FDA’s New Acting Commissioner: What is In Store for the Agency?By
Norman Sharpless, MD, became Acting Commissioner of Food and Drugs for the US Food and Drug Administration (FDA) in early April after taking the helm from FDA Commissioner Scott Gottlieb, who stepped down for personal reasons. With a new executive in, what are the key policy directions for the FDA?
Word from Acting Commissioner: stay the course
Sharpless takes on the post as Acting Commissioner from the National Institutes of Health’s National Cancer Institute (NCI), where he served as its Director beginning in October 2017. Prior to his NCI appointment, Sharpless served as the Director of the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center, having previously served as a faculty member of the UNC School of Medicine in the Departments of Medicine and Genetics and as the Wellcome Professor of Cancer Research at UNC. He spoke at the Food and Drug Law Institute’s (FDLI) Annual Conference earlier this month (May 2, 2019) in Washington, DC, a forum in which the FDA Commissioner traditionally speaks, and which Sharpless said provided him “an opportunity to reflect on the agency’s accomplishments over the past year and to chart our path moving forward.”
In short, Sharpless said that he planned to continue the policy direction advanced by former FDA Commissioner Scott Gottlieb under his tenure. “Let me say [from] the outset that I don’t anticipate extraordinary departures from the FDA’s recent priorities and course of action…Secretary Azar [US Health and Human Services Secretary Alex Azar] and the White House made it very clear to me that they have been impressed with the things that FDA has been accomplishing and they don’t want to disrupt this strong progress. There will be no pause at FDA. So we’ll continue to focus on innovation and efficiency in order to bring more new medical products more quickly to the public and to ensure that FDA’s processes are as modern, efficient, and risk-based as possible across the Agency. We want to continue to encourage the regulatory certainty, flexibility, and transparency that allows industry to innovate and the public and stakeholders to get what they need.”
Product innovation: Under Gottlieb’s tenure as FDA Commissoner, the FDA approved a record number of new molecular entities (NMEs) in 2018, eclipsing the previous record of 53 set in 1996 and the 46 NMEs approved in 2017, which had been a recent high. In his remarks at the FDLI conference, Sharpless emphasized the agency’s commitment to product innovation, including the use of the agency’s expedited approval tools, such as fast-track, breakthrough therapy, accelerated approval, and priority review designations, which were involved in 73% of the novel drug approvals by the FDA’s Center for Drug Evaluation and Research (CDER) in 2018.
Generics and biosimilars: Sharpless also emphasized the agency’s commitment to cornerstone policy initiatives under Gottlieb: the Drug Competition Action Plan, a plan to address the cost of prescription drugs by increasing drug competition by improving the process for generic-drug development, review, and approval, and the Biosimilars Action Plan, a plan designed to accelerate biosimilar competition…”[W]e had a very strong year in our work to increase competition and to help reign in prescription drug costs through advances in our generic drug and biosimilars programs,” said Sharpless in his comments. “This past fiscal year we set an all-time record of 971 full and tentative approval actions for generic drugs, including 95 first-time generic drugs. Importantly, this list includes several competitive generic therapy designations, developed to improve access and foster competition for drugs that face inadequate competition. Likewise, many of the generic approvals were of complex generics, which can involve special challenges in ‘genericizing’ and which may need additional support for their development…We launched our Biosimilars Action Plan to accelerate biosimilar competition. This plan is beginning to work: last year, we approved a record number of biosimilar products, meaning patients can receive the treatments they need while the market benefits from increased competition and ultimately lower costs.”
Drug shortages: Sharpless also stressed the continued importance of the FDA’s role in preventing drug shortages. The industry reached an inflection point in drug shortages in 2011, when the number of drug shortages, particularly generic sterile injectable drugs, rose, causing the federal government to take action to better oversee and monitor potential drug shortages. In 2011, the FDA reported 251 drug shortages in the US, of which 183, or 73%, were for injectable drugs. In July 2012, President Barack Obama signed into law the Food and Drug Administration Safety and Innovation Act (FDASIA), which provided the FDA with new authorities to help the agency combat drug shortages, including reporting requirements for manufacturers to report information about shortages to the FDA, the reasons for the shortages, and the expected duration of those shortages. FDASIA also required the FDA to establish a task force on drug shortages that is responsible for developing and submitting to Congress a strategic plan to enhance the FDA’s response to preventing and mitigating drug shortages. Continuing with its policy goal of limiting the number of drug shortages, the FDA formed last year (July 2018) a new Drug Shortages Task Force, led by Keagan Lenihan, the FDA’s Associate Commissioner for Strategic Initiatives. The task force is charged to delve into why some drug shortages remain a persistent challenge and to look for solutions to addressing the underlying causes for these shortages.
“We also have worked to limit shortages of medically necessary medications,” said Sharpless in his comments before the FDLI conference. “Last year, we successfully worked with manufacturers to prevent 160 drug shortages and identified only 54 new shortages. That’s about one fifth of the peak shortage year of 2011.”
Opioid crisis: Sharpless also addressed challenges for the FDA, most notably the ongoing opioid crisis. “This is one of the most troubling public health crises our nation has faced, causing widespread tragedy to families and undermining communities,” he said. “FDA has an important role to play in combatting the opioid crisis, both individually and in collaboration with other federal and state agencies.”
With respect to the pharmaceutical industry, he emphasized that the agency is continuing its work to support the development of drugs to treat pain that are not addictive or are abuse-deterrent. “We are planning updated guidance outlining the appropriate clinical endpoints and clinical trial approaches for the development of non-opioid drugs for use in the treatment of acute and chronic pain. And we’ll also be exploring new methods for analyzing and evaluating abuse-deterrent features,” he said.
He also emphasized how the FDA will address the opioid issue through other means, such as new packaging requirements. “Congress’s passage last year of the bipartisan Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities Act, (or the SUPPORT Act), authorized FDA to more forcefully address the opioid problem in several ways. To give you just one example, the law allows FDA to require certain packaging configurations, including short-duration packaging for outpatient dispensing. Our research suggests that for many acute pain indications where opioids are used, just a day or two of these drugs is appropriate. We’re considering whether to mandate that certain oral forms of immediate-release opioid formulations be made available in small quantities in blister packaging. You’ll be hearing more about this in the near future.”
Regulation of new modalities: Sharpless also addressed how the FDA facilitates the development of new modalities, such as gene and cell therapies, which are regulated through FDA’s Center for Biologics Evaluation and Research (CBER). “We received over 200 gene therapy INDs [investigational new drug applications] last year. Our goal is to support this work and advance the field while being transparent about our expectations. As a result, we issued numerous guidance documents with more on the way,” he said.
”The second area of CBER where we’re seeing an extraordinary pace of progress is in the development of cellular therapies and, especially, stem cell products,” he said. “We’re doing everything we can to support this growing industry. But even as we do so, we want to maintain our focus on compliance and enforcement. We won’t tolerate dangerous stem cell clinics who make dubious or unproven claims that their cellular products will treat age-related or other serious or life-threatening conditions.”
New review process for NDAs and BLAs
Aside from overarching policy initiatives, a large initiative at CDER, and outlined by CDER’s Director, Janet Woodcock at the FDLI conference, is a modernization of the FDA’s review process for new drug applications (NDAs) and biologic license applications (BLAs). That plan will be instituted over the next two years and involves six main goals:
- advancing scientific leadership to further involve academic medical scientists and patient/disease advocates, evaluate scientific gaps, and strategically foster drug development;
- achieving a more integrated, cross-disciplinary approach within the agency for drug assessments and reviews;
- having a unified post-market safety surveillance framework for benefit–risk monitoring across the product lifecycle;
- managing talent with authority provided by the FDA from the 21st Century Cures Act authorities to recruit and retain technical, scientific and professional experts and eliminate the FDA’s backlog of vacant positions;
- improving operational excellence by addressing CDER’s Office of New Drugs’ large-volume workload through greater process standardization and better-defined roles and responsibilities to enable the agency’s scientists to focus on science, not ancillary tasks; and
- facilitate knowledge management to increase the speed and efficiency of submission assessment, and increase the consistency and predictability of regulatory decision-making.
To achieve these goals, CDER is working on six main initiatives:
- integrated review for marketing applications by developing a streamlined interdisciplinary review process and template to support the new integrated review for assessing NDA/BLAs;
- IND review management by streamlining the IND scientific review processes for managing IND applications, beginning with 30-day safety reviews and protocols;
- post-market safety management by creating a standardized, consistent, and effective approach to post-market drug safety;
- assessing talent by developing an effective and consistent process for hiring, onboarding, developing and evaluating new clinical and pharmacological/toxicological reviewers;
- reorganization and transition management through the planning, coordinating, and implementing modernization and organization changes at the future Office and Division levels across the New Drugs Program; and
- administrative operations with a focus to optimize administrative and clerical staff roles, structure, and functions to enhance customer focus and employee engagement.