Standardization of the manufacturing process of excipient aliquots to COVID-19 vaccines

Introduction
To respond to the COVID-19 pandemic, health authorities have organized large-scale vaccination campaigns to protect the population. Since the beginning of the vaccination campaign in our hospital, cases of anaphylaxis are reported. Articles published in February 2021 indicate a prevalence of around 1 issue per million doses. Subsequently, our production unit was then asked to determine the excipients present in various vaccines and to evaluate the effectiveness of prick tests as a screening tool for patients at risk. These prick tests or aliquots involve dilutions of excipients containing very low volumes of allergens (< 1 mL). Ensuring the pharmaceutical quality of the raw material and production is essential. To meet these requirements and the high demand, the production unit has developed and implemented a standardized manufacturing process.

Material and method
Six raw materials (polyethylene glycol (PEG) 300, PEG 2000, PEG 3350, PEG 6000, PEG 20000, polysorbate 80) of GMP quality were diluted in 0.9% NaCl at different concentrations: 0.01%, 0.1%, 1%, 20%, 50%). For the lowest concentration, a double dilution was required. The aliquots were manufactured under horizontal laminar airflow (BPF Class A), in a controlled atmosphere zone of GMP Class C. All used raw materials are of the highest quality in accordance with the European Pharmacopoeia standard. Raw material weighing was performed using an analytical balance and controlled by gravimetric control software. Raw material dissolution was carried out using a magnetic stirrer. The final solution was filtered to 0.22 μm before conditioning in microvials. Labelling was executed in according with GMP standards.

Results
Between February 2021 and August 2022, our pharmacy manufactured 37 batches, i.e. 656 aliquots of vaccine excipients. The average batch production time was 182 minutes. Overall, producing the aliquots required approximately 106 hours of work for operators and 25.75 hours of work for pharmacists in the unit.

Conclusion
Thanks to the development of a production method and the establishment of a well-defined protocol, the manufacturing demands for COVID-19 vaccine excipient aliquots were successfully integrated into the routine activity of our pharmacy. These new requests have introduced a new field of expertise and specialization to the production unit and have allowed the allergology department to assess the risk of anaphylactic reaction prior to vaccination. They have also contributed to a better understanding of the mechanisms underlying excipient reactions.

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