Process Validation – Liquid Filling & Sealing MCQs With Answer

Introduction: Process Validation – Liquid Filling & Sealing MCQs With Answer is designed for M.Pharm students studying Scale Up & Technology Transfer (MIP 202T). This collection focuses on the scientific and regulatory aspects of validating liquid filling and sealing operations — a critical step in transferring processes from development to commercial manufacture. Questions cover key concepts such as IQ/OQ/PQ, container closure integrity, fill-weight control, aseptic filling (media fills), equipment requalification, scale-up challenges, and statistical tools used for monitoring. The MCQs aim to deepen understanding, reinforce practical knowledge, and prepare students for real-world validation activities and examinations.

Q1. What is the primary objective of process validation for liquid filling and sealing?

• To ensure the filling and sealing process consistently produces product meeting predetermined quality specifications
• To verify only that equipment installation was completed correctly
• To document cleaning procedures for all equipment
• To evaluate operator training records exclusively

Correct Answer: To ensure the filling and sealing process consistently produces product meeting predetermined quality specifications

Q2. Which document typically defines the overall strategy, responsibilities, and scope for validating a liquid filling and sealing line?

• Validation Master Plan (VMP)
• Installation Qualification (IQ) protocol
• Standard Operating Procedures (SOPs)
• Batch Manufacturing Record (BMR)

Correct Answer: Validation Master Plan (VMP)

Q3. During scale-up of a liquid filling line, which process parameter most directly affects fill accuracy and volume control?

• Fill (line) speed
• Ambient lighting conditions
• Container label design
• Operator height

Correct Answer: Fill (line) speed

Q4. Which analytical approach is most appropriate for accurately validating fill volume for liquids, including viscous formulations?

• Gravimetric (by weight) method
• Visual volumetric estimation
• UV-visible assay
• pH titration method

Correct Answer: Gravimetric (by weight) method

Q5. Which container closure integrity (CCI) test is highly sensitive and commonly used for sealed parenteral containers?

• Helium leak detection
• Dye ingress (methylene blue immersion)
• Visual inspection only
• Microbial challenge without a tracer gas

Correct Answer: Helium leak detection

Q6. In crimp sealing of vials, which parameter is considered critical to ensure a tight, hermetic seal?

• Crimp height (and roller compression)
• Capillary action of the liquid
• Operator’s handedness
• Container color

Correct Answer: Crimp height (and roller compression)

Q7. What does “worst-case” condition mean in the context of process validation for liquid filling?

• A realistic combination of process parameters and material attributes that most challenge the process capability
• An improbable extreme that will never occur in practice
• The average operating condition used during routine production
• Only the highest possible temperature recorded in the facility

Correct Answer: A realistic combination of process parameters and material attributes that most challenge the process capability

Q8. For initial process performance qualification (PPQ) of a validated liquid filling process, regulatory guidance commonly recommends demonstrating performance using how many consecutive successful batches?

• Three consecutive successful batches
• One pilot batch only
• Ten consecutive batches
• No batches are required if equipment is new

Correct Answer: Three consecutive successful batches

Q9. Who should agree and sign off the acceptance criteria for transfer and validation activities during technology transfer?

• Originator and receiving site jointly, with QA agreement
• The original development team alone
• The receiving site alone after transfer
• Only the regulatory affairs department

Correct Answer: Originator and receiving site jointly, with QA agreement

Q10. Which critical quality attribute (CQA) is most directly associated with maintaining sterility after filling and sealing?

• Container closure integrity (CCI)
• Color uniformity
• Viscosity only
• External label adhesion

Correct Answer: Container closure integrity (CCI)

Q11. What is the purpose of process capability indices (Cp and Cpk) in the context of liquid filling lines?

• To quantify process variability relative to specification limits and account for mean shift (Cpk)
• To measure operator ergonomics
• To estimate cleaning agent effectiveness
• To assess packaging artwork alignment

Correct Answer: To quantify process variability relative to specification limits and account for mean shift (Cpk)

Q12. Which non-destructive inline method is commonly used for detecting micro-leaks in sealed vials and ampoules?

• High Voltage Leak Detection (HVLD)
• Differential scanning calorimetry
• Direct plating for microbes
• pH testing of the headspace

Correct Answer: High Voltage Leak Detection (HVLD)

Q13. When should requalification of filling and sealing equipment be performed?

• After any major change and at scheduled intervals (e.g., annually) per the validation plan
• Only when equipment fails an in-process check
• Never, once originally qualified
• Only after every production shift

Correct Answer: After any major change and at scheduled intervals (e.g., annually) per the validation plan

Q14. What does “fill-to-weight” control refer to in liquid filling validation?

• Controlling and verifying fill by measuring net weight of container contents (gravimetric control)
• Visual estimation of fill level against a fill line
• Measuring headspace gas composition
• Counting units per carton

Correct Answer: Controlling and verifying fill by measuring net weight of container contents (gravimetric control)

Q15. What is the appropriate ISO classification for the immediate filling zone in an aseptic liquid filling operation?

• ISO 5 (Grade A)
• ISO 8 (Grade D)
• ISO 7 (Grade C) everywhere
• No classification is required for aseptic filling

Correct Answer: ISO 5 (Grade A)

Q16. How does increasing product viscosity typically influence filling performance during scale-up?

• It increases fill time, may reduce accuracy and cause stringing or residual drips
• It always reduces microbial contamination risk
• It reduces the need for container closure integrity testing
• It has no effect on volumetric piston fillers

Correct Answer: It increases fill time, may reduce accuracy and cause stringing or residual drips

Q17. What is the main objective of conducting a media fill during validation of an aseptic liquid filling process?

• To simulate the full aseptic process using growth medium to demonstrate absence of contamination
• To determine product potency
• To validate labeling operations only
• To measure fill weight variability

Correct Answer: To simulate the full aseptic process using growth medium to demonstrate absence of contamination

Q18. Which sealing approach is typically preferred for heat-sensitive liquid formulations to avoid thermal degradation during sealing?

• Crimping with appropriate septa/liner (mechanical seal)
• High-temperature heat-sealing directly to the liquid
• Extended oven drying
• Autoclave post-seal for sterility

Correct Answer: Crimping with appropriate septa/liner (mechanical seal)

Q19. Which statistical tool is most appropriate for real-time monitoring of fill accuracy and detecting shifts in the liquid filling process?

• Control charts (e.g., X-bar and R charts)
• ANOVA for end-of-year reporting only
• Pareto chart for ingredient costs
• Kaplan–Meier survival analysis

Correct Answer: Control charts (e.g., X-bar and R charts)

Q20. What is the primary objective of technology transfer for a liquid filling and sealing process?

• To ensure the receiving site can reproducibly manufacture the product to the same quality standards through documentation, training, and demonstration
• To transfer intellectual property without operational validation
• To change product specifications arbitrarily at the receiving site
• To eliminate the need for any validation at the receiving site

Correct Answer: To ensure the receiving site can reproducibly manufacture the product to the same quality standards through documentation, training, and demonstration

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