CSPT Sterilization Methods and Filtration Technology — Questions and Answers
Question 1: What is the minimum membrane filter pore size required to achieve sterilization by filtration of a compounded sterile preparation?
- 0.45 micron
- 0.22 micron (Correct answer)
- 1.0 micron
- 5.0 micron
Correct answer: 0.22 micron
A pore size of ≤0.22 micron (also stated as 0.2 micron) is required for sterilizing-grade filtration because it retains bacteria. Larger pore sizes (0.45 micron) are used for clarification, not sterilization.
Question 2: What are the standard parameters for terminal sterilization of a preparation by moist heat (autoclave)?
- 100°C for 30 minutes at atmospheric pressure
- 121°C for a minimum of 15 minutes at 15 psi (Correct answer)
- 130°C for 5 minutes at 20 psi
- 115°C for 30 minutes at 10 psi
Correct answer: 121°C for a minimum of 15 minutes at 15 psi
The standard autoclave cycle is 121°C at 15 psi for at least 15 minutes. This combination of temperature and pressure is sufficient to achieve a sterility assurance level (SAL) of 10⁻⁶ for terminally sterilized preparations.
Question 3: Which sterilization method is MOST appropriate for a heat-sensitive aqueous drug that cannot withstand autoclave temperatures?
- Dry heat oven sterilization at 250°C
- Gamma radiation sterilization
- Membrane filtration through a 0.22-micron sterilizing-grade filter (Correct answer)
- Ethylene oxide gas sterilization
Correct answer: Membrane filtration through a 0.22-micron sterilizing-grade filter
Membrane filtration through a ≤0.22-micron filter is the preferred method for heat-sensitive aqueous preparations. It removes bacteria and fungi without exposing the drug to destructive temperatures. Ethylene oxide is used for devices, and dry heat/radiation are not practical for liquids.
Question 4: What is 'depyrogenation,' and which method is most commonly used to achieve it on glassware and equipment?
- Removal of endotoxins; dry heat at ≥250°C for at least 30 minutes (Correct answer)
- Removal of viruses; UV radiation exposure
- Removal of bacterial spores; autoclaving at 121°C
- Removal of fungi; membrane filtration
Correct answer: Removal of endotoxins; dry heat at ≥250°C for at least 30 minutes
Depyrogenation is the destruction or removal of pyrogens (primarily bacterial endotoxins). Endotoxins are heat-stable and survive standard autoclaving; dry heat at ≥250°C for ≥30 minutes is required to destroy them on glassware and stainless steel.
Question 5: After filtering a compounded sterile preparation through a 0.22-micron membrane filter, a bubble point integrity test is performed. What does this test confirm?
- That the filter removed all particulate matter above 0.22 microns
- That the filter membrane is intact and was not compromised during filtration (Correct answer)
- That the filtrate is free of endotoxins
- That the drug concentration did not change during filtration
Correct answer: That the filter membrane is intact and was not compromised during filtration
The bubble point integrity test verifies that the filter membrane has not been punctured, torn, or otherwise compromised. A breached filter could allow microorganisms to pass through, invalidating the sterilization process. USP <797> requires post-filtration integrity testing for high-risk CSPs.
Question 6: Which of the following BEST describes 'terminal sterilization' as opposed to 'aseptic processing'?
- Sterilizing all individual components before compounding begins
- Sterilizing the final sealed container after filling to achieve a defined sterility assurance level (Correct answer)
- Using pre-sterilized disposable equipment to avoid introducing contamination
- Filtering the preparation immediately before it is administered to the patient
Correct answer: Sterilizing the final sealed container after filling to achieve a defined sterility assurance level
Terminal sterilization involves sterilizing the product after it has been filled and sealed in its final container (e.g., autoclaving a sealed vial). This is contrasted with aseptic processing, where sterile components are combined under aseptic conditions but the final container is never subjected to a sterilization step.
CSPT Sterilization Methods and Filtration Technology
What is the minimum membrane filter pore size required to achieve sterilization by filtration of a compounded sterile preparation?