How small, high-complexity testing labs can adapt to FDA LDT regulatory shifts

The landscape of laboratory-developed tests (LDTs) is fraught with uncertainty, particularly as regulatory bodies like the U.S. Food and Drug Administration (FDA) continue to explore oversight mechanisms. For small, high-complexity testing labs, this evolving environment presents unique challenges. However, it also offers opportunities to harness existing accreditation frameworks such as ISO 15189, CAP (College of American Pathologists), and NY CLEP (New York State Clinical Laboratory Evaluation Program) to build resilience and position for strategic flexibility. By leveraging these robust standards, labs can stay ahead of the curve, ensuring they are prepared to pivot as regulatory landscapes shift.

The current state of FDA LDT regulations

The regulatory framework for laboratory-developed tests (LDTs) remains a topic of significant debate and uncertainty. Historically, LDTs operated with minimal Centers for Medicare & Medicaid Services (CMS) oversight under CLIA (Clinical Laboratory Improvement Amendments). However, the FDA has consistently expressed concerns over the lack of uniform quality and safety standards, particularly for high-complexity LDT tests.

Impending FDA regulatory compliance aims to bring LDTs closer to the standards applied to in vitro diagnostics (IVDs), including requirements for clinical validation, pre-market approval, and post-market surveillance (including medical device reporting, MDR). For small, high-complexity labs, navigating these changes requires proactive preparation and the leveraging of existing accreditation frameworks to align with the future FDA requirements. These evolving standards may include the need for substantially more validation studies, expanded access to diverse and representative sample populations, and significant financial investment. By strategically planning and optimizing resources, small, high-complexity labs can better position themselves to address these heightened regulations while maintaining compliance and operational efficiency.

Table 1. Comparative analysis of the key regulatory authorities.

A comparative analysis across key regulatory authorities, as seen in Table 1, reveals the following important insights for small, high-complexity labs:

CLIA (Clinical Laboratory Improvement Amendments): While federally mandated, CLIA’s focus is limited to personnel qualifications and test accuracy. In addition, the enforcement is left up to each state’s discretion. This lack of clinical validation standards and consistent oversight highlights gaps that FDA oversight would aim to address.
NY CLEP: With its stringent pre-market test approval process, NY CLEP stands out as the most closely aligned framework to FDA’s proposed regulatory goals. Small, high-complexity labs operating under NY CLEP are already well-positioned for future FDA oversight.
CAP (College of American Pathologists): CAP accreditation provides strong alignment with FDA goals in quality management, risk management, and test validation. However, it lacks mandatory pre-market review, which will be a key feature of the impending FDA oversight.
ISO 15189: This international standard emphasizes systematic quality management processes, including defining how tests are validated against their intended use. Having this systematic quality management system already in place provides a strong foundation for labs aiming to prepare for FDA oversight.

Figure 1 illustrates how each of these key regulatory authorities align with the impending LDT regulations.

Figure 1. Key regulatory authorities alignment to impending FDA LDT regulations.

Bridging existing standards to future requirements

To navigate the evolving regulatory landscape for LDTs, small, high-complexity testing labs can proactively adapt their operations by leveraging existing accreditation frameworks. By focusing on enhancing quality systems and test validation and also preparing for pre-market review and post-market surveillance, these labs can build resilience and readiness for potential FDA requirements.

1. Enhance quality systems¹

A robust quality management system (QMS) is essential for ensuring compliance with both current and anticipated regulations. The FDA focus on consistent quality and risk mitigation underscores the importance of adopting systematic QMS practices.

ISO 15189: Promotes a risk-based approach to quality management, encouraging labs to identify and mitigate risks proactively. This creates a culture of continuous improvement that can adapt to evolving regulatory needs.
CAP: Focuses on proficiency testing and risk management, ensuring that labs not only meet current standards but are also prepared to address gaps identified during inspections.
CLIA: Provides the foundational framework for personnel qualifications and quality control, which can be enhanced with elements from ISO and CAP for a more comprehensive QMS.

Strategies to augment quality systems include conducting a gap analysis to identify areas where QMS can be strengthened, using ISO 15189 and CAP as benchmarks. Also, training staff on risk-based thinking and incorporating quality improvement tools, such as root cause analysis and process mapping are additional strategies for supplementing existing QMS structures. Establishing a system for regular internal audits to ensure continuous compliance is critical for external inspection readiness, such as an FDA audit.

2. Focus on validation^2,3

Test validation is the cornerstone of both current and future regulatory requirements. The FDA’s impending LDT oversight places a strong emphasis on analytical and clinical validation to ensure test accuracy, precision, and clinical utility. Labs can begin strengthening their validation protocols by adopting practices from frameworks like ISO 15189, CAP, and NY CLEP:

ISO 15189: Encourages a detailed approach to validation, requiring laboratories to define the process for ensuring every test meets its intended use. This aligns closely with FDA's proposed expectations for LDTs, even though analytical and clinical validation is not called for outright.
CAP: Already mandates validation and verification for all new and modified LDTs, providing a robust starting point for labs aiming to enhance their validation protocols.
NY CLEP: Requires pre-market approval of all new LDTs and modified FDA-approved tests, with rigorous validation standards for accuracy, precision, and clinical utility, which small, high-complexity labs can use as a benchmark.

Actionable steps for labs to take are developing comprehensive validation processes, such as a master validation plan, which should include test design documentation, analytical performance evaluation, and clinical utility studies. Also important is the meticulous documentation of validation efforts to ensure traceability and compliance with future regulations. Case studies and white papers from professional organizations like CAP and CLSI (Clinical and Laboratory Standards Institute) are great resources for determining validation best practices.

3. Prepare for pre-market review^4,⁵

The potential for pre-market review under FDA oversight represents a significant shift for LDTs. The FDA impending requirements indicate the potential for extensive data submission demonstrating test safety and efficacy before commercialization. Labs can look to NY CLEP as a model for meeting these stringent requirements.

NY CLEP: Already mandates test (pre-market) approval for all LDTs, which includes the review of both analytical and clinical validation. While labs might not be serving New York State residents, NY CLEP is a valuable resource for understanding future FDA expectations.

Productive actions begin with reviewing and, where possible, adopting the NY CLEP test approval processes to simulate FDA pre-market review expectations. Collaborate with regulatory consultants and industry experts to understand data submission requirements and prepare comprehensive dossiers for LDTs.

4. Prepare for post-market surveillance⁵

Post-market surveillance may overlap with existing clinical laboratory regulations and standards; however, only the FDA requires the centralized reporting of adverse events.

Strategies for implementing these additional requirements would be to develop a centralized process for documenting potential adverse events and determining the reportability based upon FDA regulations. Existing requirements for complaints, non-conformances, and root cause analysis should be leveraged for the integration of post-market surveillance into a lab’s QMS.

Monitoring updates from the FDA and professional organizations like ADLM (Association for Diagnostics and Laboratory Medicine) are crucial for staying informed about regulatory changes.

Leveraging accreditation for strategic flexibility

While each of these frameworks offers distinct benefits, their real value lies in how they can be integrated to build a resilient, adaptable, operational foundation. By aligning processes with NY CLEP, CAP, and ISO 15189 standards, labs can achieve the following:

Streamline quality management: Unified quality systems reduce redundancies and enhance efficiency, freeing up resources for innovation and growth. For instance, ISO 15189’s emphasis on risk-based thinking can be integrated with CAP’s practical guidance and NY CLEP’s stringent validation protocols to create a cohesive quality management system. This not only reduces operational inefficiencies but also ensures consistency across all testing processes.

Anticipate regulatory changes: By adhering to rigorous standards, labs are better positioned to meet future FDA requirements with minimal disruption. For example, NY CLEP’s pre-market approval processes and CAP’s validation frameworks can act as proactive measures, allowing labs to adapt quickly to new regulatory mandates. This flexibility mitigates the risks of non-compliance and costly operational overhauls.

Enhance market competitiveness: Demonstrating commitment to high standards builds trust with clinicians, patients, and partners, providing a competitive edge. A CAP accredited lab that integrates ISO 15189’s global standards and NY CLEP’s rigorous validation requirements is likely to stand out as a reliable and high-quality service provider. This not only attracts more clients but also strengthens partnerships with stakeholders who value quality and compliance.

Facilitate innovation: Robust quality frameworks create an environment where innovation can thrive, enabling labs to expand their test offerings and adapt to market demands. For example, a lab that adopts ISO 15189’s culture of continuous improvement and CAP’s focus on proficiency testing is well-equipped to develop and validate new LDTs rapidly, keeping pace with advancements in diagnostic technologies.

Practical steps for implementation

For labs looking to leverage these accreditation frameworks, Figure 2 provides a roadmap of practical steps small, high-complexity labs can take. By following these steps, labs can not only align with current accreditation frameworks but also build a resilient foundation that prepares them for the impending FDA regulations and any other future regulatory changes. This approach ensures operational excellence, mitigates risks, and positions labs as leaders in quality and innovation.

Figure 2. Roadmap of practical steps for bridging existing standards to future requirements.

Looking ahead

The uncertainty surrounding FDA LDT regulations may persist, but for small, high-complexity labs, it doesn’t have to equate to instability. By aligning with NY CLEP, CAP, and ISO 15189 standards, labs can establish a robust foundation that not only addresses today’s challenges but also empowers them to navigate and excel in a dynamic regulatory environment.

In times of change, adaptability is the cornerstone of success. For small, high-complexity labs, adopting these accreditation frameworks goes beyond compliance — it fosters resilience and positions the lab for sustainable growth in the face of regulatory enhancements.

References

Berte L, Mortschman T, Ball J, et al. Quality Management System: A model for laboratory services; Approved guideline—Fourth Edition. Clinical & Laboratory Standards Institute (CLSI). Published June 2011. Accessed January 24, 2025. https://clsi.org/media/1523/qms01a4_sample.pdf.
CAP Council on Accreditation. CAP laboratory accreditation program standards for ... College of American Pathologists (CAP). Published August 2017. Accessed January 24, 2025. https://documents-cloud.cap.org/appsuite/learning/LAP/TLTM/resources/standards/LAPstandards.pdf.
Technical Committee ISO/TEC 3212. ISO 15189:2012 Medical laboratories — Requirements for quality and competence. International Organization for Standardization (ISO). Published August 1, 2014. Accessed January 24, 2025. https://www.iso.org/standard/56115.html.
New York State Department of Health. Laboratory standards. Laboratory Standards | New York State Department of Health, Wadsworth Center. Published December 2024. Accessed January 24, 2025. https://www.wadsworth.org/regulatory/clep/clinical-labs/laboratory-standards.
Center for Devices and Radiological Health. Laboratory developed tests. U.S. Food and Drug Administration (FDA). Updated January 8, 2025. Accessed January 24, 2025. https://www.fda.gov/medical-devices/in-vitro-diagnostics/laboratory-developed-tests.