Disposables help overcome some challenges of vaccine manufacture

The vaccine sector is challenging for both R&D and manufacturing because a wide variety of technologies and techniques are required — even the largest companies find it difficult to cover all the relevant areas of expertise — and this drives up development costs and often forces companies into multiple collaborations to obtain the required expertise and technologies. It is important, therefore, to use flexible technologies that minimise complexity and costs.

The two main challenges in vaccine manufacture are yield and the time required for development and manufacture. In general, problems with yield are related to aggregation, filtration and purification issues, such as the removal of DNA. Meanwhile time required can depend on a number of additional factors, including the type of vaccine being made; for example, most producers of influenza vaccines believe that using a cell‑based approach rather than traditional egg-based methods can have a considerable impact on manufacturing times.

One strategy that can drive progress in the right direction is the use of microcarriers and anchorage‑dependent cells. Normal diploid cells usually result in less DNA contamination which leads to less aggregation and fewer challenges to reduce DNA/dose. Cells on microcarriers also generate less debris. All of this results in higher yields. Comparing cell‑based with egg‑based development approaches, firstly there is no need for any egg adaptation and the human virus can be used immediately to infect the appropriate cells. The Vero cell, for example, is a good platform technology as it can be infected with more than 20 different human viruses. Secondly, you avoid all of the scale‑up issues around handling hens and eggs. Thirdly platform approaches based on cell culture are more amenable to industrial improvements that enable shorter development times and more efficient manufacturing.

Another key challenge in vaccine manufacture is the complexity of many vaccine compositions when it comes to the immunogenic compound and additional adjuvants. From a manufacturer’s perspective, it would be ideal if vaccine composition could be simplified, as the final vaccine would have a shorter process development time and would also require fewer manufacturing steps. Simpler manufacturing processes and vaccine compositions would also help reduce costs, which is a particularly important factor for developing countries, but this is easier said than done because the most important factors of vaccine production must always be safety and efficacy.

Overcoming hurdles
Shorter development and production times, however, would enable faster time to market and quicker responses to epidemics and other emergencies. Using disposable, ready-to-use manufacturing solutions for both upstream and downstream processes could help to achieve this, as well as enable more economical and flexible manufacturing. Tools are also available that can allow for high-throughput process development or help to reduce the time required for quality control. For instance, the lead-time for the production of an influenza vaccine is approximately 6–12 months; only approximately 25% of this is the production time itself, with 50% taken up by quality control (QC) and the remaining time attributed to national control laboratories. One solution to reduce the lead-time is to use technologies such as surface plasmon resonance, which can lead to faster and more efficient QC methods.

As supply security is of great importance, vaccine manufacturers tend to be very conservative. Because of this, new technologies must be thoroughly tested and backed by quality assurance procedures that support scale-up and production.

Optimising scale up
In many instances, disposable, ready-to-use systems can help to optimise scale up to commercial production because they offer:

• Higher project throughput: shorter set-up times, shorter process times and less validation efforts/time.
• Safer operations: reduced cross-contamination, no re-use and closed systems.
• Reduced costs: lower capital expenditure, lower start-up costs, and no cleaning and cleaning validation procedures.

For upstream processing, innovations, such as disposable bioreactors and disposable connectors, are available for use in place of stainless steel technologies, while for downstream processing, products such as ready‑to‑use, single‑use filters and columns can be used. It is difficult to recommend one single process and it should be noted that there is no one‑system‑fits‑all approach.

Many vaccine manufacturers are understandably cautious about introducing innovative approaches to the manufacture of products that impact millions of people, and do not take advantage of the most recent technology to speed up manufacture.

Using disposable, ready‑to‑use manufacturing technology upstream and downstream, such as disposable bioreactor technologies, filters, chromatography columns and fluid paths, can save time, increase flexibility, and improve quality with pre‑cleaned and pre‑validated systems.