Vaccine Manufacturing, Made Possible by Vacuum

By Dr Graham Rogers

Vaccines are very much in the public eye now because of the COVID-19 pandemic. The use of vacuum is integral not only to their manufacture but also for some of the vaccines such as the Pfizer BioNtech which requires a temperature of -60oC for its storage and transport.

The use of vacuum for freeze-drying in the pharmaceutical industry is well known, but there are several steps within the synthesis where vacuum is crucial. Purification within the manufacturing process is paramount, and an ultra-high-speed centrifuge is employed to facilitate this step. The different settling coefficients or buoyancy density of the mixture's components allow the purification process to be achieved. High rotational speeds of more than 30,000 RPM are required to produce complete separation of the active species and unwanted contaminants. Such large rotational speeds will cause air friction within the mixture and result in heat generation, damaging the active components. The use of a high vacuum pump system incorporating a turbomolecular pump (TMP), and ideally a dry vacuum pump, allows heat to be extracted from the mixture as illustrated below.

Freeze drying

The critical components of vaccines are active microorganisms and enzymes, which are live, and must remain that way to be effective.

The finished live vaccine is mixed with a water-based stabilizer to form a suspension, and then the material is frozen. A vacuum is then applied with a little heat, such that the ice changes from solid to vapor or sublimes. Because of the low temperature of the sublimation process, the vaccine components remain active and undamaged.

The phase diagram for water shown below illustrates how at low pressure, the solid ice changes directly to a vapor, with no intermediate liquid phase involved.

Vapor pressure curve/saturated vapor pressure curveEMEA-Leybold-PhaseDiagram-Vaccine-Blog
Phase diagram for water

The freeze-dried vaccine can be sealed and stored under vacuum; this has the advantages of offering a long shelf life, rapid dissolution with diluent during use, and unchanged recovery characteristics. It is currently the most common method of preservation of live vaccines.

Glass Vial production

Before transportation and dispensing, the vaccine is dispensed into glass vials. The correct choice of glass is crucial to maintain the vaccine's efficacy. Only low borosilicate glass has the required high chemical stability needed to achieve the vaccine's long-term stability. It has an excellent strength to thermal expansion and contraction, essential for long-term storage at below-ambient temperatures.

Vacuum is required in two stages of the production of borosilicate vials:

  • The melting process to remove air trapped in the glass, typically operating at around 50 mbar pressure. Glass dust and high temperatures must be addressed, and traditionally liquid ring pumps have been the standard. But increasingly, to reduce running costs, both oil rotary vane and screw pumps are employed. Dry screw pumps offer an oil-free alternative.
  • The molding process requires vacuum levels of around 100 mbar. Short pump downtimes and continuous operation are critical, and again oil rotary vane, screw pumps, and dry screw pumps are increasingly used.

Transportation and Storage prior to use.

As mentioned, the first approved vaccine, Pfizer BioNtech, requires storage at -60o C. Maintaining this temperature presents a significant challenge. The use of Vacuum Insulation Panel (VIP) technology offers a method to maintain these temperatures in an energy-efficient way. VIP provides a very low thermal conductivity of 0.004W (m.K), with a typical container wall thickness of 25 -60mm. By comparison, conventional mineral wool of 150mm thickness would have a value of 0.04W (m.K).

This means not only greater efficiency but also more storage within the refrigeration unit.

This technology has more comprehensive applications for insulating older buildings without significant loss of internal space while significantly reducing the carbon footprint.

  • VIP structure comprises three parts: insulating material, a gas adsorption material (Getter), and a closed insulating film (barrier). This secure insulating barrier is pumped to a high vacuum level before sealing, thus offering exceptional insulation properties.

A typical vacuum system is shown below:

VIP productionEMEA-blog-vaccines-VIP-production

The high-speed forevacuum pumping train minimizes the time before the diffusion pump kicks in to give a rapid turnaround of the panels.


  • Using a high vacuum pumping system in conjunction with an Ultra-High-Speed centrifuge allows vaccine purification while minimizing any detrimental effect of heat on the product.
  • Vacuum freeze-drying offers long-term bulk storage before transfer to dispensing vials.
  • Production of vials is dependent on a vacuum for air removal in the melting process, and additionally, the vacuum is key to the uniform molding of the vials.
  • Vacuum Insulating Panel technology gives reliable and energy-efficient low temperatures crucial to the long-term stability of some vaccines.

Tags: High Vacuum, R&D, Ultra High Vacuum, Industrial & Process Vacuum

About Dr Graham Rogers

Dr Graham Rogers
Dr Graham Rogers has extensive experience across the world of vacuum, having been involved in the detailed specification and technical selling of the complete range of products, principally for Leybold, over the past 30 years. He brings in-depth knowledge from the metallurgy, chemical, analytical, R&D and semiconductor sectors, and has a passion for helping customers in solving problems and developing solutions that will bring real process improvements and value. Graham is a science graduate from Oxford University, UK, where he gained his degree in Chemistry and a DPhil in Physical Chemistry. His journey into vacuum science began early on in his career when worked developing semiconductor processes particularly thin film coating, this led him into the exciting and inspiring world of vacuum and eventually Leybold. We are delighted to have Graham as a resident Consultant for Leybold, where he is able to share his knowledge and insight through our vacuum academy training, videos and blogs.

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