Considerations for bioanalytical characterization and batch release of COVID-19 vaccines

Abstract

The COVID-19 pandemic has prompted hundreds of laboratories around the world to employ traditional as well as novel technologies to develop vaccines against SARS-CoV-2. The hallmarks of a successful vaccine are safety and efficacy. Analytical evaluation methods, that can ensure the high quality of the products and that can be executed speedily, must be in place as an integral component of Chemistry, Manufacturing, and Control (CMC). These methods or assays are developed to quantitatively test for critical quality attributes (CQAs) of a vaccine product. While clinical (human) efficacy of a vaccine can never be predicted from pre-clinical evaluation of CQA, precise and accurate measurements of antigen content and a relevant biological activity (termed “potency”) elicited by the antigen allow selection of potentially safe and immunogenic doses for entry into clinical trials. All available vaccine technology platforms, novel and traditional, are being utilized by different developers to produce vaccines against SARS-CoV-2. It took less than a year from the publication of SARS-CoV-2 gene sequence to Emergency Use Authorization (EUA) of the first vaccine, setting a record for speed in the history of vaccine development. The largest ever global demand for vaccines has prompted some vaccine developers to enter multiple manufacturing partnerships in different countries in addition to implementing unprecedented scale-up plans. Quantitative, robust, and rapid analytical testing for CQA of a product is essential in ensuring smooth technology transfer between partners and allowing analytical bridging between vaccine batches used in different clinical phases leading up to regulatory approvals and commercialization. We discuss here opportunities to improve the speed and quality of the critical batch release and characterization assays.

The Promises of Speeding Up: Changes in Requirements for Animal Studies and Alternatives during COVID-19 Vaccine Approval–A Case Study

“…Interviewee 4 added: "The COVID-19 vaccines, much like most modern vaccines, are exceptionally well-characterised and therefore rely on the use of in vitro methods for the batch release testing". These in vitro alternatives are more precise, robust, cheaper, and have a shorter turn-around time than in vivo animal assays [32,34]. They are also potentially more societally (and scientifically) appropriate (interviewees 4 and 9, medical sciences, society and vaccine developer representatives).…”

SARS‐CoV‐2 vaccines: A double‐edged sword throughout rapid evolution of COVID‐19

“…After a long season of challenges with the SARS‐CoV‐2 outbreak, all concerns go to the safety and potency of those available types of COVID 19 vaccines (Sanyal et al, 2021 ). Due to the lack of understanding about cross‐reactivity between coronaviruses (including SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2), the suboptimal level of neutralization of the pre‐existing antibodies against coronaviruses and SARS‐CoV‐2 vaccine could potentially result in ADE or a more severe illness.…”

Rapid Identity and Quantity CQA Test for Multivalent mRNA Drug Product Formulations

“…11,17,20,33 While future mRNA vaccines may not be developed at quite the same pace as those for COVID-19, anticipated accelerated development timelines compared to traditional vaccines and an increase in development of multivalent mRNA vaccines highlight the need for improved, rapid analytical tools that can streamline bioprocess development and optimization, formulation development, and QC testing to further reduce time to market and improve between-lab standardization. 21,32,34 In this work, we demonstrate performance of a model multiplexed nucleic acid microarray-based assay for influenza mRNA vaccine construct identity and quantification. Performance is demonstrated using vaccine-relevant model influenza hemagglutinin (HA) and neuraminidase (NA) bivalent mRNA constructs from the literature.…”