In recent years, Laboratory Developed Tests (LDTs) have garnered significant attention, particularly during the COVID-19 pandemic. If you’ve had a COVID-19 test or undergone genetic testing, it was likely an LDT. These in-vitro diagnostic (IVD) tests are designed, manufactured, and analysed within a single laboratory. Up until this point, LDTs operated under minimal FDA oversight, but now the regulatory landscape is changing significantly with new FDA regulations coming into effect. This article will explore what these new regulations mean for your lab and how to ensure compliance.
Background on LDTs
Unlike other commercial tests, LDTs are not sold or distributed to other labs or healthcare facilities. LDTs are often created because no commercial test exists for a specific condition, such as rare genetic disorders, or when existing tests need modification for particular patient populations.
Despite not being FDA-approved for marketing, Laboratory Developed Tests (LDTs) still require rigorous validation to ensure their accuracy, precision, sensitivity, and specificity. Although LDTs are not sold to other laboratories for testing, they still need to meet high standards to be reliable and effective.
Some examples of LDTs include:
- Genetic Tests: these tests identify genetic mutations that may lead to inherited disorders such as cystic fibrosis or hereditary cancers.
- Oncology Tests: LDTs can detect specific biomarkers to guide cancer treatment, such as tests for BRCA1 and BRCA2 gene mutations.
- Infectious Disease Tests: these are used to diagnose infections, such as viral load tests for HIV.
- Cardiology Tests: tests like those that measure cholesterol subfractions to assess heart disease risk.
- Prenatal Screening: tests to detect chromosomal abnormalities in foetuses, such as Down syndrome.
Prior to FDA Oversight
In 1976, the FDA gained the authority to regulate medical devices, including LDTs, but initially chose not to enforce it due to their simplicity and limited use. However, advancements in technology, especially following the Human Genome Project, have made LDTs significantly more complex and widely used. Until recently, LDTs still faced minimal regulation, leading to potential issues like unreliable tests based on weak evidence and significant risks to patients due to false-positive and false-negative results.
For example, some LDTs claimed to offer individualised health optimizations without proper validation or inaccurately screened for serious conditions like heart disease. The lack of FDA oversight allowed these problematic tests to persist, as existing regulations under the Clinical Laboratory Improvement Amendments (CLIA) only covered laboratory operations, not the tests themselves. In 2015, the FDA highlighted 20 problematic LDTs that had caused or potentially caused significant harm to patients due to inaccuracies. This underscored the urgent need for comprehensive FDA regulation to ensure the safety and reliability of LDTs. Consequently, about a month ago, the FDA decided to change its regulatory approach.
Breaking Down the New FDA Regulation
The FDA's new rule, effective April 29, 2024, classifies in vitro diagnostic products (IVDs), including LDTs, as medical devices under the Federal Food, Drug, and Cosmetic Act. This regulation establishes a phased approach over four years to enhance oversight of LDTs, requiring laboratories to comply with medical device reporting, quality system regulations, and premarket reviews, particularly for high-risk and moderate-risk tests. The objective is to ensure that LDTs are safe, effective, and reliable, thereby protecting public health and improving diagnostic accuracy.
Compliance Under the New LDT Regulation
The new FDA rule outlines a comprehensive phaseout policy for laboratory-developed tests (LDTs), spanning five stages over four years. Starting in May 2025, the FDA will expect compliance with various requirements such as adverse event reporting, quality system regulations, and premarket reviews. By 2026, additional regulations including registration, labelling, and investigational use will be enforced. High-risk IVDs will need to meet premarket review requirements by November 2027, while moderate and low-risk IVDs will follow by May 2028. Certain IVD categories, like public health surveillance tests and forensic tests, may be subject to targeted enforcement discretion policies, easing some compliance burdens. This phased approach aims to ensure safety and accuracy in diagnostic testing.
For LDT manufacturers, adopting robust Electronic Laboratory Notebooks (ELN) and Quality Management Systems (QMS) is crucial to meet these new requirements. ELNs can streamline data collection and documentation, ensuring data integrity and traceability. QMS will help manage compliance with the FDA's stringent quality standards, covering aspects such as design controls, corrective actions, and record-keeping.
The new FDA rule concerns laboratories that develop and use LDTs, impacting those involved in creating in vitro diagnostic products (IVDs) used within a single laboratory setting. The rule affects clinical laboratories, healthcare providers, and diagnostic test manufacturers, requiring them to comply with stricter regulations to ensure the accuracy, safety, and reliability of LDTs.
Why does this matter for your laboratory?
The new FDA rule is crucial as it ensures the safety, accuracy, and reliability of Laboratory Developed Tests (LDTs). By requiring compliance with medical device reporting, quality system regulations, and premarket reviews, the rule aims to protect public health. Non-compliance can result in inaccurate or unreliable test results, potentially leading to misdiagnosis, inappropriate treatments, and harm to patients. Adhering to these regulations is essential for maintaining high standards in diagnostic testing and safeguarding patient care.
FDA Rule in Action
We recently engaged with a leading company specialising in high-complexity molecular diagnostics for infectious diseases. They recognised the necessity of transitioning from paper-based ELNs to a digital ELN system due to new FDA regulations. This move is crucial for ensuring compliance with stringent requirements like enhanced data integrity, traceability, and efficient reporting.
Similarly, we collaborated with a pioneering biotech firm developing LDTs for rare genetic disorders. They shifted from traditional paper-based quality management to a digitised QMS, streamlining documentation, enhancing traceability, and meeting FDA standards more efficiently. These digital transitions have optimised workflows, improved compliance, and resulted in faster, more reliable test results.
Further resources to understand the new LDT regulations:
- FDA overview of Laboratory Developed Tests: https://www.fda.gov/medical-devices/in-vitro-diagnostics/laboratory-developed-tests
- FDA Webinar - Enforcement Policies for Certain In Vitro Diagnostic Devices - Draft Guidances: https://www.fda.gov/medical-devices/medical-devices-news-and-events/webinar-enforcement-policies-certain-in-vitro-diagnostic-devices-draft-guidances-06052024