The FDA 510(k) submission is the most common way to obtain marketing clearance for a medical device in the US. But with all the regulations in place, it can sometimes seem quite confusing to find the right approval method The following article is a small guide that provides a starting point for a successful 510(k) application.

A brief overview

An economic operator seeking to place a medical device on the U.S. market generally must submit a 510(k) form. The 21 CFR 807 Subpart E contains all the requirements for an application. Premarket approval demonstrates to FDA that a product is at least as safe and effective, i.e., substantially equivalent (SE), to an already lawfully marketed product that is not subject to a PMA. This means that the new medical device that a manufacturer wants to introduce into the U.S. market must be equivalent to a device that is already approved and compliant in the U.S. market. However, most Class I and some Class II medical devices are exempt from Premarket Notification 510(k), so only facility registration and device listing (see 21 CFR 807) are required.

The legally marketed medical device to which equivalence is drawn is commonly referred to as a “predicate” (comparator device). Any device that is legally marketed can be used as a predicate as long as it does not violate the law.

Once the device is determined to be SE, it can be marketed in the US. Determining SE is a critical aspect here and usually takes at least 90 days. Once 510(k) clearance is granted and the manufacturer and device are registered, the applicant can market the medical device immediately. However, the manufacturer should be prepared for an FDA quality system inspection at any time after 510(k) clearance.

Who is required to submit a 510(k)?

Domestic manufacturers and specification developers who introduce a medical device into the U.S. marketplace

Suppliers or distributors who make repackaging or label changes or whose workflow significantly affects the product

Foreign manufacturers/exporters or their U.S. representatives who introduce a device to the U.S. market

When is a 510(k) required?

Initial introduction of a product into commercial distribution (marketing) after May 28, 1976

Change or modification to a lawfully marketed product that could significantly affect its safety or effectiveness

When is a 510(k) not required?

Sale of unfinished product to another company for further processing.

The product is not marketed or distributed commercially

Distributing another company’s domestically manufactured product

If the existing labeling or condition of the product is not substantially altered by suppliers or distributors

The product was lawfully in commercial distribution prior to May 28, 1976, and has not been substantially changed or modified in design, components, manufacturing process, or intended use

Importer of the foreign medical device (but the foreign manufacturer must have obtained 510(k) clearance)

Your product is exempt from the 510(k)

Substantial Equivalence

Within the 510(k) process, it is very important that a medical device be substantially equivalent to an existing device. But what does substantial equivalence mean? On the one hand, it means that a product has the same intended purpose and technological properties as the predicate; on the other hand, it can mean that the medical device has the same intended purpose as the predicate but different technological properties. In the latter case, it is critical that the information submitted to FDA does not raise new questions of safety and effectiveness and demonstrates that the product is at least as safe and effective as the legally marketed product.

The submission process

Two copies of the 510(k) application must be submitted to FDA’s Center for Devices and Radiological Health (CDRH) or to the Document Control Center (DCC), a part of the Center for Biologics Evaluation and Research. One of the two copies must be an electronic copy (eCopy). First, the submitted Premarket Notification is reviewed by CDRH, then the submitted documents are reviewed by specialists such as biomedical scientists, physicians, microbiologists and others. The DCC assigns a unique control number. This number is commonly referred to as the “510(k) number” or “k-number.”

If the user fee has been duly paid and a valid eCopy has been received, the DCC will send a confirmation email, otherwise a hold letter will be sent. Within 15 days of (successful) receipt of the documents, the applicant will receive electronic notification of the outcome of the acceptance review. Subsequently, another type of review is conducted with the Substantive Review and, depending on the result, further measures such as the Substantive Interaction, Interactive Review or Additional Information (AI) Request may follow.

The decision letter, or “decision letter,” will arrive approximately 90 FDA days after the submission (calendar days between 510(k) receipt and decision, not including waiting time for AI requests), and it will include determinations as to whether the product could be considered SE or NSE (substantially equivalent or not substantially equivalent). A 510(k) that receives an SE determination is considered “clear.”

Timeline of Communication: https://www.fda.gov/medical-devices/premarket-notification-510k/510k-submission-process#timeline

Traditional 510(k).

The so-called traditional 510(k) can be used in all circumstances and is the original complete form of a 510(k) submission as outlined in 21 CFR 807. It can also be used for any initial submission or for a change to a previously cleared medical device under 510(k).

Structure and Content:

Medical device user fee cover sheet.

As another first step, it is important to complete the Medical Device User Fee Cover Sheet (MDUFMA). This requires online registration on the FDA homepage. Once registered, you will receive an identification number for payment of the user fee. Next, the MDUFMA must be mailed to a designated address and payment made. If the applicant has not paid all fees, FDA will consider the submission incomplete and will not accept it.

CDRH Premarket Review Submission Cover Sheet.

Can be downloaded from the FDA home page, is not required but may shorten the application time.

510(k) Cover Letter.

Cover letter must include the following information:

– Application date and indication that this is a 510(k) application (including what type).

– Applicant’s name, address, telephone, other

– Number of the registered establishment

– product name

– Trade name and model number

– Classification name and class in which the product is located (there is a pre-written statement if the classification is not known at the time of submission)

– Reason for a 510(k)

– Identification of predicate used to demonstrate substantial equivalence, 510(k) number, trade name, and product code – if applicable: registration number, name and address of each facility involved in the manufacturing process – if applicable: specific regulations or standards for the device.

Notes on the declaration for use

Identify and describe the specific use statement for the medical device included in the 510(k) application. This statement should be consistent with all other use instructions included in the remainder of the application package. Indicate whether the device is for prescription or over-the-counter use.

510(k) Summary or Statement.

Summary: Provides a brief summary/overview of the product and supporting information.

Declaration: is an acknowledgement that the 510(k) holder will provide a copy of the 510(k) application (with certain exclusions), but it is not recommended that a declaration be provided in lieu of a summary because anyone can then request a copy of the 510(k) application.

Truthful and accurate statements

Statement that all information submitted is true and accurate and that no facts have been concealed.

Class III Summary and Certification.

If the predicate is a Class III product, a pre-written statement must be certified.

Financial certification or disclosure statement.

If the 510(k) application contains clinical data, certain information must be provided indicating that there is no financial interest of the clinical investigators.

Compliance statements and summary reports.

Summary

Product Description

Significant equivalency discussion

Proposed labeling

Final draft of proposed labeling

Sterilization and Shelf Life

Indicate sterilization procedure and description of packaging to maintain sterility.

Biocompatibility

Software

Electromagnetic compatibility and electrical safety

Compliance with electromagnetic compatibility requirements, FDA recognizes IEC 60601-1-2, as well as IEC 60601-1-1 when the device is in contact with patients.

Performance testing – test bench

Performance testing – animal testing

Performance testing – clinical testing

Other

For medical devices that have been automatically classified as Class III after receiving an NSE determination in response to a 510(k) submission, there is another route: de novo classification. This process allows products to be reclassified to Class I or Class II.

When submitting a 510(k), some special considerations must be made regarding: biological devices, biocompatibility, combination devices, design controls, convenience kits, standards, and sterilization.

The Special 510(k) application form.

The special 510(k) is used for product modifications and utilizes the Design Controls aspect of the Quality System Directive. However, it can also be submitted for a modification to a product that has been cleared through the traditional 510(k) process. In addition, the special 510(k) allows the manufacturer to declare conformance with the Design Controls without providing data, because this notification includes a “Declaration of Conformance” with the Design Controls requirements.

The following documents are required for submitting a special 510(k):

Description of the modified medical device

Comparison with the cleared product, indicating similarities and differences

Intended use of the product

Labeling

A brief summary of design controls activities

Risk analysis

Design verification and validation

Declaration of Conformity

Abbreviated 510(k) Application

An abbreviated 510(k) (abbreviated application) may be submitted when guidance is available, a special control measure has been established, or FDA has recognized a relevant consensus standard. Generally, the review time is longer than for a special 510(k), but in some cases shorter than for a traditional 510(k).

How to get started.

Before beginning the first part for the 510(k) application, it is very important to identify one or more medical devices as “predicate” to which the desired product will be compared. This is the very first step in the entire process. It is also possible to claim equivalence for more than one product, but one of them must be declared as the primary “predicate” to simplify the decision process. The next step is to research whether there are any guidance documents published by FDA. In general, there are many product-specific guidance documents as well as general guidance documents on biocompatibility, software in medical devices, or others. These documents are usually available on the FDA’s Guidance Documents page. After these initial steps, work must be done on each part of the 510(k) structure and content. At the end, two copies of the 510(k) must be submitted to the address provided. One of the copies must be in electronic format. You should also keep a copy of the 510(k) itself, as FDA does not return copies after review.

Links for additional information:

How to prepare a traditional 510(k) submission.

Newly added guidance documents

The new 510(k) paradigm – Alternative approaches to demonstrating substantial equivalence of premarket notifications

The 510(k) program: assessing substantial equivalence of premarket notifications[510(k)]

FDA Frequently Asked Questions

If you need help with any of the paperwork and guidance for the submission process, please contact us, seleon gmbh, we will be happy to assist you!

Please note that all information and listings do not claim to be complete, are without guarantee and are for information purposes only.