Mansfield, director of the personalized medicine staff in the Office of In Vitro Diagnostics and Radiological Health at FDA, described the historical development of FDA’s policies for companion diagnostics and the main features of the companion diagnostic draft guidance. Felix Frueh, entrepreneur-in-residence at Third Rock Ventures, commented on some of the issues those policies raise. Together, they presented an overview of co-development of tests and therapeutics and outlined the challenges of and potential solutions to these issues.


The concept of companion diagnostics is not new, Mansfield said; testing for estrogen and progesterone receptor expression has been done since the 1990s to determine if a patient would benefit from hormone therapy in treating breast cancer. In 1998 FDA approved the use of the drug Herceptin in patients with breast cancer who tested positive for human epidermal growth factor receptor 2 (HER2), one of the earliest examples of a co-development companion diagnostic model before there was a formal process in place. When Herceptin was approved for use in patients with metastatic breast cancer, FDA also approved a test to examine HER2 levels. One reason for having a test was to decrease risks, Mansfield said, and Herceptin’s cardiotoxic side effects are now well known. In the case of the drugs Selzentry and Tykerb, which were approved in 2007 and whose use depends on test results, a companion diagnostic policy was not yet in place when they were approved and FDA did not apply the policy retroactively.

Recognizing that tests can be drivers of therapy, FDA began to develop guidance to reflect drug development strategies that account for genetic information. It held public discussions about pharmacogenomics, requested voluntary genomic data submissions, and addressed other issues concerning the use of genomic data to guide drug development, Mansfield said. FDA realized that a policy was needed to protect patients while also allowing companies to plan for the development of tests that would support therapeutic approval, she said. FDA also realized that companies want predictability in the regulatory process.

Companion diagnostics are tests, Mansfield emphasized, but the test performance is closely tied to the performance of the associated drug. Thus, knowledge about the test is essential to understand the safety and effectiveness of the drug. Tests for the same analyte can differ, sometimes significantly. The technology, cut-off levels, and performance can all vary, and different tests are likely to identify different populations. “You want to know all of these parameters before you decide on which test is going to be used,” Mansfield said, “and if you want to use multiple tests [you will need

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