WHO Consults On Evaluating mRNA Vaccines For Infectious Diseases
Special Considerations Outlined For COVID-19 Vaccines
Executive Summary
The World Health Organization says there is a pressing need for guidance on the evaluation of mRNA vaccines because of the rapidity with which clinical trials have progressed for COVID-19 candidate vaccines, their emergency use approval or authorization, and their subsequent widespread use.
The World Health Organization is inviting stakeholder feedback on a draft document outlining regulatory considerations for evaluating the quality, safety and efficacy of mRNA vaccines for the prevention of infectious diseases.
The ongoing COVID-19 pandemic has resulted in the mRNA platform emerging at the forefront of vaccine technology. The WHO document provides information and regulatory considerations regarding key aspects of the manufacture and quality control, and nonclinical and clinical evaluation of preventive mRNA vaccines for human use.
Although the most advanced vaccines in this class are for COVID-19, the WHO makes clear that its draft document should not be seen as providing guidance specific only to COVID-19 vaccines.
“However, in light of the current COVID-19 pandemic and corresponding speed of mRNA vaccine development, the document is intended to provide special considerations for this class of preventive mRNA vaccine as rapidly as possible,” the organization said.
It nevertheless said that it was not possible to offer conclusive recommendations on COVID-19 vaccines due to existing “knowledge gaps” in the scientific understanding of the pathogenesis of COVID-19 and related issues, such as precisely what level of immunogenicity is needed for a successful, broadly relevant and durable COVID-19 vaccine. These gaps, the WHO said, were currently being addressed by ongoing research and development efforts.
The scope of the draft document is limited to mRNA and self-amplifying mRNA (sa-mRNA) packaged in lipid nanoparticles (LNPs) for in vivo delivery of the coding sequences of a target antigen relevant to active immunization for the prevention of an infectious disease.
The document also outlines specific considerations, where appropriate, to help sponsors develop multivalent mRNA vaccines or to change the existing vaccine strain for some pathogens, such as for COVID-19.
Replicating agents, viral vectors and RNA replicons (packaged in viral proteins or encoded by plasmid DNA) are outside its scope. In addition, the document does not apply to mRNA and sa-mRNA products intended for therapeutic purposes (as opposed to active immunization). Also excluded from its scope are mRNA products expressing monoclonal antibodies for disease prevention or therapy.
Comments on the draft document will be accepted until 17 September and will be considered by the WHO’s Expert Committee on Biological Standardization.
Pressing Need
The WHO said there was a pressing need for guidance on the evaluation of mRNA vaccines because of the rapidity with which clinical trials have progressed for COVID-19 candidate vaccines, their emergency use approval or authorization, and their subsequent widespread use.
As regulatory pathways for emergency use authorization vary across the globe and not all countries have such pathways, the WHO stressed that the approval of mRNA vaccines for emergency use was outside of the scope of the draft document. However, suggestions are provided, where possible, for rapid vaccine development in the case of priority pathogens during public health emergencies.
The WHO recommends that the evaluation of mRNA vaccines must take into account: the inherent immunological, physiochemical and structural properties of mRNA; the need for formulation to ensure stability and efficient delivery; and the novel manufacturing process.
The organization said it was unable to offer specific recommendations on certain aspects of vaccines evaluation for various reasons, such as the lack of detailed information on the methods used for production of mRNA vaccines. Moreover, controls are not yet standardized for safe and efficacious mRNA vaccines, and in the case of candidate vaccines “certain details remain proprietary and thus not publicly available,” it noted.
It recommends using regulatory flexibility to support the evaluation of mRNA vaccines. “The detailed production and control procedures, as well as any significant changes in them that may affect the quality, safety and efficacy of mRNA vaccines,” should be discussed with, and approved by, the national regulatory authority on a case-by-case basis, it said.
The draft document had been developed based on available knowledge and will have to be updated as new data become available. Given that this is a dynamic field, both in terms of vaccine manufacturing technologies and clinical trial design, the WHO recommends that the document should be read in conjunction with other relevant recent guidance, including WHO disease-specific guidelines and recommendations, if available.