Vaccines: the first line of defence
Vaccines are universally regarded as the most important medical intervention for preventing influenza and reducing its health consequences during a pandemic. In the past, however, vaccines have never been available early enough and in sufficient quantities to have an impact on morbidity and mortality during a pandemic. Past problems, related to the special nature of pandemic vaccines and the inadequacy of manufacturing capacity, have endured.
Dutch influenza expert Albert Osterhaus recently reported in the journal Nature that the H5N1 strain of avian influenza could infect up to 20 percent of the world's population if a human pandemic strain emerges. Vaccine companies currently make 300 million flu shots a year, but in a pandemic, we could need billions of doses.
In 2003, nine rich nations, led by Japan and the United States, used 62% of the world's influenza vaccines. But bird flu is most rampant in poorer countries so there is a high risk that these countries will be defenceless in the early days of a pandemic. It will be very difficult to step up global vaccine production to make enough to halt a pandemic.
The worst-case scenario is that a pandemic starts within two years. We would have no vaccine and few drugs, and we would be dependent on governments and the WHO to try to extinguish the first outbreaks at source. That's why the first priority must be to prevent a pandemic emerging in the first place, by extinguishing the disease in animals. If the next pandemic were to arise five years from now, there would have been breathing space to stimulate our drug and vaccine industries to limit the damage it would cause. But that requires urgent action now.
From 11 to 12 November 2004, WHO convened a meeting to explore ways to expedite the development of vaccines against a pandemic virus. All the major influenza vaccine manufacturers were represented. The meeting specifically considered what needs to be done, by industry, regulatory authorities, governments, and WHO, to make vaccines available rapidly and in as large a quantity as possible.
Pandemic preparedness can only be achieved by collaboration of all stakeholders. Partnerships between public and private stakeholders have successfully been created at international level. Solvay Pharmaceuticals plays an important role in a number of international organizations:
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Influenza Vaccin Supply (IVS) is a specialised group within the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA). This group has been created in February 2002 to assist business leaders in vaccine companies in making necessary decisions to ensure adequate capacity to produce and distribute influenza vaccine in inter-pandemic and pandemic years;
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European Vaccine Manufacturers (EVM) is a specialised group within the European Federation of Pharmaceutical Industries and Associations (EFPIA). EVM was established in 1991 in order to promote a favourable climate for expanded vaccine protection and improved vaccine coverage in Europe, and to help sustain the innovative R&D capability of vaccine manufacturers in Europe.
Research
As matters stand, a vaccine against pandemic influenza will not be ready until at least six months after a pandemic starts. Too late: by then the worst of the pandemic would already have happened.
Researchers have already used reverse genetics to create candidate vaccines against the Influenza A/(H5N1) virus. The highly pathogenic H5N1 virus kills chicken embryos and had to be modified by altering its haemagglutinin gene to make it less deadly. Bulk antigen, protective against the H5 virus subtype, can be produced and stored in advance. But if a pandemic strain is vastly different from the vaccine strains that have already been tested, scientists will have to make a new vaccine from scratch. According to researchers they can make a vaccine strain just four weeks after they get their hands on a sample of the pandemic strain.
Gaining time with a “mock-up” vaccine
A “mock-up” vaccine contains an influenza virus from a subtype, such as H5, known to have pandemic potential. The mock-up vaccine undergoes all safety and efficacy testing required for registration by national licensing agencies. A dossier for this pandemic-like vaccine, including data on antigen content, immunogenicity, safety, and efficacy, is submitted for regulatory approval prior to the start of a pandemic. When the actual pandemic virus emerges, a variation of the dossier, with technical data specific to the pandemic virus, is then submitted for final marketing authorization, which is then rapidly granted following a fast-track procedure. To gain time, several activities can be undertaken now to lay the groundwork for rapid production of vaccines once a pandemic is declared.
Production
Vaccines are a biologic product in which a selected strain of influenza virus is grown in a medium. Chicken eggs have provided the most advantageous and reliable method for producing influenza vaccine. Current production cycles are designed to release product in time for annual vaccination campaigns – which take place before the winter season starts. However, experience shows that a pandemic virus does not follow normal seasonal rules.
At present, vaccine manufacturers have limited production capacity, which could be further constrained by the supply of lab-standard fertilized chicken eggs. A significant increase in production capacity to ensure an adequate level of pandemic vaccine supply is consequently required.
Health and other organizations worldwide are supporting efforts to develop cell-culture methods for vaccine production. Replacing the traditional egg-method by growing the virus in huge metal fermenters containing a soup of cultured cells, can provide the capacity for rapid scale-up and could allow vaccine manufacturers to keep pace with evolving influenza viruses.
Cell-culture technology
Cell culture is an emerging technology where the virus is grown on specially selected cell lines. Once the virus strain has been identified the cell culture process has the potential to reduce the start-up time for manufacturing from four weeks to two or three weeks and could result in a more predictable manufacturing process.
Using a cell culture approach to producing influenza vaccine offers a number of other benefits. Vaccine manufacturers can bypass the step needed to adapt the virus strains to grow in eggs. In addition, cell culture-based influenza vaccines will help meet surge capacity needs in the event of a shortage or pandemic, since cells may be frozen in advance and large volumes grown quickly. Finally, the cell-based influenza vaccines will provide an option for people who are allergic to eggs and therefore unable to receive the currently licensed vaccines.
Solvay Biologicals builds a new factory for cell-cultured influenza vaccine
Solvay Biologicals invests more than EUR 50 million in a new facility for the production of influenza vaccines generated through an innovative cell culture method: Influvac®TC. The new production unit is based in Weesp (Netherlands), on Solvay Pharmaceuticals’ business site.
The MDCK Cell culture-based manufacturing technology was developed by Solvay Pharmaceuticals virological laboratories in Weesp the Netherlands. It contributes to a higher level of pandemic preparedness, thanks to greater flexibility and rapid start up of production compared with current egg-based manufacturing methods.
MDCK is a mammalian cell line that has been used for decades in laboratories all over the world and for the production of veterinary vaccines. Solvay will be the first company using this cell line for the commercial production of human vaccines.
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