The Future of Vaccinations and Prefilled Syringes in Deep Cold Storage

Guillaume Lehée - R&D Innovation Leader, BD Medical - Pharmaceutical Systems

COVID-19 vaccines have been developed in response to the worldwide pandemic at an incredible rate.¹ By November 9, 2021, 7.3 billion COVID-19 vaccine doses had been delivered worldwide, with approx. 30.3 million doses administered daily.² These times have seen unprecedented challenges such as the distribution of disposable injection materials, vaccine dose availability, and cold chain logistics. Such logistics include a cold chain supply with temperatures ranging from –70°C employing specialist shipping, to 2 to 8°C when administered. It raised a question: how can future immunization campaigns be made even more effective? Prefilled syringes (PFS) have become an increasingly appealing option for the packaging and delivery of vaccinations. They could be part of the answer, as they can help reduce various issues that come with vaccine administration^3,4,5,6,9,10.

Navigating the World of Pre-Fillable Syringes

Over the years, PFS have become well-established in medicine thanks to their many benefits. PFS are ready to use as they are prefilled during the fill and finish operation at pharmaceutical companies, under Good Manufacturing Practices (GMPs) quality controls. They are filled with the right dose required for one individual vaccination. This minimizes the number of preparation steps and time at the point of vaccination,^3,4,5,6 versus vaccines supplied in vials, where the dose must be drawn from the vial with a disposable syringe. It has been calculated that, in the event of a pandemic, using PFS to vaccinate 300 million individuals in the United States might save over 3 million hours of healthcare practitioners’ time, allowing more people to be vaccinated.⁷ For this reason, PFS are known to contribute to workflow efficiency improvement.⁸

PFS are expected to provide benefits regarding patient safety, according to health professionals.⁹ Even with the most experienced healthcare professionals, human errors can occur when drawing up a vaccine dose from a vial to a syringe. As ready-to-use syringes are pre-dosed for a single injection, PFS contribute to reduced risk of dosage errors.¹⁰

In addition, as they require less preparation manipulation than vials, PFS have also been found to decrease microbial contamination during the syringe preparation procedure .

Dose Sparing and Waste Minimization

Since multi-dose vials can hold up to five or ten doses,¹⁵ it’s not uncommon for doses to be left over in the vials at the end of the day when vaccinating fewer people. Multi-dose vials must be discarded a few hours after opening due to the lack of preservative in the solution - even if all doses in the vial have not been administered.¹²

Also, to ensure that healthcare professionals can retrieve the right number of doses, multidose vials are purposely overfilled.¹³ These combined issues – discarded doses and overfill - can result in 5-25% of the vaccine product being wasted.¹⁴

Due to their “dead space,” or the volume between the fully depressed plunger and the needle tip, disposable syringes and needles used for reconstitution or administration of vaccines from a vial can generate some additional waste – up to 20% of a typical 0.5 mL vaccination dosage. According to internal data, it should be noted that specially engineered disposable syringes can reduce dead space by a factor of 10.^15,16 For glass PFS used for vaccination, the dead space should be less than ~ 0.04mL,¹⁷ of a standard vaccine dose of 0.5 mL, which is less than 10% of a standard vaccine dose.

Based on these three considerations, PFS also contribute to decrease vaccine wastage.¹⁸ 

The Deep Cold Storage Landscape

Vaccines require cold storage to maintain potency and ensure drug shelf life. Traditional protein-based vaccine formulations can be kept at temperatures ranging from 2°C to 8°C.¹⁹ Pfizer/BioNTech’s COVID-19 vaccine and Moderna’s COVID-19 vaccine both rely on the newly innovated mRNA-based vaccine technology, which necessitates storage at sub-zero temperatures. These vaccines are kept at extremely low temperatures, between -50°C to -15°C for Moderna,²⁰ and down to -90°C for Pfizer/BioNTech.²¹ mRNA vaccines are faster to develop than conventional protein-based vaccine.²² However, even with these benefits, handling mRNA vaccines in cooler storage conditions presents several difficulties. Ultra-low temperatures can cause thermodynamic phase transition of the components and materials of the filled container, such as fluid freezing,²³ rubber crossing its glass transition²⁴ and dimensions to shrink, due to material coefficient thermal of expansion, as well as thermal shock. As a result, deep cold storage could compromise the delivery system’s functionality and integrity²⁵ with potential impact on the vaccine’s contents.

When the storage requirement for mRNA COVID-19 vaccines initially surfaced, the performance of glass PFS in extremely low temperatures was unknown.

Glass PFS systems are composed of several materials and interfaces which will face various challenges. Of these key challenges, several solid materials, such as the plunger stopper, barrel and tip cap, will shrink. Elastomer components such as the plunger stopper and tip cap may cross their glass transition between -40°C and -65°C. Water and silicone components will also freeze²⁴ and, in addition, the stopper may move due to the variation of the energy of the air trapped within the headspace following an ideal gas law.²⁵ With these challenges, the device could be susceptible to leakage or weakness before or during injection. The integrity of the device is crucial to ensure the components with which it is filled remain stable throughout the manufacturing and storage process. 

Understanding the behavior of PFS components and interfaces is crucial to assess whether PFS can sustain deep cold storage temperatures. BD Medical - Pharmaceutical Systems has conducted a preliminary study investigating the effects of deep cold storage on glass PFS with a total of 2,000 PFS systems being stored at -20°C, -40°C or -80°C. Following 1-week storage at these temperatures, tests were conducted after one thermal cycle using various state-of-the-art methodologies, including Lighthouse Laser Headspace Analysis,²⁶ on numerous combinations of glass barrel coatings, formats ranging from 0.5 to 1-3 mL, varied tip and flange designs, and multiple elastomeric closures.

The Future of Vaccine Development and Delivery

In this study, the PFS functions were unaltered when stored at -20°C and -40°C. And when compared to those stored at room temperature, the count of subvisible particles and container closure integrity remained unchanged. We anticipate that the glass barrel PFS systems tested would be suitable for use when storage temperatures of -20°C and -40°C are required.

There is now an opportunity for the future of vaccine developers to consider using PFS in deep cold conditions. Being able to store vaccines in glass PFS in deep cold temperatures could significantly improve the efficiency by which they could be administered to the masses.²⁷ These applications for PFS in deep cold storage go beyond COVID-19. The use of mRNA vaccines against other viruses – for example influenza – is being investigated. Notably, following the effectiveness of Pfizer’s mRNA vaccine in the fight against COVID-19, they have recently launched a mRNA influenza vaccine trial to test its potential ahead of the predicted winter flu.²⁸

In the US national strategy for the COVID-19 response and pandemic preparedness, the federal government promised to explore dose-sparing strategies which have the potential to considerably expand vaccine supply.²⁹ If the COVID-19 vaccine was to be contained in PFS, it could support dose sparing and improve workflow efficiency, and therefore, possibly contributing to a more rapid and simplified rollout.

What Does This Mean for the Pharmaceutical Industry?

So, we must ask – what are the implications on the pharmaceutical industry? It has been demonstrated that vaccines contained in PFS not only save administration time, but also reduce dosing errors and prevent wastage.

With this study, we have opened possibilities for pharmaceutical companies to choose PFS for drugs that require deep cold storage. PFS may be considered the solution, with benefits for both patients and clinicians.

These recent results on glass PFS at sub-zero temperatures are encouraging. To further the significance of these findings, investigations into the stability of drugs contained in glass PFS in deep cold storage must be continued. Pharmaceutical companies - producers of those vaccines - and PFS suppliers should pursue these investigations together. Such partnerships would help better understand the interactions between vaccines and containers, and of PFS performance in presence of drugs, in extreme cold temperatures. Doing so will enable the acceleration and optimization of the use of glass PFS in deep cold conditions.

References

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