Keeping the U.S. Prescription Drug Supply Chain Among the Safest in the World

By: Ilisa Bernstein, Pharm.D., J.D.

The U.S. prescription drug supply is among the safest in the world, but it can be challenging to keep it that way. Criminals – both here and abroad – constantly threaten to replace safe, effective, and high-quality prescription medications with counterfeit, stolen, and otherwise substandard products.

Ilisa BernsteinRoughly 4 billion prescriptions were filled at U.S. retail pharmacies last year. That’s a lot of prescription drugs moving through the U.S. supply chain that patients are relying on. In today’s global pharmaceutical environment, in which a large percentage of FDA-approved prescription drug products are made outside of the United States, we are continuously looking for ways to keep the drug supply secure.

Substandard and falsified drugs are global problems that need global solutions and global collaboration. We cannot solve these challenges alone and we at FDA are continually looking for ways to collaborate and learn from our regulatory counterparts around the world.

I’m pleased to share an important new advancement to help protect the U.S. and global supply chain for prescription drugs and other medical products. Over the past four years, FDA led a team of international partners to create the Supply Chain Security Toolkit for Medical Products. Our collaborators included regulators from the 21-nation Asia-Pacific Economic Cooperation (APEC), non-APEC countries, industry stakeholders, representatives from non-governmental organizations, international organizations, and academia.

The goal of this collaboration was to develop strategies to better secure the medical product supply chain across APEC economies and around the world. We also aimed to enhance APEC members’ regulatory standards to secure national and global supply chains, and develop tools that regulators and industry can use for training and for implementing best practices.

The Toolkit is a comprehensive resource that covers the entire supply chain and lifecycle of medical products – from raw materials to patient use. It focuses on developing and implementing processes and procedures designed to enhance global medical product quality and supply chain security.

The Toolkit website provides detailed information and resources related to track and trace, internet sales, detection technology, and much more. The toolkit can be used by industry stakeholders and regulators from around the globe to adopt best practices and to strengthen laws and regulations to protect consumers from unsafe and substandard drug products. It also is a valuable training tool for regulators grappling with the complexities of keeping the supply chain safe.

Training will be coordinated by the United States Pharmacopeia and the University of Tennessee Health Sciences Center, which are APEC Centers of Excellence.

The tools will help regulators worldwide to PREVENT, DETECT, and RESPOND to medical products that threaten the health and safety of patients.

We all will benefit from this hard work. Together with our global partners, we will continue to combat supply chain problems as they arise and increase confidence in the legitimacy of the life-saving prescription drugs that patients rely on.

Ilisa Bernstein, Pharm.D., J.D., is Deputy Director of the Office of Compliance in FDA’s Center for Drug Evaluation and Research

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

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

‘Fight BAC:’ FDA’s Little Green Monster Still Going Strong After 20 Years

By: John Swann, Ph.D.

Twenty years ago, FDA was invaded by a hideous creature that today is still one of the most unforgettable and endearing artifacts in the FDA History vault. The giant green character (who came to life thanks to FDA staffers who wore the large ventilated costume) known as BAC, short for Bacteria, was the centerpiece of an FDA public education campaign designed to put a fearsome face on foodborne bacteria, thereby alerting Americans to the dangers of food contamination and how to avoid it in their kitchens.

BAC, the giant green character

BAC, short for Bacteria, was the centerpiece of an FDA public education campaign designed to put a fearsome face on foodborne bacteria.

The “Fight BAC campaign” grew out of the public-private Partnership for Food Safety Education, and was one of the core strategies of a 1997 report to the President on Food Safety. It wasn’t the first time FDA had developed a public health education campaign. Previous efforts used entertainers, sports figures, and others to inform the public about a variety of public health issues. But the Fight BAC campaign was one of the most effective, and BAC’s message to “Keep Food Safe from Bacteria” continues to have staying power – it’s still going strong 20 years later in support of FDA’s mission to protect and promote the health of the American public.

John Swann, Ph.D., is an FDA Historian

FDA Working to Lift Barriers to Generic Drug Competition

By: Scott Gottlieb, M.D.

Too many patients are being priced out of the medicines they need. While FDA doesn’t have a direct role in drug pricing, we can take steps to help address this problem by facilitating increased competition in the market for prescription drugs through the approval of lower-cost, generic medicines.

Dr. Scott GottliebOver the last decade alone, competition from safe and effective generic drugs has saved the health care system about $1.67 trillion. When generics are dispensed at the pharmacy, the immediate savings to each of us are clear. We could see even greater cost savings if we helped more safe and effective generic drugs get to market sooner, after patent and statutory exclusivity periods have lapsed, by addressing some of the scientific and regulatory obstacles to generic competition across the full range of FDA-approved drugs. These barriers may delay and, in some cases, ultimately deny patient access to more affordable drugs.

That’s why we’re working on a Drug Competition Action Plan. As part of this effort, today, we’re announcing in the Federal Register our intent to hold a public meeting on July 18, 2017, to solicit input on places where FDA’s rules – including the standards and procedures related to generic drug approvals – are being used in ways that may create obstacles to generic access, instead of ensuring the vigorous competition Congress intended.

Innovation in pharmaceutical development is essential because it creates new and sometimes life-saving therapies. But access to lower-cost alternatives, once patent and exclusivity periods lapse, also is critical to the nation’s health.

We know that sometimes our regulatory rules might be “gamed” in ways that may delay generic drug approvals beyond the time frame the law intended, in order to reduce competition. We are actively looking at ways our rules are being used and, in some cases, misused.

One example of such gaming is the increasing unavailability of certain branded products for comparative testing. To perform the studies required to develop a generic alternative to a branded drug, a generic sponsor generally needs 1,500 to 3,000 doses of the originator drug. I understand that generic sponsors are willing to buy these products at fair market value; but, in some cases, branded companies may be using regulatory strategies or commercial techniques to deliberately try to block a generic company from getting access to testing samples.

This might occur, for example, when branded companies might use restrictions they place in their commercial contracts or their agreements with distributors to make it hard for intermediaries in the drug supply chain to sell the drugs to generic drug developers.

We also see problems accessing testing samples when branded products are subject to limited distribution – whether the company has voluntarily adopted limitations on distribution, or the limitations have been imposed as part of a Risk Evaluation and Mitigation Strategy, or REMS, a program that FDA implements to help ensure the safe use of certain drugs. I have been made aware that, in some of those cases, branded sponsors may use these limited distribution arrangements, whether or not they are REMS-related, as a basis for blocking generic firms from accessing the testing samples they need.

Besides limiting access to testing samples, some branded companies may be using the statutory default requirement to have a single shared REMS across both the branded and generic versions of a drug as a way to block generic entry. They might prolong negotiations with the generic firms over the implementation of these single shared systems, which could delay the entry of safe and effective generic drugs onto the market.

I want to take steps to address these concerns, to make sure that we are facilitating appropriate competition in circumstances where Congress intended. The forthcoming public meeting is intended to solicit public comment to inform us of circumstances where generic competition may be thwarted by these and other techniques.

As we solicit additional information, we also are going to be looking at policy and programmatic changes to address these issues. Some of these steps may be actions we can take by using our own authorities more forcefully. Other steps might involve our need to collaborate with sister agencies.

We’re also going to be looking hard at how best to coordinate with the Federal Trade Commission in identifying and publicizing practices that the FTC finds to be anti-competitive. FDA is not the FTC. It is the FTC’s responsibility to prevent anticompetitive business practices. But Congress set out certain laws that are meant to strike a careful balance between pharmaceutical innovation and access to lower cost generic products, and FDA has an important responsibility to enforce those laws in a manner that adheres to the balance struck by Congress.

We’ll be unveiling additional aspects of our larger Action Plan and providing updates, as these initial elements are implemented. I’m confident that these actions and the dedicated work of the outstanding staff in our generic drug program will help to address the issues patients are facing today when they’re priced out of buying the drugs they need. At the meeting on July 18 we want to hear from the public about ways our current rules may not be having their intended effects, and where current policies are falling short in ensuring the careful balance between new innovation and patient access.

Our goal is to broaden access to safe and effective generic drugs that can improve access to medicines and help consumers lower their health care costs. As in all of the things we do, we will steadfastly maintain FDA’s gold standard for rigorous, science-based regulation.

Over the past five years our generic drug program staff has evolved and grown remarkably, while implementing the first generic drug user fee program. The staff has demonstrated that they can rise to new challenges and they have my full support. Their hard work will serve as a strong foundation for the program as it moves forward. I want the policy framework they operate under to be as efficient, fair, and robust as the review program that they’re operating.

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

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

Fostering Medical Innovation: A Plan for Digital Health Devices

By: Scott Gottlieb, M.D.

It is incumbent upon FDA to ensure that we have the right policies in place to promote and encourage safe and effective innovation that can benefit consumers, and adopt regulatory approaches to enable the efficient development of these technologies. By taking an efficient, risk-based approach to our regulation, FDA can promote health through the creation of more new and beneficial medical technologies. We can also help reduce the development costs for these innovations by making sure that our own policies and tools are modern and efficient, giving entrepreneurs more opportunities to develop products that can benefit people’s lives.

Dr. Scott GottliebTo this end, FDA will soon be putting forward a broad initiative that is focused on fostering new innovation across our medical product centers. I will have more to say on many elements of this initiative soon. However, today I want to focus on one critical aspect of this innovation initiative: A new Digital Health Innovation Plan that is focused on fostering innovation at the intersection of medicine and digital health technology. This plan will include a novel, post-market approach to how we intend to regulate these digital medical devices.

According to one estimate, last year there were 165,000 health-related apps available for Apple or Android smartphones. Forecasts predict that such apps would be downloaded 1.7 billion times by 2017. From mobile apps and fitness trackers to clinical decision support software, innovative digital technologies have the power to transform health care in important ways, such as:

  • Empowering consumers to make more and better decisions every day about their own health, monitor and manage chronic health conditions, or connect with medical professionals, using  consumer-directed apps and other technologies to  help people  live healthier lifestyles through fitness, nutrition, and wellness monitoring;
  • Enabling better and more efficient clinical practice and decision making through decision support software and technologies to assist in making diagnoses and developing treatment options; managing, storing, and sharing health records; and managing schedules and workflow;
  • Helping to address public health crises, such as the opioid epidemic that is devastating many American communities. In fact, FDA conducted a prize competition to encourage the development of a mobile app to help connect opioid users experiencing an overdose with nearby carriers of the prescription drug naloxone for emergency treatment.

For these and other digital technologies to take hold and reach their fullest potential, it is critical that FDA be forward-leaning in making sure that we have implemented the right policies and regulatory tools, and communicated them clearly, to encourage safe and effective innovation. In this rapidly changing environment, ambiguity regarding how FDA will approach a new technology can lead innovators to invest their time and resources in other ventures. To encourage innovation, FDA should carry out its mission to protect and promote the public health through policies that are clear enough for developers to apply them on their own, without having to seek out, on a case-by-case basis, FDA’s position on every individual technological change or iterative software development.

Congress has already taken a major step to advance these goals in the 21st Century Cures Act. Expanding upon policies advanced by FDA’s Center for Devices and Radiological Health (CDRH), the Act revised FDA’s governing statute to, among other things, make clear that certain digital health technologies—such as clinical administrative support software and mobile apps that are intended only for maintaining or encouraging a healthy lifestyle—generally fall outside the scope of FDA regulation. Such technologies tend to pose low risk to patients but can provide great value to the health care system. FDA, led by CDRH, is working to implement the digital health provisions of the 21st Century Cures Act and, in the coming months, will be publishing guidance to further clarify what falls outside the scope of FDA regulation and to explain how the new statutory provisions affect pre-existing FDA policies.

FDA will provide guidance to clarify our position on products that contain multiple software functions, where some fall outside the scope of FDA regulation, but others do not. In addition, FDA will provide new guidance on other technologies that, although not addressed in the 21st Century Cures Act, present low enough risks that FDA does not intend to subject them to certain pre-market regulatory requirements. Greater certainty regarding what types of digital health technology is subject to regulation and regarding FDA’s compliance policies will not only help foster innovation, but also will help the agency to devote more resources to higher risk priorities.

In addition to these efforts, we are also announcing today a new initiative that FDA is undertaking. This fall, as part of a comprehensive approach to the regulation of digital health tools and in collaboration with our customers, FDA will pilot an entirely new approach toward regulating this technology. This will be the cornerstone to a more efficient, risk-based regulatory framework for overseeing these medical technologies.

While the pilot program is still being developed, we are considering whether and how, under current authorities, we can create a third party certification program under which lower risk digital health products could be marketed without FDA premarket review and higher risk products could be marketed with a streamlined FDA premarket review. Certification could be used to assess, for example, whether a company consistently and reliably engages in high quality software design and testing (validation) and ongoing maintenance of its software products. Employing a unique pre-certification program for software as a medical device (SaMD) could reduce the time and cost of market entry for digital health technologies.

In addition, post-market collection of real-world data might be able to be used to support new and evolving product functions. For example, product developers could leverage real-world data gathered through the National Evaluation System for health Technology (NEST) to expedite market entry and subsequent expansion of indications more efficiently. NEST will be a federated virtual system for evidence generation composed of strategic alliances among data sources including registries, electronic health records, payer claims, and other sources. The Medical Device Innovation Consortium (MDIC), a 501(c)(3) public-private partnership, is serving as an independent coordinating center that operates NEST. In the coming weeks, MDIC will announce the establishment of a Governing Committee for the NEST Coordinating Center comprised of stakeholder representatives of the ecosystem, such as patients, health care professionals, health care organizations, payers, industry, and government. Although FDA does not own or operate NEST, we have been establishing strategic alliances among data sources to accelerate NEST’s launch with the initial version of a fully operational system anticipated by the end of 2019.

Applying this firm-based approach, rather than the traditional product-based approach, combined with leveraging real-world evidence, would create market incentives for greater investment in and growth of the digital health technology industry. Such processes could enable developers to deploy new or updated software more rapidly and would help FDA to better focus our resources.

Through these and other steps, FDA will help innovators navigate a new, modern regulatory process so that promising, safe and effective developments in digital health can advance more quickly and responsibly, and Americans can reap the full benefits from these innovations. These efforts are just one part of a much broader initiative that FDA is currently undertaking to advance policies that promote the development of safe and effective medical technologies that can help consumers improve their health. Our goal is to make sure that FDA has the most modern and efficient regulatory approaches when it comes to evaluating new, beneficial technologies.

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

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

How Creative FDA Regulation Led to First-in-the-World Approval of a Cutting-Edge Heart Valve

By: Jeffrey Shuren, M.D., J.D., and Bram Zuckerman, M.D.

Jeffrey Shuren

Jeffrey Shuren, M.D., J.D., Director of FDA’s Center for Devices and Radiological Health

Nearly six years ago FDA approved an artificial transcatheter heart valve (THV) to treat patients having severe symptoms and life-threatening heart problems such as fainting, chest pain, heart failure, irregular heart rhythms, or cardiac arrest, because one of the valves in their heart (the aortic valve) was no longer working properly and they were too sick for surgery.

Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of these patients.  But the U.S. wasn’t the trendsetter – in fact, it was the 42nd country to approve the first TAVR device, the Edwards Sapien THV.

Since that approval, FDA has sharpened its focus on patient access to innovative medical devices. On June 5th, 2017, FDA became the first regulatory body in the world to approve the most recent iteration of the Sapien valve, the Sapien 3, to treat high-risk patients whose surgically-placed aortic or mitral bioprosthetic valves were old and worn out. The Sapien 3 is intended to slip into these valves using a so-called “valve-in-valve” option, a procedure that can be done without open heart surgery through a patient’s blood vessel or a small cut in the chest.

Sapien 3

SAPIEN 3 Heart Valve Device

To narrow the gap from 42nd to first required creativity and commitment. The FDA Heart Valve Review Team first streamlined FDA’s expectations for nonclinical testing – something that had been a huge rate-limiting factor for translating innovative TAVR devices from bench to bedside. We became more consistent, predictable, and transparent about our expectations, which helped significantly reduce the total time to initiating clinical studies. And we worked closely with the industry on creative clinical trial designs and the use of other sources of clinical evidence that could demonstrate that the device is safe and effective when used in the intended patient population.

Bram Zuckerman

Bram Zuckerman, M.D., FDA’s Director, Division of Cardiovascular Devices, Center for Devices and Radiological Health

This latest approval is the most recent example of our increasing use of real-world evidence, made possible in this case by the Transcatheter Valve Therapy (TVT) Registry, a partnership of the American College of Cardiology and the Society of Thoracic Surgeons. The TVT registry collects clinical data on the performance of transcatheter valve replacement procedures performed in the U.S. once a product goes to market – including both on-label and off-label uses – making it possible, under certain circumstances, to accumulate more data faster, without the need for costly and time-consuming formal clinical trials.

Some 100,000 patients have received TAVR since FDA’s first approval in 2011, including more than 600 patients for what were then off-label, valve-in-valve uses. FDA relied on real-world evidence to evaluate the benefits and risks of this off-label use — such as the safety of the procedure, the function of the valve, and the improvement of patient symptoms – to approve the new indication for Sapien 3. This is a promising approach for the expansion of indications for other devices, provided robust registries are available.  FDA is working to broaden and improve the opportunities to leverage real-world evidence for many types of devices through the establishment of the National Evaluation System for health Technology, or NEST, which will integrate data from clinical registries, electronic health records, and medical billing claims to gather more comprehensive evidence of medical device safety and effectiveness.

CDRH Sapien 3 Reviewers

John C. Laschinger, M.D., Medical Officer, and Changfu Wu, Ph.D., Lead Reviewer, Members of FDA’s Structural Heart Devices Branch

And we’re not stopping here. U.S. medical device companies have long been accustomed to going overseas to conduct early feasibility studies (including first-in-human studies) for new heart valve devices, securing marketing authorization in other countries, and then returning to the U.S. for pivotal clinical trials before FDA approval. We’re trying to break that model with a new program that encourages early feasibility studies for new medical devices in the United States. These studies allow for early clinical evaluation of devices to provide proof of principle and initial clinical safety data, and may be appropriate early in device development when clinical experience is necessary because nonclinical testing methods are not available or adequate to provide the information needed to advance the developmental process.

Many heart valve device companies have already responded. Rather than traveling to other countries, they’re staying put in the U.S. for their early feasibility studies, saving on travel costs, enjoying more convenient communications with the investigators, and benefiting from early interactions with FDA.

These steps – along with our other reforms – will ensure that cutting-edge treatments get to U.S. patients as quickly as possible.

Jeffrey Shuren, M.D., J.D., is FDA’s Director of the Center for Devices and Radiological Health

Bram Zuckerman, M.D., is FDA’s Director, Division of Cardiovascular Devices, Center for Devices and Radiological Health

#IAmHHS: Fighting Misleading Prescription Drug Ad Claims

By: Mike Sauers

These days, you can hardly turn a magazine page, watch a TV show or sit in the lobby of your doctor’s office without seeing advertising and promotions for prescription drugs. They’re everywhere you go. And they tend to be impressive and reassuring. But are they accurate?

A big part of my career at the Department of Health and Human Services has been about helping to make sure those ads are truthful and not misleading.

At the FDA, I’m staff supervisor of the Office of Prescription Drug Promotion’s (OPDP) Advertising and Promotion Policy Staff, which helps develop policies for advertising and promotion of prescription drugs across the United States. In my job, I help make sure that drug companies’ communications of information about their prescription drugs to consumers and healthcare professionals are truthful and not misleading. In my role, I also help to make sure our stakeholders in the pharmaceutical industry understand the rules of the road.

I started my career as a drug representative in Philadelphia, promoting a pharmaceutical company’s drugs. It was a good job in a great industry.

But to be 100 percent honest, it was not personally fulfilling and I decided to pursue public service. I went back to school, earned a master in public policy from Georgetown Public Policy Institute (now McCourt School of Public Policy), and then joined HHS as a budget analyst in the Office of the Secretary through the Presidential Management Fellows Program. Working in the Office of the Secretary gave me the chance to see many of the incredible programs that HHS operates to help improve the lives of Americans on a daily basis.

After my fellowship ended, I decided to continue my HHS career at FDA by focusing on a subject area I knew very well: prescription drug advertising.

I became a regulatory review officer in OPDP and looked at specific ads aimed at doctors or consumers to make sure the claims were truthful and not misleading.

That work prepared me to move into my current role in OPDP where I lead the group that helps develop industry-wide policies for all prescription drug advertising and promotion. One of the highlights of my government service was co-creating the Bad Ad Program, an initiative designed to educate health care providers about misleading prescription drug promotion and to make it easier for them to report this activity to the agency.

It’s an awesome responsibility and very challenging, but I truly believe I am making a difference by helping to ensure that advertisements provide accurate and truthful information about the effectiveness and potential risks of prescription drugs.

You just can’t quantify the type of job satisfaction that comes from knowing that every day you come to work, you have the opportunity to make an impact.

I’m Mike Sauers. I work for the FDA and I am HHS.

Mike Sauers is a staff supervisor in FDA’s Office of Prescription Drug Promotion, Center for Drug Evaluation and Research

Mike is one of more than 79,000 people who make HHS run every day. You can share his story and see others on Twitter and Facebook using #IAmHHS.