Scale-up principles in fermentation MCQs With Answer

Scale-up principles in fermentation MCQs With Answer

This set of MCQs is designed specifically for M.Pharm students studying Bioprocess Engineering and Technology. The questions focus on essential scale-up principles encountered when moving a fermentation process from lab or pilot scale to production scale. Topics include oxygen transfer, mixing, power input, dimensionless numbers (Reynolds, Froude, power number), impeller and sparger selection, heat removal, shear effects, non-Newtonian broths, and practical scale-up strategies such as maintaining constant kLa or power per volume. Each question emphasizes conceptual understanding and application to pharmaceuticals, helping students prepare for exams and real-world process development challenges.

Q1. What is the primary objective when scaling up a fermentation process?

• Maximize vessel size regardless of process performance
• Reproduce lab-scale biological performance and product quality at larger scale
• Minimize capital cost by using the cheapest possible equipment
• Avoid aeration to reduce shear stress

Correct Answer: Reproduce lab-scale biological performance and product quality at larger scale

Q2. Which dimensionless number is most directly used to characterize flow regime and turbulent vs laminar conditions in stirred tanks?

• Froude number
• Reynolds number
• Prandtl number
• Schmidt number

Correct Answer: Reynolds number

Q3. Maintaining which parameter constant is a common strategy to preserve oxygen supply when scaling up aerobic fermentations?

• Impeller diameter
• kLa (volumetric mass transfer coefficient)
• Vessel height
• Foam volume

Correct Answer: kLa (volumetric mass transfer coefficient)

Q4. Power input per unit volume (P/V) is critical in scale-up. How is it usually expressed?

• Watts per impeller
• Watts per cubic meter
• Newton-meters
• Liters per minute

Correct Answer: Watts per cubic meter

Q5. Which scale-up criterion is most directly related to ensuring homogeneous composition and uniform temperature throughout the bioreactor?

• Constant tip speed
• Constant mixing time
• Constant vessel diameter
• Constant sparger pore size

Correct Answer: Constant mixing time

Q6. When scaling up, oxygen transfer commonly becomes limiting because:

• Gas solubility increases with volume
• Surface area to volume ratio decreases and mass transfer resistance increases
• Viscosity always decreases at larger scale
• Broth becomes fully mixed so O2 is wasted

Correct Answer: Surface area to volume ratio decreases and mass transfer resistance increases

Q7. Tip speed of an impeller is an important parameter because it directly influences:

• Sterility of the inoculum
• Shear forces experienced by cells and gas dispersion
• Heat conductivity of the vessel wall
• Aeration gas composition

Correct Answer: Shear forces experienced by cells and gas dispersion

Q8. For shear-sensitive microbial or mammalian cultures during scale-up, which impeller type is typically preferred?

• Rushton turbine
• Pitched-blade or hydrofoil (axial-flow) impeller
• Flat-blade disc impeller
• Propeller with high tip speed

Correct Answer: Pitched-blade or hydrofoil (axial-flow) impeller

Q9. The Froude number is used in scale-up to evaluate which phenomenon in bioreactors?

• Heat transfer coefficient
• Gravity-driven surface phenomena and free-surface vortices
• Mass transfer across membranes
• Enzyme kinetics

Correct Answer: Gravity-driven surface phenomena and free-surface vortices

Q10. The volumetric oxygen transfer coefficient kLa depends on several factors. Which of the following has the least direct influence on kLa?

• Gas flow rate (aeration)
• Impeller agitation speed and type
• Broth rheology and viscosity
• Sterilization cycle time

Correct Answer: Sterilization cycle time

Q11. In aerobic fermentations, the balance between OTR (oxygen transfer rate) and OUR (oxygen uptake rate) determines:

• Foam formation only
• Whether oxygen limitation or oxygen excess occurs affecting cell metabolism
• Autoclave temperature
• pH set point

Correct Answer: Whether oxygen limitation or oxygen excess occurs affecting cell metabolism

Q12. Power number (Np) is a dimensionless group used to correlate power draw of an impeller. It is primarily a function of:

• Fluid color and odor
• Impeller geometry and flow regime (Reynolds number)
• Incubation time
• Sparger material

Correct Answer: Impeller geometry and flow regime (Reynolds number)

Q13. Which sparger design change is most frequently applied during scale-up to improve gas dispersion and oxygen transfer?

• Reducing the number of sparger holes while increasing hole diameter drastically
• Using multiple-ring spargers or finer pore spargers to increase gas bubble dispersion
• Eliminating spargers and relying on headspace oxygen only
• Sealing the sparger to prevent gas flow

Correct Answer: Using multiple-ring spargers or finer pore spargers to increase gas bubble dispersion

Q14. Foam formation increases with scale. Which approach is preferred to control foam without adversely affecting culture physiology?

• Continuous high-dose chemical antifoam addition without validation
• Mechanical foam breakers combined with minimal validated antifoam usage
• Stopping aeration completely
• Increasing impeller speed to maximum

Correct Answer: Mechanical foam breakers combined with minimal validated antifoam usage

Q15. Heat removal becomes more challenging during scale-up because:

• Process heat generation decreases at larger cell densities
• Surface area to volume ratio decreases, reducing relative cooling area
• Cooling water becomes more efficient at larger volumes
• Agitation always cools the broth enough

Correct Answer: Surface area to volume ratio decreases, reducing relative cooling area

Q16. Non-Newtonian (shear-thinning) broths during scale-up often require special consideration because:

• Viscosity becomes independent of shear rate
• Apparent viscosity decreases with shear, altering mixing and oxygen transfer compared to lab scale
• They always behave like water at large scale
• They prevent sterilization

Correct Answer: Apparent viscosity decreases with shear, altering mixing and oxygen transfer compared to lab scale

Q17. Scale-down models are used in process development primarily to:

• Make small reactors cheaper
• Recreate large-scale heterogeneities and stresses in lab to predict large-scale behavior
• Avoid pilot scale altogether in all cases
• Increase sterilization time at lab scale

Correct Answer: Recreate large-scale heterogeneities and stresses in lab to predict large-scale behavior

Q18. In cascade control of aeration and agitation, which variable is commonly used as the primary controlled parameter to ensure sufficient oxygenation?

• Culture turbidity
• Dissolved oxygen concentration (DO)
• Foam height
• Vessel fill level

Correct Answer: Dissolved oxygen concentration (DO)

Q19. When scaling a fed-batch process facing oxygen limitation, which strategy can mitigate O2 limitation without changing vessel geometry?

• Reduce substrate feed rate and optimize feeding strategy to match OTR
• Increase inoculum temperature
• Eliminate agitation entirely
• Switch to closed-loop sparging with no gas exchange

Correct Answer: Reduce substrate feed rate and optimize feeding strategy to match OTR

Q20. Which practice is considered best when moving from pilot to commercial scale to reduce unexpected scale-up failures?

• Rely solely on theoretical correlations without empirical validation
• Use intermediate pilot studies, characterize kLa, mixing, heat transfer, and run representative scale-down experiments
• Skip process characterization because large vessels are standardized
• Increase agitation to maximum as a universal fix

Correct Answer: Use intermediate pilot studies, characterize kLa, mixing, heat transfer, and run representative scale-down experiments

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