Testing safety of packaging materials MCQs With Answer

Introduction: Testing the safety of packaging materials is a critical component of pharmaceutical development and post-market surveillance. For M.Pharm students studying Biological Evaluation of Drug Therapy, understanding extractables and leachables, migration mechanisms, analytical strategies and toxicological assessment is essential. This blog emphasizes practical testing workflows: selecting solvents and analytical platforms (GC-MS, LC-MS, ICP-MS), designing accelerated and real-time migration studies, and interpreting biological tests such as cytotoxicity, sensitization and genotoxicity. It also covers risk-based decision making using exposure assessment, safety thresholds and barrier technologies. The aim is to equip students with the knowledge to evaluate packaging-related risks and to design robust test plans for patient safety.

Q1. What best distinguishes ‘extractables’ from ‘leachables’ in packaging safety studies?

• Extractables are compounds that migrate into the drug product under normal storage; leachables are obtained only under aggressive laboratory extraction.
• Extractables are identified using biological assays; leachables are identified using chemical analysis.
• Extractables are compounds obtained from the packaging using aggressive conditions in the laboratory; leachables are compounds that actually migrate into the drug product under normal storage or use conditions.
• Extractables and leachables are identical terms used interchangeably in regulatory guidance.

Correct Answer: Extractables are compounds obtained from the packaging using aggressive conditions in the laboratory; leachables are compounds that actually migrate into the drug product under normal storage or use conditions.

Q2. Which analytical technique is most appropriate as a first-line screen for volatile and semi-volatile organic extractables?

• High-performance liquid chromatography with UV detection (HPLC-UV)
• Gas chromatography–mass spectrometry (GC-MS)
• Inductively coupled plasma mass spectrometry (ICP-MS)
• Nuclear magnetic resonance (NMR) spectroscopy

Correct Answer: Gas chromatography–mass spectrometry (GC-MS)

Q3. For non-volatile, polar organic extractables in aqueous-compatible packaging, which technique provides the best sensitivity and structural information?

• GC-FID
• Liquid chromatography–mass spectrometry (LC-MS)
• FTIR spectroscopy
• Atomic absorption spectroscopy (AAS)

Correct Answer: Liquid chromatography–mass spectrometry (LC-MS)

Q4. Which method is the preferred choice to quantify trace elemental impurities leaching from glass or metal-containing closures?

• HPLC-UV
• ICP-MS (Inductively Coupled Plasma Mass Spectrometry)
• GC-MS
• UV-Vis spectrophotometry

Correct Answer: ICP-MS (Inductively Coupled Plasma Mass Spectrometry)

Q5. What is the primary objective of migration testing for packaging materials?

• To determine the mechanical strength of the packaging
• To assess the color stability of packaging inks
• To evaluate the potential for chemical compounds from the packaging to migrate into the drug product under intended storage and use conditions
• To certify recyclability of packaging materials

Correct Answer: To evaluate the potential for chemical compounds from the packaging to migrate into the drug product under intended storage and use conditions

Q6. Which biological test is most directly used to screen whether a leachable has cytotoxic potential to mammalian cells?

• Ames bacterial mutagenicity test
• In vitro cytotoxicity assay (e.g., MTT, neutral red uptake)
• Accelerated aging study
• ICP-MS elemental analysis

Correct Answer: In vitro cytotoxicity assay (e.g., MTT, neutral red uptake)

Q7. According to general biological evaluation principles, which three endpoints are commonly considered when assessing packaging materials for parenteral products?

• Color, odor, and taste
• Cytotoxicity, sensitization, and irritation/inflammation
• Flammability, tensile strength, and permeability
• pH, conductivity, and refractive index

Correct Answer: Cytotoxicity, sensitization, and irritation/inflammation

Q8. In extractables studies, what does achieving an acceptable ‘mass balance’ mean?

• All detected compounds have identical mass spectra
• The total mass of the drug product equals the mass of the packaging
• The summed mass of identified extractables accounts for a substantial portion of the total extractable mass, indicating adequate analytical coverage
• No residual solvent remains in the packaging after extraction

Correct Answer: The summed mass of identified extractables accounts for a substantial portion of the total extractable mass, indicating adequate analytical coverage

Q9. What is the role of accelerated aging studies in the context of packaging safety?

• To replace all analytical testing with a single stability timepoint
• To simulate long-term storage and identify leachables that may form or migrate over the product shelf life
• To measure immediate mechanical failure of the container
• To evaluate consumer handling only

Correct Answer: To simulate long-term storage and identify leachables that may form or migrate over the product shelf life

Q10. When designing extraction solvents for a comprehensive extractables study, which selection principle is most appropriate?

• Use only water because most drugs are aqueous
• Use a single solvent that gives the highest total extractable mass
• Use a set of solvents covering a broad polarity and pH range to maximize recovery of diverse extractables
• Avoid organic solvents to prevent swelling of polymeric materials

Correct Answer: Use a set of solvents covering a broad polarity and pH range to maximize recovery of diverse extractables

Q11. Under which circumstance should genotoxicity testing be considered for a leachable identified in a drug product?

• If the leachable shows a molecular weight below 50 Da
• If structural alerts, identified substructures, or in silico predictions indicate potential genotoxic or mutagenic concern
• Only when the leachable concentration exceeds 1% w/w of the drug product
• Genotoxicity testing is never required for packaging leachables

Correct Answer: If structural alerts, identified substructures, or in silico predictions indicate potential genotoxic or mutagenic concern

Q12. What is the utility of applying a Threshold of Toxicological Concern (TTC) approach to low-level leachables?

• To automatically classify all leachables as non-toxic
• To provide a risk-based screening threshold for chemicals lacking toxicological data, guiding the need for further testing
• To replace analytical detection limits with toxicology limits
• To set regulatory labeling requirements for packaging

Correct Answer: To provide a risk-based screening threshold for chemicals lacking toxicological data, guiding the need for further testing

Q13. How are acceptance criteria for packaging safety commonly established?

• By consulting only historical supplier certificates without analysis
• By performing a toxicological risk assessment that integrates exposure estimates, analytical concentrations and relevant toxicology data
• By using a universal concentration cutoff identical for all drugs
• By measuring only mechanical integrity and ignoring chemical migration

Correct Answer: By performing a toxicological risk assessment that integrates exposure estimates, analytical concentrations and relevant toxicology data

Q14. Which sequence of analytical methods is typically recommended for a comprehensive E&L screening workflow?

• ICP-MS for organics → NMR for metals → GC-MS for non-volatiles
• GC-MS for volatiles/semi-volatiles → LC-MS for non-volatiles/polar compounds → ICP-MS for elemental impurities
• HPLC-UV only → no further analyses
• Physical testing only, then biological testing without chemical screening

Correct Answer: GC-MS for volatiles/semi-volatiles → LC-MS for non-volatiles/polar compounds → ICP-MS for elemental impurities

Q15. What is the critical function of a functional barrier (e.g., glass, metallized layer) in packaging systems?

• To improve label adhesion
• To reduce or prevent migration of packaging components into the drug product by providing a physical/chemical barrier
• To increase the apparent volume of the container
• To act as a nutrient source for microorganisms

Correct Answer: To reduce or prevent migration of packaging components into the drug product by providing a physical/chemical barrier

Q16. Which observable changes in a drug product could indicate incompatibility with a packaging material?

• Changes in API potency, formation of new impurities, pH shifts or color/turbidity changes
• Only mechanical deformation of the external carton
• Changes in ambient room humidity only
• Changes in batch manufacturing throughput

Correct Answer: Changes in API potency, formation of new impurities, pH shifts or color/turbidity changes

Q17. How is a ‘container-closure system’ best defined in the context of pharmaceutical products?

• The combination of primary and secondary packaging plus the shipping carton only
• The totality of components and materials that together contain and protect the drug product, including primary container and closure
• Only the cap used to seal a bottle
• Any packaging used after the product is dispensed to the patient

Correct Answer: The totality of components and materials that together contain and protect the drug product, including primary container and closure

Q18. Which biological assay is applied to detect the presence of pyrogenic endotoxin activity in aqueous extracts from packaging materials?

• MTT cytotoxicity assay
• LAL (Limulus Amebocyte Lysate) assay
• Ames test
• ICP-MS

Correct Answer: LAL (Limulus Amebocyte Lysate) assay

Q19. Which sample preparation strategy is most appropriate for a thorough extractables study of polymeric packaging?

• Single extraction using deionized water at room temperature only
• Multiple extractions employing solvents of differing polarity, controlled temperatures and times (including aggressive conditions) to maximize recovery of diverse extractables
• Mechanical grinding of polymer without solvent extraction
• Only headspace analysis without solvent contact

Correct Answer: Multiple extractions employing solvents of differing polarity, controlled temperatures and times (including aggressive conditions) to maximize recovery of diverse extractables

Q20. When calculating patient exposure to a specific leachable, which pieces of information are required?

• Concentration of the leachable in the drug product, dosing frequency, and patient body weight or daily dose to estimate daily intake
• Only the packaging manufacturer name and lot number
• The color of the packaging and climatic zone where stored
• The expiry date of the drug product alone

Correct Answer: Concentration of the leachable in the drug product, dosing frequency, and patient body weight or daily dose to estimate daily intake

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