Personalized Medicine: FDA Says It Is Ready

By Allyson B. Mullen – 

For many individuals, a diagnosis, be it life threatening or chronic, is scary.  However, the trial and error process that can follow the diagnosis in order to find a therapy (e.g., drug, device and/or biologic) that works best for the patient can be just as scary.  It would be wonderful if, at the time of diagnosis, or shortly thereafter, doctors could with a high degree of confidence identify what the best treatment was for that individual and avoid this process.  Many such personalized treatments are now being developed, and in the recent report “Paving the Way for Personalized Medicine – FDA’s Role in a New Era of Medical Product Development,” (the “Report”) [issued on October 30, 2013, FDA says it is preparing to address these new types of treatments from a regulatory perspective. Report at 2.

Personalized Medicine, sometimes also referred to as “precision medicine,” has been defined by the National Academy of Sciences as “the use of genomic, epigenomic, exposure and other data to define individual patterns of disease, potentially leading to better individual treatment.”  Id. at 6.  Personalized Medicine typically involves two medical products, a diagnostic test (a device) and a therapeutic.  Id. at 8.  The diagnostic is generally regulated as a medical device, and can include in vitro diagnostic assays or in vivo tests (e.g., diagnostic imaging).  Although drugs and biologics are the most obvious therapeutics where personalized medicine will be used, all types of regulated products can be therapeutics.  For example, recently three dimensional printing was used to create a personalized tracheal splint based on CT images of the patient’s airway and lungs.  Id. at 9. 

According to the Report, “the era of personalized medicine” has arrived:

• In 2011, one third of the new drugs approved had some type of genetic or biomarker data in the submission relative to efficacy, safety or pharmacokinetics;
• Since 2010, CBER has licensed seven new products which require careful matching of donors and recipients; and
• The number of submissions to CDRH’s Office of In Vitro Diagnostics and Radiological Health (OIR) involving personalized medicine has increased by more than an order or magnitude.  Id. at 54. 

The Report goes on to tout FDA and industry’s recent successes in this area.  Specifically, the Report highlights the approval of Kalydeco, the first drug to treat the underlying cause of Cystic Fibrosis, rather than the disease symptoms.  Id. at 3.  Kalydeco was an output of decades of work by the Cystic Fibrosis Foundation and Vertex Pharmaceuticals, the drug’s manufacturer.  Id.  The drug was approved in only approximately three months after its application was granted “priority review.”  Id.  FDA emphasizes that this success was a result of a “well-prepared submission, strong evidence, and a commitment on the part of all of the parties involved.”  Id. 

In achieving such a success, the Report discusses the historic and recent scientific, policy and organizational changes that FDA has made to address personalized medicine products.  Id. at 14–22.  The Report stresses that the primary challenge it needs to address related to personalized medicine is the science.  To that end, the Report enumerates a number of ways in which FDA says it is addressing the scientific challenge of personalized medicine, for example:

• Biomarker Qualification Program.  CDER is working with external scientists and clinicians to develop biomarkers with an aim of establishing a framework for encouraging development, identification and regulatory acceptance of biomarkers in drug development.
• MicroArray and Sequencing Quality Control Project.  National Center for Toxicological Research (NCTR) scientists are running this FDA-led project to “advance translational and regulatory sciences by assessing technical performance and practical utility of emerging molecular biomarker technologies for clinical application and safety evaluation.”
• Genomic Reference Library.  The National Institute of Standards and Technology (NIST) and OIR are working together to develop genomic reference material to be used in evaluating whole genome sequencing instruments.
• Clinical Trial Design and Methods.  FDA is generally working on refining clinical trial design and statistical analysis.  Specifically, the I-SPY 2 Trial, developed by the Biomarkers Consortium, which consists of FDA, the National Institute of Health (NIH), and the pharmaceutical industry, was launched in March 2010.  This trial uses an adaptive trial design to reduce the speed and cost of development for new drugs for women with high-risk breast cancer.  Id. 43–46.

However, FDA acknowledges that there are a number of other challenges that both it and industry face with respect to personalized medicine, including:

• Coordination of Multiple Products. As discussed above, personalized medicine involves two products, which raises a host of issues since each product is generally developed on its own time frame, by a different company, and each is likely subject to differing regulations (e.g., diagnostics as devices and therapeutics often as drugs and biologics and sometimes as devices);  Id. at 32–35.
• Regulation of Diagnostics.  Many of the diagnostic tests used in personalized medicine are in vitro diagnostic assays (IVDs), which can be commercialized to laboratories as a kit subject to FDA regulation as a device, or can be developed and used solely by a single laboratory as a laboratory developed test (LDT).  FDA’s efforts to regulate LDTs has been controversial (as discussed in our previous post here).  FDA has been developing a risk-based framework for regulating LDTs, although to date, nothing has been finalized. Id. at 30–32.
• Limited Understanding of Disease and Lack of Infrastructure.  With all of the new technologies, there is a mass of new data, but it is still unclear what it all means, and the infrastructure to “analyze, integrate, share, and mine” the data does not yet exist.  Id. at 56.
• Clinical Adoption of New Diagnostics.  Just as it takes FDA time to understand and accept new technology, clinicians have been slow to use new diagnostic tools, possibly due to how new the technology is, and the lack of tools to help the clinician in interpreting what the results of the tests mean.  Id. at 57.  In addition, although not mentioned in the Report, the lack of reimbursement for these new diagnostics is also a big impediment to their adoption by clinicians. 

Lastly, with all of the growth and excitement in this area, FDA says it wants to ensure that those individuals who do not have the characteristics to benefit from certain therapies are not forgotten and that all sub-classifications of disease are considered.  Id.

It is clear that advancement of Personalized Medicine through therapeutics and diagnostics is a high priority for FDA, as shown by a five-page table listing the various guidance documents that FDA has issued in this area.  Report at 24-28.  And FDA plans to issue more guidance documents in this area.  For example, CDRH’s Fiscal Year 2014 Proposed Guidance Development List includes several draft and final guidance documents related to personalized medicine, for example, a final guidance document for In Vitro Companion Diagnostic Devices, and a draft guidance for Direct to Consumer (DTC) Genetic Testing: IVDs. 78 Fed. Reg. 66746, 66746 (Nov. 6, 2013). 

In sum, there are many regulatory challenges that still face companies developing personalized therapies and diagnostics, and there is a long way for both industry and FDA to go before many of these products become realities.  There are also external factors that play a key role, such as reimbursement, health care reform, and commercial considerations.  However, the Report does describe steps FDA is prepared to take to address new therapies and technologies to help facilitate growth in the area of personalized medicine.