AMDM IVD Fall Focus Meeting 2025: From Policy to Practice in Diagnostic Regulation

The AMDM IVD Focus Fall Meeting brought together regulators, industry leaders, and diagnostic professionals for two days of focused discussion and actionable insight. The meeting focused on the current and emerging regulatory landscape for in vitro diagnostics (IVDs), providing clarity on implementation priorities, policy shifts, and the operational realities of compliance in 2026 and beyond.

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U.S. Regulation and Policy Landscape

Sessions on U.S. regulatory developments opened with reflections on the federal government shutdown and its operational effects on FDA activities. While essential health and safety functions and reviews supported by existing user-fee funds continue, many new submissions and policy initiatives remain paused until appropriations resume.

A discussion of the Loper Bright legal decision highlighted how the rescinded LDT Rule and evolving interpretations of agency authority will continue to influence FDA’s approach to laboratory-developed tests (LDTs). While FDA’s direct authority over LDTs has been clarified, the Agency may still exert oversight through several indirect pathways — including regulation of collection devices, research-use-only (RUO) products, and requirements tied to companion diagnostics during the associated drug and biologic approvals.

Beyond LDTs, speakers highlighted FDA’s expanding oversight of emerging technologies such as software-based diagnostics and wellness devices. The discussion noted the Agency’s growing attention to wellness wearables — low-risk products that promote healthy lifestyles — and the FDA’s position on software functions that may qualify for general wellness exemptions or fall under stated enforcement discretion. 

Across several sessions, a consistent message emerged: even under enforcement discretion, manufacturers are expected to maintain robust design control, validation, and quality management systems.

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2025 Legislative Priorities

Meeting discussions highlighted several legislative initiatives likely to shape the next phase of diagnostic policy:

• Protecting Access to Medicare Act (PAMA) reform, aimed at establishing a sustainable reimbursement framework for diagnostic innovation, and the Reforming and Enhancing Sustainable Updates to Laboratory Testing Services (RESULTS) Act.  The latter is a proposed bill to reform Medicare’s lab test payment system, address flaws in the current data collection method, and prevent major payment cuts that could threaten patient access to testing.
• The Patients Deserve Price Tags Act, a proposed bill that aims to increase transparency in healthcare costs. 
• The Ensuring Patient Access to Critical Breakthrough Products Act, proposed legislation that would create a four-year, automatic temporary Medicare coverage period for FDA-designated breakthrough devices, requiring CMS to make a permanent determination within that time. In contrast, TCET (Transitional Coverage for Emerging Technologies) is an administrative pathway created by CMS, which is more restrictive, limits devices to five per year, requires a separate application, and doesn’t guarantee coverage.  Of note, in September 2025, the Ways and Means Committee passed an amended version of the Ensuring Patient Access to Critical Breakthrough Products Act that excludes in vitro diagnostics from scop.
• The Medicare Multi-Cancer Early Detection Screening Coverage Act – proposed legislation to create a pathway for Medicare to cover multi-cancer early detection (MCED) blood tests after they are approved by the FDA and determined to have clinical benefit.

Together, these priorities aim to balance innovation, patient access, and predictable oversight.

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Implementing FDA’s Quality Management System Regulation (QMSR)

Although ISO 13485:2016 and the current CGMP requirements for devices in 21 CFR Part 820 are substantially similar, the FDA’s forthcoming Quality Management System Regulation (QMSR), effective February 2, 2026, incorporates ISO 13485:2016 by reference while maintaining key FDA-specific provisions.

Manufacturers already compliant with ISO 13485 should note that several FDA-specific definitions and expectations remain. Beyond the ISO clauses, the QMSR preserves historical Part 820 provisions related to:

• Risk management
• Control of records (including claims, labeling, and packaging)
• Electronic records and signatures compliance

Device manufacturers may need targeted process updates and internal training to ensure full alignment before February 2026.

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Global Regulatory Perspectives: IVDR and Health Canada

Transition to the EU In Vitro Diagnostic Regulation (IVDR) remains a critical focus area.

• Class D devices are already transitioned under the IVDR.
• Manufacturers of Class C legacy IVDs must lodge applications to a notified body for conformity assessment by May 26, 2026, and by May 26, 2027 for Class B and A (sterile) devices that were self-declared under the IVDD.

While notified body capacity has improved, review timelines remain long — often 13 to 18 months for combined QMS and product certificates.

Common issues identified during Notified Body reviews include product misclassification, inconsistent intended purpose statements, missing documents required by Annex II/III, and clinical evidence that does not meet IVDR expectations.

Health Canada updates to the Medical Device Regulations (SOR/98-282) focused on recall definitions, reporting and record-keeping, and modernization of MDEL application requirements—changes that took effect December 14, 2024.

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Companion Diagnostics (CDx): Coordination and Collaboration

The evolution of companion diagnostics (CDx) continues to highlight the increasing interdependence between drug and diagnostic development.

Conducting early-phase clinical investigations with non-CE-marked products, especially when a CDx may be in scope, remains challenging despite additional MDCG guidance. Key pain points include the adequacy of analytical performance data, clarity on roles and responsibilities (e.g., study sponsorship), and interpretation of clinical evidence when different assays are used within a study or alongside the investigational medicinal product.

EMA consultation timelines and notified body reviews remain gating factors for drug/CDx contemporaneous approval, often driving the need for parallel data strategies across jurisdictions. Successful CDx programs emphasize cross-functional collaboration—linking regulatory, clinical, and analytical teams from concept through commercialization to ensure synchronized regulatory outcomes.

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Design and Delivery: Cybersecurity, Self-Collection Devices, and Human Factors Usability Studies

Cybersecurity

Cybersecurity expectations are now embedded across the device lifecycle. FDA’s approach — consistent with NIST SP 800-218 — treats cybersecurity as part of quality system management, encompassing secure design, verification and validation, postmarket monitoring, and coordinated vulnerability disclosure.

Manufacturers were encouraged to document threat modeling, maintain vulnerability management programs, and ensure supplier controls and software updates are traceable to cybersecurity risk mitigations. Documentation should link cybersecurity risk management directly to design controls and product safety — reinforcing that security is intrinsic to device effectiveness, not an afterthought.

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Human Factors Usability Studies: Self-Collection and Over-the-Counter (OTC) Devices

Devices intended for use outside professional settings — whether self-collection kits or over-the-counter (OTC) diagnostics — must integrate risk management with user interface design to ensure safety, accuracy, and ease of use.

For self-collection devices, the user interface must be intuitive, logical, and easy to navigate to minimize handling errors and ensure adequate specimen quality. Early formative studies, conducted during development, help refine interface elements and identify use-related risks. Design simplification that prioritizes comfort, clarity, and intuitive interaction improves both sample adequacy and user confidence.

For OTC diagnostics, FDA requires human factors usability studies to demonstrate that untrained users can safely and effectively perform the test and interpret results. Simplified workflows, clear visual cues, and intuitive interfaces improve accuracy and reduce invalid outcomes. Success depends on conducting formative studies early and iteratively, as design changes can introduce new usability issues.

Summative usability studies, performed by intended users in the intended environment and incorporating the complete testing workflow, should confirm that the user interface is free from unacceptable risk.

The key takeaway: whether for self-collection or OTC IVDs, human factors usability studies are integral to safe and effective product performance. Iteration, simplicity, and communication are essential to delivering reliable results and satisfying FDA’s expectations for the growing arena of lay-user diagnostics.

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How Beaufort Can Help

As global diagnostic regulation continues to advance, success depends on transforming regulatory complexity into clear, executable strategy. At Beaufort, we help diagnostic and device manufacturers stay ahead of evolving requirements — aligning design, quality, and compliance from the earliest stages of development through market readiness.

Our multidisciplinary team translates policy into practice, guiding manufacturers through FDA and global frameworks with precision and foresight. By integrating regulatory intelligence with operational execution, we enable clients to anticipate change, strengthen quality systems, and accelerate access to innovative diagnostic technologies.

Beaufort helps innovators turn regulatory shifts into market momentum — empowering our clients to advance diagnostic technologies that can make a measurable difference.

Point-of-Care (POC) diagnostic trials for influenza are unlike any other. The season is short, virus circulation is unpredictable, and enrollment targets — particularly for influenza B — are notoriously difficult to meet. Every week counts, and missteps in site startup, patient access, or data flow can jeopardize an entire program.

At Beaufort, we’ve built our approach to meet these challenges head-on. We deliver end-to-end CRO services with proven expertise and proactive strategies that simplify complexity and safeguard timelines. Our team integrates rapid site activation, flexible patient recruitment, streamlined vendor oversight, real-time data management, and inspection-ready quality systems — ensuring sponsors capture the season and achieve submission-ready results.

Strategic & Targeted Patient Access

Meeting enrollment targets in an influenza in vitro diagnostic (IVD) trial requires a precise understanding of seasonal influenza patterns and a proactive, flexible approach to sample collection. Beaufort applies strategies that enable rapid site activation and maximize subject participation during peak influenza circulation through:

Enrollment success depends on activating the right sites at the right time — and that’s where Beaufort excels.

• Development of a seasonally aligned, high-throughput, and geographically diverse enrollment plan supported by real-time monitoring of influenza positivity rates and contingency strategies to ensure sufficient influenza B cases.
• Definition of clear inclusion criteria based on influenza-like illness (ILI) symptoms and prioritization of high-volume, high-performing sites such as urgent care centers, outpatient clinics, and pediatric practices to accelerate trial startup.
• Application of flexible and nimble enrollment processes enabling sites to rapidly identify, consent, and collect samples from eligible patients, ensuring timely completion of enrollment within the influenza season.

Streamlined Trial Operations & Delivery

The seasonality of influenza, coupled with complex logistics and vendor coordination, demands efficiency and adaptability. Beaufort structures its delivery model to keep specimen flow uninterrupted, vendors aligned, and monitoring optimized throughout the influenza season by:

• Deploying a full and experienced trial team at launch to ensure rapid scale-up ahead of peak influenza circulation.
• Harmonizing vendor and laboratory oversight with a dedicated manager streamlining contracting, specimen handling, and testing logistics.
• Optimizing clinical monitoring and site oversight for timely verification of enrollment data, sample integrity, and rapid issue resolution.
• Building a streamlined data management framework with standardized processes, real-time data reconciliation, and rapid cleaning of laboratory and clinical data streams.

Continuous specimen flow is the difference between meeting timelines and missing the season.

Together, these measures shorten startup timelines, maintain uninterrupted specimen flow, reduce operational bottlenecks, and accelerate data readiness — all essential to executing influenza IVD trials within the narrow seasonal window.

Relentless Quality Assurance from Day One

Quality and compliance are safeguarded from the very beginning. Beaufort implements measures that protect data integrity, ensure inspection readiness, and keep the trial financially on track at every stage:

• An inspection readiness program is launched from the start.
• Data quality standards are implemented across clinical monitoring and data reviews.
• Customized visual dashboards are designed to track site progress, compliance, and key milestones.
• Financial project analysis is conducted to detect, report, and mitigate potential budget variances.

These quality assurance measures reduce operational risk, minimize data cleaning burdens, prevent compliance setbacks, and keep the trial financially stable — increasing both efficiency and confidence in delivering influenza IVD trials within seasonal timelines.

Results that Meet Your Needs

Beaufort’s integrated approach to patient access, streamlined delivery, and relentless quality assurance ensures the successful execution of influenza IVD trials in seasonal respiratory infection:

• Enrollment targets are met on schedule, with a seasonally aligned and geographically diverse plan.
• Rapid site activation and flexible recruitment processes accelerate enrollment, ensuring timely completion within the influenza season.
• Real-time monitoring and proactive data management accelerate interim analysis delivery and maintain continuous visibility of site performance.
• Inspection readiness and compliance programs safeguard regulatory preparedness, while standardized quality measures reduce the incidence of data queries  and increase protocol compliance rates.
• Proactive financial oversight keeps the trial on track, with early analysis mitigating potential budget variances.

Seasonal Trials Move Fast. So Do We.

This integrated CRO services model reduces delays, prevents bottlenecks, and accelerates both enrollment and data readiness, ensuring influenza IVD trials are completed efficiently within the narrow seasonal timeframe Let’s talk about how Beaufort’s CRO services can accelerate your influenza program and deliver results on time. Contact Us Today.

Insights from the IVD Track at MedTech Summit 2025

The IVD track at MedTech Summit 2025 in Berlin brought together regulators, notified bodies, and industry experts to examine the continuously evolving regulatory landscape for in vitro diagnostics (IVDs). Over two days, discussions spanned IVDR implementation, the progress of future UK regulation, considerations for IVD and companion diagnostic performance studies, global approaches to in-house and laboratory-developed tests, readiness for EUDAMED, and the first operational experience with EU Reference Laboratories (EURLs). For regulatory leaders, the sessions underscored not only immediate compliance requirements but also broader strategic imperatives:

• Managing portfolios under changing regulations
• Strengthening post-market obligations
• Preparing now for forthcoming demands such as EUDAMED registration and EURL engagement

Success in the IVD space now requires more than regulatory awareness—it demands foresight, adaptability, and a partner who can bridge operational realities with evolving expectations. The conversations in Berlin underscored this need for strategic guidance, not just reactive compliance. Beaufort continues to lead in this space—helping sponsors anticipate change, interpret evolving requirements, and implement pragmatic solutions. The insights below highlight the most critical developments and their implications for diagnostic developers and sponsors.

IVDR Implementation in the EU

Implementation of the IVDR continues to advance. By late 2024, approximately 1,273 (QMS and product) certificates had been issued, including 377 for Class D devices and 32 for companion diagnostics, against an estimated 40,000 IVDs on the EU market.

Navigating shifting regulations requires foresight, not just compliance. Beaufort helps sponsors and manufacturers anticipate evolving requirements, implement pragmatic solutions, and accelerate patient access.

Timelines remain long. Total average time to complete QMS or Technical Documentation certifications each typically require 13–18 months, with much of that time consumed by iterative Notified Body questions and requests for supplementary evidence.  Industry and Notified Bodies have submitted proposals to establish predictable timelines.

Transitional provisions. Regulation (EU) 2024/1860 published in July 2024 allows eligible legacy IVD devices to remain available provided they undergo no “significant change” (per MDCG 2022-6), continue to comply with IVDD requirements:

Guidance and interpretation. Although more than 120 MDCG documents are now in circulation, key guidance is still missing and guidance is changing over time (e.g., Covid test down-classification from D to B and changing EMDN numbers) which is complicating planning.  Updates to documents such as MDCG 2019-6 on structured dialogue are designed to smooth Notified Body–manufacturer interactions, however the guidance focuses on the “what” without providing the “how”.  Additional new guidance is expected for IVDR orphan devices; MDCG 2019-13 on sampling devices for assessment of Technical Documentation; Q&A on the AI Act, PSUR evaluation reports, Q&A regarding IVD performance studies (now available), and a Q&A regarding distance sales among others.

Notified Body Capacity has improved. Notified bodies stressed that staffing investments have eased the bottlenecks. The real challenge now is manufacturers delaying submissions and the quality of manufacturer submissions. Files that are incomplete or inconsistent trigger lengthy review cycles.

The UK MHRA’s Developing Framework

Dual system remains in place. Great Britain (England, Scotland, and Wales) operates under MHRA’s sovereign model, while Northern Ireland continues to align with IVDR. Because the UK’s Medical Devices Regulations 2002 can only be amended rather than rewritten, MHRA has relied on a series of legally required public consultations to move reform forward.

Post-market surveillance is now fully in effect. As of June 2025, PMS obligations apply in Great Britain. These mirror EU IVDR concepts in many respects—risk-based planning, PMS plans and reports, periodic safety update reports (PSURs), trend reporting, and vigilance requirements including incident and FSCA reporting. However, reporting timelines differ, and further MHRA guidance is expected.

Premarket classification will shift to four risk classes. Future statutory instruments will align IVDs with a four-class risk framework based on patient and public health impact. Requirements for market access will be scaled accordingly. MHRA has specifically sought views on regulatory requirements for Class B IVDs, including software IVDs. Options under consideration include allowing manufacturers to self-assess conformity with the regulations while holding ISO 13485 QMS certification from a UKAS-accredited body.

Reliance and recognition models are being developed. MHRA is evaluating pathways that would allow devices already approved by trusted regulators—such as in Australia, Canada, the EU, or the USA—to access the GB market more quickly. These devices would still need to meet GB-specific requirements, including English labelling, a UK Responsible Person, unique device identification (UDI), and compliance with UK post-market surveillance (PMS) obligations.

Fees are increasing. MHRA continues to raise fees in order to sustain its role as a sovereign regulator. This trend will weigh most heavily on smaller developers.

Reform remains a long-term process. Even with consultations and amendments under way, meaningful structural change will take several years. In the meantime, companies must operate under hybrid arrangements while preparing for further reform.

Biomarker Testing in Clinical Trials

Synchronizing drug and diagnostic development timelines is essential to contemporaneous marketing authorizations. Beaufort brings the regulatory and operational expertise to assure IVD submissions are timely and complete, keeping programs aligned.

Defining medical purpose is critical. When a biomarker assay is used to determine patient inclusion or exclusion, guide therapy, or support monitoring, it is deemed to have a medical purpose under IVDR and requires a clinical performance study (CPS). By contrast, assays used solely for stratification or exploratory endpoints may fall outside IVDR scope. However, where data are intended to support CE marking, the trial must still be conducted to IVDR and ISO 20916 standards.

Obligations extend to early-phase studies. Even Phase I trials may trigger IVDR requirements if assay results influence patient management. This includes the obligation for independent monitoring of testing sites, as outlined in Article 68 and Annex XIV.

Combined studies present operational risks. Trials involving multiple pharmaceutical sponsors or diagnostic partners create challenges around data ownership, confidentiality, and clinical trial/performance study timelines. In practice, separate CTA and PS submissions are often the more reliable approach, reducing risk of delay or dispute.

Repurposing CE-marked diagnostics is not straightforward. Using an existing CE-marked diagnostic in a new therapeutic context frequently requires a new clinical performance study, along with updates to the technical documentation, risk management files, and labeling. Sponsors must anticipate these requirements early to avoid disruption.

Pharma-Diagnostic Collaboration – Combine Studies

Early alignment is essential. Regulatory strategies for diagnostics must be developed in parallel with medicinal product plans. Deferring diagnostic planning risks misalignment and late-stage delays.

Roles and responsibilities must be explicit. Collaboration agreements should clearly define who holds responsibility for regulatory submissions, who engages with regulators, and how decision-making authority is exercised across partners.

Rapid response capacity is expected. Regulators such as FDA and EMA often require answers to queries within days or even hours. Effective partnerships now require coordinated rapid-response mechanisms across pharma and diagnostic teams.

Patient access is directly affected. If companion diagnostics are not available at the time of therapeutic launch, drug approvals may stall, or patient access may be delayed. Synchronizing drug and diagnostic timelines is therefore no longer optional; it is a core requirement of development strategy.

Global Perspectives on LDTs

United States. The FDA’s attempt to regulate LDTs through a phased rule was struck down in 2024. Oversight now rests primarily with CLIA (CMS), except where LDTs are used in clinical trials, in which case FDA retains authority under IDE provisions of 21 CFR 812. Industry noted that FDA has signaled concerns when multiple LDTs are used without demonstrating even “minimal” performance; such situations are likely to trigger review discussions if sponsors later seek regulatory approval. In parallel, New York State’s CLEP program continues to operate independently, creating an additional layer of oversight.

European Union. Under IVDR Article 5(5), LDTs are restricted to in-house use within a healthcare institution, and only if no CE-marked equivalent device exists. Full application of these provisions began in May 2024. Article 6 provides the framework for distance sales, requiring that devices supplied to EU patients—whether purchased online or when EU patient samples are tested outside the Union—must still comply with IVDR requirements. In practice, this closes a potential loophole and ensures equivalent regulatory expectations for devices regardless of distribution route.

United Kingdom. Great Britain continues to rely on legacy IVDD-based provisions. Stakeholders see this as an opportunity to design a pragmatic, risk-proportionate framework, particularly for use in clinical trials, which could potentially become a model for future alignment.

Themes and challenges. Regulatory harmonization across jurisdictions remains unlikely. In the EU, reimbursement structures differ significantly by member state, compounding the regulatory complexity. Definitions of what constitutes a “healthcare institution” also vary, which affects feasibility for sponsors. At a broader level, innovation pathways remain poorly defined, and the pandemic experience underscored that preparedness depends on adaptive and flexible frameworks rather than rigid rules.

Post-Market Surveillance: Distributor Interfaces

A strong message came through on PMS under both MDR and IVDR as the new PMS requirements came into force during the conference.

Surveillance extends beyond vigilance. Vigilance addresses the reporting of serious incidents, whereas PMS requires manufacturers to establish systematic and proactive processes to detect trends, analyze data, and act on findings before they escalate into incidents.

The distributor–manufacturer relationship is central. Effective PMS cannot operate in isolation. Agreements must obligate distributors to channel customer complaints, sales representative observations, and user feedback directly to manufacturers. Contracts should require immediate notification, active participation in surveys, and cooperation in implementing CAPAs, field safety corrective actions (FSCA), or recalls.

Risk of regulator bypass. Under IVDR Article 14(6), competent authorities may approach distributors directly. Without robust contractual controls, there is a risk that distributors provide incomplete or unfavorable information. Agreements should therefore require manufacturer review and approval of responses before communications are made to regulators.

UK and EU expectations differ. The UK requires reports even where uncertainty remains, placing greater emphasis on early reporting, on user feedback, and on data gathered from other jurisdictions. Manufacturers operating in both systems must ensure PMS structures can accommodate these differing expectations.

Intersection with the AI Act. For devices incorporating artificial intelligence, the AI Act introduces obligations for monitoring and logging of performance in the field. This will necessitate even closer coordination between manufacturers and distributors to ensure that data capture and reporting are comprehensive and compliant.

EUDAMED – Phased Implementation and Practical Lessons

Phased implementation under Regulation (EU) 2024/1860.

Phased EUDAMED rollout readiness demands more than data entry—it requires cross-functional alignment and proactive planning. At Beaufort, we translate complexity into clear, actionable steps for timely implementation.

• From January 2026, mandatory use of the Actor Registration, UDI/device registration, Notified Body & Certificates, and Market Surveillance modules will apply to new devices.
• The Vigilance module will follow from Q3 2026, with full functionality expected by Q2 2027.
• Development of the Clinical Investigation/Performance Studies (CI/PS) module will continue into Q3 2026. An audit to assess CI/PS alongside the other five modules will take place once its minimum viable product has been delivered.

Operational challenges identified.

• Documentation remains voluminous and often inconsistent, spanning MDR/IVDR, MDCGs, and implementing acts.
• Unpublished “triggers” and discrepancies between the playground and production environments continue to create avoidable failures.
• Data submission routes carry differing risks: manual entry is impractical, XML upload is limited, and machine-to-machine (M2M) connections—preferred by the Commission—take six months or more to establish. Companies starting late are unlikely to achieve readiness in time.
• EUDAMED functions as a minimum viable product with little built-in validation; compliance must therefore be assured within manufacturers’ own systems.
• Portfolio prioritization is uneven. With many companies delaying registration, late surges near deadlines will overwhelm Commission support capacity.

Lessons emphasized at the Summit.

• Treat EUDAMED as a cross-functional initiative, not a project confined to regulatory teams.
• Align with other data-sharing regimes such as FDA’s GUDID and SwissDAMED to reduce duplication and ensure consistency.
• Register devices most likely to generate vigilance reports first to minimize downstream disruption.
• Do not assume the regulation is static; the Commission continues to introduce new and revised requirements with little advance notice.

EU Reference Laboratories (EURLs) – Implementation of Regulation (EU) 2023/2713

IVD Class D conformity assessment now formally involves EURLs

Role and mandated tasks. For Class D devices, EURLs are now formally embedded in the conformity assessment process. Their responsibilities include verifying manufacturer performance claims through independent laboratory testing and confirming compliance with relevant common specifications.

Designation status. As of December 2023, five laboratories had been designated, covering hepatitis/retrovirus, HIV, bacterial agents such as Treponema, and respiratory viruses. Blood grouping and parasitology are not yet covered; however, applications for devices in these categories may still be submitted to notified bodies in the absence of an EURL designation.

Operational launch. EURLs became fully operational on 1 October 2024, when the first physical batch testing began. Harmonized contractual frameworks between laboratories and notified bodies were finalized in December 2024.

Timelines for review. EURLs are required to deliver their opinions within 60 days of receiving the necessary materials. Batch testing applies to each defined production lot.

Different application scenarios.

• New applications submitted after 1 October 2024: both performance verification and batch testing are required.
• Applications lodged before 1 October 2024: batch testing is required, but performance verification is deferred until renewal.
• Devices already certified: batch testing applies immediately, with performance verification added at the next renewal.

Practical challenges observed. Manufacturers are already encountering operational hurdles, including the logistics of transporting batches and instruments, preparation of QC documentation, customs delays, and variability in laboratory transparency. Fees also differ across labs, adding complexity to planning.

Future expansion. A second round of designations is under way to cover blood grouping and additional pathogens, with further EURLs expected to come online in the coming years.

Conclusions

Collaboration is central. Structured engagement across regulators, notified bodies, distributors, and pharmaceutical partners is no longer optional. It is the mechanism through which organizations will navigate change and safeguard patient access.

The regulatory environment remains unsettled. The MedTech Summit 2025 IVD track highlighted that Europe’s IVDR implementation, the UK’s developing medical device regulatory framework, and global divergence in LDT oversight continue to evolve, with new obligations such as EUDAMED adding further complexity.

Strategic leadership is required. For senior regulatory professionals, the challenge extends beyond meeting today’s compliance requirements. Success will depend on anticipating regulatory developments, executing with discipline, and embedding foresight into portfolio and development planning.

How Beaufort Can Provide Support & Expertise

At Beaufort, we work alongside diagnostic developers, pharmaceutical sponsors, and laboratories to navigate the evolving regulatory landscape. Our team brings decades of experience in regulatory strategy, clinical performance study execution, and post-market compliance across global frameworks. We understand the practical realities of engaging with regulators, aligning cross-functional partners, and preparing for new obligations.

As the regulatory climate continues to evolve, the value of a partner who adapts to change, streamlines submissions, and provides operational oversight across jurisdictions is clear. Beaufort combines deep regulatory expertise with hands-on operational experience to ensure programs advance with confidence and patients gain timely access to innovative diagnostics.

For more information on how Beaufort can support your regulatory strategy, contact us directly at [email protected] or provide your contact information here.

From MDUFA to EUDAMED—What Regulatory Leaders Need to Know

The 2025 AMDM Annual In Vitro Diagnostics (IVD) Regulatory Meeting delivered two full days of deep insight, lively discussion, and policy-shaping perspectives across the global diagnostics landscape. Despite the absence of several EU-based presenters due to a travel strike in Belgium and limited engagement from current FDA officials, the sessions offered clarity on pressing regulatory developments and emerging industry priorities.

Day 1: U.S. Landscape, Enforcement, Quality Systems, and Innovation

US FDA Landscape & Policy Direction

• Even with significant disruptions—nearly 3,500 staff impacted by reductions in force and continued institutional knowledge loss through retirements—OHT7 remains committed to meeting MDUFA timelines. However, behind that resilience, growing concerns have emerged around internal restrictions on transparency and open scientific exchange.

QMSR Final Rule

• FDA’s alignment of 21 CFR Part 820 with ISO 13485 through the QMSR final rule is moving ahead as planned, with no indication of delay.
• With a compliance deadline of February 2026, organizations should be actively conducting gap assessments now—particularly around risk management integration, removal of inspection exceptions, training systems, supplier controls, and the management of activities to ensure integrity, inspection, storage, and operations for labeling and packaging.
• Early remediation will position companies for smoother transitions during inspections and audits.- Cybersecurity and Software Requirements.

Software, Cybersecurity & AI/ML IVDs

• Although digital health tools, software as a medical device (SaMDs), and AI/ML-enabled diagnostics are becoming more prevalent, sponsors continue to face challenges meeting the Agency’s expectations.  Cybersecurity remains a leading cause of submission refusals and delays with gaps in threat modeling, software bill of materials (SBOM) documentation, and lifecycle security plans persisting. 
• Successful development and deployment of AI/ML IVDs rely on implementation of robust design control frameworks and risk management principles, including defined risk-mitigation and post-market monitoring strategies to minimize algorithm bias.  Independent data sets for development and test, ideally on study cohort level is one method for minimizing bias and for ensuring reproducible analytical and clinical device performance.

LDT Rule Vacated

• The recent federal court ruling vacating FDA’s final LDT rule has removed near-term compliance obligations but introduced long-term uncertainty.
• While the Court determined regulation of LDTs falls under CMS and CLIA oversight, this is not a return to status quo.
• Questions remain—especially for CDx and single-site tests developed within precision medicine programs. For example, CDER and CBER may still request validation data and rely on CDRH consultation. Early engagement with drug and biologic review divisions is prudent.
• The government may repeal the court decision, but must do so by end of May 2025.

Day 2: Global Regulatory Strategy and Market Opportunities

European Union: IVDR, AI Act, and EUDAMED IVDR Transition

• The phased IVDR transition continues through 2029, but enforcement is already in motion.
• Audits are uncovering deficiencies in compliance with Article 10a—specifically in continuity of supply planning and communication protocols.
• Additional deficiencies should be anticipated if sponsors with legacy devices do not comply with the requirements of Article 10 by the end of May.

EUDAMED Rollout

• Modules for actor registration, UDI, and device listings are set to become mandatory by January 2026. Manufacturers should use the current “playground” environment to test readiness and avoid future data bottlenecks.

AI Act Integration

• High-risk AI systems will face conformity assessments embedded within MDR/IVDR processes. Notified Bodies will need specialized AI evaluation competencies.

New UK Regulations

• While Great Britian’s MDR and EU’s IVDR share many features, their divergence has important implications for global regulatory planning.
• The new post-market surveillance (PMS) regulation (effective June 16, 2025) mirrors many IVDR concepts but adds enhanced expectations around user experience and field safety corrective action notifications.  Currently there is no guidance as to whether UKCA-marked companion diagnostics being used in a clinical trial of an investigational medicinal product are expected to apply with PMS requirements due to their UKCA marking.
• The proposed UKCA premarket framework introduces international reliance mechanisms—such as recognition of CE-marked products and approvals from select peer regulators—but not all CDx or SaMDs are expected to be eligible.
• Additional statuary instruments (SIs) are expected in 2025.
  

Asia-Pacific Region: Acceleration and Modernization

• Across the Asia-Pacific region, significant regulatory modernization is underway
• Japan: Regulatory processes remain rigorous but stable, with CDx demand increasing. Reference pricing reforms are reshaping market access.
• Korea: registration is more difficult than before, however the newly-introduced Immediate Market Entry policy aims to reduce review timelines for cutting edge technologies to under 140 days.. Korea is also developing the first generative AI device review guideline.
• Singapore: released a draft document for IVD medical devices in May 2023, expanding the risk classification to include derivatives of blood, organs, or cell tissues, ensuring to ensure a broader spectrum of IVD devices is adequately regulated.
• China: Continued prioritization of in-country clinical trials, local manufacturing and cost-containment through national volume-based procurement schemes. 
•  India & Southeast Asia: India’s new classification and adverse event systems aim to harmonize regulatory control.

These developments signal growing regional harmonization with global norms—but each market still requires careful navigation and local expertise.

CDx, Rare Biomarkers, and Sample Scarcity

• Competition for retained sample use among clinical trial enrollment, patient care, scientific research, and CDx development, remains a challenge in precision medicine, particularly in rare disease. 
• Real-world data, in silico modeling, contrived samples, and bridging studies are viable when scientifically justified.
• Regulatory flexibility is possible, but only when supported by rigorous rationale and transparent engagement with FDA.

Final Reflections

Across both days, one key message emerged: regulatory harmonization may remain aspirational, but strategic alignment is achievable. The IVD Regulatory Update 2025 reinforced that sponsors must remain agile in response to regulatory change, especially as the FDA, EU, and other regions strengthen expectations around digital health, cybersecurity, and real-world evidence.

Success in 2025 and beyond will depend on a sponsor’s ability to anticipate regulatory expectations, plan with agility, and maintain open, evidence-based communication with health authorities. The IVD Regulatory Update 2025 made it clear that staying ahead requires not only technical excellence but also regulatory intelligence.

To explore how these evolving regulatory developments may affect your organization—and how we can support your IVD product strategy through this period of global change—please get in touch.

Updates to the UK Medical Device Regulations

The regulatory landscape for medical devices, including in vitro diagnostics (IVDs), in the United Kingdom (UK) is undergoing a significant transformation. This article outlines key updates to the UK’s future medical device regulations, their implications for the industry, and guidance for regulatory professionals navigating these changes.

Current Regulations Governing the Sale & Supply of In Vitro Diagnostic (IVD) Medical Devices in the UK

The UK’s regulatory framework for medical devices has evolved in response to Brexit-induced divergence from the European Union’s (EU) Medical Device Regulation (MDR) and In Vitro Diagnostic Regulation (IVDR) as well as the need to enhance patient safety while supporting MedTech innovation.

Since January 1, 2021, several changes have impacted how medical devices, including IVDs, are placed on the market in the UK.  In Great Britain (GB – England, Wales and Scotland), IVDs are currently regulated under the Medical Devices Regulations 2002 (SI 2002 No 618, as amended) (UK MDR 2002)^[1] which remains largely based on the EU Directive 98/79/EC (IVDD)^[2]. 

Under the Northern Ireland Protocol^[3], different rules apply allowing Northern Ireland to continue following EU law.  Thus, CE marking remains mandatory for devices sold in Northern Ireland, the EU, and the European Economic Area (EEA).

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Implementation of the Future Regulations

In 2022, the UK government published its “Government response to consultation on the future regulation of medical devices in the United Kingdom”[1], outlining a phased approach to reform the UK MDR.

In early 2024, the Medicines & Healthcare products Regulatory Agency (MHRA) released a regulatory roadmap detailing the 2024-2025 timelines for delivering the new framework.  This roadmap was revised in December of 2024 (version 2.0)[2] to reflect updated timelines.

Key Updates:

1. New Post-Market Surveillance (PMS) Regulations – The PMS statutory instrument (SI) was signed into law in December 2024 and will come into force in June 2025 after a six-month transition period.
2. Pre-Market SI – Changes will include new IVD classification rules, revised conformity assessment procedures, and new IVD approval pathways including international recognition routes. The necessary SI is expected to be introduced to Parliament in late 2025 and come into force in 2026.
3. Software, AI & Digital Mental Health Products – The MHRA is expected to publish new/draft guidance on AI development and deployment, cybersecurity and digital mental health technologies in 2025.
4. IVD Policy Development – New policies and guidance for Exceptional Use Authorisation and Early Access and Use are in development, with a dedicated roadmap expected by Q4 of 2025.

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NEW Post-Market Surveillance (PMS) Requirements

The Medical Devices (Post-market Surveillance Requirements) (Amendment) (Great Britain) Regulations 2024^[6]  introduced stricter obligations for manufacturers, aligning UK requirements more closely with the EU IVDR and MDR while maintaining unique GB-specific elements.  The MHRA have published guidance^[7] to aid in implementation.

Key PMS Changes for IVDs:

• Comprehensive PMS Documentation – Manufacturers must maintain a PMS system, submit detailed PMS plans, and, for certain risk classes, provide Periodic Safety Update Reports (PSURS).
• Stronger Reporting Obligations:
  • Serious public health threats – Report within 2 calendar days after the manufacturer becomes aware.
  • Death or unanticipated serious deterioration in state of health – Report within 10 calendar days after the manufacturer becomes aware. 
  • Anticipated serious deterioration in state of health – Report withing 15 calendar days after the manufacturer became aware. 
  • Field Safety Corrective Actions (FSCAs) – Report immediately upon initiation.
  • Field Safety Notices (FSNs) – Distribute to users and stakeholders without delay to mitigate risks.
• Improved Traceability and Transparency – Enhanced supply chain reporting and tracking obligations to ensure patient safety.
• Risk-Based Compliance Adjustments – PMS requirements vary by:
  • Device type (general IVDs, high-risk IVDs, etc.)
  • Basis of conformity assessment (UKCA, IVDD, or IVDR).

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Table 1 reproduces the PMS obligations specific to IVD devices based on conformity assessment^[8].  Most requirements are the responsibility of the Manufacturer; however, certain requirements may be delegated to the UK Responsible Person (UKRP)^[9].

Exceptions:  The new PMS requirements do not apply to:

• Devices subject to clinical investigation, performance evaluation or exceptional use authorisation in GB.
• Devices discontinued before the SI enforcement date (these remain subject to MED DEV 2.12 PMS requirements^[10]).
• Devices placed on the market or put into service in Northern Ireland (NI), which must follow the PMS requirements of EU MDR 2017/745 and EU IVDR 2017/746.

The MHRA has published guidance documents clarifying implementation details ^[11], including stakeholder consultation opportunities through trade associations^[12].

Table 1. PMS obligations specific to IVDs* (click to enlarge)

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Transitional Arrangements & Industry Impact

Key Transition Deadlines

Regulatory professionals must monitor the following deadlines^[13] to ensure continued market access:

• CE-Marked Devices – Transitional allowances until December 31, 2027 for most IVDs (and medical devices), with risk-class specific phase-out dates through 2030.
• UKCA Marking  – The UK is shifting towards full UKCA marking adoption, requiring  manufacturers to transition accordingly.
• Guidance & Support – MHRA has committed to publishing comprehensive guidance, with further updates expected in 2025.

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What Regulatory Professionals Should Do Now

To prepare for the upcoming changes, regulatory professionals should:

• Monitor Implementation Timelines – Stay informed on MHRA consultations, SI publications, and transition deadlines.
• Engage with MHRA Guidance – Regularly review PMS updates, UKCA transition arrangements, and new IVD-specific regulations.
• Conduct regulatory gap analyses –  Identify necessary updates to PMS documentation, quality management systems and labeling.
• Collaborate with Industry Peers – Participate in trade associations, regulatory working groups, and discussions with UK Approved Bodies.
• Plan for UKCA Transition – Develop a clear strategy for transitioning from CE to UKCA marking.

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Final Thoughts

With the UK’s evolving regulatory framework, staying ahead of the MHRA roadmap is critical for IVD manufacturers and regulatory professionals. As a trusted CRO partner, Beaufort is ready to help companies navigate these regulatory changes, maintain compliance, and ensure market access in the UK.

For more information on how Beaufort can support your UK regulatory strategy, contact us directly at [email protected] or provide your contact information here.

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[1] Medicines and Healthcare products Regulatory Agency.  Guidance Regulating medical devices in the UK.  Published 15 January 2025.  Accessed February 5, 2025.  https://www.gov.uk/guidance/regulating-medical-devices-in-the-uk#NI.

[2] Medicines and Healthcare products Regulatory Agency.  Guidance on the regulation of In Vitro Diagnostic medical devices in Great Britain. Published January 2025. Accessed February 5, 2025. https://assets.publishing.service.gov.uk/media/67863a313ef063b15dca0f47/Guidance_on_the_regulation_of_IVD_medical_devices_in_GB.pdf. 

[3] Medicines and Healthcare products Regulatory Agency.  Guidance for retailers: supplying medical devices to Northern Ireland. Last updated 5 March 2021.  Accessed February 5, 2025. https://www.gov.uk/guidance/guidance-for-retailers-supplying-medical-devices-to-northern-ireland#:~:text=A%20key%20part%20of%20the,to%20the%20relevant%20EU%20legislation

[4] Medicines and Healthcare products Regulatory Agency. Government response to consultation on the future regulation of medical devices in the United Kingdom. Published 26 June 2022.  Accessed February 5, 2025. https://assets.publishing.service.gov.uk/media/62b577f6d3bf7f0b00165a32/Government_response_to_consultation_on_the_future_regulation_of_medical_devices_in_the_United_Kingdom.pdf. [1] Medicines and

[5] Healthcare products Regulatory Agency. Medical Devices Regulatory Reform Roadmap to implementation. Version 2.0 (December 2024).  Accessed February 5, 2025. https://assets.publishing.service.gov.uk/media/6759a8827e419d6e07ce2b21/Med_Tech_Regulatory_Roadmap_V2_December_2024.pdf.

[6] The Medical Devices (Post-market Surveillance Requirements) (Amendment) (Great Britain) Regulations 2024 – UK Statutory Instruments 2024 No. 1368  Assessed February 10, 2025. https://www.legislation.gov.uk/uksi/2024/1368/contents/made

[7] Medicines and Healthcare products Regulatory Agency. Guidance The Medical Devices (Post-market Surveillance Requirements) (Amendment) (Great Britain) Regulations 2024: guidance on implementation.  Published 15 January 2025.  Accessed February 5, 2025. https://www.gov.uk/government/publications/medical-devices-post-market-surveillance-requirements/the-medical-devices-post-market-surveillance-requirements-amendment-great-britain-regulations-2024-guidance-on-implementation

[8] Medicines and Healthcare products Regulatory Agency. Guidance Post-market surveillance (PMS) obligations by medical device type. Published 15 January 2025. Accessed February 5, 2025.https://www.gov.uk/government/publications/medical-devices-post-market-surveillance-requirements/post-market-surveillance-pms-obligations-by-medical-device-type

[9] Medicines and Healthcare products Regulatory Agency. Guidance Post-market surveillance requirements for medical devices: summary of main changes. Published 15 January 2025.  Accessed February 5, 2025. https://www.gov.uk/government/publications/medical-devices-post-market-surveillance-requirements/post-market-surveillance-requirements-for-medical-devices-summary-of-main-changes

[10] Guidance MEDDEVs.  Accessed February 5, 2025. https://health.ec.europa.eu/document/download/c1a6aa0b-d8c8-498b-8ed4-9f3c6211896d_en

[11] Medicines and Healthcare products Regulatory Agency.  Guidance The Medical Devices (Post-market Surveillance Requirements) (Amendment) (Great Britain) Regulations 2024: guidance on implementation. Published 15 January 2025. Accessed February 5, 2025.  https://www.gov.uk/government/publications/medical-devices-post-market-surveillance-requirements/the-medical-devices-post-market-surveillance-requirements-amendment-great-britain-regulations-2024-guidance-on-implementation.

[12] Medicines and Healthcare products Regulatory Agency. Press release. MHRA guidance on new Medical Devices Post-Market Surveillance requirements. Published 15 January 2025.  Accessed February 5, 2025.  https://www.gov.uk/government/news/mhra-guidance-on-new-medical-devices-post-market-surveillance-requirements

[13] Medicines and Healthcare products Regulatory Agency. Infographic – Timelines for placing CE marked IVDs on the Great Britain market.  Accessed February 10, 2025.  https://assets.publishing.service.gov.uk/media/6718b88738149ce9d09e3894/Infographic_-_Devices_transition_timeline.pdf

How Beaufort’s Flexibility, Operational Excellence & Technical Expertise Drove Success for a Multicenter ICU Study

Overview

A leading global in vitro diagnostics manufacturer partnered with Beaufort to conduct a prospective, multicenter, observational clinical study in Intensive Care Unit (ICU) settings across the United States. The objective of this study was to validate a diagnostic assay in adult ICU patients diagnosed with moderate to severe kidney disease. The targeted enrollment for this study was approximately 500 adult ICU subjects across 20 clinical sites in the United States. All participants were required to have documented moderate or severe AKI at the time of enrollment (Kidney Disease: Improving Global Outcomes [KDIGO] AKI Stage 2 or Stage 3).

Project Deliverable

Beaufort was engaged to comprehensively manage the clinical study, encompassing all phases from initial site qualification and activation to final close-out activities. Beaufort led the site selection, site initiation visits, ongoing site management, clinical trial monitoring, close-out activities, and supported Institutional Review Board (IRB) submissions and communications.

Beaufort Results

Through continuous collaboration with sites, a cohesive working relationship with the Sponsor, and a results-driven approach, Beaufort achieved the following outcomes:

• Enhanced Monitoring & Data Integrity: Through a combination of on-site and remote site visits, site training, and technology-enabled assessment tools, Beaufort ensured a robust data set for the study while maintaining protocol integrity across all sites.

• Expedited Data Processing: By completing 100% source data verification two months ahead of schedule, Beaufort accelerated the timeline for data adjudication and database lock, facilitating quicker access to critical study results.

• Effective Site Partnerships: Our collaborative relationships with clinical sites ensured the smooth study execution as well as positioned Beaufort as a trusted partner for future research endeavors – further expanding our global site network.

Study Challenges & Solutions

Beaufort encountered and successfully mitigated challenges during the study start-up and enrollment phases of the project, including:

Site Start-Up:

The project commenced during the COVID-19 pandemic, which caused delays in site activation as healthcare providers prioritized immediate patient care. Key challenges encountered during site activation included resource limitations at clinical sites, and adjustments to site research management policies due to pandemic-related policy changes. Beaufort implemented the following solutions to ensure the project stayed on track:

• Proactive Communication: Through the extended site start-up phase, maintained regular and concise communication with the site Principal Investigators (PIs) and study teams, ensuring alignment and readiness despite evolving priorities.

• Flexible Support: Adapted to the shifting needs of the sites by offering tailored support, including flexible scheduling and virtual start-up meetings and training, which accommodated pandemic-related constraints.

• Digital Innovation: Leveraged technology to streamline processes, implementing electronic Site Binders, DocuSign for compliant electronic signatures in accordance with 21 CFR Part 11, and secure FTP sites for document sharing, facilitating efficient site activation in a remote environment.

• Client Focused: Worked closely with the Sponsor to adopt multiple teleconference platforms, ensuring seamless communication to accommodate different institutional preferences and minimize disruption during site start-up.

Subject Eligibility Determination:

To ensure consistent application of KDIGO staging criteria across diverse clinical sites, despite potential variations in standard practices during screening and subject eligibility, Beaufort implemented the following solutions:

• Streamlined Enrollment Process: Collaborated with the Sponsor to help efficiently guide sites through a clear and standardized eligibility assessment against a defined enrollment timeline.

• Enhanced Protocol Compliance: Developed a tool set that not only streamlined the screening process, but helped minimize protocol deviations and enabled sites to make timely, data-driven enrollment decisions, thus improving overall study efficiency.

Informed Consent:

Obtaining fully documented Informed Consent from Legally Authorized Representatives (LARs) for ICU patients within the short protocol window presented challenges. Beaufort addressed this by:

• Digital Consent Solutions: Partnered with the Sponsor to implement electronic Informed Consent processes at sites where traditional methods were impractical, ensuring compliance with U.S. Federal Regulations and protocol criteria.

• Streamlined Workflow: The use of electronic tools expedited the consent process, minimized delays, and ensured that all documentation was completed within the narrow protocol enrollment window, enhancing overall study efficiency.

Data Verification:

Maintaining data integrity through rigorous review of KDIGO staging during remote clinical monitoring activities was critical. Beaufort implemented the following solutions:

• Specialized On-Site Support: Deployed Subject Matter Experts (SMEs) to work closely with site staff, providing real-time guidance and review of the data entered into the validated tool, ensuring accuracy from the outset.

• Collaborative Monitoring: Integrated SMEs with Clinical Research Associates (CRAs) to support the review of the KDIGO staging data during monitoring preparation, and regularly trained and prepared sites to focus on achieving monthly enrollment targets.

• Efficient Data Management: Implemented an FTP site for sites to upload deidentified Source Documents and data for Beaufort CRAs to source data verify.

Study Communications:

To foster engagement with PIs and site staff during a time when on-site visits were not feasible, Beaufort employed the following creative communication strategies:

• Sustained Outreach: Maintained high levels of engagement with PIs and site staff through consistent and creative digital communication, including study newsletters, interactive weekly e-blasts, and virtual investigator meetings.

Beaufort’s comprehensive management of this multicenter ICU study exemplifies our flexibility and approach to overcoming complex challenges while maintaining high standards of data integrity, protocol compliance, and operational efficiency. By leveraging innovative digital solutions, fostering strong site relationships, and adapting to the evolving landscape during and after the COVID-19 pandemic, we delivered the project ahead of schedule and ensured the study’s success. Our proactive, client-focused approach not only met the sponsor’s objectives but also positioned Beaufort as a trusted partner for future support.

With proven expertise across various clinical settings, we are committed to helping diagnostic innovators accelerate development and bring life-changing technologies to market.

Learn more about how Beaufort can successfully support your current or future clinical trial.

Contact us today

Planning a clinical trial for medical devices, including in vitro diagnostics (IVDs), is a complex, multi-faceted process that requires strategic thinking, careful preparation, and foresight. According to industry data, nearly 30% of clinical trials fail to secure regulatory clearance or approval, often due to inadequacies in trial design, data collection, or regulatory alignment. Additionally, up to 80% of clinical trials face delays or cost overruns, primarily because of insufficient planning in areas such as subject recruitment and risk management. To help avoid these pitfalls and improve your chances of success, here are some key considerations when planning your next clinical trial.

1. Engaging Early and Often with Regulatory Authorities

There are a multitude of considerations and influencing factors that inform both regulatory strategy and study planning for your product development. To help your trial start off on the right track and meet all necessary requirements, ongoing communication with regulatory bodies is essential. In the U.S., leveraging resources like the FDA’s pre-submission process can clarify performance expectations and help align your trial with regulatory requirements. Early engagement reduces the likelihood of having to make significant adjustments late in the trial process. Regular interaction helps to address concerns before they become roadblocks. Beaufort has extensive experience partnering with sponsors who rely on our expertise navigating regulatory complexities.

2. Conducting Thorough Feasibility Studies

Clinical feasibility studies can identify potential issues with your trial design before investing time and resources on a full trial. By designing relevant and appropriate feasibility studies, you can ensure that your timeline is realistic, that the site(s) selected meet the needs of your trial, and that the trial design is viable. By evaluating the constraints your clinical trial will have on a smaller scale, you can preempt issues that can commonly occur during trial execution.

3. Risk Management and Contingency Planning

Clinical trials often face unexpected challenges, such as subject recruitment delays, supply chain disruptions, product design changes, or regulatory setbacks. Incorporating a proactive risk management strategy and developing contingency plans are crucial for minimizing the impact of these issues. Our team’s extensive risk management experience can help you rigorously evaluate, refine, and implement risk management activities that prepare you for common obstacles, keeping your trial on schedule and within budget.

4. Developing a Robust Protocol

A clear, detailed protocol is essential to a successful clinical trial. It ensures that investigators, sponsors, and other stakeholders are aligned on their roles and responsibilities, as well as ensuring consistency in execution. Having a transparent, clear protocol will minimize the potential for misunderstandings among stakeholders and also with regulatory authorities.

5. Prioritizing Site Training and Support

Comprehensive site training and supporting trial sites are essential to your success. Extensively reviewing with site personnel the specific requirements for handling devices, collecting data, or processing specimens is critical. Regular communication and support ensure consistency and adherence to trial protocols, and potentially minimizes the risk of errors and deviations.​

6. Comprehensive Monitoring

A robust Monitoring Plan guides the project team to monitor your trial properly, maintaining participant safety and data integrity. Effective monitoring ensures that the protocol is being followed and allows for early detection of issues, increasing operational efficiency. The monitoring process also enhances communication between sponsors, investigators, and sites, providing an opportunity for a quick resolution to any issues and reinforcing alignment with the overall goals of the trial. By focusing on protocol adherence and proper documentation, sponsors and sites are better prepared for potential audits, and eventually regulatory inspections.

7. Investing in Strong Data Management

For medical device trials that generate large volumes of complex data, effective data management is vital. Data must be securely and accurately collected to preserve quality and validity. Implementing robust electronic data capture (EDC) systems and adhering to Good Clinical Practice (GCP) standards will minimize errors and ensure compliance​. Beaufort’s data sciences team is able to design custom data management solutions to fit your trial, maintaining the integrity and security of your data across the entire trial.

8. Leveraging Technology for Trial Optimization

The use of advanced technologies like AI, machine learning, and automation is becoming increasingly embedded in the clinical trial management process. AI-driven patient recruitment tools and predictive analytics can improve trial efficiency, while automation in data collection reduces human error. Tools such as wearable trackers and telehealth are developing quickly to meet the needs of decentralized trials and remote monitoring. Utilizing these technologies can help streamline processes, reduce costs, and increase the likelihood of regulatory success.​

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Successful clinical trials for IVDs and other medical devices require thoughtful planning and execution. By taking these key considerations into account, sponsors can significantly improve the chances of regulatory success, stay within budget, and complete clinical trials on time.

At Beaufort, we have extensive experience guiding sponsors through the complexities of trial planning and execution. Whether it’s navigating regulatory pathways, optimizing trial design, site recruitment and management, or ensuring data integrity, we can help you successfully manage your next clinical trial from start to finish.

Learn more about our comprehensive Clinical Trial Services & Solutions or Contact Us today.

A new PCCP draft guidance outlines what elements the agency expects in these plans

As published in Today’s Clinical Lab

The U.S. Food and Drug Administration (FDA) recently issued a second draft guidance on predetermined change control plans (PCCPs) for medical devices that could influence how clinical labs modify laboratory-developed tests (LDTs).  

PCCPs are documents included in a marketing submission that:

• Describe anticipated changes to the FDA-approved or -cleared medical device;
• Detail how these changes will be implemented and validated. 

If approved, these plans allow changes without necessitating a new FDA submission, potentially accelerating a device’s modification and saving FDA review time.

Relevant to devices—including in vitro diagnostic devices (IVDs) and device-led combination products that are reviewed through the 510(k), De Novo, and pre-market approval pathways—the FDA guidance proposes a policy for PCCPs and provides recommendations on the information to include in a PCCP.   

The guidance may be of interest to the clinical laboratory community, as PCCPs may offer a way to introduce flexibility for modifying certain LDTs under the FDA’s recently issued final rule on regulating these assays.

Elements of a predetermined change control plan

A PCCP should consist of:

• Description of modifications, which outline the specific, planned changes that may be made to the device, including the specifications for the characteristics and performance of the planned modifications.
• Modification protocol, which describes verification and validation activities, including predefined acceptance criteria, that will support each modification to ensure the device remains safe and effective (or substantially equivalent) across the intended use populations.
• Impact assessment, which identifies the benefits and risks introduced by the specified, planned modifications and addresses how the verification and validation activities of the modification protocol will continue to ensure the safety and effectiveness (or substantial equivalence) of the device.

Here are the key takeaways about the FDA’s guidance on PCCPs:

• Scope: Unlike the FDA’s April 2023 draft guidance that focused on AI- and machine-learning-enabled devices, the new draft clarifies that PCCPs apply broadly, not just to these technologies.
• Purpose: The goal of a PCCP is to provide a least burdensome option for manufacturers to implement device modifications without needing to submit a new marketing submission for each modification—all while maintaining a reasonable assurance of safety and effectiveness (or substantial equivalence).
• Specificity: The modifications included in a PCCP must maintain the device within its intended use and should include specific changes that can be verified and validated.  
• Authorization: To gain authorization, a PCCP must provide enough detail to allow the FDA to assess the reasonable assurance of safety and effectiveness (or substantial equivalence).
• Implementation:  A PCCP is part of the device’s marketing authorization; therefore, the manufacturer is required to implement modifications consistent with their authorized PCCP. 

In general, the FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidance describes the agency’s current thinking on a topic and should be viewed as recommendations. The updated draft guidance on PCCPs is open for public comment for 90 days following its official issuance on August 22, 2024.

Learn more about our regulatory services or contact us today to schedule an introductory meeting. 

6 Strategies to Help You Meet FDA Requirements and Maintain Market Access

On April 29, 2024, the US Food and Drug Administration (FDA) issued a long-anticipated final rule asserting its authority to regulate laboratory-developed tests (LDTs) as medical devices (“Medical Devices; Laboratory Developed Tests” (89 FR 37286) (“LDT Final Rule”)). This rule, effective May 6, 2024, marks a significant shift from the FDA’s previous enforcement discretion for LDTs, impacting stakeholders across the diagnostics industry.

Below are key highlights of the final rule and how laboratories offering LDTs may begin preparing to meet the new requirements and timelines.

Redefining LDTs as In Vitro Diagnostic (IVD) Medical Devices

The FDA’s final rule makes explicit that in vitro diagnostic products are medical devices under the Federal Food, Drug, and Cosmetic Act (FD&C Act; 21 CFR § 809.3) “including when the manufacturer of the IVD is a laboratory”. While the laboratory community views LDTs as laboratory testing services, FDA defines LDTs as IVDs that are intended for clinical use and that are designed, manufactured, and used within a single laboratory that is certified under the CLIA and meets the regulatory requirements under CLIA to perform high complexity testing.

Phaseout of Enforcement Discretion

Over the next four years, the FDA will phase out its enforcement discretion for most LDTs. By May 6, 2028, all IVDs offered as LDTs must comply with FDA regulations akin to those for other FDA-regulated medical devices.  This includes implementing robust quality management systems, adhering to rigorous reporting practices, fulfilling establishment registration and device listing obligations, and undergoing FDA premarket review where applicable.  The phased approach aims to provide laboratories with time to adjust to the new regulatory landscape while ensuring patient safety and maintaining access to accurate diagnostic testing.

The phaseout policy applies to “IVDs offered as LDTs” defined by the FDA as IVDs that are manufactured and offered as LDTs by laboratories that are certified to perform high complexity testing under CLIA, and used within such laboratories, even if those IVDs do not fall within FDA’s traditional understanding of an LDT because they are not designed, manufactured, and used within a single laboratory.

Implementation Stages and Requirements

STAGE 1: Medical Device Reporting Requirements

Beginning on May 6, 2025, which is 1 year after the publication date of the final LDT rule, laboratories offering IVDs as LDTs must comply with Stage 1 requirements, which include medical device reporting requirements (21 CFR part 803), corrections and removals (21 CFR part 806), and quality system (QS) requirements for establishing and maintaining complaint files (21 CFR 820.198).

These requirements will be new to laboratories because they are distinct from those under Clinical Laboratory Improvement Amendments (CLIA) (42 CFR Part 493). While CLIA mandates procedures for managing complaints related to the quality of laboratory testing services, the FDA’s requirements under 21 CFR 820.198 specifically pertain to managing complaints related to medical devices. This includes establishing and maintaining procedures to receive, review, and evaluate complaints alleging device deficiencies.

STAGE 2: Registration and Listing, Labeling, and Investigational Device Exemption Requirements

Beginning on May 6, 2026, laboratories offering IVDs as LDTs must comply with Stage 2 requirements.  These encompass establishment registration and device listing obligations (510 of the FD&C Act, 21 CFR part 607, and 21 CFR part 807 (excluding subpart E)), labeling requirements (section 502 of the FD&C Act and 21 CFR parts 801 and 809, subpart B); and investigational device exemption requirements (section 520(g) of the FD&C Act and 21 CFR part 812).

Compliance will demand understanding and adherence to FDA specifications for labeling, including formatting and content stipulations under 21 CFR parts 801 and 809, as well as ensuring the inclusion of Unique Device Identifiers (UDIs) on labels for traceability throughout the device lifecycle. Establishing a relationship with a UDI issuing agency is necessary to obtain UDIs and assign them to each device model or version, ensuring that the identifier contains essential information such as device identifier, production identifier, and, where applicable, lot or serial number.

Laboratories must also adhere to FDA’s regulatory framework for investigational use of medical devices, when IVDs offered as LDTs are used in clinical investigations. This will include determining the appropriate IVD risk (significant, non-significant, or IDE exempt), obtaining necessary study approvals, and ensuring ongoing compliance throughout the investigation.

STAGE 3: Quality System Regulations (QSR) Implementation

Beginning on May 6, 2027, laboratories offering IVDs as LDTs must comply with Stage 3 requirements, which encompass specific QSR requirements outlined in 21 CFR 820.  These include implementing design controls, purchasing controls, and corrective and preventive actions (CAPA).

On February 2, 2024, FDA issued a final rule amending the device QS regulation, 21 CFR part 820, to align more closely with international consensus standards for devices (89 FR 7496, available at https://www.federalregister.gov/d/2024-01709).When the final rule takes effect, FDA will also update the references to provisions in 21 CFR part 820 in this guidance to be consistent with that rule.

Key Components of Design Controls: Central to QSR compliance are Design Controls, a structured approach to product development that ensures devices meet specified requirements and are safe and effective for their intended use. Laboratories developing IVDs as LDTs must establish and maintain processes and procedures that encompass the following key components:

• Design and Development Planning (DDP): Laboratories will be required to create a comprehensive DDP outlining the design control activities and milestones for each device. This plan defines roles and responsibilities of team members involved in the design process and sets out a clear roadmap for development.
• Design Inputs: Laboratories will be required to translate user needs and intended use into specific design inputs.  Design inputs encompass functional, performance, and safety requirements that the device must meet to fulfill its intended purpose. These inputs serve as the foundation for subsequent design activities.
• Design Outputs: Laboratories must generate detailed design outputs that specify device characteristics, including drawings, specifications, and other relevant documentation. Design outputs must demonstrate the design meets the design inputs and must be meticulously documented to ensure traceability and compliance.
• Design Reviews: Laboratories must conduct systematic design reviews at critical stages of development to evaluate progress, identify any issues or shortcomings, and verify alignment with design requirements.  These reviews ensure that potential problems are identified early and addressed promptly to maintain project timelines and product quality.
• Design Verification: Verification involves rigorous testing and analysis to confirm that the device functions as intended. This process ensures that design outputs meet the specified design inputs and are validated through objective evidence. Verification activities must be well-documented and include testing protocols, results, and conclusions.
• Design Validation: Validation is conducted under defined operating conditions to ensure that the final device meets user needs and intended use. This stage involves comprehensive testing in simulated or actual use environments, including software validation and risk analysis where applicable. Validation activities provide assurance that the device is safe, effective, and suitable for its intended clinical application.
• Risk Management: Throughout the design process, laboratories must implement a systematic approach to identify, analyze, control, and monitor risks associated with the device throughout the design process in compliance with the current version of International Organization for Standardization (ISO) 14971.
• Design Transfer: Ensures a smooth transition of the approved design to production through design transfer activities. This stage includes verification that production processes can consistently produce devices that meet design specifications.
• Design Changes: Laboratories must establish procedures for managing design changes. throughout the device lifecycle. Evaluation, documentation, and validation of design changes are required before implementation to prevent unintended alterations that could compromise device safety, efficacy, or intended use. Any modifications must be carefully controlled and documented to maintain regulatory compliance.

STAGE 4: Premarket Review for High Risk IVDs Offered as LDTs

Beginning on November 6, 2027, laboratories offering Class III IVDs as LDTs must comply with Stage 4 requirements, requiring FDA premarket approval (PMA) before marketing.  This entails comprehensive analytical and clinical evaluations to demonstrate device safety and effectiveness, aligning with stringent FDA review standards under 21 CFR 814.20.  The PMA application must include all elements required under 21 CFR 814.20, unless omissions can be justified by the applicant.

Separately, the FDA’s Center for Devices and Radiological Health (CDRH) intends to initiate the reclassification process for certain IVDs currently classified as Class III (high-risk devices) to Class II (moderate-risk devices). This reclassification would potentially enable these tests to undergo review through the less burdensome premarket notification (510(k)) pathway instead of the premarket approval (PMA) pathway, the most stringent type of FDA medical device review. 

However, the FDA will only consider reclassification for Class III devices if the agency has sufficient information (i.e., experience) to establish special controls that, together with general controls, provide a reasonable assurance of safety and effectiveness for these tests.  As a result, only those Class III IVDs for which the FDA can establish appropriate special controls will be eligible for down classification to Class II. 

STAGE 5: Premarket Review for Moderate and Low Risk IVDs Offered as LDTs

Beginning on May 6, 2028, laboratories offering Class II moderate-risk and Class I low-risk IVDs as LDTs must submit a 510(k) premarket notification demonstrating substantial equivalence to legally marketed devices, unless exempt. This stage also allows for alternative pathways like De Novo classification requests for devices lacking predicate devices but deemed safe and effective under general or special controls.

Additionally, certain other premarket submissions, such as Humanitarian Device Exemption applications or Biologics License Applications (BLAs), may also be appropriate depending on the specific circumstances of the IVD offered as an LDT.

Of note, for IVDs that rely on or otherwise incorporate software (including off-the-shelf software) or that meet the definition of a “cyber device” (Section 524B(c) of the FD&C Act), premarket submissions will need to be inclusive of documentation for FDA’s review and evaluation. For IVDs offered as LDTs already on the market, if a premarket submission has been received by the beginning of Stage 4 or Stage 5 (as applicable), the FDA intends to exercise enforcement discretion during the review period to ensure continued patient access to these devices without interruption.

The agency’s phaseout transition aims to enhance FDA oversight and ensure the safety and effectiveness of LDTs, by aligning expectations for regulatory compliance with that of commercially distributed medical devices. This phased approach is intended to allow laboratories time to comply with the new regulatory framework while continuing to meet the needs of patients and healthcare providers for accurate diagnostic testing.

Notably the amended regulation and phaseout policy do not change other requirements for laboratories, including requirements under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), which are separate from requirements under the FD&C Act.

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Continued General Enforcement Discretion Approach for Certain IVDs

The FDA’s LDT Final Rule, in comparison to its proposed rule, broadens the scope of LDTs for which the agency intends to continue exercising general enforcement discretion. This means that the FDA will generally not enforce any applicable requirements for the following:

• 1976-Type LDTs: These tests use manual techniques and are performed by laboratory personnel with specialized expertise and rely on clinical-use (not research use only) components.
• Certain Human Leukocyte Antigen (HLA) Tests for Transplantation: Specifically, histocompatibility testing when used in connection with organ, stem cell, and tissue transplantation to perform HLA allele typing, for HLA antibody screening and monitoring, or for conducting real and “virtual” HLA crossmatch tests.
• Forensic Tests: Tests intended solely for forensic (law enforcement) purposes.
• US Department of Defense (DoD) or the Veterans Health Affairs (VHA) LDTs: LDTs manufactured and performed within the VHA or DoD and used for patients tested and treated within the DoD or VHA.

Tests manufactured and offered for use exclusively for public health surveillance are also not affected by the phaseout policy.

Targeted Enforcement Discretion Approach for Other IVDs   

Additionally, the FDA has outlined a targeted enforcement discretion approach for certain other categories of LDTs. Under this approach, the FDA intends not to enforce certain applicable requirements for these IVDs. This decision is based on the FDA’s assessment that tests in these categories are unlikely to pose significant risks, or they are conducted under circumstances that inherently mitigate potential risks. These IVDs offered as LDTs include:

• Certain Modified Versions of Another Manufacturer’s 510(k) Cleared or De Novo Authorized Test
• LDTs Approved by New York State Department of Health’s Clinical Laboratory Evaluation Program (NYSDOH CLEP)
• LDTs for Unmet Needs Manufactured and Performed by Laboratories in an Integrated Healthcare System
• Currently Marketed LDTs (i.e., prior to May 6, 2024) and “Not Significantly Modified”
• Non-Molecular Antisera LDTs for Rare Red Blood Cell (RBC) Antigens for Transfusion Compatibility

The table below provides a high-level summary of the key categories of LDTs under FDA enforcement discretion and the regulatory requirements to which compliance is expected in Stages 1 through 5 of the agency’s phaseout policy.

Importantly, there are additional limitations to the agency’s enforcement discretion policies. For example, for LDTs that are modified versions of another manufacturer’s 510(k) cleared or De Novo authorized test, the FDA’s enforcement discretion policy exempting premarket review only applies when the modification was made following design control and other quality system requirements and in a manner that could not “significantly affect the safety or effectiveness of the test and does not constitute a major change or modification in intended use, and where the modified test is performed only in the laboratory making the modification”. Otherwise, FDA expects premarket submissions from laboratories modifying a third party’s 510(k) cleared or De Novo authorized test for the same types of changes for which FDA would expect a premarket submission from the original manufacturer making changes to its own IVD.

Similarly, any “significant modifications” to an LDT marketed before May 6, 2024 will require meeting compliance expectations that align with the phaseout policy. And, for LDTs for unmet needs manufactured and performed by laboratories in an integrated healthcare system, enforcement discretion would end when an FDA-authorized test that addresses the unmet need becomes available.

Moreover, as with any enforcement discretion policy, FDA may update any of these policies as circumstances warrant or if the circumstances that inform these policies change, consistent with FDA’s good guidance practices (section 701(h) of the FD&C Act, 21 CFR 10.115).  Additionally, regardless of the phaseout timeline and enforcement discretion policies for certain IVDs, FDA retains discretion to pursue enforcement action for violations of the FD&C Act at any time.

Laboratories will need to determine the FDA’s applicable regulations and enforcement discretion policies that apply to each of their LDTs.  This will guide decisions on compliance pathways and documentation requirements and help in determining needed resources.

6 Strategies to Help You Get Started

1. Stay Informed
   • Stay abreast of legislative developments and regulatory changes that may impact LDT regulation.
   • This includes proposed legislation, and changes in enforcement policies as well as FDA announcements, guidance documents, webinars, and other resources.
2. Understand FDA Requirements
   • Become familiar with FDA definitions, requirements, and expectations for LDTs.
   • This includes understanding the differences between LDTs and FDA-cleared/approved tests and knowing when FDA regulation applies.
3. Know your Test Status
   • Determine the FDA’s applicable regulations and enforcement discretion policies that apply to each type of LDT.
   • This will guide decisions on compliance pathways and documentation requirements and help in determining needed resources.
4. Quality System Compliance
   • Evaluate your laboratory’s CLIA Quality Management System (QMS) against FDA’s Quality System Regulations (QSR) to identify gaps.
   • Begin planning necessary changes to align with FDA requirements, ensuring documentation and processes meet regulatory standards.
5. Document Decisions and Rationale
   • Document decisions related to regulatory compliance, including rationale for enforcement discretion or alternative compliance strategies based on FDA policies.
   • Document compliance with FDA’s conditions for enforcement discretion, if applicable.
6. Plan for FDA Submissions
   • Assess whether FDA premarket submissions are necessary for your LDTs based on FDA requirements, the tests intended use and classification according to the FD&C Act necessary to reasonably assure safety and effectiveness.
   • Develop timelines and strategies for compiling necessary documentation and data to support submissions, if applicable.

How Beaufort Can Help

The phased approach aims to enhance FDA oversight while allowing laboratories time to adapt to new regulatory standards. However, laboratories should proactively prepare for compliance to ensure continued market access for their LDTs.

Our team of regulatory, quality, and clinical experts can help laboratories navigate the new regulatory landscape and ensure readiness for upcoming compliance milestones. We offers comprehensive support including:

• Training
  • Develop and conduct staff training sessions to ensure thorough understanding of and preparedness for the new regulatory requirements.
  • Customize training materials to address specific impacts of the FDA’s evolving standards on daily operations.
  • Incorporate interactive elements and case studies to enhance comprehension and application of compliance measures
• Assessment
  • Assess LDT current inventory and pipeline, determine the FDA’s applicable regulations and enforcement discretion policies that apply to each type of LDTs
  • Conduct gap assessments to identify necessary modifications in current quality systems, processes, operations, and documentation.
  • Address Quality Management System (QMS) gaps integrating both CLIA and FDA requirements
  • Develop regulatory strategies inclusive of considerations of NYSDOH CLEP approvals
  • Identify test(s) that may require additional analytical or clinical evaluation
• Compliance
  • Map compliance timelines
  • Document decisions related to regulatory compliance, including rationale for enforcement discretion or alternative compliance strategies based on FDA policies
  • Develop new Standard Operating Procedures (SOPs)
  • Prepare 21 CFR 820-compliant design control documentation
  • In the event premarket notifications are required, facilitate discussions with the agency through the pre-submission process, and prepare necessary pre-market submissions (Q-Sub, 510(k), De Novo, HDE, PMA)
• Readiness
  • Conduct mock inspections

Contact us to learn more about our services and how we can assist in meeting FDA requirements and maintaining market access for your LDTs.