As the industry well knows, bringing a new product to market is a painstakingly long process. Generally, it takes about a decade to develop a new vaccine and typically between two and five years to develop the manufacturing process for a new product. Then, to build a stainless-steel facility from scratch and get it commissioned? That’s usually about another three years.
Very few people, therefore, thought we would see a viable COVID-19 vaccine in use before 2022. Yet here we are in mid-2021 with approximately 3.5 billion vaccine doses administered globally at the time of writing — a truly remarkable achievement for the thousands of people worldwide who have worked tirelessly to make it possible.
This success would not have been possible with traditional methods. We needed rapid, proactive, disruptive innovation to open up new possibilities — not just in developing the vaccine itself, but in being able to manufacture it on an industrial scale and at a speed never before seen in the biopharma industry.
Two Danaher operating companies— Pall Corporation, which specializes in filtration, separation, and purification technologies; and Cytiva, a global provider of technologies and services for therapeutic development and manufacture — have been intimately involved in the race to develop viable COVID-19 vaccines and have experienced first-hand the breakthroughs and innovations that have gone into this remarkable success.
Here are their stories.
The blueprint for a billion doses
In the spring of 2020, the University of Oxford contacted Pall to enlist their help with what would become one of the greatest biopharma manufacturing challenges of all time: to design the process that would enable them to produce billions of doses of their new viral vector in a fraction of the time it had taken for similar products previously. Not only did it need to deliver speed, but this process also needed to be simple, scalable, and easy to implement in many different manufacturing sites to achieve the same product no matter where it was manufactured in the world.
Pall already had significant expertise on viral vector manufacturing, having already developed over 30 large-scale, viral-vector-based processes in the biopharma industry prior to the pandemic, creating a blueprint that could be used for the manufacture of many future viral vector therapies, including standardized manifold designs, equipment lists and processes. The team at Pall applied their process development expertise and production know-how to design and establish a process for the Oxford/AstraZeneca COVID-19 vaccine.
This combination of technical expertise and experience of scaling production processes with Pall’s integrated manufacturing solutions for gene therapy and vaccines turned out to be vital in accelerating the speed at which the COVID-19 vaccine process could be developed. Instead of starting from scratch, the Pall team had already created a repeatable template for viral vector manufacturing that covered 80% of what would be needed with the Oxford/AstraZeneca vaccine — they simply then needed to customize the equipment, consumables and workflows based on the specific requirements of this project.
This automated, end-to-end integrated, platform solution was developed to tackle the challenge of scaling up manufacturing for gene therapy. The scalable platform can also address issues that arise when genomic products are manufactured using individual manufacturing steps. For instance, single-use technologies allow for easy scale-up from the laboratory scale to full current Good Manufacturing Practice (cGMP) commercial operation. The company’s single-use platform achieves this by keeping the materials of construction the same for its comprehensive range of disposable solutions for upstream through downstream to formulation and filling processes. This approach can provide the same robustness, reliability and batch records required for commercial manufacturing.
Because of such standardization, the team was able to configure the equipment solutions and manifold designs without needing to go through lengthy validation processes — reducing risk and cutting out what normally takes up a huge portion of the process development timeline.
Taking manifolds as an example: There are over 20 contract manufacturing organizations (CMOs) working to manufacture the vaccine, each using more than 50 different manifolds in each bioprocess. This could potentially lead to hundreds or even thousands of different manifold designs being used around the world. Thanks to the standardized processes deployed on this project, the same manifolds were used across the entire project — simplifying the supply chain and adding certainty and consistency for manufacturing teams, wherever they are in the world.
And because of the use of single-use technologies, the team was able to develop a scalable manufacturing process for the COVID-19 vaccine in just eight weeks. This allowed for the first commercial batch at one of Oxford/AstraZeneca’s contract manufacturing partners in the UK to be run only 60 days after starting to work on the process itself — a remarkable turnaround time on a truly groundbreaking global project.
Scaling up with flexible factories
In January 2020, the Coalition for Epidemic Preparedness Innovations (CEPI) — considered one of the most influential organizations in the fight against COVID-19 — asked Australia’s University of Queensland to generate the raw materials for clinical trials of a vaccine that had not even been developed. What’s more, they planned to start clinical trials for the vaccine in just 16 weeks — an exceptional timescale for something of this nature. The university quickly turned to Cytiva, a long-time collaborator, for help on this vital project.
By Feb. 8, with Cytiva’s experience and hands-on assistance, the University of Queensland had a plan in place to speed up the timeline to a matter of months, rather than the usual one and a half to three years. This was despite the fact that this particular vaccine included an innovative structure called a molecular clamp.
To achieve this in time, multiple processes had to run in parallel. Cytiva started by providing key process development expertise to build the first-generation purification approach, and a scalability plan that included technology transfer to the Cytiva site in the U.S. where the clinical material for next phases of clinical trials would be used. The entire process was coupled with a strict supply chain plan, disposables, and chromatography resins, ensuring critical material would be available to progress through the clinical steps.
Cytiva also had to rapidly innovate and speed up its own development processes to meet the timescales. They developed, in real time, a new chromatography resin that was not yet commercially available and introduced it into the process. This helped optimize product purification and accelerate to process scalability.
But what really made a difference in this vaccine development project was the decision to take an end-to-end approach that made the factory incredibly flexible. It provided fast deployment and accelerated access to production with adaptable, scalable processes. Each step of the plan was re-imagined, from the bench to future manufacturing.
This end-to-end, single-use technology-based manufacturing process approach was fully automated and integrated. Cytiva used its flexible manufacturing platform, which made it possible to “copy and paste” the manufacturing process to multiple sites around the world, with speed and reliability in order to get the same result — a consistently effective vaccine.
For the future
There is a great variety of ways vaccines can be produced, for COVID-19 or for any other infectious disease. Each one is unique, and there is no single silver bullet solution to manufacture every vaccine in the most effective way. But it is possible to standardize key elements to significantly accelerate process development and manufacturing — a balance that we as an industry have not been able to strike until now.
The shift from stainless steel to single-use has been crucial. Now, by embracing new innovations in manufacturing — whether using a flexible factory approach, or by standardizing key aspects of the manufacturing process — we believe we can rapidly advance biopharma’s ability to bring vaccines and other new therapeutics to market faster.
This year demonstrated how industry-wide collaboration enables innovations in drug development and greater speed to market. Major and complex challenges require a diversity of experience, backgrounds, and cultures to foster solutions. We must embrace a collaborative spirit to develop life-saving treatments the world needs.