- Speech by
Remarks by Anna Abram
Deputy Commissioner for Policy, Planning, Legislation and Analysis
The Galien Forum
New York, New York
Thank you, Susan and thank you to The Galien Forum for inviting me to speak today. It is an honor to be asked to participate in this day-long discussion on what is being done to address some of our nation’s greatest health challenges.
Very clearly FDA has an important seat at the table as patients, scientists, health care providers, payers, and industry grapple with the scientific and policy issues surrounding opioid addiction, drug pricing, clinical trial modernization, and leveraging cutting-edge tools and processes. In fact, all four issues are high priority areas for FDA Commissioner Scott Gottlieb.
Twenty years ago, Susan was the chief medical officer at Genentech when FDA approved the company’s monoclonal antibody, Herceptin, for the treatment of HER2 positive metastatic breast cancers. On the same day, FDA approved a test to detect HER2 protein overexpression in breast cancer cells. It marked the dawn of a new era of cancer treatment and the beginning of what many hoped would be an exciting trend toward co-development of molecularly-targeted therapies with tests that could identify the right therapies for the right patients. FDA responded to this new era by quickly moving to build and shape a regulatory framework that would help usher in the emergence of tailored medical products.
Today, the intense amount of discovery and translation going on around the human genome and gene therapy and other areas of medicine are providing new ways to address human disease. But just as FDA was challenged at the dawn of personalized or precision medicine, we are challenged again to continue to modernize our approach to evaluating innovations -or more simply stated, to keep up. This has meant, in many cases, creating new approaches that are better suited to the efficient evaluation of these advances without compromising FDA’s science-based standards.
Today I’d like to tell you what steps we’re taking to stay ahead amidst so much biomedical innovation, in particular, by ensuring a world-class workforce, collaborating across the Agency and updating some of our regulatory approaches.
FDA relies on having a world-class scientific staff to evaluate innovative medical products and keep up with ever-changing technologies. And while our world-class facilities are certainly a draw, staffing has been a challenge for FDA, especially in those disciplines where there is already a short supply of experts and stiff competition from the private sector. FDA currently has a workforce of more than 18,000 people and of those, 10,000 were hired in the past decade. Yet, we’re still striving to catch up and to make our hiring processes more efficient. Too many of the positions supported by user fees remain vacant, even while our overall attrition rate is about 5 percent annually.
The FDA Reauthorization Act of 2017, or FDARA, which reauthorized our human drug, device, and biologics medical product user fee programs, included an FDA commitment to complete the modernization of the hiring infrastructure and other enhancements. Dr. Gottlieb’s first step in meeting these commitments was to order a comprehensive baseline assessment of our hiring process. The report was issued about a year ago. It found that only 31% of hiring managers in our drugs and biologics centers were satisfied with the quality of their new hires. Moreover, both our Center for Biologics and Center for Drugs had vacancy rates of about 14 percent – about double what is common for other government agencies - and the end-to-end hiring process took from 150 to 550 days.
We have several initiatives underway to address these challenges. We launched a hiring pilot to test a totally redesigned end-to-end hiring process that has already shown results in reducing the total time to hire by 50% and is setting a new gold standard for FDA hiring practices.
Second, we hired an associate director for our Scientific Staffing Team who has a background in both regulatory science and recruitment and outreach. The Team represents the agency at scientific conferences and is forging strategic relationships with academic institutions and professional associations to bring in promising young scientists. Third, we stood up another hiring team focused on physician hiring. It has already succeeded in reducing the time to hire physicians by 80%. And we are taking steps to showcase FDA as an employer of choice for workers in the Washington metro area.
The new pay authority under the 21st Century Cures Act, which allows FDA to bring on top candidates at competitive salaries, is also helping. Of the Cures hires we have made to date, 50% of the new hires stated they would not have been able to come to the FDA for lower pay – an excellent metric for this new hiring and pay authority.
Another way we’re laying the groundwork for success is to rethink how we are organized. No one person and no one office could possibly stay abreast of today’s biomedical advances or address the complexity of today’s many health challenges. Creating environments that enhance collaboration, teamwork, and knowledge-sharing are the keys to success.
FDA has a history of fruitful collaboration with a wide variety of medical and scientific organizations including those in biomedical research, the drug, biologics and medical device industries, academia, global organizations, as well as patients and their advocacy groups. We also collaborate internally with cross-agency groups such as our Senior Science Council, our Nanotechnology Task Force, and our Emerging Science Work Group, the latter of which is tasked with horizon scanning for new technology.
Now we’re breaking down siloes on a more operational basis. We’re changing how we organize ourselves as part of the medical product review process and moving away from a structure that had people working in discrete organizational units that often operated as independent entities rather than as an integrated team that functioned together to share best practices and knowledge. Instead, we’re evolving toward a more team-based approach that integrates people from different disciplines and across different states of a product’s lifecycle.
Our efforts began over a year ago when FDA launched its Oncology Center of Excellence (or OCE) to leverage the combined skills of regulatory scientists and reviewers with expertise in drugs, biologics, and devices (including diagnostics). Authorized by the 21st Century Cures Act, OCE is FDA’s first inter-center institute that focuses on a specific disease area rather than type of product. And its interdisciplinary work is already yielding significant advances. Last May, FDA approved for adult and pediatric patients the first cancer treatment based on a tumor’s biomarker rather than the tumor’s site or cell type. Testing was permitted using a single therapeutic approach for patients with different tumor types rather than requiring separate development programs for each disease site.
The lessons we have learned from creating and operationalizing OCE will be applied elsewhere within FDA. Our goal is to be more disease-focused and more integrated across the disciplines involved in drug review and better able to evaluate and analyze data. Our Center for Drug Evaluation and Research is currently planning to reorganize its Office of New Drugs in this way.
And organizational changes are also afoot at the Center for Devices and Radiological Health where we’re combining the Office of Compliance, Office of Device Evaluation, Office of Surveillance and Biometrics, and Office of In Vitro Diagnostics and Radiological Health into a new Office of Product Evaluation and Quality (OPEQ). OPEQ will be a Total Product Life Cycle, or TPLC, Office. TPLC reflects a holistic approach that takes into account all of the information and programs CDRH is responsible for, which impact the design, production, and use of medical devices and electronic products. The new configuration will eventually comprise seven different Offices of Health Technology which will be responsible for pre-market review, post-market surveillance and manufacturing quality and compliance to ensure patients have access to safe, effective and high-quality technology. There will also be offices dedicated to the medical device clinical evidence programs, and another dedicated to the medical device regulatory programs implemented within CDRH.
Finally, there’s one other important way in which we’re poised for success by being flexible, transparent and creative in our regulatory approaches, while upholding FDA’s “gold standards.” This means taking advantage of innovative approaches that are better suited to the efficient evaluation of new technology but to do so without comprising FDA’s science-based and regulatory standards. A prime example is our approach to cell-based regenerative medicine.
Last November, FDA released a comprehensive policy framework for the oversight of regenerative medicine products that include cell therapies, therapeutic tissue engineering products, human cell and tissue products, and combination products using any such therapies or products, as well as gene therapies that lead to a durable modification of cells or tissues (including genetically-modified cells). The framework includes two final and two draft guidance documents that, among other things, more clearly describe the distinction between products that require premarket authorization and those that do not. We’ve recently followed that up by issuing a complementary policy framework for the development review and approval of gene therapies. The suite of six scientific guidance documents we issued in July are intended to serve as the building blocks of a modern, comprehensive framework for this new field. Peter Marks, director of our Center for Biologics Evaluation and Research will have more to say when he speaks to you this afternoon.
Flexibility also marks our approach to the regulatory framework we’ve adopted for genomic and genetic testing using next generation sequencing. We issued final guidance in April that explains how test developers may rely on clinical evidence from FDA-recognized public databases to support clinical claims while providing assurance of the accurate clinical evaluation of the test results. A second guidance provided recommendations on the design, development and analytical validation of these tests.
To the extent that the FDA can ensure that our regulatory requirements are streamlined, predictable, and science-based, we can help reduce the time, uncertainty, and cost of medical product development, and that includes the development of branded drugs as well as generic and biosimilar alternatives.
The high price of prescription drugs has certainly been one of the most controversial issues confronting the biopharmaceutical industry in recent years. Drug pricing is a major concern for the public and for the Administration. The fact is, new medical innovations will not benefit patients and consumers if people cannot afford to access these innovations. To further encourage drug competition and help bring greater efficiency and transparency to the generic drug approval process, we launched the Drug Competition Action Plan last year. This includes further streamlining the generic drug review process to increase efficiency and effectiveness with the ultimate goal of more approvals; reducing the so-called “gaming” that frustrates and delays generic drug approvals and extends brand monopolies beyond what Congress intended with the Hatch-Waxman Amendments of 1984; and supporting the development and enhanced review of complex generic drug products to make it easier for companies to bring generic competition to this important category of branded drugs.
Being able to “genericize” a complex drug can be a high-value opportunity for a generic drug developer. These higher-value generic business opportunities can help underwrite the costs of other generic applications at a time when we believe the generic industry is facing new economic pressures from rising costs, supply chain consolidation, increased competition and declining reimbursement on many generic medicines. Moreover, because brand-name versions of complex drug products are often higher-priced than many other brand name drugs, any steps we can take to encourage the development of generic competitors for complex drugs may have an outsized impact on access, and drug spending.
Achieving a competitive marketplace for therapeutic biological products is equally crucial and, in fact, is becoming more important every day. Biologics are used to treat many serious illnesses, including rare genetic disorders, autoimmune disease and cancer and they often offer the only effective or available treatment option. They currently account for about a third of new drugs approved by the FDA but represent almost 40 percent of all prescription drug spending and account for 70 percent of the growth in drug spending from 2010 to 2015, according to a Rand study.
The FDA has approved 12 biosimilars, including two biosimilars for cancer, including a biosimilar to Herceptin, and interest remains high in these products with nearly 60 development programs enrolled in FDA’s Biosimilar Biological Product Development Program. While that’s good news, so far, only a fraction of the biosimilars approved have gone to market due in part to obstacles in the marketplace.
To accelerate biosimilar competition, Dr. Gottlieb launched a four-part Biosimilars Action Plan in July to enhance regulatory predictability and encourage market understanding. It focuses on achieving greater review efficiencies, providing more regulatory clarity through guidance, reducing gaming intended to unfairly delay market competition, and developing educational materials that will address knowledge gaps about these products.
To further reduce the cost of drug development and potentially lower drug costs, FDA is working across our medical product centers to make clinical trials more efficient, by facilitating innovative trial designs and patient-centered endpoints.
For example, we’re encouraging the use of master clinical trial protocols, such as basket, umbrella and platform trials, which involve a common clinical trial infrastructure to study one or more interventions in multiple diseases or a single disease with multiple interventions, each targeting a biomarker-defined population or disease subtype. Seamless trial designs are being used in oncology that compress the traditional trial phases into one large, continuous trial. Such approaches may be able to reduce the number of patients needed for clinical development and the time it takes to complete necessary studies—thus reducing costs, while also enabling investigators to learn more about a product’s efficacy and safety and help regulators and sponsors detect efficacy and safety signals earlier in the development process.
FDA is also exploring the development of predictive models based on natural history data, which may be able to obviate the need for placebo arms in some clinical trials for rare diseases by allowing researchers to estimate what a subject’s outcome would have been if they had not received an experimental therapy. And we’re encouraging more widespread use of modeling and simulation in both new and generic drug product development that can be used to organize diverse data sets, explore alternate study design strategies, and predict performance.
Clinical trials are often conducted in specialized and controlled research settings and can still leave critical questions unanswered, particularly about the effects of a medical product after it is used by a broader population over an extended period. Over the past decade, FDA has begun to harness real world data to help us answer some of these questions. Our work with the Sentinel System was initially focused on postmarket surveillance but FDA is actively evaluating the potential uses of real-world evidence to support pre-market regulatory decisions. And FDA’s Center for Devices and Radiological Health recently issued guidance that provides recommendations that will enable clinical investigators to understand how FDA will evaluate data collected from routine medical care and how FDA will determine whether the collected evidence is appropriate to support regulatory decision making.
Finally, a word on opioid addiction since you’ll be discussing that topic today. The FDA has taken significant steps across the life cycle of these drugs to reduce the risk of opioid addiction and death, including requiring generic and branded sponsors of extended-release and long-acting opioids to make education available to prescribers. And for the first time, this requirement is being expanded to include immediate-release formulations as well. We’re also using our existing drug safety surveillance resources to explore how we can create benchmarks for more rational opioid prescribing through product labeling or REMS. Together, with the application of modern tools, we believe it’s possible to work with prescribers to create rational opioid prescribing standards for acute pain that can lower the risk of opioid addiction and drug diversion, while keeping these powerful medicines available for patients with severe pain such as from metastatic cancer.
We’re also doing what we can to encourage the development of opioids that are harder to manipulate and abuse. While not abuse-proof, these formulations can make certain types of abuse, such as crushing a tablet to snort or dissolving a capsule to inject more difficult or less rewarding. Several abuse-deterrent products have been approved, but they are only available as more expensive, brand-name products, many of which are not covered by payors. Last year we issued a final guidance to assist industry in the development of generic versions of approved abuse-deterrent formulations and in July we posted three revised product-specific guidances.
The drug naloxone is a potentially life-saving treatment that can reverse the effects of an opioid overdose, usually within minutes, if quickly administered. Although naloxone is a critical tool that individuals, families, first responders and communities can use to help reduce opioid overdose deaths, there is still a need to improve access to this drug. Earlier this week FDA announced an upcoming advisory committee meeting to solicit input and advice on strategies to increase the availability of naloxone products. One of the issues to be discussed at the two-day meeting in December is whether naloxone should be co-prescribed with all or some opioid prescriptions to help reduce the risk of an overdose.
As you will hear at today’s conference, there are any number of novel approaches under development to treat disease from cancer therapies to the human microbiome as well as novel policy approaches to our most challenging public health problems like opioid addiction. This is truly an exciting time in science and medicine, with increasing insights and advances that hold tremendous potential and promise to improve the health and well-being for so many. FDA must be as modern as the cutting-edge innovations we are responsible for regulating, ensuring our frameworks and processes are streamlined, predictable, and science-based. We are actively taking steps to advance modern and efficient regulatory frameworks built on strong infrastructure, staffing, collaborations and cutting-edge science.