The more we know about rare diseases, the more likely we are to find safe and effective treatments

By: Janet Woodcock, M.D.

Janet WoodcockYou may be inclined to think that rare diseases affect only a tiny fraction of the more than 320 million people in our country. That’s true about a single rare disease. But there are about 7,000 rare diseases. If you add them all together, there are about 30 million – or almost one in ten — people in the U.S. with some form of rare disease. Sadly, although great progress has been made in some areas, many of these people have no FDA approved drug to cure their condition, help them feel better, or even slow the disease’s progress.

That’s why I am pleased about FDA’s support for an exciting new tool researchers are using to study rare diseases. It’s a new database with information about the diseases’ “natural history.”

“Natural history” is the scientific term to describe how a disease would progress with no treatment. Since a disease can affect different people differently, scientists must study many cases of a disease to acquire a thorough understanding of its natural history. Well-conducted studies of natural history can yield vital information about:

  • Biomarkers, demographic, genetic, and environmental variables that correlate with the course and stages of the disease;
  • Identification of patient subpopulations with different characteristics and effects of the disease;
  • Patient perspectives on what aspects of disease are most important to treat; and,
  • How to quantify those aspects so that they can serve as useful outcome measures for clinical trials.

But when it comes to rare diseases, their natural histories frequently are not fully understood because there are simply not enough cases that have been observed and studied. This lack of knowledge limits researchers’ ability to study rare diseases and develop new treatments. Knowledge of natural history is essential for developing more efficient clinical trial designs. It also could help reduce the length and cost of drug development and, possibly, contribute toward greater predictability of clinical development programs.

Recently The National Organization for Rare Diseases (NORD), has teamed up with the patient advocacy group that represents people with the rare disease known as Von Hippel Lindau disease. This is a condition with many debilitating symptoms that also predisposes individuals to benign and malignant tumors. The Von Hippel Lindau Alliance and NORD have created an online tool that enables people with this rare disease to enter information about their experiences with the disease, such as the progression of symptoms, and to add to this information at intervals throughout their lives.

This tool is now helping researchers compile valuable data about the natural history of Von Hippel Lindau disease. The even better news is that this tool is universal.  If it can be used effectively to help researchers better understand Von Hippel Lindau disease, it can do the same for other rare diseases as well!

Importantly, this online tool was developed with direct input from patients, as well as patient organizations, researchers, FDA, and other international drug regulatory agencies.

The natural history tool has important features such as these:

  • It protects  the security and privacy of personal information, while making valuable information available to a researcher or drug developer interested in creating a new therapy for a rare disease;
  • It can be used by patients or health care professionals;
  • It helps make sure that text and online tools data are accurate.

FDA is committed to working with patient advocates and other organizations to support natural history studies for rare diseases.  We encourage the use of natural history data collection tools to describe natural history for many rare diseases. It is our deeply felt hope and wish that we can then take steps toward developing and approving new therapies for persons with rare diseases.

Janet Woodcock, M.D., is the Director of FDA’s Center for Drug Evaluation and Research

For more information about the NORD patient registry tool, visit their website: http://rarediseases.org/patient-orgs/registries

And please read: A Pivotal Moment for the Treatment of Rare Diseases — Address by Dr. Margaret A. Hamburg to the NORD Rare Diseases and Orphan Products Breakthrough Summit

FDA Invites Students to Sharpen their Research Skills

By: Nysia George, Ph.D., and Tom Powers

NCTR Intern Claire Boyle, a graduate student from Florida State University

NCTR Intern Claire Boyle, is a graduate student from Florida State University. Get this and other NCTR photos on Flickr.

Biology. Chemistry. Bioinformatics. Toxicology.

Practical, hands-on laboratory work is important for all college students who want to become scientists—but, for many of them, such experiences are out of reach.

That’s one of the reasons why every summer, our National Center for Toxicological Research (NCTR)—FDA’s internationally acclaimed toxicological research center in Jefferson, Arkansas—hosts a special internship program for science students interested in toxicology research.

The 2014 program was exceptionally successful for both the students and the Center.

Applications poured in from more than 200 students pursuing a variety of majors in universities from coast-to-coast. The competition was intense, and the 21 selected students came from schools in 13 states. But they were all alike in two fundamental ways: they were top students, and were eager to hone their scientific skills in real FDA laboratories.

NCTR Intern Luis Valencia, a senior from Texas A&M University

NCTR Intern Luis Valencia, is a senior from Texas A&M University. Get this and other NCTR photos on Flickr.

During their 10 weeks at NCTR, the students worked on projects varying from the development of bioinformatics and statistical methods for RNA sequencing data, to evaluating effects of silver nanoparticles in plastic food containers. They conducted in-vitro experiments; examined effects of nicotine treatment; gained lab experience in cell culture; and were trained in computational modeling or statistical programming.

Each student’s experience was unique and addressed the student’s interests.

The interns gave the program top grades. For example Claire Boyle, a graduate student from Florida State University, said about the lab work: “I like it a lot more than classes. There they tell you that you can do research once you get into the real world. I’ve never had an opportunity to do that before coming here [to NCTR], and that’s the aspect of the program I like best. It’s given me insight into what I want to do for the rest of my life!”

Luis Valencia, a senior from Texas A&M University, echoed similar praise. “This isn’t some pointless classroom assignment; this is the FDA. Something you discover [in this lab] could save a life.” He continued, “I’m having a great experience at NCTR. [My NCTR mentor] let me design my own experiment and helps me a lot. I’m already on my second trial and we’re getting good results.”

The internship program, which was partly funded by the FDA’s Office of Minority Health, is one of the many ways NCTR reaches far and wide to strengthen the scientific foundations of our agency. We engage with scientists within FDA and across other government agencies, industry, and academia to develop scientific information that is vital for sound regulatory policy. We cooperate with colleagues abroad to advance international standardization of regulatory science. And we’re mindful that all quest for knowledge starts with education.

If you are a science student interested in toxicology research, or if you know someone who is, it’s not too early to consider the NCTR’s 2015 internship program. To qualify for admission, a candidate must meet the GPA requirements and provide evidence of success in science courses. He or she will also need letters of recommendation and a personal statement describing his or her research interests.

If you believe you have what it takes, you could be among the select few chosen to join us in the summer of 2015. Applications are accepted throughout the month of February. We look forward to your application!

For more information about the program go to: Summer Student Research Program (NCTR)

For more information about the FDA Office of Minority Health go to: Minority Health

Nysia George, Ph.D., is the National Center for Toxicological Research’s Intern Program Coordinator.

Tom Powers is the National Center for Toxicological Research’s Communication Officer.

FDA’s giant NMR magnet puts more imaging power into our regulatory science

By: Carolyn A. Wilson, Ph.D.

Carolyn A. WilsonThe word spin might make you think of someone trying to influence your opinion. But in physics, spin refers to an intrinsic property of certain subatomic particles that make some nuclei act like small magnets. That kind of spin is key to a powerful laboratory technique scientists use to study complex, carbon-based biological products at the atomic and molecular level.

This technique, called nuclear magnetic resonance (NMR), uses a strong, external magnetic field and radio waves to trigger the release of electromagnetic energy from atoms with nuclei that have spin. Computers convert these data into contour plots that resemble topographic land maps. Scientists use these data to determine the locations of atoms in relation to each other in molecules. This enables them to create three-dimensional models they can hold in their hands and study, or 3D images they can rotate on a computer screen.

Scientists in FDA’s Center for Biologics Evaluation and Research (CBER) are using NMR to study two types of molecules relevant to the vaccines against bacterial and viral disease that we regulate: polysaccharides (long chains of sugar molecules), which occur in either the cell wall or the capsule surrounding some disease-causing bacteria, and shorter chains of sugars called oligosaccharides. Oligosaccharides are found in viruses and are also part of bacterial vaccines.

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Scientists at FDA discuss construction of the facility that will house the new NMR. From left to right: Hugo F. Azurmendi (CBER), Kang Chen (CDER), Darón I. Freedberg (CBER) & Marcos D. Battistel (CBER). Get this and other FDA photos on Flickr.

The microbes need these molecules to cause disease, so CBER scientists are using NMR to study how the structure of such polysaccharides and oligosaccharides triggers production of antibodies against the microbes that carry these molecules. The methods developed by CBER scientists will allow evaluation of licensed and investigational polysaccharide vaccines by using NMR to determine if those vaccines were developed in a manner consistent with these insights into how the structure of these molecules triggers antibody production. In addition, the outcomes of these studies might provide information that manufacturers could use to design novel polysaccharide vaccines that are safe and effective.

Insights into the structures of polysaccharides that play critical roles in generating protective immune responses would be especially useful in confronting dangerous pathogens for which there are no vaccines. Two such pathogens, the bacteria Neisseria meningitidis B and Escherichia coli K1, cause meningitis (a potentially fatal inflammation of the brain and spinal cord). The capsules surrounding these bacteria contain a polysaccharide called polysialic acid. This molecule is unusual because it doesn’t trigger antibody production when injected by itself into adult humans, but people infected with bacteria that have polysialic acid in their cell walls or capsules do produce antibodies against it. One logical explanation for this difference is that “free” polysialic acid has a somewhat different structure than polysialic acid on bacterial cell walls. But, using NMR, CBER scientists found that polysialic had the same structure whether free or as part of the pathogen. Figuring out why only bound polysialic acid triggers antibody production might help researchers develop much needed vaccines for these bacteria. Soon they will have a new NMR facility at the White Oak campus that could help them solve that puzzle.

NMR "Stick" Model; NMR studies at CBER are providing insights into the atomic and molecular ins and outs of polysialic acid, a molecule found on the surface of bacteria, including some that cause meningitis. This work is aimed at helping researchers develop safe and effective vaccines against such bacteria that are based polysialic acid. Using the NMR data from their studies, the CBER scientists created two models of polysialic acid, a “stick” model and a “solid spheres” model, shown in the two short animated videos (above and below).

NMR “Stick” and “Solid Spheres” Models: NMR studies at CBER are providing insights into the atomic and molecular ins and outs of polysialic acid, a molecule found on the surface of bacteria, including some that cause meningitis. This work is aimed at helping researchers develop safe and effective vaccines against such bacteria that are based polysialic acid. Using the NMR data from their studies, the CBER scientists created two models of polysialic acid, a “stick” model (above) and a “solid spheres” model (below), shown in these two short animations.

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NMR “Solid Spheres” Model

The NMR spectrometer in the new facility will have a magnet that is much stronger than those previously used at FDA. The stronger the magnet, the more precise the data generated by NMR and the more precise the models that can be developed from this data.

To put this into perspective, the clinical application of NMR, called magnetic resonance imaging (MRI), uses magnets with strengths of 1.5 to 3 units of magnetic power called Tesla. The strength of NMR magnets at CBER is now about 16.4 Tesla (700 megahertz). The new NMR facility at White Oak will have a strength of 19.9 Tesla (850 megahertz)—about 6 times that of hospital MRI machines. In fact, the magnet is so powerful that the machine is isolated in a special room with walls thick enough to block its magnetic field from pulling unsecured metallic objects toward it. In the photograph you can see the NMR team visiting the facility as it is being prepared for the arrival of the machine.

CBER will share the new NMR spectrometer with the Center for Drug Evaluation and Research (CDER), which will use it to do extremely sensitive assessments of the purity of heparin and of the structures and properties of protein therapeutics.

This powerful magnetic molecular “microscope” is one way that FDA incorporates new technology into its regulatory science work to protect and promote the nation’s health.

Carolyn A. Wilson, Ph.D., is Associate Director for Research at FDA’s Center for Biologics Evaluation and Research.

Regulatory Science Collaborations Support Emergency Preparedness

By: Jean Hu-Primmer, M.S.

Scientists love a challenge. And coordinating government agencies, healthcare providers, and numerous additional partners to protect public health in emergency situations is definitely a challenge.

Jean Hu-Primmer

Jean Hu-Primmer, Director of Regulatory Science Programs in FDA’s Office of Counterterrorism and Emerging Threats.

FDA’s Medical Countermeasures Initiative (MCMi) is working with federal agencies (through the Public Health Emergency Medical Countermeasures Enterprise), product developers, healthcare professionals, and researchers, among other partners, to help translate cutting-edge science and technology into safe, effective medical countermeasures. Through these collaborations, MCMi supports research to help develop solutions to complex regulatory science challenges.

Data are critical to help FDA evaluate the safety and effectiveness of medical countermeasures—products that can save lives—during public health emergencies. But collecting data in the midst of an emergency is exceptionally challenging. Working with the Biomedical Advanced Research and Development Authority (BARDA), FDA is teaming with critical care physicians nationwide to help address these challenges.

Under a contract awarded last month, FDA and BARDA will work with the U.S. Critical Illness and Injury Trials Group (USCIITG) to gather important information about medical countermeasures used during public health emergencies. Physicians will help address challenges with collecting and sharing data rapidly in emergencies, including streamlining electronic case reporting for clinical trials and rapidly disseminating key findings to FDA and other stakeholders to support clinical decision-making.

During this four-year project, USCIITG will also develop and pre-position a simple influenza treatment protocol in 10 hospitals throughout the U.S. during the 2015-2016 influenza season. The project will help doctors more easily use an investigational treatment protocol for patients with severe influenza, and test the data collection and reporting system during peak times. The goal is to help streamline the process during future influenza seasons and emergencies.

When it is not ethical or feasible to test the effectiveness of products in humans—such as countermeasures for potential bioterror agents—products may be approved under the Animal Rule. When products are approved under the Animal Rule, FDA requires additional studies, called phase 4 clinical trials, to confirm safety and effectiveness. In addition to the MCMi work, BARDA is funding USCIITG to investigate conducting phase 4 clinical studies during public health emergencies. USCIITG partners will train on these protocols, have them reviewed through their Institutional Review Boards (a requirement for all human studies), and create plans for enactment. USCIITG will then conduct an annual exercise to test these plans, a unique approach to broader science preparedness.

MCMi has also recently awarded regulatory science contracts to support other aspects of emergency preparedness, including two projects to investigate decontamination and reuse of respirators in public health emergencies (awarded to Battelle and Applied Research Associates, Inc.), and an award to support appropriate public use of medical countermeasures through effective emergency communication.

Our work involves big challenges. Through regulatory science, and through new and expanding collaborations, we continue to address these challenges to better prepare our nation to use medical countermeasures in emergencies.

Want to help? We’re currently accepting submissions for additional research to support medical countermeasure preparedness. If you have an idea for a new medical countermeasure regulatory science collaboration, we’d love to hear from you.

You can also visit BARDA’s MCM Procurements and Grants page for more information.

Jean Hu-Primmer, M.S., is Director of Regulatory Science Programs in FDA’s Office of Counterterrorism and Emerging Threats.

FDA and the Cybersecurity Community: Working Together to Protect the Public Health

By: Suzanne Schwartz, M.D., M.B.A.

Cyber vulnerabilities – bugs or loopholes in software codes or other unintentional access points – are a real and constant threat to our networked laptops, mobile phones, or tablets. The Heartbleed virus and security breaches at major retailers are just a few recent examples of exploits of this hazard that have been in the news.

Suzanne SchwartzWhat you may not know is that there is a coordinated network of cybersecurity researchers, software engineers, manufacturers, government staffers, information security specialists, and others who share the responsibility of discovering and closing these security gaps. As a result, many vulnerabilities are detected and fixed before they seriously affect the public.

Medical devices that contain computer hardware or software or that connect to computer networks are subject to the same types of cyber vulnerabilities as consumer devices. The consequences of medical device breaches include impairing patient safety, care, and privacy. And as in the case of consumer devices, strengthening the cybersecurity of medical devices requires collaboration and coordination among many stakeholders, as well as a shared sense of responsibility for reducing the cybersecurity vulnerabilities.

This is why on October 21-22, 2014 the FDA, the Department of Homeland Security (DHS), and the Department of Health and Human Services (DHHS) will host a public meeting, Collaborative Approaches for Medical Device and Healthcare Cybersecurity.   The purpose of the meeting is to catalyze collaboration in the health care and public health sector to more fully address medical device cybersecurity. The meeting will bring together medical device manufacturers; health care providers; biomedical engineers; IT system administrators; professional and trade organizations; insurance providers; cybersecurity researchers; local, state and federal government staffs; and representatives of information security firms. They will explore topics such as:

The cybersecurity of medical devices is an important part of public health safety, and the FDA has a significant role. In addition to convening this meeting, the FDA entered into a partnership with the National Health – Information Sharing and Analysis Center (NH-ISAC), a non-profit organization that closely cooperates with government agencies, and numerous health care and public health organizations. The partnership will enable FDA and NH-ISAC to share information about medical device cybersecurity vulnerabilities and threats. It will foster the development of a shared risk framework where information about medical device vulnerabilities and fixes is quickly shared among health care and public health stakeholders.

In addition, on October 1 the FDA released a final guidance for the Content of Premarket Submissions for Management of Cybersecurity in Medical Devices. The guidance recommends that manufacturers consider cybersecurity risks as part of the design and development of a medical device, and submit documentation to the FDA about the risks identified and controls in place to mitigate those risks. We think this will help improve the cybersecurity of medical devices and help contribute to the strengthening of our Nation’s health care cybersecurity infrastructure.

The FDA shares the responsibility of managing and reducing cybersecurity risks with many other stakeholders, and we look forward to hearing from them at the public meeting on October 21-22. We’re committed to working together to build a comprehensive cybersecurity infrastructure that can detect and respond to vulnerabilities in a timely way and that best protects the public health.

Suzanne B. Schwartz, M.D., M.B.A., is Director of Emergency Preparedness/Operations & Medical Countermeasures (EMCM) at FDA’s Center for Devices and Radiological Health.

FDA’s Program Alignment Addresses New Regulatory Challenges

By: Margaret A. Hamburg, M.D.

Over the last year, a group of senior FDA leaders, under my direction, were tasked to develop plans to modify FDA’s functions and processes in order to address new regulatory challenges. Among these challenges are: the increasing breadth and complexity of FDA’s mandate; the impact of globalization on the food and medical product supply chains; and the ongoing trend of rapid scientific innovation and increased biomedical discovery.

Margaret Hamburg, M.D.The Directorates, Centers and the Office of Regulatory Affairs (ORA) have collaborated closely to define the changes needed to align ourselves more strategically and operationally and meet the greater demands placed on the agency. As a result, each regulatory program has established detailed action plans. Specifically, each plan describes the steps in transitioning to commodity-based and vertically-integrated regulatory programs in the following areas: human and veterinary drugs; biological products; medical devices and radiological health; bioresearch monitoring (BIMO); food and feed; and tobacco.

These action plans focus on what will be accomplished in FY 2015 and outline the need to develop detailed future plans for the next five years in some cases. The plans represent what each Center and ORA have agreed are the critical actions to jointly fulfill FDA’s mission in the key areas of specialization, training, work planning, compliance policy and enforcement strategy, imports, laboratory optimization, and information technology.

Because each Center has a unique regulatory program to manage, there are understandably variations among the plans. However, there are also common features across most of the plans: the need to define specialization across our inspection and compliance functions; to identify competencies in these areas of specialization and develop appropriate training curricula; to develop risk-based work planning that is aligned with program priorities and improves accountability; and to develop clear and current compliance policies and enforcement strategies.

Below are some highlights from the plans that illustrate these features:

  • Establish Senior Executive Program Directors in ORA. In the past, for example, the Center for Drug Evaluation and Research (CDER) would work with several ORA units responsible for the pharmaceutical program. Now, the Centers will have a single Senior Executive in ORA responsible for each commodity program, allowing ORA and the Centers to resolve matters more efficiently.
  • Jointly develop new inspection approaches. The Center for Devices and Radiological Health (CDRH) and ORA plan, for example, will begin to focus some inspections on characteristics and features of medical devices most critical to patient safety and device effectiveness. ORA investigators will perform these inspections utilizing jointly developed training.
  • Invest in expanded training across ORA and the Centers. The Center for Biologics Evaluation and Research (CBER) and ORA will jointly develop a biologics training curriculum, redesign investigator certification, and cross-train Center and ORA investigators, compliance officers and managers.
  • Expand compliance tools. Field investigators will be teamed with subject matter experts from the Center for Food Safety and Applied Nutrition and the Center for Veterinary Medicine to make decisions in real time, working with firms to achieve prompt correction of food safety deficiencies and to help implement the preventive approaches outlined by the FDA Food Safety Modernization Act (FSMA). If industry does not quickly and adequately correct critical areas of noncompliance that could ultimately result in food borne outbreaks, we will use our enforcement tools, including those provided under FSMA, as appropriate.
  • Optimize FDA laboratories. ORA and the various Centers will establish a multi-year strategic plan for ORA scientific laboratory work, including hiring and training analysts, purchasing and using equipment, and allocating resources and facilities. At the same time, ORA is committed to conducting an ongoing review of its labs to ensure that they are properly managed and operating as efficiently as possible.
  • Create specialized investigators, compliance officers, and first-line managers. A bioresearch monitoring (BIMO) working group is developing a plan for a dedicated corps of ORA investigators to conduct BIMO inspections, and a dedicated cadre of tobacco investigators is being established.

Working together to implement these action plans will take time, commitment, and continued investment and we’ll need to monitor and evaluate our efforts. These plans will help us implement the new FSMA rules announced in September, as well as the Agency’s new medical product quality initiatives under the FDA Safety and Innovation Act and Drug Quality and Security Act.

FDA’s Program Alignment is a well-thought out approach that responds to the needs of a changing world. I look forward to the ways in which these action plans will ultimately enhance the FDA’s public health and regulatory mission.

Margaret A. Hamburg, M.D., is Commissioner of the U.S. Food and Drug Administration

Re-scheduling prescription hydrocodone combination drug products: An important step toward controlling misuse and abuse

By: Douglas C. Throckmorton, M.D.

Hydrocodone is the most prescribed opioid in the United States, including 137 million prescriptions in 2013. While it is useful in the treatment of pain, it has also contributed significantly to the very serious problem of opioid misuse and abuse in the United States. With the aim of curbing this misuse and abuse, new prescribing requirements go into effect today for hydrocodone combination products, which include products such as Anexsia, Lorcet, Vicodin, and some cough suppressants that contain both hydrocodone and another active ingredient, such as acetaminophen.

Douglas C. Throckmorton, M.D.Under a final rule issued by the U.S. Drug Enforcement Administration (DEA), hydrocodone combination products are now in a more restrictive category of controlled substances, along with other opioid drugs for pain like morphine and oxycodone.  After a scientific review, FDA made the recommendation that DEA take this step in December 2013. We concluded that hydrocodone combination products meet the criteria for control under Schedule II of the Controlled Substances Act, and we believe DEA’s new rule will help limit the risks of these potentially addictive but important pain-relieving products.

Here are some of the key changes that will occur with the reclassification of hydrocodone from a Schedule III drug to a Schedule II drug:

  • If a patient needs additional medication, the prescriber must issue a new prescription. Phone–in refills for these products are no longer allowed.
  • In emergencies, small supplies can be authorized until a new prescription can be provided for the patient.
  • Patients will still have access to reasonable quantities of medication, generally up to a 30-day supply.

After DEA requested a scientific and medical recommendation from FDA regarding a change of schedule for hydrocodone combination products in 2009, FDA considered the eight statutorily required factors related to the abuse potential of hydrocodone. These included such questions as the products’ actual or relative potential for abuse, their liability to cause psychic or physiological dependence, and dangers they might pose to public health. After a thorough analysis of the available information, including a public Advisory Committee meeting to solicit input from outside experts and patients (the committee recommended upscheduling by a vote of 19 to 10), HHS recommended to DEA that hydrocodone combination products be reclassified into Schedule II.

We also recommended two other actions we believe are critical to maximizing the benefits to the public health of rescheduling hydrocodone:

  • Include rescheduling in a broad-based set of actions targeting abuse prevention. In particular, HHS identified a need to work with prescribers and patients to make certain that patients are prescribed the right number of doses of hydrocodone for a patient’s need to avoid unused hydrocodone being available for abuse.
  • Continue to monitor the use and abuse of hydrocodone combination products carefully to assess the impact of rescheduling on public health. Based on the results of this monitoring, we may need to take additional actions to support the appropriate use of hydrocodone combination products while reducing their tragic abuse.

FDA understands that it is crucial to achieve a goal of balancing the risk of abuse and misuse with the need to maintain access to these important medications that provide needed relief to people in pain. Rescheduling hydrocodone combination products is one important action in support of this goal.

Douglas C. Throckmorton, M.D., is Deputy Center Director for Regulatory Programs in FDA’s Center for Drug Evaluation and Research

Advancing the development of new “targeted drug therapies” by enhancing the science of biomarkers

By: Issam Zineh, PharmD, MPH, FCP, FCCP

A key area of new drug development lies in the field of targeted therapies, sometimes called “personalized medicines,” which are drugs tailored to the genetic makeup of individual patients. These drugs are called targeted therapy because health care professionals can use clinical test results from a patient to select a specific drug that has a higher likelihood of being effective for that particular person. FDA is working with a wide range of scientists and scientific organizations to help advance the fundamental biomedical science necessary to support this growing field.

Issem ZinehThe successful development of targeted therapies requires biomarkers – measureable indicators in the body such as proteins or DNA changes – to identify patients at risk of worsening disease and those with a high likelihood of treatment benefit or experiencing treatment failure. Having biomarkers that can help health care professionals diagnose disease, identify the stage of a disease, or predict patient response to treatment also has the potential to make drug development more efficient. For example, biomarkers can be used to identify patients to enroll in clinical trials, which can make trials smaller or shorter because the drug’s effect is measured only in people who are likely to respond. There are now several drugs on the market that were developed with a biomarker-based diagnostic test that can be used in the clinic to identify patients. Examples include Xalkori (crizotinib) and Tarceva (erlotinib), used to treat forms of lung cancer, and Zelboraf (vemurafenib), used to treat certain types of melanoma (skin cancer).

Biomarkers can be helpful in the development of new therapies, whether or not they are targeted therapies. For example, identifying reliable biomarkers that can substitute for clinical “endpoints” can speed up drug development. This is because showing that a drug has a meaningful effect on a biomarker is generally easier and takes less time than showing that the drug has positive effect on the way a patient feels, functions, or survives.  The availability of established biomarkers may also attract greater interest and investment in a drug’s development and can help minimize financial losses with earlier identification of poor performing drugs.

The ability to identify useful biomarkers depends on how well scientists understand the disease for which they are seeking treatment. In some disease areas, such as cancer and infectious diseases, we have made great progress in understanding disease processes and the ways to affect these processes with drug therapy. In less well-developed areas, FDA is working to promote biomarker-based strategies in drug development. For example, we currently have a process for “qualifying” biomarkers for regulatory purposes.

Recently, FDA teamed with the Brookings Institution’s Engelberg Center for Health Care Reform to host a public workshop to help advance biomarker science for therapeutic product development. Discussions helped to identify and to propose solutions for scientific challenges for biomarker applications in early and late phase clinical trials for new drugs, as well as best practices for successful biomarker-based programs. Some opportunities highlighted in the discussion include:

  • Clear standards about the evidence needed to support use of biomarkers;
  • Infrastructure and policies that promote development of tests used to identify patients for trials and in the clinic, particularly tests designed to evaluate many biomarkers at one time;
  • New models and networks for clinical trials that will accelerate both biomarker and new product development; and,
  • Methods to assess treatment effects in small populations identified by sequencing technologies.

Public input from this workshop will be used to help FDA in its decision making and communications about biomarkers. As part of its mandate under the Prescription Drug User Fee Act Reauthorization of 2012, FDA is committed to advancing the development and use of biomarkers in medical product development. The public workshop was a significant step in helping us fulfill this obligation. Finding ways to advance the identification and use of biomarkers in drug discovery and development also has been a focus of the House Energy & Commerce Committee’s recent 21st Century Cures initiative. We look forward to continued efforts to advance biomarkers, which will help bring important new therapies to patients in need.

Issam Zineh, PharmD, MPH, FCP, FCCP, is Director, Office of Clinical Pharmacology, Office of Translational Sciences, in FDA’s Center for Drug Evaluation and Research

FDA Invents: How Technology Transfer Gets FDA Inventions from Lab to Marketplace

By: Alice Welch, Ph.D.

If you think the term “government invention” is an oxymoron—well, think again. You may be surprised to learn that many of the breakthrough technologies that shape our lives today are the brainchildren of government researchers—including those at FDA.

Alice WelchTake the Internet and that GPS in your car or on your cell phone. Both technologies were developed by the U.S. Department of Defense —as were the turbine engines that power the wind farms generating some 6% of our nation’s electrical energy. Those long-lasting radial tires on your vehicle? They’re reinforced with a material five times tougher than steel that was developed by a NASA partnership. And you can thank the government for your flu shot and the development of many other life-saving vaccines such as those for hepatitis A and B and HPV.

Government funding is also critical in supporting and accelerating research in academia and industry that leads to game-changing innovations. Technologies like bar code scanners, Internet search-engines, and the touch screens on your tablet and smartphone might not have been possible without the research funding from the National Science Foundation.

Like other government agencies, FDA drives innovation in its own mission-critical work by supporting collaborative research with external partners and by transferring our life-saving inventions to the commercial market. Making all of this happen is a dedicated team of experts from across the agency that forms FDA’s Technology Transfer Program.  Managed from within the Office of the Chief Scientist, the Technology Transfer Program means many things at FDA.

To our researchers, it means they can access unique resources, participate in scientific collaborations, or obtain the technical expertise they need to make their research possible. These resources support and complement the work underway in FDA’s research laboratories. Whether it’s conducting research into how a blood product becomes a commercially produced therapy, or how to improve vaccine manufacturing, or tracking how patients use a product, the research of FDA’s scientists is fundamental to informing FDA’s evaluation of the safety and effectiveness of our regulated products.

To FDA inventors, Technology Transfer means they can get their inventions translated into commercial products that protect and promote public health. A little known fact is that in the course of their research, FDA scientists regularly gain new scientific insights and invent novel technologies or processes. The Technology Transfer team helps move these technologies to the private sector under license agreements so that new products in areas like vaccines, food-pathogen detection systems, counterfeit drug detection, and manufacturing can be created and made available on the market. To give you a sense of what we mean when we say that “FDA drives innovation,” in the last few years alone, our researchers have produced and reported about 20 patentable inventions annually.

And for FDA’s many collaborators, Technology Transfer means they’re able to engage with our researchers to solve scientific problems and create solutions to support FDA’s regulatory mission. To establish these collaborations and get the right resources for FDA researchers, our Technology Transfer team uses special tools or legal agreements, such as Material Transfer Agreements, Confidential Disclosure Agreements, Research Collaboration Agreements, and Cooperative Research and Development Agreements.

Each of these tools is designed to meet the needs of the research project at hand. They enable FDA researchers to obtain materials not available at the agency and to establish successful scientific exchanges with experts in the scientific community—at universities, small businesses, nonprofits or for-profits, or other government agencies.

Technology Transfer’s efforts may not be the stuff of headlines, but they’ve produced huge dividends for public health. They’ve helped guide FDA researchers through negotiating agreements, to establish collaborations, and to ensure that the tools they use to report, transfer and protect the patents of technologies align with legal and policy requirements. Look for my next few blog posts, where I’ll highlight some exciting, high-impact public health contributions based on FDA inventions.

Learn more:

FDA Researchers Build Partnerships to Advance Innovations

Alice Welch, Ph.D, is Director of FDA’s Technology Transfer Program

New Data Dashboard Tool Shares FDA’s Inspection, Compliance and Recall Data

By: Douglas Stearn

Douglas StearnAs part of our commitment to transparency FDA is pleased to announce that we have released a new online tool to provide insight into our compliance, inspection, and recall activities.

This new dynamic tool represents a departure from the downloadable spreadsheet-based datasets that we have posted in the past. Instead, the FDA data dashboard presents information in an easy-to-read graphical format. It also provides access to the underlying data allowing anyone interested to see related data and trends.

Our new dashboard provides data for FY 2009 to FY 2013, and allows access to data on:

  • inspections;
  • warning letters;
  • seizures and injunctions;
  • and statistics, specifically for recalls.

We plan to update the data semi-annually.

The dashboard is staged in a cloud environment, and it allows you to:

  • download information for additional analysis;
  • manipulate what you see by selecting filters;
  • rearrange the format of datasets and the way columns are sorted;
  • drill down into data; and
  • export charts and source information for further review.

We developed this new dashboard after President Obama issued a Presidential Memorandum on Regulatory Compliance in January 2011.

The President directed federal agencies to make publicly available compliance information easily accessible, downloadable and searchable online, to the extent feasible and permitted by law. FDA formed internal working groups that same year to develop recommendations for enhancing the transparency of our operations and decision-making processes. These working groups identified an online tool as a way to present compliance and enforcement data in a user-friendly manner. The dashboard represents the latest example of our commitment to compiling and posting a wealth of FDA data  for public review and feedback.

FDA works within a global environment and is carrying out more inspections around the world. We collaborate with regulatory authorities across the globe to protect public health. Our data dashboard provides information about inspections in this global environment, and makes this information more readily accessible to the public. Now you can use the dashboard to see this kind of inspection-related information to better understand our regulatory decisions.

A “feedback mechanism” is available so you can send comments, questions or concerns directly to us at FDADataDashboard@fda.hhs.gov.

This rollout effort is part of FDA’s continuing commitment to share inspection, compliance, and recall data. We will continue to update the FDA data dashboard and provide public access to this timely and important information.

Douglas Stearn is Director of the Office of Enforcement and Import Operations within FDA’s Office of Regulatory Affairs