An Alternative to the Scale-up and Distribution of Pandemic Influenza Vaccine - With baculovirus-based production in disposable equipment, vaccine can be available 10 to 12 weeks after an outbreak. -


An Alternative to the Scale-up and Distribution of Pandemic Influenza Vaccine
With baculovirus-based production in disposable equipment, vaccine can be available 10 to 12 weeks after an outbreak.

BioPharm International Supplements

Lowering Manufacturing Costs

Novavax contracted Jacobs Engineering (Conshohocken, PA) to provide a conceptual design and cost estimate of a facility for making influenza vaccine using the VLP manufacturing technology in disposables. The plant, which would be capable of producing 75 million doses per season, would be one-third the size of a facility of similar capacity designed for vaccine production in eggs or mammalian cell culture (assuming the same dose).

The cost of the new facility is estimated at $40 million, one-twelfth the cost of the mammalian cell culture facility at 50 million doses per season. The savings result in part from the higher yield, but mainly from the use of disposable manufacturing systems. Instead of large, fixed stainless-steel equipment, connected by a maze of piping and process controls, with automated cleaning and sterilization systems, the disposable approach uses free-standing skids with removable liners, flexible tubing, and disposable filters and chromatography columns. The result is the avoidance of the ever increasing cost of stainless steel, as well as the need for the clean-in-place and sterilize-in-place equipment, parts washers, and clean steam generators required for traditional processes. Further, other facility systems, like contaminated waste collection and kill systems and water-for-injection (WFI) systems are small, because all product contact parts arrive presterilized and are discarded after one use without cleaning. (In a traditional manufacturing process using stainless-steel equipment, cleaning processes contribute the vast majority of the volumes of purified water). This disposables-based approach also requires much less labor. An apparent waste issue of the disposable approach is the volume of plastics that are discarded. However, these high-energy plastic side streams can be incinerated with the cogeneration of power to minimize their environmental impact.

Scale-Up Speed

The smaller, less-complicated facility also can be built, commissioned, qualified, and validated much more quickly. The sequential validation of multiple water and steam systems is avoided; as well as the cleaning and sterilization validation required to begin process execution. The final Novavax facility will use manufacturing systems identical to those used in the pilot plant, so no scale-up is required, only the confirming validation runs duplicating what has already been intensely validated during the process development. The result is project execution in about two years, compared to four to six years for a traditional facility. The shorter time supports earlier availability of product for a pandemic, as well as faster recovery of the investment permitted by the shorter and less expensive project.

Comparison of Variable and Fixed Costs

Figure 3. Comparison of the relative variable and fixed costs of traditional vaccine production facilities and insect cell culture–based production.
From a cost of goods sold (COGS) perspective, the cost of insect-cell based VLP vaccine is equivalent to the egg-based influenza manufacturing process based on current yields (Figure 3). However, the mix of costs is quite different. Although eggs are a relatively expensive raw material, the remaining raw material costs of egg-based flu vaccines are low. By comparison, the disposable equipment in the Novavax process (e.g., reactor bags, chromatography resin/columns) are more costly. The 7-to 10-fold higher yields of the Novavax system make the per-dose costs reasonable, however, and additional yield gains should provide a COGS advantage for insect-cell based production. One key advantage of the disposable approach is the low labor requirements, because equipment is not cleaned and because the early steps of the egg-based system (i.e., the handling of the eggs) is very labor intensive. Thus, these factors cancel each other out , making the overall variable costs of the two approaches very similar (per gram of HA).

On the fixed cost side, however, the disposable approach has a significant advantage. Lower capital costs mean less depreciation as a fixed cost. Likewise, the lower energy consumption of disposables (no cleaning/sterilization, lower water use) also reduces fixed costs in the facility. The more important implication of low fixed costs, however, is that high facility capacities are not needed to reduce the unit cost impact of the fixed costs. That is, you loose the need for economies of scale and hence you can effectively build a smaller plant, suited for the local population, rather than a large plant to cover many regions.

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