Q.1 What is the primary purpose of sterilizing a bioreactor before inoculation?
To increase the temperature of the culture medium
To remove all living microorganisms that could compete with the production strain
To adjust the pH of the medium
To enhance oxygen solubility
Explanation - Sterilization eliminates unwanted microbes that could out‑compete or contaminate the desired production organism, ensuring a pure culture.
Correct answer is: To remove all living microorganisms that could compete with the production strain
Q.2 Which sterilization method is most commonly used for heat‑stable bioreactor components?
Filtration
Radiation
Autoclaving at 121 °C for 30 min
Chemical fumigation
Explanation - Autoclaving applies moist heat at 121 °C for a sufficient time to achieve a 10⁻⁶ reduction in viable spores, making it the standard for heat‑stable parts.
Correct answer is: Autoclaving at 121 °C for 30 min
Q.3 What is the D‑value in sterilization terminology?
The time required to reduce the microbial population by 90 % at a given temperature
The total energy required for sterilization
The temperature at which sterilization occurs
The dosage of radiation needed for sterilization
Explanation - The D‑value (decimal reduction time) quantifies how long a process must be applied to achieve a one‑log (90 %) reduction in viable organisms.
Correct answer is: The time required to reduce the microbial population by 90 % at a given temperature
Q.4 In a bioreactor, which component is most vulnerable to microbial contamination during operation?
Stainless‑steel vessel walls
Heat exchangers
Sampling port
Pumps
Explanation - Sampling ports are frequently accessed, making them a common entry point for contaminants if not properly sealed and sterilized.
Correct answer is: Sampling port
Q.5 What does the term "sterile filtration" refer to?
Removing particles larger than 0.45 µm
Passing the culture through a 0.2 µm filter to remove microorganisms
Filtering out dissolved gases
Using a filter to adjust pH
Explanation - A 0.2 µm membrane filter retains bacteria and most fungi, providing a sterile liquid without applying heat.
Correct answer is: Passing the culture through a 0.2 µm filter to remove microorganisms
Q.6 Which of the following is NOT a typical source of contamination in a bioreactor system?
Improperly sterilized raw materials
Leaking seals
Excessive agitation speed
Airborne spores
Explanation - While high agitation can cause shear stress, it does not directly introduce contaminants; the other options are direct contamination pathways.
Correct answer is: Excessive agitation speed
Q.7 What is the main advantage of using a dry heat sterilizer for metal tools?
It requires lower temperatures than moist heat
It penetrates packaging materials better
It can sterilize oil‑containing equipment without degradation
It removes all spores instantly
Explanation - Dry heat sterilization (e.g., 160 °C for 2 h) is suitable for oil‑resistant equipment because it does not cause moisture‑related corrosion.
Correct answer is: It can sterilize oil‑containing equipment without degradation
Q.8 Which parameter is most critical when using gamma radiation for sterilization?
Dose rate (kGy/h)
Ambient temperature
pH of the product
Conductivity of the medium
Explanation - The absorbed dose (kGy) determines the extent of microbial inactivation; dose rate affects processing time and uniformity.
Correct answer is: Dose rate (kGy/h)
Q.9 In the context of contamination control, what does the term "aseptic technique" mean?
Using chemicals to kill all microorganisms
Working in a sterile environment to prevent introduction of microbes
Heating all equipment to 100 °C
Filtering air through HEPA filters only
Explanation - Aseptic technique involves practices that maintain sterility of the product and equipment throughout handling.
Correct answer is: Working in a sterile environment to prevent introduction of microbes
Q.10 Which sterilization method would you choose for a heat‑sensitive enzyme solution?
Autoclaving
Dry heat sterilization
Filtration
Boiling
Explanation - Filtration removes microbes without exposing the solution to high temperatures that could denature the enzyme.
Correct answer is: Filtration
Q.11 What is the Z‑value in sterilization kinetics?
The temperature increase needed to reduce the D‑value by one log cycle
The total time required for complete sterilization
The dose of radiation needed for a 50 % kill
The number of cycles needed for sterilization
Explanation - The Z‑value indicates the temperature change required to achieve a ten‑fold reduction in D‑value, reflecting thermal resistance.
Correct answer is: The temperature increase needed to reduce the D‑value by one log cycle
Q.12 Which material is most commonly used for bioreactor vessel construction due to its corrosion resistance and ease of sterilization?
Aluminium
Stainless steel (304/316)
Copper
Polypropylene
Explanation - Stainless steel resists corrosion, tolerates high temperatures, and withstands repeated autoclave cycles, making it ideal for bioreactors.
Correct answer is: Stainless steel (304/316)
Q.13 Which of the following is a common indicator organism used to validate sterilization processes?
Escherichia coli
Bacillus subtilis spores
Saccharomyces cerevisiae
Lactobacillus acidophilus
Explanation - B. subtilis spores are highly resistant to heat and are therefore used as a worst‑case indicator for sterilization validation.
Correct answer is: Bacillus subtilis spores
Q.14 During a steam sterilization cycle, why is the “hold time” important?
It allows the temperature to drop slowly
It ensures that the entire load reaches the required temperature for enough time to achieve sterility
It helps in drying the equipment
It reduces the pressure inside the autoclave
Explanation - Hold time maintains the target temperature for a specified period, guaranteeing that all microbes are inactivated throughout the load.
Correct answer is: It ensures that the entire load reaches the required temperature for enough time to achieve sterility
Q.15 Which type of filter membrane pore size is typically used for sterilizing a liquid feed in a bioprocess?
0.45 µm
1.0 µm
0.2 µm
5 µm
Explanation - A 0.2 µm pore size effectively removes bacteria and most fungi, providing a sterile filtrate for bioprocesses.
Correct answer is: 0.2 µm
Q.16 What is the main limitation of using UV light for sterilizing a bioreactor vessel?
It can only sterilize surfaces and not opaque liquids
It requires very high temperatures
It damages the stainless‑steel walls
It leaves chemical residues
Explanation - UV light has limited penetration depth and cannot sterilize through opaque media; it is mainly used for surface decontamination.
Correct answer is: It can only sterilize surfaces and not opaque liquids
Q.17 Which of the following best describes a ‘clean‑in‑place’ (CIP) system?
A system that cleans the bioreactor without disassembly using circulating cleaning solutions
A portable cleaning unit that must be removed after each batch
A manual cleaning process using brushes
A system that only cleans the external surfaces of equipment
Explanation - CIP allows automated cleaning of internal surfaces while the equipment stays in its operational position, reducing downtime and contamination risk.
Correct answer is: A system that cleans the bioreactor without disassembly using circulating cleaning solutions
Q.18 What is the purpose of a ‘sterile air filter’ in a bioreactor system?
To cool the reactor
To remove particulates and microorganisms from incoming air
To increase oxygen solubility
To regulate humidity
Explanation - Sterile air filters (often HEPA) ensure that air entering the bioreactor does not carry microbes that could cause contamination.
Correct answer is: To remove particulates and microorganisms from incoming air
Q.19 Which parameter must be monitored to ensure the effectiveness of a chemical sterilant (e.g., peracetic acid) in a closed system?
pH of the sterilant solution
Color of the solution
Electrical conductivity
Magnetic field strength
Explanation - The antimicrobial activity of many chemical sterilants is pH‑dependent; maintaining the correct pH ensures optimal efficacy.
Correct answer is: pH of the sterilant solution
Q.20 Why is it important to validate the sterilization cycle for each new bioreactor design?
Because each design may have different heat transfer characteristics affecting sterilization efficacy
Because validation is a legal requirement only for pharmaceutical products
Because it improves the speed of the process
Because it reduces the need for aseptic techniques
Explanation - Different geometries, materials, and volumes alter how heat penetrates, making cycle validation essential for ensuring sterility.
Correct answer is: Because each design may have different heat transfer characteristics affecting sterilization efficacy
Q.21 Which of the following statements about endotoxins is TRUE?
They are easily destroyed by standard autoclaving
They are components of the cell wall of Gram‑positive bacteria
They can cause pyrogenic reactions even after the microorganisms are killed
They are only a concern in anaerobic fermentations
Explanation - Endotoxins (lipopolysaccharides) from Gram‑negative bacteria remain active after sterilization and can induce fever in humans.
Correct answer is: They can cause pyrogenic reactions even after the microorganisms are killed
Q.22 What is the main function of a ‘steam trap’ in a sterilization system?
To accelerate steam flow
To remove condensate while retaining steam pressure
To filter out microorganisms from steam
To cool the steam before it enters the vessel
Explanation - Steam traps discharge condensate that would otherwise reduce temperature and pressure, ensuring efficient sterilization.
Correct answer is: To remove condensate while retaining steam pressure
Q.23 In a bioreactor, which of the following actions most directly reduces the risk of cross‑contamination between batches?
Increasing agitation speed
Using disposable single‑use bioreactor bags
Lowering the temperature
Increasing the aeration rate
Explanation - Single‑use systems eliminate the need for cleaning and sterilization between runs, thereby removing a major source of cross‑contamination.
Correct answer is: Using disposable single‑use bioreactor bags
Q.24 Which of the following is NOT a typical indicator of a contamination event during a fermentation run?
Unexpected drop in pH
Sudden increase in dissolved oxygen consumption
Stable optical density
Off‑color of the broth
Explanation - A stable optical density usually indicates no abnormal growth; contamination typically causes unexpected changes in growth parameters.
Correct answer is: Stable optical density
Q.25 What does the term “log reduction” mean in the context of microbial sterilization?
A reduction of microorganisms by a factor of 10
A reduction of microorganisms by a factor of 100
A reduction of microorganisms by a factor of 1,000
All of the above, depending on the log number
Explanation - Each log reduction corresponds to a ten‑fold decrease; 1‑log = 10×, 2‑log = 100×, 3‑log = 1,000×, etc.
Correct answer is: All of the above, depending on the log number
Q.26 Which sterilization method is most suitable for inactivating viral contaminants in a biopharmaceutical product?
Autoclaving
Gamma irradiation
Dry heat
Filtration through 0.2 µm membrane
Explanation - Gamma rays can penetrate liquids and inactivate viruses without the need for high temperatures that could degrade the product.
Correct answer is: Gamma irradiation
Q.27 During a CIP cycle, why is it important to maintain a minimum temperature of 80 °C for the cleaning solution?
To ensure the solution stays liquid
To increase the solubility of organic residues and enhance cleaning efficiency
To sterilize the cleaning solution
To prevent corrosion of stainless steel
Explanation - Higher temperatures improve the dissolution and removal of proteinaceous and lipid residues from the equipment surfaces.
Correct answer is: To increase the solubility of organic residues and enhance cleaning efficiency
Q.28 Which of the following is a primary advantage of using a closed‑system bioreactor over an open‑system?
Higher oxygen transfer rates
Reduced risk of environmental contamination
Simpler temperature control
Lower capital cost
Explanation - Closed systems limit exposure to the external environment, decreasing the likelihood of contaminant entry.
Correct answer is: Reduced risk of environmental contamination
Q.29 What is the typical concentration range for peracetic acid when used as a sterilant in CIP processes?
0.1–0.2 % (w/v)
1–2 % (w/v)
5–10 % (w/v)
10–15 % (w/v)
Explanation - Low concentrations (0.1–0.2 %) of peracetic acid are effective for sterilization while minimizing corrosion and material degradation.
Correct answer is: 0.1–0.2 % (w/v)
Q.30 Which type of bioreactor material is inherently single‑use and eliminates the need for sterilization?
Glass
Stainless steel
Polypropylene disposable bag
Carbon steel
Explanation - Single‑use bioreactors made from disposable polymers are pre‑sterilized and discarded after each batch, removing sterilization steps.
Correct answer is: Polypropylene disposable bag
Q.31 What is the purpose of a ‘validation run’ after establishing a new sterilization protocol?
To test the speed of the process
To confirm that the protocol reliably achieves sterility under routine conditions
To calibrate temperature sensors
To train operators
Explanation - Validation runs provide evidence that the sterilization cycle consistently meets sterility requirements before full‑scale use.
Correct answer is: To confirm that the protocol reliably achieves sterility under routine conditions
Q.32 In the context of contamination control, what does the acronym ‘HEPA’ stand for?
High Efficiency Particulate Air
Highly Effective Purifying Apparatus
Heat‑Evaporated Particle Analyzer
Hydro‑Electrical Particle Assay
Explanation - HEPA filters remove at least 99.97 % of particles ≥0.3 µm, making them essential for sterile air supply in bioprocessing.
Correct answer is: High Efficiency Particulate Air
Q.33 Which of the following best describes a ‘sterile barrier’ in a bioreactor system?
A physical component that prevents microbial ingress, such as a sealed lid or filter
A chemical disinfectant applied to the vessel walls
A temperature sensor used during sterilization
An electronic lock on the control panel
Explanation - Sterile barriers are designed to keep microbes out while allowing necessary transfers (e.g., gases, liquids).
Correct answer is: A physical component that prevents microbial ingress, such as a sealed lid or filter
Q.34 When using a steam sterilizer, why is it important to purge air from the chamber before introducing steam?
Air reduces the temperature of the steam
Air pockets can prevent steam from contacting all surfaces, leading to incomplete sterilization
Air increases the pressure too quickly
Air reacts chemically with steam
Explanation - Air insulation reduces heat transfer; proper venting ensures steam fills the chamber and contacts all surfaces.
Correct answer is: Air pockets can prevent steam from contacting all surfaces, leading to incomplete sterilization
Q.35 Which method can be used to monitor the effectiveness of a sterilization cycle in real time?
Measuring the pH of the liquid inside the vessel
Using a thermocouple to log temperature and time data (T‑D curve)
Counting bubbles in the gas inlet line
Observing color change of the vessel walls
Explanation - Temperature‑time data (T‑D profile) are recorded to verify that the required conditions for sterilization were met.
Correct answer is: Using a thermocouple to log temperature and time data (T‑D curve)
Q.36 What is a typical microbiological limit for endotoxin levels in parenteral products?
5 EU/mL
0.5 EU/mL
50 EU/mL
500 EU/mL
Explanation - Regulatory guidelines often set an endotoxin limit of ≤5 endotoxin units (EU) per milliliter for injectable products.
Correct answer is: 5 EU/mL
Q.37 Which of the following is a common cause of post‑sterilization contamination in a bioreactor?
Improper autoclave temperature
Failure to properly seal sampling ports after sampling
Using too much cleaning solution
Excessive agitation
Explanation - If sampling ports are not resealed correctly, microorganisms can enter the sterile environment after sterilization.
Correct answer is: Failure to properly seal sampling ports after sampling
Q.38 What is the primary reason for using a ‘sterile connection’ (e.g., welded, aseptic valve) when linking two bioprocess vessels?
To reduce pressure loss
To prevent microbial ingress during transfer
To improve heat transfer
To increase flow rate
Explanation - Sterile connections maintain a closed, aseptic pathway, ensuring that transferred material remains uncontaminated.
Correct answer is: To prevent microbial ingress during transfer
Q.39 Which factor most influences the choice between steam sterilization and chemical sterilization for a given component?
The component’s color
Material compatibility (heat‑sensitivity vs. chemical resistance)
The size of the component
The brand of the sterilizer
Explanation - Heat‑sensitive items cannot withstand steam, while chemically sensitive items may degrade under harsh chemicals, dictating the method.
Correct answer is: Material compatibility (heat‑sensitivity vs. chemical resistance)
Q.40 In a bioreactor, what does the term ‘bioburden’ refer to?
The amount of biomass produced
The total number of viable microorganisms present before sterilization
The concentration of nutrients in the medium
The electrical power consumption of the system
Explanation - Bioburden is the microbial load that must be reduced to achieve a sterile product during the sterilization step.
Correct answer is: The total number of viable microorganisms present before sterilization
Q.41 Why is it important to perform a ‘dry‑out’ phase after an autoclave cycle?
To remove residual moisture that could promote microbial growth after sterilization
To increase the temperature further
To cool down the equipment rapidly
To change the pressure inside the chamber
Explanation - Moisture left after sterilization can support microbial growth; a dry‑out phase minimizes this risk.
Correct answer is: To remove residual moisture that could promote microbial growth after sterilization
Q.42 Which of the following statements about “single‑use” bioreactors is FALSE?
They eliminate the need for cleaning and sterilization between batches
They can only be used for small‑scale processes
They reduce cross‑contamination risk
They are pre‑sterilized by the manufacturer
Explanation - Single‑use bioreactors are available in a range of sizes, including large industrial scales; the statement is inaccurate.
Correct answer is: They can only be used for small‑scale processes
Q.43 What is the main advantage of using a “passive” sterilization method like dry heat over an “active” method like steam?
Faster cycle time
No need for moisture control
Lower temperature requirement
Higher penetration depth
Explanation - Dry heat sterilization does not require water management, simplifying the process for moisture‑sensitive items.
Correct answer is: No need for moisture control
Q.44 Which analytical technique is commonly employed to detect low‑level microbial contamination in a sterile product?
Gas chromatography
Polymerase chain reaction (PCR)
Fourier‑transform infrared spectroscopy
High‑performance liquid chromatography
Explanation - PCR amplifies specific DNA sequences, enabling detection of trace amounts of microbial contaminants.
Correct answer is: Polymerase chain reaction (PCR)
Q.45 When a bioreactor uses an inline sterilizing filter, what is the most critical specification of that filter?
Pore size of 0.2 µm or smaller
Filter material color
Length of the filter housing
Weight of the filter
Explanation - A pore size ≤0.2 µm ensures that bacteria are removed, maintaining sterility of the fluid stream.
Correct answer is: Pore size of 0.2 µm or smaller
Q.46 What does the term ‘CIP‑SIP’ stand for in bioprocessing?
Cleaning‑In‑Place and Sterilization‑In‑Place
Continuous‑Input‑Processing – Standard‑Integrated‑Procedure
Chemical‑Induced‑Purity – Systematic‑Inactivation‑Protocol
Control‑Intensive‑Process – Safety‑In‑Practice
Explanation - CIP‑SIP refers to automated cleaning and sterilization of equipment without disassembly, essential for maintaining sterility.
Correct answer is: Cleaning‑In‑Place and Sterilization‑In‑Place
Q.47 Which of the following is a primary reason for performing a ‘media fill’ test?
To verify the sterility of the final product
To assess the aseptic technique of operators and the integrity of the process
To determine the optimal nutrient composition
To calibrate flow meters
Explanation - Media fills simulate a production run using a sterile growth medium to detect breaches in aseptic practice.
Correct answer is: To assess the aseptic technique of operators and the integrity of the process
Q.48 Why is it important to control the humidity level inside a sterilization chamber?
High humidity reduces the risk of static discharge
Moisture is required for effective heat transfer during steam sterilization
Low humidity improves the speed of the cycle
Humidity does not affect sterilization
Explanation - Steam sterilization relies on saturated steam; sufficient humidity ensures efficient heat transfer and microbial kill.
Correct answer is: Moisture is required for effective heat transfer during steam sterilization
Q.49 Which material property is most critical when selecting a tubing for sterile feed lines?
Thermal conductivity
Chemical compatibility with the feed medium
Electrical conductivity
Magnetic permeability
Explanation - Tubing must not leach contaminants or degrade when in contact with the sterile feed solution.
Correct answer is: Chemical compatibility with the feed medium
Q.50 What is the most effective way to reduce the bioburden on raw material containers before they enter the cleanroom?
Washing with tap water
Dry heat sterilization
UV irradiation
Wiping with a 70 % ethanol solution
Explanation - 70 % ethanol rapidly disinfects surfaces, reducing microbial load without leaving residues that could affect the material.
Correct answer is: Wiping with a 70 % ethanol solution
Q.51 In the context of sterilization, what does the term “over‑kill” refer to?
Using a higher temperature than required, leading to equipment damage
Applying a sterilization cycle that exceeds the necessary lethality, ensuring a safety margin
Killing more microbes than expected, causing product loss
Using too much chemical sterilant
Explanation - Over‑kill provides a margin of safety to guarantee sterility, especially important for high‑risk products.
Correct answer is: Applying a sterilization cycle that exceeds the necessary lethality, ensuring a safety margin
Q.52 Which of the following is a standard test to verify the integrity of a sterile filter after use?
Bubble point test
Tensile strength test
pH test
Conductivity test
Explanation - The bubble point test checks for leaks or breaches by measuring the pressure required to force air through the filter.
Correct answer is: Bubble point test
Q.53 What is the primary reason that high‑pressure steam is used rather than hot water for sterilization?
Steam provides higher temperatures at lower pressures
Steam has a higher heat transfer coefficient, allowing faster and more uniform sterilization
Water cannot be heated above 100 °C
Steam is cheaper than water
Explanation - Steam’s latent heat enables rapid heat delivery and penetration, making it more efficient for sterilization than hot water.
Correct answer is: Steam has a higher heat transfer coefficient, allowing faster and more uniform sterilization
Q.54 Which type of bioreactor design inherently reduces the risk of contamination due to its geometry?
Open‑top vessel
Horizontal drum with multiple access ports
Single‑use bag with sealed inlet/outlet ports
Stirred‑tank with a removable lid
Explanation - A sealed, disposable bag eliminates many access points where contaminants could enter, lowering contamination risk.
Correct answer is: Single‑use bag with sealed inlet/outlet ports
Q.55 During a sterilization validation, a batch of Bacillus spores shows a 6‑log reduction. What is the probability that any viable spores remain?
1 in 10⁶
1 in 10³
1 in 10⁹
1 in 10¹²
Explanation - A 6‑log reduction means the original population is reduced by a factor of 10⁶; thus, the chance of a surviving spore is 1/1,000,000.
Correct answer is: 1 in 10⁶
Q.56 What is the purpose of using a “sanitizing agent” after a CIP cycle but before a SIP cycle?
To reduce the microbial load to a level where sterilization can be more effective
To increase the temperature of the system
To neutralize residual chemicals
To add nutrients for the next culture
Explanation - Sanitization lowers the bioburden, making the subsequent sterilization step more reliable and potentially shorter.
Correct answer is: To reduce the microbial load to a level where sterilization can be more effective
Q.57 Which of the following best describes a “critical control point” (CCP) in a bioprocessing sterilization workflow?
Any step where a deviation could compromise product sterility
The point where the product is packaged
The temperature of the ambient room
The brand of equipment used
Explanation - CCPs are stages where loss of control can lead to contamination; they require monitoring and corrective actions.
Correct answer is: Any step where a deviation could compromise product sterility
Q.58 Why is it important to monitor the pressure inside a sealed bioreactor during a sterilization cycle?
Pressure affects the rate of microbial growth
Correct pressure ensures steam can reach all surfaces and maintain the required temperature
Pressure determines the pH of the medium
Pressure is unrelated to sterilization
Explanation - Adequate pressure keeps steam in the saturated phase, delivering consistent heat for effective sterilization.
Correct answer is: Correct pressure ensures steam can reach all surfaces and maintain the required temperature
Q.59 What is the typical autoclave cycle time (including heat‑up, hold, and cool‑down) for a 200 L stainless‑steel bioreactor?
30 min total
45 min total
90 min total
120 min total
Explanation - Large vessels often require 30 min heat‑up, 30 min hold at 121 °C, and 30 min cool‑down to ensure uniform sterilization.
Correct answer is: 90 min total
Q.60 Which of the following is NOT a typical component of a bioreactor's sterilization system?
Steam generator
Heat exchangers
Vacuum pump
Radiation source
Explanation - While radiation can sterilize products, most bioreactors rely on steam, heat exchangers, and vacuum for CIP/SIP; radiation is not standard equipment.
Correct answer is: Radiation source
Q.61 What does the abbreviation ‘ISO’ refer to in the context of cleanroom standards for bioprocessing?
International Organization for Standardization
Integrated Sterilization Operations
In‑situ Oxidation
Industrial Safety Office
Explanation - ISO develops and publishes international standards, including those for cleanroom classification (e.g., ISO 5).
Correct answer is: International Organization for Standardization
Q.62 Which of the following best explains why a bioreactor may be equipped with a ‘thermal sensor array’?
To monitor temperature distribution throughout the vessel during sterilization
To control the pH of the culture
To adjust agitation speed
To measure oxygen concentration
Explanation - Multiple sensors provide real‑time temperature maps, ensuring all zones reach sterilization criteria.
Correct answer is: To monitor temperature distribution throughout the vessel during sterilization
Q.63 Which of the following is the most common method for validating the sterility of a finished biopharmaceutical product?
Direct microscopic count
Membrane filtration followed by incubation
Spectrophotometric analysis
Electrical conductivity measurement
Explanation - Samples are filtered, the filter is incubated, and any microbial growth indicates contamination.
Correct answer is: Membrane filtration followed by incubation
Q.64 Why is it advisable to use disposable sterile connectors for critical fluid transfers in a bioprocess?
They are cheaper than reusable connectors
They eliminate the need for cleaning and sterilization, reducing contamination risk
They increase the flow rate
They improve the taste of the product
Explanation - Disposable connectors provide a sterile barrier for each use, removing potential points of failure from cleaning.
Correct answer is: They eliminate the need for cleaning and sterilization, reducing contamination risk
Q.65 In the context of CIP, what does the term “detergent concentration” refer to?
The amount of surfactant used to solubilize organic residues
The temperature of the cleaning solution
The pH of the cleaning solution
The speed of the pump
Explanation - Detergents contain surfactants that emulsify and remove proteins, lipids, and other fouling materials during cleaning.
Correct answer is: The amount of surfactant used to solubilize organic residues
Q.66 What is the effect of using a higher steam pressure (e.g., 2 bar instead of 1 bar) during sterilization?
It reduces the sterilization temperature
It increases the temperature of saturated steam, potentially reducing required hold time
It has no effect on temperature
It decreases the effectiveness of sterilization
Explanation - Higher pressure raises the boiling point of water, producing steam at higher temperature and enhancing microbial kill rates.
Correct answer is: It increases the temperature of saturated steam, potentially reducing required hold time
Q.67 Which of the following is a recommended practice for preventing contamination during the sampling of a sterile bioreactor culture?
Open the vessel to the lab environment for sampling
Use a sterile, closed‑loop sampling system with pre‑sterilized tubing
Sample using a regular pipette directly from the vessel
Collect samples after the bioreactor has been cooled to room temperature
Explanation - Closed‑loop systems maintain sterility by preventing exposure of the culture to the environment.
Correct answer is: Use a sterile, closed‑loop sampling system with pre‑sterilized tubing
Q.68 Which of the following best describes the concept of “validation of the cleaning process” (VCP)?
Testing that cleaning removes all visible dirt
Demonstrating that the cleaning procedure consistently meets predefined cleanliness criteria
Measuring the time required for cleaning
Ensuring the cleaning chemicals are inexpensive
Explanation - VCP proves that cleaning reliably removes residues and microbial load to acceptable levels.
Correct answer is: Demonstrating that the cleaning procedure consistently meets predefined cleanliness criteria
Q.69 Why might a bioprocess engineer select a ‘radiation sterilizer’ over steam for a particular component?
The component is heat‑sensitive and cannot withstand autoclave temperatures
Radiation is cheaper than steam
Radiation provides a lower level of sterility
Steam does not work in the presence of oxygen
Explanation - Radiation can sterilize without heat, making it suitable for thermolabile items.
Correct answer is: The component is heat‑sensitive and cannot withstand autoclave temperatures
Q.70 Which of the following is a common method for detecting endotoxin contamination in a sterile product?
Limulus Amebocyte Lysate (LAL) assay
Gram staining
PCR for bacterial DNA
Mass spectrometry
Explanation - The LAL assay uses horseshoe crab blood enzymes that clot in the presence of endotoxins, providing a sensitive detection method.
Correct answer is: Limulus Amebocyte Lysate (LAL) assay
Q.71 What is the primary purpose of a ‘pass‑through’ sterilization chamber in a bioprocess facility?
To increase the temperature of incoming materials
To allow transfer of items between areas while maintaining sterility
To store sterile products
To mix chemicals
Explanation - Pass‑through chambers provide a sealed environment for moving equipment or materials without exposing them to the non‑sterile environment.
Correct answer is: To allow transfer of items between areas while maintaining sterility
Q.72 When a bioreactor is equipped with an inline UV sterilizer for feed water, which parameter must be monitored to ensure effectiveness?
UV dose (mJ/cm²)
pH of the water
Conductivity of the water
Viscosity of the feed
Explanation - The UV dose determines the extent of microbial inactivation; it must be sufficient to achieve the required log reduction.
Correct answer is: UV dose (mJ/cm²)
Q.73 Which of the following is a typical sign that a sterilization cycle has failed?
The temperature sensor reads lower than the set point
The steam pressure is higher than expected
The autoclave door does not close
The cycle completes faster than usual
Explanation - Insufficient temperature indicates that the required lethal conditions were not achieved, leading to a failed sterilization.
Correct answer is: The temperature sensor reads lower than the set point
Q.74 In a bioreactor, what is the function of an ‘air filter’ placed on the inlet gas line?
To humidify the incoming air
To remove particulates and microorganisms before air enters the vessel
To increase the oxygen concentration
To cool the air
Explanation - Air filters (often HEPA) prevent airborne contaminants from being introduced via the gas supply.
Correct answer is: To remove particulates and microorganisms before air enters the vessel
Q.75 Which of the following best describes the concept of ‘sterile barrier technology’ (SBT) in modern bioreactors?
Use of disposable components that form a closed, sterile path for fluids and gases
Applying high voltage to kill microbes
Using magnetic fields to repel bacteria
Coating surfaces with antimicrobial paints
Explanation - SBT employs single‑use, pre‑sterilized parts (e.g., bags, tubing, filters) to maintain sterility throughout the process.
Correct answer is: Use of disposable components that form a closed, sterile path for fluids and gases
Q.76 What is the typical size of a bacterial spore that must be retained by a sterilizing-grade filter?
0.5 µm
0.2 µm
1 µm
5 µm
Explanation - A 0.2 µm pore size effectively retains bacterial spores, the most resistant form of microorganisms.
Correct answer is: 0.2 µm
Q.77 Why is it important to monitor the residual moisture content of a product after sterilization?
Moisture can cause corrosion of equipment
High moisture can support microbial growth post‑sterilization
Moisture affects the electrical conductivity of the product
Moisture changes the color of the product
Explanation - Residual water provides a niche for microbes; drying reduces the risk of post‑sterilization contamination.
Correct answer is: High moisture can support microbial growth post‑sterilization
Q.78 Which of the following is a key advantage of using a ‘modular’ bioreactor system for sterility control?
Simplified cleaning and sterilization of individual modules
Higher power consumption
Larger footprint
Increased complexity of control systems
Explanation - Modular designs allow isolated cleaning/sterilization of each module, reducing cross‑contamination risk and downtime.
Correct answer is: Simplified cleaning and sterilization of individual modules
Q.79 In a CIP system, what is the purpose of a ‘neutralization step’ after using an acidic cleaning solution?
To raise the temperature of the system
To adjust the pH back to neutral, protecting downstream equipment from corrosion
To increase the cleaning efficiency
To add nutrients for the next batch
Explanation - Neutralizing the acid prevents corrosion of stainless‑steel components and prepares the system for the next operation.
Correct answer is: To adjust the pH back to neutral, protecting downstream equipment from corrosion
Q.80 What is the main reason to perform a ‘bioburden study’ before establishing a sterilization cycle?
To determine the initial microbial load that the sterilization process must reduce
To measure the pH of the culture medium
To assess the electrical conductivity of the system
To evaluate the mechanical strength of the vessel
Explanation - Knowing the bioburden helps calculate the required lethality (log reduction) for a validated sterilization cycle.
Correct answer is: To determine the initial microbial load that the sterilization process must reduce
Q.81 Which of the following is considered a “critical parameter” for a steam sterilization cycle?
Ambient room temperature
Steam temperature, pressure, and exposure time
Color of the vessel
Length of the power cable
Explanation - These parameters directly influence the microbial kill rate and must be tightly controlled and monitored.
Correct answer is: Steam temperature, pressure, and exposure time
Q.82 Why is a “double‑check” system often used for critical valves in sterile bioprocessing lines?
To increase the flow rate
To provide redundancy, ensuring the valve remains closed if one component fails
To reduce the cost of the system
To simplify the control software
Explanation - Redundant sealing prevents accidental exposure of sterile streams to the environment.
Correct answer is: To provide redundancy, ensuring the valve remains closed if one component fails
Q.83 What is the recommended method for verifying that a sterilizing filter has not been compromised during use?
Measuring pressure drop across the filter
Visual inspection for discoloration
Performing a bubble point test after use
Weighing the filter before and after use
Explanation - The bubble point test detects leaks or breaches that could allow microorganisms to pass through.
Correct answer is: Performing a bubble point test after use
Q.84 Which of the following best explains why ‘laminar flow hoods’ are used in aseptic processing?
They heat the work area to sterilize the product
They provide a unidirectional airflow that sweeps away contaminants from the work zone
They increase the humidity to keep microbes alive
They generate ultrasonic waves to kill bacteria
Explanation - Laminar flow hoods maintain a sterile environment by delivering filtered air in a smooth, laminar stream over the work surface.
Correct answer is: They provide a unidirectional airflow that sweeps away contaminants from the work zone
Q.85 What is the impact of using a higher concentration of peracetic acid (e.g., 0.5 % vs 0.2 %) in a SIP cycle?
It shortens the required exposure time for the same sterility assurance level
It reduces the risk of corrosion on stainless steel
It eliminates the need for a drying phase
It increases the temperature of the sterilization chamber
Explanation - Higher concentrations provide greater antimicrobial activity, allowing a shorter contact time while achieving the same log reduction.
Correct answer is: It shortens the required exposure time for the same sterility assurance level
Q.86 Which of the following statements about “cleanroom classification” is correct?
ISO 5 cleanrooms have more particles per cubic meter than ISO 8
ISO 8 cleanrooms have stricter particle limits than ISO 5
ISO 5 cleanrooms allow up to 100,000 particles ≥0.5 µm per cubic meter
ISO 8 cleanrooms are typically used for aseptic manufacturing
Explanation - Higher ISO numbers denote less stringent cleanliness; ISO 5 is cleaner than ISO 8.
Correct answer is: ISO 5 cleanrooms have more particles per cubic meter than ISO 8
Q.87 When validating a sterilization cycle, which statistical approach is commonly used to demonstrate sterility assurance level (SAL) of 10⁻⁶?
Poisson distribution analysis
Linear regression
Fourier analysis
Chi‑square test
Explanation - The Poisson model predicts the probability of zero surviving organisms, used to calculate SAL.
Correct answer is: Poisson distribution analysis
Q.88 What is the main purpose of an “air‑lock” entry system in a sterile production area?
To regulate temperature
To prevent the direct entry of contaminants from the outer environment
To increase airflow speed
To provide additional lighting
Explanation - Air‑locks create a controlled transition zone, reducing the chance that contaminants bypass the cleanroom barrier.
Correct answer is: To prevent the direct entry of contaminants from the outer environment
Q.89 Which factor most directly affects the rate of heat penetration during steam sterilization of a bioreactor?
The conductivity of the steam
The surface area‑to‑volume ratio of the vessel
The color of the vessel
The ambient humidity
Explanation - A higher surface‑area‑to‑volume ratio allows heat to reach the interior more quickly, improving sterilization efficiency.
Correct answer is: The surface area‑to‑volume ratio of the vessel
Q.90 Which of the following is a primary reason for implementing a ‘restricted access barrier system’ (RABS) in a bioprocess facility?
To limit personnel exposure to hazardous chemicals
To provide a physical barrier that maintains sterility while allowing limited operator interaction
To increase the speed of production
To reduce the need for HVAC systems
Explanation - RABS combine barriers with limited access points, preserving aseptic conditions while enabling necessary interventions.
Correct answer is: To provide a physical barrier that maintains sterility while allowing limited operator interaction
Q.91 What is the effect of a ‘log‑reduction value’ of 5 on an initial microbial load of 10⁶ CFU?
Final count = 10 CFU
Final count = 100 CFU
Final count = 1 CFU
Final count = 0 CFU
Explanation - A 5‑log reduction reduces the count by a factor of 10⁵; 10⁶ CFU ÷ 10⁵ = 10 CFU remaining.
Correct answer is: Final count = 10 CFU
Q.92 Why is it critical to perform a ‘sterility test’ on the final product before release?
To confirm that the product meets pH specifications
To verify that no viable microorganisms are present, ensuring patient safety
To measure the product’s viscosity
To determine the product’s color
Explanation - Sterility testing confirms that the product is free of live microbes, a regulatory requirement for injectable drugs.
Correct answer is: To verify that no viable microorganisms are present, ensuring patient safety
Q.93 Which of the following best describes the concept of ‘cleanliness class’ for a bioprocessing area?
The classification based on the number of personnel allowed
The classification based on the allowed number of particles per cubic meter
The classification based on the size of the equipment
The classification based on the temperature of the room
Explanation - Cleanliness classes (e.g., ISO 5, ISO 7) specify maximum allowable particle counts for a given particle size.
Correct answer is: The classification based on the allowed number of particles per cubic meter
Q.94 What is the main advantage of using an “automated” CIP‑SIP system over a manual one?
Higher cost
Reduced human error and consistent repeatability
Longer cycle times
More labor required
Explanation - Automation ensures that each step follows the exact parameters, minimizing variability and contamination risk.
Correct answer is: Reduced human error and consistent repeatability
Q.95 Which of the following is a typical validation endpoint for a CIP cycle?
Achieving a final temperature of 100 °C
Demonstrating that the total organic carbon (TOC) level is below a pre‑defined limit
Measuring the pH of the cleaning solution
Ensuring the water flow rate exceeds 10 L/min
Explanation - TOC testing confirms that organic residues have been effectively removed after cleaning.
Correct answer is: Demonstrating that the total organic carbon (TOC) level is below a pre‑defined limit
Q.96 Why is it important to maintain a positive pressure differential in a sterile production area?
To keep the temperature stable
To prevent unfiltered air from entering the space
To reduce the humidity
To increase the oxygen concentration
Explanation - Positive pressure forces air out through any leaks, preventing ingress of potentially contaminated air from surrounding areas.
Correct answer is: To prevent unfiltered air from entering the space
Q.97 Which of the following statements about “endotoxin removal” is correct?
Endotoxins can be removed by standard sterile filtration (0.2 µm)
Endotoxin removal often requires specialized adsorbent columns or ultrafiltration
Endotoxins are destroyed by autoclaving
Endotoxins are only a concern in viral vaccines
Explanation - Because endotoxins are small (≈10 kDa), they can pass through standard 0.2 µm filters and need specific removal strategies.
Correct answer is: Endotoxin removal often requires specialized adsorbent columns or ultrafiltration
Q.98 What is the main reason for using a “sacrificial filter” in a sterile bioprocess line?
To provide an extra barrier that can be discarded if it becomes clogged or compromised
To increase the flow rate
To add nutrients to the process
To heat the fluid
Explanation - Sacrificial filters protect downstream equipment; they are replaced after each batch to maintain sterility.
Correct answer is: To provide an extra barrier that can be discarded if it becomes clogged or compromised
Q.99 Which of the following is a key factor in determining the frequency of filter replacement in a sterile filtration system?
The color of the filtered fluid
The cumulative volume filtered and pressure drop across the filter
The ambient room temperature
The brand of the filter
Explanation - As volume increases, fouling leads to higher pressure drop; exceeding set limits mandates filter change.
Correct answer is: The cumulative volume filtered and pressure drop across the filter
Q.100 What is the typical sterilization temperature for a standard steam autoclave used in bioprocessing?
100 °C
121 °C
150 °C
180 °C
Explanation - Standard autoclave cycles use saturated steam at 121 °C for a defined hold time to achieve sterilization.
Correct answer is: 121 °C
Q.101 Which of the following best explains why ‘validation’ is performed only once for a sterilization process?
Once validated, the process never needs to be checked again
Validation is a one‑time event; subsequent runs are assumed to be identical
Validation establishes that the process works; routine monitoring ensures continued performance
Validation is unnecessary for bioprocessing
Explanation - Initial validation proves the method; ongoing monitoring (IQ/OQ/PQ) confirms that each run remains within specifications.
Correct answer is: Validation establishes that the process works; routine monitoring ensures continued performance
Q.102 Which of the following is the most appropriate method to de‑contaminate a stainless‑steel bioreactor after a chemical sterilization cycle?
Rinse with sterile water followed by a sterile air purge
Leave the chemical inside for 24 h
Heat the vessel to 200 °C
Expose the vessel to UV light for 5 min
Explanation - Thorough rinsing removes residual chemicals; sterile air purge ensures no water remains that could support microbial growth.
Correct answer is: Rinse with sterile water followed by a sterile air purge
Q.103 Which of the following best describes the term “aseptic fill” in biopharmaceutical manufacturing?
Filling the product under sterile conditions to avoid microbial contamination
Filling the product with a high temperature liquid
Filling the product after a heat‑kill step
Filling the product using a disposable container
Explanation - Aseptic fill involves transferring a sterile product into sterile containers without breaking sterility.
Correct answer is: Filling the product under sterile conditions to avoid microbial contamination
Q.104 What is a common method for verifying the integrity of a welded sterile connection?
Visual inspection only
Helium leak testing
Measuring the temperature of the weld
Weighing the welded part
Explanation - Helium leak detection is highly sensitive and can identify tiny leaks that would compromise sterility.
Correct answer is: Helium leak testing
Q.105 Why is it important to control the temperature of the cooling water used after a SIP cycle?
To prevent thermal shock to the equipment
To ensure rapid cooling and reduce the window for post‑sterilization contamination
To increase the pressure inside the vessel
To change the pH of the product
Explanation - Quick cooling minimizes the time the vessel remains at temperatures conducive to microbial survival, lowering contamination risk.
Correct answer is: To ensure rapid cooling and reduce the window for post‑sterilization contamination
Q.106 Which of the following is the most effective way to reduce the risk of airborne microbial contamination in a production suite?
Increasing the room temperature
Using HEPA filtration and maintaining positive pressure
Opening windows for ventilation
Running fans at high speed
Explanation - HEPA filters remove airborne particles; positive pressure prevents unfiltered air from entering the suite.
Correct answer is: Using HEPA filtration and maintaining positive pressure
Q.107 What is the primary reason for performing a ‘dry heat sterilization’ of glassware rather than steam?
Glass can crack under steam pressure
Dry heat removes moisture that could support microbial growth after sterilization
Dry heat is faster
Steam cannot sterilize glass
Explanation - Dry heat sterilizes while leaving the glass dry, preventing moisture‑related contamination.
Correct answer is: Dry heat removes moisture that could support microbial growth after sterilization
Q.108 Which of the following is a common cause of filter fouling during sterile filtration?
High temperature of the feed stream
High concentration of proteins and particulates in the feed
Low pressure across the filter
Use of de‑ionized water
Explanation - Proteins and particulates can accumulate on the filter surface, increasing pressure drop and reducing flow.
Correct answer is: High concentration of proteins and particulates in the feed
Q.109 What is the recommended action if a sterilization cycle fails the temperature validation criteria?
Proceed with the process anyway
Investigate the cause, re‑run the cycle, and document corrective actions before proceeding
Ignore the data and continue
Reduce the hold time in the next cycle
Explanation - A failed validation indicates a risk; the process must be corrected and validated before use.
Correct answer is: Investigate the cause, re‑run the cycle, and document corrective actions before proceeding
Q.110 Which of the following best describes the principle behind a ‘passive’ sterilizer (e.g., dry heat oven) compared to an ‘active’ sterilizer (e.g., autoclave)?
Passive sterilizers require no electricity
Passive sterilizers rely on natural convection and heat transfer without pressurization
Passive sterilizers use chemicals instead of heat
Passive sterilizers operate at higher temperatures
Explanation - Dry heat ovens use ambient air heating and do not pressurize the chamber, unlike active steam systems.
Correct answer is: Passive sterilizers rely on natural convection and heat transfer without pressurization
Q.111 Why is it important to perform regular calibration of temperature sensors in sterilization equipment?
To ensure accurate temperature readings, guaranteeing that sterilization parameters are truly met
To keep the sensors warm
To reduce electricity consumption
To change the color of the display
Explanation - Accurate temperature data are essential for verifying that the required lethal conditions have been achieved.
Correct answer is: To ensure accurate temperature readings, guaranteeing that sterilization parameters are truly met
Q.112 Which of the following best defines “sterility assurance level” (SAL)?
The probability that a product is sterile, expressed as a decimal (e.g., 10⁻⁶)
The temperature at which sterilization occurs
The time required to sterilize a product
The pressure inside the sterilizer
Explanation - SAL quantifies the likelihood of a viable organism remaining after sterilization; a SAL of 10⁻⁶ means a one‑in‑million chance.
Correct answer is: The probability that a product is sterile, expressed as a decimal (e.g., 10⁻⁶)
Q.113 What is the purpose of using a ‘sterilizing-grade gasket’ in a bioreactor’s lid assembly?
To provide a mechanical seal only
To maintain a sterile barrier by preventing microbial ingress when the lid is closed
To increase the temperature inside the vessel
To act as a catalyst for the reaction
Explanation - Sterilizing‑grade gaskets are made of materials that can withstand sterilization cycles while maintaining an airtight seal.
Correct answer is: To maintain a sterile barrier by preventing microbial ingress when the lid is closed
Q.114 Which of the following is a common indicator of inadequate drying after a SIP cycle?
Presence of condensation on the vessel walls
Higher than expected pressure
Reduced agitation speed
Increased pH of the medium
Explanation - Condensation indicates that moisture remains, which could foster microbial growth if not removed.
Correct answer is: Presence of condensation on the vessel walls
Q.115 What is the primary rationale for using a ‘two‑stage’ sterilization process (e.g., heat followed by chemical) in some bioprocesses?
To reduce the cost of sterilization
To achieve higher sterility assurance by combining different mechanisms of microbial kill
To shorten the overall cycle time
To increase the temperature of the product
Explanation - Combining heat and chemical methods provides redundancy and can target a broader range of microorganisms.
Correct answer is: To achieve higher sterility assurance by combining different mechanisms of microbial kill
Q.116 Which of the following is an essential step in the design of a bioreactor to minimize contamination risk?
Including as many access ports as possible
Designing smooth, weld‑free interior surfaces that are easy to clean and sterilize
Using rough interior surfaces to increase mixing
Placing components in hard‑to‑reach locations
Explanation - Smooth, seamless surfaces reduce crevices where microbes can hide and simplify cleaning/sterilization.
Correct answer is: Designing smooth, weld‑free interior surfaces that are easy to clean and sterilize
Q.117 Which type of bioreactor is most commonly associated with the use of a ‘closed‑loop sterile sampling system’?
Open‑top flask
Stirred‑tank bioreactor
Bubble column reactor
Fed‑batch bioreactor with a sealed sampling valve
Explanation - Fed‑batch processes often require intermittent sampling; a sealed valve maintains sterility during these events.
Correct answer is: Fed‑batch bioreactor with a sealed sampling valve
Q.118 What is the most common cause of filter breach during sterile filtration?
Excessive pressure exceeding the filter’s rated limit
Low temperature of the feed stream
Use of distilled water
Running the filter at low flow rates
Explanation - Applying pressure beyond the filter’s design can cause physical damage, creating pathways for microbes.
Correct answer is: Excessive pressure exceeding the filter’s rated limit
Q.119 Which of the following best describes the purpose of a ‘sterility test’ using the direct inoculation method?
Incubating the product directly to detect any microbial growth
Measuring the pH of the product over time
Assessing the product’s color stability
Testing the product’s viscosity
Explanation - Direct inoculation places the product into growth media to observe any microbial proliferation, confirming sterility.
Correct answer is: Incubating the product directly to detect any microbial growth
Q.120 Why is it critical to validate the ‘air flow pattern’ in a laminar flow hood used for aseptic work?
To ensure the hood operates at the correct temperature
To confirm that unfiltered air does not reach the work area, preserving sterility
To increase the humidity inside the hood
To reduce electricity consumption
Explanation - A validated airflow pattern guarantees that any contaminants are swept away, maintaining a sterile environment.
Correct answer is: To confirm that unfiltered air does not reach the work area, preserving sterility
Q.121 Which of the following statements about “steam under pressure” is TRUE for sterilization?
Higher pressure reduces the boiling point of water
Higher pressure increases the temperature of saturated steam, enhancing microbial kill
Pressure has no effect on steam temperature
Low pressure is preferred for faster sterilization
Explanation - Increasing pressure raises steam temperature (e.g., 2 bar → ~121 °C), allowing faster and more effective sterilization.
Correct answer is: Higher pressure increases the temperature of saturated steam, enhancing microbial kill
Q.122 What is the primary function of a ‘sterilizing filter’ placed on the inlet line of a bioreactor’s feed medium?
To adjust the pH of the feed
To remove microorganisms before the feed enters the sterile bioreactor
To increase the temperature of the feed
To add nutrients to the feed
Explanation - A sterilizing filter (0.2 µm) ensures that the feed medium remains free of viable microbes, preserving aseptic conditions.
Correct answer is: To remove microorganisms before the feed enters the sterile bioreactor