he vaccine landscape was already changing prior to COVID-19, with new technologies such as mRNA, DNA, and viral vector vaccines, and novel populations for their use, including many vaccines being developed for adults. Then COVID-19 brought forward strides in development and a whole series of new challenges. It reignited interest in vaccines among regulators, vaccine developers, and the wider health system. However, vaccines are still underappreciated and undervalued. Despite being one of the cornerstones of public health, vaccines are approved across the world for only 34 pathogens, though many more pathogens lead to serious disease. Unfortunately, vaccines only attract a small proportion of government funding compared to medicines.

Key messages and recommendations to address these issues were developed by a multistakeholder workshop led by the Centre for Innovation in Regulatory Science (CIRS), which brought together senior representatives from pharmaceutical companies, regulatory agencies, National Immunization Technical Advisory Groups (NITAGs), health technology assessment (HTA) agencies, payers, and academia to discuss policy challenges in the vaccine landscape and to make recommendations on regulation and funding strategies for vaccines.

Derisking Vaccine Development

Approximately 10% of vaccine candidates for viral infectious diseases in phase 2 trials proceed to licensing within 10 years; this is an area that needs further derisking. The large clinical trial populations required to demonstrate efficacy and length of observation needed makes vaccine clinical development particularly challenging compared to development of other medicinal products. Although there is work underway on correlates of protection, an early proof of concept that derisks clinical development is not always possible for vaccines. In addition, participants in vaccine trials are healthy volunteers; this generates a different benefit-risk assessment than when treating infected patients.

Succeeding or failing more quickly in vaccine development is important, as it allows developers to reallocate resources to more promising programs, diversify targets, and work on multiple technologies. Having correlates of protection that predict vaccine efficacy in clinical trials with healthy individuals and accepted immune-bridging approaches can speed up development and significantly reduce risk.

Several developers recommended early engagement with government and public health professionals involved in national immunization programs as vital to getting a better assessment of the potential vaccine demand, as well as better understanding of the best pathway to market access for these products.

Vaccines are Undervalued

There is a need to reflect on just how important vaccines are for society and public health. Even with the existence of very effective vaccines against shingles and influenza, adult uptake is much lower than desirable, particularly after the peak of the COVID-19 pandemic. While most people are not opposed to vaccines, there is more apathy and hesitancy since the COVID-19 pandemic subsided.

Vaccines accrue a relatively big part of their value through broader economic and societal benefits, such as their impact on the productivity of the population, which is not well recognized by current HTA (Health Technology Assessment) methods. A recent Office of Health Economics (OHE) study showed that adult vaccines can return up to 19 times their initial investment to society, by preventing and reducing morbidity and mortality, reducing healthcare costs, increasing productivity and social equity, and delivering other broader societal values. However, evidence gaps remain for some of the broader elements of the value of immunization programs.

Evolving Vaccine Regulation

The applicable regulatory framework for assessing vaccines is very dependent on the jurisdiction and target indication. Having a structured approach and guidance from the regulator is critical. For example, the publication of FDA guidance on what would be a successful COVID-19 vaccine was pivotal during the pandemic.

All stakeholders recognized that the COVID-19 pandemic was an extreme situation, and some of the approaches employed during the pandemic may not be sustainable in the long run. However, it is also recognized that it would be a missed opportunity not to leverage specific efficiencies gained, such as additional opportunities for early engagement and greater use of reliance and recognition, in the routine review of vaccines and other medical products.

Use of surrogate endpoints (and particularly, correlates of protection) which are reasonably likely to predict the clinical benefit, in combination with managing uncertainty through post-approval effectiveness studies, will be useful to support vaccine regulation.

Developers and regulators are exploring the use of platform approaches for vaccines, such as mRNA, protein subunit, viruslike particle, and viral vector vaccines, which can be quickly updated to the pathogen that is causing the next pandemic, or more broadly enable the use of existing knowledge about related products to simplify development and regulatory review of a related vaccine. However, not all countries are at the same stage of utilization of platform technology, and more detailed regulatory guidance is still required.

There are also regulatory complexities in terms of how vaccines are classified and reviewed within and across jurisdictions. For example, in the US, mRNA vaccines are reviewed by the FDA CBER Office of Vaccine Research and Review , but if the indication is oncology or rare diseases, it is reviewed by the Office of Therapeutic Products. In Europe, if mRNA is used in a preventative vaccine, the product is not considered a gene therapy medicinal product (GTMP). However, when used as a therapeutic mRNA vaccine, it is classified as a GTMP. A common lexicon and harmonized definition of preventative vaccines vs. therapeutic vaccines would help to boost international collaboration.

How to Better Support Health Economic Assessment of Vaccines

The value of vaccination to the broader healthcare system and economy must be better considered in HTA methodologies. Ongoing iterative HTA that allows value-based prices to be updated over time, as evidence on the benefits of a particular vaccine develops, is critical.

National Immunization Technical Advisory Groups (NITAGs) have a fundamental role in shaping immunization policies and recommending vaccines but, unlike regulatory and HTA bodies, are not typically involved in scientific advice consultations. There needs to be a formal and iterative process for information exchange between developers, NITAGs, and HTA bodies, also incorporating the patient perspective, to align on the best possible value for public health.

NITAG capacity and capability are key challenges to solve as vaccines continue to be used for a wider range of diseases and in more populations. Increasingly, NITAGs make recommendations specific to different subpopulations, which is complex and requires more resources. Therefore, greater government investment in NITAG resources and an increase in the range of expertise of NITAG reviewers is needed. It is important to maintain the independence of the NITAGs and carefully manage any perception of conflict of interest.

Infographic summary of the workshop from CIRS 2024 Vaccines Workshop Synopsis.