FDA Finalizes the Guidance on Least Burdensome Provisions
Taking a Risk-Based Approach to Regulatory Approvals and Enforcements
Congress first added the Least Burdensome provisions to the Food, Drug and Cosmetics Act (FD&C) through Food and Drug Administration Modernization Act (FDAMA) of 1997. Additional provisions were added through the FDA Safety and Information Act (FDASIA) in 2012 and the 21st Century Cures Act (Cures Act) in 2016. These provisions are intended to ensure that the FDA does not place undue burdens on manufacturers when requesting additional information to determine substantial equivalence for 510(k) device clearance, or to assess device safety and effectiveness for Pre-Market Approval (PMA). Although these provisions do not change the standards for 510(k) clearance or PMA, they do require the FDA to request only what is necessary, and to consider the role of post-market information in ensuring a reasonable level of safety and effectiveness.
Least burdensome is defined as the minimum amount of information necessary to adequately address a relevant regulatory question or issue through the most efficient manner at the right time.
The FDA’s approach to the least burdensome regulatory process has evolved over the years, and now they have finalized a new guidance document to also include the role of post-market information in reducing the burden on pre-market requirements. In many ways, this presents a new opportunity for medical device manufacturers to accelerate innovation and adapt more efficient compliance activities.
Notable among the guiding principles is the idea of using post-market information to reduce the burden on the type and amount of premarket information needed for a regulatory decision (i.e. clearance or approval). FDA also plans to tailor its regulatory approach to different devices to fit the technology and underlying innovation lifecycle. This is very appropriate and timely to facilitate rapid innovation through new advancements in artificial intelligence and 3D printing. FDA is also very open to using data gathered in markets outside the US and-real world evidence (RWE) from electronic health records, medical claims data and device-specific registries. This is a significant shift in FDA’s approach and offers a great opportunity for the device industry.
Examples of a new FDA approach:
A PMA for a pacemaker electrode was approved by the FDA using clinical data captured through a remote monitoring system in a prospective registry. A next generation tumor profiling test was reviewed using a curated precision oncology database.
The finalized guidance provides details of the new FDA approach with specific examples for:
· The minimum information necessary
· The most efficient means
· The right time
· Least burdensome compliance policies
More efficient alternate approaches to clinical data requirements such as leveraging historical data, real world data, non-clinical data and computer simulations are now possible. Reducing the burden on traditional clinical studies may now include approaches such as historical control groups, studies with non-comparative outcomes, subject as own control and adaptive study designs. Use of a benefit-risk approach allows the FDA to balance data requirements to demonstrate safety with evolving needs of the patient population. In some situations, greater uncertainty in device safety may be acceptable for a breakthrough innovation with a potential to offer significant benefits to patients.
The concept of right time refers to striking a balance between premarket and post-market information by taking a total product life cycle approach to medical devices. Using a risk-based approach, it may be possible to utilize post-market controls such as Quality System Regulation (QSR), post-approval studies, post-market surveillance and adverse events reporting to limit the amount of information needed at given point in time.
Even more encouraging a risk-based approach to compliance and enforcement policy of certain products. As an example, the FDA recently announced that it does not intend to apply its oversight to certain mobile medical applications and general low-risk wellness products. A recent Medical Device Enforcement and Quality Report provides a good example of how the FDA has taken selective enforcement action against high-risk devices and organizations that are slow to take actions in response to post-market safety issues. FDA has also exercised enforcement discretion for devices with medical necessity and where the risk to switching to a new device is higher than continuing with the existing device when it is found to be non-compliant.
In FDA’s view, by streamlining regulatory processes and removing or reducing unnecessary burdens associated with FDA regulatory activities, patients can have earlier and continued access to beneficial products.
The least burdensome approach is an opportunity for the industry to take a fresh look at its own approach to seeking regulatory approval and compliance. In preparing for FDA decision on a new product, gather the most relevant information needed at the time. Prepare it in a format that presents the information in a clear manner and easily understood. Think of new approaches to demonstrate safety and efficacy, seek early FDA feedback and respond to follow up inquiries in a timely manner.
Apply a least burdensome approach internally to sustain a high degree of regulatory compliance. Review existing procedures for unnecessary requirements, simplify and streamline to improve both efficiency and effectiveness of internal audits. Risk-based decision making across all areas of the Quality Management System (QMS) using data from post-market surveillance is one way to benefit from this new approach!
The Least Burdensome Provisions – Concepts and Principles, February 2019
FDA Safety and Innovation Act, March 2018
21st Century Cures Act, March 2018