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.
Table 3. Single-use, disposable options across the production train
The Engineering Challenge of Biosafety: GMP Versus BSL
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).
Table 4. The key opposing facility design principles
Manufacturing Flexibility and the 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).
Figure 2. A top-down facility design approach
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.
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.
Figure 3. Design triangle for a multipurpose, multiproduct facility (MPP)