Introduction to biopharmaceutical considerations MCQs With Answer

Introduction: This quiz set on Introduction to Biopharmaceutical Considerations is designed for M.Pharm students to reinforce core concepts that underlie the development, evaluation, and clinical use of biopharmaceuticals. Questions focus on pharmacokinetics and pharmacodynamics of biologics, stability and degradation pathways, formulation and excipient selection, immunogenicity, analytical and bioassay considerations, biosimilarity assessment, and regulatory quality attributes. Each item challenges you to apply theoretical knowledge to practical scenarios encountered in modern bio-analytical and formulation development. Use these MCQs to test comprehension, identify knowledge gaps, and prepare for exams or research tasks in biopharmaceutical development.

Q1. Which property most directly distinguishes biopharmaceuticals from small-molecule drugs?

• Molecular complexity and large molecular weight
• Lower cost of production
• Greater metabolic stability in all cases
• Complete oral bioavailability

Correct Answer: Molecular complexity and large molecular weight

Q2. Which of the following is a primary mechanism contributing to loss of potency in therapeutic proteins during storage?

• Hydrolysis of polymer backbone
• Protein aggregation
• Ionization of small-molecule contaminants
• Vaporization of excipients

Correct Answer: Protein aggregation

Q3. In the context of biologics, which critical quality attribute (CQA) most directly affects immunogenicity risk?

• pH of the formulation buffer
• Glycosylation pattern and sequence variants
• Container color
• Inert gas headspace volume

Correct Answer: Glycosylation pattern and sequence variants

Q4. Which analytical approach is best suited for quantifying functional activity of a monoclonal antibody?

• Size-exclusion chromatography (SEC)
• Cell-based potency bioassay
• UV spectrophotometry at 280 nm
• Dynamic light scattering (DLS)

Correct Answer: Cell-based potency bioassay

Q5. What is the main purpose of performing forced-degradation studies on a biopharmaceutical candidate?

• To find the cheapest excipient
• To identify likely degradation pathways and degradation products
• To test patient adherence under real-world conditions
• To maximize protein expression yield in cell culture

Correct Answer: To identify likely degradation pathways and degradation products

Q6. Which factor most strongly limits the oral delivery of therapeutic proteins?

• Low receptor affinity in the gut
• Enzymatic degradation and poor permeability across intestinal epithelium
• Excessive solubility
• High lipophilicity

Correct Answer: Enzymatic degradation and poor permeability across intestinal epithelium

Q7. What is the principal advantage of pegylation of a therapeutic protein?

• Increases immunogenicity
• Reduces molecular weight
• Prolongs systemic circulation and reduces renal clearance
• Makes the protein more acidic

Correct Answer: Prolongs systemic circulation and reduces renal clearance

Q8. Which storage recommendation is typically critical for most monoclonal antibody products?

• Storage at room temperature for 6 months
• Storage refrigerated at 2–8 °C and protection from freeze–thaw cycles
• Storage in direct sunlight to prevent aggregation
• Frequent agitation to maintain homogeneity

Correct Answer: Storage refrigerated at 2–8 °C and protection from freeze–thaw cycles

Q9. In biosimilar development, the most important evidence to demonstrate similarity to the reference product is:

• Identical manufacturing site
• Comprehensive analytical comparability including structural and functional characterization
• Same brand name
• Using an identical cell line as originator

Correct Answer: Comprehensive analytical comparability including structural and functional characterization

Q10. Which excipient is commonly used to stabilize proteins by preventing surface adsorption and aggregation?

• Sodium chloride at 5 M concentration
• Non-ionic surfactants such as polysorbate 20 or polysorbate 80
• Strong acids like hydrochloric acid
• Semi-volatile organic solvents

Correct Answer: Non-ionic surfactants such as polysorbate 20 or polysorbate 80

Q11. What does the term “immunogenicity” refer to in the context of protein therapeutics?

• Ability of a drug to penetrate the blood–brain barrier
• Likelihood of eliciting an undesirable immune response such as anti-drug antibodies
• Rate of enzymatic degradation in vitro
• Capacity to increase plasma viscosity

Correct Answer: Likelihood of eliciting an undesirable immune response such as anti-drug antibodies

Q12. Which degradation pathway is commonly promoted by exposure to light in proteins?

• Photodegradation leading to oxidation of susceptible amino acids like tryptophan and methionine
• Complete peptide bond hydrolysis within seconds
• Spontaneous glycosylation
• Polymerization into polysaccharide chains

Correct Answer: Photodegradation leading to oxidation of susceptible amino acids like tryptophan and methionine

Q13. For biologics, which pharmacokinetic parameter is most often prolonged relative to small molecules and is a key design consideration?

• Renal clearance due to glomerular filtration
• Volume of distribution approaching total body water
• Terminal half-life due to recycling via FcRn (neonatal Fc receptor)
• First-pass hepatic extraction

Correct Answer: Terminal half-life due to recycling via FcRn (neonatal Fc receptor)

Q14. Which in vitro test is most appropriate to monitor size variants (monomer/aggregate distribution) in a protein formulation?

• Reverse-phase HPLC
• Size-exclusion chromatography (SEC)
• pH titration curve
• Mass spectrometry for small ions

Correct Answer: Size-exclusion chromatography (SEC)

Q15. What role does glycosylation play in therapeutic antibodies?

• Has no effect on function or half-life
• Influences stability, effector functions, and pharmacokinetics
• Always leads to immediate degradation
• Makes antibodies fluorescent for imaging

Correct Answer: Influences stability, effector functions, and pharmacokinetics

Q16. Which manufacturing parameter is considered a Critical Process Parameter (CPP) for biologic product quality?

• Color of the operator’s gloves
• Cell culture temperature and pH during recombinant protein expression
• Brand of laboratory notebooks used
• Ambient office lighting

Correct Answer: Cell culture temperature and pH during recombinant protein expression

Q17. An in vitro–in vivo correlation (IVIVC) for a biologic is challenging because:

• Biologics always have immediate and predictable absorption
• Biologic activity depends on complex folding, post-translational modifications, and host interactions that are hard to model in vitro
• Small-molecule dissolution tests are identical to biologic assays
• There is no need to correlate since biologics are always injected

Correct Answer: Biologic activity depends on complex folding, post-translational modifications, and host interactions that are hard to model in vitro

Q18. Which assay format is most suitable for detecting anti-drug antibodies in patient serum samples?

• Competitive binding ELISA or bridging immunoassay
• Gas chromatography–mass spectrometry (GC-MS)
• Colorimetric pH paper test
• Thermogravimetric analysis

Correct Answer: Competitive binding ELISA or bridging immunoassay

Q19. Why are low endotoxin limits critical in biologic formulations?

• Endotoxins act as stabilizers for proteins
• Endotoxins can trigger severe pyrogenic and inflammatory responses in patients
• Endotoxins increase product potency
• Endotoxin presence improves shelf-life

Correct Answer: Endotoxins can trigger severe pyrogenic and inflammatory responses in patients

Q20. Which regulatory concept emphasizes identification and control of sources of variability in biologic manufacturing to ensure consistent product quality?

• Good Laboratory Practice (GLP) only
• Quality by Design (QbD)
• Patent exclusivity
• Advertising guidelines

Correct Answer: Quality by Design (QbD)

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