Table 3.

Advantages and limitations of single-use bioreactors as whole and specific single-use platforms.

Platform	Advantages	Drawbacks/Limitations
Single-use bioreactors	Compatible with GMP guidelines Pre-sterilised—no CIP and SIP necessary Closed systems—minor contamination risk Reduced downtime and higher productivity Lower overall environmental impact than reusable systems Lower initial investment	Risk of leachables—possible cell growth impairment Maximum scale limited by material resistance Environmental impact of vessel manufacturing, packaging, shipping, and disposal throughout the whole process High running costs
Stirred tank	Vast know-how and characterisation Available at many different scales Availability of empirical correlations and criteria for variable estimation and scale-up Variety of agitation mechanisms Some are naturally compatible with perfusion	High overall shear stress Heterogeneity of shear stress distribution—existence of hot-spots and stagnated zones
Fixed bed	Low shear stress High surface-to-volume ratio and small footprint Naturally compatible with perfusion	Formation of concentration gradients Cell harvesting only possible at the end of the culture Difficult cell monitoring
Hollow fibre	Low shear stress High surface-to-volume ratio and small footprint Semipermeable membrane system, allowing for indirect mass exchange Naturally compatible with perfusion	Formation of concentration gradients Cell harvesting only possible at the end of the culture Difficult cell monitoring Susceptibility to fouling Expensive operation Available only at a single scale (2.1 m2)
Rotary cell culture system	Low shear stress Simulated microgravity environment No air bubbles Some are naturally compatible with perfusion	Formation of concentration gradients Available only at low scales (up to 50 mL)
Rotating bed	Low shear stress High surface-to-volume ratio and small footprint Intermittent contact with medium and headspace Naturally compatible with perfusion	Cell harvesting only possible at the end of the culture Difficult cell monitoring
Rocking motion	Efficient mixing with low shear stress No air bubbles Some are naturally compatible with perfusion Available at many different scales	Resonance phenomenon—spike of shear stress at certain rocking velocities Some cell deposition and microcarrier sticking to vessel walls
Vertical-Wheel	Efficient mixing with low shear stress Vessel format avoids cell settling beneath the impeller Narrow gradients of energy dissipation rate Available at many different scales Naturally compatible with perfusion starting from the 3 L scale	Still not well characterised Small-scale (100 mL and 500 mL) bioreactors not controlled and incompatible with perfusion