Investigating the Food and Drug Administration Biotherapeutics Review and Approval Process: Narrative Review (Preprint)

BACKGROUND The development, review, and approval process of therapeutic biological products in the United States presents two primary challenges: time and cost. Advancing a biotherapeutic from concept to market may take an average of 12 years, with costs exceeding US $1 billion, and the product may still fail the US Food and Drug Administration (FDA) approval process. Despite the FDA’s practices to expedite the approval of new therapies, seeking FDA approval remains a long, costly, and risky process. OBJECTIVE The objective of this paper is to explore the factors and gaps related to the FDA review and approval process that contribute to process inefficiencies and complexities as well as proposed methods and solutions to address such gaps. This paper also aims to investigate the available modeling efforts for the FDA approval process of therapeutic biological products. METHODS A narrative review of literature was conducted to understand the scope of published knowledge about challenges, opportunities, and specific methods to address the factors and gaps related to the review and approval of new drugs, including therapeutic biological products. Relevant peer-reviewed journal articles, conference proceedings, book chapters, official reports from public policy professional centers, and official reports and guidelines from the FDA were reviewed. RESULTS Of the 23 articles identified in this narrative literature review, none modeled the current FDA review and approval process structure to address issues related to the robustness, reliability, and efficiency of its operations from an external point of view. Although several studies summarize the FDA approval process with clarity, in addition to bringing to light the problems and challenges faced by the regulatory agency, only a few attempts have been made to provide solutions for the problems and challenges identified. In addition, although several reform models have been discussed, these models lack the application of scientific methodologies and modeling techniques in understanding FDA as a complex sociotechnical system. Furthermore, tools and methods to assess the efficacy of the models before implementation are largely absent. CONCLUSIONS The findings suggest the efficacy of model-based systems engineering approaches for identifying opportunities for significant improvements to the FDA review and approval process. Using this holistic approach will serve several investigative purposes: identify influential sources of variability that cause major delays, including individual, team, and organizational decision making; identify the human-system bottlenecks; identify areas of opportunity for design-driven improvements; study the effect of induced changes in the system; and assess the robustness of the structure of the FDA approval process in terms of enforcement and information symmetry. CLINICALTRIAL