All vials are not the same: Potential role of vaccine quality in vaccine adverse reactions

Abstract

A recent commentary in this journal proposes looking beyond polyethylene glycols (PEG) when investigating anaphylactic reactions to mRNA COVID-19 vaccines [1]. It suggests examining other ingredients in those vaccines as potential causes of anaphylaxis. We agree with the need to broaden the scope when investigating vaccine adverse reactions, but we propose going beyond vaccine ingredients. A recent study reported that 581 people with anaphylaxis histories from previous vaccine shots did not develop anaphylaxis after receiving the Pfizer/BioNTech mRNA COVID-19 vaccine [2], suggesting that the vaccine ingredients might not always be the cause for anaphylaxis associated with this vaccine. While both active and inactive ingredients of a vaccine may be the cause of some adverse reactions, another possible cause to consider is subpar quality of the individual vial. We suggest taking the quality of individual vaccine vials into account in an adverse reaction investigation, i.e., a serious adverse reaction, anaphylaxis or other types, might be caused by one defective vial out of many good-quality vials. An argument for this possibility is that vaccine adverse reactions are not always reproducible on re-exposure [3], which hints at an element of chance. For example, a recent retrospective study found that 159 patients who had immediate reactions to the first dose of mRNA COVID-19 vaccines, including 19 individuals with anaphylaxis after the first-dose, tolerated the second dose [4]. The reason for this is unclear at this time. It is not inconceivable that the first and second doses may respectively involve vials of different quality, and therefore elicit different responses from a person. When the defect rate is low, it is highly unlikely that a given person will receive two bad doses in a row. For example, if the defect rate is 1 per 105, the probability that a given person receiving two bad doses is 10-10. Indeed, focusing entirely on vaccine ingredients in adverse reaction investigations may leave an investigation unsolved when good-quality ingredients are not the cause. In Sweden, high counts of narcolepsy were noticed after immunization with Pandemrix (an H1N1 influenza vaccine) in 2009 [5]. Investigations that focused on the adjuvant in Pandemrix failed to establish a causal link between narcolepsy and the adjuvant [6]. To this date, the cause has not been identified [7]. The culprit might have been a few defective vials in the batch delivered exclusively to Sweden rather than the adjuvant or other ingredients. Collecting quality data on every vial before injection might have prevented those narcolepsy incidents, but such a practice is not currently in place. In fact, the current quality control system for vaccines is not well equipped to catch a few defective vials among many good-quality ones unless the defects are visible to human eyes. In this commentary, we introduce an emerging noninvasive inspection technology—water proton nuclear magnetic resonance (wNMR)—that could be used for fast and reliable quantitative inspection of sealed and labelled vials of liquid drug products. wNMR could be used to quantitatively inspect every vial before product release at the production site, before injection at the vaccination site, and anywhere in between. We discuss vials in this commentary, but other primary containers for liquid drug products such as syringes, pens, bottles, etc., could also be inspected by wNMR.