Quality control tests for containers and closures are critical for ensuring pharmaceutical product safety, stability, and sterility. This overview introduces B.Pharm students to essential concepts: container closure integrity (CCI), leak testing (helium, vacuum decay, pressure decay), dye ingress, microbial challenge, seal strength, moisture and oxygen transmission rates (WVTR/OTR), extractables and leachables, visual inspection, and packaging validation. You will learn relevant USP/ICH/ISO methods, acceptance criteria, common materials (glass, HDPE, PVC, rubber stoppers) and practical failure modes. Understanding instrumentation, sampling plans, and regulatory expectations prepares you for QC roles in pharma manufacturing and stability studies. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What is the primary goal of Container Closure Integrity (CCI) testing in pharmaceuticals?
- To measure the chemical compatibility of materials
- To confirm physical dimensions of containers
- To ensure a container–closure system prevents ingress or egress of contaminants
- To determine the color stability of labels
Correct Answer: To ensure a container–closure system prevents ingress or egress of contaminants
Q2. Which of the following tests is considered a qualitative method for detecting gross leaks?
- Helium mass spectrometry
- Dye ingress (colored solution) test
- Vacuum decay quantitative analysis
- High voltage leak detection with calibrated meter
Correct Answer: Dye ingress (colored solution) test
Q3. Helium leak detection is commonly chosen because it provides which major advantage?
- It is the least expensive option
- It has very high sensitivity for micro-leaks
- It requires no specialized instrumentation
- It is always a destructive test
Correct Answer: It has very high sensitivity for micro-leaks
Q4. Which method detects leaks by monitoring pressure change after creating a vacuum or pressure differential?
- Dye ingress test
- Visual inspection under magnification
- Vacuum decay/pressure decay
- Extractables study
Correct Answer: Vacuum decay/pressure decay
Q5. Compared to dye ingress, what is a primary limitation of the dye test?
- It is too sensitive for production testing
- It provides only qualitative, low-sensitivity results and may miss micro-leaks
- It cannot detect gross leaks
- It requires helium as tracer gas
Correct Answer: It provides only qualitative, low-sensitivity results and may miss micro-leaks
Q6. Which test specifically challenges a closure system for microbial penetration under defined conditions?
- Seal strength test
- Microbial ingress (microbial challenge) test
- Helium leak test
- OTR measurement
Correct Answer: Microbial ingress (microbial challenge) test
Q7. What does WVTR (Water Vapor Transmission Rate) quantify?
- The rate at which oxygen permeates a container
- The mass of water vapor transmitted through a material per area per time
- The amount of extractable substances released into water
- The visual clarity loss of a polymer over time
Correct Answer: The mass of water vapor transmitted through a material per area per time
Q8. Which material generally provides the best intrinsic moisture barrier for liquid parenteral packaging?
- Unplasticized PVC (uPVC)
- Glass (amber borosilicate)
- Low-density polyethylene (LDPE)
- Paperboard
Correct Answer: Glass (amber borosilicate)
Q9. What is the difference between extractables and leachables?
- Extractables are measured under exaggerated conditions; leachables are found under normal storage conditions
- Leachables are always toxic; extractables are inert
- Extractables are only organic; leachables are only inorganic
- There is no difference; the terms are interchangeable
Correct Answer: Extractables are measured under exaggerated conditions; leachables are found under normal storage conditions
Q10. Which USP chapter specifically addresses container closure system integrity evaluation for sterile products?
- USP <1163>
- USP <1207>
- USP <905>
- USP <571>
Correct Answer: USP <1207>
Q11. Seal strength (peel test) for blisters and pouches is primarily used to assess what?
- Chemical compatibility of the drug and packaging
- Mechanical integrity of the seal and its resistance to opening
- Headspace oxygen concentration
- Visual appearance of the label
Correct Answer: Mechanical integrity of the seal and its resistance to opening
Q12. Which technique is best for assessing ultra-low leak rates in complex assemblies like lyophilized vials with stoppers?
- Visual inspection only
- Dye ingress with methylene blue
- Helium mass spectrometry leak detection
- Simple manual torque measurement
Correct Answer: Helium mass spectrometry leak detection
Q13. Which parameter is most relevant when evaluating oxygen ingress risk for an oxygen-sensitive drug?
- Headspace volume only
- OTR (Oxygen Transmission Rate) of the packaging system
- Seal color
- Label font size
Correct Answer: OTR (Oxygen Transmission Rate) of the packaging system
Q14. Which of the following is a destructive test for container-closure systems?
- Vacuum decay integrity test performed nondestructively
- Helium leak detection with intact system
- Peel strength measurement of a blister seal
- Automated visual inspection using cameras
Correct Answer: Peel strength measurement of a blister seal
Q15. Why is headspace gas analysis performed during CCI evaluation?
- To detect particulate visible by naked eye
- To determine internal gas composition and detect ingress or changes in packaging atmosphere
- To measure seal peel strength
- To quantify extractables in organic solvents
Correct Answer: To determine internal gas composition and detect ingress or changes in packaging atmosphere
Q16. Which test would be preferred to detect very small pinholes in polymeric pouches used for sterile barriers?
- Dye ingress immersion
- Bubble emission (vacuum immersion) test
- Visual inspection with unaided eye
- Standard label adhesion test
Correct Answer: Bubble emission (vacuum immersion) test
Q17. What is a common regulatory expectation when CCI testing is performed for sterile marketed products?
- Only one sample per batch needs testing indefinitely
- Appropriate validation with defined acceptance criteria and periodic monitoring
- No documentation is required if visual inspection is done
- Testing can be skipped for glass containers
Correct Answer: Appropriate validation with defined acceptance criteria and periodic monitoring
Q18. Which packaging feature provides a tamper-evident barrier commonly used on bottles?
- Heat transfer label
- Induction-sealed foil liner under the cap
- Paper wrap around cap
- Embossed container base
Correct Answer: Induction-sealed foil liner under the cap
Q19. Which test uses a microbial broth and incubation to evaluate closure resistance to microbial ingress?
- Helium leak test
- Microbial challenge (broth immersion) test
- OTR measurement
- Peel strength testing
Correct Answer: Microbial challenge (broth immersion) test
Q20. Which factor most influences the rate of leachables from a polymer closure into an aqueous drug product?
- Ambient label printing method
- Contact time, temperature, and solvent polarity of the product
- Color of the closure
- Size of the bottle cap logo
Correct Answer: Contact time, temperature, and solvent polarity of the product
Q21. Automated visual inspection machines are primarily designed to detect which defects?
- Micro-leaks below 10 µm
- Visible defects such as particulate, fill level deviations, broken seals, or foreign matter
- OTR values
- Helium concentration in headspace
Correct Answer: Visible defects such as particulate, fill level deviations, broken seals, or foreign matter
Q22. Which of the following is a non-destructive, gas-based test commonly used to screen finished parenteral vials for leaks?
- Destructive burst test
- Helium leak testing or vacuum decay performed nondestructively
- Peel-to-open blister test
- Dissolution testing
Correct Answer: Helium leak testing or vacuum decay performed nondestructively
Q23. During packaging validation, extractables studies are run to:
- Determine the mechanical strength of the container
- Identify potential chemical components that may leach under exaggerated conditions
- Measure headspace oxygen only
- Verify label adhesion
Correct Answer: Identify potential chemical components that may leach under exaggerated conditions
Q24. Which acceptance outcome best indicates a pass in a microbial ingress challenge?
- Growth observed in all challenged units
- No microbial growth in any challenged units after incubation
- Partial growth in control units only
- Immediate turbidity during immersion
Correct Answer: No microbial growth in any challenged units after incubation
Q25. What is the main advantage of vacuum decay over dye ingress for production-level CCI testing?
- Vacuum decay is qualitative while dye ingress gives numeric leak rate
- Vacuum decay is typically non-destructive, quantitative, and suitable for automation
- Vacuum decay always requires chemical solvents
- Vacuum decay cannot detect leaks in rigid containers
Correct Answer: Vacuum decay is typically non-destructive, quantitative, and suitable for automation
Q26. Which measurement is directly related to the permeability of a closure or film to oxygen?
- WVTR (Water Vapor Transmission Rate)
- OTR (Oxygen Transmission Rate)
- Peel strength
- Seal width in mm
Correct Answer: OTR (Oxygen Transmission Rate)
Q27. In extractables testing, exaggerated conditions typically include:
- Lower temperatures and shorter times
- Elevated temperatures, aggressive solvents, and prolonged exposure
- Only visual inspection at room temp
- Exposure to ultrasonic waves only
Correct Answer: Elevated temperatures, aggressive solvents, and prolonged exposure
Q28. Which closure type is generally considered to provide the most consistent hermetic seal for lyophilized parenterals?
- Screw caps without crimping
- Crimped aluminum seals over rubber stoppers (aluminum crimp caps)
- Snap-on plastic lids
- Paper seals under the cap
Correct Answer: Crimped aluminum seals over rubber stoppers (aluminum crimp caps)
Q29. Which test result would most directly indicate a change in headspace oxygen that could compromise an oxygen-sensitive drug?
- Increased WVTR measurement
- Measured increase in headspace oxygen by headspace gas analysis
- Higher peel strength of blister seal
- Change in label color on exposure to light
Correct Answer: Measured increase in headspace oxygen by headspace gas analysis
Q30. Why is sampling plan and statistically justified sample size important in CCI studies?
- To reduce documentation requirements
- To ensure representative evaluation and acceptable confidence in product integrity across a batch
- Because regulatory agencies require sampling of every single unit
- To replace routine stability testing
Correct Answer: To ensure representative evaluation and acceptable confidence in product integrity across a batch
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