Ensuring Compliance with FDA’s Final Rule for Laboratory Developed Tests (LDTs)

The FDA’s final rule regulating Laboratory Developed Tests (LDTs) marks a pivotal shift in compliance requirements for clinical laboratories. Adapting to these regulations requires a strategic approach that aligns with FDA expectations and existing CLIA requirements. For many laboratories, navigating this transition poses challenges due to limited experience with FDA processes.

RQM+ offers a systematic, flexible approach designed to guide laboratories through this regulatory shift, ensuring compliance without disrupting operations.

This technical brief outlines our structured methodology for guiding laboratories through the transition from CLIA-based compliance to full FDA compliance, incorporating comprehensive gap assessments, risk mitigation strategies, and long-term regulatory planning. Readers will gain valuable insights that can inform their compliance strategies, making this brief a worthwhile resource regardless of the specific approach.

Background

The FDA’s decision to regulate LDTs as medical devices introduces several key challenges:

• Developing compliance strategies for full and partial enforcement discretion requirements within the final rule

• Meeting Medical Device Reporting (MDR) requirements

• Transitioning from CLIA to FDA Quality System Regulation (QSR) compliance

• Implementing design control and risk management processes

• Understanding FDA expectations for IVD validation versus CLIA requirements for LDTs

• Adapting to new premarket submission obligations

To remain competitive and maintain market access, laboratories must proactively align their Quality Management Systems (QMS) and product classifications with the FDA's final rule.

Who RQM+ Supports

RQM+ offers strategic consulting services to a diverse range of organizations impacted by the FDA’s final rule on LDTs. Our services are tailored to each client’s unique needs and existing framework rather than providing a one-size-fits-all solution.

• Clinical Laboratories: High-complexity labs developing proprietary LDTs that must transition from CLIA to FDA oversight.

• Hospitals & Academic Medical Centers: In-house diagnostic labs requiring compliance with FDA premarket review and QMS requirements.

• Specialty & Genetic Testing Companies: Providers of high-risk or novel diagnostic tests who need risk classification and regulatory submission strategies.

• IVD Manufacturers & Companion Diagnostics Developers: Companies collaborating with laboratories to ensure compliance with FDA regulations.

• Biotech & Pharmaceutical Companies: Firms developing biomarker-driven LDTs now subject to new regulatory scrutiny.

• Investors & Private Equity Firms: Entities assessing regulatory impacts on LDT-focused portfolio companies.

Case Study:
LDT Assessment & Remediation Project

A leading CLIA-certified specialty testing laboratory partnered with RQM+ to transition to FDA compliance under the final rule.

Challenge

The laboratory faced a significant regulatory shift, requiring an evaluation of its quality system, product classifications, and regulatory readiness. Despite a strong compliance history under CLIA, the lab lacked experience with FDA expectations and processes. Given its large test menu, including FDA-cleared tests, 
FDA-modified tests, and in-house developed LDTs, it needed to maintain CLIA-compliant processes with minimal disruption while adapting to new FDA requirements.

Solution

RQM+ conducted a comprehensive gap assessment to identify areas where the laboratory’s existing QMS and product development processes did not align with FDA expectation.

Outcomes

• Identified compliance gaps for each stage of the final rule’s phased implementation
• Developed a strategic transition plan to meet FDA requirements
• Created a roadmap for remediation and premarket submission strategies for high-risk LDTs
• Provided ongoing guidance to ensure continued alignment with FDA compliance deadlines

Detailed Summary Of Key Activities

1. Regulatory Strategy and Change Impact Assessment

   • Conducted a detailed review of the test menu, including the regulatory status of each test and applicability of full or partial enforcement discretion policies.
   • Evaluated the potential use of the “grandfathering” partial exemption for tests marketed before May 6, 2024, assessing the risks and benefits based on prior and planned modifications.

2. Complaint Handling and Medical Device Reporting (MDR) Gap Assessment

   • Reviewed the lab’s existing complaint handling procedure and electronic tracking system to identify gaps in meeting FDA complaint record requirements.
   • Clarified the distinction between FDA-defined “complaints” and those governed by CLIA or business needs.
   • Analyzed one year of historical complaints to determine which would be FDA-reportable.
   • Developed a strategy for updating complaint procedures and electronic tracking systems for Stage 1 compliance.

3. Test Validation Review

   • Assessed validation procedures, ensuring alignment with FDA’s emphasis on individual test performance validation rather than CLIA’s process-driven approach.
   • Evaluated a subset of validations across all LDT technologies, identifying gaps and providing remediation strategies aligned with the staged implementation of the final rule.
   • Provided guidance on efficient use of FDA pre-submission requests.

4. Quality Management System (QMS) Gap Analysis 

   • Conducted a comparative analysis of the lab’s CLIA-compliant QMS against FDA Quality System Regulation (21 CFR 820) and the FDA’s Quality Management System Regulation (QMSR), which 
     aligns with ISO 13485:2016.
   • Established a remediation roadmap for achieving Stage 3 compliance by May 6, 2027.

Key Compliance Milestones & Deadlines

• May 6, 2025: MDR, Complaint Handling, Correction & Removal Reporting.

• May 6, 2026: Establishment Registration, Device Listing, Labeling, IDE.

• May 6, 2027: Full QSR implementation, including design controls, CAPA, and supplier management.

• November 6, 2027: Premarket review for high-risk LDTs (IVDs).

• May 6, 2028: Premarket review for moderate and low-risk LDTs.

Why Partner with RQM+

RQM+ is a trusted regulatory partner with deep expertise in IVDs, LDTs, and FDA compliance. Our tailored, strategic support ensures laboratories meet regulatory deadlines while maintaining operational efficiency.

Take Action Now: Contact RQM+ today to discuss how we can support your LDT compliance journey.

About the Author

Margot Borgel, Ph.D. is an expert in the technical and regulatory requirements of in vitro diagnostics (IVDs) and laboratory developed tests (LDTs) with over 12 years of experience in both the US and EU markets.

She was recently appointed to the CLSI Strategic Laboratory-Developed Test (LDT) Final Rule Advisory Group, which was established to support CLSI’s response to LDT regulation. At RQM+. She helps clients meet regulatory requirements for IVDs and LDTs through strategic regulatory support and guidance throughout the entire product lifecycle. She also performs regulatory intelligence activities at RQM+ to ensure compliance to the ever-changing IVD regulatory landscape.

Margot holds a BSc and Ph.D. in Chemistry and has IVD experience within the industry as well as with an EU notified body. A strategic thinker and collaborator, she has an extensive scientific background in assay development, IVD manufacturing, process improvement, regulatory requirements, and quality management systems. She is a subject matter expert for performance evaluation and clinical requirements, international standards, and guidance documents for IVDs and LDTs.

Margot is passionate about supporting companies looking for market access of their innovative test systems and IVDs and takes on every project as if family was on the other side of the diagnostic.

Feel free to connect with Margot on LinkedIn here.