MedImmune cleared to offer Flumist the reverse genetics treatment
influenza vaccines, the US Food and Drug Administration (FDA) has
approved the use of reverse genetics technology in the production
of MedImmune's seasonal intranasal vaccine Flumist and its
refrigerator-safe version, CAIV-T, allowing them to be the first on
the market using this technique.
Reverse genetics technology, also known as "plasmid rescue," enhances the safety, specificity, reliability and efficiency with which new vaccine strains can be produced and so has the potential to transform the face of the vaccine manufacturing industry.
Most influenza vaccine manufacturing companies and governmental agencies are now using reverse genetics technology in their development of pandemic vaccine candidates because it allows them to avoid working directly with the infectious, circulating pandemic strains.
But as the owner or exclusive licensee of the key patent estates for use of the reverse genetics technology in human influenza vaccines and the FDA approval now in the bag, MedImmune has the upper hand over the competition, offering other influenza vaccine manufacturers non-exclusive licences to this technology for use in manufacturing seasonal or pandemic vaccines.
"No licence agreement has been made yet but we are in touch with several parties," MedImmune spokeswoman Clarencia Stephen told In-PharmaTechnologist.com.
"Next season's supply of around 3m doses has already been submitted, but MedImmune's 2007/2008 production will be made using reverse genetics technology."
In the conventional vaccine manufacturing method, which dates back to the 1960s, two flu strains with the preferred features for a new vaccine are injected into an egg and their genes reassort naturally.
Researchers sift through as many as 256 possible combinations of viruses to find one that displays the desired antigens and is still able to grow inside an egg.
This "classical reassortment" approach requires a lot of time-consuming guesswork by scientists, making the creation of new vaccine strains the production-limiting step in the influenza vaccine manufacturing process.
In reverse genetics, manufacturers can custom make a flu vaccine by assembling genes that code for the desired features.
They do this by splicing genes together and manufacturing the seeds of the vaccine in mammal cells - in MedImmune's case, kidney cells from an African green monkey. This allows them to also remove any harmful pieces of the flu virus and change its reproduction rate.
Although the vaccine still needs to be grown inside eggs for large-scale production, reverse genetics adds more reliability to the manufacturing process, making vaccines available more quickly.
There is a realistic alternative to egg-derived vaccines - cell culture production which is faster and does not rely on the availability of eggs - but because changing the manufacturing system at present will likely cost billions of dollars, this will not be a factor for several years.
Nevertheless, reverse genetics will have no impact on the formulation of Medimmune's Flumist and how it is administered, which means there is no reason to expect FluMist's record of disappointing sales, overproduction and under-adoption to change as a result of the new technology.
Still MedImmune is hoping CAIV-T, its investigational intranasal, cold-adapted trivalent influenza vaccine will not have the same problems that FluMist encountered.
Apart from Flumist and CAIV-T, MedImmune has already begun applying its plasmid rescue technology to pandemic research efforts.
Last month, the National Institutes of Health (NIH) began enrolling participants in a Phase I study of an intranasal H5N1 influenza vaccine candidate based on MedImmune's live, attenuated vaccine technology, which also utilised reverse genetics technology.
