Interest in innovative vaccines that use messenger ribonucleic acid (mRNA) and viral vectored technologies was among the key draws at this year’s World Vaccine Congress (WVC) on April 3-6 in Washington, D.C. This follows the massive success of the vaccine platforms in quickly responding to the COVID-19 pandemic, saving countless lives. Quality-focused solutions developed by USP to support availability and trust in the COVID-19 vaccines – and continuing adoption and evolution of the technologies for future applications – was a key focus of my address to WVC attendees.
The World Vaccine Congress is among the largest conferences dedicated to vaccines, covering a wide range of vaccine topics, such as manufacturing, experimental research, and related policy solutions. Hosting over 3,200 attendees from around the world, the event is well known as a place where vaccine scientists and stakeholders from across the healthcare ecosystem can gather to network and forge collaborations to facilitate advancements in the field.
During my standing-room-only presentation, I updated attendees on key USP activities in the vaccines space with a major focus on USP toolkits and guidelines designed to aid manufacturers, distributors, and healthcare providers in supplying trusted, quality vaccines, including those based on mRNA and viral vector platforms. These include USP’s draft guidelines on analytical procedures for mRNA vaccine quality and viral vectored vaccine quality.
The first versions of the analytical procedures for mRNA and viral vectored vaccine quality were published in February and March 2022, respectively. These guidelines defined critical quality attributes (CQA) for these new vaccine platforms, along with appropriate methods for their monitoring and control. The documents were developed in collaboration with input from the USP Vaccine Advisory Group and from Expert Committees consisting of independent subject matter experts, regulators, and other stakeholders from across the vaccine community. In supporting a shared understanding of quality, the guidelines help accelerate future product development, guide successful scale-up of manufacturing, and fuel regulatory confidence that manufacturers are employing best practices and appropriate quality controls when using these new modalities.
The guidelines were just one part of a broad portfolio of solutions developed by USP to respond to the COVID-19 pandemic through work with global regulatory organizations, industry, healthcare providers, and other stakeholders. Beyond the mRNA and viral vectored vaccine quality guidelines, USP solutions included the COVID-19 vaccine handling toolkit and international guide, that assembled in a single resource operational strategies addressing potential efficiency gaps in vaccine delivery to help provide more shots in arms. USP solutions also included COVID-19 vaccine quality assessment toolkits. These resources were published between January 2021 and January 2022.
Over the past year, USP has again reached out to the vaccine community for further input to improve the initial versions of the mRNA and viral vectored vaccine quality guidelines. Over 300 comments were received for the mRNA guidelines, resulting in a second edition of the guidelines that added a range of additional testing methods including a high level listing of upstream testing methods and a more detailed and inclusive set of downstream testing methods for drug substance through to drug product as well as method donations from leaders in the field. Similarly, the viral vectored guidelines public outreach resulted in well over 100 comments, which will contribute towards an updated version that includes additional methods of control focused on manufacturing CQAs.
During round table discussions at the WVC, it was clear many stakeholders had reviewed the second iteration of the mRNA vaccine guidelines. Likely due to the relative newness of the mRNA platform, there was much interest in the details of production and methods for CQA control throughout the process. Beyond its application for COVID-19 vaccines, mRNA vaccine technology has been advanced as a promising solution for addressing future pandemics as well as other infectious diseases such as rabies, Zika, and cytomegalovirus infection. Several mRNA-based products are also in clinical development for cystic fibrosis and various cancers. Reflecting that versatility, USP’s latest mRNA guidelines go beyond COVID-19 and encompass a broader range of mRNA products with methods and information that can be applied to other mRNA drug products such as those for cell and gene therapy, cancer treatment, and metabolic disorders. USP efforts going forward will include verification of methods, development of physical standards, and additional USP-NF chapters to cover methods in more detail.
Emerging products leveraging mRNA vaccine technology include self-replicating forms. These forms contain a replicase that allows for decreased amount of delivered mRNA to the recipient’s cells, which is expanded once in the cells, rather than non-replicating forms where the total effective dose must be delivered along with its encapsulating lipid shell. In this way the delivered mRNA dose, along with its lipid shell, can be reduced. Meanwhile, viral vectored vaccines are now in development for nasal inoculation, which may provide improved balance of immune response.
As these and other novel platforms advance, USP will continue to stay on the cutting edge of science – in collaboration with global stakeholders – to develop guidelines, best practices, and standards that aid manufacturers, regulatory agencies, and healthcare providers in ensuring availability of trusted, quality products.
