Elisabeth Vachette, Head of Product Management for Bags/Mixing/Tanks at Sartorius Stedim Biotech, discusses the challenges associated with distributing a vaccine to the global population with Dr Kevin Robinson
With a number of COVID-19 vaccines now in Phase III trials, manufacturers and governments must focus more and more on the logistics and practicality of distributing a vaccine around the world.
As with every other aspect of vaccine development during a pandemic, speed is of the essence. If a vaccine is effective but difficult to distribute, it will be nearly impossible for the vaccine to reach all the people who need it in a timely way.
Competing vaccines may quickly takeover. Below, Elisabeth Vachette discusses some of the main challenges and factors that must be considered to ensure that the vaccine can be distributed efficiently.
KSR: What challenges are manufacturers specifically tasked with when trying to figure out how to effectively distribute a vaccine for COVID-19?
EV: As with every other aspect of COVID-19 vaccine development, manufacturers don’t have the luxury of time. They are expected to produce and transport millions of doses that are ready-to-go … if and when they get regulatory approval.
There are two key aspects to managing this situation. The first is to invest in new manufacturing facilities and supply chain infrastructure. The second is risk mitigation — to stay agile and ready to negotiate any future challenges so manufacturing and distribution can continue.
For example, many companies are ensuring their supply chain is localised in different parts of the world. This removes some of the vulnerability that global supply chains often have if they rely on certain countries for key components. With a localised approach, a problem that occurs in the United States can be offset with resources in Europe.
This should limit the scope and severity of supply chain delays. The downside is that this increases the complexity of manufacturing — particularly the fill/finish stage of packaging the vaccine in its sterile vial.
Elisabeth Vachette, Head of Product Management for Bags/Mixing/Tanks, Sartorius Stedim Biotech
KSR: What tactics can we use to address this accelerated timeline?
EV: In addition to localising the supply chain, another tactic is to maximise single-use systems. This allows us to build extensive manufacturing capabilities that can pivot quickly to the task at hand.
Single-use technologies can be implemented and validated much faster than traditional stainless-steel facilities, with large-scale manufacturing capacity reached in less than 12 months. Manufacturers can get started on commercial production immediately through a pilot facility while building a dedicated facility to increase scale.
These systems are designed to be flexible, which is particularly valuable for COVID-19 vaccines, which will likely experience huge swings in demand based on accessibility and competition.
Along with scalability, single-use systems offer many advantages in situations with an accelerated timeline:
KSR: What factors do we need to consider when transporting the vaccine both locally and internationally?
EV: Some challenges apply to all vaccines, whereas others are unique to the different modes of action. For all vaccines, it is important to consider the shipping containers and bags used in their manufacturing process. These must be able to withstand different forces, such as the shocks, vibrations and compressions that can occur during air, road or marine shipment.
Following the proper protocols to monitor and validate the shipment can help to mitigate risks that may compromise the integrity of the product. ASTM International and The International Safe Transit Association both provide guidelines for shipment testing to co-ordinate the safe transportation of vaccines from start to finish.1,2
In addition to this, vaccines have different stability profiles, which refers to how they react to changes in temperature and light. Some vaccines react poorly to heat, whereas others struggle with cold temperatures or too much light.
Two of the leading vaccines in development — Pfizer/BioNTech and Moderna — use a gene-based mRNA technology that requires storage at temperatures as low as –80 °C. By contrast, non-live, inactivated or protein vaccines are typically less sensitive to heat.
Developers are optimising their formulations to help improve vaccine stability. This has allowed some live vaccines to be stable at room temperature (a max of 25 °C). The differences in stability mean that manufacturers must factor in how to maintain an acceptable temperature during the transportation process.
Certain adjuvants present in the vaccine can also make them more susceptible to freezing during transportation.
Lower temperatures may be harder to maintain, especially for low-to-middle income countries.
Single-use suppliers such as Sartorius provide end-to-end logistic solutions for cold chain or frozen bulk drug substances transportation and processing that have been extensively qualified according to the most severe standards (ASTM D4169).
KSR: How can manufacturers decrease the risks associated with transporting vaccines?
EV: Manufacturers can improve the ease of transportation by understanding quality requirements and using Quality by Design principles as a basis for product development. Specifically, working to increase vaccine thermostability during development will make the distribution process easier.
A more stable vaccine requires less oversight when it comes to maintaining a consistent temperature during transportation.
Another way to make transportation easier is to identify partners located in different areas. Traditionally, manufacturers have been centralised in a few key locations. By utilising partners from all over the world, transportation distances are decreased.
For example, the AstraZeneca and University of Oxford vaccine candidate that is in Phase II/Phase III trials has manufacturing deals with groups around the world. They have a deal with manufacturers in Mexico to produce the vaccine for Latin America, another deal with a group in Europe.3,4
It is also important that developers select reliable partners. Manufacturers should look for partners that use the proper validation protocols, such as the ASTM or ISTA standards, for shipment and ensure that these guidelines for shipment testing are being followed.
It is also good to look for a partner who uses electronic monitoring, which has been recommended by the World Health Organization (WHO) guidelines. This allows for testing of the robustness of the distribution channels in addition to electronic temperature recording.