Risk Wise

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Once the EMEA pandemic plan is initiated, marketing authoriza-

tion holders would begin development work on the identified

pandemic strain such that it could be included into the mock-up

vaccine, to create a pandemic vaccine. As this was being done and

the manufacture and control of the vaccine was being progressed,

there would be active collaboration and discussions between EMEA

and associated experts, and the vaccine manufacturers. This process

would result in the ‘rolling review’, which has been introduced to

further facilitate the development and availability of pandemic

vaccines. This approach provides the opportunity for manufactur-

ers to submit data as it becomes available, and obtain an EMEA

regulatory view on an ongoing basis.

At the end of the rolling review procedure, the marketing autho-

rization holder of a mock-up dossier vaccine would then formally

apply for a variation (a change to the marketing authorization of

the vaccine) by supplying full information to CHMP on the vaccine

including the new pandemic influenza strain. This variation would

be processed quickly – normally within a few days – as most of

the data would be comparable to that generated for the strain, which

was reviewed during the assessment of the mock-up vaccine and

the new data reviewed during the rolling review. Once the variation

had been approved by the European Commission and a commis-

sion decision given, the vaccine would be available for use.

In the event of a pandemic, the public will be aware of the situa-

tion in a similar timeframe to the commission, member states and the

agency; thus, the handling of communications will become crucial

especially when public confidence is at risk. An EMEA pandemic

communications policy on this aspect is in place to deal with the

matters within its remit, taking care of the interface and roles and

responsibilities of other interested parties, including the commis-

sion, ECDC and member states.

Pre-pandemic vaccines

Further to the first authorizations of mock-up vaccines in 2007, it

became clear that European public health authorities were consid-

ering alternative uses of these vaccines, such as for prime-boost

strategies (for example, priming poultry workers) in the pre-

pandemic phase. They also wanted to stockpile the mock-up vaccines

for use when the pandemic is declared and before the actual

pandemic vaccine becomes available. Given that the mock up

vaccines were authorized with the condition that they would only be

used following the introduction of the actual pandemic strain after

pandemic onset, an alternative approach was required. To address

this issue, in 2007 the guideline on influenza vaccines prepared from

viruses with the potential to cause a pandemic and intended for use

outside of the core dossier (that is, not mock-up vaccine) context

(‘pre-pandemic vaccines’) was developed.

A pre-pandemic vaccine has subsequently been authorized by

EMEA/European Commission. Since pre-pandemic vaccines can be used

at any time after the marketing authorization has been granted, a more

extensive clinical testing programme, including a larger safety database

for all ages and risk categories, has to be established before licensing.

Future approaches for pandemic influenza vaccines

Seasonal influenza vaccines are composed of three circulating seasonal

influenza strains (two A subtypes and one B strain). At present, mock-

up vaccines only contain one influenza strain. Both seasonal and

pandemic influenza vaccines contain inactivated influenza virus, which

is grown and inactivated before being purified/processed to various

extents depending upon the product. Traditional produc-

tion methodologies have relied on the use of hens’ eggs

for manufacture, the availability of which, especially

during a pandemic, is more difficult to assure. A few

manufacturers do now have procedures in place to manu-

facture influenza vaccines using cell culture technology,

which is more easily controlled.

Live attenuated influenza vaccines are composed of

an attenuated (non-pathogenic) strain containing the

antigen from the virulent disease causing strain

(seasonal or pandemic circulating strain) which has been

engineered to grow at lower temperatures, such as that

of the human nose. This concept appears to have several

advantages, not least the ease of administration (nasal

spray) rather than injection. It is also easy to grow;

although, it does still utilize hens’ eggs. There are already

seasonal live attenuated influenza vaccines authorised

outside of the EU.

Other vaccines are also being developed, namely recom-

binant subunit influenza vaccines, containing the

antigenic components (haemagluttinin or neuraminidase)

of the seasonal/pandemic influenza strain, grown by

recombinant DNA technology. DNA vaccines are also

under development, whereby the H gene would be

injected into humans who, using their own cellular

machinery, produce H protein against which an immune

response would be elicited. These technologies have

potential advantages in eliminating the need for hens’ eggs

and markedly increasing production capacity.

Tetravalent vaccines are a combination of the three

seasonal strains plus one strain with pandemic potential

(such as H5N1). This approach might seem promising

for allowing priming of a large part of the population.

Conclusions

EMEA has been actively delivering guidance and stim-

ulating debate with the industry, resulting in marketing

authorization applications for mock-up pandemic and

pre-pandemic influenza vaccines. During this period

there has been, and continues to be, good cooperation

with European vaccine manufacturers. EMEA has also

identified the need and put in place a system allowing

the agency to undertake its role fully in the event of an

influenza pandemic. To strengthen the plan, we have

also looked at more general operational aspects in the

form of business continuity planning and training, and

organized appropriate meetings both internally and at

the European level, to address these issues.

Finally, EMEA continues to work in close collabora-

tion with the EU national competent authorities and

other colleagues involved with pandemic preparedness

(European Commission, ECDC, member states). EMEA

also collaborates internationally in this area with WHO,

US FDA, Health Canada).

The views expressed in this article are the personal views of

the authors and may not be necessarily understood or quoted

as being made on behalf of or reflecting the position of the

EMEA or one of its committees or working parties.