Critical systems audit – WFI & purified water MCQs With Answer

Introduction

This blog provides an M.Pharm-focused quiz set on critical systems audits for Water for Injection (WFI) and Purified Water systems. It is designed to reinforce practical and regulatory knowledge needed for auditing, qualification, monitoring and troubleshooting water systems in pharmaceutical manufacture. Questions cover system design, materials, sanitization strategies, analytical controls (conductivity, TOC, microbial and endotoxin testing), sampling strategy, validation (IQ/OQ/PQ), and regulatory expectations from pharmacopeias. Each MCQ is crafted to reflect real audit scenarios and decision points encountered during inspections and compliance activities so postgraduate students can prepare for exams and practical audits with a deeper, applied understanding of water system critical controls.

Q1. Which primary objective should a critical systems audit of WFI and purified water focus on?

• Checking operator uniforms and personal hygiene only
• Verification of system design, control of contamination, validation status and monitoring effectiveness
• Determining the most cost-effective chemical sanitizer
• Assessing marketing claims of water suppliers

Correct Answer: Verification of system design, control of contamination, validation status and monitoring effectiveness

Q2. What is the key regulatory distinction between Water for Injection (WFI) and Purified Water?

• WFI is used exclusively for oral liquid products while Purified Water is for injections
• WFI must meet endotoxin/pyrogen requirements and historically be produced by distillation or an approved equivalent; Purified Water has less stringent endotoxin expectations
• Purified Water must be sterile while WFI does not require any specific production method
• There is no difference; both terms are interchangeable in pharmacopeias

Correct Answer: WFI must meet endotoxin/pyrogen requirements and historically be produced by distillation or an approved equivalent; Purified Water has less stringent endotoxin expectations

Q3. Which set of routine analytical controls is essential for monitoring the quality of pharmaceutical water systems?

• pH only
• Conductivity, TOC, microbial count and, for WFI, endotoxin testing
• Color, turbidity and taste panel
• Only daily visual inspection of tanks and piping

Correct Answer: Conductivity, TOC, microbial count and, for WFI, endotoxin testing

Q4. What is the preferred material and surface finish for internal piping and vessels in WFI/purified water distribution?

• Uncoated carbon steel with rough finish
• PVC piping with smooth inner bore
• 316L stainless steel with electropolished or mechanically polished internal surface
• Copper tubing with threaded joints

Correct Answer: 316L stainless steel with electropolished or mechanically polished internal surface

Q5. The main purpose of a continuously circulating distribution loop in a water system audit is to:

• Ensure water pressure for downstream users only
• Maintain uniform temperature, prevent stagnation and reduce microbial growth
• Allow intermittent flushing instead of dedicated microbiological monitoring
• Store large volumes of water for long-term use

Correct Answer: Maintain uniform temperature, prevent stagnation and reduce microbial growth

Q6. In the context of water system audits, what is a ‘dead leg’ and why is it problematic?

• A storage tank vent line; it improves system aeration
• A short unused branch of piping that promotes stagnation and biofilm formation
• A certified bypass valve used for maintenance operations
• A filter location that removes particulate matter

Correct Answer: A short unused branch of piping that promotes stagnation and biofilm formation

Q7. Which sanitization approach is generally preferred for controlling microbiological contamination in WFI distribution systems?

• Intermittent cold-water flushing without heat
• Thermal sanitization (sustained elevated temperatures) where system design permits
• Exclusive use of mechanical scrubbing of internal surfaces
• Applying household detergents via manual dosing

Correct Answer: Thermal sanitization (sustained elevated temperatures) where system design permits

Q8. Total Organic Carbon (TOC) monitoring is most useful in audits because it:

• Directly measures microbial species present
• Indicates organic contamination from biofilm, process residues or cleaning agents
• Is equivalent to conductivity and therefore redundant
• Measures only inorganic ionic contaminants

Correct Answer: Indicates organic contamination from biofilm, process residues or cleaning agents

Q9. What is the typical pore size for sterilizing point-of-use filters used on WFI lines supplying aseptic operations?

• 10 µm
• 1 µm
• 0.45 µm
• 0.2 µm

Correct Answer: 0.2 µm

Q10. During qualification of a water system, the correct sequence of standard qualification stages is:

• PQ → IQ → OQ
• OQ → PQ → IQ
• IQ → OQ → PQ
• PQ → OQ → IQ

Correct Answer: IQ → OQ → PQ

Q11. When planning a sampling strategy for a purified water distribution loop audit, which locations are essential?

• Only the storage tank inlet
• Multiple points including tank outlet, loop return, representative point-of-use taps and recently serviced areas
• Only the point nearest the water production unit
• Only after chemical sanitization events

Correct Answer: Multiple points including tank outlet, loop return, representative point-of-use taps and recently serviced areas

Q12. Alert and action levels in water monitoring are used to:

• Replace the need for trend analysis entirely
• Trigger investigation and corrective/preventive actions when water quality deteriorates
• Only record data for archival without follow-up
• Provide marketing data for water suppliers

Correct Answer: Trigger investigation and corrective/preventive actions when water quality deteriorates

Q13. Which analytical test is the standard method for detecting bacterial endotoxin in pharmaceutical water or product samples during audits?

• Gram staining
• Limulus Amebocyte Lysate (LAL) assay
• ATP luminescence for endotoxin
• Conductivity measurement

Correct Answer: Limulus Amebocyte Lysate (LAL) assay

Q14. Which water generation technology is most effective at removing pyrogenic endotoxin from feed water?

• Standard reverse osmosis without additional treatment
• Distillation (simple or multi-effect) and properly validated membrane technologies with endotoxin removal capability
• Activated carbon adsorption alone
• Settling and sedimentation

Correct Answer: Distillation (simple or multi-effect) and properly validated membrane technologies with endotoxin removal capability

Q15. If conductivity is within limits but TOC shows a sudden increase, an auditor should suspect:

• A rise in dissolved inorganic salts
• An onset of organic contamination such as biofilm growth or cleaning agent residues
• Faulty conductivity probe only
• Low microbial counts

Correct Answer: An onset of organic contamination such as biofilm growth or cleaning agent residues

Q16. Repeated recovery of Pseudomonas spp. from several loop sample points most likely indicates:

• Effective sanitization practices
• Systemic biofilm formation within distribution piping or components
• Transient contamination from sampling bottles only
• Incorrect conductivity calibration

Correct Answer: Systemic biofilm formation within distribution piping or components

Q17. According to modern pharmacopeial expectations, which statement about WFI production options is correct?

• WFI may only be produced by large open tanks and must be stored cold
• Many pharmacopeias accept distillation or suitably designed membrane-based systems if validated to remove endotoxin and meet quality attributes
• WFI production does not require validation if final testing meets limits
• Only single-pass RO without polishing is acceptable for WFI generation

Correct Answer: Many pharmacopeias accept distillation or suitably designed membrane-based systems if validated to remove endotoxin and meet quality attributes

Q18. What is an important venting requirement for WFI storage tanks observed during audits?

• Open atmospheric venting with no filtration
• Venting through a 0.2 µm sterile filter or comparable microbial-retentive filter
• Venting is unnecessary for pressurized tanks
• Use of a large unfiltered breather valve to equalize pressure quickly

Correct Answer: Venting through a 0.2 µm sterile filter or comparable microbial-retentive filter

Q19. Which document is most critical to review during an audit to confirm routine monitoring and corrective actions for a water system?

• Marketing brochures from equipment suppliers
• SOPs for sampling, monitoring, sanitization and the trending and CAPA procedures
• Employee vacation schedules
• Architectural blueprints without P&ID or SOPs

Correct Answer: SOPs for sampling, monitoring, sanitization and the trending and CAPA procedures

Q20. If an auditor finds persistently high TOC but low microbial counts and normal conductivity, the most appropriate immediate conclusion is:

• The system is fully compliant and no action is necessary
• Organic contamination (residual cleaning agents or non-ionic organics) is present and further investigation into sources and sanitization efficacy is required
• Only the conductivity probe is malfunctioning and TOC can be ignored
• Microbial testing frequency should be reduced

Correct Answer: Organic contamination (residual cleaning agents or non-ionic organics) is present and further investigation into sources and sanitization efficacy is required

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