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

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

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

21st Century Cures Act: Making Progress on Shared Goals for Patients

By: Robert M. Califf, M.D.

Today, President Obama signed into law the 21st Century Cures Act, which, I am pleased to report, builds on FDA’s ongoing efforts to advance medical product innovation and ensure that patients get access to treatments as quickly as possible, with continued assurance from high quality evidence that they are safe and effective.

Robert CaliffCures will greatly improve FDA’s ability to hire and retain scientific experts. One of our ongoing challenges has been recruiting and retaining the experts we need in specialized areas to allow us to get our work done and meet our growing responsibilities. This is an especially important need given the tremendous advances in biological sciences, engineering, information technology and data science. Preventive, diagnostic and therapeutic strategies will become more complex with much greater potential for benefit and in some cases greater risk if used without adequate evidence to exclude risks that exceed potential benefits.

This new law rightly recognizes that patients should play an essential role in the development of drugs and devices to diagnose and treat their disease, since patients are in a unique position to provide essential insights about what it is like to live with and fight their disease. That’s been our perspective as well, and it’s why FDA has continued to advance the science of patient input through our patient-focused drug development program and our partner with patients program for medical devices. As it is, Cures will enhance these ongoing efforts to better incorporate the patient’s voice into FDA’s decision-making.

Cures will also support our efforts to modernize and improve efficiency in clinical trial design. This has been an important FDA priority for decades, but exciting new approaches are now available, and we need to develop a common understanding of which designs should be used for which clinical issues. In cancer, for example, we’re already weighing the use of common control trials, which share a control arm, involve multiple different drugs for the same indication, and may even involve different companies. One of the benefits of using a common control arm is that the overall number of patients who need to be recruited and enrolled decreases, thereby optimizing clinical trial resources and potentially shortening the time it takes to get a new study off the ground

Even without the benefit of Cures, patients have been well-served by FDA’s program efficiencies, emphasis on early meetings, and use of expedited pathway programs to speed approval and delivery of new drugs and devices to patients. Rather than passively processing product applications, FDA works to advise companies and inventors from the earliest stages of the development process on the kinds of medical products needed, how to do the necessary research, and how to viably and effectively translate from concept to product. This not only means that important new products will be developed as efficiently as possible but also that medicines and devices with no chance of success are identified much earlier so that money isn’t wasted on futile development. These programs have been embraced by developers of medical products in this country, and they are making a real and positive difference.

In the United States, the FDA uses expedited programs (fast track, priority review, accelerated approval, and breakthrough therapy) for drugs and biologics more than comparable drug and biologic regulators in other countries use theirs and as a result FDA is the first to approve a majority of novel drugs compared to our foreign counterparts.

For devices, this past year was the first full year of operation for FDA’s expedited access pathway (EAP) program, which helps speed the development and availability of certain medical devices that demonstrate the potential to address unmet medical needs for life-threatening or irreversibly-debilitating diseases or conditions. So far, we have granted 24 devices access to this program. Cures builds on EAP by creating the breakthrough device pathway.

The law establishes other new programs as well. For instance, the Limited Population pathway will help streamline the development programs for certain antibacterials and antifungals intended to treat targeted groups of patients suffering from serious or life-threatening infections where unmet need exists due to lack of available therapies. Approvals of these antimicrobials are expected to rely on data primarily targeting these limited populations. The statement “Limited Population” will appear prominently next to the drug’s name in labeling, which will provide notice to healthcare providers that the drug is indicated for use in a limited and specific population of patients. The limited population statement, additional labeling statements describing the data, and FDA review of promotional materials, will help assure these drugs are used narrowly to treat these serious and life-threatening infections while additional evidence is generated to assess safety and effectiveness for broader use.

Cures also creates a new program for  the development of regenerative medicine products, an important and exciting new field that deserves this special focus. The program designates drugs as regenerative advanced therapies and takes appropriate actions to improve the efficiency of development and to enhance the exchange of information among FDA, researchers and developers. An especially important element of this program is the creation of a research network and a public-private partnership to assist developers in generating definitive evidence about whether their proposed therapies indeed provide clinical benefits that are hoped for.

Looking ahead, much still needs to be done to spur product development. There have yet to be successful therapies identified for certain diseases, such as Alzheimer’s disease, where underlying scientific knowledge is still lacking.  In addition, we are only at the early stage in building a national evidence generation system based on registries, claims data, and electronic health records that will be a rich source of post-market data and an avenue for conducting more efficient research. Last week we published a consensus of FDA leadership on the use of real world evidence in the New England Journal of Medicine, focusing on the misperception that randomized trials and real world data are incompatible.  In fact, the use of randomization within the context of clinical practice will constitute a major advance in evidence generation and we are actively encouraging proposals with this combination of randomized trials conducted in real world practice. Cures provides support for continued exploration of the use of real world evidence in the regulatory context.

The law also addresses drug firms providing healthcare economic information to payers and formulary committees. This complex area will require careful delineation of principles to guide information exchange to enable these entities to appropriately assess the value of drugs.

With Cures, great progress has been made towards our shared goal of advancing regulatory science so that we can continue to speed the discovery, development, and delivery of medical products to prevent and cure disease and improve health while sustaining the evidence framework that enables assurance to the public of the safety and effectiveness of medical products. We are excited about the major advances in NIH funding, and welcome the increasing focus on rigorous translational science and data sharing reflected in the bill. Furthermore the funding of opioid addiction treatment and mental health services is a major positive element for our country and consistent with tremendous needs that we recognize.

FDA now stands ready to work with Congress, our sister federal agencies and the medical products ecosystem to implement these important provisions as we continue to work on behalf of all Americans to protect and promote public health and promote innovation in this exciting time.

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