P108: Exploring Regulatory Trends and Precedents with an Internal Database of FDA-Approved Companion Diagnostics (CDx) in Oncology
Poster Presenter
Namosha Mohite
Assistant Director, US Regulatory Affairs Liaison
Bayer United States
Objectives
Describe the process and value of building a Companion Diagnostics (CDx) database to collect and gather information scattered across numerous sources and analyze trends to support regulatory strategy and decision making.
Method
We collected information from different sources: the FDA “List of Cleared or Approved Companion Diagnostic Devices”, FDA’s Medical Device Database, and the Drugs@FDA database. We covered all CDx approved between 1997 and Dec 2023 and created a searchable database (using Excel).
Results
The created database breaks down the information in the FDA CDx list into specific and easy to filter values and adds additional information (such as CDx submission and approval dates, corresponding drug approvals, etc.) from other sources. The information was analyzed and the following quantitative data was derived.
Overall, 62 CDx were approved between 1997 and Dec 2023, with an upwards trend (since 2011). Majority of the approvals were for CDx associated with oncology drugs (98%, n=205). Of all approvals, 43% of CDx indications were not approved contemporaneously. Some of the reasons for non-contemporaneous approvals included expansion of the CDx indication (not specifically linked to a drug approval) or post marketing commitment for a companion diagnostic as mentioned in the drug approval letters.
In terms of types of applications, almost all CDx approvals used the Pre-Market Approval (PMA) (initial and supplemental) pathway (97%). The other approval pathways were the 510(k), the 513(f)(2) and the Humanitarian Device Exemption. The majority of PMA/sPMA approvals were reviewed within 150 and 180 days.
The majority of tumor samples were from tissue (68.3%), followed by liquid (27.3%) and bone marrow (4.4%). The most common analytical platform/technology was Next-Generation Sequencing (NGS) (41.5%), and then Polymerase Chain Reaction (PCR) (29.8%), Immuno-Histo-Chemistry (IHC) (19.5%), In Situ Hybridization (ISH) (8.3%), and others (imaging and electrochemiluminescence) (1.0%). With the first NGS based CDx approved in 2016, the use of this technology has grown since then.
The highest number of CDx indications approved were for non-small cell lung cancer (NSCLC) (36.1%), followed by breast cancer, colorectal cancer, acute myeloid leukemia (AML), and ovarian cancer (respectively 17.1%, 7.8%, 5.9%, and 4.9%).
Conclusion
With increasing number of companion diagnostic approvals, the overwhelming amount of information from numerous scattered sources often complicates the strategic decision-making process. In addition to the FDA’s “List of Cleared or Approved Companion Diagnostic Devices”, there is an immense amount of publicly available information on FDA website in regard to CDx approvals, making it time-consuming for a regulatory professional to access and analyze all the information. This database allows a professional to access, filter, and analyze information and trends over time by consolidating publicly available information in one spot and supplement decision making for therapeutic product and CDx development.
In contrast to FDA’s list of approved/cleared CDx, this database can be utilized to assess the regulatory strategy used for the development of the companion diagnostic device (i.e. concomitant approval with the associated therapeutic product, provision of the CDx to satisfy a post market commitment for the drug or a follow-on CDx). However, the database has some limitations. Firstly, it was not always feasible to confirm the regulatory strategy for the companion diagnostic device in case when there was no co-approval. In some cases, it proved difficult to identify the drug approvals (approval date and indication) associated with the CDx approval.
The database can also be used to search for regulatory precedents (e.g., looking for CDx approved in a specific tumor type or for a specific target), identifying in which scenarios drugs got approved under the condition to provide a clinical validation study to establish the performance of a companion diagnostic device in a post market commitment study.
Overall, this database is a great tool for regulatory strategists when defining CDx development and registration strategy.
