Bruno Baney

Scientists researched, developed and tested COVID-19 vaccines in record time — then the race to manufacture and deliver them to health care sites around the world began.

To save lives, the vaccination program was rapidly rolled out. On the front line, pharmacists, nurses and doctors worked day and night to vaccinate the most vulnerable patients first.

As soon as the breakthrough mRNA vaccine was approved for use, its long-term cold storage criteria made the headlines. Many traditional vaccine formulations are stored at around 2°C to 8°C, yet in this case, much colder conditions were needed.

Cold storage for a vaccine being used on this scale was unprecedented. More questions came from health reporters when it became apparent that the vaccines wouldn’t be delivered in pre-filled syringes, ready for injection, but in separate vials, that had to be drawn up in to a syringe, then administered to patients.

Questions about the impact of deep cold storage on glass prefilled syringes (PFS) also surfaced. The first wave of mRNA vaccines had been distributed in separate vials. But could future vaccines be delivered more efficiently in glass PFS?

Cold storage ensures drug potency and shelf life. But low temperatures can induce changes in container dimensions, lead to thermodynamic phase transition — turning liquid to solid and vice versa, or rubber crossing glass transition — and thermal shock.

To try to answer some of these questions, BD Medical Pharmaceutical Systems began investigating the impact of extremely low temperatures on glass PFS when the storage requirement for mRNA COVID-19 vaccines first emerged.

For pharmacists and health care workers, using a PFS reduces the complexity of the vaccination process. The syringe is already filled, so the vaccine is ready to administer straight away, there is no need for dose preparation — from removing vials from their boxes and drawing the drug from multidose vial up into the syringe, to administering the injection.

PFS provide the correct dose, ready for injection, also reducing the risk of drug and bacterial contamination. Patient and pharmacist safety is one other aspect. Having the vaccine dose already prepared requires less manipulation of syringes and accordingly reduces the likelihood of needlestick injuries. There is also less drug wastage.

Workflow efficiency improves. Research by Claudia Pereira and David Bishai of the Johns Hopkins Bloomberg School of Public Health published in Expert Review of Vaccines concluded at the occasion of the last flu pandemic (2010) that in a pandemic situation where 300 million Americans would require vaccination, PFS would save 3.12 million hours in health care worker time, worth $111.1 million.

We needed to know more about the impact of cold storage on these devices. We knew the benefits of PFS in vaccination programs, we faced many questions from customers about the impact of deep cold storage on PFS, but we didn’t have data on this topic at that time. When COVID-19 hit, no one in the marketplace knew what would happen for PFS in such conditions, with the exception of a BD product used in storage at -25°C. We needed to look at the materials used in our designs — glass, plastics, rubbers, lubricants, and the ups and downs of materials in cold storage.

From previous research on biologics storage in containers and years of experience in prefilled syringe containers, we had the knowledge of and scientific background in material and contact science, analytical and molecular chemistry, mechanical modelling to study the physics and the effects of low-temperature storage on the functional performance of a syringe — along with the opportunity to extend our capabilities to external labs. So we started research in June 2020.

Our researchers’ team conducted a comprehensive analysis of approximately 2,000 pre-filled syringes after deep cold storage at -20°C and -40°C. Tests were conducted on several combinations of glass barrel coatings, formats — from 0.5 to 3 mL — different tip and flange designs, and multiple elastomeric closures with various state-of-the-art methods, including Lighthouse Laser Headspace Analysis, at these temperatures. The study showed that glass PFS did not present any risks when stored down to -20°C and -40°C and that key product functions were unaltered. Importantly, the count of subvisible particles and container closure integrity remained unchanged when compared to those stored at room temperature.

Our research is ongoing. We keep assessing the performance at even lower temperatures. In this study, the important parameter that wasn’t evaluated is ultimately behavior in the presence of the drug itself. In the future, we look forward to partnering with pharmaceutical companies to advance PFS in deep cold conditions — and helping those on the front line who are performing the vital task of delivering the vaccines to patients.

Bruno Baney is vice president of R&D for Pharmaceutical Systems at BD.