Introduction 

Many facilitated regulatory pathways (FRPs) have been developed with a goal of accelerating regulatory authorization processes, as can be found in FRPath. As a developer, leveraging facilitated regulatory pathways and collaborations is essential for enabling timely access to safe and effective medical products, vaccines and devices during public health emergencies (PHEs). However, these pathways face several limitations that can hinder their effectiveness. This review explores the constraints of FRPs, drawing insights from developers and regulators with firsthand experience in their use and development. A recommendation is made for an alternative pathway.

Constraints

Alignment of Submission Timeframes and Dossier Requirements 

One significant challenge is the difficulty in aligning review timelines and submission requirements across different regulatory agencies. This misalignment can lead to delays in the approval process, whether a country is reviewing independently or as part of a collaboration. Despite collaborative efforts generally requiring identical submission dossiers across all partners, except for region-specific modules, applications must still meet specific national regulatory requirements. This can complicate the process, especially in regions with formalized parallel pathways for regulatory evaluation and health technology assessments. This can lead to extensive and cumbersome documentation preparation, particularly concerning Chemistry, Manufacturing, and Controls (CMC) data, as well as country specific labelling requirements. 

Differing Risk Tolerances and Data Interpretation 

Regulatory agencies often have varying risk tolerances and interpretations of data. This can lead to delays or rejections, particularly in collaborations, if one agency’s stringent standards influence the collective decision-making process. In the context of vaccines, this may be further exacerbated by other public health considerations as well as availability of other vaccines.  

Speed of Market Authorization 

While regulatory collaborations aim to expedite market authorization, this is not always achieved uniformly. For example, during the COVID-19 pandemic, ACCESS worksharing was deemed too slow for vaccines and therapeutics, necessitating alternative information-sharing mechanisms.

Scope

Initiatives like Project Orbis are limited in scope, currently covering only oncology drugs. Expanding such frameworks to include other critical areas like vaccines remains a challenge due to public health considerations, population and exposure differences and manufacturing and packaging differences.

Resources 

Some members of collaborative initiatives often lack the resources to lead or fully participate, leading to underutilization of these frameworks. Regional collaborative mechanisms often rely heavily on a few entities to lead and perform the bulk of the regulatory work or in the case of AVAREF the need for adequately staffed secretariat to facilitate and drive the work and timelines. This can lead to inefficiencies and delays, particularly during health emergencies during which many medicines, vaccines and devices are in development, flooding regulators.  

Regulatory Agility 

The COVID-19 pandemic highlighted the need for regulatory agility. Many regulatory authorities lacked the capacity to perform all core functions effectively, leading to reliance on better-resourced authorities. This dependence can delay decision-making and hinder timely access to medical products. Decisions about reliance or recognition are often made unilaterally without prior consultation with reference agencies. This can lead to inconsistencies and a lack of awareness among the agencies involved. Additionally, many countries lack legislative texts formally allowing reliance and or emergency pathways. 

Examples of pathways and associated limitations 

African Regional Collaborations

Similarly, African collaborative pathways have mainly worked with generic drugs rather than vaccines during a pandemic. Most regional African mechanisms have relied primarily on one or two main entities in each region to perform the bulk of the review work, with Zazibona being the most developed. 

ASEAN Joint Assessment Procedure 

The ASEAN joint assessment procedure is very slow. Regulators in Southeast Asia did not use it during the COVID-19 pandemic, instead relying on reliance or de facto recognition processes. This trend is likely to continue in future pandemics.

EMA’s OPEN Initiative 

The EMA’s OPEN initiative allows non-EU regulators to participate in the scientific evaluation of certain medicines. While it aims to harmonize regulatory approaches and speed up patient access, the initiative can be limited by the independence of participating authorities and the complexity of coordinating parallel reviews. 

MHRA Initiative on Recognition 

The MHRA initiative on recognition has several criteria that make it excessively restrictive. Although the rapid timeframe of the “Recognition A” process is attractive to industry, several conditions can move a product to the slower “Recognition B” scheme or even to full MHRA evaluation. These conditions include products with conditional approval, first-in-class new active substances, and clinical trials utilizing single-arm data and/or real-world evidence. 

Recommendation

The Collaboration and Convergence: Recommendations for Future Public Health Emergencies and Streamlined Regulatory Submission Process are proposed, targeting submission of a single dossier with a single package and label to all participating countries at the same time. This strategy offers the greatest potential for equitable access.