Executive summary

Since 2022, FDA has released a combination of a final rule aligning the Quality System requirements with ISO 13485 (the QMSR final rule) and multiple final and draft guidances that adjust or clarify what PMA and HDE submissions should contain to address quality-management expectations. Collectively, these actions: (1) align U.S. quality expectations with ISO 13485 by February 2, 2026; (2) tailor the amount and format of manufacturing and quality-system information FDA expects in PMA/HDE submissions (e.g., modularizing manufacturing/BIMO, leveraging VIP appraisals, and clarifying when 30‑day notices vs. annual reports are appropriate for production/quality software changes); and (3) embed QMSR (21 CFR part 820) design-control outputs and related risk-management documentation directly into topic-specific content expectations (e.g., cybersecurity, software, human factors, PCCPs). Access to each underlying rule or guidance is provided below via FDA media links and Federal Register citations ^{1931942262272941908726164121144181297235}.

Rulemaking context that drives QMSR expectations in PMA/HDE

• Quality Management System Regulation (QMSR) Final Rule. On February 2, 2024, FDA issued a final rule that amends 21 CFR part 820, incorporating ISO 13485:2016 by reference and aligning U.S. device quality-system requirements with international standards; the rule takes effect February 2, 2026 (Federal Register 89 FR 7496). This change underpins the quality-system expectations that PMA/HDE submissions must meet once effective. Official access: https://www.federalregister.gov/d/2024-01709 ¹⁹³¹⁹⁴.

• Proposed QSR amendments (background). FDA’s earlier proposal to amend 21 CFR part 820 (87 FR 10119; February 23, 2022) laid the groundwork for the final QMSR rule and is frequently cross‑referenced in device guidances that discuss PMA/HDE content. Official access: https://www.federalregister.gov/documents/2022/02/23/2022-03227/medical-devices-quality-system-regulation-amendments ^2232952351.

Significance: These rulemakings do not by themselves prescribe PMA/HDE dossier sections, but they change the quality-system benchmark to which manufacturing methods, facilities, and controls described in PMA/HDEs must conform. Guidances issued since 2022 increasingly reference this alignment and indicate FDA will update references in guidances as the QMSR effective date approaches ^23518161.

Final guidances that affect PMA/HDE submission content in relation to QMSR

Enforcement Policy for Certain Supplements for Approved PMA or HDE Submissions (final, Nov 2, 2023)

• What changed: Clarifies FDA’s enforcement approach for certain PMA/HDE supplements tied to manufacturing changes and quality-system controls, referencing current 21 CFR part 820 and FDA’s move to align with ISO 13485. It emphasizes documenting changes in device master records and change-control records consistent with part 820, with updates anticipated as QMSR is finalized ^{226228225224223227}.
• Access: FDA guidance PDF at https://www.fda.gov/media/138265/download (issued November 2, 2023; superseding earlier versions) ²²⁶²²⁷.

Fostering Medical Device Improvement: FDA Activities and Engagement with the Voluntary Improvement Program (VIP) (final, Sept 15, 2023)

• What changed: Provides modified PMA/HDE submission formats for VIP participants (e.g., 30‑Day Change Notices, Manufacturing Site Change Supplements, and Manufacturing Modules). When VIP appraisals demonstrate quality maturity and part 820 compliance, FDA may accept streamlined content, reducing duplicative quality-system detail in the PMA/HDE submission package ^{294291292289293}.
• Access: https://www.fda.gov/media/158180/download ²⁹⁴.

Transitional Enforcement Policy for Ethylene Oxide Sterilization Facility Changes for Class III Devices (final, 2024)

• What changed: For PMA (180-day) and HDE (75-day) site change supplements, sponsors must include information demonstrating manufacturing/sterilization at the new site complies with the Quality System Regulation (21 CFR part 820). FDA may exercise limited enforcement discretion during transitions if notification and timely supplements are provided ^190188191189.
• Access: https://www.fda.gov/media/183833/download ¹⁹⁰.

Premarket Approval Application and Humanitarian Device Exemption Modular Review (final, 2025)

• What changed: Requires manufacturing and Bioresearch Monitoring (BIMO) to be submitted as standalone modules in modular PMA/HDEs, rather than bundled with other disciplines. This modularization references Quality System information, aligning with QMSR expectations and clarifying how reviewers will see manufacturing/QS content organized ⁸⁷⁸⁵.
• Access: https://www.fda.gov/media/73513/download ⁸⁷.

Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions (final, Sept 27, 2023)

• What changed: Updates PMA/HDE documentation expectations to show cybersecurity is integrated into design controls (21 CFR 820.30), including risk management and software validation outputs. Encourages use of a Secure Product Development Framework, emphasizing that QMSR design-control outputs are central to premarket demonstrations of safety/effectiveness ^252729302628.
• Access: https://www.fda.gov/media/119933/download ²⁶.

Content of Premarket Submissions for Device Software Functions (final, June 14, 2023)

• What changed: Supersedes 2005 guidance and clarifies software documentation expected in PMA/HDE submissions, tied to design controls (e.g., software validation and risk analysis under 21 CFR 820.30). Aligns content expectations with QMSR-consistent design-control principles ^164166163.
• Access: https://www.fda.gov/media/153781/download ¹⁶⁴.

Computer Software Assurance (CSA) for Production and Quality System Software (final, Sept 24, 2025)

• What changed: Clarifies when PMA/HDE supplements or 30‑day notices are required for changes in production/quality-system software. Risk-based approach: changes not affecting safety/effectiveness can be reported in annual reports; if they may affect safety/effectiveness, use a 30‑day notice. Aligns with the QMSR final rule timelines (effective Feb 2, 2026) ^123124121.
• Access: https://www.fda.gov/media/188844/download; related rulemaking context cited at 89 FR 7496 ^{123124121125122}.

Marketing Submission Recommendations for a Predetermined Change Control Plan (PCCP) for AI‑Enabled Device Software Functions (final, 2024)

• What changed: For PMAs, FDA must deny approval if manufacturing methods or controls do not conform to QMSR; PCCP modifications must be executed consistent with the manufacturer’s quality system. Ties PMA approval and PCCP implementation to part 820/QMSR conformance, anticipating updated references as the 2026 effective date approaches ^{181182183184185307}.
• Access: https://www.fda.gov/media/166704/download; QMSR rule at 89 FR 7496 ¹⁸¹.

Breakthrough Devices Program (final, 2023)

• What changed: For PMA pathways, FDA may accept less QS/manufacturing detail under specific conditions (e.g., good compliance history, limited new risks) and may defer certain preapproval inspections, using declarations and current risk analyses to support earlier approval; inspections would follow within 12 months. Notes the ongoing alignment to ISO 13485 via QMSR rulemaking ^296297298295.
• Access: https://www.fda.gov/media/162413/download ²⁹⁷.

Technical Considerations for Medical Devices with Physiologic Closed‑Loop Control Technology (final, 2023)

• What changed: Provides PMA/HDE submission recommendations, while acknowledging the pending alignment of part 820 with ISO 13485 and committing to update guidance references upon the rule’s effect—directly signaling how QMSR alignment affects future submission content references ²³⁵.
• Access: https://www.fda.gov/media/154994/download ²³⁸; QSR amendments context at 87 FR 10119 ²³⁵.

Draft guidances that map PMA/HDE content to QMSR (for comment; not yet final)

Content of Human Factors Information in Medical Device Marketing Submissions (draft, Dec 9, 2022)

• What changed (proposed): Recommends PMA/HDE submissions include human factors engineering documentation that reflects design verification/validation as required under 21 CFR part 820 design controls, connecting QMS outputs to premarket content ^16131730114.
• Access: https://www.fda.gov/media/163694/download ¹⁶.

Computer Software Assurance for Production and Quality System Software (draft, Sept 13, 2022)

• What changed (proposed): Risk-based clarification of when to use PMA/HDE annual reports vs. 30‑day notices for production/QS software changes based on potential impact on safety/effectiveness—anticipating QMSR alignment ¹⁴⁹¹⁴⁵.
• Access: https://www.fda.gov/media/161521/download ¹⁴⁹.

Predetermined Change Control Plans for Medical Devices (draft, 2024)

• What changed (proposed): Requires PCCPs in PMAs to be implemented consistent with the manufacturer’s quality system; FDA will deny PMA approval if manufacturing methods/controls do not conform to QSR/QMSR. PMA annual reports should summarize PCCP changes and labeling updates. Notes the QMSR final rule timing (effective Feb 2, 2026) ^139140144143.
• Access: https://www.fda.gov/media/180978/download ¹⁴⁴.

Artificial Intelligence‑Enabled Device Software Functions: Lifecycle Management and Marketing Submission Recommendations (draft, Jan 7, 2025)

• What changed (proposed): Recommends PMAs include QMSR‑related documentation (e.g., design controls, design validation, change management) and, where appropriate, performance monitoring plans as conditions of approval. Links guidance references to the QMSR rule (effective Feb 2, 2026) ^{265266267312270}.
• Access: https://www.fda.gov/media/184856/download ²⁶⁵²⁶⁹.

Patient‑Matched Guides to Orthopedic Implants (draft, June 28, 2023)

• What changed (proposed): Clarifies that PMA submissions for these guides should demonstrate compliance with design controls (21 CFR 820.30) and process validation (21 CFR 820.75) where results cannot be fully verified by inspection/testing—linking QMSR practices to submission evidence ²⁷¹²⁷².
• Access: https://www.fda.gov/media/169792/download ²⁷⁵.

Essential Drug Delivery Outputs for Devices Intended to Deliver Drugs and Biological Products (draft, 2024)

• What changed (proposed): For PMAs, emphasizes inclusion of design verification/validation data and control strategies consistent with QMSR design controls (21 CFR 820.30) to ensure Essential Drug Delivery Outputs across the lifecycle ^919293949596.
• Access: https://www.fda.gov/media/179545/download ^91929496.

How these changes affect PMA/HDE sponsors

• Alignment with ISO 13485: By February 2, 2026, the quality benchmark that PMA/HDE manufacturing methods, facilities, and controls must meet transitions to the QMSR framework that incorporates ISO 13485:2016 by reference. Sponsors should ensure their quality documentation in PMAs/HDEs maps cleanly to ISO 13485‑aligned expectations and anticipate guidance reference updates as the effective date approaches ^19319418161.

• Tailored submission content and formats: Sponsors can leverage modular PMA/HDE structures to present manufacturing and BIMO as standalone modules, enabling clearer, early submissions and staged reviews of quality system information ⁸⁷. VIP participants may reduce duplicative detail in selected manufacturing submissions (e.g., 30‑Day notices, site change supplements, manufacturing modules) when appraisal evidence demonstrates part 820 compliance and robust performance ²⁹⁴.

• Risk‑based change reporting: For production and quality-system software that supports PMA/HDE devices, use annual reports when changes do not affect safety/effectiveness and 30‑day notices when they may—supported by risk assessments commensurate with device impact, per CSA guidance ^123124121149.

• Topic‑specific documentation mapped to design controls: FDA’s cybersecurity, software, and human‑factors guidances explicitly tie PMA/HDE content to QMSR design‑control outputs (risk management, software validation, verification/validation evidence) to substantiate reasonable assurance of safety and effectiveness ^2616416.

• PCCPs anchored in the quality system: For change‑adaptive technologies (including AI‑enabled devices), PCCPs in PMAs must be consistent with the manufacturer’s quality system; lack of QMSR conformance is grounds for denial. Post‑approval implementation of PCCP changes must follow established QMS procedures, with summary reporting in PMA annual reports where specified ¹⁸¹¹⁴⁴.

Direct access to key documents

• QMSR Final Rule (effective Feb 2, 2026): 89 FR 7496; https://www.federalregister.gov/d/2024-01709 ¹⁹³¹⁹⁴.
• Enforcement Policy for Certain Supplements for Approved PMA or HDE: https://www.fda.gov/media/138265/download ²²⁶²²⁷.
• VIP Guidance (modified formats for PMA/HDE manufacturing submissions): https://www.fda.gov/media/158180/download ²⁹⁴.
• EO Sterilization Facility Changes (Class III; PMA/HDE site change supplements): https://www.fda.gov/media/183833/download ¹⁹⁰.
• Modular PMA/HDE Review (manufacturing and BIMO as standalone modules): https://www.fda.gov/media/73513/download ⁸⁷.
• Cybersecurity in Medical Devices (QMS + premarket content): https://www.fda.gov/media/119933/download ²⁶.
• Device Software Content (premarket documentation expectations): https://www.fda.gov/media/153781/download ¹⁶⁴.
• CSA for Production and Quality System Software (final): https://www.fda.gov/media/188844/download ^123124121125.
• PCCP for AI‑Enabled DSFs (final): https://www.fda.gov/media/166704/download ¹⁸¹.
• Breakthrough Devices Program (allowances for QS info and inspections): https://www.fda.gov/media/162413/download ²⁹⁷.
• Physiologic Closed‑Loop Control Tech (final): https://www.fda.gov/media/154994/download ²³⁸.
• Human Factors (draft): https://www.fda.gov/media/163694/download ¹⁶.
• CSA (draft): https://www.fda.gov/media/161521/download ¹⁴⁹.
• PCCPs for Medical Devices (draft): https://www.fda.gov/media/180978/download ¹⁴⁴.
• AI‑Enabled DSFs Lifecycle (draft): https://www.fda.gov/media/184856/download ²⁶⁵.
• Patient‑Matched Guides (draft): https://www.fda.gov/media/169792/download ²⁷⁵.
• Essential Drug Delivery Outputs (draft): https://www.fda.gov/media/179545/download ^91929496.
• Proposed QSR amendments (background): 87 FR 10119 (Feb 23, 2022): https://www.federalregister.gov/documents/2022/02/23/2022-03227/medical-devices-quality-system-regulation-amendments ^2232952351.

Notes on scope

Several searched documents focused on topics like 510(k) templates, user fees, appeals, postmarket surveillance, and other administrative or technical subjects. They did not introduce formal changes to PMA/HDE content in relation to QMSR and are therefore not listed above as PMA/HDE‑QMSR content updates ^{3132333435369799102169170171172173174109110111112113114}. Where 510(k)‑focused drafts referenced the QMSR final rule, those notices reflect the broader regulatory alignment rather than PMA/HDE‑specific content changes ⁶¹⁶³.

Bottom line

• The most consequential formal change is the QMSR final rule (89 FR 7496) that aligns U.S. quality system requirements with ISO 13485 by February 2, 2026, and will cascade into FDA guidance references and PMA/HDE quality expectations ^19319418161.
• Multiple final guidances already operationalize how quality‑system outputs should appear in PMA/HDE content (e.g., cybersecurity, software, CSA, VIP, EO sterilization changes, modular review), and several draft guidances outline additional QMSR‑linked content expectations (e.g., human factors, PCCPs, AI‑enabled DSFs, patient‑matched guides, essential drug delivery outputs), all accessible at the FDA links provided above ^{2262272941908726164121144181297235}.