Aseptic process simulation (APS)/ media fill questions EUGMP- Annex-1
Questions 1. What is another name for an Aseptic Process Simulation (APS)?
A. Sterility test
B. Media fill
C. Endotoxin challenge
D. Cleaning validation
Answer: B
Questions 2. What is the purpose of periodic APS?
A. To replace routine monitoring
B. To verify the effectiveness of controls for aseptic processing
C. To validate HVAC systems
D. To validate sterilization cycles
Answer: B
Questions 3. APS should not be considered the primary means to:
A. Train operators
B. Identify equipment failures
C. Validate the aseptic process
D. Detect microbial contamination
Answer: C
Questions 4. Effectiveness of an aseptic process is primarily determined through:
A. APS only
B. Environmental monitoring alone
C. Process design and process controls
D. Operator interviews
Answer: C
Questions 5. Selection of nutrient media/surrogate should be based on:
A. Cost
B. Availability
C. Ability to imitate physical product characteristics
D. Shelf life
Answer: C
Questions 6. When surrogate materials are used, they must:
A. Be coloured
B. Inhibit microbial growth
C. Not inhibit microbial growth
D. Be non-nutrient
Answer: C
Questions 7. APS should imitate:
A. Only the filling step
B. Only sterilization steps
C. The full routine aseptic manufacturing process
D. Only interventions
Answer: C
Questions 8. APS should start after:
A. Final packaging
B. Sterilization and decontamination cycles
C. Shipping
D. Labeling
Answer: B
Questions 9. For non-filterable formulations, APS should assess:
A. Cooling time
B. Additional aseptic steps
C. Container size only
D. Only filtration performance
Answer: B
Questions 10. When aseptic manufacturing uses inert gas, APS should use:
A. Nitrogen
B. Oxygen
C. Carbon dioxide
D. Air, unless anaerobic simulation is intended
Answer: D
Questions 11. Processes requiring sterile powder addition should use:
A. Water
B. Non-sterile powder
C. Acceptable surrogate in same containers
D. Air
Answer: C
Questions 12. Separate simulations of individual unit operations should be:
A. Routine
B. Avoided unless justified
C. Always used
D. Used for powders only
Answer: B
Questions 13. Lyophilization APS should represent:
A. Only freezing stage
B. Entire aseptic processing chain
C. Only stoppering
D. Only drying
Answer: B
Questions 14. Lyophilization APS should avoid:
A. Loading trays
B. Chamber dwell
C. Freezing solution that prevents microbial recovery
D. Stoppering
Answer: C
Questions 15. APS design factors for lyophilization include:
A. Room temperature only
B. Air to break vacuum
C. Increased pressure
D. Reduced air flow only
Answer: B
Questions 16. APS should consider maximum time between:
A. Labeling and packing
B. Lyophilizer sterilization and use
C. Shipment and receipt
D. Validation and requalification
Answer: B
Questions 17. APS should consider maximum time between filtration and:
A. Labeling
B. Sterilization
C. Lyophilization
D. Cooling
Answer: C
Questions 18. APS must include:
A. Cooling operations only
B. All aseptic manipulations and interventions
C. Only manual interventions
D. Only automated operations
Answer: B
Questions 19. Interventions in APS should be based on:
A. Operator preference
B. Cost savings
C. Risk to product sterility
D. Availability of equipment
Answer: C
Questions 20. APS should not be used to justify:
A. Risk assessments
B. Training programs
C. Practices that pose unnecessary contamination risks
D. Cleaning schedules
Answer: C
Questions 21. APS planning should identify worst case conditions including:
A. Warehouse temperature
B. Container size and line speed
C. Shipping delays
D. Vendor qualification
Answer: B
Questions 22. Representative container/closure sizes should be selected based on:
A. Marketing requirements
B. Operator convenience
C. Validation justification
D. Customer preference
Answer: C
Questions 23. Bracketing may be used when:
A. No data exist
B. Products share equivalent container/closure configurations
C. Operators change
D. Equipment is new
Answer: B
Questions 24. APS should consider maximum permitted holding times for:
A. Labels
B. Sterile product and exposed equipment
C. Finished product
D. Cleaning solutions
Answer: B
Questions 25. Filled volume in APS should allow:
A. No headspace
B. Minimal inspection
C. Media contact and microbial growth detection
D. Rapid filling only
Answer: C
Questions 26. Inert gas in routine manufacturing should be substituted by air unless:
A. Oxygen levels are high
B. Anaerobic simulation is required
C. Cost is high
D. Operators request otherwise
Answer: B
Questions 27. Selected nutrient media must grow:
A. Only fungi
B. At least 10 new species
C. Reference microorganisms and representative local isolates
D. Only bacteria
Answer: C
Questions 28. Detection method for microbial contamination should be:
A. Cost-effective only
B. Scientifically justified
C. Operator-selected
D. Optional
Answer: B
Questions 29. APS duration must challenge:
A. Only HVAC systems
B. Only operators
C. Process, operators, and environment
D. Only intervention frequency
Answer: C
Questions 30. APS should consider differences in:
A. Shipping methods
B. Shift structures and operator presence time
C. Label designs
D. Storage racks
Answer: B
Questions 31. APS should simulate normal manufacturing interruptions such as:
A. Cleaning validation
B. Equipment relocation
C. Shift changeovers and vessel recharging
D. Annual shutdowns
Answer: C
Questions 32. During APS, environmental monitoring should be:
A. Reduced
B. Increased to double
C. Conducted as in routine production
D. Not required
Answer: C
Questions 33. APS for campaign manufacturing should simulate:
A. Only the beginning
B. Only the end
C. Both beginning and end risks
D. No campaign conditions
Answer: C
Questions 34. End-of-campaign APS may be used for:
A. Replacement of routine APS
B. Additional assurance or investigation
C. Eliminating interventions
D. Reducing environmental monitoring
Answer: B
Questions 35. Use of end-of-campaign APS must be justified in:
A. Equipment manuals
B. Controlled copy files
C. The Contamination Control Strategy (CCS)
D. Operator training logs
Answer: C
Questions 36. Residual product in APS must not:
A. Increase filling time
B. Affect operator speed
C. Negatively impact microbial recovery
D. Change temperature settings
Answer: C
Questions 37. APS should avoid boiling-over because it:
A. Wastes time
B. May affect contaminant viability
C. Prevents filling
D. Increases media cost
Answer: B
Questions 38. APS interventions should be:
A. More frequent than routine
B. Less frequent
C. Representative of routine frequency
D. Avoided
Answer: C
Questions 39. APS should replicate worst-case loading by:
A. Using minimal trays
B. Using largest number of trays
C. Reducing load time
D. Eliminating loading
Answer: B
Questions 40. APS should represent maximum:
A. Room humidity
B. Operator uniforms
C. Loading duration with chamber open
D. Number of operators
Answer: C
Questions 41. Simulation air should be used instead of nitrogen to:
A. Simplify cleaning
B. Reduce oxygen levels
C. Expose organisms to growth conditions
D. Reduce cost
Answer: C
Questions 42. APS must include inherent and corrective interventions because:
A. They increase media use
B. They represent contamination risks
C. They shorten manufacturing
D. They reduce operator involvement
Answer: B
Questions 43. APS should ensure turbidity detection by:
A. Increasing headspace
B. Reducing media volume
C. Using coloured containers
D. Changing stopper colour
Answer: A
Questions 44. APS should cover:
A. Only sterile filtration
B. Only filling
C. All aseptic steps until container sealing
D. Only documentation
Answer: C
Questions 45. APS must not be used to justify:
A. Preventive actions
B. Poor aseptic practices
C. Risk assessments
D. Training improvements
Answer: B
Questions 46. APS should use surrogate powders that:
A. Sterilize easily
B. Are heavier than product
C. Do not inhibit microbial growth
D. Increase turbidity
Answer: C
Questions 47. APS environmental monitoring must cover:
A. Only grade A
B. Minimum time
C. Entire simulation duration
D. Only viable monitoring
Answer: C
Questions 48. APS container size selection must be:
A. Based on batch size
B. Arbitrary
C. Justified by worst-case assessment
D. Chosen by supplier
Answer: C
Questions 49. APS process simulation must be:
A. Shorter than routine
B. Sufficient to challenge operators and environment
C. Only operator-focused
D. Done once per product lifecycle
Answer: B
Questions 50. APS should simulate risks at beginning and end of campaign to:
A. Reduce campaign duration
B. Avoid environmental monitoring
C. Demonstrate no sterility risk
D. Shorten APS cycle
Answer: C
Questions 51. For sterile active substances, APS batch size should be:
A. As small as possible
B. Large enough to represent routine operation
C. Irrelevant to the process
D. Based only on operator preference
Answer: B
Questions 52. APS batch size must simulate:
A. Average case only
B. Worst-case intervention operations
C. Only manual activities
D. Only automated processes
Answer: B
Questions 53. All simulated materials should be subjected to:
A. Chemical purity testing
B. Microbial evaluation
C. Sterility testing only
D. Operator inspection alone
Answer: B
Questions 54. Simulation materials should not:
A. Be nutrient-rich
B. Be sterile
C. Compromise microorganism recovery
D. Be used in multiple batches
Answer: C
Questions 55. APS must be performed as part of:
A. Routine cleaning
B. Initial validation
C. Environmental monitoring
D. Batch release testing
Answer: B
Questions 56. Initial validation requires how many consecutive satisfactory APS?
A. 1
B. 2
C. 3
D. 5
Answer: C
Questions 57. APS should cover:
A. Only day shift
B. Only night shift
C. All working shifts
D. The busiest shift only
Answer: C
Questions 58. APS must be repeated how often for periodic revalidation?
A. Every month
B. Once per year
C. Twice a year (~every 6 months)
D. Every 2 years
Answer: C
Questions 59. Each operator should participate in at least one successful APS:
A. Every month
B. Every 2 years
C. Annually
D. Weekly
Answer: C
Questions 60. APS may be performed after the last batch prior to:
A. Labeling
B. Long periods of inactivity
C. Packaging
D. Distribution
Answer: B
Questions 61. APS should be performed before:
A. Routine calibration
B. Decommissioning or relocation of a line
C. Label printing
D. Staff meetings
Answer: B
Questions 62. For manual operations, each operator must initially complete:
A. 1 APS
B. 2 APS
C. 3 consecutive successful APS
D. 10 APS
Answer: C
Questions 63. Operator APS revalidation for manual processes should occur:
A. Every 2 years
B. Monthly
C. Approximately every 6 months
D. Only when issues arise
Answer: C
Questions 64. APS batch size must mimic:
A. The smallest batch possible
B. The average batch
C. The routine aseptic manufacturing batch size
D. A pilot batch
Answer: C
Questions 65. Number of units for APS should:
A. Be random
B. Simulate representative aseptic activities
C. Be fixed by regulatory authorities
D. Never exceed 1000 units
Answer: B
Questions 66. Typical APS unit count is:
A. 100–500 units
B. 500–1500 units
C. 5000–10000 units
D. Over 50,000 units
Answer: C
Questions 67. For production batches under 5000 units, APS should use:
A. Half the batch size
B. A fixed 1000 units
C. At least the batch size
D. Twice the batch size
Answer: C
Questions 68. APS filled units should be:
A. Frozen
B. Autoclaved
C. Agitated, swirled, or inverted
D. Left untouched
Answer: C
Questions 69. APS must incubate:
A. Only visually perfect units
B. All integral units, including cosmetic defects
C. Only 50% of filled units
D. Only units from the first hour
Answer: B
Questions 70. Units discarded during APS must be:
A. Arbitrarily removed
B. More than routine production removals
C. Removed only if consistent with production SOPs
D. Never incubated
Answer: C
Questions 71. Units removed during set-up or interventions should be:
A. Thrown away
B. Incubated separately
C. Added to acceptance criteria
D. Counted as failures
Answer: B
Questions 72. Discarded materials that contact product contact surfaces should be simulated with:
A. Water
B. Buffer
C. Nutrient media
D. Non-sterile solvent
Answer: C
Questions 73. APS units must be incubated in containers that are:
A. Any color
B. Clear
C. Dark
D. Amber only
Answer: B
Questions 74. If the actual product container is opaque, APS can use:
A. Different shapes
B. Clear containers of identical configuration
C. Any available container
D. Only original containers
Answer: B
Questions 75. If clear identical containers cannot be used, the manufacturer must:
A. Skip the APS
B. Reduce unit count
C. Develop a validated detection method
D. Shorten incubation time
Answer: C
Questions 76. Contaminating microorganisms must be identified to:
A. Genus level
B. Species level when practical
C. Strain level always
D. Only by morphology
Answer: B
Questions 77. APS units should be incubated:
A. After long delays
B. Without unnecessary delay
C. At room temperature only
D. Only after 48 hours
Answer: B
Questions 78. Incubation conditions must be:
A. Arbitrary
B. Chosen by operator preference
C. Scientifically justified and validated
D. Based on cost
Answer: C
Questions 79. APS units must be inspected by personnel who are:
A. The most senior
B. Appropriately trained and qualified
C. External auditors only
D. Untrained but experienced
Answer: B
Questions 80. APS inspection conditions should:
A. Be dimly lit
B. Facilitate microbial detection
C. Mirror warehouse lighting
D. Be outdoors
Answer: B
Questions 81. Positive controls involve inoculating units with:
A. Media only
B. Water
C. Reference organisms and local isolates
D. Operator-selected organisms
Answer: C
Questions 82. Target outcome for APS is:
A. ≤1% growth
B. Zero growth
C. ≤5 contaminated units
D. Any level is acceptable
Answer: B
Questions 83. Any contaminated APS unit results in:
A. A warning
B. A passed APS
C. A failed APS
D. Repeat testing not required
Answer: C
Questions 84. A failed APS requires:
A. No investigation
B. Immediate line shutdown only
C. Root cause investigation
D. Automatic personnel retraining regardless of cause
Answer: C
Questions 85. After a failed APS, how many successful repeat APS runs are normally required?
A. 1
B. 2
C. 3
D. 5
Answer: C
Questions 86. Review after APS failure must include:
A. Only new batches
B. All production since the last APS
C. Only environmental records
D. Only cleaning logs
Answer: B
Questions 87. Unreleased batches made since the last successful APS must:
A. Automatically pass
B. Be excluded from review
C. Be evaluated for release risk
D. Be destroyed
Answer: C
Questions 88. All products manufactured after a failed APS should be:
A. Sold immediately
B. Quarantined
C. Relabeled
D. Returned to supplier
Answer: B
Questions 89. If APS failure is due to operator activity, they should be:
A. Dismissed
B. Limited in activity until retrained and requalified
C. Given additional breaks
D. Transferred to QC
Answer: B
Questions 90. Production may resume only after:
A. Operator approval
B. Paperwork is completed
C. Successful revalidation
D. A manager signs off
Answer: C
Questions 91. APS documentation must include:
A. Weather conditions
B. Reconciliation of units
C. Packaging specifications
D. Supplier qualifications
Answer: B
Questions 92. APS documentation must justify:
A. The cost of media
B. Why units were not incubated
C. Operator vacation days
D. Why shifts were changed
Answer: B
Questions 93. All interventions during APS must include:
A. Photos
B. Video footage
C. Start/end times and operator name
D. Only date
Answer: C
Questions 94. Microbial monitoring data must be:
A. Stored separately
B. Included in APS batch record
C. Deleted after use
D. Optional
Answer: B
Questions 95. APS should be aborted only when:
A. Operators disagree
B. Written procedures require commercial lots to be handled the same
C. Media expires
D. Incubators are full
Answer: B
Questions 96. An investigation is required if an APS is:
A. Partially completed
B. Aborted
C. Passed
D. Shortened
Answer: B
Questions 97. Initial validation must be repeated when the aseptic process has:
A. High output
B. Been in operation continuously
C. Been inactive for an extended period
D. No staff changes
Answer: C
Questions 98. Initial validation must be repeated when there are changes to:
A. Payroll
B. Facility painting
C. Process, equipment, or environment
D. Staff uniforms
Answer: C
Questions 99. Addition of a new container or closure combination requires:
A. Label reprinting
B. No action
C. Repeat of initial validation
D. Removal of old containers
Answer: C
Questions 100. APS acceptance criteria include:
A. Zero growth in all incubated units
B. ≤10 contaminated units
C. Growth in ≤5 units
D. Growth only in clear containers
Answer: A
Reference – EU Guidelines for GMP- Annex-1