Case Study: Large-scale Manufacture of HIV Vaccines

The generalized processing steps involved in the manufacture of an AIDS vaccine are as follows:

• Master and working seed banks: To ensure that the starting materials are identical for each batch, all biological processes begin with a vial from a certified seed bank system for microbial or animal cells, or virus.
• Growth: Fermentation in a series of increasingly large bioreactors develops the desired quantities of cells to produce the product. In viral processes, the cells are usually grown to maximum density, then infected with the virus and maintained to maximize virus production.
• Harvest: The active vaccine intermediate is separated from the growth media using cross-flow or dead-end filtration, or centrifugation.
• Purification: The active vaccine intermediate is purified by filtration and chromatography.
• Bulk filling: Purified vaccine intermediate is formulated to final bulk, or API, specifications and filled into appropriate sterile bulk containers.
• Final product filling and packaging: Final formulated vaccine is filled into syringes, vials or other final delivery containers, lyophilized if necessary, labeled, packaged and prepared for shipment to the final destination.

Once the candidate vaccine is selected through pre-clinical trials and phase I/II clinical trials, process development should be initiated. The current regulation is that clinical materials must be closely representative of the final product and must be made in cGMP compliance. The transformation from laboratory methods to industrial processes adds many layers of scientific, technical, regulatory and organizational knowledge to vaccine production. The application of knowledge and wisdom in the various fields involved in vaccine industrialization usually produces a successful product.