A mock-up vaccine is a type of flu vaccine that is developed well before a pandemic has started. Because the strain of flu virus that will cause a future pandemic is not known, pharmaceutical companies cannot start to prepare a vaccine containing the correct flu virus until a pandemic has started. To get around this problem, the mock-up procedure (also known as the 'core dossier' procedure) allows vaccine manufacturers to gain an authorisation for a prototype pandemic vaccine in advance of a pandemic. This approach is unique to pandemic vaccines.
Before a flu pandemic has started
Mock-up vaccines contain a strain of flu virus that is not currently circulating in humans and to which very few people have been exposed. Pharmaceutical companies can gain authorisation for mock-up vaccines after they have carried out full studies looking into how the vaccine is made (its 'quality'), as well as its safety and its immunogenicity (its ability to trigger the production of antibodies against the virus).
A mock-up vaccine is not intended for use until, firstly, a flu pandemic has started and, secondly, the flu virus responsible has been identified and included in the vaccine. The mock-up vaccine is specially designed to mimic the final vaccine in two ways:
- in the way the vaccine is 'constructed': the methods used to prepare the virus, as well as the composition of the vaccine;
- in the way the vaccine is used, in people who have no existing protection against the virus.
Because of this the information obtained from the studies with the mock-up vaccines can be used to predict the safety and protective effect of the final vaccines.
To gain authorisation for a mock-up vaccine, the company needs to submit the information from its studies to the European Medicines Agency. In particular, the mock-up vaccine must show that it brings about an appropriate level of protection: according to criteria laid down by the Agency, at least 70% of the people in which the vaccine is studied must develop protective levels of antibodies for the vaccine to be approvable. If the vaccine's benefits are judged to outweigh its risks, the vaccine will be authorised, but this authorisation will be under 'Exceptional Circumstances'. This is because full information on the final vaccine's safety and effectiveness during a pandemic will only be available once a pandemic has started and the flu virus responsible has been included in the vaccine.
During a pandemic
Once a pandemic has been officially declared, the company can replace the flu strain in the mock-up vaccine with the strain causing the pandemic. It can then carry out further studies looking at the quality of the final pandemic vaccine, and start studies investigating the vaccine's safety and effectiveness in human volunteers.
To speed up the review process, the company supplies the data on the change of virus strain to the Agency. These data are supplied as soon as they are available in a 'rolling review' pattern, rather than waiting until it has collected a full dossier of evidence from studies. Once the data are considered to be sufficient to show that the benefits of the final pandemic vaccine outweigh its risks, the company is asked to formally submit a 'variation' application to change the flu strain in the authorised vaccine. The Agency's scientific committee, the CHMP, will then make a recommendation to the European Commission within five days for final approval. This will include recommendations on how the vaccine should be used in different groups of patients.
As soon as the decision has been issued by the European Commission, the vaccine can be made available for use. This will occur as quickly as possible, within 10 to 20 days of the CHMP's positive opinion.
Data from clinical studies
Because of the emergency nature of flu pandemics, the amount of information collected on the final pandemic vaccine is limited at the time of authorisation. Although a company needs to demonstrate that that its vaccine can be manufactured appropriately with the new flu virus strain, only preliminary data from clinical studies of the final vaccine may be available at the time of authorisation of the final vaccine. Further testing of the vaccine's safety and effectiveness will continue to take place after administration of the vaccine has begun. The CHMP will continue to evaluate all of the data generated from the ongoing trials once the vaccine is being used.
Based on decades of experience with seasonal flu vaccines, insertion of a new virus strain in a vaccine should not substantially affect the safety or level of protection offered by the final pandemic vaccine once it contains the pandemic flu virus strain. The combination of a full package of information on the mock-up vaccine, supplemented by the data on the manufacture of the pandemic virus strain, is therefore sufficient to demonstrate the vaccine's benefits and risks when it is used in the pandemic situation. In addition, if there are limited data on the final vaccine, the CHMP will also take information from the published literature and from previous pandemics into account in reaching its opinion on whether the vaccine can be authorised, as well as data from disease control centres.
To confirm that the final vaccines are as safe and effective as expected, their effects will be closely monitored after they have been authorised. This is especially important for certain groups of patients for whom limited data are expected to be available at the time of the final pandemic vaccine's authorisation, such as children and pregnant women.
Authorisation of pandemic flu vaccines using the 'mock-up' approach