Comparing the Characteristics and Use of Facilitated Regulatory Pathways by ICH and Maturing Agencies
Editor’s note: This article is adapted from a presentation made by the author, the executive director of the Centre for Innovation in Regulatory Science (CIRS), at the DIA EuroMeeting on April 8 in Hamburg, Germany, as part of the session “New Approaches to the Approval of Innovative Medicines,” chaired by David Jefferys, senior vice president, Eisai Europe, UK.*
Facilitated regulatory pathways (FRPs) are alternatives to standard regulatory pathways that accelerate the development, submission, regulatory review and patient access to important medicines with a positive benefit-risk balance for serious diseases or unmet medical need. Society must be willing to accept uncertainty about the benefits and harms of new medicines approved through these pathways because of the serious risks of the disease, the lack of effective therapies and the belief that the initial data generated are reasonably predictive of clinical benefit, despite uncertainty about the true value of the therapy. Reviews conducted via FRPs go by various names and made up 58% and 50% of all new active substance approvals at the U.S. Food and Drug Administration (FDA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) in 2014, and 13% at the European Medicines Agency (EMA).
Adaptive pathways is a scientific concept for medicine development and data generation that allows for early and progressive patient access to a medicine. In the EU, this approach makes use of the existing regulatory framework for medicines and applies primarily to areas of high medical need and where data may be hard to collect via traditional routes. The adaptive pathways approach is part of EMA efforts to improve timely access for patients to new medicines and is based on four principles: iterative development or approval in stages, beginning with a restricted patient population then expanding to wider patient populations; the confirmation of the benefit-risk balance of a product, following a conditional approval based on early data using surrogate endpoints, considered predictive of important clinical outcomes; the gathering of evidence through real-life use to supplement clinical trial data; and the early involvement of patients and health-technology-assessment bodies in discussions on a medicine’s development. Elements of some FRPs are observed in adaptive pathways (conditional license followed by data collection, conversion to full license).
FRP STAKEHOLDER PERCEPTIONS: SURVEY 1
In late 2014, colleagues and I conducted a perception survey of industry members, regulators, health technology assessors and patient groups to gain insights into personal opinions regarding FRPs This survey was also designed to characterize the key elements of FRPs, understand the barriers to their implementation and to provide guidance about stakeholder interest, acceptance and concerns to those who are developing and seeking to implement these novel systems. Survey responders, including 80 individuals from 50 organizations around the world, were asked to rate the usefulness of currently available FRPs at the FDA, EMA and PMDA. Notwithstanding their increasing use, whilst 62% of participants indicated that FDA pathways are fit for purpose, EMA pathways and PMDA pathways were regarded as useful by only 11% and 7% of respondents respectively. The full results of this survey can be found at Liberti L, Stolk P, McAuslane N, Somauroo A, Breckenridge AM, Leufkens H: Adaptive licensing and facilitated regulatory pathways: A survey of stakeholder perceptions. Clin Pharmacol Ther. 2015 Apr 15.
FRPS IN EMERGING NATIONAL REGULATORY AUTHORITIES: SURVEY 2
The importance of FRPs has also increased for emerging national regulatory authorities because of an expanding portfolio of products for neglected diseases and, along with the World Health Organization, these agencies are expanding their commitment to new treatments for local populations. A descriptive study to assess characteristics and common elements of currently implemented FRPs in emerging national regulatory agencies (NRAs) was conducted to understand the diversity and similarities of these FRPs, identify common processes, help with the ongoing assessment and development of national regulatory systems and provide evidence for international organizations to help focus strategies for increasing regulatory capacity at emerging NRAs.
In the study, using 33 FRPs from 29 countries around the world, 27 FRP characteristics were assessed and organized as procedural (rules/activities related to overall process; 18 characteristics) or substantive (those used to determine how the evidence supports the outcome; nine characteristics) and five sequential regulatory activities were identified: those describing ways for agencies to assist the sponsor to facilitate the submission or review (six characteristics); criteria for the acceptance of the regulatory dossier (nine characteristics); review process attributes (four characteristics); decision criteria (four characteristics); post-authorization and disengagement activities (four characteristics).Study results indicated diversity by region in FRP characteristics, suggesting a role for further engagement with emerging NRAs in their design and implementation. Common FRP processes could help inform the development of novel, globally aligned, accelerated development and regulatory authorization pathways for products that meet unmet serious public health challenges. The full survey results can be found at Liberti L, Breckenridge A, Hoekman J, Leufkens H, Lumpkin L, McAuslane N, Stolk P, Zhi K, Rägo L. J Public Health Policy. 2016 Mar 10. doi: 10.1057/jphp.2016.8).
All parties with a stake in healthcare are on a learning curve regarding the development and implementation of FRPs and numerous issues remain to be resolved such as the future role of FRPs in mature and emerging NRAs, how current FRPs can best be improved, the impact of health technology assessment on FRPs in the global medicine development environment and the need to inform patients and healthcare professionals of the pros and cons of FRPs and to develop a methodology for the communication of that information.
*CIRS - The Centre for Innovation in Regulatory Science - is a neutral, independent UK-based subsidiary company, forming part of the Intellectual Property and Science business of Thomson Reuters. The mission of CIRS is to maintain a leadership role in identifying and applying scientific principles for the purpose of advancing regulatory and HTA policies and processes. CIRS provides an international forum for industry, regulators, HTA and other healthcare stakeholders to meet, debate and develop regulatory and reimbursement policy through the innovative application of regulatory science. It is governed and operated for the sole support of its members’ activities. The organisation has its own dedicated management and advisory boards, and its funding is derived from membership dues, related activities and grants. For more information, go to www.cirsci.org.