No need for the cooler

The provision of instantly injectable, thermo-stable vaccines in tropical temperatures could make cold storage problems a thing of the past. Nova Bio-Pharma Technologies believes it has the technology

With the HydRIS platform, the membrane is attached to a conventional syringe and flushed with liquid, enabling the redissolved product to be rapidly injected

The provision of instantly injectable, thermo-stable vaccines in tropical temperatures could make cold storage problems a thing of the past. Nova Bio-Pharma Technologies believes it has the technology

Simple and cost-effective ways of making vaccines stable – even at tropical temperatures – have been developed by the specialist manufacturer Nova Bio-Pharma Technologies. The innovative technology removes the need for fridges, freezers and associated infrastructure like electricity, thereby reducing the costs and waste involved in storing and distributing vaccines while offering significant practical advantages.

The technology has the potential to solve many of the problems that pharmaceutical and biotech companies have around stabilising the medicines of tomorrow, including those for vaccination efforts in the developing world, in battlefield situations and in emergency vehicles.

The technology is also capable of working with live vaccines for both human and veterinary use, with the potential for use across all vaccination programmes worldwide.

The pioneering technology is based on two main platforms – VitRIS (Vitrified Readily Injectable Suspension) and HydRIS (Hypodermic Rehydration Injection System).

But what is really sparking interest from within the pharmaceutical sector is what the company believes to be the world’s only fully validated cGMP aseptic spray drying facility for the production of clinical material.

Nova developed and owns what it believes to be the only technology capable of delivering any instantly soluble, spray-dried powder vaccine. The process has huge capacity advantages over lyophilisation and so accelerates the time to market of such products.

Nova has now received requests for even bigger capacity machines to be built in the future, which it is exploring currently.

John Seaton, commercial and financial director at Nova, said: ‘The spray drying facility is in full operation and proving very interesting to the pharmaceutical industry. The main advantage over lyophilisation is the capacity, because the spray dryer is a continuous process, so the production speeds and high quality make this an attractive proposition.

‘We have already spray dried for one client for three continuous days, and two of our existing clients have asked us to build them a dedicated facility that would be much bigger than the existing dryer. We have also seen interest from new potential customers, which is very exciting. It is clear that spray drying is picking up momentum and I think there is huge potential in this form of vaccine production.’

As a method of creating powder for existing and novel products, Nova is looking at spray drying a number of therapeutic peptides, to be co-delivered with another excipient that enhances the immune response. The company is also looking at spray drying liposomes as a separate delivery mechanism – a tiny bubble (vesicle) made out of the same material as a cell membrane (lipid bilayer) – in order to reformulate therapeutic proteins and other therapeutic agents in a dry form.

proof of concept

Scientists at Oxford University recently carried out a proof-of-concept study on Nova’s patented HydRIS platform and the results were published in the journal Science Translational Medicine.1 The core principle of the HydRIS technology is the formation of sugar-glass stabiliser matrix on a fibrous membrane/surface with thermal stability.

The Oxford team showed it was possible to store two different virus-based vaccines on sugar-stabilised membranes for 4–6 months at 45°C without any degradation. The vaccines could be kept for a year and more at 37°C with negligible losses in the amount of viral vaccine re-obtained from the membrane. When required the membrane is then attached to a conventional syringe and flushed with liquid, with the re-dissolved product quickly and simply injected.

The HydRIS platform could be modified for a range of other applications, such as oral or topical delivery of stabilised vaccines or therapeutics for both human and animal use.

The work by Oxford University demonstrated one successful application of Nova’s patented HydRIS technology platform, but Nova has already successfully stabilised a wide range of viral and conventional vaccines, which is also proving interesting to the pharmaceutical sector.

Seaton sees it as one of the most exciting developments in the pharma and biotech industries, especially as it can be used for highly unstable products, such as novel vaccines for malaria: ‘We have had a number of serious enquiries from high profile names in the pharma industry. There has been a lot of interest because we have proven success in storing and delivering live vaccines for both humans and veterinary, which is a fantastic development for the industry.

‘The benefits it offers to our customers – with many now looking for more efficient, cost-effective ways of delivering drugs – and the impact it can have abroad, cannot be overstated.’

The second platform, VitRIS, is based on the well-established industrial process of spray drying. The pharmaceutical product is mixed under sterile conditions with water-soluble glass formers and dried as a solid, non-crystalline glass using an aseptic spray-dryer.

The outcome of this first part of the process is spherical, highly polished microspheres in which the product is immobilised and stabilised. The microspheres could either be suspended in a non-aqueous liquid or used as a rapidly dissolving powder, ready for injection.

‘Both platforms provide advantages at all stages of the pharmaceutical value chain and were designed for ease and convenience of administration, with true availability at the point of care,’ says Seaton. ‘They can improve the way pharma products are made, stored and delivered, including those based on freeze-drying.’

Trials have shown the platforms can be successfully applied to a large number of preparations including live biologics (virus/bacteria), vaccines, insulin, monoclonal antibodies, recombinant growth hormones, proteins, enzymes and nucleic acids.

global problem

Preparing vaccines that do not need refrigeration has been identified as one of the major unsolved problems in global health. In the developed world, maintaining the cold chain is estimated to cost up to $200m (£125m) p.a. and increases the cost of vaccination by 14–20%.2

In the developing world, that infrastructure can be missing or incomplete and presents a great barrier to effective vaccination schemes.

At its state-of-the-art facilities in Leicester, UK, Nova has now developed world-class expertise in aseptic processing of complex pharmaceuticals using sterile isolation technology. The technology could be applied to both low value/high volume production (such as mass vaccination programmes); and high value/low volume products like bio-defence/therapeutic vaccines, which require rapid deployment in a user-friendly format (such as for the emergency services/armed forces). The platforms will be useful for blood plasma and haemoglobin transfer – a potentially major benefit for the emergency services and the defence industry.

There are also applications for medical implants: for example, devices containing stabilised, highly concentrated spray-dried powder as part of a device implanted into the body and pumped out into the bloodstream – surviving at body temperature – for patients with chronic conditions.

The technologies are very adaptable to a range of uses and Nova is now developing new methods of delivery beyond injectables, such as oral delivery and topical administration – e.g. eye- and ear-drops. It can produce spray dried ‘flowable’ powder for inhalation, intranasal and epicutaneous (stabilised ‘paste’) delivery, for example for medicated plasters for burns.

These technologies also have a role to play in facilitating brand differentiation, thus extending the life cycle of marketed products and in turn patent protection.

references

1. R. Alcock et al, Science Translational Medicine. 2010. Vol. 2, Issue 19, p.19 ra12

2. World Health Organisation www.who.int/vaccine_research/documents/Report%20McKinsey%20Business%20Plan%20Flu3.pdf

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