Leveraging FDA Resources to Encourage Students to Pursue STEM Careers

By: Richard Pazdur, M.D.

When I was in high school, I spent summers working as a restaurant dishwasher, grocery store stock boy and gardener in northwest Indiana. The idea of spending those weeks learning about science and medicine would not have been an option for me at that time.

Dr. Rick Pazdur and Members of Summer Scholars

Richard Pazdur, M.D., Director of the FDA Oncology Center of Excellence, poses with the first class of the OCE Summer Scholars Program. Sara Horton, M.D., project lead, (far left) and Alice Kacuba, project coordinator, (second from right) joined the group, which includes a variety of backgrounds, including two childhood cancer survivors interested in biomedical careers.

Yet, it is precisely those students who may not have access to specialized learning opportunities that we need to attract to science, technology and medicine to continue progress in these fields and ensure the diversity of our scientific workforce.

In particular, oncology and hematology are falling behind other areas of medicine in the adequate representation of racial and ethnic minorities in the physician workforce. Only 2.3% of practicing oncologists self-identified as black or African American, and 5.8% self-identified as Hispanic in a 2016 survey by the American Society of Clinical Oncology (ASCO). According to census figures, 13% of the U.S. population is black or African American, and 18% is Hispanic.

That’s part of the reason why the Oncology Center of Excellence recently launched its pilot Summer Scholars Program, designed to introduce students to oncology drug development and career opportunities in government, regulatory medicine, and cancer advocacy. With the cancer incidence expected to increase 45% by 2030, according to the National Cancer Institute (NCI), we will need the talents of many more tech-savvy students from diverse backgrounds furthering their studies in our medical schools and university science labs.

Dr. Rick Pazdur and two Summer Scholars

Richard Pazdur, M.D., Director of the FDA Oncology Center of Excellence, asks Diamond McCoy, 17, of H.D. Woodson High School in Washington, D.C., and Camden Wiseman, 17, of the Thomas Jefferson High School for Science and Technology, in Alexandra, Va., about their plans for the upcoming academic year. The two were part of OCE’s first Summer Scholars Program, which seeks to encourage tech-savvy students to pursue their studies in medicine and other STEM fields.

We recently welcomed 11 Washington, D.C., area high school students to FDA’s main campus in Silver Spring for six weeks – from June 26 to August 4. The group includes students with a variety of backgrounds and experiences, including some who are part of a STEM – Science, Technology, Engineering, and Math — program at their schools and two who are childhood cancer survivors interested in biomedical careers. Our requirements for the program include that they be in good academic standing and at least 16 years old.

Sara Horton, M.D., a breast cancer clinical reviewer and one of three staff members in the FDA Office of Hematology and Oncology Products (OHOP) who collaborated to develop the Summer Scholars Program, says that partnering with the D.C.-area public schools was the first thing that came to her mind in planning this program.

She told me that we decided to focus on students who may never have had an opportunity like this, as well as childhood cancer survivors. Dr. Horton reminded me that high school is a very special stage of development when students typically start thinking about where they fit in the world, what should they do, and who should they be.

We’re excited about introducing young people with STEM aspirations to professions in science and medicine they may have never known existed.

The curriculum includes basic and translational science, drug manufacturing, clinical trials, regulatory review, patient advocacy, and marketing. Lectures in those areas will be augmented by field trips to the NIH Clinical Center, NCI, Howard University College of Medicine, and ASCO.

In addition, students will be introduced to patient advocacy lobbying with Kids v. Cancer and accompany that group on a trip to Capitol Hill. They also are invited to a workshop at the drug manufacturing company AstraZeneca. Even medical students usually don’t have this type of opportunity to learn about the work we do at FDA until they are out of medical school.

Gregory Reaman, M.D., associate director for oncology sciences in OHOP and one of the program organizers, says the program is as interactive as possible for this age group. Most of the students will not have had much, if any, exposure to the field of oncology, while the cancer survivors will have had the experience of receiving treatment. We hope they will bring their experiences to us so we can all learn to be better advocates for patients.

Dr. Reaman, a pediatric oncologist, worked at a state mental hospital one summer. He says it confirmed his interest in medicine – just not psychiatry! We hope this experience will be as transformative for these students.

The lecture curriculum covers what we are calling the “Basics of Oncology,” including cancer treatments, endpoints for clinical trials, data analysis, statistics, pharmacy, microbiology, genetics, genomics, drug promotion, and patient advocacy.

Students also have the opportunity to work on professional skills such as writing, networking, and communication, and meet regularly with their mentors from FDA staff. At the end of the program, students will give short presentations to the OCE on a topic of interest to them.

Alice Kacuba, R.N., M.S.N., chief of regulatory project management staff in OHOP’s Division of Oncology Products 1 and one of the program organizers, told me that she hopes the agency’s diverse staff will leave a lasting impression on the students. She said she excelled in science, but saw very few female role models in science in the 1970s. Since becoming a nurse, “STEM education has become my passion, as my nieces and nephews can attest,” she said.

The OCE Summer Scholars Program is a pilot this year, but could be expanded next year to high school students nationally. Cooperation with offices within FDA and external organizations has been exceptional. We hope this will be a one-of-a-kind experience for the students as well as our oncology staff here at FDA.

Richard Pazdur, M.D., is the Director of the FDA Oncology Center of Excellence

Building a Strong FDA Workforce to Bring Scientific Advances to Patients

By: Scott Gottlieb, M.D.

The key to FDA’s public health mission, and its ability to bring innovative new therapies to patients, is the technical, scientific, and clinical expertise of its people. As the products that we’re asked to review become more complex and specialized, so do the technical demands on our workforce. Our staff must remain current with the dramatic advances in science and medicine and meet the increasing demands that globalization and other trends place on our core consumer protection functions.

Dr. Scott GottliebAs a result, FDA continually faces the challenges related to building and maintaining a diverse, talented, and dedicated professional workforce. However, we’re committed to doing what’s necessary to tackle these challenges and maintain a strong FDA — one that attracts and preserves world-class talent.

Most recently, I’ve requested a comprehensive effort to evaluate our hiring practices and procedures. We know that our traditional approach to recruiting and hiring is not as efficient as it should be to attract, hire, and retain the types of experts we need now and anticipate to need over the longer term. What’s more, we’re increasingly competing with better-resourced entities in the private sector for the same limited pool of people with very specific clinical and scientific skills and training. These are challenges that our current approach to hiring did not anticipate. It’s critical that we modernize the process for recruiting personnel into these specialized positions within our Agency’s programs.

As part of a new effort, and consistent with Secretary Price’s Reimagine HHS initiative, we’ll be piloting new hiring procedures aimed at better supporting the hiring goals required to meet FDA’s evolving needs. I’m very pleased that Melanie Keller, currently head of the Office of Management in our Center for Drug Evaluation and Research, has agreed to lead this effort on a full-time basis. She’ll be running the pilot from a newly created position inside the Office of Medical Products and Tobacco.

A central part of this new effort will involve more directly aligning the administrative hiring procedures and the scientific staffing objectives of our programs. Thus, the directors of the medical product centers participating in the pilot will be closely involved in overseeing the new initiative. They’ll help ensure that the scientific objectives of our review programs are more closely reflected in the recruitment and hiring process. We want to make sure that FDA’s existing experts are more personally involved in hiring our new experts. Although we face similar challenges across many of our programs, the pilot will initially focus on PDUFA- related positions in our drug and biologics programs while we develop our new model.

To take on this new effort, we’re establishing a dedicated group of full-time staff with the responsibility to ensure that we reliably and predictably identify, recruit, and efficiently hire the scientific personnel the Agency needs. Professional staff from our centers with experience recruiting specialized scientific and medical staffing will be key members of this new pilot effort. Staff from the Office of Operations will assist with the identification of potential candidates from key scientific disciplines.

The first order of business will be to address hiring into the positions supported by our PDUFA commitments. Too many of these positions remain vacant, and the backlog is substantial. Finding the right people and bringing them on staff quickly has proved difficult. Our goals will be to speed the hiring process while improving the retention of scientific and technical experts. We’ll aim to reduce and eventually eliminate the backlog of vacant positions while demonstrating the utility of our new hiring model. I encourage scientific professionals and technical experts who wish to join an outstanding workforce serving the public health to review the available job opportunities at FDA.gov.

I’m heartened by the progress FDA’s reauthorization legislation is making through Congress, and I look forward to its final passage. In the meantime, the new efforts I’ve outlined here will provide a solid foundation for recruitment and for responsibly managing our user fee resources. The reauthorization, coupled with key provisions in the 21st Century Cures Act— which give FDA the authority to bring on top candidates at competitive salaries — will greatly assist us as we modernize our recruitment policies, systems, and procedures. All of these efforts will strengthen FDA’s core functions, enabling us to ensure that safe and effective advances can reach the patients who need them as efficiently as possible.

Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

FDA Collaborates to Promote Safety, Quality in Clinical Trials Done in India

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By Leslie Ball, M.D., Letitia Robinson, Ph.D., R.N, and Elizabeth Wiley, M.D., J.D., M.P.H.

After more than 16 hours of travel, we touch down in Mumbai late in the evening and are greeted by a wave of heat and humidity as we exit the airport terminal. As we drive from the airport to the hotel, the vast Mumbai skyline is striking. India is home to 17% of the world’s population but accounts for about 20% of the global disease burden including both communicable and non-communicable diseases.

As a result, India holds a vast potential for clinical research and has become a global leader in the production of generic drugs. An estimated 40% of generic drugs imported into the U.S and used by American consumers are manufactured in India. Generic medications play a critical role in reducing drug costs for both patients and payers.

Leslie Ball, M.D., FDA Assistant Commissioner of International Programs and Elizabeth Wiley, M.D., J.D., M.P.H., AAAS Science and Technology Policy Fellow

Leslie Ball, M.D., Assistant Commissioner of International Programs (left), and Elizabeth Wiley, M.D., J.D., M.P.H., AAAS Science and Technology Policy Fellow, share some highlights from their recent training trip to India.

In an effort to promote the safety and efficacy of imported drugs, the FDA’s Office of International Programs (OIP) and the agency’s India Foreign Office have adopted a strategic engagement approach which includes inspections, targeted engagements including training, and the collection and use of data to inform FDA decision-making.

The purpose of our trip in mid-May was to participate in a joint training workshop for Indian regulators, academic representatives, and the drug industry on scientific and ethical standards for clinical trials. In addition to representatives from FDA, the European Medicines Agency, the Indian Central Drugs Standard Control Organization, and the Drug Information Association (DIA) were part of this first joint training.

FDA presenters included Jennifer Adams, M.P.H., Assistant Director, FDA India Office, and Sam Haider, Ph.D., Deputy Director of FDA’s Center for Drug Evaluation and Research (CDER) Office of Study Integrity and Surveillance. Sean Kassim, Director, CDER’s Office of Study Integrity and Surveillance, and Mathew T. Thomas, M.B., M.S., Senior Advisor, CDER’s Office of Scientific Investigations, provided critical planning for the event.

Recent changes in Indian regulation of clinical trials have seemingly impacted the number of registered drug clinical trials. Based on data from clinicaltrials.gov, registered drug clinical trials in India declined from 2010 to 2015. These numbers are predicted to increase in response to recent regulatory changes in an effort to create a more supportive regulatory environment in India. Moreover, there has been a sharp increase in the number of bioavailability or bioequivalence studies in India over the last decade as India has become the world’s largest supplier of generic drugs.

Letitia Robinson, Ph.D., R.N., Director of the FDA India Office.

The collaborative workshop, hosted by DIA, included an intensive two-day whirlwind of sessions, discussions, and case studies addressing key quality and ethical issues in clinical trials. Workshop participants included sponsors, contract research organizations, firms conducting bioavailability or bioequivalence studies, clinical investigators, regulators and academic researchers. These joint workshops sought to provide practical training on emerging issues, regulatory updates, clinical trial data integrity and inspectional methods. The specific goals of these workshops include:

  • Identifying general concepts in inspections of clinical investigators, clinical trial sites, ethics committees, and bioanalytical study sites;
  • Identifying techniques for maintaining data integrity in clinical trials; and
  • Reviewing inspections to develop evidence and determining appropriate observations to include in inspection reports.

The panels featured regulators from India, Europe, and the United States, as well as industry representatives. Participants fielded many questions on inspections, regulations, and standards – all in an effort to promote data integrity, credible and accurate results, and protection of subjects in clinical trials.

These questions helped clarify areas of harmonization among far-flung regulatory authorities, as well as differences such as the requirements for compensation of clinical trial participants after injury in India.

A second training in mid-May in Hyderabad, known as the City of Pearls and a technology center within India, began with a new audience of industry, academic and regulatory representatives. And, much like Mumbai, participants quickly engaged in two days of intense lectures, case studies and discussions with no shortage of questions and comments.

Informal feedback from participants was overwhelmingly positive and suggested that significant progress toward the goal of FDA participation in these workshops, including ensuring necessary capacity within regulatory and academic communities is developed and contributes to a sustainable training curricula, had been achieved.

Leslie Ball, M.D., is FDA Assistant Commissioner for International Programs; Letitia Robinson, Ph.D., R.N., is the incoming Director, FDA India Office; and Elizabeth Wiley, M.D., J.D., M.P.H., is an AAAS Science & Technology Fellow, Office for International Programs

Two Recent Scientific Advances Underscore an Encouraging Future for Precision Medicine at FDA

By: Janet Woodcock, M.D.

FDA helps bring precision medicine – in the form of targeted therapies — to people living with diseases that have specific genetic features.

Two recent FDA drug approvals point to an encouraging future for “precision medicine” — an approach for disease treatment that tailors medical therapies, including medications, to the needs of individual patients. These approvals involve diseases resulting from particular genetic characteristics identified by laboratory testing.

  • In mid-May, FDA announced that we expanded the approval of Kalydeco (ivacaftor), enabling a larger number of patients with cystic fibrosis (CF) to benefit from the drug. The expanded approval includes CF patients with one of 23 additional rare mutations. Kalydeco is now indicated for 33 CF mutations, up from 10 previously.
  • Also in May, we announced expanded approval for Keytruda (pembrolizumab) to treat patients whose cancers have a specific genetic feature. This is the first time FDA has approved a cancer treatment based on a genetic feature, rather than the location in the body where the cancer originated.

Janet WoodcockFDA has approved many more advances in precision medicines, also called “targeted therapies.” In the past 3 years alone, our Center for Drug Evaluation and Research has approved more than 25 new drugs that benefit patients with specific genetic characteristics. And we have approved many more new uses — also based on specific genetic characteristics — for drugs already on the market. Some of these drug approvals are for patients with rare genetic disorders. Others are new targeted therapies to treat cancer, hepatitis C, or HIV. Medication dosing for specific diseases may also be tailored to the individual.

Precision medicine holds great promise, but to continue developing targeted therapies, we will need scientific advances in the use and development of “biomarkers.” Biomarkers are indicators in the body that can be measured—like blood pressure, blood sugar, and tumor size. Tests to identify genetic variants are another form of biomarker. Biomarkers can enable health care professionals and researchers to identify patients at risk of disease, determine the stage of a disease, and predict the likelihood that a patient will benefit from a drug. They also play a role in drug development. A particular biomarker, for example, can be used to identify appropriate candidates for a clinical trial, such as those patients likely to respond to treatment. This can make it easier and faster to recruit patients and may result in a shorter time for drug approval. In a similar way, biomarkers can sometimes identify positive treatment effects before traditional clinical endpoints would. For instance, biomarkers might show a tumor shrinking before improvement in a patient’s condition is detected. So, using biomarkers in clinical trials can speed up the time it takes for an investigative drug to reach a patient.

The ability to identify useful biomarkers depends on how well scientists understand the disease they are seeking to treat. In some areas, such as cancer and infectious diseases, we have made real progress in understanding how these diseases develop and how to treat them with drug therapy. FDA continues to encourage drug developers to use strategies based on biomarkers. One way we do that is by ensuring that a given biomarker is really able to single out those patients who are likely to respond to a specific drug. Another way is using biomarkers to identify people whose disease is progressing rapidly. Beyond working on biomarkers for individual products, FDA also works with stakeholders and scientific consortia in qualifying biomarkers that can be used in the development of many drugs. Once qualified, these biomarkers may be used in the specified manner by any drug sponsor.

New provisions under the recently passed 21st Century Cures Act provide direction and opportunity for FDA to strengthen the science of biomarkers and to advance precision medicine. We believe it is important to make drugs such as Kalydeco and Keytruda available to as many patients as can benefit from them. FDA is actively pursuing more advances in targeted therapies.

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

How FDA Plans to Help Consumers Capitalize on Advances in Science

By: Scott Gottlieb, M.D.

We’re at a point in science where new medical technologies hold out the promise of better treatments for a widening number of vexing conditions. Over the last few decades, science has enabled fundamental advances in our understanding of the genetic and protein bases of human disease. These developments are already being translated into new medicines. In more cases, these treatments target the underlying mechanisms that drive different diseases. These advances hold out the promise of arresting and even curing a growing number of diseases.

Dr. Scott GottliebTo build upon such opportunities, FDA will soon unveil a comprehensive Innovation Initiative. It will be aimed at making sure our regulatory processes are modern and efficient, so that safe and effective new technologies can reach patients in a timely fashion. We need to make sure that our regulatory principles are efficient and informed by the most up to date science. We don’t want to present regulatory barriers to beneficial new medical innovations that add to the time, cost, and uncertainty of bringing these technologies forward if they don’t add to our understanding of the product’s safety and benefits.

This imperative is driven by our mandate to promote the public health. It includes a responsibility to make sure that we’re taking steps, within the scope of our existing responsibilities, to also help facilitate access to new innovations once FDA approves them. Access to advances in medical care is a critical component of public health. And the price of new technology affects the ability of people to access these new treatments. We therefore need to be mindful of the costs of our regulatory processes, to the degree that these costs also affect the availability of new innovations, and the way that they are ultimately priced.

New medical innovations are ultimately priced to a measure of the cost of the capital it takes to develop these technologies. This is true not only when it comes to the direct costs of research and development. Cost is also a function of the time and uncertainty of these endeavors.

For these reasons, as part of our public health mandate, we need to make sure that we’re taking a risk-based approach in everything we do. The 21st Century Cures Act gave FDA many new authorities and resources to accomplish this mission. “Cures” provides FDA with tools aimed at modernizing our regulatory programs. The goal of many of these efforts is to make sure that we’re taking every appropriate step to facilitate access to safe and effective new innovation.

Today we announced our detailed work plan for the steps we’re taking to implement different aspects of Cures. I want to highlight one example of these steps, which we’re investing in, and will be expanding on, as part of our broader Innovation Initiative. It’s the use of in silico tools in clinical trials for improving drug development and making regulation more efficient.

In silico clinical trials use computer models and simulations to develop and evaluate devices and drugs. Modeling and simulation play a critical role in organizing diverse data sets and exploring alternate study designs. This enables safe and effective new therapeutics to advance more efficiently through the different stages of clinical trials. FDA’s efforts in modeling and simulation are enabled through multiple collaborations with external parties that provide additional expertise and infrastructure to advance the development of these state-of-the-art technologies.

FDA’s Center for Drug Evaluation and Research (CDER) is currently using modeling and simulation to predict clinical outcomes, inform clinical trial designs, support evidence of effectiveness, optimize dosing, predict product safety, and evaluate potential adverse event mechanisms. We’ll be putting out additional, updated guidance on how aspects of these in silico tools can be advanced and incorporated into different aspects of drug development.

A variety of drug development, regulatory, and therapeutic questions are addressed by CDER through modeling and simulation strategies. CDER’s Office of Translational Sciences (OTS) uses these same strategies in the review of Investigational New Drugs Applications (INDs) and New Drug Applications (NDAs). To take just one example of the benefits of these approaches, as we enter an era of drug individualization, modeling and simulation that incorporates aspects of individual physiology and genetics in drug metabolizing enzymes is being used to identify patient subgroups that need dose adjustments. These approaches are incorporated to assess the combined effect of drug interactions, renal impairment, and hepatic insufficiency in patients, with clinical management strategies described in drug labeling where appropriate.

Another example is the use of modeling and simulation to assist in the creation of natural history databases to support model-based drug development. This could make clinical trials more efficient—for example, by enabling FDA to model some aspects of the behavior of the placebo arm in clinical trials. Right now, FDA is collaborating with scientists to develop such natural history models in Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, and muscular dystrophy. An important objective of modeling and simulation is to better evaluate the behavior of new treatments in rare disease populations that are inherently hard to study due to their small size.

To advance these opportunities, we need to continue to invest in high performance computing. These computing capabilities are becoming a key requirement to the ability of our review staff to manipulate the large data sets that are now a common feature of drug applications. FDA is actively working to expand the agency’s capabilities in high performance computing, and to explore modeling approaches and enhance their regulatory impact, through an effort enabled by the work of the agency’s Scientific Computing Board.

FDA’s device center is also an integral part of this work. The Center for Devices and Radiological Health (CDRH) is also building in silico regulatory models for product design and evaluation, including the development of a digital library of models and a family of “virtual patients” for device testing. An important goal is consistency. We need to make sure that the adoption of these strategies is consistent across different medical products and across the agency.

FDA is working hard to maximize the authorities and resources Congress granted us to advance medical innovation for patients. To ensure smooth coordination and communication across the agency, we established an intra-agency Cures Steering Committee. Since enactment of the nearly 1,000-page law on December 13, 2016, the team has conducted a detailed analysis of the law’s provisions, compiled a list of all of its FDA-related requirements, and is helping to advance the work teams that will enable FDA to deliver on the law’s opportunities. Today, we’re posting an initial list of our Cures deliverables. It will eventually become a tracking tool to help the public follow our progress.

As you can see from the list, we’ve already implemented several important Cures provisions. Section 1002 of Cures authorized $500 million in new funding over 9 years to help FDA cover the cost of implementing certain parts of the law. Consistent with the law’s requirements, we developed a draft work plan demonstrating how FDA would use that funding, subject to annual appropriations. We submitted the draft work plan to FDA’s Science Board for its consideration at a public meeting in May. Today we’re posting the final work plan that we delivered to Congress on June 9th. It includes the recommendations from FDA’s Science Board.

Among some of the other noteworthy actions that we’re pursuing under Cures:

  • Our Center for Biologics Evaluation and Research (CBER) is implementing the Regenerative Medicine Advanced Therapy, or RMAT designation. This new process provides another pathway to access FDA’s existing expedited programs, and is available for certain cell therapies, therapeutic tissue engineering products, and certain combination products. The goal of these efforts is to help foster the development and approval of these novel products. We’ve already received almost two dozen requests for RMAT designation and granted four such designations to date. To continue to advance these opportunities, we’ll be announcing this September a comprehensive framework for the development and proper FDA oversight of regenerative medicine. This new policy effort will comprise a series of new guidance documents covering many aspects of the regulation of regenerative medicine products. It will be announced as part of our Innovation Initiative. It will delineate our policies for appropriate and efficient regulatory oversight of regenerative medicine products, in order to demonstrate their safety and effectiveness. It will also create an accessible framework that will enable providers to more easily collaborate on proving these principles for regenerative products that are advanced within local medical institutions. We want to help facilitate these scientific advances, which hold out tremendous potential for treating and even curing diseases. To achieve these goals, we need to make sure that we have a modern regulatory framework in place that can allow innovators to meet the statutory requirements for demonstrating safety and effectiveness.
  • The newly established Oncology Center of Excellence is the first inter-center institute at FDA that focuses on a specific disease area rather than type of product. It’s designed to take advantage of the synergies that can be achieved by coordinating the clinical review of products across FDA’s drug, device, and biologic centers to make the development of oncology and hematology medical products more efficient. This new center will allow our expert review staff to work together and take a life-cycle approach to the development and post-market regulation of new cancer treatment options.
  • Under provisions of Cures, CDRH exempted more than 70 Class I device types from the requirement to submit to FDA a 510(k) submission. CDRH also proposed exempting another 1,000+ Class II device types from having to submit a 510(k) submission based on an initial determination that premarket review is not necessary to provide a reasonable assurance of safety and effectiveness. This action will decrease regulatory burdens on the device industry and eliminate private costs and expenditures.
  • To further align our regulatory requirements with the provisions of Cures, CDRH also amended its current regulations to allow more devices to qualify for a humanitarian device exemption for small patient populations. We’ll allow researchers to seek approval for device clinical trials through a central institutional review board rather than mandating the use of local review boards. Under the provisions of Cures, CDRH has also published the list of reusable device types for which FDA will require validated instructions for use and validation data regarding cleaning, disinfection, and sterilization in 510(k)s. These new requirements go into effect on August 8, 2017.
  • Finally, last month CDER, working with CBER, issued a plan for the development and issuance of patient-focused drug development guidances. The workshops and the new guidance will set forth our plan to facilitate a more systematic approach to gathering and using patient perspectives to inform FDA’s regulatory decision-making.

We’re at the beginning of a transformative era in science and medical technology. Through our implementation of Cures, and our efforts to build on its provisions through a new Innovation Initiative, we hope that our collective efforts will help consumers benefit from this new progress. FDA’s headway in pursuing the opportunities enabled by Cures illustrates the agency’s enthusiasm and commitment to the law—both its letter and its spirit. Please bookmark the Cures web page and our tracker to follow our progress as we work to vigorously advance these shared goals.

Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

FDA Science: Working at the Speed of Emerging Technologies

By Luciana Borio, M.D.

Let’s face it, we’ve all gotten used to nearly instant access to almost anything.

Today, with a tap of an app, we order a car ride, a book, or pizza for dinner. Need to navigate past traffic in downtown city streets? No problem. There’s an app for that, too.

Some may wonder: Why hasn’t rapid medical product development partaken of this need for speed that has reshaped other sectors of our economy? Well, in many ways, it has.

Innovation is happening extraordinarily fast in the biomedical sciences and at FDA. As FDA’s Acting Chief Scientist responsible for leading and coordinating FDA’s cross-cutting scientific and public health efforts, I see close up that years of scientific research, collaboration, and investment are paying off.

FDA Acting Chief Scientist Lu Borio

FDA Acting Chief Scientist Luciana Borio

When I testified at a congressional hearing recently, my colleague, Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases, gave a tangible example of what I mean. He said it took his team about three months to begin clinical testing of a Zika vaccine candidate developed from scratch. In 2003, it took the same team 18 months to develop a candidate vaccine to address the SARS outbreak and begin clinical testing of that product.

And in just over two decades, a disease like multiple sclerosis has gone from being untreatable to one for which clinicians are nearly “flummoxed by the options,” according to a headline I saw recently.

There is a reason for this success. In the last several years, scientists have identified and begun using “safety-risk biomarkers.” Rather than those for efficacy, these biomarkers identify which patients are at highest risk for certain adverse events. They have opened up an array of therapeutic options for patients who might do just fine with some treatments that may not otherwise have been developed due to our previous inability to properly assess their risk.

None of these successes would be possible without our FDA product reviewers working at breakneck pace to guide these innovative development programs.

It’s not always fully understood that FDA scientists play an essential role in advancing many biomedical innovations. That’s why we invite the public to participate in a two-day Science Forum at FDA every other year to showcase the agency’s robust scientific research and the important work done by our 11,000 scientists.

Just as industry focuses on product development research and academia focuses on the scientific foundation, FDA research concentrates on creating test methods and developing knowledge of processes to ensure that our products are safe and effective or, with tobacco, at least with reduced harm.

I like to think that this year’s Science Forum was better than ever. Over two days, hundreds of participants were treated to 230 scientific posters and some 50 presentations by FDA scientists and others, organized under eight broad categories:

  1. Identification and Evaluation of New Biomarkers;
  2. FDA Response to Urgent Public Health Needs;
  3. Microbiome and Human Health;
  4. Advanced Manufacturing and 3D Printing;
  5. Omics Technologies at FDA;
  6. Patient and Consumer Engagement and Communication;
  7. Computational Modeling and Simulation at FDA; and,
  8. Current Progress in Nanotechnology Research at FDA.

Four poster sessions during the two days augmented the presentations that featured the authors of studies describing the methodology, challenges, and results of their research one-on-one with those at the forum. Among the meaty topics discussed were:

  • The emerging technology of additive manufacturing and medical devices, produced by 3D printing. Bioengineers at FDA’s Center for Devices and Radiological Health have positioned themselves at the forefront of knowledge and research about this cutting-edge manufacturing process, by looking into patient matching, imaging, and phantoms. With our proactive posture, FDA is paving the way for safe and effective innovation that will usher in life-saving advanced treatments for patients.
  • The growing use in medical products of nanomaterials – equal to about one-billionth of a meter – so small that they can’t be seen with a regular microscope. Silver nanoparticles are now used in wound dressing for their antimicrobial properties. And liposomal nanoparticles are used as drug carriers to reduce toxicity and increase circulation time in the blood. Characterizing these complex nanomaterials is challenging. FDA scientists highlighted their analytical methods for characterizing nanomaterials in over-the-counter FDA-regulated products. This will help us with assessing risk, developing industry guidelines for characterizing nanomaterials, postmarket surveillance, and determining shelf life of nanomaterials in consumer products.
  • In the area of food safety, FDA has contributed to enhancing antimicrobial resistance monitoring in a collaborative effort with USDA and the Centers for Disease Control and Prevention. And, genomics studies conducted by FDA scientists have demonstrated that we can use the emerging technology whole genome sequencing as an effective tool for predicting antimicrobial resistance of certain foodborne pathogens.

Not all of our essential research deals with cutting-edge technology. Scientists from FDA’s Center for Tobacco Products (CTP) shared their work on water pipe, or hookah, smoking. Water pipes, a centuries-old method of smoking, are becoming an increasingly common method of tobacco smoking in young adults. A rare and serious lung disease – water pipe-induced acute eosinophilic pneumonia – has been reported among these smokers. One of the forum’s posters described how CTP scientists identified the disease and made physicians aware of it.

And, as a sign of the times, mobile communications also were part of the poster sessions. Healthy Citizen @FDA will be a holistic, citizen-centric mobile platform for FDA to collaborate and communicate with citizens to improve public health outcomes and to receive timely FDA alerts.

Of course, events like these are equally valuable for what happens before and after the formal presentations. From the snippets of conversation I picked up in the hallways, FDA and outside scientists had plenty of opportunity to interact, share ideas, and even discuss potential collaborations.

Those who attended the 2017 Science Forum gained a deeper understanding of the cutting-edge science we do at FDA to protect and promote the public health. And those who missed the Forum have the option of watching the recorded presentations on FDA’s website. We look forward to future opportunities to share more of the exciting advances we’re making with our partners in the scientific community.

Luciana Borio, M.D., is FDA’s Acting Chief Scientist

America’s Got Talent – Regulatory Science Style

By: Stephen Ostroff, M.D.

Veni Vidi Vici. It translates into English as “I came, I saw, I conquered.” It also happens to be the name chosen by one of the winners of the recently held America’s Got Regulatory Science Talent Competition.

America's Got Regulatory Science Event

Dr. Ostroff and FDA staff discuss projects with students from the University of Maryland CERSI.

FDA recognizes that young scientists are our future. Now in its fifth year, America’s Got Regulatory Science Talent is one of a number of initiatives FDA supports to encourage young scientists to pursue careers in the rapidly maturing field of regulatory science.

Each year, teams from the University of Maryland’s Center of Excellence in Regulatory Science and Innovation (CERSI), and the University of Rochester’s Clinical and Translational Science Institute (CTSI), compete by presenting their proposed solutions to a current challenge in regulatory science. The students identify the needs by consulting eight priority areas identified in FDA’s Strategic Plan for Regulatory Science.

Winners are decided by a panel of judges after evaluating each presentation for its quality and novelty, and the proposed solution’s potential significance and feasibility. The winning teams come to FDA to formally present their ideas and have discussions with Agency scientists who are working in their project area. The event, held on April 12th, was sponsored by the Office of Regulatory Science and Innovation (ORSI) which is located in the Office of Chief Scientist. The winning teams certainly came, saw, and conquered.

This year’s winners are:

University of Maryland CERSI

Dr. Ostroff with the University of Maryland teams

Dr. Ostroff with the teams from the University of Maryland CERSI

1st Place Team – Veni Vidi Vici

A high-visibility universal labelling system to communicate risks of hazardous drugs. Wonder if your prescription medication has some dangerous side effects that may be noted in “fine print” – or even nowhere – on the label? A universal symbol in red and yellow in a prominent place on the label is the “Veni Vidi Vici” Team’s solution.

2nd Place Team – Biomarker Boys

Platform to improve transparency for biomarker integration in Accelerated Approval pathway. Tackling a challenge experienced in this growing area of biomedical innovation, the “Biomarker Boys” created a form that facilitates transparent and structured integration of biomarkers into rare disease state drug development.

University of Rochester CTSI

Dr. Ostroff with the University of Rochester teams

Dr. Ostroff with the teams from the University of Rochester CTSI

1st Place Team – Simple English Explanation Directive (SEED)

Making clinical trial results more accessible and functional. Team “SEED” takes the incredibly complicated language that is often found when describing a clinical trial, and puts it in easy-to-understand form.

2nd Place Team – 3-Defining Patient Matched Implants

A streamlined process to test 3-D printed personalized implants. The “3-Defining Patient Matched Implants” Team decided that a quality systems approach is needed to streamline the process of validating the integrity of individual patient-matched 3-D printed implant systems. Their proposal introduces an alternative approach to the current method used in 3-D printing to ensure implants are safe for implantation.

This competition reminds us that good science makes for good regulation. And it was great to see the outside-the-box thinking and innovative approaches these contestants took in addressing some of the challenges that FDA faces with the products we regulate. It’s also a good reminder that the future of regulatory science depends on training and education – and we cannot underestimate the importance of educational activities like these.

The innovative approaches from this year’s teams also show the power of collaboration, mirroring the collaborative approach FDA takes in leveraging the brainpower of our teams of scientists, engineers, statisticians, social and behavioral scientists, medical officers, communicators, and others. The teams from the University of Maryland and the University of Rochester demonstrate just how teamwork produces great results.

Congratulations to the schools for organizing the competitions and to the FDA mentors who encouraged the competitors. Each year the quality of the work improves and I’m certain it will benefit patients and consumers over the coming years. Please check out this year’s talent –including a presentation from a freshman at Maryland. Who knows? Maybe one of these students will be FDA Commissioner some day!

To see the finalists present their innovative solutions to regulatory science challenges, visit FDA’s America’s Got Regulatory Science Talent web page.

Stephen Ostroff, M.D., is currently Acting Commissioner of the U.S. Food and Drug Administratio

FDA flickr photos from FDA’s America’s Got Regulatory Science Talent 

2016: A Record-setting Year for Generic Drugs

By: Kathleen “Cook” Uhl, M.D.

Over the last 10 years, generic drugs have saved the U.S. healthcare system about $1.68 trillion. I’m pleased to report that 2016 was a record-setting year for FDA’s generic drug program, a result that will help generate further cost savings for American consumers, while assuring the quality of these generic products.

Kathleen "Cook" UhlAnd the timing couldn’t be better amid concerns about rising drug prices.

Last year, FDA’s Office of Generic Drugs (OGD) in the Center for Drug Evaluation and Research generated the highest number of approvals in the history of FDA’s generic drug program – more than 800 generic drug approvals, including both full approvals and tentative approvals. (Tentative approvals are granted to applications ready for approval from a scientific perspective, but cannot be fully approved due to patents or exclusivities on the brand-name drug.) Last year’s performance surpassed 2015’s previous record of 726. Many of these approvals were for “first-time generic drugs,” meaning the introduction of a generic counterpart for a brand-name product for which there was previously no generic. That’s typically the first step towards lower drug prices because multiple generic versions of brand-name drugs drive price competition, leading to more affordable drugs.

An important factor in OGD’s record-setting performance has been the Generic Drug User Fee Amendments (GDUFA) of 2012, a landmark legislation negotiated with the generic drug industry, which completely reshaped the generic drug program at FDA. Among other things, it authorized funds for FDA to hire additional reviewers, modernize the review of generic drug applications, expand facility inspection capabilities, advance IT infrastructure for generic application review, and perform other regulatory actions. This is the first time Congress has authorized a user fee program specifically for generic drugs. It’s a five-year program, up for renewal October 1, 2017. GDUFA I has challenged OGD to reach a variety of goals while maintaining or improving the quality of the review process.

2016 Office of Generic Drugs Annual Report CoverWith the assistance of many other offices throughout FDA, OGD is on track to meet, or has already met, all of our GDUFA commitments. In addition to increased approvals and tentative approvals, FDA improved communications processes to alert industry to deficiencies in their applications, which reduces the number of review cycles and supports faster approvals.

We also are making a significant effort to spur generic drug development. For example, GDUFA Regulatory Science priorities contribute valuable research to generic drug development. Our efforts are geared to helping the generic drug industry develop validated scientific methods for demonstrating bioequivalence and assuring therapeutic equivalence to the brand-name counterpart. We are translating the results of these scientific efforts into generic drug product development via recommendations for specific drug products, which assist the generic drug industry during product development.

These are just a few of the exciting developments for 2016. Our annual report tells the rest of the story.

Despite these developments in 2016, a lot remains to be done as we approach the end of our first-ever five-year GDUFA program. We look forward to working with industry, the research community, physicians, lawmakers, and other stakeholders to help American consumers and advance use of generic drugs in our nation’s health care system.

Kathleen “Cook” Uhl, M.D., is FDA’s Director, Office of Generic Drugs in the Center for Drug Evaluation and Research

Mixing Kentucky Spirits with Food Safety to Protect Spent Grains Used to Feed Animals

By: Jenny Murphy, M.S.

“Spent grains” is the general term for the remnants of corn, rye, barley and other grains used to make alcoholic beverages. While they are a byproduct of human-food production, spent grains have a long history of being used as a valuable source of nutrients to feed many animal species. They also have been the subject of ongoing concerns among beverage distillers and brewers over the past few years as the FDA drafted rules that will implement the FDA Food Safety Modernization Act (FSMA).

Jenny Murphy holding spent grains

Jenny Murphy, a consumer safety officer in FDA’s Center for Veterinary Medicine (CVM), with handful of dried spent grain at the Wild Turkey distillery. In background, from left: Shannon Jordre, a consumer safety officer in CVM’s Division of Compliance, Jim Sanders, Distillery Manager at the Wild Turkey Distillery, Steve Barber, director of FDA’s Cincinnati District Office, and Jennifer Erickson, a regulatory policy analyst in CVM’s Office of Surveillance and Compliance.

Those concerns brought an FDA team to the rolling hills of central Kentucky this month to visit distilleries and a craft brewery and to meet members of the distilled spirits and brewers industry. The team was led by Stephen Ostroff, M.D., who was then FDA’s deputy commissioner for foods and veterinary medicine and who is now the acting FDA commissioner. I represented the agency’s Center for Veterinary Medicine (CVM) because of the connection between spent grains and animal health.

Congress included language in FSMA to exempt most alcoholic beverage manufacturing facilities from most of the FSMA requirements. But every day these manufacturers produce tons of spent grain, which are commonly used as animal food rather than being discarded in a landfill. Whether or how spent grains would be regulated under FSMA has been a point of some uncertainty for industry.

Based on the information available at this time, FDA considers the potential animal food safety hazards associated with spent grains from the alcoholic beverage industry to be minimal. The agency has assured these manufacturers that they will only be required to ensure that the byproducts are properly labeled and kept safe from contamination while they are held for distribution if these conditions are met: They continue to follow current good manufacturing practice (CGMP) requirements for human food in the production of their alcoholic beverages, and the resulting spent grains are not further processed. If the grains are further processed, such as by drying, they must follow CGMP requirements, with the flexibility to follow either the human food or animal food CGMPs.

But we have been encountering some confusion among brewers and distillers about these CGMP requirements for human and animal foods and how they would apply to spent-grain products. We wanted to reach a greater level of understanding on both sides, and what better place to do that? Kentucky is, after all, the birthplace of bourbon, according to the Kentucky Distillers Association. Recognized by Congress as a distinctively American product, bourbon is a $3 billion industry in Kentucky that generates 15,400 jobs. Kentucky also has a growing craft beer brewing industry.

containers of wet spent grain

Adam Watson (center), managing member and brewer at Against the Grain Brewery in Louisville, shows the visitors the containers of wet spent grain waiting for pickup outside the brewery.

We were a large group – about 20 participants from FDA’s headquarters and district office, the Kentucky Department of Agriculture, the state Division of Regulatory Services based at the University of Kentucky, and industry, including the Distilled Spirits Council and Brewers Association. Over the course of two days, we visited the Woodford Reserve, Wild Turkey, Jim Beam’s Booker Noe plant and Clermont distilleries, as well as the Against the Grain brewery.

This opportunity for education and outreach was extremely productive for all involved. FDA participants were able to allay many concerns and provide clarity about the framework for the CGMPs that the distillers and brewers are expected to meet for both human and animal food. And the distillers and brewers opened their doors, bringing us into their world in a way that was very informative and instructive. There is no substitute for actually seeing how these beverages are produced and how the spent grains are handled.

Although the basic processes are the same, each of the distillers and brewers we visited approaches its work somewhat differently. When it comes to spent grains, there are some operations that simply hold the grain and others with more elaborate processes to distribute the grain because of the large volume produced. We learned distinctions in terminology as the distillers showed us a variety of spent grain products, including wet and dry grains, syrups and cakes.

FDA engaged in this kind of outreach when the FSMA rules were taking shape. Now that the regulations are becoming a reality, we believe these conversations are just as important to help food producers understand what’s expected and avoid any misunderstandings. For FDA, these exchanges help us better understand what, if any, challenges industry may be facing as they strive to meet these new requirements.

Our next step is to take the knowledge we acquired and the lessons we learned and use them to help shape training for regulators and outreach to this industry in support of our shared commitment to keep both human and animal foods safe.

Click here to view FDA’s flickr album from this month’s visit to Kentucky.

Jenny Murphy, M.S., is a consumer safety officer in FDA’s Center for Veterinary Medicine

FDA Advisory Committees: Independent, Informed, Essential, and Evolving

By: Robert M. Califf, M.D.

One of the most common concerns raised when I meet with medical leaders is the need to improve the function of FDA’s Advisory Committees (ACs). ACs play a key role in FDA’s decision-making process by providing independent expert advice on extraordinarily complex issues. Just as importantly, they offer a forum for open and transparent discussion about these processes. As their name suggests, ACs are only advisory, but they can yield unique insights into understanding the balance of benefits and risks of products.

Not every product is brought to an advisory committee — when the answers are clear, the FDA makes decisions without consulting an AC. But when products present challenging issues or involve developing areas of science, the views of experts in relevant fields can provide essential perspective needed to make good decisions.

They also provide a barometer for the public on Agency thinking in a given field and offer insight into Agency decision-making and requirements for successful product development in a particular setting. The views expressed and votes taken can have financial impacts on companies and can lead to changes in how investments are made in therapeutic areas. So it is not surprising that the deliberations and views of ACs often receive significant media attention.

ACs have been the subject of ongoing discussions concerning their impartiality, their transparency, and how they affect decisions made about FDA-regulated products. In response to these concerns, the FDA is taking a closer look at the AC meeting process to determine what changes may be needed to ensure that ACs remain able to provide crucial expert advice relevant to the uncertainties that prompt such meetings.

Robert Califf

The process of engaging the expertise needed for ACs requires careful consideration, and the goal of ensuring that such a critical function leads to the best advice with optimal public trust by eliminating or managing conflicts is embedded in both law and culture at FDA. Experts who comprise ACs generally are classified as “special government employees” (SGEs) of the FDA. As such, they must declare any potential conflicts of interest and undergo a rigorous financial screening to ensure that they do not have a conflict or apparent conflict that could preclude their participation. SGEs are also expected to be free of intellectual bias that may foreclose their ability to consider the data and questions with an open mind.

Sometimes, a compelling interest can justify allowing a SGE with a potential conflict to participate. In such a case, the prospective AC member must be granted a waiver or appearance authorization, which provide a mechanism for clearly delineating the reasons for allowing that person to participate and requires disclosing the conflict. This aspect of the AC process has evolved over time, becoming increasingly complex and burdensome.

In 2007, the Food and Drug Administration Amendments Act (FDAAA) restricted the FDA’s ability to use waivers for SGEs as part of an effort to reduce bias among AC members by allowing minimal or no financial conflicts. This led to concerns from multiple stakeholders about whether the FDAAA provision was in fact discouraging the most qualified experts from serving on ACs and thus depriving FDA of the best possible guidance on important scientific issues.

In response to these concerns, Congress included a provision in the 2012 Food and Drug Administration Safety and Innovation Act (FDASIA) that encouraged FDA to weigh an AC member’s conflicts against the need for that participant’s scientific expertise. However, despite this added flexibility, there are many who believe FDA has not been aggressive enough in advocating for waivers — a circumstance that they believe has sometimes resulted in difficulty obtaining the optimal expertise needed to address the complex problems typically brought to ACs. And some outside the Agency have wondered whether this means FDA is moving to reduce use of ACs.

The process for AC participation itself has led to other criticisms. Across academia, the AC system is seen as overburdened with unnecessary paperwork. Additionally, FDA has faced criticism that the concept of an “imputed interest” is interpreted so that academic leaders with significant experience and insight are considered to have conflicts relating to grants and contracts held by faculty members at the same institution — even if they themselves have no involvement with the project. The proliferation of roadblocks to serving as an SGE has led some within FDA and key leaders in various scientific fields to question the value of ACs in their current form.

After indepth discussion with the medical product and tobacco Centers, OMPT initiated a process improvement evaluation using Lean concepts, which comprise an industrial engineering toolset used for process improvement. These tools were applied to the AC process to fully understand the administrative requirements for planning meetings and screening potential SGEs. We are confident that administrative processes, both inside FDA and for SGEs, will be streamlined as a result.

The next step will be to evaluate current policies and identify areas where the evaluation of conflicts of interest for SGEs can be modernized. We must consider questions such as the criteria for disqualifying AC members from specific activities, the appropriate scope of “imputed interests,” and the interrelationship between the advisory role of AC members and the decisional role of Agency employees.

Even more importantly, we must engage in wide-ranging discussions inside and outside FDA about the best ways for the Agency to get the advice it needs to make critical decisions that protect and promote the health and safety of all Americans. To obtain the best expertise possible, we must optimally configure and administer our ACs.

There is no question that we must appropriately address potential conflicts for our SGEs.  However, we must also ensure that experts working in their fields are not unnecessarily foreclosed from participation in the AC process. As we continue to improve the mechanics of ACs and to reduce unnecessary administrative burdens, we must also address the appropriate mix of expertise on committees, so that FDA scientists and staff get the advice they need to make the best decisions on behalf of the American public.

Robert M. Califf, M.D., is Commissioner of the U.S. Food and Drug Administration