FDA Submissions & ISO 13485: QMS for 510(k), De Novo & PMA

Device classification drives submission pathways

The three most common regulatory pathways to gain market access in the U.S. are the 510(k) premarket notification, De Novo classification request, and Premarket Approval (PMA). For Class I and II devices that are not exempt, and where a legally marketed predicate exists, a 510(k) submission is generally required. If no predicate device exists, a De Novo request allows the FDA to evaluate the new device and assign it to Class I or II based on risk. Class III devices, include those that are found to be “not substantially equivalent,” as well as those that are life-supporting or life-sustaining, intended for preventing impairment of human health, or that present a potential unreasonable risk of illness or injury. These devices typically require PMA, the most rigorous premarket submission process.

Regardless of whether you're pursuing a 510(k), De Novo, or PMA submission, one constant remains: the need for a compliant Quality Management System (QMS). Your QMS supports traceability across design, risk, manufacturing, and validation and verification (V&V) processes, and must be fully prepared for FDA inspections. It’s not just a regulatory formality, your QMS forms the foundation for your submission documentation and ongoing product lifecycle compliance.

The regulatory framework for quality: 21 CFR Part 820 and the transition to QMSR

The requirement for a Quality system is established in 21 CFR Part 820.5, which states that “Each manufacturer shall establish and maintain a quality system that is appropriate for the specific medical device(s) designed or manufactured, and that meets the requirements of this part.”

This regulation ensures that quality is built into every stage of product development and production considering the risk classification of the device and any applicable exemptions.

Beginning February 2, 2026, the FDA will formally adopt ISO 13485:2016 by reference as part of the revised 21 CFR Part 820, now renamed the Quality Management System Regulation (QMSR). This update reflects the FDA’s alignment with international regulatory standards and aims to reduce the burden on manufacturers operating in multiple markets.

Under the new 21 CFR Part 820.10, manufacturers subject to this regulation must:

“(a) Document. Document a quality management system that complies with the applicable requirements of ISO 13485 (incorporated by reference, see § 820.7) and other applicable requirements of this part; and”

This shift means that device manufacturers will need to ensure their QMS not only complies with ISO 13485 but also continues to meet FDA-specific expectations such as complaint handling, post-market surveillance, and reporting.

Behind the submission file: Ensuring your FDA submission reflects a live QMS

Some manufacturers treat FDA submissions, whether 510(k), De Novo, or PMA, as standalone projects. But the FDA expects your submission to reflect an operating, compliant QMS, rather than being a separate submission file disconnected from the QMS records.

As previously stated, under 21 CFR Part 820 (and soon the ISO 13485-aligned QMSR), your QMS should already be generating the design, risk management, validation, and production records included in the submission. When companies delay QMS implementation or create documents only for FDA submission, they risk:

·         Inconsistencies between submission files and actual production processes,

·         Approval delays with additional Information (AI) Letters,

·         Deficiency letters due to incomplete or uncontrolled document; and

·         Findings in the FDA inspection.

FDA submissions should be an output of your QMS and not a separate, parallel process. ISO 13485 gives you the structure to ensure your submission files are complete, consistent, and defensible. To align with this approach, consider the following:

·         Start ISO 13485 implementation early in development and not after design freeze.

·         Build your DHF / Design and Development File, Risk Management File, and V&V files under QMS control from the start.

·         Use document control for all submission-relevant files.

·         Design your device using the risk management outputs as your design inputs.

·         Ensure your PMS system actively monitors safety and performance trends.

·         Use management reviews to prepare for FDA inspections.

While not exhaustive, the table below outlines keyways ISO 13485 supports compliance with 510(k), De Novo, and PMA requirements.

US Regulatory Pathways

Final thoughts

 For any FDA pathway, 510(k), De Novo, or PMA, your submission should originate from a compliant QMS, not developed in isolation. ISO 13485 helps you build and maintain that system. It connects your design, risk, testing, and production records so they are consistent, complete, and ready for FDA review. With the new QMSR aligning with ISO 13485, this connection is more important than ever.

Starting your QMS early means fewer surprises later: fewer delays, fewer inspection issues, and a smoother path to market. A good QMS is essential for FDA submission success.