FDA’s Review Process Shows Preferential Treatment of NMEs for Unmet Medical Needs
​​[Posted on: Thursday, April 5, 2018]

This week FDA posted a review of its drug approval process based on the principle of benefit-risk-assessment that shows it gives special consideration to new molecular entities (NMEs) intended for diseases with few or no treatment options with regards to market approval decisions. Over the last decade, FDA emphasized the value of putting the safety and efficacy information collected in support of the market approval of a given drug in the context of the disease and the patients it intends to treat. Per the applicable laws and regulations, FDA must approve a product based on the extensive clinical and non-clinical evidence presented in the market approval applications. However, the process is filled with subjective interpretations of the data based on the reviewers’ preferences and training. The reviewers must determine that the drug is effective and that its expected benefits outweigh its potential risks to patients. This is particularly true for NMEs when the molecule is first of its kind and there is scant precedent data with FDA for clinical experience. However, for such drugs there should be other considerations such as urgent medical need. Sponsors tried to drive these additional considerations via meetings with reviewers, patient advocates and Advisory Committee meetings, leading to variability in FDA decisions driven by the efforts by the developers. Efforts to make the FDA review process and decisions for NMEs more clear and transparent to all stakeholders started in 2009 when CDER and CBER began developing a process for evaluating and communicating the benefit-risk assessments of products being reviewed. The efforts got formalized in 2013 when FDA published the Benefit-Risk-Framework (BRF). Under the BRF, FDA instructed its reviewers to also consider factors such as the severity of the disease, how well patients’ medical needs are addressed by currently available therapies, degrees of uncertainty that the information included in the NDA or BLA will extrapolate to the real-world use of the product, and if any REMS or other risk management tools can manage specific risks in the post-market phase of the product. The program was implemented in 2013-2015, and additional features such as patient-focused drug development were added. In 2015 FDA contracted a third party to review and evaluate the BRF process who reviewed 43 products approved in the year 2015-2016. The review found that the BRF process is liked by the industry and most FDA reviewers, however, since it is applicable to only NMEs, its scope is limited to very few of the total products approved by the FDA. The BRF assessments are posted along with the rest of the review packages at drugs@FDA and are hard to find in the wealth of documents posted by FDA. FDA plans to continue the BRF process and increasingly include patients’ perspectives to its decisions, however, by focusing only on NMEs it is likely shortchanging the transparency initiative. The benefits of the BRF should be expanded to non-NMEs as well, as the same criteria can be applied to new formulations, new uses of previously approved drugs, and new combinations. At present FDA has no announced plans to expand BRF to all products but as it gains experience with the process, we should expect transparent benefit risk assessments for all regulatory decisions.