Critical Material Attributes (CMA) MCQs With Answer

Introduction

This set of MCQs on Critical Material Attributes (CMAs) is designed for M.Pharm students studying Pharmaceutical Manufacturing Technology. It focuses on how material properties of APIs and excipients influence critical quality attributes (CQAs) and overall product performance. Questions cover identification, measurement techniques, regulatory expectations under QbD, risk assessment, analytical methods (e.g., XRPD, DSC, laser diffraction), and practical control strategies. These items aim to deepen understanding of how CMAs such as particle size, polymorphism, moisture content, and flowability affect formulation development, scale-up, stability, and in-process control, preparing students for both academic exams and industry practice.

Q1. Which of the following best defines a Critical Material Attribute (CMA) in the context of pharmaceutical development?

• A material property that has no impact on product performance
• A material attribute that, when varied, can affect Critical Quality Attributes (CQAs) and patient safety
• A manufacturing parameter controlled only during regulatory inspection
• An attribute related solely to packaging materials

Correct Answer: A material attribute that, when varied, can affect Critical Quality Attributes (CQAs) and patient safety

Q2. Which analytical technique is most appropriate for quantifying crystallinity and detecting polymorphic forms of an API?

• Laser diffraction particle size analysis
• X-ray powder diffraction (XRPD)
• High performance liquid chromatography (HPLC)
• Karl Fischer titration

Correct Answer: X-ray powder diffraction (XRPD)

Q3. In risk assessment for CMAs, which tool is commonly used to prioritize material attributes based on severity, occurrence, and detectability?

• Design of Experiments (DoE)
• Failure Mode and Effects Analysis (FMEA)
• Thermogravimetric analysis (TGA)
• Fourier-transform infrared spectroscopy (FTIR)

Correct Answer: Failure Mode and Effects Analysis (FMEA)

Q4. Which CMA is most likely to directly influence tablet disintegration time and dissolution rate?

• Bulk density of the primary packaging
• API particle size distribution
• Color of the tablet coating
• Label font size

Correct Answer: API particle size distribution

Q5. Moisture content of an excipient is considered a CMA because:

• It only affects the visual appearance of the dosage form
• It can alter chemical stability, tablet hardness, and powder flow, impacting CQAs
• It has no effect on downstream processing
• It is irrelevant for solid oral dosage forms

Correct Answer: It can alter chemical stability, tablet hardness, and powder flow, impacting CQAs

Q6. Which PAT (Process Analytical Technology) tool is frequently used for real-time monitoring of particle size during milling?

• Near-infrared spectroscopy (NIR) for moisture only
• Focused Beam Reflectance Measurement (FBRM)
• Gas chromatography (GC)
• Ultraviolet-visible spectroscopy (UV-Vis)

Correct Answer: Focused Beam Reflectance Measurement (FBRM)

Q7. Polymorphism as a CMA is critical because different polymorphs can differ in:

• Regulatory classification only
• Solubility, dissolution rate, stability, and bioavailability
• Tablet color exclusively
• Container closure compatibility only

Correct Answer: Solubility, dissolution rate, stability, and bioavailability

Q8. Which measurement is most appropriate to assess powder flowability as a CMA during tablet manufacturing?

• Melting point determination
• Angle of repose and Carr’s index (compressibility)
• pH measurement
• Optical rotation

Correct Answer: Angle of repose and Carr’s index (compressibility)

Q9. During formulation development, a CMA demonstrating high variability batch-to-batch should prompt:

• Ignoring the attribute if the final product passes release tests
• Investigation, tighter incoming material specifications, and control strategies
• Immediate market recall without investigation
• Changing brand name of the product

Correct Answer: Investigation, tighter incoming material specifications, and control strategies

Q10. Which thermal technique is commonly used to detect melting points, polymorphic transitions, and glass transition temperatures relevant to CMAs?

• Dissolution testing
• Differential scanning calorimetry (DSC)
• Laser diffraction
• Karl Fischer titration

Correct Answer: Differential scanning calorimetry (DSC)

Q11. In a QbD framework, how are CMAs typically used within a Design Space?

• CMAs are ignored when defining Design Space
• CMAs are inputs evaluated to determine acceptable ranges that ensure CQAs within specification
• Design Space only considers equipment variables, not material properties
• CMAs are only used for labeling decisions

Correct Answer: CMAs are inputs evaluated to determine acceptable ranges that ensure CQAs within specification

Q12. Which of the following is NOT typically considered when designating an attribute as a CMA?

• The attribute’s potential impact on safety and efficacy
• Availability of a routine analytical method to measure the attribute
• Whether the attribute changes tablet color
• Observed correlation between attribute variability and CQA failure modes

Correct Answer: Whether the attribute changes tablet color

Q13. Why is particle size distribution of an excipient like microcrystalline cellulose considered a CMA in tableting?

• It only affects the taste of the tablet
• It influences compactibility, porosity, and content uniformity
• It determines the pharmaceutical company’s profit margin
• It is irrelevant for granulation and compression

Correct Answer: It influences compactibility, porosity, and content uniformity

Q14. Which technique is most suitable for accurate low-level moisture determination of hygroscopic APIs?

• Laser diffraction
• Karl Fischer titration
• UV-Vis spectrophotometry
• X-ray powder diffraction

Correct Answer: Karl Fischer titration

Q15. A CMA may require a control strategy. Which of the following is an example of such a strategy?

• Conducting no testing and assuming consistency
• Setting acceptance specifications, incoming material testing, and supplier qualification
• Relying only on final product testing to detect issues
• Changing the dosage form without analysis

Correct Answer: Setting acceptance specifications, incoming material testing, and supplier qualification

Q16. Which instrument provides rapid, non-destructive analysis of chemical composition and is used as PAT for blend uniformity monitoring?

• Thermogravimetric analysis (TGA)
• Near-infrared spectroscopy (NIR)
• Laser diffraction
• Differential scanning calorimetry (DSC)

Correct Answer: Near-infrared spectroscopy (NIR)

Q17. Bulk and tapped density as CMAs are primarily used to predict which downstream property?

• API chemical structure
• Powder flow and tablet weight variation
• Melting point of the excipient
• Color stability under light

Correct Answer: Powder flow and tablet weight variation

Q18. Which CMA is most directly related to the potential for content uniformity failure in low-dose tablets?

• Coating gloss
• API segregative tendency due to particle size and density differences
• Label artwork complexity
• Tablet packaging material thickness

Correct Answer: API segregative tendency due to particle size and density differences

Q19. Which statement about setting specification limits for a CMA is correct?

• Specification limits for CMAs are arbitrary and not linked to CQAs
• Limits should be science-based, derived from risk assessment, DoE, and clinical impact
• Wider limits are always preferred to reduce rejections
• Once set, CMA limits never need re-evaluation

Correct Answer: Limits should be science-based, derived from risk assessment, DoE, and clinical impact

Q20. During scale-up, a previously non-critical material attribute becomes critical. The appropriate response is to:

• Ignore it because initial studies showed it was non-critical
• Perform root cause assessment, update risk assessment, and implement additional controls and testing
• Stop production permanently
• Change the active ingredient

Correct Answer: Perform root cause assessment, update risk assessment, and implement additional controls and testing

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