previous chapter). The list of reported advantages of implementing SUBs and other

disposables is long (see Table 6.4) and still growing as more and more adoptions take

place. Several studies demonstrated competitive virus and recombinant protein yields

plus comparable cell growth characteristics for SUBs compared to stainless steel

bioreactors [89]. The use of SUBs entails unique physical and chemical criteria that

must be fulfilled: welds and polymeric multilayer films in the plastic bags must be

compliant with pharmacopoeia standards (e.g., free of any leachables and ex-

tractables). Special attention must be paid to safety precautions to prevent bag

TABLE 6.4

Pros and cons of disposable bioreactors

Reported advantages

Reported disadvantages

Comparable process yields

Elimination of costs and

downtime related to cleaning

operations

Scalability limitations: 6000 L is

currently largest working volume

Elimination of CIP/SIP

water and steam costs

Reduction of capital equipment

design, installation, and

validation cost

Unproven process robustness

Shorter plant commission

and start-up times

Reduction of initial capital

investment and cost of goods

Materials inventory, storage, and

repetitive purchases required

Reduction of plant footprint

Improvement of compliance

values (reduces error potential)

Vendor dependency, possible

supply chain shortages

Flexible footprint

Ease of material transfer between

diverse biosafety levels

Novel validation demands and

process layout and flow designs

Reduction of overall carbon

footprint

Ease of GMP “cold chain

logistics” and “good storage

practice”

Observed variability in vendor

“maturity” and capabilities

Reduction of production

facility service

requirements

Simplified and accelerated

product changeover and

turnaround

Development of new industry and

regulatory standards and

definitions

Enables flexible approaches

in process flow and layout

Reduction of process flow and

equipment modification costs

Product containment failure

concerns

Rapid site-to-site facility

transfer

Support of existing process

sensing, monitoring, modeling,

and control

Connectivity issues:

Standardization and continued

solutions required

Plug-and-play approach

Increased plant capacity,

flexibility, and campaigning

Pharmacopoeia standards:

Leachables and extractables

Good scalability within

available system sizes

Ease in reconfiguration and

extension of production facilities

Open questions about carbon

footprint and plastic waste

Reduction of contamination

risk

Reduction of lot and product

cross contamination risk

Standards for bag/tubing manifold

systems

Elimination of hazardous

cleaning materials

Increased sterility assurance

(irradiation over steam)

Lack of robust ON/OFF sterile

connectors

Reprinted and adapted from [ 90]. CIP: clean in place, SIP: steam in place.

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Bioprocessing of Viral Vaccines