Scaling up vaccine manufacturing: Challenges & solutions

Scaling up vaccine manufacturing is one of the biggest challenges producers have to face. To be prepared for the approval of vaccines and guarantee worldwide access to vaccines when needed, it is essential to prevent bottlenecks. However, not every company has the production capacity and technology for large vaccine manufacturing scale-up missions at hand. This challenge calls for new inventions to implement scalable solutions.

In this article, we will dive deeper into why scale up vaccine manufacturing is important, which challenges manufacturers face in the process and how these challenges can be addressed.

When is it time to scale up vaccine manufacturing?

There are several time and labor-intensive steps that precede scale up vaccine manufacturing. The different stages in vaccine development involve a number of case studies in preclinical trials, typically testing the products in small mammals like mice or rats in the beginning.

If vaccine candidates show good results, they enter the first of three phases of clinical trials. In case they show satisfying immunization rates in humans and the vaccine has been approved by the specific country’s health regulation authority, the production on a larger scale can start. However, manufacturers often take the risk of starting with preparations and adaptations for the scale-up process of vaccine manufacturing even before regulatory approval, enabling them to start mass production as soon as possible.

In times like the recent coronavirus pandemic, which put the entire global health in jeopardy and vaccine supply was needed quickly, trial lengths could be shortened significantly in order to start vaccine production processes earlier.

Authorities such as the U.S. FDA or the EMA (European Medicines Agency) are able to issue an Emergency Use Authorization (EUA), to ensure the public health. This happened in the case of mRNA vaccines, with Pfizer-BioNTech’s COVID-19 vaccine being the first mRNA vaccine ever to be accepted by an organization recognized by the World Health Organization (WHO).¹ 

Challenges for vaccine manufacturers when upscaling

There are different situations where vaccine manufacturing is necessary in a short time scope. This could be the case as seen in the recent pandemic, but also in winter months when flu shots against infectious diseases and new variants are in high demand.

Apart from the investment that is involved in the production of biopharmaceuticals, there are several challenges in vaccine development that need to be considered, not only in case of health emergencies.

Limited space capacities

Sometimes, the problems which have to be faced in pharmaceutical manufacturing are as simple as limited space capacities. The manufacturing process of vaccines is laborious and involves many steps until the final vaccine doses can be shipped. It is therefore important to take initiatives to expand vaccine manufacturing capacity when it is needed.

In order to prevent bottlenecks due to a lack of manufacturing capacity, this can be outsourced, either through partnerships with CDMOs or other pharma companies that have the required equipment and space at hand or through scalable technological solutions.

Staff shortages

When vaccines have to be produced within a short timeframe, staff shortages in pharmaceutical companies are a big challenge. In the long-term, this can even lead to downtimes and delays in the production of biologics.

The  global demand for vaccines is high, but the resources not only in regard to production components like vials, filters or tubing but in trained personnel are often low. Intellectual property in how to handle equipment etc. has proved to be as important as having the right technology available.² 

Supply chain delays

Vaccines are composed of sensitive substances that need efficient cold chain handling and a controlled environment that does not expose them to any kind of contamination for safe patient use. To achieve this goal, the supply chain, starting from acquisition of raw materials and ending at the distribution of vaccine doses, has to run smoothly.

The risk of supply chain issues is particularly high at the touchpoints of manufacturer, CRO and CDMO. Additionally, errors when planning new construction sites have to be avoided, e.g. supported by EPC contracts or A&E firms.

Adherence to regulatory requirements

During every step of vaccine manufacturing, specific regulatory requirements have to be met to ensure the safety of the finished product for the patient.³ Every manufacturing site is monitored in terms of technology and manufacturing processes by regulatory health authorizations in the specific country. The process of earning a license to produce vaccines is costly and time-consuming.

Manufacturing facilities have to prove that the risk for contamination of vaccine components is kept at a minimum through current good manufacturing practices (cGMP). These involve aseptic fluid handling as well as a controlled temperature environment, as protein substances like antibodies or mRNA are very sensitive to temperature changes. After the license is obtained, the products are regularly tested for quality and compliance to changing or new regulatory standards, such as Annex1.^3 4 

Why scale up vaccine manufacturing, then?

Although scale up vaccine manufacturing comes with many challenges, it is absolutely necessary to act quickly to prevent downtime.

Having new, approved technologies at hand, it is crucial to provide accessibility as soon as possible. Nevertheless, this is the purpose of vaccine development in the first place: provision of drug products to patients worldwide – be it low-income, high-income or middle-income countries.

Solutions to succeed in upscaling vaccine production

A number of solutions for upscaling vaccine production have been made available: These range from the streamlining of cold chains to automated fluid management and more flexible technology to overall better preparation in case of approvals of new vaccines.

Streamlining cold chains

With the higher demand for biologicals like vaccines and antibody therapies, the pharmaceutical market has changed. It is now more common than ever that different manufacturing sites are involved in the production of a product. Therefore, it is often necessary to transport substances in large quantities and freeze them to prevent protein degradation.

The bigger the volume, the harder it is usually to guarantee freezing at highest product viability. Innovative cold chain solutions in vaccine development, such as plate freezers used in combination with single-use bags, have shown improved results for more homogeneous freezing - also at very large volumes - and a reduced risk for protein denaturation overall.⁵ 

Automating fluid management

Due to the many regulatory requirements involved in vaccine manufacturing, automated fluid management in biopharma is an approach to minimize the risk for contamination and product loss through human error.

There are a number of fluid management solutions for vaccine manufacturers on the market, which range from closed end-to-end systems to automated solutions for individual steps – including homogenizing, aliquoting, filtering, freezing, thawing and filling.

Being prepared all along – with scalable single-use solutions

When it comes to upscaling vaccine manufacturing, it is most important to be prepared, as circumstances and demands can change quickly. This is why the landscape of vaccine manufacturing calls for more flexible solutions that allow for quick and efficient upscaling when the hour strikes.

To cater to this need, Single Use Support has developed scalable solutions for cold-chain handling in vaccine manufacturing from upstream to downstream bioprocessing. Its automated fill and filtration system RoSS.FILL is able to fill bottles and single-use bags with a capacity of up to 300 litres per hour and can easily be scaled up by attaching multiple racks. The modular setup of the aliquoting system even allows for aseptic filling of more than 800L per batch, when attaching multiple racks.

Furthermore, single-use bags in protective shells can be transferred to automated and scalable RoSS.pFTU, a plate freezing platform that can be scaled up to 400 liters and more per batch. The platform is also compatible with bottles by other manufacturers and allows for a monitored and controlled freezing process.

All of Single-Use Support’s equipment is designed to help manufacturers take the step from small batches in clinical trials to large-sized batches in upscaling vaccines quickly and improve overall manufacturing quality for safe products.