Filling and sealing of vials is a critical unit operation in parenteral manufacturing, combining sterile vial filling, stoppering, crimping, and inspection under strict GMP and aseptic processing. B.Pharm students should understand equipment types (peristaltic, piston, rotary fillers), sealing methods (aluminum crimp, heat seal), lyophilization integration, container-closure integrity, validation, environmental controls, sterilization techniques, particulate control and process monitoring. Knowledge of vial materials, elastomeric stoppers, cold chain, and regulatory expectations ensures product safety and stability. This topic links pharmaceutical engineering, quality assurance, and microbiology to prevent contamination and ensure dose accuracy. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which filler type delivers accurate fixed volumes using a reciprocating mechanism ideal for parenteral vials?
- Peristaltic filler
- Piston filler
- Spray nozzle filler
- Overflow filler
Correct Answer: Piston filler
Q2. What is the primary purpose of stoppering in vial processing?
- To label the vial
- To maintain sterility and container-closure integrity
- To cool the product rapidly
- To improve visual appearance
Correct Answer: To maintain sterility and container-closure integrity
Q3. Which sealing method is most commonly used to secure elastomeric stoppers on glass vials in parenteral manufacturing?
- Screw cap sealing
- Aluminum crimp with flip-off cap
- Heat-sealed polymer cap
- Chemical adhesive seal
Correct Answer: Aluminum crimp with flip-off cap
Q4. In aseptic filling, which area must meet ISO 5 (Grade A) unidirectional airflow requirements?
- Material storage room
- Operator gowning area
- Filling and stoppering zone
- Packaging and labeling area
Correct Answer: Filling and stoppering zone
Q5. Which method is the most sensitive for non-destructive container-closure integrity (CCI) testing of vials?
- Dye ingress immersion test
- Visual inspection under light
- Helium leak detection
- Microbial ingress challenge
Correct Answer: Helium leak detection
Q6. Why are elastomeric stoppers siliconized for injectable vials?
- To increase stopper hardness
- To reduce friction during insertion and prevent coring
- To make stoppers transparent
- To act as an antimicrobial coating
Correct Answer: To reduce friction during insertion and prevent coring
Q7. During freeze-drying (lyophilization) of vials, when is in-chamber stoppering typically performed?
- Before freezing the product
- After primary drying while under vacuum
- Only after removal from the lyophilizer at ambient pressure
- During freezing to lock the cake
Correct Answer: After primary drying while under vacuum
Q8. What is the purpose of an overfill allowance in vial filling?
- To increase manufacturing speed
- To ensure accurate delivered dose accounting for residues and handling losses
- To allow vials to be resealed if needed
- To comply with labeling requirements
Correct Answer: To ensure accurate delivered dose accounting for residues and handling losses
Q9. Which factor is most critical for achieving high filling accuracy in a vial filling line?
- Color of the vial
- Pump calibration and gravimetric verification
- Operator height
- Label adhesion strength
Correct Answer: Pump calibration and gravimetric verification
Q10. What pore-size membrane filter is routinely used for sterilizing solutions before aseptic filling?
- 0.45 µm
- 0.22 µm
- 1.2 µm
- 5.0 µm
Correct Answer: 0.22 µm
Q11. What is the role of unidirectional laminar airflow in the immediate filling zone?
- To provide temperature control only
- To supply sterile gas for product reaction
- To sweep particulates away and minimize contamination risk
- To humidify the environment
Correct Answer: To sweep particulates away and minimize contamination risk
Q12. Why is an inert gas overlay (e.g., nitrogen) applied to some injectable products during filling?
- To improve fragrance
- To prevent oxidation and reduce headspace oxygen
- To increase filling speed
- To sterilize the product
Correct Answer: To prevent oxidation and reduce headspace oxygen
Q13. What is the function of a crimping tool in vial sealing?
- To apply labels to vials
- To secure the aluminum cap onto the vial neck and stopper
- To fill the vial with liquid
- To sterilize the stopper
Correct Answer: To secure the aluminum cap onto the vial neck and stopper
Q14. In process qualification, what does PQ (Performance Qualification) demonstrate?
- Design intent of the equipment
- Installation correctness
- Consistent performance under simulated routine conditions
- Calibration of measurement devices only
Correct Answer: Consistent performance under simulated routine conditions
Q15. Which technique is most effective for depyrogenation of glass vials?
- Autoclaving at 121°C for 15 minutes
- Dry heat depyrogenation at high temperature
- Washing with water for injection (WFI)
- Ultrasonic cleaning
Correct Answer: Dry heat depyrogenation at high temperature
Q16. Which nondestructive test is commonly used for routine CCI testing of sealed vials on production lines?
- Dye ingress immersion
- Vacuum decay testing
- Destructive crack testing
- Microbial challenge test
Correct Answer: Vacuum decay testing
Q17. Why is visual inspection of vials performed after filling and sealing?
- To verify color of the cap
- To detect particulates, fill level deviations, and stopper defects
- To measure vial wall thickness
- To test chemical potency
Correct Answer: To detect particulates, fill level deviations, and stopper defects
Q18. What is the main advantage of Clean-in-Place (CIP) and Sterilize-in-Place (SIP) systems in filling lines?
- They reduce product potency
- They enable automated cleaning and sterilization without disassembly
- They increase manual inspection needs
- They eliminate the need for validation
Correct Answer: They enable automated cleaning and sterilization without disassembly
Q19. Which environmental parameters are essential to monitor continuously in a vial filling area?
- Sound level and humidity only
- Airborne particle counts and viable microbial counts
- Lighting intensity and temperature only
- Staff movement patterns
Correct Answer: Airborne particle counts and viable microbial counts
Q20. What does the term “hold time” refer to in aseptic filling operations?
- Time the operator spends on break
- Time between sterilizing filtration and final filling that must be validated and minimized
- Time taken for label application
- Time for package transit to warehouse
Correct Answer: Time between sterilizing filtration and final filling that must be validated and minimized
Q21. Which stopper material is widely preferred for parenteral vials due to low gas permeability and chemical compatibility?
- Nitrile rubber
- Butyl rubber
- Natural rubber latex
- Silicone rubber sheet
Correct Answer: Butyl rubber
Q22. What is the main cause of “coring” when piercing elastomeric stoppers?
- Excessive vial fill volume
- Improper needle design or piercing technique causing stopper fragments
- Using glass stoppers instead of elastomeric
- High ambient humidity
Correct Answer: Improper needle design or piercing technique causing stopper fragments
Q23. What is the purpose of a “wash and blow” step on a vial filling line?
- To sterilize product inside the vial
- To remove dust/particles and dry the vial before filling
- To label vials automatically
- To cool the vials after filling
Correct Answer: To remove dust/particles and dry the vial before filling
Q24. Which regulatory document specifically provides detailed guidance on sterile product manufacture and aseptic processing for EU GMP?
- ICH Q8
- EU GMP Annex 1
- USP <797>
- ICH Q9
Correct Answer: EU GMP Annex 1
Q25. How does nozzle immersion depth during filling affect product quality?
- It only affects labeling speed
- It controls droplet formation and prevents splashing or aerosol generation
- It determines stopper hardness
- It is irrelevant to filling accuracy
Correct Answer: It controls droplet formation and prevents splashing or aerosol generation
Q26. What does the term “fill-finish” encompass in parenteral production?
- Raw material synthesis only
- Final steps to fill, seal, and prepare sterile products for distribution
- Sales and marketing activities
- Bulk compounding without packaging
Correct Answer: Final steps to fill, seal, and prepare sterile products for distribution
Q27. Which monitoring approach directly assesses air microbiological quality during an aseptic fill?
- Surface ATP testing only
- Active air sampling for viable microorganisms
- Particle counting only
- Temperature logging
Correct Answer: Active air sampling for viable microorganisms
Q28. Why is particulate control in vial filling crucial for parenteral products?
- Particles can improve drug potency
- Particulates may cause patient harm like embolism and immune reactions
- Particles only affect cosmetic appearance
- Particles reduce packaging costs
Correct Answer: Particulates may cause patient harm like embolism and immune reactions
Q29. What role does the crimp cap liner (sealing liner) play in vial sealing?
- Acts as a decorative element
- Provides hermetic seal and compatibility between stopper and cap
- Serves as a desiccant
- Labels the vial content
Correct Answer: Provides hermetic seal and compatibility between stopper and cap
Q30. Which practice helps minimize drug adsorption to vial surfaces and maintain potency?
- Using high-adsorption glass types
- Selecting Type I borosilicate glass, controlling siliconization, and optimizing formulation
- Increasing storage temperature intentionally
- Using untreated metal vials
Correct Answer: Selecting Type I borosilicate glass, controlling siliconization, and optimizing formulation
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