Cell-Culture–Based Manufacturing: Meeting the Challenge of 21st Century Influenza - Influenza vaccines traditionally required yearly redevelopment to address changes in flu strains. With breakth

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Cell-Culture–Based Manufacturing: Meeting the Challenge of 21st Century Influenza
Influenza vaccines traditionally required yearly redevelopment to address changes in flu strains. With breakthrough technologies, however, the variables of yearly redevelopment can be reduced—accelerating time to market while reducing costs.


BioPharm International


The insect cell and baculovirus system has the necessary requirements for the manufacture of HA–Fc influenza vaccine. Recombinant baculoviruses can be constructed quickly and, unlike mammalian cell lines, do not require a period of selection and expansion before production can begin. The yields of similar proteins are also fairly uniform and can accommodate the scale required for real use. Cervarix, the new GlaxoSmithKline (GSK) vaccine for human papillomavirus, is manufactured using baculovirus technology, as is Protein Science's influenza candidate, FluBlØk, which consists of three recombinant hemagglutinin (rHA) proteins. Insect cells have been shown to have glycosylation pathways that are similar to those of mammalian cells, so the glycosylation of the HA region is similar to that of mammalian-derived vaccines. A key requirement is to achieve a high yield of purified HA–Fc vaccine by optimizing culture conditions via proprietary expertise developed for virus-like particle production using baculoviruses. A variety of fermenter technologies, including fed batch, perfusion, and "Wave bag" technology, are amenable to insect cell culture.

Additional benefits from an insect cell system include the following:

  • Insect cells typically grow faster than mammalian cells, reducing the production times and costs of batch production.
  • Insect cells cannot be infected by mammalian viruses, so the need for viral removal steps and validation is reduced, adding to the safety profile of insect-derived vaccines and reducing time and cost to get to clinical trials.

Ahead of an emergent strain shift capable of leading to a pandemic, a suitable vaccine cannot be definitively identified. Some national policies include stockpiling H5 vaccine, assuming that the shift from the currently prevalent H3 will be to H5, and that cross-strain protection within H5 assists in at least some degree of protective priming. However, neither of these two assumptions may hold true. To speed up approval of a new vaccine against an emergent strain, both the US Food and Drug Association (FDA) and the European Agency for the Evaluation of Medicinal Products (EMEA) have established approval processes, though with some differences. The EMEA's declared approach is to approve a "mock dossier," whereby the additional approval requirements are modest if prior mock dossier approval has been gained. Working within the emergent regulatory framework is essential during product development and to date, EMEA approval has been achieved by GSK and Novartis.

Summary

By using a platform technology, ImmBio is reducing the variables associated with having to redevelop vaccine production each year to adapt to the evolution of predominant flu strains. Eden Biodesign has been chosen by ImmBio as a partner to develop this flu vaccine platform technology. This choice is based on Eden Biodesign's expertise in vaccine and other biotech product development through to clinic and market, including preparation of the quality sections for clinical trial and product licensing applications. Eden is developing a manufacturing process for ImmBio's ImmunoBodies fusion protein to maximize yield while reducing production times and costs. Many parameters add up to making a successful marketed product; a key starting point involves attention to developing and documenting a scalable, rapid, and low-cost manufacturing process and its accompanying analytical technology. By dealing early with problems typically associated with late-phase product development, total product development times and costs can be reduced significantly.

Amanda Shipman is a project manager at Eden Biodesign, National Biomanufacturing Centre, Liverpool, United Kingdom, +44 (0)151 728 1750,
.

Graham Clarke is chief executive officer at ImmBio, Babraham Research Campus, Babraham, Cambridge, United Kingdom, +44 (0)1223 496 1177,
.


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