Vaccine manufacturing: The future is 'disposable'

As the threat of new viruses like avian influenza have heightened the need for greater speed and safety in vaccine production, single use technologies are proving far more safe and economic than traditional cleaning techniques, according to Pall's vaccine application development director.

Speaking at the World Vaccine Congress in Montreal, Helene Pora stressed the challenges posed by cleaning/cleaning validation and separation/purification, pointing out that 70 per cent of development and production time is devoted to quality and safety controls, thus underscoring the importance of eliminating unnecessary steps like cleaning through the use of disposables.

Cleaning and cleaning validation issues are particularly critical when it comes to the type of products that are being handled in vaccine production, such as potentially potent microorganisms in upstream parts of the process.

According to Dr Pora, the elimination of cleaning and cleaning validation associated with disposables provides fewer opportunities for operator error and compliance failures.

It also significantly cuts time and labour, reduces the risks of cross-contamination and limits dramatically the use of chemicals and water including WFI.

"Although manufacturers do have recurring costs with disposables, re-usable or stainless steel systems require significant capital investment and are considerably more expensive when you consider the time and labour involved in cleaning and cleaning validation," Dr Pora told In-PharmaTechnologist.com.

"Disposables can be supplied pre-assembled and pre-sterilised to further reduce labour, and they require less space than stainless steel counterparts."

In her presentation, Dr Pora also discussed ways of significantly reducing the 30 or more steps required to separate and purify conjugate vaccines as another way to improve quality and time-to-market.

The use of ultrafiltration technologies in lieu of size exclusion chromatography greatly simplifies separation and purification steps in conjugate vaccine production.

These vaccines protect infants and young children from infectious diseases such as meningitis and invasive pneumonia.

"A core step during conjugate vaccine production is fractionation, which is used to separate polysaccharides into specific size classes for attachment to proteins, and while fractionation is traditionally performed using size exclusion chromatography, ultrafiltration provides a faster, simpler method of capturing specific size polysaccharides," said Dr Pora.

"Size exclusion chromatography has a low flow rate and is a difficult and time-consuming process when used for polysaccharide fractionation.

"Ultrafiltration also eliminates the need for column packing and costly chromatography resins."

Disposable technologies also play an important role in the production of conjugate vaccines by providing an efficient polishing step with significant speed and cost benefits over conventional beaded resin column chromatography.

A disposable, pre-packed membrane column can remove contaminants at up to 100 times the speed of resin-based chromatography.

"A disposable technology, such as Pall's Mustang ion exchange membrane chromatography, eliminates cleaning and cleaning validation, improves operator safety, reduces cross-contamination risks, and lowers installation, labor, and maintenance costs," Dr Pora said.

"Mustang membrane chromatography also provides a very high throughput because of its very high flow rate and very high capacity for large molecular weight components, such as DNA, reducing bottlenecks in manufacturing."

Dr Pora sees vaccine manufacturers implementing a growing number of disposable technologies into their development and production processes to speed time to market of vaccines and avoid many compliance pitfalls.

She added that in the case of flu vaccines, the industry is moving from egg-based vaccine production processes, which are long and difficult, to faster, more advanced cell-based methods that enable the use of a greater number of disposable technologies.