The US Food and Drug Administration's (FDA) Center for Drug Evaluation and Research (CDER) has released its strategic regulatory plan for the upcoming five-year period, reflecting a refined vision and new realities it says it will need to face in order to advance the regulation of pharmaceutical and biological products.
FDA and its regulatory centers for drugs, devices and biologics regulatory put out targeted plans meant to guide the agency and its component centers over the course of years, allowing it to address larger challenges that no single one-year budget plan alone could address.
In the past, FDA has identified ongoing challenges like globalization, regulatory capacity and increasing product complexity as ones it needed to address. And while CDER concedes that these challenges haven't gone away, it says it intends to focus on some new challenges as well based around four primary objectives:
- Smarter Regulation
- Scientific Innovation
- Lean Management
- Business Modernization
Smart Regulation, Also Known as Predictable Regulation
The first, smarter regulation, should be familiar to anyone who has ever heard FDA talk about "regulatory science," a favorite topic of discussion for FDA Commissioner Margaret Hamburg. But even more than developing new tools to advance the regulation of safer and more effective products, CDER's strategic plan says it needs to do a better job at establishing policy frameworks and consistent expectations for products.
"A major component of CDER's role in drug development involves minimizing the regulatory uncertainty for regulated industry," CDER wrote. However, it conceded that regulatory uncertainty remains a challenge thanks to factors both within and outside of its control. Some companies with novel products may experience uncertain conditions by virtue of FDA genuinely being unsure about how to best regulate a product and its evolving thought process during the course of a review. In other cases, FDA may exhibit a "lack of consistency" across similar products, leading to "ambiguity about what is required to meet FDA's standards for an affirmative decision."
This, FDA said, can result in "misdirected efforts both in the regulated industry and at the agency"-a major challenge given the economic restraints on the budgets of both.
The good news: CDER has a fix-or fixes-in the works intended to make its regulatory processes considerably more predictable.
"CDER efforts to produce smarter regulation are expected to result in regulatory decision processes that feature enhanced predictability, transparency, and efficiency," it explained. So-called "smarter regulation" will result in a process that is more consistent, less burdensome and costly, and more flexible, it added.
Many of these efforts have already begun, and are expected to impact review transparency, communication during reviews, benefit-risk assessments, patient-focused drug development, risk control standardization, quality by design, and a long list of other projects.
The second, scientific innovation, is intended to address a simple and alarming truth about drug development: despite "significant advancements in basic research," the cost to develop a new drug has dramatically increased in recent decades. Worse, more drugs than ever are failing to ever reach the market, including about half of those that enter late-stage clinical testing.
FDA said it's looking to put new resources into figuring out how it can better leverage advances in regulatory and basic science with the end goal of permitting quicker, easier development of products. For example, by validating pharmacogenomics markers, it will permit approvals for narrower patient populations, avoiding those for whom the drug might have more risks than benefits.
FDA said it's also looking to include patient-reported outcome assessments (PROs) in its drug review process, with the stated intent of figuring out how patients perceive acceptable levels of risk.
But many other challenges have no simple answer. Despite their small intended populations, drugs for rare diseases require large amounts of resources to review because regulators have little prior experience in understanding the disease or its outcome measures. Biotechnology products are highly complex and even subtle variations, often resulting from manufacturing changes, can negatively affect their safety and efficacy profile.
But as with the first category, FDA says it has a range of projects underway to better address those challenges and others.
The Business of Regulation
The final two categories, lean management and business modernization, reflect the non-scientific challenges the agency faces in ensuring that products are made available to consumers.
FDA said that if other industries were any indication of success, by implementing lean management techniques-as it plans to do-it could recognize time savings of between 30 and 40 percent.
"This approach looks at a business process in terms of the value it creates for its customers, and then works to eliminate unnecessary activity that does not contribute to added value," FDA explained. And while that might be easy enough for a company to do with an obvious definition of "customer," it could be a great deal more difficult to determine who CDER's ultimate "customer" is-industry, patients, bureaucrats in the executive branch or legislators who determine its yearly budget.
But even if a definition of customer is elusive, CDER said that it's looking to find efficiencies in general.
"Importantly, lean management calls for a view of the organization that is horizontal and cross-cutting," it explained. "This approach has particular applicability to CDER's operating model which requires collaboration across offices to perform the mission-specific core regulatory activities. These activities engage not only the regulatory science disciplines but also center experts in policy, planning, informatics, analysis, management, and communications."
The report indicates that CDER is in the process of rolling out lean management techniques, and will continue to do so for the next several years. The effort will involve a "non-trivial amount of work," regulators noted.
FDA also said that it's working on standardizing the submission formats for the data it receives in the hopes of being able to move more of it into the digital "cloud." At present, FDA said it manages almost 21 miles of linear feet of paper records at considerable cost relative to its digital counterparts.
CDER Strategic Plan: 2013-2017