Real World Data For 505(b)(2) Development Programs
​[Posted on: Thursday, December 15, 2016]

The 505(b)(2) regulatory pathway is primarily designed to get FDA approval of new indications of previously approved products. A provision in the 21st Century Cures Act, that became the law this week, could create a promising expedited approval pathway for 505(b)(2) products. Developers of such products need to conduct randomized clinical trials (RCTs) for the new indication. The new law contains two requirements for FDA. First, FDA should consider patient experience data for approval of new products and for post-marketing obligations. And second, that FDA should create a process to use Real World Evidence (RWE) in support of market approval of products. Both these provisions could potentially boost approval of new indications for approved products, thereby not only making it easier to seek approval under the 505(b)(2) pathway, but also provide an incentive to convert off-label information to on-label information without having to do RCTs. Most products have uses beyond what they are initially approved for. These new uses many a times become evident once the product becomes available in the market. Information on the new uses of approved products almost entirely stems from clinical experience with off-label prescription by physicians. FDA does not restrict off-label prescription by doctors but does not allow companies to use this information for promotion of products. However, it has been successfully argued that truthful, non-misleading information about off-label uses is legal forcing FDA to re-think its policies for off-label promotion of products. It’s a regulatory conundrum as allowing off-label promotion discourages companies to seek formal FDA approval for new indications. The new law gives both FDA and companies a win-win solution. Off-label use data can be easily collected from electronic health records (EHRs), claims and billing data, product and disease registries, and data gathered through personal devices and health applications. Such data is already collected, analyzed, and published in medical journals. Companies are allowed to disseminate such articles describing off-label uses of products. Using these data to establish justification for a 505(b)(2) NDA should be relatively easy and quick. The new law creates the regulatory mandate for FDA to implement a program for companies to seek market approval using RWE. There are some concerns about RWE. EHR and insurance claims data will need to be collected and organized for data mining and credibility by randomization and measures to reduce bias. Methods to analyze data should be prospectively planned. Data collected from other sources such as personal devices, health-related apps, and social media may raise questions about reliability and quality of the data. FDA acknowledges that RWE can provide valuable information particularly for observational studies; however it has concerns about replacing RCTs with RWE. But for the well-established off-label uses where truthful non-misleading data is available, using RWE to reduce or even eliminate need for RCTs is a real possibility. In the end, one size may not, and should not, fit all. Manufacturers looking to use RWE must work to address FDA’s concerns regarding the quality of data while FDA must keep an open mind. Use of RWE is already encouraged for medical devices, so FDA needs to take the next step for other products. As we said above, win-win.