Largely because of the COVID pandemic, but also thanks to recent outbreaks of avian flu globally, Ebola in Africa, and monkeypox in Europe, there is widespread demand for new vaccines to protect people against infectious diseases.¹ Furthermore, there is a need for those vaccination responses to be rapid, efficacious, and cost-effective, if they are to outpace new viral threats emerging in all corners of the world. In this article, we consider how modern technologies, and learnings from the past few years, can be leveraged to prevent disruptions to the world’s vaccine supply.

The need for speed

The extremely rapid vaccine response to COVID, made possible from decades of scientific progress in the fields of virology, immunology, epidemiology, and clinical medicine, was truly wondrous.²

In fact, the speed with which the first COVID vaccine was developed, approved, and rolled out across the world set a new bar for Biopharma.

It is now broadly acknowledged that hastening the pathway from vaccine discovery to commercialization is not just desirable, it is an achievable step in our preparations to defend humanity against future pandemics. In recognition of this, the Coalition for Epidemic Preparedness Innovations (CEPI) has set an aspirational 100-day mission to make a safe and effective vaccine against any virus.³ This would give more people much faster access to more effective vaccines against a broader spectrum of infectious diseases.

Recombinant protein vaccines, which are obtained by conventional genetic engineering, are based on the proteins of target pathogens that can activate our immune systems. Unlike other types of vaccines that use viral genetic codes or viral vectors, recombinant protein vaccines use only the antigenic proteins themselves. This means that they cannot cause disease and they generally do not need to be frozen for storage. Their efficacy, intrinsic clinical safety, easy storage, and industrial production scalability has already positioned them as the leading human vaccine technology.

Today’s challenge is to make them as quickly and cost-effectively as possible—ideally, within 100 days!

Rethinking systems

Rethinking the production system for vaccines, with a view to shortening the time it takes for them to reach patients, could be the key to being better prepared for future health crises.

At the R&D stage, for instance, there may be difficulties in selecting the right antigen, or the product might be subject to long development cycles. Such challenges may be tackled by applying advanced technology platforms. Better optimized cell line selection can expedite clone choice, while higher throughput assessment, capacity to conduct parallel development, and automated cell line selection, cell culture and downstream development can all have significant impacts on timelines.

Even once an effective vaccine has been developed and approved, significant challenges remain in manufacturing. This was particularly evident during the COVID pandemic, when vaccine production chains struggled to keep up with global demand. It has been suggested that the main causes for supply disruptions and delays included an insufficient number of vaccine manufacturing facilities, a lack of tech-transfer capability, inefficient arrangement of production stakeholders, and critical shortages in raw materials.⁴

Addressing these manufacturing challenges involves the development of scalable processes, at vaccine manufacturing facilities that have the capacity to produce the required volumes of vaccine. It is also vitally important that those facilities have secure and stable supply chains. Certainly, following widespread disruptions to supply chains in recent years, due to the COVID pandemic and other geopolitical issues, ensuring that any facility has the necessary network to meet its supply chain requirements consistently and reliably has become a key factor in choosing a manufacturing partner.

In summary, it is possible to accelerate recombinant protein vaccine development and manufacturing, but doing so involves investment in facilities, infrastructures, technologies and equipment, and strong international supply networks, which not all Biotech or Pharma/Biopharma companies possess in-house.

Building speed

As recently as five years ago, CDMOs were not commonly used to produce vaccines. However, in the wake of COVID, the world’s vaccine manufacturing footprint has altered. While four leading vaccine development companies still account for over 80% of the global vaccine market, these organizations faced significant challenges in responding to the pandemic. Suddenly finding themselves with insufficient capacity to provide the huge volumes of vaccines required, not to mention the well-known problems with supply chains during the pandemic, these organizations engaged CDMOs with rapid access to external resources and expertise. CDMOs, due to their unique infrastructure, global presence, expertise, and capacity, were able to ramp up capabilities where they were needed to produce large quantities of vaccines in a timely manner. Many CDMOs, especially the larger ones, were also able to leverage long-term relationships with suppliers to implement alternative strategies to address supply chain disruptions.


As a result of the pressures placed on the industry during the pandemic to provide vaccines at an unprecedented rate, and thanks to the investments made by CDMOs to respond to those pressures, timelines have certainly changed. For example, the graph below shows the evolution of mAb timelines since 2015, and similar patterns have been seen with other recombinant proteins used for vaccines. While a typical CMC timeline from DNA to IND application in 2015 would have been approximately 24 months, by 2023 the same pathway was expected to take only 10 months. In fact, WuXi Vaccines streamlined vaccine development and manufacturing to such an extent that it was able to shorten the IND development timeline of a COVID vaccine to just 6 months. Such achievements can only be achieved by leveraging technical strengths, CMC, regulatory capabilities, technical platforms, and commercial facilities.

For example, accelerating vaccine production can involve the use of existing high throughput screening (HTS) strategies. Several modern technologies now provide sufficient data to drive the change from manual to automation, and this in turn can have a meaningful impact on the speed of vaccine development. For example, applying automation and digitalization to a mature HT process development and in-process testing platform at WuXi Vaccines immediately enabled a fast and systematic approach to purifying and verifying process samples, troubleshooting, and process optimization. Automated liquid handlers drove greater productivity, streamlined workflows, and optimized assay precision and consistency, while automated buffer exchangers and customizable automated workflow equipment gave scientists access to HT end-to-end solutions.

In addition, new technologies such as modular and flexible manufacturing technologies, including single-use bioprocessing systems, bring important benefits. Compared with conventional stainless-steel bioreactor facilities, the use of multiple single-use bioreactors offers a highly flexible, cost-competitive manufacturing strategy, ideally suited to the fluid demands of the vaccine market. These systems can be rapidly deployed for scaling up or scaling out to meet changing demands and easily repurposed for different vaccine candidates.

Continuing the broad application of automation through to the end of manufacture, fill and finish services are an important added offering. GMP production capabilities with fully automated, fully programmable sterile fill systems for vials and pre-filled syringes can offer a streamlined finish while minimizing waste and maximizing safety.

Overall increases in capacity are also required to readily respond to the next pandemic. Where appropriate, this may involve the upgrade of existing sites and a reallocation of resources. During the pandemic, WuXi Vaccines upgraded a drug substance plant from BSL-1 to BSL-2 in just four months, resulting in a 20-fold increase in production capacity. This upgrade enabled a top 10 Pharma company to bring its first vaccine product to market in record time. To further address scale-up risk to commercial manufacturing, a scale out strategy to produce products at larger quantity with multiple upstream scales has been established at WuXi Biologics to mitigate the risk while reducing the cost of goods.

WuXi Vaccines has also invested in new facilities, including a new manufacturing site in Ireland that is enabling a leading vaccine company to launch and manufacture an innovative high-volume product. This site is strategically located to optimize manufacturing talent acquisition and efficient global distribution of the product. The facility recently achieved its notable milestone and will initiate Technology Transfer. In addition, commissioning qualification and validation (CQV) activities have been continued. The site’s QC potency lab became operational in July 2020 and received its GMP certificate from the Ireland Health Products Regulatory Authority (HPRA) in July 2022. Currently, over 160 employees are working at the WuXi Vaccines Ireland site.

Business relationships must also be strengthened to ensure the continuity of reliable supply chains. For recombinant protein vaccine developers, this includes access to effective GMP-grade adjuvants, which have been known to cause bottlenecks in production. Therefore, it is important for CDMOs to make sure they have a strong supply chain for these adjuvants, or the ability to produce their own. For example, WuXi Vaccines offers alum adjuvant re-sterilization and suspension product filling capabilities, while continuing to collaborate with external adjuvant providers on the development of novel adjuvants, to meet all manufacturing needs.

End-to-end

Over the past few years, the vaccines industry has learned a lot. Many of those lessons have already been put into action, but we must keep learning, collaborating, and investing, to make sure we are prepared for the next global health emergency. Our frontline armaments in this future battle against the unknown must be large capacity sites, equipped with the best available facilities, with automated HTP workflows for process development and highly flexible, cost-competitive manufacturing strategies.

It is our vision that every vaccine can be made by building an open-access platform with the most comprehensive capabilities and technologies in the global biologics industry. We believe open access is important for integrating high-quality, consistent healthcare in all corners of the world. For recombinant protein vaccines, WuXi Vaccines can stand on the shoulders of WuXi Biologics, drawing on the technical strength of its biologics development platform, its R&D experience, its well-established partnerships, and its manufacturing facility network. These connections and resources, coupled with a huge amount of flexibility, allowed us to adapt during the pandemic and solidify a commitment to offering end-to-end solutions along the vaccine supply chain.

Together with our supply chain partners, customers, and collaborations with global non-governmental organizations, WuXi Vaccines is enabling global vaccine development and manufacturing by applying the best integrated open technology platforms, and by leveraging a range of technical strengths, premium quality capabilities and commercial facilities. To date, WuXi has contributed COVID vaccine supplies to more than 180 countries.⁵

WuXi Vaccines, with WuXi Biologics, offers one of the largest capacities for single-use bioreactor operations in the industry, as well as a powerful network of facilities in Europe, North America and Asia. Our sites provide a truly end-to-end service from vaccine development to scaled-up and commercial manufacturing for any global customer. With the expertise and capacity to provide integrated services that compress timelines to market, we are dedicated to accelerating vaccine development and manufacturing.

Our ultimate goal, of course, is to achieve CEPI’s aspirational 100-day timeline.3 We believe it can be done for recombinant protein vaccines. 

References

1. de Pinho Favaro MT, Atienza-Garriga J, Martínez-Torró C, et al. Recombinant vaccines in 2022: a perspective from the cell factory. Microb Cell Fact. 2022 Oct 5;21(1):203.
2. Saag, M. Wonder of wonders, miracle of miracles: the unprecedented speed of COVID-19 science. Physiological Reviews 2022 102:3, 1569-1577.
3. CEPI. Delivering Pandemic Vaccines in 100 Days, 2022.
4. Feddema JJ, Fernald KDS, Schikan HGCP, van de Burgwal LHM. Upscaling vaccine manufacturing capacity – key bottlenecks and lessons learned. Vaccine. 2023 Jul 5;41(30):4359-4368.
5. Dong J. Preparing for the next Pandemic. Genetic Engineering and Biotechnology News, May 2023.

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Jason He is Executive Director and CMC Head of WuXi Vaccines of Blue Bell, PA. He has 17 years of vaccine development experience with growing responsibilities in vaccine R&D and commercialization of recombinant proteins, conjugates, and VLPs at Merck & Co., WuXi Biologics, and WuXi Vaccines. Jason received his B.S. in Chemistry from Peking University, and Ph.D. in Biochemistry from University of Pennsylvania.