Introduction: Protein drugs and monoclonal antibodies are key biopharmaceuticals widely used in modern therapy. This topic covers therapeutic proteins, antibody structure (Fab/Fc), mAb engineering, pharmacokinetics, immunogenicity, manufacturing (CHO cells, glycosylation), purification (Protein A), formulation, stability, and safety concerns. B. Pharm students should understand mechanism of action, Fc-mediated effects (ADCC, CDC), antigen binding, antibody types (murine, chimeric, humanized, human), biosimilars versus originals, and analytical methods (ELISA, SDS-PAGE, SEC). Practical knowledge of dosing routes, cold chain, and regulatory quality (CMC) is essential for developing and handling protein therapeutics. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which of the following best defines protein drugs?
- Small molecule compounds synthesized by chemical reactions
- Biological macromolecules such as peptides, enzymes, and monoclonal antibodies used therapeutically
- Vitamins and minerals used as supplements
- Radioactive isotopes used in imaging
Correct Answer: Biological macromolecules such as peptides, enzymes, and monoclonal antibodies used therapeutically
Q2. Which antibody region is primarily responsible for antigen binding?
- Fc region
- Hinge region
- Fab region
- Constant light chain only
Correct Answer: Fab region
Q3. Which Ig class is most commonly used for therapeutic monoclonal antibodies due to its long serum half-life?
- IgA
- IgM
- IgG
- IgE
Correct Answer: IgG
Q4. What suffix in a monoclonal antibody name indicates a humanized antibody?
- -omab
- -ximab
- -zumab
- -umab
Correct Answer: -zumab
Q5. What is the role of the neonatal Fc receptor (FcRn) in antibody pharmacokinetics?
- Promotes antibody aggregation in plasma
- Mediates antibody degradation in lysosomes
- Recycles IgG and extends its serum half-life
- Facilitates antigen presentation to T cells
Correct Answer: Recycles IgG and extends its serum half-life
Q6. Antibody-dependent cellular cytotoxicity (ADCC) primarily involves engagement of which effector cell receptor?
- FcγRIII (CD16) on natural killer cells
- Toll-like receptors on macrophages
- B cell receptor on B lymphocytes
- Complement receptor 1 on erythrocytes
Correct Answer: FcγRIII (CD16) on natural killer cells
Q7. Which ligand is commonly used in affinity chromatography to purify IgG monoclonal antibodies?
- Protein A
- Gelatin
- Polyethylene glycol
- Chitosan
Correct Answer: Protein A
Q8. Why is glycosylation critical for monoclonal antibody function?
- It only affects protein color and has no functional role
- It alters antibody solubility, effector functions, and immunogenicity
- It converts antibodies into enzymes
- It ensures antibody penetration into the nucleus
Correct Answer: It alters antibody solubility, effector functions, and immunogenicity
Q9. Which host cell line is most widely used for commercial monoclonal antibody production?
- Escherichia coli
- Saccharomyces cerevisiae
- Chinese hamster ovary (CHO) cells
- Baculovirus-infected insect cells only
Correct Answer: Chinese hamster ovary (CHO) cells
Q10. What is a major consequence of protein aggregation in therapeutic formulations?
- Reduced molecular weight of the drug
- Increased immunogenicity and potential loss of efficacy
- Enhanced oral bioavailability
- Guaranteed sterilization of the product
Correct Answer: Increased immunogenicity and potential loss of efficacy
Q11. What is the primary purpose of pegylation of therapeutic proteins?
- To increase proteolytic degradation
- To reduce molecular weight for renal clearance
- To increase half-life and reduce immunogenicity
- To change antigen specificity
Correct Answer: To increase half-life and reduce immunogenicity
Q12. An antibody-drug conjugate (ADC) consists of which three components?
- Antibody, radionuclide, and lipid carrier
- Antibody, linker, and cytotoxic payload
- Small molecule drug, sugar, and peptide
- Enzyme, cofactor, and substrate
Correct Answer: Antibody, linker, and cytotoxic payload
Q13. How do biosimilars differ from small-molecule generics?
- Biosimilars are exact chemical copies of the original biologic
- Biosimilars are natural extracts with unknown composition
- Biosimilars are highly similar but not identical to original biologics due to complex structure and manufacturing
- Biosimilars are always produced in bacterial systems only
Correct Answer: Biosimilars are highly similar but not identical to original biologics due to complex structure and manufacturing
Q14. What distinguishes neutralizing anti-drug antibodies (ADAs) from non-neutralizing ADAs?
- Neutralizing ADAs increase drug potency
- Neutralizing ADAs bind and inhibit the biological activity of the therapeutic
- Non-neutralizing ADAs always cause immediate hypersensitivity
- Non-neutralizing ADAs are only found with small molecules
Correct Answer: Neutralizing ADAs bind and inhibit the biological activity of the therapeutic
Q15. Which route is commonly used for initial administration of many monoclonal antibodies in a clinical setting to ensure full bioavailability?
- Oral
- Intravenous infusion
- Topical
- Inhalational
Correct Answer: Intravenous infusion
Q16. Complement-dependent cytotoxicity (CDC) is initiated when which component binds to antibody Fc regions?
- C1q
- Factor VIII
- Albumin
- CRP (C-reactive protein)
Correct Answer: C1q
Q17. Which formulation variables are most important for maintaining protein drug stability?
- pH, ionic strength, temperature, and excipients
- Color of the vial and label font
- Packaging barcode style only
- Magnetic field exposure exclusively
Correct Answer: pH, ionic strength, temperature, and excipients
Q18. Which analytical technique is commonly used to quantify monoclonal antibodies in biological samples?
- ELISA (enzyme-linked immunosorbent assay)
- Gram staining
- Polarimetry
- Thin-layer chromatography
Correct Answer: ELISA (enzyme-linked immunosorbent assay)
Q19. What does SDS-PAGE primarily separate proteins by?
- Electrical charge only
- Hydrophobicity only
- Molecular weight under denaturing conditions
- Antigen-binding affinity
Correct Answer: Molecular weight under denaturing conditions
Q20. Why is the isoelectric point (pI) important for protein drug formulation?
- It determines the color of the solution
- It affects solubility, aggregation propensity, and interaction with excipients
- It converts proteins into carbohydrates
- It dictates the protein’s DNA sequence
Correct Answer: It affects solubility, aggregation propensity, and interaction with excipients
Q21. Which assay is standard for endotoxin detection in protein therapeutics?
- LAL (Limulus amebocyte lysate) test
- ELISA for antibodies
- SDS-PAGE
- Bradford protein assay
Correct Answer: LAL (Limulus amebocyte lysate) test
Q22. What pore size is typically used for sterile filtration of biologic drug solutions?
- 5.0 µm
- 0.45 µm
- 0.22 µm
- 10 µm
Correct Answer: 0.22 µm
Q23. Which handling practice most reduces damage from freeze–thaw cycles for protein drugs?
- Repeatedly freezing and thawing at room temperature
- Aliquoting into single-dose containers and minimizing freeze–thaw events
- Heating to 60°C before each use
- Vigorously vortexing after each thaw
Correct Answer: Aliquoting into single-dose containers and minimizing freeze–thaw events
Q24. Approximately what is the typical serum half-life of human IgG antibodies?
- 2–4 hours
- 24–48 hours
- 10–21 days
- 6 months to 1 year
Correct Answer: 10–21 days
Q25. The monoclonal antibody rituximab has which nomenclature suffix indicating its origin?
- -omab indicating fully murine
- -ximab indicating chimeric
- -zumab indicating humanized
- -umab indicating fully human
Correct Answer: -ximab indicating chimeric
Q26. FcRn binding to IgG is pH-dependent. At which pH does FcRn bind IgG most strongly to enable recycling?
- Neutral pH (~7.4)
- Acidic pH (~6.0) found in endosomes
- Basic pH (~9.0)
- It binds equally at all pH values
Correct Answer: Acidic pH (~6.0) found in endosomes
Q27. What is the recommended storage temperature range for many commercial monoclonal antibody formulations?
- Room temperature (20–25°C)
- Freezer (< -20°C) only
- Refrigerated (2–8°C)
- Body temperature (37°C)
Correct Answer: Refrigerated (2–8°C)
Q28. Checkpoint inhibitor monoclonal antibodies used in oncology typically target which pathways?
- PD-1/PD-L1 and CTLA-4 immune checkpoints
- Insulin signaling pathways
- Renin–angiotensin system only
- Vitamin D receptor activation
Correct Answer: PD-1/PD-L1 and CTLA-4 immune checkpoints
Q29. Which method is most appropriate for detecting high-molecular-weight aggregates in a protein drug formulation?
- Size-exclusion chromatography (SEC)
- Gas chromatography
- pH titration only
- Colorimetric sugar assay
Correct Answer: Size-exclusion chromatography (SEC)
Q30. Which factors increase the immunogenicity risk of a therapeutic protein?
- Human amino acid sequence, low aggregation, and high purity
- Nonhuman sequence motifs, aggregates, and process-related impurities
- Oral administration and high lipid solubility only
- Use of sterile water without excipients
Correct Answer: Nonhuman sequence motifs, aggregates, and process-related impurities
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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