Filling and sealing of infusion fluids is a critical area in parenteral manufacturing that combines aseptic processing, sterile filling techniques, and robust sealing methods to ensure patient safety. B. Pharm students must understand container types, aseptic environments, filtration and sterilization (0.22 µm filters, terminal sterilization), container closure integrity (CCI) tests, and regulatory expectations such as GMP and USP standards. Key concepts include visual inspection, microbial control, validation (media fills), and leak-detection methods (dye ingress, vacuum decay). Mastery of these topics helps prevent contamination, ensure sterility, and maintain product quality. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What is the primary purpose of using a 0.22 µm sterilizing-grade filter during infusion fluid production?
- To remove pyrogens only
- To retain bacteria and most spores
- To sterilize the final container by heat
- To remove dissolved gases
Correct Answer: To retain bacteria and most spores
Q2. Which cleanroom classification corresponds to the EU GMP Grade A (ISO standard) for aseptic filling zones?
- ISO 8
- ISO 7
- ISO 5
- ISO 4
Correct Answer: ISO 5
Q3. What is a media fill (process simulation) used to validate in aseptic filling operations?
- Filter integrity testing
- Cleanroom air particle counts
- Microbial contamination risk of the aseptic process
- Container closure integrity
Correct Answer: Microbial contamination risk of the aseptic process
Q4. Which container closure integrity (CCI) test is non-destructive and suitable for routine production checks?
- Dye ingress test
- Vacuum decay test
- Microbial challenge test
- Helium leak detection (destructive)
Correct Answer: Vacuum decay test
Q5. During filling of infusion fluids, which pump type is preferred for accurate volumetric filling of low to moderate viscosity solutions?
- Centrifugal pump
- Peristaltic or piston filler
- Gear pump
- Axial flow pump
Correct Answer: Peristaltic or piston filler
Q6. Which sealing method is commonly used for glass vials with rubber stoppers in parenteral production?
- Heat shrink welding
- Capping with aluminum crimp and flip-off seal
- Ultrasonic welding of plastic
- Adhesive sealing
Correct Answer: Capping with aluminum crimp and flip-off seal
Q7. What is the main advantage of isolator technology over traditional laminar flow hoods for aseptic filling?
- Lower capital cost
- Reduced barrier to operator intervention
- Improved containment and lower contamination risk
- No need for HEPA filters
Correct Answer: Improved containment and lower contamination risk
Q8. Which regulatory document provides global guidance for GMP of sterile medicinal products, including filling and sealing?
- ICH Q1A
- USP 800
- EU GMP Annex 1
- ICH Q9
Correct Answer: EU GMP Annex 1
Q9. What is the main purpose of overfill in infusion bags and vials?
- To compensate for dead volume and administration losses
- To increase shelf life
- To improve visual inspection
- To allow re-sterilization
Correct Answer: To compensate for dead volume and administration losses
Q10. Which test specifically assesses particulate matter in infusion fluids?
- Endotoxin test (LAL)
- Particulate matter test (USP <788>)
- Sterility test
- pH measurement
Correct Answer: Particulate matter test (USP <788>)
Q11. Why are preservatives generally avoided in most infusion fluids intended for intravenous administration?
- They are ineffective against microbes
- They can cause adverse reactions and are unsuitable for large-volume IVs
- They reduce solution clarity
- They increase particulate counts
Correct Answer: They can cause adverse reactions and are unsuitable for large-volume IVs
Q12. Which sterilization method is unsuitable for heat-sensitive infusion solutions and thus commonly replaced by filtration?
- Ethylene oxide sterilization
- Gamma irradiation
- Autoclaving (steam sterilization)
- Dry heat sterilization
Correct Answer: Autoclaving (steam sterilization)
Q13. What is bubble point testing primarily used to verify in sterile filtration?
- Filter wetting properties and integrity
- Particle size distribution in the fluid
- Chemical compatibility of the filter
- Microbial load before filtration
Correct Answer: Filter wetting properties and integrity
Q14. During sealing, what critical parameter must be controlled for aluminum crimp caps on vials?
- Torque and crimp height
- Temperature of the crimper only
- pH of the solution
- Ambient humidity only
Correct Answer: Torque and crimp height
Q15. Which contamination source is most likely introduced during manual loading of vials into a filling machine?
- Particulate contamination only
- Airborne microbes and operator-borne contamination
- Endotoxins from packaging
- Chemical contaminants from solvents
Correct Answer: Airborne microbes and operator-borne contamination
Q16. What is the acceptable endotoxin limit for most large-volume parenteral solutions (EU guideline example)?
- 0.25 EU/mL for all IV fluids
- 5 EU/kg/hr general safety limit for IV infusions
- 50 EU/mL
- There are no limits for endotoxins in parenterals
Correct Answer: 5 EU/kg/hr general safety limit for IV infusions
Q17. Visual inspection of filled infusion containers should detect which defects?
- Only color variation
- Particulates, seal defects, fill level variation, and container damage
- Only microbial contamination
- Only label misprints
Correct Answer: Particulates, seal defects, fill level variation, and container damage
Q18. What is the principle behind dye ingress testing for container closure integrity?
- Detecting helium leaks with a tracer gas
- Applying vacuum to detect outgassing
- Using a dye solution to reveal breaches under pressure or vacuum
- Measuring electrical resistance across the seal
Correct Answer: Using a dye solution to reveal breaches under pressure or vacuum
Q19. Which parameter is critical when validating automated filling accuracy for infusion syringes or vials?
- Ambient light levels
- Dispense volume precision and accuracy (CV% and mean error)
- Operator eye color
- Color of the filling machine
Correct Answer: Dispense volume precision and accuracy (CV% and mean error)
Q20. In aseptic processing, what is “vertical laminar flow” primarily used for?
- To cool the room
- To direct HEPA-filtered air downwards over the critical area to sweep away particles
- To sterilize products by airflow heating
- To humidify the cleanroom
Correct Answer: To direct HEPA-filtered air downwards over the critical area to sweep away particles
Q21. Why is routine HEPA filter integrity testing important in aseptic filling suites?
- Filters increase microbial load
- To ensure the filter continues to provide required particle removal efficiency
- To monitor pH of the room air
- To lubricate the filters
Correct Answer: To ensure the filter continues to provide required particle removal efficiency
Q22. What role does aseptic gowning of operators play in filling and sealing of infusion fluids?
- Only to meet aesthetic standards
- To reduce operator-shed particles and microbes in the critical zone
- To increase production speed
- To cool operators during work
Correct Answer: To reduce operator-shed particles and microbes in the critical zone
Q23. Which microbial test is mandatory to demonstrate the sterility of filled infusion products?
- Sterility test per pharmacopeial methods (e.g., USP <71>)
- Only endotoxin test
- Only visual inspection
- Only environmental monitoring
Correct Answer: Sterility test per pharmacopeial methods (e.g., USP <71>)
Q24. During batch release, which documentation is most critical to confirm correct filling and sealing?
- Batch manufacturing record with fill weights, calibration logs, and CCI results
- Only the sales invoice
- Only the marketing authorization
- Only the cleaning SOP
Correct Answer: Batch manufacturing record with fill weights, calibration logs, and CCI results
Q25. Which of the following is a destructive CCI test often used in development to detect very small leaks?
- Vacuum decay
- Dye ingress
- Bubble immersion under vacuum
- Helium leak detection with mass spectrometry
Correct Answer: Helium leak detection with mass spectrometry
Q26. What is the main purpose of in-process environmental monitoring during aseptic filling?
- To replace end-product sterility testing
- To provide data on airborne and surface contamination trends during production
- To test product potency
- To measure fill volume
Correct Answer: To provide data on airborne and surface contamination trends during production
Q27. For single-use plastic infusion bags, which sealing technology is commonly applied?
- Induction sealing with foil
- Ultrasonic or heat welding of thermoplastic films
- Cork stoppers
- Crimping with metal caps
Correct Answer: Ultrasonic or heat welding of thermoplastic films
Q28. Which practice helps minimize particulate generation during filling and sealing operations?
- Using unpolished metal surfaces in contact areas
- Minimizing friction, using smooth materials, and controlling wear of machine parts
- Increasing personnel movement in the aseptic zone
- Using open containers during filling
Correct Answer: Minimizing friction, using smooth materials, and controlling wear of machine parts
Q29. What does a successful media fill result typically indicate about an aseptic filling process?
- That the product is free of endotoxins
- That the process can consistently produce sterile product under simulated conditions
- That filters removed all particulates
- That seals are always perfect
Correct Answer: That the process can consistently produce sterile product under simulated conditions
Q30. Which is the most appropriate immediate corrective action if a visual inspection detects particles in a filled infusion batch?
- Release the batch with a note
- Investigate root cause, quarantine affected units, and perform trend analysis
- Ignore and continue production
- Change the label only
Correct Answer: Investigate root cause, quarantine affected units, and perform trend analysis
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