This informative presentation will start with an oncology-centric discussion of current US companion diagnostic (CDx) regulation with focus on FDA Pilot Program for Oncology Drug Products Used with Certain In Vitro Diagnostic Tests (“the pilot”). And it will generalize to relevant FDA CDx/Dx regulatory policies such as LDT rule and down-classification. Attendees will benefit from discussion of the Pilot including potential challenges related to implementation, comparison to current CDx regulation and explore the implications of a changing US regulatory landscape related to CDx and drug development.

FDA’s classification system determines the required regulatory pathway for devices and the scope of applicable regulations and requirements. Manufacturers may seek Class II designation but be stuck with Class III because of precedent regarding intended use and technology. FDA intends to reclassify many types of IVDs from Class III to Class II. This session will explain which tests may be affected and what reclassification means for laboratories and diagnostic companies.

FDA published a proposed rule in October 2023 to more clearly assert their authority to regulate Laboratory Developed Tests (LDTs). FDA also recently announced their intention to down-classify most in vitro diagnostic (IVD) tests that are currently Class III. This talk will provide a summary of the key aspects of these FDA proposals and will also cover the potential impact(s) to companion diagnostics and drug clinical trials.

Laboratory-developed tests (LDTs) have been subject to FDA enforcement discretion for decades, but in the last ten years, the Agency has expressed a desire for greater oversight. Guidance documents and attempts at legislation have failed, so in the Spring of 2024, FDA released regulations placing LDTs into the medical device regulatory framework. This change has the potential to dramatically change the diagnostic testing landscape, particularly for clinical laboratories that develop LDTs.

Companion diagnostic devices play a crucial role in personalized medicine by helping healthcare professionals identify the most appropriate treatment for a patient based on their genetic, molecular, or other specific characteristics. Due to the unique nature of these devices, there are several regulatory considerations that must be taken into account to ensure their safety and effectiveness. These considerations include regulatory authorities, classification, clinical and analytical validation, and labeling.

The majority of approved companion diagnostics (CDx) support precision medicine endeavors in oncology fueled by research and the growing knowledge base on genetic pathways related to cancers. There are several additional disease areas in which CDx has the potential to improve the likelihood of success for therapeutic products in development, including immunology, neurological diseases, and rare/orphan diseases. Despite the potential for expanded use of CDx, regulatory hurdles pose a key challenge. The current regulatory paradigm for CDx may need to evolve for further expansion of the utility of CDx in disease areas other than oncology.

The mission of the Center for Biologics Evaluation and Research (CBER) is to ensure the safety, purity, potency, and effectiveness of biological products.  The newly formed Division of Clinical Evaluation General Medicine oversees development programs for a diverse array of serious and life-threatening diseases.  Companion diagnostics are essential to many of these development programs, and their regulation is nuanced and complex.  Recognizing the challenges to developing novel therapeutic products, including gene, cell, and regenerative medicine therapies, CBER is committed to innovation and flexibility while maintaining standards for product safety and effectiveness.

Drug and diagnostic co-development has accelerated the availability of novel therapeutics. This session will focus on key regulatory changes and potential impact on bringing companion diagnostics to market. Lessons learned from partnerships between pharma and diagnostic stakeholders and future trends will be shared.

We have developed a novel framework based on advanced analytic methods to simultaneously validate all candidate companion diagnostic tests without increasing the size of clinical trials and samples. We conclude this novel strategy is preferred over the existing methods (such as noninferiority external concordance, attenuation factor, and missing data imputation) from the perspective of data totality and benefit-risk principle.

• How do the FDA's expectations for LDT compliance with IDE requirements impact pharmaceutical clinical trials?
• What should the expectations be of both labs and sponsors in the case of routine testing used for clinical trials?
• What additional clarity are you looking for when it comes to the Final Rule, what would you like to see the Agency do?​

The global regulatory landscape for companion diagnostics has evolved. Co-development planning should consider ex-US regulatory strategy early to mitigate costly barriers to entry or delays in global testing. This presentation will include a brief overview of current regulatory landscape for companion diagnostics as well as potential strategies for addressing upcoming regulatory challenges in co-development.

With the implementation of the new EU regulation on in vitro diagnostics (IVDR) in May 2022, notified bodies will be required to perform a conformity assessment for companion diagnostics (CDx). As part of the conformity assessment of a CDx, the notified body consults the European Medicines Agency on a scientific opinion on the suitability of the CDx with the concerned medicinal product(s), which will be discussed.