John Meyer
Associate Editor
Loyola University Chicago School of Law, J.D. 2019

In recent years, the FDA has examined a record number of revolutionary medical devices, many of which have been genetic tests. Genetics has taken the world by storm. The medical world continues to look toward genetics as a promising next step in revolutionizing treatment, while the American public has shown a growing interest in learning more about themselves through services like Ancestry and 23andMe. In an effort to gain a foothold on the rapidly developing field of technology, the FDA has recently made efforts to modernize its approach by issuing new guidance to ensure the validity of these tests.

Efforts to Enhance and Modernize

Since its formation in 1906, the U.S. Food and Drug Administration (FDA) has been responsible for protecting the public health through safety and efficacy standards while also helping to promote innovation of new products. The dichotomy of their mission can sometimes be a fine line to walk, but the FDA is the agency best suited for this responsibility. Their commitment to both safety and innovation is clear in their recent statement about their “efforts to enhance and modernize” their medical device regulation.

As a part of their “Action Plan” the FDA commits to taking a closer look at its existing regulatory structure.  The FDA hopes to harmonize pre- and postmarket controls in order to increase their effectiveness. Ideally this will allow the FDA to better protect the public while also generating more data to improve regulation which may also lead innovation for developers.

Precision Medicine

While not the focus of the “Action Plan,” the FDA has recently made a news release about next generation sequencing (NGS) tests used in precision medicine. According to the FDA, precision medicine represents an attempt to develop the most effective treatments by tailoring them to “genes, environments, and lifestyles.” One of the most powerful ways to achieve this goal is through NGS.

NGS is a valuable type of genetic test. While NGS does not sequence the entire human genome, it involves must larger segments than more traditional testing. Previously, most genetic testing used in the medical practice focused on identifying specific genes or mutations. This larger scale testing is better suited for understanding the bigger picture of an individual’s health. However, due to the complexity of the results and a limited understanding of genetics direct impact on health, the FDA has issued two sets of guidance, creating a flexible regulatory scheme capable of growing with the technology.

Guidance for Clinical Validity

Issued on April 18, 2018, the first guidance document focuses on ensuring the clinical validity of all genetic tests. The FDA acknowledges the clinical uses of NGS in “risk prediction, diagnosis, and treatment selection for a disease or condition.” However, developers must establish clinical validity, a determination of how effectively a test can accurately detect a specific analyte, prior to marketing its product. An analyte is a biological marker of genetic variation.

One major hurdle to this assurance is the way most genetic information is stored. The rapid adoption of genetic testing is allowing scientists to identify more genetic variants, but when labs identify and study new variants, they often keep the data private. This prevents the spread of scientific evidence. In response, the FDA guidance suggests that a publically accessible “genetic variant database” would be instrumental in demonstrating clinical validity, furthering innovation, and informing treatment decisions. Developers could use a public database to demonstrate that the results of its tests are reproducible.

The guidance suggests this form of public database as the ideal solution to the FDA’s goal of protection of public health and inspiring innovation; however, it also acknowledges the truth of industry. Many research organizations maintain their studies in proprietary databases, and the FDA does not limit proof of clinical validity to a public database. The guidance is a strong proposal, but in the end it will be up to developers and researchers how they decide to proceed with the results of their studies.

Guidance for Analytical Validity

The second guidance document issued by the FDA focuses on analytical validity. In addition to proving that a test is accurately detecting a specific analyte, the developer must demonstrate analytical validity—meaning the analyte detected is linked to a specific disease or condition. This process is complicated due to the extensive nature of NGS tests, as they will likely identify genetic variants that scientists have not yet associated with a disease or condition.

This guidance specifically sets out the FDA’s standards to determine analytical validity. The FDA goes further and proposes that in the future it may implement these standards in conjunction with its assurances of clinical validity from the first guidance and proper labeling requirements in order to allow quicker access to the market. This would allow NGS tests to bypass the more complicated process of FDA premarket approval, for the much less demanding premarket clearance process. If implementation is successful, the clearance process could identify what the FDA needs to protect public health while limiting the burden of what innovators must provide.

The FDA’s response to the developments in the genetic field, including NGS, has demonstrated its continued dedication to its mission. However, the FDA has still not completed the formation of its regulatory framework. The FDA has held several workshops attempting to develop standards but acknowledges that it has yet to find adequate standards to prove analytical validity necessary as proof of safety and effectiveness. As with all guidance, the two genetic testing documents are not legally binding, but instead reflect the FDA’s current thinking and an attempt to develop a flexible framework for regulation. The guidance leaves the future in the hands of industry to join the FDA in a cooperative effort to develop an efficient framework.