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All vaccines need to be sterile - this is achieved by sterile filtration of the adjuvant nanoemulsion or the whole process is conducted in a sterile environment. Both of these incur challenges and costs.
Creating a nanoemulsion with a precise distribution curve and droplet size is challenging, but will affect the ease with which the emulsion can be sterile filtered.
Microfluidics equipment has successfully been used for decades in the manufacture of nanoemulsion adjuvants. With the same energy input it produces 55% smaller emulsions compared to other techniques.
Microfluidizer technology produces precisely controlled droplet sizes and distribution curves which creates nanoemulsions that can be successfully sterile filtered even at high volume throughputs with minimal yield losses.
Adjuvants can be produced at production scale where the results are directly scalable from the lab across the range of Microfluidics equipment.
Vaccine adjuvants are critical in improving the effectiveness of vaccines.
Adjuvants are ingredients added to a vaccine to help induce a more potent immune response and improve the efficacy of a vaccine. They can also serve to reduce the amount of antigen needed in the production of the vaccine, enabling more treatments to be manufactured.
The original adjuvants were insoluble aluminium salts (alum) which were commercially used in many well-known vaccines. However, alum is not an effective adjuvant in every case - so other options were investigated.
The response was to create the now commonly used adjuvants which are oil-in-water emulsions such as MF59 (Novartis) and adjuvant systems 03 (AS03 from GSK), both have been used in seasonal flu vaccines as well as pandemic influenza vaccines.
The key to creating a successful vaccine adjuvant is precisely controlling the droplet size and the distribution curve as this determines the stability of the nanoemulsion and affects the ease with which the emulsion can be sterile filtered.
Because most adjuvanted vaccines are administered through injections it means that they must be sterile as they are obviously being injected into the body. In the manufacturing process, either the emulsified adjuvant is sterilized or the whole manufacturing process has to take place in a sterile environment.
There are a variety of ways in which vaccine adjuvants are manufactured
Microfluidics high shear processing equipment has been used for decades to manufacture nanoemulsion adjuvants.
Microfluidizer technology combines a fixed geometry Interaction ChamberTM and a constant pressure intensifier pump which means that virtually the entire batch is passed through the Microfluidizer processor at the required shear rate. This results in small particle sizes with a narrow size distribution.
Results are repeatable and scalable from lab to production scale. Parallel arrangements of identical microchannels ensure linear scalability. Large volumes can be produced at tens of liters per minute at the same particle size and PSD as achieved in the lab.
It compares favourably to the use of High Pressure Homogenisers (HPH). These devices are commonly used for cell disruption in the lab, however, scale up can cause inconsistencies as the way the cells are ruptured changes at production scale. Multiple valves can be required, which must be cleaned and reinstalled by those with specialist training.
Users of the Microfluidizer processors find that they are easy to use and clean. Multiple users can be comfortable with the technology as they do not require specialist skills to use the equipment.
Advantages of Microfluidizer Technology for creating vaccine adjuvant nanoemulsions
Results are reliably scaled from lab to production
Large batch sizes can be manufactured in the thousands of litres on the production-scale equipment
High shear processing efficiently size reduces particles with tight PSDs
Consistent particle size distributions are created from the ability to scale up the Interaction ChambersTM
The technology is cGMP approved
Microfluidizer technology has been proven time and again by market leading research institutes and manufacturers
Microfluidics machines produce stable nanoemulsions which enable post process sterile filtration to be more easily conducted.
The Microfluidics processor has been shown to produce up to 55% smaller emulsions with the same energy input of alternative methods. In addition, these emulsions were less polydisperse.
In tests, the Microfluidizer processor consumed less power than alternative manufacturing methods as fewer passes were needed to achieve the target particle size and at a lower pressure.
MF59 is the first oil-in-water emulsion.
MF 59 was the first squalene based, oil-in-water emulsion which was licensed and commercialized by Novartis for adding to their influenza vaccines.
It has been licensed around the world and has been shown to have significant impact on the immunogenicity of pandemic influenza vaccines.
MF59 has been licensed in Europe for pandemic flu vaccines and used for H1N1 pandemic flu vaccine in 2009 (Clark et al., 2009)
The process for manufacturing MF59 involves high-speed mixing into a coarse emulsion which is then passed repeatedly through a Microfluidizer® processor to produce an oil-in-water emulsion of uniform small droplet sizes (<160nm). The emulsion can then be sterile filtered and filled into vials.
Microfluidics also supply small scale lab equipment for use in research studies which is fully scalable to the production units.