Early-Stage Considerations for the Manufacture and Delivery of Vaccines

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The speed of development of COVID-19 vaccines in response to the global pandemic has been extraordinary; the progress made by the pharmaceutical industry to create effective vaccines has been supported by fill/finish operations and packaging manufacturers to ensure the delivery and safe transportation of the vaccines.

With expected high demand for COVID-19 vaccines for the next few years, the pharmaceutical industry should assess the optimal vaccine delivery solutions as vaccine rollout continues and evolves.

New vaccines are initially packaged in vials—which are easier to handle in a laboratory environment than prefilled syringes or blow-fill-seal containers—and are simple and cheap. Commercial launch can be expedited by releasing a new vaccine in the same vial container used in early development, shelf life, stability, and extractables and leachables studies, eliminating the need to repeat tests for a different container, and saving time and expense needed to investigate alternative primary packaging options.

Vials are versatile; in addition to liquids, they can be used to package lyophilized and cryogenic products, as well as those in powder form. Vials can also be used to package multiple doses in a single container, an important consideration when global fill/finish capacity is in short supply, as was the case in 2020 when the COVID-19 pandemic struck. By using larger vials that can hold five or six doses—as was the case for the Pfizer-BioNTech and Moderna vaccines approved under FDA Emergency Use Authorization—the number of doses that can be filled using available filling capacity will be significantly higher than if single-dose packaging is used.

Multi-dose vials are the fastest route to deliver the billions of vaccinations needed in a short period of time to combat the pandemic. For non-pandemic applications, however, vaccine delivery typically transitions into another format for commercialization, most likely a prefilled syringe, as development moves into Phase II or Phase III clinical trials.

The shift to a prefilled syringe also is a lifecycle management tactic once a vial-packaged vaccine is established in the marketplace. The transition, however, requires analysis of the formulation, product stability, and consideration of how the vaccine will be administered to patients.

Converting from vial to syringe

In general terms, glass vials are the preferred option for primary packaging when speed to market is the key driver in drug product development. A prefilled syringe is preferred if ease of use or patient experience are more important than speed or if minimizing product waste is important.

If a vaccine formulation is stable in liquid form, there are few challenges to change from a vial to a syringe format. If there are stability issues, reformulation will be required; this decision will be influenced by the nature of the vaccine, preferred shipping methods, and the container options.

Human factors should be addressed when considering a packaging format change. During the COVID-19 pandemic, some patients avoided visits to healthcare providers, leading to more remote medical consultations. For patients requiring routine injections, the use of self-administered prefilled syringes may become a trend necessitating new safety systems or autoinjectors.

Currently any cryogenic product must be packaged in a vial. Internal research is underway at the author’s company to analyze how syringes are affected by a freeze-thaw cycle. If data show that efficiency and mechanical performance are not compromised, vaccines that need to be stored at frozen or cryogenic temperatures could be frozen as single doses in syringes. Prefilled syringes could facilitate administration to patients outside a mass vaccination center setting.

All vials, including multidose vials, are intentionally overfilled to guarantee that the healthcare worker will be able to retrieve the correct number of doses from a vial. The overfill can result in unused vaccine that is not administered to patients. For example, FDA granted Pfizer-BioNTech permission to extract six doses of its COVID-19 vaccine from vials originally approved for five doses due to excess overfill (1).

Prefilled syringes, which contain the exact dose, reduce waste of the drug product and are suitable for routine vaccinations such as influenza. While research is still in the early stages, it is expected that SARS-CoV-2 infections are likely to continue and the new COVID-19 vaccines may migrate to a single-dose prefilled syringe to reduce waste and avoid expiration of unused doses.

Several factors must be considered when converting from a vial delivery method to a prefilled syringe. If the product is not in liquid form, reformulation will be required. Product stability in the syringe must be established before pre-marketing studies commence.

A logistical hurdle when migrating from a vial-filled product into a prefilled syringe is identifying the capacity needed for the fill/finish operations. For innovator drug companies, fill/finish can be done in-house or by a contract manufacturing organization with the equipment and experience required to process the preferred container and the capability to handle that type of product. In-house manufacture may require investment in new capacity for a dedicated line for mass production of a single product or a flexible filling operation that can handle multiple products and different size vials. Flexible capacity has been crucial in the current efforts to fill COVID-19 vaccines.

Different drug containment solutions for vaccines

The popularity of different container types varies regionally and typically is influenced by the cost of shipping and warehousing. In North America and Europe, small formats such as 2R and 6R vials predominate, while in Latin America and Asia, larger multidose vials are more common. For COVID-19 vaccines, however, larger vials are being used globally because of the billions of doses required to achieve widespread vaccinations. In addition, vials are easier to transport because they pack more closely than syringes within blisters.

The most common size prefilled syringe is 1 mL with either a staked 5/8-in needle for intramuscular injection or a luer-lock adapter to allow a healthcare professional to select the appropriate needle. Currently, the market demands see an approximately 2:1 split between adapter and staked needle, according to market research by the author’s company. While the vast majority of staked needles are 25 gauge and 3 bevel, there is a trend towards using a 5-bevel needle to reduce the patient’s pain perception.

For other vaccines, approximately 40% of the vaccine containers used today are syringes, with a high growth both in volumes and value. For these syringes, a compound annual growth rate of 8% in volume and 5% in value is anticipated from 2020 to 2024 (2).

COVID-19 has changed the vaccine development landscape dramatically; more than 230 COVID-19 vaccines are in development; however, only three vaccines plan to launch in syringe format (3).

To date, syringe-filling capacity has not been impacted by high demand as much as vial-filling demand. By reprioritizing production space can be created to manufacture billions of vaccines to meet global needs. However, the author estimates that overall fill/finish capacity for vials and syringes is not sufficient.

Both formats have their advantages and should be considered as potential options at the start of development programs. The COVID-19 pandemic has posed significant challenges to the vaccine fill/finish industry, and glass containers are playing a crucial role in getting vaccines to the general population. Depending on the future global needs for vaccinations, prefilled syringes may gain a significant market share.

References

1. FDA, Fact Sheet for Healthcare Providers Administering Vaccine, www.fda.gov, Feb. 25, 2021.
2. IQVIA, Proprietary data.
3. WHO, “The COVID-19 Candidate Vaccine Landscape and Tracker,” www.who.int, accessed Feb. 8, 2021.

About the author

Daniel Martinez is syringe product manager, Stevanato Group.

Article Details

Pharmaceutical Technology
Vol. 45, No. 4
April 2021
Pages: 26–28

Citation

When referring to this article, please cite it as D. Martinez, “Early-Stage Considerations for the Manufacture and Delivery of Vaccines,” Pharmaceutical Technology 45 (4) 2021.