Process Chemistry: synthetic strategy and stages of scale-up MCQs With Answer

Introduction: This quiz collection on Process Chemistry: synthetic strategy and stages of scale-up is tailored for M.Pharm students to strengthen practical and conceptual understanding required in pharmaceutical process development. It covers route selection, convergent vs linear approaches, impurity control, safety and hazard evaluation, solvent and reagent choices, process optimization, and the critical stages of lab-to-pilot-to-plant scale-up. Questions integrate mechanistic, operational and regulatory considerations — including heat and mass transfer, mixing, telescoping, crystallization, PAT, and environmental impact — to prepare students for real-world decision-making in process chemistry. Use these MCQs to assess readiness for design, troubleshooting, and risk-managed scale-up of APIs.

Q1. Which factor is most critical when selecting a synthetic route for late-stage pharmaceutical process development?

• Maximum number of steps irrespective of yields
• Lowest cost of starting materials only
• Overall route robustness, impurity profile and scalability
• Use of the most modern reaction regardless of safety

Correct Answer: Overall route robustness, impurity profile and scalability

Q2. Convergent synthesis is often preferred over linear synthesis because:

• It always reduces the number of purification steps
• It allows parallel preparation of fragments, improving overall yield and time
• It eliminates the need for protecting groups
• It guarantees avoidance of any impurities

Correct Answer: It allows parallel preparation of fragments, improving overall yield and time

Q3. During scale-up, which heat transfer parameter typically becomes most challenging for highly exothermic reactions?

• Thermal conductivity of the final API
• Surface area to volume ratio decreasing and limiting heat removal
• Viscosity decreasing with scale
• Increase in reagent purity

Correct Answer: Surface area to volume ratio decreasing and limiting heat removal

Q4. What is the primary purpose of reaction calorimetry at lab and pilot scales?

• To measure the molecular weight of reactants
• To determine the caloric intake of operators
• To quantify heat release, characterise thermal profile and assess runaway risk
• To calculate final product solubility only

Correct Answer: To quantify heat release, characterise thermal profile and assess runaway risk

Q5. Telescoping in process chemistry refers to:

• Using a tall reactor to improve mixing
• Performing multiple reaction steps in one reactor without isolation of intermediates
• Scaling a reaction by increasing the number of operators
• Switching solvents between every step to improve yield

Correct Answer: Performing multiple reaction steps in one reactor without isolation of intermediates

Q6. Which solvent selection criterion is most aligned with green chemistry principles for process development?

• Lowest solvent boiling point irrespective of toxicity
• Solvent with the best aesthetic properties
• Lowest toxicity, recyclability and minimal environmental impact
• Most expensive solvent to ensure purity

Correct Answer: Lowest toxicity, recyclability and minimal environmental impact

Q7. In impurity control strategy, the term “specified impurity” usually refers to:

• Any impurity below 10% w/w
• Impurities that are toxic irrespective of level
• Impurities that must be identified, quantified and limited by regulatory guidelines
• Only inorganic salts formed during workup

Correct Answer: Impurities that must be identified, quantified and limited by regulatory guidelines

Q8. Which change is most likely to affect mixing efficiency when scaling a reaction from lab to pilot plant?

• Reduction in catalyst concentration
• Geometric similarity of stirrer and vessel ensuring identical Reynolds number
• Increase in viscosity and larger vessel diameter altering flow regimes
• Using the same stirrer rpm regardless of scale

Correct Answer: Increase in viscosity and larger vessel diameter altering flow regimes

Q9. Process Analytical Technology (PAT) is primarily used to:

• Replace all offline analytical tests
• Provide real-time monitoring and control to ensure consistent product quality
• Increase the regulatory burden without operational benefit
• Only measure final product assay

Correct Answer: Provide real-time monitoring and control to ensure consistent product quality

Q10. Which of the following best describes a critical quality attribute (CQA) in process chemistry?

• A manufacturing schedule parameter
• A property that must be maintained within limits to ensure product quality, such as purity or particle size
• Any attribute that changes daily
• An attribute related only to packaging aesthetics

Correct Answer: A property that must be maintained within limits to ensure product quality, such as purity or particle size

Q11. Which hazard evaluation tool is commonly applied in early-stage process safety to identify potential failure modes?

• GMP audit checklist
• HPLC method validation
• HAZOP (Hazard and Operability study) or preliminary process hazard analysis (PHA)
• Marketing risk assessment

Correct Answer: HAZOP (Hazard and Operability study) or preliminary process hazard analysis (PHA)

Q12. When moving from batch to continuous flow for a hazardous exothermic reaction, a primary advantage is:

• Unlimited residence time guaranteeing higher impurity formation
• Improved heat transfer and safer handling of small reaction volumes
• Increased operator exposure due to manual transfers
• Reduced need for analytics

Correct Answer: Improved heat transfer and safer handling of small reaction volumes

Q13. Which crystallization parameter most directly impacts final particle size distribution in scale-up?

• Color of the solvent
• Cooling rate and supersaturation profile
• Number of operators present
• Molecular weight of impurities only

Correct Answer: Cooling rate and supersaturation profile

Q14. A key objective of impurity profiling during development is to:

• Ignore genotoxic impurities until commercialization
• Identify, quantify, determine origin and control impurities throughout the process
• Replace analytical methods with theoretical predictions only
• Limit testing to final API without studying intermediates

Correct Answer: Identify, quantify, determine origin and control impurities throughout the process

Q15. Which metric best indicates process efficiency when comparing two synthetic routes?

• Number of academic references cited
• Process mass intensity (PMI) and overall isolated yield combined with impurity burden
• Only the lowest reaction temperature used
• Length of the patent document

Correct Answer: Process mass intensity (PMI) and overall isolated yield combined with impurity burden

Q16. What is the main role of a pilot plant in the stages of scale-up?

• To conduct full commercial production without documentation
• To validate process conditions, gather engineering data, demonstrate reproducibility and identify scale-dependent issues
• To market the product before regulatory approval
• To eliminate the need for process validation at commercial scale

Correct Answer: To validate process conditions, gather engineering data, demonstrate reproducibility and identify scale-dependent issues

Q17. Which of the following is a common control strategy to manage runaway risk for an exothermic step?

• Omitting cooling systems to force slower reactions
• Implementing automated quench systems, dilution, and interlocks based on calorimetry data
• Increasing reactant feed rate without monitoring
• Relying solely on operator visual checks

Correct Answer: Implementing automated quench systems, dilution, and interlocks based on calorimetry data

Q18. Polymorphism control is important because different polymorphs can affect:

• Only the color of the tablet film
• Dissolution rate, bioavailability, stability and manufacturability
• Regulatory classification but not performance
• Only the smell of the API

Correct Answer: Dissolution rate, bioavailability, stability and manufacturability

Q19. Which approach helps reduce formation of impurities during a multi-step scale-up?

• Increasing reaction concentration without studying side reactions
• Designing robust chemistry: choosing selective reagents, controlling temperature, stoichiometry and using in-process controls
• Skipping workup steps to save time
• Always using stronger acids to speed reactions

Correct Answer: Designing robust chemistry: choosing selective reagents, controlling temperature, stoichiometry and using in-process controls

Q20. In regulatory submissions, demonstrating control of the manufacturing process typically requires:

• Only a single batch record from lab scale
• Comprehensive data on reproducibility, critical parameters, impurity control, validation batches and change control history
• Proof that the process was invented by a named scientist
• Only marketing claims about yield improvement

Correct Answer: Comprehensive data on reproducibility, critical parameters, impurity control, validation batches and change control history

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