Education - Vaccines - theory and advances

Along side this, CBS have introduced a second element to the technology that brings immediate and direct advantages. THE SNAPJET INJECTOR is hand-powered, simple and inexpensive, it can be used by literally anyone to painlessly and safely inject drugs and vaccines in the field. Designed to be pre-filled with stable liquid vaccines, it can be delivered rapidly outside the refrigerated ‘cold chain’ and stored at room temperature for months, even years, before use. Once removed from its sterile packaging, it is held against the arm and a single push downwards injects the vaccine. It does not even need to be shaken before use because the stable-liquid technology keeps the vaccine and PFC in stasis. Importantly, once the vaccine is injected, the needle remains inside the SNAPJET and the injector can be disposed of without risk of needle-stick injury which is becoming an increasing concern in both the developed and developing world. This combination of Biostability’s stable liquid technology and the SNAPJET injector provides, for the first time, a drug and vaccine delivery system which is economic, requires no refrigeration, and is remarkably simple to use in the field.

The new technology also offers the potential of slow release vaccines, which may overcome the need for boosters. In addition, thermostable vaccines do not require reconstitution, which is a major cause of vaccine safety and wastage problems. The stable vaccines will enable children in remote areas of the world to be reached by vaccination programmes. It will also allow emergency response teams to store vaccines in readiness for outbreaks of disease, and business travellers and the military to carry vaccines with them.

Research and trials have already been completed in co-operation with vaccine manufacturers to convert vaccines such as Tetanus, hepatitis B, Hib-conjugate and a new highly unstable Meningitis A conjugate vaccine into stable liquids. Beyond the technology for stabilising vaccines, Biostability has also invented a unique disposable injector that avoids the problems associated with traditional syringes and needles. While further research continues in the lab into areas like multivalent vaccines, our business focus is on moving our stable liquid technology from the laboratory into the field as quickly as practically possible.

A new technology based on processes two billion years old promises to revolutionise the international vaccine programme - enabling children, even in remote areas, to receive cheaper and safer immunisation

A UK vaccine technology that is set to revolutionise the industry has received £950k funding from the Department for International Development (DFID) to bring to production a pentavalentⁱ childhood vaccine that can be stored without refrigeration. The award was made by the Rt Hon Hilary Benn, Secretary of State for International Development at The Royal Society of Medicine, London.

The new ‘stable liquid’ technology, developed by Cambridge Biostability Limited (CBL), will enable vaccines to be stored for long periods in a range of environmental conditions, removing the need for refrigeration and reconstitution. Currently 50 per cent of all vaccines are wasted partly due to suspected or real temperature damage.

As a result of this revolutionary technological development, CBL has been recently named Most Promising Angel Funded Business at the British Business Angels Association first annual conference and also received the Innovation Award at the CEN (Cambridge Evening News) Business Excellence Awards held in March this year.

CBL raised £4m last year from business angels. London Business Angels, a syndicate of 10, and Vijay Saggar put in the lion's share between them, with more than 70 further angels, 40 of them in Cambridge, putting in between £5,000 and £50,000 a piece*. Vijay Saggar is one of the board of directors for CBL.

Paul Rewrie, Commercial and Operations Director for CBL, comments: “We are delighted to receive such an honour. Members of BBAA are leading figures in the angel investment community and their opinions are highly respected. “With support from the BBAA, CBL has been able to develop a technology which will benefit the people who really eed to be vaccinated in the developing world.“

The World Health Organisation estimates the cost of vaccinating a child at approximately $30ⁱⁱ. The cold chain is a major burden to vaccine programmes with an estimated cost of $200-300m per annum. Savings from removing the ‘cold chain’ alone would enable the vaccination of an additional 10 million children worldwide within existing budgets.

In collaboration with CBL, the vaccine is to be manufactured by Panacea Biotec, based in New Delhi, rated as India’s second largest biotechnology company.

The stable vaccines will enable children in remote areas of the world to be reached by vaccination programmes. It will also allow emergency response teams to store vaccines in readiness for outbreaks of disease, and business travellers and the military to carry vaccines with them.

The Rt Hon Hilary Benn, Secretary of State for International Development, comments: “The good health we take for granted in the UK is due in great part to our vaccination programme. The widespread and effective use of vaccines has protected children in the UK against diseases such as measles, rubella, tetanus, whooping cough and diphtheria and given parents piece of mind. We want to make this a reality for children and their parents in the developing world.

Two million children die each year from preventable diseases. This new British technology, funded by DFID, allows vaccines to be used in remote areas and at extreme temperatures and will mean more children than ever before will have access to life-saving vaccinations.”

Martin Friede, World Health Organisation, was asked to evaluate the applicability of the new stable-liquid technology on behalf of DFID he comments: “The World Health Organisation recognises the need for developing thermostable vaccines that do not require a cold chain for storage or reconstitution, and promotes the research and development of technological solutions to achieve this objective. WHO would like to see continued research of such technologies to render them broadly applicable.”

Thermostable Vaccine Technology

The new technology is based on a natural phenomenon where some plants and creatures can remain in a desiccated state for hundreds of years and then return to life. They do this by increasing the sugar content of their bodily fluids. When rehydrated they ‘return to life’.

CBL’s stable liquid vaccine technology uses a similar process. Embedded in sugar beads or microspheres and suspended in an inert liquid, the vaccines can be stored without refrigeration until needed. When injected, in the same way as a traditional vaccine, the sugar beads dissolve in the bodily fluids to release the vaccine.

Sugar beads also prevent the interaction of vaccines prior to injection therefore, multiple or multivalent vaccines can be developed using this technology and given in the same shot. The sugar can also be adapted to dissolve more slowly, thereby releasing vaccines over time. This would remove the need for boosters.

The technology has been developed in Cambridge UK by Dr Bruce Roser, Chief Scientific Advisor for CBL, who comments that all the components are currently in use in medicine and that the stable liquid vaccines meet the requirements for WHO: “A completely stable, ready-to-inject vaccine overcomes many of the current issues identified by WHO. In addition, since the CBL stable liquid formulations are anhydrous, they are inherentlbacteriostatic because bacteria require water to multiply. Thus the need for antiseptics is eliminated.”

Of the 132 million children born each year almost one third (34 million) are not reached by routine vaccination. Two million will die from a vaccine preventable disease and many more will be maimed for life. Tetanus killed 30,000 people last year, and yet it costs only US$1.20 to protect mother and child.ⁱⁱⁱ

The pentavalent vaccine is to be produced by Panacea Biotec, Rajesh Jain Jt. Managing Director, who comments: “In the last two decades, Indian companies have made significant progress in providing much needed health solutions to the people of India and their role is being recognised in various international markets as well.

The vaccine world is undergoing a radical rethink about how vaccines might be stored and administered. At Panacea Biotec we feel that all stakeholders should be given access to innovations, which are proved to be effective and efficient. We are delighted that Panacea Biotec is taking a world leading role by manufacturing this revolutionary vaccine.”

CBL plans to licence the technology to vaccine companies and discussions are already underway with a number of organisations. It will also provide outsourced production on shorter runs using its own facilities in Cambridge this will shorten the time to market.

*Source – ‘Hi-tech firm wins top 'angel' award’: Cambridge Evening News, 9 June 2005

i Pentavalent vaccine - Diphtheria, Tetanus, Pertussis, Hib (Haemophilus influenzae type b,) Hepatitis B

ii WHO estimates the cost to vaccinate a child at $30. The cost of vaccination varies highly from country to country further data is available at:

ⁱⁱⁱ DPT consists of a series of immunizations to prevent diphtheria, pertussis and tetanus. To be fully immunized, children must receive three doses of the vaccine before their first birthday. Complete coverage with DPT (DPT3) is a particularly valuable indicator of countries' performance of routine immunization, http://www.childinfo.org/eddb/immuni/current.htm

Cambridge Biostability Limited based in Cambridge, UK, has developed a revolutionary technology, which reformulates existing vaccines into ready-to-inject stable liquids requiring no refrigeration or reconstitution.

The company was established by: Dr Bruce Roser, chief Scientist and leading authority of drug stabilisation and delivery, and Dr David Stone, Chairman, founded of BioFocus plc and author of more 50 publications.

The company has a portfolio of patents and is entering into a number of agreements to licence and provide outsourced production of ‘stable liquid’ vaccines.

The CBL process is based on a process called anhydrobiosis, which is well known in nature. Some organisms are able to survive in a dried-up form for hundreds of years. Water within the cells is replaced with a sugar solution that thickens when water is excluded to a point of solidifying as a glass and the organism dries out. Cells are kept in a state of suspended animation until re-hydration occurs and the organism – plant, animal or bacteria – returns to life.

This process is being applied for the first time to vaccines. Sugar hardens to form a non-crystalline glass. So the vaccine is first spray-dried using the sugar syrup to form microscopic glass spheres. The dry vaccine is then suspended in an approved inert liquid, which can be injected into muscle where bodily fluids reactivate the vaccine.

Since the CBL stable liquid formulations are anhydrous, they are inherently bacteriostatic, as bacteria require water to multiply. Thus the need for antiseptics such as thiomerosal is eliminated.

Several vaccines, including hepatitis B, Hib and tetanus toxoid, have already been prepared using stable liquid technology.

Further background about the technology is available on www.biostability.com. Including:

- Case-study from The Meningitis Vaccine Programme: a partnership created in 2001 by the World Health Organisation and the Programme for Appropriate Technology in Health (PATH). The project’s principal goal is the control of epidemic meningitis in Africa through the development, testing, licensure and wide use of conjugate meningococcal vaccines

About the cold chain

All vaccines are sensitive biological substances and all will lose their potency – that is, their ability to give protection against disease - with time. This loss of potency becomes faster as vaccines are exposed to higher temperatures. In order to maintain their quality, all vaccines must be continuously stored at the appropriate temperature from the time they are manufactured up until the moment of use. Once vaccine potency is lost, it cannot be regained or restored, and without proper care, any vaccine may eventually lose all its potency. If this occurs, the vaccine will no longer provide any protection against the target disease and is then useless. In some cases, heat exposure leading to loss of vaccine potency may also cause the vaccine to become more reactogenic.

The system used for keeping and distributing vaccines in good condition is called the 'cold chain'. This consists of a series of storage and transport links, all of which are designed to keep the vaccine at the correct temperature until it reaches the user. Cold chain is a major expense and logistical issue for vaccine programmes, for further information about the cold chain please visit: http://www.who.int/vaccines-access/vacman/coldchain/the_cold_chain_. htm

Most wastage occurs due to the need to discard after reconstitution, suspected or real temperature damage, expiration of vaccine, and breakage or loss of vials.

See http://www.who.int/vaccines-access/vacman/reconst/vaccinereconstitution.htm for information on reconstitution. The main problems with reconstitution are use of dirty needles to remove doses (causing contamination), use of incorrect diluent, vaccine wastage (as the vaccine can only be kept for 6 hours), or keeping the vaccine beyond 6 hours after reconstitution – allowing any bacteria that may have entered the vial to grow.

DFID’s is supporting the partnership between CBL and Panacea Biotec through the Business Linkage Challenge Fund, a programme that provides grants to private sector led linkage projects that earn returns for the private sector and help to reduce poverty.

The BLCF is a cost sharing grants programme that supports commercial linkages between private sector companies. Grants in the range of £50,000 to £1 million are available on a competitive basis, with at least a one for one match of private sector resources invested to grant received. The objectives of the BLCF are to support private sector led projects that are in the commercial interests of the private sector promoters, and as such will continue through commercial returns beyond any period of grant support, and that also reduce poverty, either through employment or income earning opportunities, or through the poor benefiting as consumers.

The BLCF currently supports a wide range of projects across many sectors, with more than £22 million in private sector resources invested alongside the £11 million of grants already committed. The next application round has a deadline of 22 October 2004. The BLCF is managed by Deloitte, contact Jack Newnham (jgnewnham@deloitte.co.uk). More details through www.challengefunds.org.

About Panacea Biotec

Panacea Biotec is a leading research based Health management company, with an annual turnover of approx. Rs. 285 Crore (US$ 70 million approx). Panacea Biotec manufactures and markets vaccines, bio- pharmaceutical and pharmaceutical (Rx and OTC) based products of international quality. All Panacea Biotec plants are accredited by international agencies and they follow current Good Manufacturing Practices, as per WHO guidelines.

Established as a medicine shop in 1927, the company now ranks as the second largest Biotechnology Company and among the top 50 pharmaceutical companies of India. It is only one of the few health management companies of Indian origin, which is strategically poised to take up new challenges in the post WTO era.

A major initiative in this direction is the setting up of 3 Research & Development Center in North India which house 110 scientist and has earned the recognition of Ministry of Science and Technology, Govt. of India.

The Global Alliance on Vaccines and Immunisation helps countries plan and fund immunisation programmes. It is an international partnership between governments, vaccine, manufacturers and organisations such an UNICEF, WHO and the World Bank. The Vaccine Fund is the financing resource created to support the GAVI immunisation goal. Since 2000 GAVI and the Vaccine Fund have disbursed $265 million to 69 countries bringing basic vaccines to 8 million more children