Skip to main content
Premium Trial:

Request an Annual Quote

FDA Launches Regulatory Science Initiative with Personalized Rx Focus Areas


By Turna Ray

The US Food and Drug Administration this week outlined a "strategic framework" that it intends to follow in order to align its regulatory activities with scientific advancements, including new developments in genomics and personalized medicine.

"Recent breakthroughs in science and technology — ranging from sequencing of the human genome to advances in the application of nanotechnology to new medical products — have the potential to transform our ability to prevent, diagnose and treat disease," the agency said in a report describing its new regulatory science initiative. "These developments will result in moving treatment strategies towards approaches that are tailored or personalized to individual patients, thus maximizing the benefit of treatments while decreasing their safety risks."

The report, called Advancing Regulatory Science, outlines research areas to which the FDA plans to apply "the bulk" of its $25 million FY 2011 budget increase designated for regulatory science initiatives. The President’s total FY 2011 budget request for the FDA is $4 billion, an increase of $756 million over FY 2010.

Through external collaborations with industry, academia, and other government entities, the FDA plans to focus on "transforming product development" in the area of toxicology and personalized medicine. Other collaborations will concentrate on advancing the science of regulating emerging technologies; information sciences for health outcomes; and addressing unmet public health needs.

"A new office dedicated to regulatory science will lead strategic development and coordination within FDA, and early efforts will focus on recruiting key personnel and building senior leadership," the report notes.

The agency defines regulatory science as "the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products." Since her confirmation last year, FDA Commissioner Margaret Hamburg has publicly stated on several occasions that she intends to improve the agency's scientific and regulatory expertise to usher in more innovative treatments and advanced technologies.

Also as part of its FY 2011 regulatory science activities, the agency plans to expand its network of Centers of Excellence in Regulatory Science and integrate their work with the efforts of other clinical research networks. "Funding for external programs would be competitive and focus on pilot and feasibility studies to form Centers of Excellence," the agency states in its report.

"There is no single discovery — no magic bullet — to address our unique set of modern scientific regulatory challenges," the report states. "But one thing is clear: if we are to solve the most pressing public health problems we face today, we need new approaches, new collaborations, and new ways to take advantage of 21st century technologies."

Regulatory Science Ongoing

The report highlights several areas in which the agency has already invested in advancing regulatory science. One such project in the area of personalized medicine is the agency's support of the Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2, or I-SPY 2, trial, which began in March.

The trial, which involves the FDA, the National Institutes of Health, and several pharmaceutical partners, is working to develop breast cancer treatments tailored to the molecular profile of specific tumors. Women with newly diagnosed, locally advanced breast cancer are genetically tested first for various biomarkers, in order to guide them to the right drug.

[ pagebreak ]

"During the trial, drugs in development are individually targeted to the biology of each woman’s tumor using specific genetic or biological markers," the FDA states in the report. "By applying an innovative trial design, researchers will use data from one set of patients’ treatments to treat other patients — more quickly eliminating ineffective treatments and drugs."

The trial has facilitated new drug application filings and has helped study participants test the value of various non-traditional trial designs with the help of various diagnostic tools, FDA said.

Before getting treatment, women enrolled in the study have their tumors evaluated for estrogen receptor status, progesterone receptor status, and HER2 status. Study participants receive testing with Agendia's TargetPrint HER2 and its breast cancer recurrence test MammaPrint.

Another area of focus for FDA's regulatory science research is in the area of modernizing safety testing to speed up drug development. "Unfortunately, new drug candidates often fail late in development after significant investments have already been made toward their development," the agency states in the report, noting that the most common reasons for failure are liver, kidney, and cardiovascular toxicities. "It is critical to identify potential safety issues as early in the development process as possible, before human studies are performed."

In this regard, the FDA is collaborating with the European Medicines Agency to join industry and academia in identifying and qualifying biomarkers for detecting drug-induced kidney toxicity in animal models. Under the collaboration, the FDA and EMEA have already validated several toxicity biomarkers that the Predictive Safety Testing Consortium identified using microarrays.

"These biomarkers provide a non-invasive strategy for detecting kidney toxicity in animal models and are more sensitive and specific than traditional tests," the FDA said.

Future Areas

The agency acknowledged in the report that it needs to do much more in order to keep up with advances in science.

FDA's independent Science Board determined in a 2007 report evaluating the agency's capabilities that the lack of FDA expertise in evaluating emerging scientific technologies is putting “American lives … at risk."

"While the world of drug discovery and development has undergone revolutionary change — shifting from cellular to molecular and gene-based approaches — FDA’s evaluation methods have remained largely unchanged over the last half-century," the FDA Science Board said in its report.

Recognizing that the FDA "lacks the tools to recognize" the potential of promising medical treatments, the agency said in this week's report that it aims to make "creative advances in regulatory science" in order to "change the landscape" of how drugs are developed and evaluated.

"We can modernize product development and develop new tools, standards, assays, disease models and science-based pathways to improve the speed, efficiency, predictability, capacity and quality of the entire process, from development to evaluation to manufacturing," the agency notes.

Some areas for the agency's future focus of using regulatory science include improving the safety of pain medications and developing vaccines, drugs, and diagnostics for tuberculosis.

"We are facing a global epidemic of prescription pain medicine abuse and misuse. At the same time, patients in agonizing pain are often left undertreated. New pain pathways have been discovered and new medicines are being developed that can help," the FDA said in the report. "But to accelerate the delivery of new treatments to patients, we need to find better pain models, measurement tools (including patient-reported assessments) and clinical trial designs to enable development of effective medications with less potential for abuse."

[ pagebreak ]

For the treatment of TB, the agency is backing research into the prevention, diagnosis, and treatment of the disease. Specifically, the agency is focused on quickly evaluating TB treatments and vaccines, "including identifying markers that can predict cure and protection."

Additionally, the agency is supporting efforts to develop tests to rapidly diagnose TB and identify treatment resistance.

Several organizations are trying to identify biomarkers and personalized treatments for TB. Recently, the NIH awarded $3 million to Boston Medical Center to identify biomarkers for the bacterium that causes tuberculosis and to study reactions to TB in the human genome. Akonni Biosystems also received a $3 million Challenge Grant from the NIH to further develop a test for multi-drug-resistant and extensively drug-resistant tuberculosis on its TruDrop gel-drop PCR microarray biochip technology.

The development of treatments for infectious diseases is another area where the FDA wants to modernize its capabilities. Through the use of biomarkers, blood tests, and medical images, the FDA aims to predict the safety and efficacy of treatments for global infectious diseases.

"Knowledge of genetic sequences can enable us to produce products such as DNA and recombinant vaccines, or needed treatments and diagnostic tests, more quickly and safely without using the pathogen in manufacturing," the FDA said. "The use of platform technologies of this sort may offer the potential to scale up production more rapidly."

With the help of advanced platform technologies the agency estimates that it may be possible to produce "large amounts of new influenza vaccines for a pandemic in weeks, rather than months."

Additionally, technologies such as virus-like particle, live vector, DNA vaccines, or recombinant protein expression systems "can be used for detection or diagnosis, such as high-throughput assays for antibody, antigen and nucleic acid detection," the agency noted.

Finally, the FDA is also planning to bolster the use of new technologies, such as cell culture methods, genomics, microarrays, proteomics, and metabolomics, to identify biomarkers to reduce the dependence of animal toxicology testing in drug development.

"Investments in analysis of large sets of data would provide valuable information for understanding how classes of chemicals cause toxicity," the FDA said in its report. "These approaches require new instrumentation, platforms, and databases, and training for FDA scientists to enable them to use and interpret data from these approaches."