On October 27, 2025, the Food & Drug Administration (FDA) issued a draft guidance describing the quality management system (QMS) information it expects in premarket approval (PMA) and humanitarian device exemption (HDE) submissions under the forthcoming Quality Management System Regulation (QMSR). The QMSR, which incorporates ISO 13485:2016 and ISO 9000:2015 Clause 3 by reference, will replace the existing Quality System (QS) Regulation by amending 21 C.F.R. Part 820, effective February 2, 2026.
While the QMSR will apply to all medical devices marketed in the United States, including those authorized through the 510(k) and de novo pathways, this draft guidance specifically addresses QMS documentation for PMA and HDE submissions. The FDA has not yet issued guidance on how QMSR expectations should be reflected in 510(k) or de novo submissions, which are not generally required to provide documentation of the manufacturing facility’s compliance with the QS Regulation, and pre-decision inspections are not standard for these applications. For de novo requests, the FDA has previously clarified that inspections may occur in limited circumstances, typically to gather information on critical or novel manufacturing processes, and do not generally assess comprehensive quality system compliance.
Shift to an ISO 13485–Based Framework
The draft guidance signals a major transition from the FDA’s legacy, U.S.-centric QS Regulation to a globally harmonized, risk-based system aligned with ISO 13485. Beginning in February 2026, PMA and HDE submissions, as well as associated preapproval inspections, will be evaluated against this new standard.
While the basic submission format (e.g., per-facility organization) remains familiar, the FDA now recommends additional elements such as:
- DUNS numbers for all manufacturing sites.
- A plan for Unique Device Identification (UDI) System assignment and maintenance.
- A dedicated QMSR module for modular PMAs.
- Mapping of QMS content directly to ISO 13485 clauses. The draft guidance organizes expectations by ISO 13485 clauses and recommends providing the described clause-linked documentation.
The FDA notes that when using eSTAR for electronic submissions for PMAs, applicants should ensure the required information is captured. The draft guidance also recommends inclusion of both procedures and representative evidence, such as an example validation plan, protocol, or report for environmental or contamination controls; sample process validation reports; and a production flow diagram identifying manufacturing steps and the responsible entity when multiple facilities are involved.
Further information on the PMA review process is available on the FDA’s webpage. Additional details on the modular submission process for PMA and HDE applications can be found in the FDA’s guidance document, “Premarket Approval Application and Humanitarian Device Exemption Modular Review.”
Expanded Regulatory Linkages
The draft guidance explains that, in addition to meeting ISO 13485 requirements, a full description of the quality management system in a marketing submission should also address a specific set of additional regulatory requirements. These requirements are identified in 21 C.F.R. 820.10(b) as necessary to fully comply with the relevant ISO 13485 provisions, including UDI, device tracking, medical device reporting (MDR), and corrections and removals, as well as record control and device labeling and packaging controls.
The draft guidance also references updated provisions for record control and labeling and packaging (21 C.F.R. 820.35 and 820.45) and requests sample UDIs and Global Unique Device Identification Database (GUDID) records. Importantly, manufacturers should provide risk-based justifications throughout their submissions explaining the rationale behind cleanliness classifications, supplier controls, validation strategies, and corrective and preventive action activities.
Risks of Noncompliance: Why QMSR Readiness Is Critical for Medtech Companies
Medtech companies should recognize that failure to meet the new QMSR requirements can have significant business consequences, including the risk of the FDA denying a marketing application. Under the Federal Food, Drug, and Cosmetic Act (FD&C Act), PMA and HDE marketing submissions are required to include a “full description” of the methods, facilities, and controls used for manufacturing, processing, packing, and installing the device. The draft guidance makes clear that if a PMA or HDE application does not adequately demonstrate that manufacturing methods and controls conform to the QMSR, or if insufficient information is submitted, the FDA is required to deny approval under the FD&C Act.
Preapproval inspections are also a critical part of the submission review process for PMAs and HDEs. In a perfect world, the applicant and the FDA would coordinate a preapproval inspection early in the review process, there would be no significant observations, and the good manufacturing practice preapproval process would proceed smoothly. However, this is not the reality where most firms find themselves. Preapproval inspections often occur very late in the review process, which means that even relatively minor issues identified during the inspection can cause delays in the final approval decision. If the FDA finds major deficiencies in quality or manufacturing processes during the preapproval inspection, the stakes are even higher. Addressing these findings at this late stage can significantly delay the application review process or even result in an application denial, impacting product launch timelines, affecting investor confidence, and allowing competitors to gain market share.
Prepare for Compliance: Cross-Functional Coordination
To prepare for QMSR implementation, companies should conduct a comprehensive gap analysis comparing their existing QS-based systems to the ISO 13485–aligned framework. Given the breadth of the new requirements, broader collaboration among relevant teams and external partners will be critical. Regular cross-functional meetings, centralized document management, and strong internal communication will help maintain consistency and readiness across departments. For example:
- Quality and Manufacturing should lead updates to procedures, risk rationales, and validation documentation.
- Regulatory Affairs should ensure alignment with submission structure and evolving FDA expectations.
- R&D should verify that design controls, risk management, and verification/validation activities meet ISO 13485 principles.
- Clinical Affairs and Post-Market Surveillance should ensure complaint handling aligns to MDR processes and that production/postproduction feedback is integrated into risk management.
- Supply Chain and Procurement should evaluate supplier qualification, monitoring processes, and documentation under the new risk-based requirements.
- IT and Document Control can help ensure traceability, version control, and electronic document readiness for inspection and submission. Manufacturers should be ready to provide clause-mapped document/record controls and samples of UDI and GUDID records for the subject device if possible.
Proactive QMSR compliance is not just a regulatory obligation. It is a critical business strategy. Timely and robust preparation helps ensure uninterrupted market access and supports long-term growth. Now is the time for medtech companies to review their new product development plans and quality systems, address any gaps, and ensure their submissions are comprehensive, well-documented, and fully aligned with the FDA’s new expectations under the QMSR.
We encourage medical device manufacturers to begin QMSR transition planning without delay. By identifying gaps early, clearly documenting risk-based rationales, and fostering structured collaboration among internal teams and external partners, your organization will be well-positioned for successful submissions and inspections under the new QMSR framework by February 2026.
Alston & Bird’s FDA Drug & Device team regularly assists medtech companies with quality system compliance, addressing manufacturing challenges, conducting gap assessments, developing documentation strategies, and supporting cross-functional implementation. We also help companies prepare for FDA inspections and provide guidance on inspection response. Please contact us if you would like guidance or support to ensure your organization is fully prepared for successful premarket submissions and inspections under the new QMSR framework.
Interested parties can submit comments on this draft guidance document to Docket Number FDA-2025-D-4051.
If you have any questions, or would like additional information, please contact one of the attorneys on our FDA: Drug & Device team.
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