Characterization of critical reagents in ligand-binding assays: enabling robust bioanalytical methods and lifecycle management

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

References

• 1  Vugmeyster Y, Xu X, Theil FP, Khawli LA, Leach Mw. Pharmacokinetics and toxicology of therapeutic proteins: Advances and challenges. World J. Biol. Chem.3(4),73–92 (2012).
  MedlineGoogle Scholar
• 2  Shankar G, Shores E, Wagner C, Mire-Sluis A. Scientific and regulatory considerations on the immunogenicity of biologics. Trends Biotechnol.24(6),274–280 (2006).
  Medline CASGoogle Scholar
• 3  Lee JW, Kelley M. Quality assessment of bioanalytical quantification of monoclonal antibody drugs. Ther. Deliv.2(3),383–396 (2011).
  CASGoogle Scholar
• 4  Nowatzke WL, Rogers K, Wells E, Bowsher RR, Ray C, Unger S. Unique challenges of providing bioanalytical support for biological therapeutic pharmacokinetic programs. Bioanalysis3(5),509–521 (2011).
  CASGoogle Scholar
• 5  Chirmule N, Jawa V, Meibohm B. Immunogenicity to therapeutic proteins: impact on PK/PD and efficacy. AAPS J.14(2),296–302 (2012).
  Medline CASGoogle Scholar
• 6  Lee JW, Kelley M, King LE et al. Bioanalytical approaches to quantify 'total' and 'free' therapeutic antibodies and their targets: technical challenges and PK/PD applications over the course of drug development. AAPS J.13(1),99–110 (2011).
  Medline CASGoogle Scholar
• 7  Desilva B, Smith W, Weiner R et al. Recommendations for the bioanalytical method validation of ligand-binding assays to support pharmacokinetic assessments of macromolecules. Pharm. Res.20(11),1885–1900 (2003).
  Medline CASGoogle Scholar
• 8  Viswanathan CT, Bansal S, Booth B et al. Quantitative bioanalytical methods validation and implementation: best practices for chromatographic and ligand-binding assays. Pharm. Res.24(10),1962–1973 (2007).
  Medline CASGoogle Scholar
• 9  Shankar G, Devanarayan V, Amaravadi L et al. Recommendations for the validation of immunoassays used for detection of host antibodies against biotechnology products. J. Pharm. Biomed. Anal.48(5),1267–1281 (2008).
  Medline CASGoogle Scholar
• 10  O’hara DM, Theobald V, Egan AC et al. Ligand-binding assays in the 21st century laboratory: recommendations for characterization and supply of critical reagents. AAPS J.14(2),316–328 (2012).▪▪ Recent White Paper detailing important recommendations and guidelines for maintaining and characterizing ligand-binding assay critical reagents.
  MedlineGoogle Scholar
• 11  Staack RF, Stracke JO, Stubenrauch K, Vogel R, Schleypen J, Papadimitriou A. Quality requirements for critical assay reagents used in bioanalysis of therapeutic proteins: what bioanalysts should know about their reagents. Bioanalysis3(5),523–534 (2011).
  CASGoogle Scholar
• 12  Chirino AJ, Mire-Sluis A. Characterizing biological products and assessing comparability following manufacturing changes. Nat. Biotechnol.22(11),1383–1391 (2004).▪ Highlights expected chemical and physical changes and relevant characterization assessment of biotech products following a manufacturing change.
  Medline CASGoogle Scholar
• 13  Stubenrauch K, Wessels U, Lenz H. Evaluation of an immunoassay for human-specific quantitation of therapeutic antibodies in serum samples from non-human primates. J. Pharm. Biomed. Anal.49(4),1003–1008 (2009).
  Medline CASGoogle Scholar
• 14  Kozlowski S, Swann P. Current and future issues in the manufacturing and development of monoclonal antibodies. Adv. Drug Deliv. Rev.58(5–6),707–722 (2006).
  Medline CASGoogle Scholar
• 15  Liu H, Gaza-Bulseco G, Faldu D, Chumsae C, Sun J. Heterogeneity of monoclonal antibodies. J. Pharm. Sci.97(7),2426–2447 (2008).
  Medline CASGoogle Scholar
• 16  Sola RJ, Griebenow K. Effects of glycosylation on the stability of protein pharmaceuticals. J. Pharm. Sci.98(4),1223–1245 (2009).
  Medline CASGoogle Scholar
• 17  Zheng K, Bantog C, Bayer R. The impact of glycosylation on monoclonal antibody conformation and stability. MAbs3(6),568–576 (2011).
  MedlineGoogle Scholar
• 18  Dubois M, Fenaille F, Clement G et al. Immunopurification and mass spectrometric quantification of the active form of a chimeric therapeutic antibody in human serum. Anal. Chem.80(5),1737–1745 (2008).
  Medline CASGoogle Scholar
• 19  Lu Q, Zheng X, Mcintosh T et al. Development of different analysis platforms with LC–MS for pharmacokinetic studies of protein drugs. Anal. Chem.81(21),8715–8723 (2009).
  Medline CASGoogle Scholar
• 20  Li H, Ortiz R, Tran L et al. General LC–MS/MS method approach to quantify therapeutic monoclonal antibodies using a common whole antibody internal standard with application to preclinical studies. Anal. Chem.84(3),1267–1273 (2012).
  Medline CASGoogle Scholar
• 21  Zhang Z, Pan H, Chen X. Mass spectrometry for structural characterization of therapeutic antibodies. Mass Spectrom. Rev.28(1),147–176 (2009).▪▪ Comprehensive review detailing the general approaches and advantages of MS analysis for structural characterization of therapeutic antibodies.
  Medline CASGoogle Scholar
• 22  Kaltashov IA, Bobst CE, Abzalimov RR, Wang G, Baykal B, Wang S. Advances and challenges in analytical characterization of biotechnology products: mass spectrometry-based approaches to study properties and behavior of protein therapeutics. Biotechnol. Adv.30(1),210–222 (2012).
  Medline CASGoogle Scholar
• 23  Ryan MH, Petrone D, Nemeth JF, Barnathan E, Bjorck L, Jordan RE. Proteolysis of purified IgGs by human and bacterial enzymes in vitro and the detection of specific proteolytic fragments of endogenous IgG in rheumatoid synovial fluid. Mol. Immunol.45(7),1837–1846 (2008).
  Medline CASGoogle Scholar
• 24  Damen CW, Chen W, Chakraborty AB et al. Electrospray ionization quadrupole ion-mobility time-of-flight mass spectrometry as a tool to distinguish the lot-to-lot heterogeneity in N-glycosylation profile of the therapeutic monoclonal antibody trastuzumab. J. Am. Soc. Mass Spectrom.20(11),2021–2033 (2009).
  Medline CASGoogle Scholar
• 25  Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharm. Res.27(4),544–575 (2010).▪▪ Thorough review describing chemical and physical stability of protein therapeutics as well as the key contributing factors.
  MedlineGoogle Scholar
• 26  Gaza-Bulseco G, Liu H. Fragmentation of a recombinant monoclonal antibody at various pH. Pharm. Res.25(8),1881–1890 (2008).
  Medline CASGoogle Scholar
• 27  Bertolotti-Ciarlet A, Wang W, Lownes R et al. Impact of methionine oxidation on the binding of human IgG1 to Fc Rn and Fc gamma receptors. Mol. Immunol.46(8–9),1878–1882 (2009).
  Medline CASGoogle Scholar
• 28  Gaza-Bulseco G, Faldu S, Hurkmans K, Chumsae C, Liu H. Effect of methionine oxidation of a recombinant monoclonal antibody on the binding affinity to protein A and protein G. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.870(1),55–62 (2008).
  Medline CASGoogle Scholar
• 29  Wei Z, Feng J, Lin HY et al. Identification of a single tryptophan residue as critical for binding activity in a humanized monoclonal antibody against respiratory syncytial virus. Anal. Chem.79(7),2797–2805 (2007).
  Medline CASGoogle Scholar
• 30  Banks DD, Hambly DM, Scavezze JL, Siska CC, Stackhouse NL, Gadgil HS. The effect of sucrose hydrolysis on the stability of protein therapeutics during accelerated formulation studies. J. Pharm. Sci.98(12),4501–4510 (2009).
  Medline CASGoogle Scholar
• 31  Goetze AM, Liu YD, Arroll T, Chu L, Flynn GC. Rates and impact of human antibody glycation in vivo. Glycobiology22(2),221–234 (2012).
  Medline CASGoogle Scholar
• 32  Chelius D, Jing K, Lueras A et al. Formation of pyroglutamic acid from N-terminal glutamic acid in immunoglobulin gamma antibodies. Anal. Chem.78(7),2370–2376 (2006).
  Medline CASGoogle Scholar
• 33  Vlasak J, Ionescu R. Heterogeneity of monoclonal antibodies revealed by charge-sensitive methods. Curr. Pharm. Biotechnol.9(6),468–481 (2008).
  Medline CASGoogle Scholar
• 34  Wang W, Nema S, Teagarden D. Protein aggregation--pathways and influencing factors. Int. J. Pharm.390(2),89–99 (2010).
  Medline CASGoogle Scholar
• 35  Ejima D, Tsumoto K, Fukada H et al. Effects of acid exposure on the conformation, stability, and aggregation of monoclonal antibodies. Proteins66(4),954–962 (2007).
  Medline CASGoogle Scholar
• 36  Sahin E, Grillo AO, Perkins MD, Roberts CJ. Comparative effects of pH and ionic strength on protein-protein interactions, unfolding, and aggregation for IgG1 antibodies. J. Pharm. Sci.99(12),4830–4848 (2010).
  Medline CASGoogle Scholar
• 37  Mason BD, Schoneich C, Kerwin BA. Effect of pH and light on aggregation and conformation of an IgG1 mAb. Mol. Pharm.9(4),774–790 (2012).
  Medline CASGoogle Scholar
• 38  Den Engelsman J, Garidel P, Smulders R et al. Strategies for the assessment of protein aggregates in pharmaceutical biotech product development. Pharm. Res.28(4),920–933 (2011).
  Medline CASGoogle Scholar
• 39  Paul R, Graff-Meyer A, Stahlberg H et al. Structure and function of purified monoclonal antibody dimers induced by different stress conditions. Pharm. Res.29(8),2047–2059 (2012).
  Medline CASGoogle Scholar
• 40  Luo Q, Joubert MK, Stevenson R, Ketchem Rr, Narhi LO, Wypych J. Chemical modifications in therapeutic protein aggregates generated under different stress conditions. J. Biol. Chem.286(28),25134–25144 (2011).
  Medline CASGoogle Scholar
• 41  Staub A, Guillarme D, Schappler J, Veuthey JL, Rudaz S. Intact protein analysis in the biopharmaceutical field. J. Pharm. Biomed. Anal.55(4),810–822 (2011).
  Medline CASGoogle Scholar
• 42  Houde D, Peng Y, Berkowitz SA, Engen JR. Post-translational modifications differentially affect IgG1 conformation and receptor binding. Mol. Cell. Proteomics9(8),1716–1728 (2010).
  Medline CASGoogle Scholar
• 43  Robinson NE. Protein deamidation. Proc. Natl Acad. Sci. USA99(8),5283–5288 (2002).
  Medline CASGoogle Scholar
• 44  Zheng JY, Janis LJ. Influence of pH, buffer species, and storage temperature on physicochemical stability of a humanized monoclonal antibody LA298. Int. J. Pharm.308(1–2),46–51 (2006).
  Medline CASGoogle Scholar
• 45  Vlasak J, Bussat MC, Wang S et al. Identification and characterization of asparagine deamidation in the light chain CDR1 of a humanized IgG1 antibody. Anal. Biochem.392(2),145–154 (2009).
  Medline CASGoogle Scholar
• 46  Wakankar AA, Borchardt RT, Eigenbrot C et al. Aspartate isomerization in the complementarity-determining regions of two closely related monoclonal antibodies. Biochemistry46(6),1534–1544 (2007).
  Medline CASGoogle Scholar
• 47  Rehder DS, Chelius D, Mcauley A et al. Isomerization of a single aspartyl residue of anti-epidermal growth factor receptor immunoglobulin gamma2 antibody highlights the role avidity plays in antibody activity. Biochemistry47(8),2518–2530 (2008).
  Medline CASGoogle Scholar
• 48  Beck A, Bussat MC, Zorn N et al. Characterization by liquid chromatography combined with mass spectrometry of monoclonal anti-IGF-1 receptor antibodies produced in CHO and NS0 cells. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.819(2),203–218 (2005).
  Medline CASGoogle Scholar
• 49  Franey H, Brych SR, Kolvenbach CG, Rajan RS. Increased aggregation propensity of IgG2 subclass over IgG1: role of conformational changes and covalent character in isolated aggregates. Protein Sci.19(9),1601–1615 (2010).
  Medline CASGoogle Scholar
• 50  Liu H, May K. Disulfide bond structures of IgG molecules: structural variations, chemical modifications and possible impacts to stability and biological function. MAbs4(1),17–23 (2012).
  Medline CASGoogle Scholar
• 51  Cordoba AJ, Shyong BJ, Breen D, Harris RJ. Non-enzymatic hinge region fragmentation of antibodies in solution. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.818(2),115–121 (2005).
  Medline CASGoogle Scholar
• 52  Xie H, Chakraborty A, Ahn J et al. Rapid comparison of a candidate biosimilar to an innovator monoclonal antibody with advanced liquid chromatography and mass spectrometry technologies. MAbs2(4), (2010).▪ Provides example of applying LC–MS analysis to easily characterize and compare innovator and biosimilar mAbs.
  MedlineGoogle Scholar
• 101  US FDA. Guidance for Industry: Bioanalytical Method Validation.www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070107.pdf
  Google Scholar
• 102  US FDA. Guidance for Industry: Assay Development for Immunogenicity Testing of Therapeutic Proteins.www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM192750.pdf
  Google Scholar
• 103  US FDA. Guidance for Industry: Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products.www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073488.pdf
  Google Scholar
• 104  US FDA. Guidance for Industry: Q5E Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process.www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073476.pdf
  Google Scholar