FDA Premarket Notifications 510(k): A Practical Guide for Medical Device Manufacturers

The FDA Premarket Notification pathway, commonly known as the 510(k), is the most widely used route to market for medical devices in the United States. Primarily applying to moderate risk devices, it requires manufacturers to demonstrate that a new device is at-least-as-safe and effective as a legally marketed predicate device. Crucially, a 510(k) is not an approval. It is a clearance decision based on substantial equivalence. Understanding how the 510(k) programme works is essential for manufacturers because the choice of predicate, evidence strategy and submission quality directly influence review timelines, regulatory risk and commercial readiness.

What is a 510(k)?

A 510(k) is a premarket notification submitted to the FDA under Section 510(k) of the Federal Food, Drug and Cosmetic Act and implemented through 21 CFR Part 807 Subpart E. The purpose of the submission is to show that the subject device is substantially equivalent to a legally marketed device that is not subject to PreMarket Authorisation (PMA) or De Novo. Substantial equivalence means that the subject device has the same intended use as the predicate and either has the same technological characteristics, or has different technological characteristics that do not raise new questions of safety and effectiveness and is supported by appropriate data. If the FDA agrees, it issues a clearance letter and assigns a unique 510(k) number, allowing the device to be marketed in the United States.

Who Submits a 510(k)?

The submitter is usually the legal manufacturer or specification developer responsible for the design, labelling and claims of the device. In some cases, an initial US importer or distributor may act as the submitter if they assume regulatory responsibility. Contract manufacturers do not typically submit 510(k)s unless they also control the device design and labelling. Foreign manufacturers must appoint a US Agent and, following clearance, must register their establishment and list the device with the FDA before commercial distribution.

When is a 510(k) Required?

A 510(k) is required for most Class II devices and for some Class I and Class III devices that are not exempt and do not require De Novo or PMA. Typical triggers include introducing a new device to the US market under a regulation and product code that requires 510(k) clearance or making significant changes to a device already cleared under 510(k). Significant changes can include new materials, design modifications that affect performance, new indications for use, new sterilisation methods or major software updates. The FDA provides detailed guidance on deciding when to submit a new 510(k) for changes to an existing device, including specific guidance for software modifications. A 510(k) is not required for devices that are exempt under their classification regulation, pre-amendment devices that have not been significantly changed or devices that will be reviewed under De Novo or PMA pathways instead.

Types of 510(k) Submissions

The FDA recognises three primary types of 510(k) submissions. Choosing the appropriate type influences the format and review strategy but not the user fee. Before describing each type, it is important to note that all routes ultimately require demonstration of substantial equivalence.

1. Traditional 510(k):

• The default and most common pathway. 
• Used for original submissions and for many significant modifications to existing devices. 
• Includes full technical documentation, comprehensive predicate comparison and all necessary supporting data.

2. Special 510(k):
   • Intended for certain design changes made by a manufacturer to its own legally marketed device. 
   • The intended use must remain the same and the changes must not introduce new questions of safety or effectiveness.
   • This pathway relies heavily on design controls and risk management documentation and can offer a shorter review when appropriate.
3. Abbreviated 510(k):
   • Used when FDA guidance documents, special controls or recognised consensus standards apply. 
   • Still contains the core elements of a traditional submission but leverages declarations of conformity and summary test reports rather than full raw data sets. 
   • Often used in conjunction with the Safety and Performance-Based Pathway when predefined performance criteria are met.

High Level 510(k) Strategy Development

A successful 510(k) begins with a clear regulatory strategy. Manufacturers must first confirm that the product meets the FDA definition of a medical device and identify the applicable classification regulation, product code and device class. It is essential to confirm whether the device is exempt, subject to 510(k), eligible for De Novo or requires PMA. EU MDR or UKCA classifications should never be assumed to align with US classification. Additional US-specific requirements such as radiation-emitting product rules or CLIA categorisation for IVDs must also be considered.

Once classification is confirmed, manufacturers must identify a suitable predicate and determine the appropriate submission type. Predicate selection requires careful evaluation of intended use, technological characteristics, materials, energy sources and post-market history. For borderline cases or novel features, an FDA Pre Submission (Pre-Sub) is often advisable to obtain feedback on predicate choice and testing strategy before committing to full submission development.

Evidence Planning and Gap Assessment

After predicate selection, manufacturers should perform a structured gap assessment comparing the subject device to the predicate, applicable FDA guidance documents, special controls and recognised consensus standards. This assessment defines the testing and documentation plan. Evidence typically includes bench performance testing, biocompatibility evaluation, electrical safety and EMC testing, software verification and validation, cybersecurity assessment, sterilisation and packaging validation, shelf-life testing and human factors engineering. Animal or clinical data may be required when bench and non-clinical data are insufficient to address residual risk or new questions of safety and effectiveness. Evidence planning must be aligned with design controls and risk management to ensure traceability.

Data Generation and Documentation

Testing must be executed according to predefined protocols and applicable standards. Manufacturers should maintain a complete design history file and device master record, including design inputs and outputs, risk management files, verification and validation reports and change control documentation. Labelling must be drafted in US format and aligned with claims, including instructions for use, packaging labels and any patient labelling. Consistency across documentation is critical because discrepancies often lead to FDA questions or additional information requests.

Compiling and Submitting the 510(k)

Most 510(k)s must now be submitted using the FDA’s electronic Submission Template and Resource (eSTAR), an electronic PDF template. All sections of the eSTAR must be completed, even if only to justify why a section is not applicable. Manufacturers should ensure consistency across device description, risk management, testing and labelling. Internal or external expert review before submission helps identify gaps and reduce the risk of refusal to accept. The appropriate user fee must be paid, and the submission is then uploaded via the CDRH Customer Collaboration Portal.

FDA Review Process and Timelines

Following receipt, the FDA assigns a 510(k) number and conducts an acceptance review within approximately 15 calendar days to determine whether the submission is administratively complete. If deficiencies are identified, the submission may be refused to accept and placed on hold until they are addressed. Once accepted, substantive review begins. The FDA aims to provide substantive interaction within 60 calendar days. Interactions may occur through informal questions or through a formal Additional Information request, which places the submission on hold until a complete response is provided within 180 days. Failure to respond results in withdrawal. The FDA performance goal for 510(k) review is typically 90 FDA days, excluding time on hold. Final outcomes are either Substantially Equivalent clearance or Not Substantially Equivalent, in which case De Novo or PMA may be considered.

Practical Tips and Common Pitfalls

Successful 510(k)s depend on strong predicate strategy, early FDA engagement for novel issues, rigorous and clearly presented testing, disciplined submission logistics and proactive anticipation of reviewer questions. Manufacturers should invest time upfront in predicate selection, use FDA databases and summaries to understand precedent and consider reference devices where appropriate. Testing data should be clearly linked to risks and intended use, presented with concise summaries and acceptance criteria. Independent mock reviews and careful validation of eSTAR before submission help avoidable delays.

Post Clearance Obligations

After clearance, manufacturers must register their establishment, list the device and maintain a compliant quality management system under 21 CFR 820 or the forthcoming QMSR aligned with ISO 13485. Complaint handling, MDR reporting and post-market surveillance must be implemented. Any subsequent device modifications must be assessed to determine whether a new 510(k) is required or whether changes can be managed within existing clearance through design control and risk management.

LFH supports medical device manufacturers across the full 510(k) lifecycle, from regulatory strategy and predicate selection to evidence planning, eSTAR compilation and FDA interaction management. Our team helps clients prepare clear, robust submissions that reduce regulatory risk and support efficient US market entry.

FAQ – FDA Premarket Notifications 510(k)