FDA’s new LDT regulation underscores the vital role of IVD CROs in compliance and safety. Phased over four years without grandfathering, it highlights the necessity for IVD CROs’ regulatory expertise and their key role in aligning LDTs with stringent standards, marking a significant shift in the IVD landscape.
Introduction
The Food and Drug Administration (FDA) recently released a groundbreaking proposed rule on September 29, 2023, aiming to transform its existing approach toward Laboratory-Developed Tests (LDTs). This paradigm shift directly impacts In Vitro Diagnostic products (IVDs) and their regulation. The proposed rule presents a layered plan for LDTs, phasing out FDA’s longstanding policy of enforcement discretion. For stakeholders in the IVD sector, including clinical laboratories and LDT manufacturers, the implications of this proposed rule are monumental.
Key Points to Consider as the FDA regulates LDTs
- Modification to IVD Definition: The FDA aims to explicitly categorize LDTs as IVDs within the scope of 21 CFR Part 809.3, thus making them subject to FDA’s medical device regulations, including premarket review.
- Phased Implementation: The FDA proposes to gradually roll back its enforcement discretion policy for LDTs, segmenting the regulatory shifts over five distinct stages across a four-year period.
- No Grandfather Clause: Unlike previous considerations, the new proposal doesn’t plan to “grandfather” existing LDTs. Public commentary on this subject is invited.
- Test Exemptions: Specific test types, such as forensic and human leukocyte antigen tests, are marked for exemption from enhanced regulatory oversight.
- Comment Period: Stakeholders have until December 4, 2023, to submit their feedback on the proposed rule.
Background on FDA Regulation for LDTs and IVDs
IVDs have traditionally been subject to rigorous regulatory scrutiny under various heads:
- 510(k) premarket notification or premarket approval (PMA)
- Quality system regulation
- Medical device reporting
- Registration and listing
- Labeling
These IVDs also fall under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). LDTs, a specialized category within IVDs, have long operated under enforcement discretion, essentially receiving less stringent oversight. This approach historically aligned with the perception of LDTs as low-risk products, but the proposed rule acknowledges the evolved complexity and widespread use of LDTs in modern healthcare.
The Evolving Landscape of LDTs
Over the past 50 years, the role of LDTs has changed dramatically, making the FDA regulation of Laboratory Developed Tests increasingly crucial. Their growing prevalence and the technical sophistication involved have prompted calls for stronger regulatory oversight. These significant developments have culminated in the FDA’s renewed perspective on LDTs. Shedding its previous stance of general enforcement discretion, the FDA Laboratory Developed Tests Regulation now aims to redefine LDTs broadly, addressing potential regulatory gaps and emphasizing the need for robust public health protection.
The Road Ahead: Implications and Recommendations
The phased implementation approach impacts various aspects of medical device regulation:
- Medical Device Reporting: Will be the first area where enforcement discretion will cease.
- Quality Systems: Expected to come under scrutiny three years after the final policy is published.
- Premarket Review: To be phased in 3.5 to four years after the final policy, impacting high-risk IVDs first and then trickling down to moderate-risk and low-risk IVDs.
Given these imminent changes, clinical labs offering LDTs must prepare for enhanced regulatory compliance and for increased FDA regulation of Laboratory developed tests. These labs should develop protocols for both analytical and clinical validity, ensuring alignment with new regulatory expectations.
Synergies with the EU’s IVDR roll-out
In Europe, a similar regulation, the In Vitro Diagnostic Regulation (IVDR), is being phased in, emphasizing the importance of compliance for in house developed tests. Under IVDR, laboratories must ensure that their Technical Documentation and Quality Management System are up-to-date and comply with the regulation and the national law. Failure to comply with the IVDR can result in serious consequences, including fines, loss of accreditation, and even closure of the laboratory.
Furthermore, laboratories that develop in-house IVDs will be required to comply with similar requirements for manufacturing as commercial IVD manufacturers. This means that laboratories must ensure that their IVDs meet high standards for safety and performance, which can only be achieved through rigorous testing and validation.
It is important to note that the IVDR specifically includes in-house developed tests, including LDTs and CE marked IVDs modified by laboratories. If an equivalent CE marked device is available on the market or IVD product is manufactured at an industrial scale, the laboratory cannot use exemption for LDT´s provided in the IVDR (Article 5.5) and must CE mark the IVD. MDx CRO has recently published an article assessing the impact of the IVDR on LDTs.
Conclusion: An Industry in Transition
As specialists in quality, regulatory, and clinical consultancy focused on IVDs, MDx CRO advises stakeholders to take proactive measures in anticipation of these sweeping regulatory changes. Judicial challenges and public feedback could alter the timeline for the FDA to start regulating LDTs, but there’s no doubt that enhanced regulation of LDTs is on the horizon, already in full force in Europe.
Comments on the Proposed FDA Rule should be submitted by December 4, 2023, to help shape this crucial regulatory development. It is an opportune time for the industry to engage in open dialogue and to prepare for the inevitable changes that lie ahead.
