Filling and sealing of ampoules is a critical unit operation in sterile parenteral manufacturing that ensures product sterility, accurate dosing, and container‑closure integrity. This topic covers ampoule materials (Type I borosilicate glass), filling technologies (vacuum, piston, gravity), flame and automatic sealing, sterilization strategies, aseptic processing, and quality control tests such as visual inspection, dye/helium leak testing, particle counting and media‑fill validation. Understanding process parameters, common defects (delamination, incomplete seals, particulates), environmental requirements (ISO classifications) and regulatory expectations (USP sterility and CCI guidelines) is essential for B. Pharm students preparing for industry roles. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which filling method is commonly used to minimize air entrapment and ensure accurate dosing when filling small volume ampoules?
- Gravity filling
- Piston dosing
- Vacuum filling
- Peristaltic pump filling
Correct Answer: Vacuum filling
Q2. What is the preferred glass type for manufacturing sterile ampoules used for parenteral products?
- Type III soda‑lime glass
- Type II treated glass
- Type I borosilicate glass
- Tempered glass
Correct Answer: Type I borosilicate glass
Q3. What is the primary purpose of flame sealing ampoules after filling?
- To sterilize the entire ampoule contents
- To create a hermetic glass seal and locally sterilize the neck
- To anneal the glass and remove stresses
- To apply a tamper‑evident cap
Correct Answer: To create a hermetic glass seal and locally sterilize the neck
Q4. Why is headspace control important during ampoule filling and sealing?
- It determines label adhesion quality
- It affects thermal expansion during sterilization and seal integrity
- It changes the ampoule color
- It reduces glass strength
Correct Answer: It affects thermal expansion during sterilization and seal integrity
Q5. Which defect is typically associated with chemical attack on glass and results in flaking or particle formation inside ampoules?
- Incomplete seal
- Delamination (glass flaking)
- Overfilling
- Under‑vacuum
Correct Answer: Delamination (glass flaking)
Q6. For a heat‑stable injectable, which terminal sterilization method is commonly used for sealed ampoules?
- Ethylene oxide sterilization
- Moist heat sterilization (autoclaving)
- Gamma irradiation
- Filtration sterilization after sealing
Correct Answer: Moist heat sterilization (autoclaving)
Q7. Which container‑closure integrity (CCI) test is considered highly sensitive for detecting very small leaks in ampoules?
- Dye ingress test
- Vacuum decay
- Helium leak detection
- Pressure hold test
Correct Answer: Helium leak detection
Q8. What is the purpose of a media‑fill (process simulation) test in ampoule aseptic manufacturing?
- To validate fill‑volume accuracy
- To validate the aseptic process by simulating production with growth media
- To test glass strength under heat
- To determine particle counts in headspace
Correct Answer: To validate the aseptic process by simulating production with growth media
Q9. Which environmental classification is required at the immediate filling point for aseptic ampoule filling?
- ISO Class 8
- ISO Class 7
- ISO Class 5
- Unclassified area
Correct Answer: ISO Class 5
Q10. What is a common reason for using nitrogen blanketing during ampoule filling?
- To increase humidity in the room
- To prevent oxidation and reduce oxygen in headspace
- To heat the formulation
- To sterilize ampoules
Correct Answer: To prevent oxidation and reduce oxygen in headspace
Q11. Which equipment step removes particulate and soluble contaminants before ampoule filling?
- Flame sealing
- Washing with purified water (WFI) and drying
- Annealing
- Visual inspection
Correct Answer: Washing with purified water (WFI) and drying
Q12. Which QC method is commonly used for detecting subvisible particles in ampoule contents?
- Visual inspection only
- Light obscuration particle counting
- pH testing
- Thermal gravimetric analysis
Correct Answer: Light obscuration particle counting
Q13. What is the main risk associated with incomplete or poor sealing of an ampoule?
- Enhanced label adhesion
- Loss of sterility and potential contamination
- Improved dissolution rate
- Increased glass strength
Correct Answer: Loss of sterility and potential contamination
Q14. Which machine operation simultaneously melts and closes the neck of a glass ampoule in automated production?
- Crimping machine
- Flame sealer (automatic ampoule sealer)
- Ultrasonic welder
- Lid application machine
Correct Answer: Flame sealer (automatic ampoule sealer)
Q15. Which test is a simple method to detect gross leaks in sealed ampoules by immersion?
- Dye ingress (methylene blue) test
- Helium mass spectrometry
- High precision vacuum decay
- Light scattering
Correct Answer: Dye ingress (methylene blue) test
Q16. What is annealing of glass ampoules performed to achieve?
- Increase internal pressure
- Relieve thermal stress and reduce risk of cracking
- Sterilize the contents
- Improve chemical resistance
Correct Answer: Relieve thermal stress and reduce risk of cracking
Q17. Which type of biological indicator is commonly used to validate moist heat sterilization cycles?
- Geobacillus stearothermophilus spore strips
- Bacillus subtilis chemical indicators
- Escherichia coli culture
- Pseudomonas aeruginosa swabs
Correct Answer: Geobacillus stearothermophilus spore strips
Q18. What process parameter is most critical during flame sealing to ensure a proper hermetic seal?
- Ambient room humidity
- Flame temperature and dwell time
- Label printing speed
- Filling pump horsepower
Correct Answer: Flame temperature and dwell time
Q19. Which regulatory USP chapter specifically addresses container‑closure integrity concepts relevant to ampoules?
- USP <71> Sterility Tests
- USP <381> Containers
- USP <1207> Package Integrity Evaluation
- USP <797> Compounding
Correct Answer: USP <1207> Package Integrity Evaluation
Q20. What is the purpose of a visual inspection step in ampoule production?
- To determine formulation potency
- To detect visible defects such as particulates, under/overfill and poor seals
- To sterilize the ampoule exterior
- To measure glass thickness
Correct Answer: To detect visible defects such as particulates, under/overfill and poor seals
Q21. During aseptic filling, why is laminar airflow (HEPA filtered) used at the filling point?
- To increase temperature for sealing
- To provide unidirectional clean air and minimize particulate contamination
- To reduce formulation viscosity
- To dry the ampoule exterior
Correct Answer: To provide unidirectional clean air and minimize particulate contamination
Q22. Which analytical method is used to quantify submicron particles and organics that may arise from glass‑formulation interaction?
- Visual inspection
- Size exclusion chromatography
- Flow imaging and LC/MS (combination of particle analysis and chemical testing)
- pH paper test
Correct Answer: Flow imaging and LC/MS (combination of particle analysis and chemical testing)
Q23. What is the main advantage of automatic ampoule sealing over manual flame sealing in production?
- Higher variability in seal quality
- Increased labor requirements
- Consistent seal quality, higher throughput and improved operator safety
- Ability to seal plastics only
Correct Answer: Consistent seal quality, higher throughput and improved operator safety
Q24. Which phenomenon indicates potential incompatibility between formulation and glass that may release ionic species into solution?
- Underfilling
- Cloudiness, pH shift or ion leaching
- Proper annealing
- Excess headspace
Correct Answer: Cloudiness, pH shift or ion leaching
Q25. Why is process validation (including media fills) essential for aseptic ampoule filling?
- To qualify labels
- To ensure consistent sterility assurance and identify process weaknesses
- To speed up sealing
- To test glass color uniformity
Correct Answer: To ensure consistent sterility assurance and identify process weaknesses
Q26. Which of the following is a common cause of air bubbles or foam formation during ampoule filling?
- Using degassed formulation
- Rapid filling speed and improper nozzle immersion
- Proper vacuum filling
- Filling under nitrogen blanket
Correct Answer: Rapid filling speed and improper nozzle immersion
Q27. What is the role of a particle monitoring program in ampoule filling suites?
- To count staff entering the area
- To track and control particulate levels to meet ISO classification requirements
- To measure glass thickness
- To validate label adhesion
Correct Answer: To track and control particulate levels to meet ISO classification requirements
Q28. Which method is typically used to wash ampoules prior to filling to ensure removal of residues?
- Dry wiping with cloth
- Sequential rinses with purified water (WFI) and filtered air drying
- Soaking in ethanol only
- Flame wiping
Correct Answer: Sequential rinses with purified water (WFI) and filtered air drying
Q29. Which final product test confirms the sterility of filled and sealed ampoules before release?
- pH test
- Sterility test as per pharmacopeial methods (e.g., USP <71>)
- Viscosity measurement
- Thermogravimetric analysis
Correct Answer: Sterility test as per pharmacopeial methods (e.g., USP <71>)
Q30. Which preventive step reduces the risk of glass particles entering the ampoule during sealing?
- Using cold flame sealing
- Proper flame control, correct neck cutting technique and post‑sealing inspection
- Skipping washing step
- Increasing headspace excessively
Correct Answer: Proper flame control, correct neck cutting technique and post‑sealing inspection
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.
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