Introduction: Quality control tests for parenteral products are essential to ensure safety, sterility, potency, and stability of injectable formulations. B. Pharm students must understand sterility testing, bacterial endotoxin (pyrogen) assays, particulate matter determination, container-closure integrity, and sterility assurance levels. Key techniques include membrane filtration, direct inoculation, Limulus Amebocyte Lysate (LAL) tests, light obscuration, and environmental monitoring of aseptic processing areas. Regulatory guidelines (USP, Ph. Eur., ICH) and validation principles guide sampling, acceptance criteria, and documentation. Mastery of these QC tests helps prevent contamination, ensure patient safety, and support batch release. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which test is the official pharmacopoeial method for detecting bacterial endotoxins in parenteral products?
- Rabbit pyrogen test
- Limulus Amebocyte Lysate (LAL) assay
- Membrane filtration sterility test
- Plate count method
Correct Answer: Limulus Amebocyte Lysate (LAL) assay
Q2. In sterility testing by membrane filtration, which medium combination is commonly used to detect aerobic and anaerobic organisms?
- Tryptic Soy Broth and Fluid Thioglycollate Medium
- MacConkey Agar and Mannitol Salt Agar
- Blood Agar and Chocolate Agar
Correct Answer: Tryptic Soy Broth and Fluid Thioglycollate Medium
Q3. The acceptance limit for endotoxin in an intravenous drug with a maximum human dose of 2 IU/kg for a 70 kg person is best expressed as:
- Total endotoxin units per container
- EU per mL based on maximum dose
- CFU per mL
- Sterility assurance level (SAL)
Correct Answer: EU per mL based on maximum dose
Q4. Which of the following methods is commonly used for particulate matter testing in parenteral products according to USP?
- Light obscuration particle counter
- Microscopic direct visual counting only
- Viscometry
- Flame photometry
Correct Answer: Light obscuration particle counter
Q5. What is the primary purpose of container-closure integrity (CCI) testing for parenterals?
- To determine viscosity of the formulation
- To verify microbial and particulate barrier of the container system
- To measure endotoxin levels
- To assess chemical stability of the drug substance
Correct Answer: To verify microbial and particulate barrier of the container system
Q6. Which sterilization method is considered a terminal sterilization technique suitable for heat-stable parenterals?
- Autoclaving (moist heat)
- Aseptic filtration only
- Gamma irradiation for all products
- Ethylene oxide for aqueous solutions
Correct Answer: Autoclaving (moist heat)
Q7. During sterility testing, why is sample size and number important?
- It affects the drug potency
- It influences the probability of detecting contamination and compliance with statistical requirements
- It determines the dissolution rate
- It changes the endotoxin content
Correct Answer: It influences the probability of detecting contamination and compliance with statistical requirements
Q8. Which of the following describes the principle of the Limulus Amebocyte Lysate clotting assay?
- Endotoxin inhibits clotting of lysate
- Endotoxin induces clot formation of horseshoe crab blood lysate
- Endotoxin oxidizes chromogenic substrate releasing color
- Endotoxin reduces turbidity in a solution
Correct Answer: Endotoxin induces clot formation of horseshoe crab blood lysate
Q9. For aseptic processing, what is the main reason for environmental monitoring of air and surfaces?
- To measure API concentration in the air
- To assess the bioburden and control contamination risks in cleanrooms
- To determine humidity for stability
- To measure endotoxin levels on surfaces
Correct Answer: To assess the bioburden and control contamination risks in cleanrooms
Q10. A bacterial endotoxin limit (EL) is most directly calculated from which of the following?
- Maximum human dose in EU/kg
- Batch size in liters
- Number of containers per batch
- Sterility test incubation time
Correct Answer: Maximum human dose in EU/kg
Q11. Which of the following tests can replace the rabbit pyrogen test for parenterals under modern regulatory practice?
- Membrane filter sterility test
- Limulus Amebocyte Lysate (LAL) or bacterial endotoxin test
- Viscosity measurement
- Optical rotation
Correct Answer: Limulus Amebocyte Lysate (LAL) or bacterial endotoxin test
Q12. What does SAL (Sterility Assurance Level) of 10^-6 signify?
- One in a million probability of a viable microorganism surviving sterilization
- Six organisms survive per batch
- Sterility is guaranteed
- Sterility test positive rate is 10^-6
Correct Answer: One in a million probability of a viable microorganism surviving sterilization
Q13. In microbial limit testing for non-sterile products, which organisms are typically enumerated as part of total aerobic microbial count?
- Only Gram-negative rods
- Total aerobic bacteria and yeasts/molds counts
- Only Clostridium spp.
- Only Staphylococcus aureus
Correct Answer: Total aerobic bacteria and yeasts/molds counts
Q14. Which dye ingress method is used for container-closure integrity testing of fragile parenteral containers?
- Helium leak testing
- Dye immersion under vacuum
- Light obscuration
- LAL kinetic method
Correct Answer: Dye immersion under vacuum
Q15. The primary advantage of membrane filtration sterility testing over direct transfer (bottle) method is:
- It requires no sterile technique
- It allows testing of large-volume or particulate-containing solutions by filtering through membrane
- It is faster for incubation results
- It reduces endotoxin levels
Correct Answer: It allows testing of large-volume or particulate-containing solutions by filtering through membrane
Q16. Which indicator would you use to monitor steam penetration into a load during autoclave sterilization?
- LAL reagent
- Biological indicator containing Geobacillus stearothermophilus spores
- pH indicator strips
- Particulate counter
Correct Answer: Biological indicator containing Geobacillus stearothermophilus spores
Q17. What is the main limitation of the rabbit pyrogen test compared to the LAL test?
- Cannot detect endotoxins
- High variability, ethical concerns, and detects only fever-causing substances, not specific for endotoxin
- It is cheaper and faster
- Requires membrane filtration
Correct Answer: High variability, ethical concerns, and detects only fever-causing substances, not specific for endotoxin
Q18. Which USP chapter provides procedures for particulate matter in injections?
- USP <71> Sterility Tests
- USP <788> Particulate Matter in Injections
- USP <85> Bacterial Endotoxins Test
- USP <1116> Microbiological Control
Correct Answer: USP <788> Particulate Matter in Injections
Q19. Kinetic chromogenic LAL assays detect endotoxin by measuring which output?
- Change in turbidity only
- Color development rate proportional to endotoxin concentration
- pH change
- Decrease in fluorescence
Correct Answer: Color development rate proportional to endotoxin concentration
Q20. During microbial challenge tests for terminal sterilization validation, population and D-value determination are important because:
- They define heat capacity of the autoclave
- They quantify resistance of microorganisms to the sterilization process and help calculate required lethality
- They determine container-closure integrity
- They measure endotoxin generation
Correct Answer: They quantify resistance of microorganisms to the sterilization process and help calculate required lethality
Q21. Which of the following best describes a bacterial endotoxin limit (EL) expression?
- EU per dose or EU per mL depending on route and dose
- CFU per container
- Micrograms of protein per mL
- Number of positive sterility tests
Correct Answer: EU per dose or EU per mL depending on route and dose
Q22. Which environmental monitoring method captures viable airborne particles in cleanrooms?
- Surface ATP swab only
- Active air sampling using impaction or filtration devices
- Gravimetric analysis
- Light obscuration for particles
Correct Answer: Active air sampling using impaction or filtration devices
Q23. For small-volume parenterals (SVPs), particulate limits per container for particles ≥10 µm according to USP are typically:
- Not specified
- Less stringent than large-volume parenterals
- Specific numeric limits such as ≤6000 particles/container for ≥10 µm depending on method
- Measured only visually
Correct Answer: Specific numeric limits such as ≤6000 particles/container for ≥10 µm depending on method
Q24. Which assay is used to determine endotoxin interference caused by product components and requires a positive product control?
- Sterility test
- Validation of the LAL assay using inhibition/enhancement test with spike recovery
- Particulate matter count
- Bioburden total count
Correct Answer: Validation of the LAL assay using inhibition/enhancement test with spike recovery
Q25. Which of the following is TRUE about aseptic filtration as a sterilization method for parenterals?
- It is suitable for particulate-laden, heat-stable solutions
- It is a terminal sterilization method
- It removes microorganisms by membrane retention and requires validation of filter integrity
- It eliminates the need for aseptic processing controls
Correct Answer: It removes microorganisms by membrane retention and requires validation of filter integrity
Q26. A preservative effectiveness test (PET) for multi-dose parenteral containers assesses what?
- Sterility of single-dose units
- Antimicrobial preservation capability over time against challenge organisms
- Endotoxin content after storage
- Particulate generation during agitation
Correct Answer: Antimicrobial preservation capability over time against challenge organisms
Q27. Which of the following best explains why non-sterile sampling and aseptic technique are critical during sterility testing?
- To reduce endotoxin levels
- To avoid false positives due to external contamination and ensure test validity
- To increase particulate counts
- To sterilize the test samples
Correct Answer: To avoid false positives due to external contamination and ensure test validity
Q28. When validating a sterilization cycle, the F0 value relates to which attribute of the process?
- Filter pore size used in aseptic filtration
- Equivalent minutes of sterilization at 121°C for moist heat processes
- Endotoxin removal efficiency
- Particulate reduction factor
Correct Answer: Equivalent minutes of sterilization at 121°C for moist heat processes
Q29. Which control is most important to prevent endotoxin contamination in water for injection (WFI) used for parenteral manufacturing?
- Maintaining sterile filters only
- Controlling microbial growth, biofilm prevention, and proper depyrogenation of equipment
- Using only glass containers
- Measuring pH daily
Correct Answer: Controlling microbial growth, biofilm prevention, and proper depyrogenation of equipment
Q30. During sterility testing, a growth promotion test is performed to:
- Ensure media can support growth of microorganisms and validate negative sterility results
- Promote sterility of the sample
- Increase endotoxin recovery
- Measure particle counts
Correct Answer: Ensure media can support growth of microorganisms and validate negative sterility results
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
Mail- Sachin@pharmacyfreak.com