Level Up your Documentation Processes and Systems to Comply with FDA Final Rule Stages 1 & 2

FDA’s ruling on enforcement of in vitro diagnostic (IVD) medical device requirements for laboratory-developed tests (LDTs) was published in May of 2024. Barring delays from legal or legislative action, enforcement of Stage 1 will begin in 9 months. We’ve previously reviewed relevant scenarios under which later stages of the enforcement rollout may not apply, but noted that nearly all labs who continue to run LDTs will need to comply with Stages 1 and 2. In our last post, we examined the requirements of these two stages more closely. Today, let’s consider how current LDT regulations’ requirements compare to requirements for Stages 1 and 2 stated in the FDA rule. We will also explore how compliance with the FDA requirements may impose different degrees of burden depending on the molecular laboratory setting. 

Bridging the Gap: CLIA, CAP, and the LDT Rule 

The FDA's new LDT rule introduces a regulatory framework that overlaps with existing requirements from CLIA (Clinical Laboratory Improvement Amendments) and CAP (College of American Pathologists) accreditation. While there are some similarities, there are also notable differences that laboratories must navigate to ensure compliance across all fronts. 

CLIA and CAP, which is the largest deeming authority under CLIA for complex molecular diagnostic testing, have long been the primary regulatory bodies governing laboratory practices with a focus on analytical and clinical validity. The LDT rule, however, extends beyond these traditional domains to encompass risk-based oversight of test design, manufacturing, and performance characteristics. 

Laboratories that have been diligently following CLIA and CAP guidelines may find themselves well-positioned to meet certain aspects of FDA requirements, such as complaint systems, personnel qualifications, and proficiency testing. However, the FDA’s emphasis on device-focused reporting, listing, and labeling represents significant additions to compliance needs required of laboratories who market LDTs. 

To bridge this gap, laboratories will need to evaluate their existing processes and documentation against the FDA’s requirements.  

Moreover, the LDT rule introduces a new level of scrutiny on the intended use claims and promotional materials associated with LDTs. Laboratories will need to ensure that their claims can be supported by robust analytical and clinical performance data and that their marketing materials accurately reflect the test's intended use and limitations. 

While the transition may be challenging, particularly for smaller laboratories with limited resources, the LDT rule aims to harmonize regulatory oversight with that of other medical devices, promoting consistency and patient safety. By proactively aligning their practices with the LDT rule, laboratories can not only ensure compliance but also demonstrate their continued commitment to improving quality and transparency. 

If your laboratory is actively running LDTs today, or if you have invested in the development of an LDT that you hope to launch in the next year, you likely serve clinicians and patients who rely on your tests. It seems unthinkable to cease operations and ask your customers to look elsewhere or even to abandon your test menu and test development roadmap and switch exclusively to off-the-shelf IVDs by May 2025. Fortunately, the final rule anticipated this, and your lab need only comply with Medical Device Reporting (MDR), correction and removal reporting, and complaint file requirements by May 2025 (Stage 1). By May 2026 (Stage 2), your lab must meet registration and listing requirements, labeling requirements, and, if applicable, investigational use requirements. A lab can continue running existing LDTs or even newly launched LDTs through April 2027 without additional regulatory burden. We’ll go into more detail on Stages 1 and 2 requirements by laboratory type below. 

If your lab normally seeks New York State Clinical Laboratory Evaluation Program (NYS CLEP) approval, you’ll still need to comply with Stages 1 and 2. Likewise, if your lab is integrated into a healthcare system and your LDTs serve unmet needs, Stages 1 and 2 again apply. The only reasons a clinical NGS lab would be exempt from Stages 1 and 2 are if the lab is a Veteran’s Affairs Administration or Department of Defense lab, or if the lab’s test menu comprises off-the-shelf or “kitted” FDA-authorized IVDs exclusively. While your lab may make the decision to move towards kitted IVDs, planning to comply with Stages 1 and 2 gives you a 2+ year runway to refine your strategy and evaluate IVDs on the market. 

FDA's New LDT Rule: Impact on Different Laboratory Settings 

The FDA's new LDT rule will have varying impacts on different types of laboratories, depending on their size, scope, and the specific tests they offer. Let's explore how the Stage 1 and Stage 2 requirements might affect different laboratory settings and the unique challenges each type will face. 

Hospital Laboratories 

Stage 1: Hospital laboratories, often embedded within larger healthcare systems, will need to integrate these regulatory requirements into their existing processes. New activities include coordinating between multiple departments, training diverse staff members, and ensuring consistent reporting across all units. Implementing standardized procedures for adverse event reporting and corrective actions will require significant effort and coordination. 

Stage 2:  Hospital labs must also manage the administrative burden associated with the registration and listing process, especially given the high volume and variety of tests they perform. Ensuring that all test labels meet FDA standards and managing investigational use compliance will necessitate ongoing education and resource allocation to maintain compliance. 

Commercial Laboratories 

Stage 1: Commercial laboratories, which often offer a wide range of diagnostic tests, will need to add new systems and processes to meet Stage 1 requirements. Compliance with MDR, correction and removal reporting, and Quality System (QS) requirements will require these labs to invest in sophisticated quality management systems and reporting mechanisms. The high throughput and diversity of tests mean that documenting and promptly reporting any adverse events or corrections will require automation using technology. Ensuring that all staff are trained and that systems are in place to handle the volume of data and reports will be a major undertaking. 

Stage 2:  Given the extensive test menu, commercial labs should devote significant resources to registration and ongoing compliance with labeling standards. Additionally, managing compliance with investigational use requirements will entail meticulous tracking and documentation, especially for labs involved in developing and testing new diagnostic technologies. 

Specialty Laboratories 

Stage 1: Specialty laboratories, such as those focused on genetic testing, rare diseases, or oncology, often handle complex and high-risk tests, making compliance with adverse event reporting and quality systems crucial. They must develop specialized training programs for staff and ensure that quality management systems are tailored to the unique nature of their tests. Furthermore, these laboratories will need to implement these changes without disrupting ongoing specialized testing services. 

Stage 2: For specialty laboratories, Stage 2 compliance will involve registering and listing highly specialized LDTs with the FDA, ensuring that labeling is precise and meets all regulatory requirements. Investigational use compliance will be particularly relevant for labs conducting cutting-edge research or developing innovative tests. New processes include navigating the complexities of obtaining Investigational Device Exemptions (IDEs) and ensuring all clinical investigations comply with FDA regulations while coordinating closely with research partners. 

Small Independent Laboratories 

Stage 1: Small independent laboratories will need to invest in new software or systems for quality management and reporting to comply with MDR, correction and removal reporting, and QS requirements. They must also train staff to handle these new responsibilities.  

Stage 2: Stage 2 requirements including updating registrations and ensuring accurate labeling may be entirely novel concepts requiring the support of external expertise or collaborations with larger institutions to effectively meet these regulatory demands. 

Academic and Research Laboratories 

Stage 1: Academic and research laboratories that develop LDTs for research or limited clinical use will need to establish procedures for reporting and quality management, which may involve training research staff on regulatory requirements and integrating compliance processes into their research workflows. They must balance these new regulatory compliance with the need for research and innovation. 

Stage 2: Stage 2 requirements could impact the pace of research and development, as additional administrative steps will be required before tests can be used in clinical studies or practice. These laboratories should prepare to navigate the new compliance requirements without hindering research progress, which will require careful planning and a clear allocation of resources to each type of activity. 

Does one of the above laboratory profiles resonate with you? Successful compliance with Stages 1 and 2 may require operating in some unfamiliar territory. But it will be carried by your lab’s ongoing commitment to quality, a familiar and worthy objective. 

Are you ready to begin? Position your laboratory to meet the elevated patient safety standard brought by Stage 1. Velsera is standing by to help. Get in touch by writing to us at Quality.Team@velsera.com, and sign up for our newsletter at the bottom of this page.  

The information presented here is not intended as legal or regulatory advice but rather as a brief introduction to the subject matter. Compliance with the FDA’s final rule may rely on factors and requirements not listed here, and any person or entity subject to the final rule is encouraged to obtain professional advice specific to their situation.