Enhancing Vaccine Regulation for Pandemic Preparedness

Strengthening regulatory frameworks is critical in ensuring that vaccines are quickly approved and distributed. Using a systematic approach, gaps in key areas of the regulatory system can be identified, prioritized, and effectively addressed through regulatory capacity building and education of regulatory professionals.

The World Health Organization Global Benchmarking Tool was developed to evaluate regulatory systems objectively and systematically, identify strengths and areas for improvement, guide interventions, and monitor progress in strengthening the regulatory system. Consistent and regular training of national regulators can also complement regulatory systems strengthening efforts by focusing on the identified gaps.

The diverse and fragmented regulatory environment in Asia and the Pacific calls for regulatory convergence[1] and cooperation to facilitate timely and equitable access in the region. Stable, well-functioning national regulatory authorities in the region listed as WHO Maturity Level 3 and 4 and WHO Listed Authorities, such as those in the People’s Republic of China, India, Indonesia, Republic of Korea, Singapore, Thailand, and Viet Nam, could foster regional regulatory cooperation and serve as reference agencies for lower-resourced regulatory agencies.

Such cooperation could be facilitated by formalized processes and relationships such as memoranda of understanding. For example, Singapore’s Health Sciences Authority has adopted a confidence-based regulatory approach that leverages the decisions of established and trusted regulatory agencies through formal recognition mechanisms and has expedited reviews without compromising the robustness of regulatory decisions. This has reduced approval timelines to 90 working days from 270 working days for the Health Sciences Authority’s full evaluation route under its verification evaluation system.

Confidence-based approaches can be adopted in various stages of the vaccine life cycle. The ASEAN Mutual Recognition Arrangement on Good Manufacturing Practice Inspection enables member states to leverage on the regulatory inspections performed by other member states. It is legally binding for member states to recognize one another’s good manufacturing practice certificates, benchmarked against the international Pharmaceutical Inspection Cooperation Scheme.

Regulatory cooperation can range from legally-binding mechanisms in the form of mutual recognition agreements and reliance mechanisms to other forms of cooperation such as joint collaborative assessments, report sharing and work sharing. Work sharing can promote mutual learning and the sharing of best practices among participating national regulatory authorities and can encourage regulatory convergence. For industry, the work-sharing model can be commercially attractive, providing simultaneous access to multiple countries and shorten timelines with the consolidation of questions.

While cooperation on vaccine regulation is still nascent, there are other examples of regulatory cooperative mechanisms. Work sharing is practiced by Access Consortium, comprising the national regulatory authorities of Australia, Canada, Singapore, Switzerland and the United Kingdom. A similar coalition is the Opening Procedures at EMA to Non-EU authorities (OPEN) initiative, led by the EMA, which partners Australia, Brazil, Canada, Japan, Switzerland and WHO in joint assessments. In Asia and the Pacific, the Indo-Pacific Regulatory Strengthening Program, comprising Cambodia, Indonesia, Laos, Myanmar, Papua New Guinea, Thailand, and Viet Nam, and supported by Australia, successfully expedited approval of the antimalarial tafenoquine in Thailand in 2019 in its joint review.

While the work-sharing model has its advantages, the following points also need to be considered:

• Participating national regulatory authorities may have different priority drug lists and approval timelines.
• Participating national regulatory authorities may have different technical requirements.
• Lack of clarity in regulatory decisions could impact company filing strategies.

Convergence of regulatory requirements can further contribute to successful work-sharing collaborations. One way to incentivize the alignment of key regulatory requirements is the creation of a consensus on indicators that measure overall efficiency of the work-sharing pathway, which participating countries can jointly work towards. Regional regulatory convergence efforts include the APEC Action Plan on Vaccination Across the Life-Course, which sets key policy targets to achieve by 2030. Priorities for alignment include post-approval change management, labeling, and packaging.

Post-market surveillance is important in ensuring the safety and efficacy of vaccines. Systems such as the FDA’s Vaccine Adverse Event Reporting System and WHO’s Global Vaccine Safety Initiative provide structured frameworks to identify and mitigate adverse events post-vaccine rollout.

The use of real-world data and real-world evidence during the COVID-19 pandemic allowed for the identification and management of rare adverse events, maintaining a high safety standard for vaccines distributed globally.

Rolling submissions and evaluation of clinical efficacy data were the hallmark of regulatory agility during COVID-19. Such a risk-based approach requires that the risks be managed with a robust post-market surveillance framework. Besides real-world data from ongoing trials, a robust vaccine vigilance framework could include:

• Participation in international drug safety monitoring networks, such as the WHO Programme for International Drug Monitoring and the Uppsala Monitoring Centre’s Vigibase—the largest drug safety data repository.
• Implementing a post-market surveillance framework in lower-resourced settings using the WHO Project 3S (Smart Safety Surveillance) stepwise strategy, which include implementing legal frameworks, providing dedicated budgets, and digitalization of adverse event reporting.
• Detailed record keeping of vaccinations under national immunization registries.
• Encouraging timely reports of adverse events by industry, healthcare professionals, and the public.
• Data mining of adverse events from electronic health records.

Multisectoral collaborations promote knowledge sharing and can build regulatory capacity. One good practice is early industry engagement during pre-submission consultations, which facilitates industry alignment with key regulatory requirements and helps regulators familiarize with product innovations.

Think-tanks can help drive regulatory systems strengthening and promote policy innovation in the region by convening stakeholders and experts. In this regard, it is also important to partner with the wider community of stakeholders, key opinion leaders, and the public—especially in risk communication. This requires ongoing proactive involvement to share accurate information in a timely and transparent manner to build trust. Concerns should be addressed to swiftly counter misinformation and falsehoods.

Looking back, regulation had played an enabling role that proactively guided the development and application of scientific advancements for the novel vaccine technologies that were pivotal in stemming the COVID-19 pandemic. The exemplary regulatory agility, risk-based and collaborative approaches used by many mature national regulatory authorities to facilitate global vaccines access embodied this inherent understanding of regulation’s enabling role.

As the paradigm shifts towards a wider recognition of science being enabled by good regulation, all stakeholders have a shared responsibility in forging a secure future, with equitable access to breakthrough vaccines for all.

Sustainable regulatory system strengthening requires a concerted effort from all stakeholders. Adopting systematic approaches to identify and address gaps in regulatory systems, along with sustained regulatory capacity building and training will support sustainable regulatory systems strengthening. At the same time, regulatory convergence and cooperation among stakeholders help pave the way towards timely and equitable vaccine access.

Strengthen regulatory systems and capacity building

• A systematic approach to strengthening the regulatory system using the World Health Organization Global Benchmarking Tool
• Sustained capacity building and education of regulatory professionals

Regulatory convergence and cooperation

• Leverage regulatory assessments made by reference agencies through formal recognition arrangements
• Promote work sharing and joint assessments, with formalized processes and relationships
• Indicators can be created to measure work sharing efficiency

Risk-based approach with robust post-market surveillance

• Participate in surveillance networks
• Upskill competencies in post-market surveillance and pharmacovigilance
• Adopt post-market surveillance framework such as the proposed WHO 3S (Smart Safety Surveillance) stepwise strategy

Enhance multisectoral collaboration

• Offer early industry engagement during pre-submission regulatory consultations as a standard approach
• Drive multisectoral collaboration
• Partner the wider community of stakeholders

This article reflects a collaborative effort, with insights from Prof. Silke Vogel of Duke-NUS Medical School, and Dr. Ye Xu, Dr. Benjamine Coghlan, and Dr. Patrick Osewe of Asian Development Bank.

Note: The ADB-CoRE Vaccine Regulation Project aims to inform the ADB Human and Social Development Sector Group on the vaccine regulatory landscape in Asia and the Pacific, focusing on Bangladesh, India, Indonesia, Republic of Korea, and Singapore. Initiated in 2022, it has facilitated public-private vaccine stakeholder engagements among ADB developing member countries and produced country-specific and regional vaccine landscape analysis and recommendations.

^[1] The Asia-Pacific Economic Cooperation (APEC) defines regulatory convergence as the alignment of requirements through gradual adoption of harmonized international guidance, standards, and scientific principles.

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