Filtration methods in downstream processing MCQs With Answer

Introduction: Filtration is a cornerstone of downstream processing in biopharmaceutical manufacturing, used for clarification, concentration, sterilization and polishing of biologics. This quiz set focuses on filtration methods — including depth, cake, membrane (micro-, ultra-, and nanofiltration), tangential flow versus dead-end modes, filter aids, precoat techniques, fouling control, and validation considerations. Designed for M.Pharm students, the questions probe both theoretical concepts (pore size, molecular weight cut-off, transmembrane pressure, flux behavior) and practical aspects (material compatibility, integrity testing, scale-up challenges). Use these MCQs to assess and deepen your understanding of how filtration choices impact product quality, yield, sterility and process economics in bioprocess engineering.

Q1. Which filtration method is most appropriate for removing cell debris from a fermentation broth while minimizing filter clogging during large-scale clarification?

• Dead-end microfiltration with small pore size membranes
• Depth filtration using graded porous media
• Ultrafiltration in dead-end mode
• Sterile 0.22 µm cartridge filtration

Correct Answer: Depth filtration using graded porous media

Q2. Which parameter best describes the smallest particle size reliably retained by a membrane filter in ultrafiltration?

• Pore size in nanometers
• Molecular weight cut-off (MWCO)
• Nominal pore rating in micrometers
• Sterilizing grade designation

Correct Answer: Molecular weight cut-off (MWCO)

Q3. In tangential flow filtration (TFF), what is the primary advantage of crossflow over dead-end filtration for protein concentration?

• Higher volumetric throughput with zero retentate recirculation
• Continuous removal of retained solids along the membrane surface to reduce fouling
• Ability to use smaller pore size membranes without loss of flux
• Complete sterilization of permeate without additional steps

Correct Answer: Continuous removal of retained solids along the membrane surface to reduce fouling

Q4. Which filter material is most commonly chosen for sterile filtration of protein solutions due to low protein binding and chemical resistance?

• Cellulose acetate
• PES (polyethersulfone)
• Nylon 66
• Polytetrafluoroethylene (PTFE)

Correct Answer: PES (polyethersulfone)

Q5. Fouling in membrane filtration commonly leads to which of the following immediate effects?

• Increase in permeate flux at constant transmembrane pressure
• Decrease in transmembrane pressure for constant flux operation
• Decline in permeate flux and rise in required transmembrane pressure
• Improved selectivity of the membrane without cleaning

Correct Answer: Decline in permeate flux and rise in required transmembrane pressure

Q6. Which technique is specifically used to protect a membrane filter from cake formation during clarification by applying a thin layer of precoat material?

• Depth filtration
• Precoat filtration
• Backflushing
• Crossflow scouring

Correct Answer: Precoat filtration

Q7. When designing a filtration process for a biologic, which of the following is the most critical consideration for selecting sterile filters for final drug product sterilization?

• Membrane color and aesthetic properties
• Pore size and validated integrity test methods
• Price per filter only
• Ability to withstand extreme pH only

Correct Answer: Pore size and validated integrity test methods

Q8. What is the principal purpose of filter aids such as diatomaceous earth in cake or depth filtration?

• To chemically react with impurities and degrade them
• To form a porous, high-permeability matrix that increases filtrate clarity and prevents rapid clogging
• To sterilize the feed stream
• To decrease solids capture efficiency

Correct Answer: To form a porous, high-permeability matrix that increases filtrate clarity and prevents rapid clogging

Q9. Which of the following best describes the difference between microfiltration and ultrafiltration?

• Microfiltration is for separating dissolved solutes; ultrafiltration removes suspended cells
• Microfiltration uses lower transmembrane pressures and larger pore sizes than ultrafiltration
• Ultrafiltration has larger pores and lower selectivity than microfiltration
• They are identical processes with different names

Correct Answer: Microfiltration uses lower transmembrane pressures and larger pore sizes than ultrafiltration

Q10. Integrity testing of sterile membrane filters after filtration typically includes which method to confirm filter performance?

• Visual inspection for membrane color change
• Bubble point or pressure hold/leak test
• Measuring permeate conductivity only
• Weighing the filter before and after use

Correct Answer: Bubble point or pressure hold/leak test

Q11. In the context of membrane filtration, what does specific flux (L/m2·h·bar) describe?

• Volume of retentate produced per hour
• Permeate flux normalized to transmembrane pressure
• The molecular weight cut-off of the membrane
• Porosity of the membrane material

Correct Answer: Permeate flux normalized to transmembrane pressure

Q12. Which operational strategy is commonly employed to mitigate concentration polarization in tangential flow ultrafiltration?

• Reducing crossflow velocity to minimum
• Increasing crossflow velocity or shear at the membrane surface
• Sealing the membrane module to eliminate permeate flow
• Switching to dead-end mode exclusively

Correct Answer: Increasing crossflow velocity or shear at the membrane surface

Q13. For removal of endotoxins from a protein solution, which membrane characteristic is most relevant?

• Hydrophobicity of the membrane only
• Molecular weight cut-off and surface charge interactions
• Porosity measured in percentage only
• Color and transparency of the membrane

Correct Answer: Molecular weight cut-off and surface charge interactions

Q14. Which filtration technique is preferred when the goal is to concentrate a therapeutic protein while also exchanging buffer (diafiltration)?

• Dead-end microfiltration
• Tangential flow ultrafiltration (TFF)
• Depth filtration with filter aid
• Sterile 0.22 µm cartridge filtration

Correct Answer: Tangential flow ultrafiltration (TFF)

Q15. During scale-up of a filtration process, which parameter should be conserved to maintain similar fouling behavior and flux performance?

• Pore size alone regardless of flow conditions
• Shear rate or crossflow velocity at the membrane surface
• Filter housing color and dimensions
• Operator work schedule

Correct Answer: Shear rate or crossflow velocity at the membrane surface

Q16. Which statement about backwashing as a fouling control method is correct?

• Backwashing is effective for irreversible adsorption fouling of membranes
• Backwashing reverses cake and pore-blocking by reversing flow through the filter
• Backwashing increases the permanent deposition of foulants
• Backwashing eliminates the need for chemical cleaning in all cases

Correct Answer: Backwashing reverses cake and pore-blocking by reversing flow through the filter

Q17. What is the typical pore size used for sterilizing-grade membrane filters for aqueous pharmaceutical solutions?

• 5.0 µm
• 0.45 µm
• 0.22 µm
• 50 nm

Correct Answer: 0.22 µm

Q18. Which downstream processing challenge is filtration uniquely suited to address compared to centrifugation?

• Efficient continuous removal and containment of very fine colloidal solids with lower shear on products
• High-speed separation of large dense particles only
• Complete desalting of small molecules without further steps
• Generation of sterile dried powders directly

Correct Answer: Efficient continuous removal and containment of very fine colloidal solids with lower shear on products

Q19. Which cleaning protocol component is essential for removing organic foulants (proteins) from membrane surfaces?

• Low-pH rinses only
• Enzymatic or alkaline cleaning agents with appropriate contact time
• Pure water flush at ambient temperature only
• Air drying without chemicals

Correct Answer: Enzymatic or alkaline cleaning agents with appropriate contact time

Q20. Which statement best reflects the regulatory expectation for filter validation in biopharmaceutical sterile filtration?

• Validation is optional if the filter looks intact after use
• Filters must be qualified, and sterilizing processes validated including integrity testing and microbial retention studies
• Only chemical compatibility needs documentation, not microbial retention
• Single batch testing of permeate without routine integrity checks is sufficient

Correct Answer: Filters must be qualified, and sterilizing processes validated including integrity testing and microbial retention studies

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