FDA Proposes Sweeping Drug Development Changes

FDA Commissioner Scott Gottlieb, MD

FDA Commissioner Scott Gottlieb, MD

In an effort to promote the most promising opportunities and to address complex drug development issues, U.S. Food and Drug Administration (FDA) Commissioner Scott Gottlieb, MD, this week introduced several “fundamental advances” regarding how the agency evaluates drugs for safety and effectiveness, as well as the manner in which clinical trials are guided.

“These include adaptive approaches to clinical development such as the introduction of seamless trial designs or master protocols or tissue agnostic product approvals,” Gottlieb said in a June 4 statement. “Each allow us to better marry the scientific prospect more closely to the approaches that can best unlock these opportunities.”

As Gottlieb explained, “this includes the more widespread use of modeling and simulation, the greater use of real-world evidence in the pre- and post-market setting, and the adoption of better tools for collecting and evaluating more real-time safety information after products are approved.”

While some of the changes can be achieved internally at FDA, others “are going to be achieved through more modern and scientifically rigorous approaches to how we collect and evaluate clinical data as part of the drug development process,” Gottlieb noted.

To advance these public health goals, Center for Drug Evaluation and Research (CDER) Director Dr. Janet Woodcock has proposed to her center an important series of new steps to modernize the organization and functions of CDER’s Office of New Drugs.

Woodcock outlined some key components of FDA’s proposed new direction:

  • Recruiting the best and brightest individuals from many disciplines – Scientific leadership is vital for FDA’s ongoing success. After hiring talented scientists, “we need to develop long-term career paths for them, so they can become our next generation of seasoned leaders,” she said. FDA recruitment efforts, strengthened by hiring incentives and other provisions in a new law called the 21st Century Cures Act, will help provide the staffing necessary for continued success in supporting the development and approval of innovative new therapies that meet previously unmet medical needs.
  • Enhancing FDA’s focus on multidisciplinary teams – Setting standards for approval and assessing innovative new drugs requires large and well-coordinated teams of highly trained professionals with many different types of expertise. CDER’s Office of New Drugs (OND) has a staff of more than 1,000 individuals who work together in many ways. New drug development and approval also requires coordination across many offices within CDER, including the Office of Translational Sciences (OTS), the Office of Surveillance and Epidemiology (OSE), and the Office of Pharmaceutical Quality (OPQ). A central component of our proposed changes involves stronger integration of staff so they can better work together—within and across offices, a concept we refer to as “integrated assessment.” Previously, CDER reviewers would seek consults from specialists in other scientific disciplines (as issues were identified in the course of review). For greater collaboration, a cross-disciplinary team will be assigned to work on a new drug application at the outset.
  • Prioritizing operational excellence – Staff throughout CDER face a “staggering pace” of work, much of which involves attention to detailed administrative procedures. FDA’s new proposal would centralize project management functions within OND. CDER currently has 19 separate review divisions that regulate drugs. Over time, many divisions have developed procedures specific to their areas of review. We are proposing a single and consistent process: One organization with one process. “Our aim is to enable our scientific and clinical experts to focus on what they know best—science and medicine—and our regulatory experts to manage the many processes we conduct.”
  • Improving knowledge management – “The information we process in our work is vast and diverse,” Woodcock said. Knowledge management is essential to control the data the agency receives from outside sources as well as what we generate from within the FDA. The agency plans to enhance [information technology] capabilities and access to information to better enable the storage and management of the collected experience of scientific review staff. Accurate historic information from many past drug reviews is essential to informing current and future reviews—and to assure consistent regulatory decision-making. “In addition to enabling greater efficiency, these envisioned changes will help us to better understand the diseases intended to be treated by the drugs we evaluate for approval—another way we aim to enhance our knowledge management,” Woodcock said.
  • Emphasizing the importance of safety across a drug’s lifecycle – Safety remains a key component of FDA’s new plans. The agency promised to work to establish a unified post-market safety surveillance framework to monitor the benefits and risks of drugs across their lifecycles, both before and after approval.
  • Incorporating the patient voice – Patients are the FDA’s most important stakeholder and our vision includes incorporating the patient voice in modern patient-focused drug development. “All the elements in our proposal have a common thread: they ultimately serve to improve health for patients,” she said.

Gottlieb added, “We believe that some of the new organizational structures we’re considering could also allow our review staff to have more time for reviewing and providing feedback to sponsors on clinical protocols.”

One goal is to engage sponsors earlier in the development process to ensure that trial designs are efficient and structured in the most effective way to identify risks and measure benefit.

“Equally important,” Gottlieb said, “there will also be more ability to engage external stakeholders, such as disease specialists, academic researchers, and regulatory partners at other agencies…and with patient-focused drug development becoming a reality, ongoing relationships and interactions with patient groups are becoming an important part of our regulatory practices.”

Author: Michael Causey