- Speech by
Deputy Commissioner for Policy, Legislation, and International Affairs - Food and Drug Administration ( March 2019 - January 2021 )
(Remarks as prepared for delivery)
Thank you for that kind introduction. I’m honored to have the opportunity to join you for Biocom’s Annual “Celebration of Life” event and share with you some of the great work being done at FDA.
FDA is a very special place. It is a strong agency with a vital public health mission. I am truly humbled to be able to serve alongside my FDA colleagues on behalf of patients and the public and continue to be impressed with the agency’s world-class workforce made up of scientists, doctors, lawyers, policy makers, communicators, and so many others.
In thinking about the focus of this evening – celebrating life—I couldn’t help but reflect on how FDA, in pursuit of our patient and consumer focused mission to protect and promote public health, contributes to saving and improving the quality of life in so many ways. Patients and consumers are at the heart of what we do and why we do it. Every day, FDA’s talented professionals come to work focused on advancing our critical public health mission. And, they do so ever-mindful that FDA is a science-based agency that depends on high quality, reliable scientific evidence. The decisions we make about health and health care that affect patients, healthcare providers, and developers of medical products, are informed by our ability to apply the most advanced science in support of the innovation, development and evaluation of drugs, biologics, and medical devices intended to treat, diagnose, and prevent disease.
In a few short weeks, we’ll be entering a new decade. While we can’t know for certain what the next 10 years will hold, I am certain of this: the past decade was a truly remarkable period for the life sciences and for FDA.
Let’s reflect just a bit. We’ve essentially seen cures for such previously intractable diseases as cystic fibrosis and Hepatitis C, as well as important advances in cancer treatment. Both science and medicine doubled down on the promise of patient-focused therapies, selecting the right treatment for the right patient, resulting in the advancement of immunotherapy and the first FDA-approved gene therapy products. And now we’re grappling with how regulators should address the so-called n-of-1 products - therapies that are individualized down to a single person, an issue that two of our center directors, Dr. Janet Woodcock and Dr. Peter Marks, addressed in a recent New England Journal of Medicine editorial.
Thanks to the rise of patient-focused therapies, treatments for rare diseases have been a success story. Last year alone, in what was another record-breaking year, we had 94 new approvals for orphan drug indications, including 35 novel drugs and biologics with orphan drug designation. That’s the highest number in the history of the Orphan Drug Act. As 2019 draws to a close, so far there have been 269 orphan designations of drugs and biologics and approvals of 14 novel orphan drugs and biologics.
While these are heartening statistics, there are still thousands of rare diseases with no approved treatments. That’s why FDA continues to fund clinical trials and natural history studies on rare diseases and is also looking at various ways to enhance how to incorporate the patient experience into FDA’s regulatory discussions.
In this patient-focused paradigm, patient engagement is increasing, including relying more on patients themselves as a rich source of information, which has been a key focus of biomedical development in the past decade. During this period we saw new tools to measure patient reported outcomes and patient preferences. Having these tools is just the beginning. FDA has become an important contributor to international collaborative efforts to standardize the collection and analysis of such patient data in order to generate scientifically- rigorous evidence to assist in regulatory decision making.
FDA is dedicated to advancing patient-focused product development in many other ways. For instance, we sought advice about our approach to a variety of conditions through our patient focused drug development mechanism; we created a medical device committee comprised entirely of patients and caregivers; we set up a new Patient Affairs Staff as a central entry point for patients who don’t know where to begin when contacting the agency, we launched the Rare Disease Listening Sessions program to help us better understand disease burden, daily impacts and patient priorities when it comes to medical product development for rare diseases; and most recently, we created the Patient Engagement Collaborative, a forum for the patient community and regulators to discuss increasing patient engagement in medical product development and regulatory discussions at FDA.
Concurrent with this greater focus on leveraging modern advances on behalf of patients has been the early adoption of manufacturing processes such as 3D printing and advanced manufacturing, including continuous manufacturing (CM), that adapt well to small batches for individualized treatments. Four years ago, there was just one FDA product approved to be made via continuous manufacturing technology that uses modern monitoring and controls within a closed loop system in which raw material is continuously added on one end and a finished drug product emerges on the other.
Congress has been greatly supportive of FDA over the decade, providing the agency with new tools and authorities. In many ways, the objectives of these new tools are to support the agency in tackling the public health challenges that we confront, striving to be as modern and efficient as possible in our processes, and leveraging the incredible scientific advances we are seeing and will see in the years to come. Or more simply put, to support the agency in doing it better. For example, Congress established a new pathway for biosimilars, breakthrough therapy designation for drugs and biologics, provisions that would allow for increased stakeholder involvement in FDA processes, and tools to combat the opioid epidemic. And that doesn’t account for the long list of enhancements in the 21st Century Cures Act. Cures created a priority review pathway for breakthrough medical devices, the regenerative medicine advanced therapy designation program, and a limited population approval pathway for antibacterial and antifungal drugs, among other things. It also established a clear process for biomarker acceptance and qualification, helped advance the use of modern trial designs and real-world evidence, and gave FDA authority to provide grants to encourage advanced and continuous manufacturing, just to name a few.
Cures even contributed to a rethinking of how FDA should be organized by authorizing the creation of the Oncology Center of Excellence—a center of excellence that I like to call our “catalyst” in fighting cancer—that focuses on specific diseases rather than types of products, sparking efforts to break down silos.
The past decade also saw a significant growth in the workforce of the agency staffing up from 10,000 to 18,000 people during this time period. Thanks to provisions in the Cures Act, we have important new hiring tools to bring the brightest and best to FDA so we can do more than just keep up with cutting-edge biomedical developments. These tools position us to now take a more active role in joining the external scientific community to create a collaborative environment further fostering innovation.
One thing hasn’t changed at FDA. Our standards. Our commitment to safeguard the American people is unwavering. Drugs, biologics and medical devices continue to undergo a rigorous evaluation of safety, quality, and effectiveness before they can be marketed in the U.S. And yet, by using a variety of tools for expedited development and review, we’re still outpacing other major markets for the number of and the time it takes for our approvals. In 2018, FDA approved 60 products containing new active substances compared to 40 by the European Medicines Agency, 34 by Health Canada, and 32 by the Japan Pharmaceuticals and Medical Devices Agency, according to the British-based think tank Centre for Innovation in Regulatory Science. The think tank estimates that among these regulatory authorities, FDA had the shortest median approval time – 244 days – in that same year, likely due to the wide use of such tools as Breakthrough Therapy and Fast Track designations.
In sum, the last decade has been distinguishable and worthy of celebration. But, as we enter a new decade, many complex and challenging issues remain for both FDA and for you, so let me next turn to highlighting just a few of these challenges.
One challenge that continues to confront us are high and rising drug prices, which understandably are a growing concern with patients, the medical community and FDA.
Although FDA doesn’t play a direct role in how drugs are priced, we can and do play a role indirectly, by facilitating robust and timely market competition, which, in many cases, can lead to lower prices.
Generic drugs are a good example of that. Today, they account for about 90% of all prescription drugs dispensed in the U.S. With their large market penetration and a cost that is typically 75 to 90 percent less than their brand name competitors, generic drugs have had a profound dollars and cents effect on patients and the U.S. health care system, saving the U.S. health care system about $293 billion in 2018.
But some challenges to generic development of certain products remain, such as efficiently advancing the approval of first generics and genericizing complex products, and that’s where we’ve been focusing our attention. While we expect to see fluctuations in our approval numbers from month to month based in part on what is submitted to us for assessment, in fiscal year 2019, FDA approved 1,171 generic drugs, which included 935 full approvals and 236 tentative approvals, breaking our all-time record of 971 set the year before. In this last fiscal year, we approved 125 applications for first generics of medicines with no generic competition, including drugs to treat conditions such as pulmonary arterial hypertension, breast cancer, seizures, depression and various infections.
To help product developers of these difficult to genericize complex products, we issued product specific guidance documents – 205 in fiscal year 2018 and 226 in fiscal year 2019. To give you an idea of how important these guidance documents can be, just look at the approval numbers of the 138 complex products we approved in fiscal year 2019, 95% had a published product specific guidance document.
Biologics, which represent almost 40% of all prescription drug spending, play an outsized role in rising drug prices, accounting for 70% of the growth in drug spending from 2010 to 2015. It’s been nearly 10 years since Congress established an approval pathway for biosimilar and interchangeable products in 2010. It took a while to get the pathway up and running, including writing foundational guidances to provide clarity around the biosimilars pathway and support development of these products. But the program is now showing much promise, with FDA approval of 25 biosimilar products for nine different reference products. Studies are underway to determine whether marketing of some of these approved biosimilars have had an effect on patient access.
To further encourage biosimilar product development, we’re working to reduce opportunities for gaming FDA requirements or otherwise unfairly delaying competition. We’re also working to further regulatory clarity and efficiency through guidance, scientific engagement and transparency.
Given the relative newness of biosimilars, FDA also has in place a multi-faceted plan to educate clinicians, patients and payors about biosimilar and interchangeable products through audience-appropriate, innovative educational materials, including videos, webinars and updated webpages.
At Congress’ direction, we are transitioning certain protein products such as insulin and insulin analogs, to be regulated under the Public Health Service (PHS) Act, which governs the regulation of biosimilar and interchangeable products, so that, as of March 23, 2020, they will be regulated under the PHS Act like other biologics, opening the door for the development of biosimilar and interchangeable insulin products that may be more affordable.
What that means is that some products, including products like insulin that are in great demand and have seen price hikes, may be more readily available through this new pathway and open to biosimilar competition.
This in turn can lead to the development of more affordable biosimilar insulin products, including products that are interchangeable with branded insulins, without any compromise in safety and effectiveness.
In advance of this March 2020 transition, FDA is working on building a solid scientific and regulatory foundation for the review and approval of proposed biosimilar and interchangeable insulin products. We held a public hearing to seek public input on the topic and we have been providing advice to potential applicants who are interested in pursuing a development program – and so far, there’s been quite a lot of interest in it.
Another way that FDA helps to lower drug prices is by facilitating product innovation. We seek to provide efficient, predictable and science-based oversight to help reduce the time and uncertainty of bringing new drugs and biologics to market, factors that can ultimately reduce the corresponding cost of drug development.
Thanks in part to the Cures Act, FDA is helping to encourage innovation by modernizing our science-based framework for clinical trials, encouraging more use of biomarkers and embracing flexible, transparent, and innovative approaches to regulate new categories of products including regenerative medicine. And if some of these new products provide new options for patients where there is currently little or no competition, their entry can also contribute to lowering drug prices.
Drug shortages are another challenge we continue to confront. Drug and biologic shortages can have a devastating effect on patients who may experience treatment delays, receive alternative treatments that are not as effective or well-tolerated, or may have to forgo treatment. These outcomes can prolong patient suffering, contribute to disease progression, and result in other adverse health outcomes that reduce patient well-being and increase morbidity.
In response to a congressional request, FDA convened an inter-agency Drug Shortages Task Force to study drug shortages in the U.S., prepare a report on the root causes, and make recommendations for enduring solutions. The report, released last month, found that drugs that went into shortage between calendar years 2013 – 2017 tended to be older drugs, generics, and sterile injectables. Most shortages were associated with a manufacturing or product quality problem. Unlike more typical markets, the prices of the drugs in shortage often do not rise significantly after a supply disruption so there is little incentive for drug manufacturers to increase production to a level that meets demand.
The report recommended three enduring solutions. First, creating a shared understanding of the impact of drug shortages on patients and the contracting practices that may contribute to shortages; developing a rating system to incentivize drug manufacturers to invest in quality management maturity for their facilities; and promoting sustainable private sector contracts to make sure there is a reliable supply of medically important drugs.
Antimicrobial Resistance and the One Health Initiative
I also want to highlight a public health concern that we should all take extremely seriously: antimicrobial resistance. Every year, at least two million Americans are sickened by serious infections caused by antimicrobial-resistant pathogens, such as MRSA. And at least 23,000 people die as a direct result of these infections.
Although bacteria may naturally develop resistance to antimicrobials, usually through genetic changes, the misuse and overuse of both human and animal antimicrobials is accelerating this process.
Unfortunately, public concern over antimicrobial resistance has not spurred an increase in the number of new antimicrobials in part because of challenging market conditions that do not provide an adequate return on investment. We have a few tools at our disposal to help foster new product development. One is to designate a drug as a Qualified Infectious Disease Product, or QIDP, if we get a request for designation from the drug’s sponsor before the submission of an application. If designated as a QIDP, the drug may be eligible for priority review, fast track designation, and may qualify for a 5-year extension of its exclusivity. Since the program was created in 2012, we’ve approved 18 QIDP designated drugs. But we continue to consider and explore whether there are potential changes to the Generating Antibiotic Incentives Now or GAIN, passed in 2012 as part of the Food and Drug Administration Safety and Innovation Act (FDASIA), which authorized QIDP, that could better focus the program to promote the development of novel antibacterial and antifungal drugs.
We now have another tool thanks to the Cures Act, the Limited Population Pathway for Antibacterial and Antifungal Drugs or the LPAD Pathway, to advance development and approval of antibacterial and antifungal drugs to treat serious or life-threatening infections in a limited population of patients with unmet needs. Approval under the LPAD pathway may be supported by a streamlined clinical development program that may involve smaller, shorter or fewer clinical trials. To inform healthcare providers, the product’s labeling must clearly state that the drug has been shown to be safe and effective only for use in a limited population. So far, two anti-bacterial drugs have utilized this new pathway. The latest LPAD pathway approval was in August for a drug to treat a highly treatment resistant form of tuberculosis. To further implement the program, we issued a draft guidance in June 2018 and held a public meeting this past July and are pleased to report we’re receiving meaningful early interest from innovators.
Another way to combat antimicrobial resistance is to prevent the overuse of antibiotics in animals. Until recently, medically important antimicrobials could be used in the feed or drinking water of food-producing animals not only to protect against disease in those animals but also to promote growth, which increased the risk that resistant bacteria could be transferred to humans, potentially making these drugs less effective to treat human disease. FDA is promoting the judicious use of antimicrobials in food-producing animals. As the result of the successful implementation of a strategy developed by FDA that relied on collaboration between the agency and stakeholders, medically-important antimicrobial use in the feed and drinking water of food-producing animals has been brought under veterinary oversight and such drugs may no longer be used in healthy animals for food production purposes.
The judicious use of antibiotics in animals is part of our broader thinking known as the One Health Initiative, which views the health of people, animals, and the environment as intertwined. By building bridges between physicians, veterinarians, environmental scientists, and public health professionals, the initiative aims to promote, improve, and defend the health and well-being of all species. For instance, under this way of thinking, our Center for Veterinary Medicine evaluates whether a new animal drug application is not only safe and effective for the animal itself but what its impact might be on people who are giving the drug, are in contact with the animals, or consume food derived from the animal, as well as consider how the environment may be affected by the use of that animal drug.
And now I’d like to turn to a topic that is of critical importance: FDA’s leadership in preparing for and responding to public health threats. Through its Medical Countermeasures Initiative, FDA plays a critical role in supporting industry and U.S. Government partners to advance development of safe and effective drugs, vaccines and devices, including diagnostic tests, for a variety of chemical, biological, radiological, and nuclear threats, including emerging infectious diseases such as pandemic influenza and Ebola.
In the last year alone, FDA approved 28 medical countermeasures, including the first drug with an indication to treat smallpox, an auto-injector for chemical nerve agent preparedness, three tests to detect Zika virus IgM antibodies, and the first rapid diagnostic test to detect Ebola virus antigens. In addition, this past year, through enhanced engagements with the Department of Defense, FDA has helped to make available a variety of life-saving products to address military-specific needs. And our scientists have made important progress toward achieving a universal vaccine for influenza. FDA’s commitment to providing clear development pathways, frequent and consistent stakeholder engagements far exceeding “PDUFA” commitments, and investments in the science and tools needed to make regulatory decisions and address regulatory challenges are what have made these achievements possible.
FDA has also been a leader in global health security and international response efforts. For example, FDA is a critical response partner working to end the ongoing Ebola outbreak in the Democratic Republic of the Congo – which has killed thousands. Currently, although there are no FDA-approved vaccines or drugs to prevent or treat Ebola, FDA continues to support sponsors who are seeking FDA approval of certain investigational medical products and significant progress is being made. We are working closely with U.S. Government partners, medical product developers, the World Health Organization, and international regulatory counterparts to ensure access to the most promising candidates.
And, on the diagnostic front, FDA has authorized a number of diagnostic tests to detect Ebola for emergency use. Currently, there are ten Ebola diagnostic tests available for emergency use under FDA’s Emergency Use Authorization (EUA) authority – one rapid antigen test and nine molecular tests. Just last month, we approved the first rapid diagnostic test to detect Ebola virus antigens in certain specimens. The test is important because one of the most important tools in stopping these outbreaks is quickly diagnosing patients and supporting safe and dignified burials.
In the coming weeks, World AIDS Day will be observed, and so I’d also like to highlight some of our work to combat HIV and AIDS. Thanks to the power of groundbreaking medical research and the dedication of many, we have shifted the prognosis for HIV to a manageable illness. Despite our progress on HIV/AIDs approximately 1.1 million people in the U.S. live with HIV today and about 1 out of every seven of these people don’t know they are infected with the virus. After about 5 years of substantial declines, the number of annual HIV infections began to level off in 2013, to about 39,000 infections per year. The President’s plan for Ending the HIV Epidemic seeks to provide the hardest hit communities with the additional expertise, technology and resources required to address the epidemic in their communities.
FDA’s role is to help spur the development of effective treatments, more accurate diagnostic tests, reliable blood donor screening and rigorous public education programs.
Since the start of the HIV epidemic, FDA has approved 29 anti-retroviral drugs, including the first monoclonal antibody. FDA experts are also reviewing and providing drug development advice on new formulations such as injectables and implants. And FDA has also been at the forefront of HIV prevention. Last month we approved the second pre-exposure prophylaxis drug intended for certain adults who are not HIV-infected, but at high risk of infection, and we are supporting scientific investigation of vaccines that would protect people from HIV infection.
FDA also plays an important role in the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), launched in 2003 to address the global HIV/AIDS epidemic by stimulating the development of new HIV therapies, including new combinations of existing branded medicines, to be purchased with American funds at low cost and made available in countries that lacked good access to treatment.
Under PEPFAR, FDA encourages sponsors worldwide to submit U.S. marketing applications for single entity, fixed-dose combination and co-packaged versions of previously approved antiretroviral therapies. To cut down review time, FDA uses its expedited review process for PEPFAR drugs. FDA issues Tentative Approvals for drugs that would otherwise receive Final Approval but for the existence of a patent and/or exclusivity. Drugs under the PEPFAR program receiving FDA Tentative Approval are not eligible for marketing in the U.S., but they can be marketed outside the U.S. and money from the PEPFAR program can be used to procure them. Since PEPFAR began, FDA has approved or tentatively approved 222 antiretroviral applications.
Despite all of these previous efforts, we’re not letting up in our efforts on this critical public health front. Last year, FDA initiated a pilot program to provide the World Health Organization (WHO) with minimally-redacted reviews of two tentatively or fully approved ARV drugs. The WHO in turn may be able to use this information to expedite its own drug review and the dossier can in turn be shared with countries participating in the WHO’s Collaborative Registration Procedure or CRP, set up to help resource-constrained countries review drugs faster for their own market. The goal of these efforts is to combat the global HIV/AIDS epidemic by helping patients around the world in need of medicines get them sooner.
Global Policy and Strategy
PEPFAR is a reminder that there is an important international component to what FDA does every day. After all, there are over 134,000 foreign facilities exporting FDA-regulated products to the United States every year, about 72 percent of active pharmaceutical ingredients manufacturers are located outside of the U.S.; 70 percent of biologics sales are imports and about 35 percent of medical devices used in this this country come from abroad.
Many of these products are entering from developing countries, emerging markets or via multinational supply chains.
FDA has responded to the complexity of these global product trends by maintaining offices in important markets in China, India, Europe and Latin America. Our staff there collect information, conduct inspections and seek to build strong coalitions and partnerships with regulatory authorities, industry, academia, multilateral organizations, non-governmental organizations, and other relevant institutions to share information about FDA science-based regulations and requirements and, in certain cases, to help the country strengthen their own regulatory systems.
Medical product development is a global enterprise, and FDA is actively pursuing innovative opportunities for international collaboration. FDA’s leadership in response to global health threats such as Ebola is an obvious example. A new and less known example is Project Orbis, a framework for concurrent submission and review of oncology products known as Project Orbis. Developed by Dr. Richard Pazdur, Director of the FDA’s Oncology Center of Excellence, Project Orbis brings international regulatory agencies together in order to reduce delays in regulatory submissions and improve timely access to cancer products across the globe. Dr. Pazdur and other FDA colleagues, including colleagues from our Office of Global Policy and Strategy, worked with Health Canada and the Australian Therapeutic Goods Administration on a collaborative review of supplemental applications for a combination treatment for certain patients with advanced endometrial cancer. Under Project Orbis, FDA was able to facilitate simultaneous regulatory decisions across the three international agencies, increasing global access to this medicine, encouraging innovation and raising the overall standard of care globally. The project was so successful that it could be a model going forward.
Nutrition Innovation Strategy
So far, I’ve talked a lot about treatments and cures. But medical products alone won’t promote public health. More than 20% of all deaths in the United States in 2015 were attributable in part to a poor diet. So here is an opportunity to improve life for so many people.
FDA already does significant work in strengthening nutrition and working to improve the public’s health, through our efforts in nutrition labeling and in creating a healthier food supply. We’re building on this important work with our comprehensive, multi-year Nutrition Innovation Strategy, which seeks to reduce preventable death and disease caused by poor nutrition by ensuring that consumers have access to accurate information to support healthy food choices and by fostering the development of healthier foods. By putting calories on the menu, modernizing claims, and implementing the first major update to the Nutrition Facts label in over two decades, we’re empowering consumers with information to make healthy food choices. And we are close to proposing a new definition for the “Healthy” claim on food labels and have been working diligently on the claim “Natural.”
Another way we are seeking to reduce preventable death and disease related to poor nutrition is by encouraging industry to innovate to produce healthier foods that consumers want. FDA is continuing to move forward on short-term sodium reduction targets for various food categories to foster a healthier food supply. FDA is also exploring how to modernize our standards of identity which are like recipes for what must be in the food – or not in the food. We know that many standards were established decades ago and have not been recently amended to reflect changes in consumer expectations or opportunities for innovation – including the ability to produce healthier foods. For instance, some companies might want to use a salt substitute for part of the sodium chloride in a standardized food to promote sodium reduction. We had a public meeting on modernizing standards of identity just a few weeks ago, and this will continue to be an important area of work as we look to advance modern approaches to our consumer-focused public health mission.
To conclude, I will return to what I said at the outset of my remarks—patients and consumers are at the heart of what FDA does every day to protect and promote public health, impacting and improving the lives of the American people in so many diverse and critical ways. FDA is responsible for overseeing a wide range of products that account for 20 cents of every dollar spent by U.S. consumers. That’s a big responsibility. We can’t assume it alone. It is clear that we must continue to build on our current efforts and collaborate with our many stakeholders to advance our vital public health mission. We look forward to your continued support of and partnership in this endeavor. You’re the ones who put your companies on the line for product discovery and development, you’re the ones who market to healthcare providers and consumers. Ten years from now, a celebration of life event will depend very much on all of you. Thank you for what you do on behalf of consumers and patients.