Pre-Drawn Syringes of Comirnaty for an Efficient COVID-19 Mass Vaccination: Demonstration of Stability

Abstract

Moving towards a real mass vaccination in the context of COVID-19, healthcare professionals are required to face some criticisms due to limited data on the stability of a mRNA-based vaccine (Pfizer-BioNTech COVID-19 Vaccine in the US or Comirnaty in EU) as a dose in a 1 mL-syringe. The stability of the lipid nanoparticles and the encapsulated mRNA was evaluated in a “real-life” scenario. Specifically, we investigated the effects of different storing materials (e.g., syringes vs. glass vials), as well as of temperature and mechanical stress on nucleic acid integrity, number, and particle size distribution of lipid nanoparticles. After 5 h in the syringe, lipid nanoparticles maintained the regular round shape, and the hydrodynamic diameter ranged between 80 and 100 nm with a relatively narrow polydispersity (<0.2). Samples were stable independently of syringe materials and storage conditions. Only strong mechanical stress (e.g., shaking) caused massive aggregation of lipid nanoparticles and mRNA degradation. These proof-of-concept experiments support the hypothesis that vaccine doses can be safely prepared in a dedicated area using an aseptic technique and transferred without affecting their stability.

Stability Study of mRNA-Lipid Nanoparticles Exposed to Various Conditions Based on the Evaluation between Physicochemical Properties and Their Relation with Protein Expression Ability

“…Vortex mixing is a common operation in the laboratory; however, it should be avoided or kept as brief as possible. Selmin et al reported that strong mechanical stress, such as vortexing, leads to LNP aggregation and degradation of the enclosed mRNA [25], which is consistent with the results of this study. In addition, the possibility of aggregation was examined by collecting from a vial; however, the physicochemical properties and biological activity of LNP did not change each time when collected from the same vial on five separate occasions (Figure 5).…”

“…Salmin et al reported that mRNA-LNPs aspirated in syringes maintained their physicochemical properties for about a day, independent of syringe material, but the strong mechanical stress of manually pumping 40 times resulted in particle aggregation [25]. We prepared our experiment to determine whether LNPs could aggregate due to aspiration pressure, as they were collected from the vial through a syringe needle.…”

The Storage and In-Use Stability of mRNA Vaccines and Therapeutics: Not A Cold Case

“…This profile indicates that particle physical stability is not a major risk when a chemically stable API is used. However, the internal structure of mRNA containing particles is different from those containing siRNA 7 and mRNA-LNP particles are more likely to disintegrate upon mechanical stress, such as shaking and dropping of vials 91 , 92 . Another example is the formation of layers of aggregates on filter surfaces during sterile filtration 93 .…”

“…Two studies on real-life in-use stability of mRNA-LNP DP have been published. First, the stability of mRNA-LNPs during storage between being drawn into of syringes and being injected was monitored 92 . The second study looked at the stability of left-over material in vials of Comirnaty 91 .…”

“…Unfortunately, neither experimental data nor details to support this claim can be found in the public domain so far. Moreover, it remains to be fully established if the chemical degradation process of mRNA is the only critical quality attribute for vaccine performance as is indicated by observations e.g., by Kudsiova et al, and Selmin et al on mRNA-LNP particle size and aggregation 91 , 92 . Such considerations play a key role in determining the selection of primary containers and secondary packaging, as well as the need for temperature monitoring devices during shipping and transport, for example, as described for COVID vaccines by Ramakanth et al 149…”