New FDA Regulations for Laboratory-Developed Tests

Laboratory-Developed Tests (LDTs) were initially governed by the Medical Device Amendments of 1976, and the Food and Drug Administration was not enforcing applicable requirements for most LDTs. But this is going to change, given the evolving and more risky nature of modern LDTs.

On May 6, 2024, the FDA announced a final rule amending its regulations and explicitly pronouncing in vitro diagnostic products (IVDs), even when the manufacturer of the IVD is a laboratory, to be devices under the Federal Food, Drug, and Cosmetic Act (FD&C Act). With this amendment, it aims to make LDTs safer and more effective.

The FDA is also finalizing a policy to increase oversight of IVDs offered as LDTs in a phased manner over the next four years to implement targeted enforcement discretion policies for specific categories of laboratory-manufactured IVDs.

The Need for FDA Regulations for LDTs

Laboratory-developed tests, or LDTs, are in vitro diagnostic products (IVDs) used clinically. They are designed, manufactured, and used within a single laboratory and must comply with the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulatory requirements to perform high-complexity testing.

IVDs are used for the collection, preparation, and examination of specimens taken from the human body, including blood, saliva, or tissue. This is tested to measure or detect substances or analytes such as proteins, glucose, cholesterol, or DNA, providing insights into the patient's health. The sample tested is used to diagnose, monitor, or determine the treatment for various diseases and conditions.

LDTs were initially used for very specialized patient needs, were localized, used in small volumes, and were primarily low-risk in nature. However, due to improved transportation and technological capabilities, business reach has expanded, and LDT use is now more widespread, covering larger and more diverse populations. In fact, large laboratories are accepting specimens from across states.

Access to high-tech instrumentation and software also enables laboratories to work with large volumes of specimens, and the outcomes play a crucial role in critical healthcare-related decision-making. As a result, there is a greater need to regulate their activities and better protect public health by ensuring the safety and effectiveness of IVDs offered as LDTs. Patient access and reliance are other important public health considerations that must be accounted for.

The new rule is a result of years of working with industry stakeholders since 2010 to prevent any false test results or claims that could cause patient harm.

IVDs offered as LDTs generally are required to comply with the applicable requirements in a four-year period under the phaseout policy in the following five stages:

• Stage 1: By May 6, 2025, compliance with

• medical device reporting (MDR) requirements
• correction and removal reporting requirements
• quality system (QS) requirements regarding complaint files.

• Stage 2: By May 6, 2026, compliance with

• requirements such as registration and listing, not covered during other stages of the phaseout policy
• labeling requirements
• investigational use requirements

• Stage 3: By May 6, 2027, compliance with

• QS requirements (except complaint files, which are already addressed in stage 1)

• Stage 4: By November 6, 2027, compliance with

• premarket review requirements for high-risk IVDs offered as LDTs (IVDs that may be classified into class III or that are subject to licensure under section 351 of the Public Health Service Act), unless a premarket submission has been received by the beginning of this stage in which case FDA intends to continue to exercise enforcement discretion for the pendency of its review.

• Stage 5: By May 6, 2028, compliance with

• premarket review requirements for moderate-risk and low-risk IVDs offered as LDTs (that require premarket submissions), unless a premarket submission has been received by the beginning of this stage in which case FDA intends to continue to exercise enforcement discretion for the pendency of its review.

The FDA will also exercise enforcement discretion and for certain categories of IVDs manufactured by a laboratory, it may not enforce some or all applicable requirements. Some IVDs may be governed by more than one enforcement discretion policy.

ComplianceQuest EQMS and Design Controls for Compliance with the New Rule

ComplianceQuest is a cloud-based compliance and product development solution that aligns with ISO standards. It helps businesses in a variety of industries such as manufacturing, life sciences, and automotive to design and develop products more efficiently and with compliance to applicable standards.

Lab Investigations: ComplianceQuest’s Laboratory OOS module enables compliance with systematic and efficient laboratory investigations. It facilitates consistent lab investigations easy for QA and QC teams with pre-built workflows and customizable checklists that offer guidance and ensure compliance, every time. The solution allows laboratory teams to initiate a phase 2 investigation whenever necessary, conduct a full production review, and then escalate to a CAPA if needed to ensure high-quality products.

It also is aligned with GLP, ISO, and other regulatory authorities and standards that require a consistent, thorough, and well documented investigation process that is right for the first time. Implementing the CQ solution will make laboratories ready for compliance with the new FDA requirements quickly and efficiently, meeting deadlines easily.

Design Controls: ComplianceQuest’s Design Controls Solution provides visibility into the product design process, making it easy for teams to collaborate and design high quality products, all the while guaranteeing compliant and comprehensive documentation. It enables tracking of actions, deliverables, and timelines, assign actions to team members, and follow up on them to make sure they are completed on time.

CQ’s Product Design Management solution makes documentation effortless for quality and engineering teams. All steps, requirements, outputs, reviews, and changes are well documented and easily shareable/printable at the click of a button. Approvals, signatures, revisions, and meeting notes are also automatically documented, with built-in revision control for design files. This ensures compliance with regulatory and quality standards such as 21 CFR 820.30 and ISO 13485.

Quality: The ComplianceQuest EQMS is a comprehensive solution enabling risk, change, documentation, complaints, and training management. It helps automate and schedule audits and inspections to proactively identify and mitigate risks and nonconformances. For laboratories, it can help ensure end-to-end quality to improve compliance and shorten development cycles.

To know more, request a meeting with CQ Expert here: https://outreach.compliancequest.com/calendar/team/t/3#/select-time