Biosimilar drug products (generic biologics) MCQs With Answer

Biosimilar drug products (generic biologics) MCQs With Answer

Introduction: This quiz collection is designed for M.Pharm students preparing in Modern Bio-Analytical Techniques (MPA 202T) to deepen understanding of biosimilar drug products. It focuses on analytical, functional and regulatory aspects crucial to establishing biosimilarity — including comparability strategies, critical quality attributes, higher-order structure, glycosylation, aggregation, host-cell impurities, potency and immunogenicity assessments, and regulatory expectations like extrapolation and interchangeability. Questions emphasize real-world analytical methods (LC-MS, HILIC, CD, DSC, SEC, cell-based assays), statistical similarity approaches and study design considerations. Use these MCQs to test and strengthen your ability to critically evaluate similarity dossiers and design robust analytical programs for biosimilars.

Q1. What is the defining regulatory concept of a biosimilar product?

• A biologic that is chemically identical to the reference product and manufactured by the same process
• A biologic that is highly similar to a reference product with no clinically meaningful differences in safety, purity, and potency
• A small-molecule generic made by a different manufacturer but with the same active moiety
• A therapeutic protein with the exact same excipients and container closure as the reference

Correct Answer: A biologic that is highly similar to a reference product with no clinically meaningful differences in safety, purity, and potency

Q2. Which regulatory approach is central to modern biosimilar development across major agencies (EMA, FDA, WHO)?

• Full de novo clinical development identical to originator biologics
• Stepwise comparability using analytical, nonclinical and targeted clinical studies guided by totality of evidence
• Approval solely on the basis of identical primary sequence without any functional testing
• Approval after single-arm safety studies only

Correct Answer: Stepwise comparability using analytical, nonclinical and targeted clinical studies guided by totality of evidence

Q3. Which analytical technique is most definitive for confirming the primary amino acid sequence of a therapeutic protein?

• Size-exclusion chromatography (SEC)
• Peptide mapping by liquid chromatography-mass spectrometry (LC-MS)
• Circular dichroism (CD)
• Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)

Correct Answer: Peptide mapping by liquid chromatography-mass spectrometry (LC-MS)

Q4. Which critical quality attribute (CQA) most directly influences pharmacokinetics and potential immunogenicity of glycoprotein biologics?

• Primary amino acid sequence
• Glycan structure and site-specific glycosylation profile
• Residual host cell DNA
• Viscosity of the formulation

Correct Answer: Glycan structure and site-specific glycosylation profile

Q5. Which pair of techniques is most appropriate to assess higher-order structure (HOS) of a monoclonal antibody?

• HILIC-UPLC and MALDI-TOF MS
• Circular dichroism (CD) and differential scanning calorimetry (DSC)
• ELISA and cell-based bioassay
• SEC and capillary isoelectric focusing (cIEF)

Correct Answer: Circular dichroism (CD) and differential scanning calorimetry (DSC)

Q6. Which analytical methods are most commonly used and complementary to detect and characterize protein aggregates?

• HPLC peptide mapping and glycan mapping
• Size-exclusion chromatography (SEC) and analytical ultracentrifugation (AUC)
• qPCR and host cell protein ELISA
• HILIC glycan profiling and MALDI imaging

Correct Answer: Size-exclusion chromatography (SEC) and analytical ultracentrifugation (AUC)

Q7. For a monoclonal antibody biosimilar, which assay type best demonstrates retained biological function relevant to efficacy?

• Antigen-binding ELISA only
• Cell-based functional bioassays that measure mechanism-specific activity (e.g., ADCC, receptor signaling)
• SDS-PAGE under reducing conditions
• Measurement of total protein by UV absorbance

Correct Answer: Cell-based functional bioassays that measure mechanism-specific activity (e.g., ADCC, receptor signaling)

Q8. What statistical or analytical principle underlies acceptance of similarity between biosimilar and reference product?

• Assertion of identical manufacturing process is sufficient
• Equivalence or non-inferiority testing guided by predefined acceptance criteria and orthogonal analytical methods (totality of evidence)
• Only clinical outcomes decide similarity without analytical data
• Qualitative similarity without quantitative metrics is accepted

Correct Answer: Equivalence or non-inferiority testing guided by predefined acceptance criteria and orthogonal analytical methods (totality of evidence)

Q9. Which justification is required to support extrapolation of indications from the reference product to a biosimilar?

• Only identical excipients must be proven
• Scientific rationale including mechanism of action, receptor expression, PK/PD and immunogenicity across indications
• Approval in one indication automatically grants all other indications
• Demonstration of identical packaging prevents need for extrapolation data

Correct Answer: Scientific rationale including mechanism of action, receptor expression, PK/PD and immunogenicity across indications

Q10. Which statement best describes the U.S. FDA interchangeability designation for biosimilars?

• Interchangeability is automatically granted to any approved biosimilar
• Interchangeability requires additional switching studies demonstrating no increased risk after alternating between products
• Interchangeability is unrelated to switching or substitution at pharmacy level
• Interchangeability only applies to small-molecule generics

Correct Answer: Interchangeability requires additional switching studies demonstrating no increased risk after alternating between products

Q11. Which analytical strategy is ideal for detection and identification of residual host-cell proteins (HCPs)?

• Total nitrogen assay only
• HCP-specific ELISA for quantitation and LC-MS/MS for identification of individual HCP species
• Glycan analysis by HILIC
• Peptide mapping without enrichment

Correct Answer: HCP-specific ELISA for quantitation and LC-MS/MS for identification of individual HCP species

Q12. Which technique combination is most appropriate for in-depth glycan profiling of a monoclonal antibody?

• Capillary electrophoresis (CE) and SDS-PAGE
• HILIC-UPLC of fluorescently labeled glycans combined with MS for structural assignment
• SEC-MALS and refractive index detection
• qPCR and endotoxin assay

Correct Answer: HILIC-UPLC of fluorescently labeled glycans combined with MS for structural assignment

Q13. Regulatory guidance commonly cites which upper limit for residual host-cell DNA per dose for many biologicals?

• More than 100 ng per dose is acceptable
• Less than 10 ng per dose as a general threshold
• No limit is necessary if purification is validated
• Exactly 50 ng per dose is required

Correct Answer: Less than 10 ng per dose as a general threshold

Q14. What is the primary purpose of forced degradation studies in biosimilar development?

• To assess batch-to-batch manufacturing variability only
• To identify degradation pathways and develop stability-indicating analytical methods
• To increase potency by stressing the molecule
• To determine the exact immunogenic epitopes

Correct Answer: To identify degradation pathways and develop stability-indicating analytical methods

Q15. Why are orthogonal analytical methods important in biosimilarity assessment?

• They allow elimination of biological assays altogether
• They confirm findings using different physical or chemical principles, increasing confidence in results
• They are only useful for small molecules
• They decrease regulatory scrutiny by introducing more variability

Correct Answer: They confirm findings using different physical or chemical principles, increasing confidence in results

Q16. How does the FDA distinguish nonproprietary names of biologics and biosimilars?

• No differentiation; same INN is always used
• Use of a core nonproprietary name plus a four-letter, meaningless suffix to distinguish products
• Use of the manufacturer’s name appended to the INN only
• WHO biological qualifier is exclusively adopted by FDA

Correct Answer: Use of a core nonproprietary name plus a four-letter, meaningless suffix to distinguish products

Q17. Which manufacturing factor most often contributes to differences between biosimilar and reference products?

• Choice of expression cell line and upstream process conditions that alter post-translational modifications
• Type of vial used for packaging only
• Identical growth medium guarantees identical CQAs
• Using the same buffer composition ensures identical glycosylation

Correct Answer: Choice of expression cell line and upstream process conditions that alter post-translational modifications

Q18. For comparative pharmacokinetic (PK) evaluation of a biosimilar monoclonal antibody, which study design is commonly appropriate?

• Randomized, parallel-group PK study in healthy volunteers or suitable patient population with predefined equivalence margins
• Open-label, single-arm study in patients with no comparator
• Non-randomized, dose-escalation tox study only
• Cross-over design in healthy volunteers for long half-life antibodies without washout

Correct Answer: Randomized, parallel-group PK study in healthy volunteers or suitable patient population with predefined equivalence margins

Q19. Which components are essential when assessing immunogenicity of a biosimilar?

• Only preclinical animal antibody data are required
• Validated binding antibody assays, neutralizing antibody assays, and clinical correlation of immune responses
• Only in vitro T-cell proliferation assays
• Only measuring aggregate levels is sufficient

Correct Answer: Validated binding antibody assays, neutralizing antibody assays, and clinical correlation of immune responses

Q20. Under what circumstances can clinical efficacy trials be abbreviated or reduced in biosimilar approval?

• When analytical and functional data, plus PK/PD and immunogenicity evidence, convincingly demonstrate similarity and relevant PD markers exist
• When the biosimilar sponsor requests waiving all clinical studies without justification
• Only when the reference product has been withdrawn from the market
• When the biosimilar has different mechanism of action but similar excipients

Correct Answer: When analytical and functional data, plus PK/PD and immunogenicity evidence, convincingly demonstrate similarity and relevant PD markers exist

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