Design space and risk assessment MCQs With Answer

Introduction:

This collection of MCQs on Design Space and Risk Assessment is tailored for M.Pharm students preparing for advanced coursework and exams in Pharmaceutical Manufacturing Technology. The questions emphasize regulatory concepts such as ICH Q8/Q9/Q10, the establishment and application of design space, identification of Critical Quality Attributes (CQAs) and Critical Process Parameters (CPPs), and quantitative and qualitative risk assessment tools (FMEA, Ishikawa, DoE, PAT). Each item tests conceptual understanding, practical implications for process development and control strategy, and the linkage between experimental design and regulatory flexibility. Use these MCQs to deepen your analytical skills for robust process design, scale-up decisions, and lifecycle management of pharmaceutical processes.

Q1. What does the term “design space” represent under ICH Q8(R2)?

• The set of predefined acceptable manufacturing sites for a product
• The multidimensional combination and interaction of input variables and process parameters that have been demonstrated to provide assurance of quality
• A fixed range of batch sizes for validated processes
• The documented stability limits for the final drug product

Correct Answer: The multidimensional combination and interaction of input variables and process parameters that have been demonstrated to provide assurance of quality

Q2. Which of the following best describes a Critical Quality Attribute (CQA)?

• A process parameter that can be measured easily during manufacturing
• A physical, chemical, biological or microbiological property that should be within an appropriate limit to ensure product quality
• A regulatory document required for product registration
• A statistical tool used in Design of Experiments

Correct Answer: A physical, chemical, biological or microbiological property that should be within an appropriate limit to ensure product quality

Q3. Which risk assessment method assigns numeric scores to severity, probability, and detectability to prioritize risks?

• Ishikawa (Fishbone) Diagram
• Failure Mode and Effects Analysis (FMEA)
• Process Flow Diagram (PFD)
• Root Cause Analysis (RCA)

Correct Answer: Failure Mode and Effects Analysis (FMEA)

Q4. In the context of design space development, what role does Design of Experiments (DoE) primarily play?

• It documents the regulatory submission content
• It enables systematic exploration of factor effects and interactions on CQAs to build predictive models
• It replaces the need for any process validation
• It sets the final packaging specifications

Correct Answer: It enables systematic exploration of factor effects and interactions on CQAs to build predictive models

Q5. Which statement about movement within an approved design space is correct?

• Any movement within the design space is considered a regulatory change requiring prior approval
• Movement within an approved design space is generally not considered a change and does not require prior regulatory approval
• Movement is allowed only for scale-up but not for parameter adjustment
• Movement within design space is prohibited after initial approval

Correct Answer: Movement within an approved design space is generally not considered a change and does not require prior regulatory approval

Q6. What is the Proven Acceptable Range (PAR) in process validation terminology?

• A statistically derived wide range of values without connection to product quality
• A narrower range of process parameters justified by data during validation that ensures consistent product quality
• A theoretical limit imposed by equipment manufacturer
• The maximum allowable impurity concentration in the finished product

Correct Answer: A narrower range of process parameters justified by data during validation that ensures consistent product quality

Q7. Which parameter is most likely to be considered a Critical Process Parameter (CPP)?

• Color of the outer carton
• Compression force that affects tablet hardness and dissolution
• Invoice number used for shipping
• Office room temperature in administrative areas

Correct Answer: Compression force that affects tablet hardness and dissolution

Q8. Which tool is most appropriate for visualizing potential root causes of a quality problem in a process flow?

• Kaplan-Meier plot
• Ishikawa (Fishbone) Diagram
• ANOVA table
• Pareto chart

Correct Answer: Ishikawa (Fishbone) Diagram

Q9. In FMEA, the Risk Priority Number (RPN) is calculated by multiplying which three factors?

• Frequency, Duration, and Cost
• Severity, Occurrence (probability), and Detectability
• Accuracy, Precision, and Stability
• Yield, Throughput, and Efficiency

Correct Answer: Severity, Occurrence (probability), and Detectability

Q10. Which of the following best describes a control strategy in the context of design space and lifecycle management?

• A list of vendors approved to supply raw materials
• A planned set of controls, derived from product and process understanding, that ensures process performance and product quality
• A static document used only during regulatory inspections
• A marketing strategy for new product launch

Correct Answer: A planned set of controls, derived from product and process understanding, that ensures process performance and product quality

Q11. How does Process Analytical Technology (PAT) integrate with design space concepts?

• PAT is only used for final product testing and is unrelated to design space
• PAT provides real-time or near-real-time measurements that support control of CPPs and enable operation within the design space
• PAT obligates manufacturers to halt processes when any variation occurs
• PAT replaces the need for any raw material testing

Correct Answer: PAT provides real-time or near-real-time measurements that support control of CPPs and enable operation within the design space

Q12. Which statistical output from a DoE is most useful for visualizing the relationship between two factors and one response?

• Survival curve
• Contour plot (response surface)
• Boxplot of residuals only
• Time series chart

Correct Answer: Contour plot (response surface)

Q13. During scale-up, which risk is specifically important to assess when moving from lab to pilot to commercial scale?

• Changes in branding and labeling
• Scale-dependent changes in mixing, heat transfer, or mass transfer that affect CQAs
• Employee turnover in quality assurance
• Office ergonomics in the development lab

Correct Answer: Scale-dependent changes in mixing, heat transfer, or mass transfer that affect CQAs

Q14. What does a high detectability score in FMEA indicate?

• The failure mode is easy to detect before it reaches the customer
• The failure mode is difficult to detect with current controls
• The failure mode has low severity
• The failure mode has high occurrence but is benign

Correct Answer: The failure mode is difficult to detect with current controls

Q15. Which approach provides a probabilistic assessment of risk by simulating parameter variability and its effect on CQAs?

• Deterministic mass balance
• Monte Carlo simulation
• Simple linear regression without variability
• Qualitative brainstorming only

Correct Answer: Monte Carlo simulation

Q16. What is the difference between “design space” and “proven acceptable range (PAR)”?

• Design space is a regulatory concept; PAR has no regulatory relevance
• Design space may be multidimensional and allow flexibility; PAR is a validated single-parameter range within which the process has been proven to produce acceptable quality
• They are identical concepts used interchangeably
• PAR refers to packaging dimensions while design space refers to manufacturing sites

Correct Answer: Design space may be multidimensional and allow flexibility; PAR is a validated single-parameter range within which the process has been proven to produce acceptable quality

Q17. Which activity is essential for demonstrating control strategy effectiveness throughout the product lifecycle?

• One-time process validation only
• Ongoing monitoring, trending, and periodic review (continual improvement)
• Exclusive reliance on vendor quality certificates
• Changing specifications annually without data

Correct Answer: Ongoing monitoring, trending, and periodic review (continual improvement)

Q18. In a DoE for tablet formulation, a significant interaction between binder level and granulation time means:

• Each factor affects the response independently and their combined effect is additive
• The effect of binder level on a CQA depends on the granulation time, so both must be considered together in the design space
• Granulation time can be ignored during optimization
• The DoE is invalid and must be discarded

Correct Answer: The effect of binder level on a CQA depends on the granulation time, so both must be considered together in the design space

Q19. Which regulatory documents are most directly related to integrating design space and risk assessment into pharmaceutical development?

• ICH Q1A (Stability), ICH Q3A (Impurities)
• ICH Q8 (Pharmaceutical Development), ICH Q9 (Quality Risk Management), and ICH Q10 (Pharmaceutical Quality System)
• Pharmacopoeial monographs only
• Good Laboratory Practice (GLP) guidelines only

Correct Answer: ICH Q8 (Pharmaceutical Development), ICH Q9 (Quality Risk Management), and ICH Q10 (Pharmaceutical Quality System)

Q20. Which of the following is a key benefit of establishing a design space for a manufacturing process?

• Guaranteed elimination of all deviations and batch failures
• Regulatory flexibility to make adjustments within the space without prior approval and improved understanding of process robustness
• Replacement of quality control testing entirely
• Reduction of product shelf-life requirements

Correct Answer: Regulatory flexibility to make adjustments within the space without prior approval and improved understanding of process robustness

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