Process Validation – Granulation MCQs With Answer

Introduction: Process validation for granulation is a critical component of pharmaceutical scale-up and technology transfer. This blog presents focused MCQs to help M.Pharm students understand the principles, regulatory expectations, and practical control strategies for wet and dry granulation. Emphasis is placed on identifying critical process parameters (CPPs) and critical quality attributes (CQAs), applying design of experiments (DoE), using PAT tools for end-point detection, and translating lab-scale knowledge to commercial scale while ensuring robustness and product quality. These questions are designed to deepen conceptual understanding and prepare students for real-world validation activities and regulatory scrutiny.

Q1. Which of the following best describes the primary objective of process validation in granulation?

• To demonstrate consistent production of granules meeting predefined quality attributes
• To minimize raw material costs during granulation
• To increase equipment throughput irrespective of quality
• To establish a fixed manufacturing schedule without changes

Correct Answer: To demonstrate consistent production of granules meeting predefined quality attributes

Q2. Which parameter is commonly considered a Critical Quality Attribute (CQA) for granules used in tablet compression?

• Granule particle size distribution (PSD)
• Color of the packaging material
• Ambient humidity of the administrative office
• Manufacturer’s logo on the hopper

Correct Answer: Granule particle size distribution (PSD)

Q3. During wet granulation, which process parameter most directly influences granule growth and consolidation?

• Binder solution addition rate and total liquid-to-solid ratio
• Tablet coating pan rotation speed
• Final packaging method
• Ambient lab lighting

Correct Answer: Binder solution addition rate and total liquid-to-solid ratio

Q4. Which PAT (Process Analytical Technology) tool is frequently used for real-time monitoring of moisture and end-point in wet granulation?

• Near-infrared spectroscopy (NIR)
• UV-visible spectrophotometer
• Atomic absorption spectroscopy
• X-ray diffractometer

Correct Answer: Near-infrared spectroscopy (NIR)

Q5. For scale-up of a high-shear wet granulation process, which similarity criterion addresses the balance between gravitational and inertial forces?

• Froude number similarity
• Reynolds number similarity for laminar flow
• Arrhenius activation energy equivalence
• Henry’s law constant matching

Correct Answer: Froude number similarity

Q6. In roller compaction (dry granulation), which parameter is most critical for controlling ribbon density and subsequent granule properties?

• Roll pressure (compaction force)
• Spray drying inlet temperature
• Granulation solvent pH
• Tablet coating thickness

Correct Answer: Roll pressure (compaction force)

Q7. Which experimental approach is most appropriate to identify critical process parameters and develop a design space for granulation?

• Design of experiments (DoE) with multivariate analysis
• Single-run one-factor-at-a-time testing only
• Arbitrary process changes during commercial production
• Visual inspection without data collection

Correct Answer: Design of experiments (DoE) with multivariate analysis

Q8. Which granule attribute is directly related to the compressibility and tablet tensile strength?

• Granule porosity and bulk/tapped density
• Printer font used on the label
• Ambient office temperature
• Batch numbering system

Correct Answer: Granule porosity and bulk/tapped density

Q9. For a validated granulation process, which metric indicates short-term process capability with respect to specification limits?

• Cpk (process capability index)
• LOD (limit of detection)
• MIC (minimum inhibitory concentration)
• pH of the granulation liquid

Correct Answer: Cpk (process capability index)

Q10. Which in-process control is most useful to determine wet granulation end-point when using a high-shear mixer?

• Torque/power consumption profile of the impeller
• Final product lot number
• Operator’s subjective feel only
• Color of the mixer lid

Correct Answer: Torque/power consumption profile of the impeller

Q11. When transferring a wet granulation process from lab to pilot scale, which change is LEAST likely to be linearly scalable?

• Granule mixing dynamics due to equipment geometry
• Binder solution chemical composition
• Solubility of API in binder
• Target particle size for downstream compression

Correct Answer: Granule mixing dynamics due to equipment geometry

Q12. Which quality attribute should be monitored to control risk of over-wetted granules leading to downstream processing problems?

• Loss on drying (residual moisture) of granules
• Tablet color uniformity
• Barcode readability
• Room lighting intensity

Correct Answer: Loss on drying (residual moisture) of granules

Q13. In granulation validation, what is the primary purpose of a robustness study?

• To determine the effect of small, deliberate variations in CPPs on CQAs
• To reduce raw material testing
• To speed up validation by skipping small-scale trials
• To test commercial packaging equipment only

Correct Answer: To determine the effect of small, deliberate variations in CPPs on CQAs

Q14. Which statement about granule particle size distribution (PSD) is TRUE with respect to tablet performance?

• Narrow PSD with appropriate mean size improves content uniformity and flow
• Very broad PSD always enhances tablet tensile strength
• PSD does not impact dissolution or bioavailability
• Smaller mean size always improves flowability

Correct Answer: Narrow PSD with appropriate mean size improves content uniformity and flow

Q15. During validation, which sampling approach provides representative assessment of granule properties in a batch?

• Stratified sampling across multiple locations and times during the batch
• Single grab sample from one location
• Sampling only the first and last gram produced
• Sampling outside the production area

Correct Answer: Stratified sampling across multiple locations and times during the batch

Q16. Which design space concept allows approved operable ranges for CPPs without regulatory re-approval as long as movement remains within the space?

• Design space as defined by QbD (Quality by Design)
• Fixed single set-point control only
• Ad hoc process changes without documentation
• Uncontrolled process drift

Correct Answer: Design space as defined by QbD (Quality by Design)

Q17. Which of the following is a commonly used end-point indicator in fluid-bed granulation?

• Outlet air humidity and product temperature profile
• Tablet hardness measurement during granulation
• UV absorbance of the mixer lid
• Buffer capacity of the formulation

Correct Answer: Outlet air humidity and product temperature profile

Q18. For validation documentation of a granulation process, which element is essential to demonstrate reproducibility?

• Multiple consecutive successful batches with demonstrated CQA compliance
• Single successful lab-scale experiment only
• Operator testimonials without data
• Photographs of equipment only

Correct Answer: Multiple consecutive successful batches with demonstrated CQA compliance

Q19. Which formulation factor most influences the granule friability and robustness during handling?

• Binder type and concentration
• Colorant selection for the tablet coating
• Supplier logo on the raw material bag
• Shape of the manufacturing building

Correct Answer: Binder type and concentration

Q20. When conducting scale-up verification, which outcome would most strongly indicate successful scale translation of granulation?

• Key CQAs (PSD, moisture, compressibility) remain within target ranges and tablet performance is equivalent
• Visual appearance of granules looks similar only
• Cycle time increases significantly without assessing quality
• Operator notes that the process “feels” the same

Correct Answer: Key CQAs (PSD, moisture, compressibility) remain within target ranges and tablet performance is equivalent

Download