The Qualitative Value of Facilitated Regulatory Pathways in Europe, USA, and Japan: Benefits, Barriers to Utilization, and Suggested Solutions

Pharmaceutical Medicine https://doi.org/10.1007/s40290-020-00372-7 ORIGINAL RESEARCH ARTICLE The Qualitative Value of Facilitated Regulatory Pathways in Europe, USA, and Japan: Benefits, Barriers to Utilization, and Suggested Solutions Magdalena Bujar1 · Neil McAuslane1 · Lawrence Liberti1 Accepted: 15 December 2020 © The Author(s) 2021 Abstract Background Despite the growing application of facilitated regulatory pathways (FRPs), little attention has focused on assessing the perception of pharmaceutical companies regarding their usefulness beyond increasing timeliness. Objectives The aim of this study was to characterize the perceived value of four key FRPs, based on industry experiences in using these pathways. In addition, we sought to characterize the perceived impact based on benefits and barriers as well as suggested solutions for their use and recommendations as identified by companies, to outline how these FRPs may be further evolved as tools for expediting the development and regulatory review of important medicines. Methods A study was undertaken to characterize the perceived value and impact of US FDA (i.e., Breakthrough Therapy Designation, Fast Track), European Medicines Agency (i.e., PRIME), and Japanese Pharmaceutical and Medical Devices Agency (i.e., Sakigake) FRPs through a comprehensive analysis of strengths, weaknesses, opportunities, and threats (SWOT) as well as suggested solutions based on industry experiences with their use. The finalized survey comprised six questions and was sent to senior management in regulatory affairs departments at 22 multinational pharmaceutical companies in March 2019, with a deadline for completion by April 2019. The responses were analyzed using descriptive statistics. SWOT and free-text responses were reviewed and manually grouped into key themes according to high concordance. Results Survey results were returned by 11 pharmaceutical companies. Based on their perceived value and positive impact, the evaluated FRPs seem to be generally recognized as helpful tools for ensuring timely development and review of important medicines while ensuring multistakeholder involvement. Respondents overwhelmingly felt that the Breakthrough Therapy Designation carried a positive influence, both within and outside their organizations. Following closely with a positive although varied perception was Sakigake, but respondents exhibited more ambivalence about Fast Track and PRIME. Companies felt the impact of the FRPs was generally positive for most stakeholders except for health technology assessors/ payers, highlighting the need to better align FRPs with flexible access and reimbursement pathways to expedite the equitable availability of high‐quality, safe, effective medicines. Conclusions This study highlighted common recommendations across all four FRPs (relating to resource optimization, education, alignment, and communication to improve effective use), as well as agency-specific recommendations, some of which are already being addressed by the regulators. 1 Background * Magdalena Bujar 1 Centre for Innovation in Regulatory Science (CIRS), London, UK Facilitated regulatory pathway (FRP) is now a widely adopted term [1] that refers to pathways that offer alternatives to the standard medicines development and registration by accelerating the development, submission, or regulatory review of important medicines. Initially, mature agencies such as the European Medicines Agency (EMA), the US Vol.:(0123456789) M. Bujar et al. Key Points Facilitated regulatory pathways (FRPs) have had a documented positive impact on their primary objective of shortening development and review times of important medicines; however, evaluations of their qualitative value and impact are limited. This study identifies the perceived value and impact of key FRPs (i.e., US FDA’s Breakthrough Designation and Fast Track, the European Medicines Agency’s PRIME, and the Japanese Pharmaceutical and Medical Devices Agency’s Sakigake) and potential solutions for barriers to their use. Company respondents generally considered the studied FRPs as useful tools to facilitate timely development and review of important medicines and involvement of multiple stakeholders, especially the US Breakthrough Therapy Designation and Japanese Sakigake. FDA, and Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) introduced pathways to speed the regulatory review process timelines. More recently, these agencies introduced FRPs that aim to not only speed the review but also help expedite the development of important new medicines (e.g., generally medicines that have the potential to meet an unmet need for a serious or life-threatening condition). These FRPs include FDA Fast Track and Breakthrough Therapy Designation (BTD) introduced in 1997 and 2012, respectively; PMDA Sakigake, launched in 2015; and EMA Priority Medicines (PRIME) in 2016. Others, such as the EMA Conditional and Exceptional Circumstances Marketing Authorizations, FDA Accelerated Approval, and PMDA Conditional Early Approval also offer routes to grant approval for medicines based on initial data that demonstrate plausible clinical benefit or on an unvalidated surrogate or intermediate endpoint, in which the applicant is required to provide comprehensive clinical data in the future that demonstrate actual clinical benefit and a maintained positive benefit-to-risk profile. Details regarding each of these programs are summarized in agency guidances [2–4] and have also been described in recent publications, including the impact of FRPs on time [5–10]. The various FRPs may contribute to shorter development and review timelines by encouraging early dialog between companies and agencies, regulatory guidance on the development program from agencies, increased frequency of updates based on evolving safety–efficacy data in the context of unmet need, and reduced cycle times for regulatory feedback. An additional and important goal for these pathways was to shift the perception of regulators from being primarily “gate-keepers” who keep unsafe and ineffective products off the market to also being “enablers” of true innovation, where urgency to meet patient need drives progress in approving new therapeutic options for unmet medical conditions [11]. FRPs are therefore key in ensuring timely development and regulatory review of medicines for unmet medical need, as well as in a crisis situation, such as a pandemic. Nevertheless, studies evaluating the impact and value of FRPs are limited. In one study of basic principles, Liberti et al. [1] assessed survey-based feedback from regulators, health technology assessment (HTA) bodies, pharmaceutical companies, patient advocacy groups, and academia around their perception of FRPs. This first-pass inquiry focused on perceived strengths and weaknesses of key FRPs, including the concept of an “adaptive licensing pathway”. At that time, the following impediments to the widespread (...truncated)