Pandemic Flu Preparedness: A Manufacturing Perspective - Scalability, speed, and biosafety will be critical in the event of an influenza pandemic. The containment needs of an avian flu strain could pr


Pandemic Flu Preparedness: A Manufacturing Perspective
Scalability, speed, and biosafety will be critical in the event of an influenza pandemic. The containment needs of an avian flu strain could present additional challenges.

BioPharm International

Table 3. Single-use, disposable options across the production train
An incomplete list of single-use disposable options that can be integrated at various stages in manufacturing is shown in Table 3. Although by no means comprehensive, some of these technologies are available today, and many more are currently in development. These improved or novel methods are aimed at increasing throughput, improving aseptic intermediate operations, and improving containment.

The Engineering Challenge of Biosafety: GMP Versus BSL

Table 4. The key opposing facility design principles
When designing production and laboratory facilities for higher biosafety levels (i.e., BSL2+ or BSL3), due consideration must be given to opposing biocontainment design principles with good manufacturing practices. Although GMPs keep contaminants "out of the manufacturing space" and thereby ensure the quality of the end product, they do not ensure safety for operating personnel and the environment. Biosafety guidelines, in turn, identify the product (such as a novel pandemic strain) as a high risk to the environment in the event of release, and hence, the guidelines label the product itself as a "contaminant" that is required to be "fully contained within the manufacturing space." While working with a low-biological-risk product, good manufacturing practices would assume highest priority; however, when working with highly pathogenic organisms, biosafety measures would have to take precedence over GMPs. This factor adds complexity to the operations and layout of a standard multiproduct manufacturing space (Table 4).

Manufacturing Flexibility and the Design Approach

Figure 2. A top-down facility design approach
Manufacturing flexibility translates into optimal facility utilization to handle multiproduct campaigns. This approach would have to account for a broad range of production or process platforms, and thus the conceptual design of such a facility begins with the product(s) and the manufacturing process(es) (Figure 2).

Early stage process development and engineering assess the scalability and feasibility of disposable or novel technologies for potential process improvements; these features become the basis for a large-scale manufacturing strategy. Although resulting recommendations could significantly affect the facility design and layout, segregation of production lines in a multiproduct facility is critical to avoiding the risk of cross-contamination. Operating to the recommended biosafety level classification for biocontainment becomes important with increasing biological risk of the micro-organism in the event of release or accidental exposure. Flow considerations of raw materials, personnel, finished goods, and waste according to good manufacturing practices, plus biosafety measures, define the conceptual layout of the facility.

Figure 3. Design triangle for a multipurpose, multiproduct facility (MPP)
Scenario analyses and iterative approaches are then needed to test the requirements of scalability, speed, and biocontainment (Figure 3) before the conceptual project moves into the engineering phase. Fast-tracked project execution based on modular engineering principles can typically deliver such a facility in 12 to 14 months from the start of the detailed design to the end of commissioning.

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