Additional Information (AI) to the 510(k);

Ø  Date of the FDA's request for additional information; and

Ø  The requested information in an organized manner


6    510(k) Decision Letter

The FDA has a 90-day deadline for making a 510(k) decision under the MDUFA. The number of calendar days, excluding the days the submission was put on hold due to an AI request, that passed between the date the 510(k) was received and the date of an MDUFA decision is known as the "FDA Days." Findings of substantially equivalent (SE) or not substantially equivalent are included in MDUFA Decisions for 510(k) submissions (NSE).

The FDA will send the determination letter to the submitter via email at the address specified in the 510(k) cover letter after a decision has been made.

A 510(k) is deemed "cleared" if it receives a SE decision. Each week, the FDA updates the 510(k) database with newly cleared 510(k)s. The 510(k) Summary or 510(k) Statement and the Indications for Use (IFU) will be attached to the SE letter. A SE package is made up of the IFU and the 510(k) Summary or Statement. Each month, complete SE packages are posted. Since the IFU is seen as an attachment to the SE letter, it will not be signed. As a result, the SE letter's signature will be valid for both the letter and the IFU.

The FDA will issue a Missed MDUFA Communication, which is written feedback to the submitter to be discussed in a meeting or teleconference, including the major outstanding review topic areas or other reasons that are preventing the FDA from reaching a final decision, with an estimated date of completion, if the FDA does not reach an MDUFA decision within 100 FDA days (that is, 10 days after the MDUFA goal).

In order to determine substantial equivalence, the FDA adopts a decision-making procedure that includes several key judgment factors.

510(K) SUBMISSION PROGRAM

A submitter may choose from three types of Premarket Notification 510(k) submissions to seek marketing clearance for their device when appropriate for review under the 510(k) Program: Traditional, Special, and Abbreviated.
According to 21 CFR 807, the original submission type was the traditional programme. To speed up the assessment of specific submission types subject to 510(k) regulations, the FDA created the Special and Abbreviated 510(k) Programs in 1998. The New 510(k) Paradigm guidance previously provided an overview of these programmes. The Abbreviated 510(k) Program and the Special 510(k) Program are two separate guidance documents that the FDA divided from "The New 510(k) Paradigm" guideline in 2019. When a 510(k) submission satisfies specific criteria, the Special 510(k) and Abbreviated 510(k) submission types may be employed.

1      Traditional 510(k)

The Traditional 510(k) may be used for any original 510(k) or for a change to a previously cleared device under 510(k).

The FDA generally reviews Traditional 510(k) submissions within 90 days of receipt. It is always possible to request marketing authorization for a device through the 510(k) Program by using the Traditional 510(k) Program.

2      Special 510(k)

If the method(s) to analyze the change(s) are well-established and the results can be appropriately examined in a summary or risk analysis format, device manufacturers may opt to submit a Special 510(k) for adjustments to their own current device. For devices that produce biological products at the point of care, a Special 510(k) would typically not be appropriate because there would not be a well-established way to assess such changes and/or the performance data would not be reviewable in a summary or risk analysis format.

As identified in the guidance The Special 510(k) Program, design or labeling change(s) to an existing device (including certain changes to the indications for use) may be appropriate for a Special 510(k) when:

Ø  The manufacturer who has the legal right to market the current device has proposed the change;

Ø  Performance data are not required, or if they are, well-established methods are available to assess the change;

Ø  And all performance data required to support substantial equivalence can be reviewed in a summary or risk analysis format.

3      Abbreviated 510(k)

Device manufacturers may choose to submit an Abbreviated 510(k) when the submission relies on:

Ø  FDA guidance document(s),

Ø  Demonstration of compliance with special control(s) for the device type, or

Ø  Voluntary consensus standard(s).

The required components listed in 21 CFR 807.87 [Traditional 510(k)] must be included in an abbreviated 510(k) submission. To aid in the review of a submission, businesses choose to include brief reports on the usage of guidance papers, special controls, or declarations of compliance with FDA regulations in an Abbreviated 510(k) submission. When submitting an Abbreviated 510(k), manufacturers who rely on widespread adoption of a voluntary consensus standard must provide the rationale for this adoption as well as any supporting evidence or data.

HOW TO SUBMIT A 510(K)

A 510(k) submission must be submitted as an eSTAR or eCopy.

Online:

Send eSTAR or eCopy premarket submissions online through the CDRH Customer Collaboration Portal (CDRH Portal)

By Mail:

The FDA only intends to accept 510(k) submissions saved to a form of electronic storage media and mailed to the FDA if they are received by the FDA before October 1, of every year.

Mail your submission to the current mailing address for CDRH's DCC and a link to CBER's DCC's mailing address are provided on the eCopy Program for Medical Device Submissions webpage.

We advise you to use registered mail with a return receipt or a commercial delivery service to transmit your 510(k) to the FDA so that a signed receipt of delivery will be provided.

The FDA should send you an acknowledgment of receipt with the allocated 510(k) number.

After the FDA receives the submission, the review procedure is described on the 510(k) Submission Process webpage.

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