Over the last decade, Targeted Therapies, Personalized and Precision Medicine have become part of our vocabulary, representing a new way of thinking in how we address cancer and hematological malignancies. The conventional one disease one treatment model is being replaced by individualized care that is catered towards a patient’s unique needs. However, to be successful, these new approaches depend on the availability of accurate and reliable diagnostic tests to help determine which therapeutic product will be most appropriate and effective for an individual. The U.S. Food and Drug Administration (FDA) plays a critical role in advancing personalized and precision medicine.

Currently, the FDA is at work on a regulatory platform that is set to ensure accuracy while promoting innovation. The optimization of the FDA’s regulatory oversight on personalized medicine was a popular topic at this year’s American Association of Cancer Research’s Annual Meeting in New Orleans, LA. Several presentations discussed current efforts to improve the co-development of treatment and companion diagnostic tests by advancing the regulatory process and updating current standards, as well as initiatives in improving the way Next Generation Sequencing data is validated and accessed. [1]

Companion and Complementary Diagnostics 
In the session “FDA Regulation of Companion and Complementary Diagnostics” (Saturday, Apr 16, 2016, 11:00 AM -12:00 PM) Pamela L. Bradley and David Litwack, both from the U.S. Food and Drug Administration, Silver Spring, MD, discuss general principles that can advance co-development programs and share lessons learned from the numerous successful co-development programs in oncology. The presentation emphasized how the role of FDA regulation becomes especially important when a ‘companion’ diagnostic (test) is required for the safe and effective use of a specific therapeutic product. In various cases certain FDA regulatory requirements apply, including contemporaneous marketing authorizations. This means that development programs for a novel therapeutic, as well as the diagnostic test, need to be co-developed in a process that ensures the reliability and safety of both companion test and treatment.

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Bradley and Litwack also discussed so-called complementary diagnostics. While similar, complementary diagnostics, which can provide important information for individual benefit-risk decisions related to treatment with a particular therapeutic product, are not the same as companion. The presentation clarified that while a complementary diagnostic is able to provide additional information as to how a drug might be used, it is not the same as a companion diagnostic, which is essential for the safe and effective use of a drug. Since complementary diagnostics add another factor to the regulatory process, there is even greater need to advance and modernize FDA approval processes and standards- a topic that was further discussed by the FDA’s Katherine Donavan and Laura Koontz (U.S. Food and Drug Administration, Silver Spring, MD) in an educational session later that Saturday. [2]

New FDA Initiatives
In the educational session “New FDA Initiatives in Personalized Medicine” (Saturday, Apr 16, 2016, 3:00 PM -4:30 PM), Donavan and Koontz provided a broad overview of current cross-agency initiatives as well as agency efforts to enable the regulatory flexibility needed to accelerate diagnosis and treatment in oncology. Topics included the Precision Medicine Initiative, laboratory developed tests, next generation sequencing, and the development of accurate and relevant clinical databases.

During the first portion of the presentation, Donovan described some of the lessons learned from past companion diagnostic approvals, as well as how the FDA is currently defining both companion and complimentary diagnostics. The importance of co-approval when it comes to companion drug diagnostic combinations was also emphasized. In fact, the FDA is actively looking to evolve the current co development model in several ways. One of these has been the creating of a co-development “How-to” manual, which will provide important consideration points for both therapeutic and diagnostic development programs, with the goal of supporting contemporaneous market authorization. This draft guidance is currently being developed and reviewed internally, and will include advice on how to plan ahead for test validation, guidance on co-development and clinical trial designs, as well as important points for planning ahead for FDA review and contemporaneous approval. [3]

Afterwards, Laura Koontz gave a broad overview of the Precision Medicine Initiative (PMI): a research effort launched by President Obama in 2015 that aims to enable and empower the researchers, clinicians, and patients, by advancing the research, technology, and policies relating to individualized care. There are several factors that will enable the success of PM. Above all, safe and accurate diagnostic tests are essential, as they can reliably identify an individual variation and select treatments accordingly. At the forefront of these tests is the use of Next Generation Sequencing (NGS), which can identify thousands — even millions — of genetic variants in order to use these results to diagnose or predict an individual’s risk of developing many different conditions or diseases. [4]

Next Generation Sequencing (NGS)
Since each individual’s DNA varies slightly, NGS is powerful tool allowing scientists to look for meaningful DNA differences that can suggest a person’s risk to disease, current health state, and very importantly, predict response to particular treatments. Currently, NGS technologies are rapidly entering clinical practice, but there are a number of regulatory issues and challenges that these types of tests face. In response to these challenges, the FDA is working toward the goal of developing and implementing an adaptive standards-based regulatory approval which works toward ensuring quality and relevance of data from NGS tests. Recently, the PrecisonFDA web platform was launched in efforts to reach this goal. Precision FDA is an online portal which allows researchers and industry and government professionals to come together and promote innovation while developing a science behind interpreting NGS. [5] [6]

Another important factor for the advancement of NGS tests is making sure that researchers and clinicians can access reliable and quality genomic data. In order to do so, the healthcare system must be leveraged so that data gathered from genomics can be systematically kept and organized. Curative data bases are essential in providing important clinical evidence, and according to Koontz, the FDA is looking into whether or not a regulatory grade database could be used as a source of information to support the link between a specific genetic variant and disease. “To really implement this, we need to address issues of data quality,” emphasized Koontz, “the FDA wants to be able to say that use of these meets our requirements for clinical validity, and ensure that the data is high quality, and that any assertion made is as accurate as possible and based on current knowledge.”

Finally, Koontz further noted the importance of the development of new targeted therapies, a topic widely discussed throughout the conference, and how research and regulatory policies need to catalyze the advancement of these treatments, while protecting patients at the same time. And while targeted therapies and personalizing treatment adds layers of complexity and regulatory challenges, the FDA is focused on modernizing to meet the needs of a new era in precision medicine. “We are working diligently to propose standards with the input of the scientific community”, stated Koontz, “and we are really looking at standards that can be updated as the science and technology advance.”


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