Overview

A Regulatory Innovations Consortium (RIC) of industry experts from developers who are building platforms for vaccine manufacturing was launched by CEPI in October 2023.  The goal was to collaborate globally to propose, review and align on principles for use of platforms to enable rapid deployment of vaccines and other countermeasures in high-risk populations as soon as the evidence supports it.  That goal was expanded upon to include other regulatory innovations needed for further acceleration.    

Within the RIC, the Collaboration & Convergence workstream was established to recommend regulatory innovations that optimize regulatory frameworks for emergency preparedness.

Methodology for Developing Recommendations

The RIC Collaboration & Convergence workstream conducted an extensive evaluation of the existing regulatory collaborative pathways under standard and pandemic conditions using COVID 19, Ebola Zaire, and other outbreaks as case studies.   Key activities included:

• Reviewing global collaborative regulatory pathways, such as reliance mechanisms and best practices.

• Analyzing the reliance pathway usage via the CIRS 2020 survey and assessing the WHO Collaborative Registration Procedure (CRP).

• Synthesizing lessons learned from COVID-19, Ebola Zaire, and other outbreaks to understand areas what flexibilities already in place should be kept and where regulatory processes could be improved.

The analysis identified gaps in current public health emergency (PHE) response processes and opportunities to implement innovations to optimize regulatory frameworks for emergency preparedness.

Gaps in the PHE Response Process

The gaps identified in the PHE response process were:

• Collaborative procedures during PHEs often exceed the capacity of National Regulatory Authorities (NRAs) and coordinating bodies due to the significant time needed for coordination.

• Some existing collaboration procedures require alignment of participants prior to approval, which can take significant extra time when compared with independent review

• Different NRAs recognize different reference authorities, potentially leading to varied regulatory expectations for dossier content and submission timing.

• NRAs who do not participate in information sharing may require more resources for review and miss opportunities for quick identification and understanding of risks and mitigation strategies.

• Varied submission timelines create inequitable vaccine and countermeasure access across regions.

• Lack of information sharing among NRAs can delay decision making, risk identification and mitigation.

• Multiple independent inspections and parallel processes divert resources from critical production and distribution tasks.

These gaps highlight the urgent need for streamlined and coordinated regulatory frameworks to effectively manage PHEs.

Building on Regulatory Flexibilities from Previous PHEs to Strengthen Future Processes

Examples of regulatory flexibilities from previous PHEs that enabled regulatory agility, accelerating decision-making to grant Emergency Use Authorization (EUA) or marketing authorization (MA) are provided below.  

• Open communication between NRAs and stakeholders, waiving statutory requirements for meetings

• Consolidation of clinical trial phases, and simplification of the clinical trial submission processes for faster approvals

• Streamlined Emergency Use Authorization (EAU) and Marketing Authorization Application (MAA) dossier packages by including only essential data and fewer documents where applicable, submitted in eCTD format

• Rolling submissions and reviews

• Certificates of analysis from National Control Laboratories instead of conducting traditional lot release testing

• Standardization of packaging and prescribing information by adopting electronic English-only artwork

• Implementation of digital solutions such as electronic prescribing information (ePI) accessible via QR codes to provide critical product details, extend shelf-life, provide real-time updates on product stability, and provide translations of the English leaflet included in the package.

• Coordination of joint inspections by reference authorities, with outcomes recognized by other NRAs to reduce resource strain and delays.

These flexibilities can be fully leveraged and directly applied at Day 0 to address some of the current gaps in the PHE regulatory processes.

Key Recommendations to Address Gaps

Some recommendations could be implemented immediately in public health emergencies, following what has been done successfully in the past.  Other recommendations may take longer to implement because alignment among many stakeholders is needed.  Near term and longer-term recommendations are provided below.

Near Term Implementation

1. Streamlined Submission Process1

• NRAs could establish guidance to allow use of harmonized single, English-only global EUA and MAA dossiers, aligned with ICH standards, simultaneously accessible to NRAs via a secure cloud-based platform.

• Expedited distribution of assessment reports from WHO-Listed Authorities (WLAs) to support NRAs in making accelerated emergency use and marketing authorization decisions

2. Global and Regional PHE Processes¹

• NRAs could expand collaborative and reliance-based regulatory pathways at global and regional levels, as needed, based on outbreak epidemiology to streamline decision-making.

3. Regulatory Convergence and Harmonization

• NRAs could maintain key regulatory flexibilities introduced during previous PHEs as stated above in “Building on Regulatory Flexibilities from Previous PHEs to Strengthen Future Processes.” 

Longer Term Implementation

Implement a flexible regulatory approach that allows for combining different levels of collaboration among WHO-Listed Authorities (WLAs) and National Regulatory Authorities (NRAs) to evaluate and authorize vaccines during PHEs.  

1. Formal Coordination Body

   • Rely on a coordination body, such as WHO, a WLA, or another public health entity, to facilitate streamlined processes, procedural alignment, regular information sharing, and facilitate timely patient access to vaccines during public health emergencies.

2. Collaborative Assessment by a Coalition of WHO Listed Authorities (WLAs) and WHO Maturity Level 3 NRAs

   • Identify one or two WLAs or NRAs who have achieved WHO Maturity Level 3 according to the Global Benchmarking Tool in each region impacted by a PHE to lead or participate in parallel collaborative assessments, ensuring timely information sharing, regular joint meetings with stakeholders, and independent regulatory decisions by each WLA or NRA based on the shared assessment.  Existing collaborations among WLAs could be leveraged.

Risk Mitigation Strategies

To support the success of these recommendations, the following strategies address potential barriers:

• Sovereignty Concerns:  NRAs can decide to assess all, some or none of the data and dossier, based on capacity, policies, platform understanding, and level of trust for other reviewing National Regulatory Authorities (NRAs) and then conduct a benefit-risk assessment based on the significance of the PHE in the country.

• Timely Product Availability: Promote early procurement and regional manufacturing to ensure equitable access and prevent supply-chain disruptions.