Overview of biosimilars and regulatory concepts MCQs With Answer

Introduction: This quiz set offers M.Pharm students a focused review of biosimilars and the core regulatory concepts essential for development, approval, and post-marketing oversight. It covers scientific principles such as analytical comparability, critical quality attributes, immunogenicity, and clinical study designs, alongside regulatory pathways and guidance from authorities like EMA, FDA and WHO. The questions emphasize practical understanding of naming, interchangeability, extrapolation of indications, pharmacovigilance and manufacturing challenges including glycosylation and host cell impurities. These MCQs are designed to reinforce classroom learning, prepare students for exams, and build readiness for roles in biologics development, regulatory affairs, quality control, and pharmacovigilance.

Q1. Which of the following best defines a biosimilar?

• A biologic product that is identical in every respect to the reference product
• A biologic product with minor differences that has no clinically meaningful differences in safety, purity, and potency compared to the reference product
• A small-molecule generic equivalent of a biologic
• A novel biologic with a new mechanism of action

Correct Answer: A biologic product with minor differences that has no clinically meaningful differences in safety, purity, and potency compared to the reference product

Q2. Which regulatory pathway in the United States is specifically used to approve biosimilars?

• Traditional Biologics License Application (BLA) under 351(a)
• Abbreviated New Drug Application (ANDA)
• Biosimilar application under 351(k) of the Public Health Service Act
• New Drug Application (NDA)

Correct Answer: Biosimilar application under 351(k) of the Public Health Service Act

Q3. In the comparability exercise for a biosimilar, which type of analytical assessment is considered most sensitive to detect structural differences?

• Simple concentration assays
• High-resolution mass spectrometry and peptide mapping
• Basic SDS-PAGE under reducing conditions
• Visual inspection of color and clarity

Correct Answer: High-resolution mass spectrometry and peptide mapping

Q4. What is extrapolation of indications in biosimilar regulation?

• Using the biosimilar in indications only after conducting separate clinical trials for each indication
• Approving a biosimilar for additional indications of the reference product based on totality of evidence without new clinical trials for each indication
• Limiting biosimilar use to a single indication to avoid regulatory complexity
• Granting approval only when the mechanism of action is identical for all indications

Correct Answer: Approving a biosimilar for additional indications of the reference product based on totality of evidence without new clinical trials for each indication

Q5. Which quality attribute is critically influenced by the cell line and culture conditions and often affects immunogenicity and activity?

• pH of the final formulation
• Glycosylation pattern, including N-linked glycans
• Container closure type
• Cryoprotectant concentration

Correct Answer: Glycosylation pattern, including N-linked glycans

Q6. Which guideline specifically addresses comparability for biotechnology-derived products and is commonly referenced for biosimilars?

• ICH Q1A (Stability)
• ICH Q5E (Biotechnology-derived pharmaceuticals: comparability)
• ICH Q3C (Impurities – residual solvents)
• ICH Q9 (Quality Risk Management)

Correct Answer: ICH Q5E (Biotechnology-derived pharmaceuticals: comparability)

Q7. Which is the primary objective of preclinical and analytical comparability studies for a biosimilar?

• To demonstrate superiority over the reference product
• To establish clinical efficacy in a new patient population
• To detect potential differences in structure, function, and impurities that could affect clinical performance
• To replace all clinical trials with in vitro data

Correct Answer: To detect potential differences in structure, function, and impurities that could affect clinical performance

Q8. In the context of biosimilars, what does the term “interchangeability” mean in the United States?

• A biosimilar that may be substituted at the pharmacy without prescriber intervention only if it is considered interchangeable by FDA
• A biosimilar that is therapeutically inferior to the reference product
• A biosimilar that cannot be used in place of the reference product under any circumstances
• A biosimilar that automatically receives market exclusivity

Correct Answer: A biosimilar that may be substituted at the pharmacy without prescriber intervention only if it is considered interchangeable by FDA

Q9. Which study design is often required by regulators to support interchangeability designation?

• Single-dose PK study without switching
• Multiple-switching clinical study comparing alternating use of biosimilar and reference product
• Only in vitro binding assays
• Cross-sectional observational study after approval

Correct Answer: Multiple-switching clinical study comparing alternating use of biosimilar and reference product

Q10. Which of the following is a key element of pharmacovigilance specific to biologics and biosimilars?

• Monthly patient surveys unrelated to adverse events
• Traceability by brand name, batch/lot number, and manufacturer
• Only spontaneous reporting without product identification
• Exempting biosimilars from adverse event reporting for five years

Correct Answer: Traceability by brand name, batch/lot number, and manufacturer

Q11. Which impurity is of particular concern in biologics manufacturing due to its potential to provoke immune responses?

• Residual organic solvents
• Host cell proteins (HCPs)
• Inorganic salts
• Preservatives like benzyl alcohol

Correct Answer: Host cell proteins (HCPs)

Q12. Which analytical technique is commonly used to assess higher-order structure of a protein biosimilar?

• UV-visible spectroscopy only
• Circular dichroism and differential scanning calorimetry
• Thin-layer chromatography
• HPLC for small molecules

Correct Answer: Circular dichroism and differential scanning calorimetry

Q13. When selecting a reference product for global development of a biosimilar, regulators typically expect which approach?

• Use of any biologic product on the market as reference regardless of authorization status
• Use of the locally authorized reference product or a bridging strategy if a non-local reference is used
• Use of a biosimilar as the reference
• Manufacturers can avoid referencing the original product entirely

Correct Answer: Use of the locally authorized reference product or a bridging strategy if a non-local reference is used

Q14. What is the FDA’s current recommendation for nonproprietary naming of biosimilars?

• Use the exact same nonproprietary name as the reference product without qualifiers
• Assign a nonproprietary name with a unique, meaningless four-letter suffix attached to the core name
• Use a completely different nonproprietary name unrelated to the reference
• Only use brand names for biosimilars and avoid nonproprietary names

Correct Answer: Assign a nonproprietary name with a unique, meaningless four-letter suffix attached to the core name

Q15. Which clinical endpoint is most often used in confirmatory studies for monoclonal antibody biosimilars?

• Unrelated safety endpoint with no clinical relevance
• Sensitive efficacy endpoint that can detect clinically meaningful differences, such as objective response rate or disease activity score
• Only surrogate lab markers without clinical correlation
• Patient satisfaction questionnaires exclusively

Correct Answer: Sensitive efficacy endpoint that can detect clinically meaningful differences, such as objective response rate or disease activity score

Q16. Which of the following best describes “totality of evidence” in biosimilar development?

• Decision based solely on one pivotal clinical trial
• Integrated assessment of analytical, functional, nonclinical, and clinical data to demonstrate biosimilarity
• Approval based only on manufacturing process similarity
• Using only post-marketing surveillance to prove similarity

Correct Answer: Integrated assessment of analytical, functional, nonclinical, and clinical data to demonstrate biosimilarity

Q17. Which risk management activity is critical for biosimilars due to potential immunogenicity concerns?

• Routine environmental monitoring only
• Active immunogenicity monitoring with pre-specified assays and post-marketing surveillance
• Skipping immunogenicity assessment because biosimilars are safe by definition
• No follow-up after approval

Correct Answer: Active immunogenicity monitoring with pre-specified assays and post-marketing surveillance

Q18. Which manufacturing change is most likely to require a comparability assessment for a licensed biologic?

• Minor color change in external packaging
• Change in cell line or major change in upstream process affecting glycosylation
• Change in supplier of non-critical paper labels
• Typographical correction in documentation

Correct Answer: Change in cell line or major change in upstream process affecting glycosylation

Q19. Under EMA guidance, what is the role of a head-to-head pharmacokinetic (PK) study in biosimilar development?

• It is unnecessary if analytical similarity is established
• It helps demonstrate comparable exposure and supports bridging to clinical efficacy data
• It is only used to establish superiority of the biosimilar
• It replaces all immunogenicity testing

Correct Answer: It helps demonstrate comparable exposure and supports bridging to clinical efficacy data

Q20. Which of the following best explains why small differences in microheterogeneity between a biosimilar and its reference product may be acceptable?

• Microheterogeneity never affects biological function or safety
• Regulators allow any differences without justification
• If differences are characterized and shown not to impact critical quality attributes, safety, or efficacy, they can be acceptable under the totality of evidence
• Because biosimilars are chemically synthesized, microheterogeneity is irrelevant

Correct Answer: If differences are characterized and shown not to impact critical quality attributes, safety, or efficacy, they can be acceptable under the totality of evidence

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