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Analytical Comparison of Antibody-drug Conjugates Based on Good Manufacturing Practice Strategies

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Abstract

The production of antibody-drug conjugates (ADCs) has been in great demand in the field of cancer therapeutics. Although cysteine-based conjugation is the most common and well known process for producing ADCs, multiple analytical methods are required for accurate drug-antibody ratio (DAR) determination due to the heterogeneity of the ADCs. Here we report various analytical methods for DAR analysis of traditional cysteine-based ADCs; additionally, apply a good manufacturing practice (GMP) strategy to produce a four hundred milligram ADC batch for use in good laboratory practice (GLP) studies. The work described herein not only evaluates several analytical performances but also provides guidance for future phase appropriate ADC production while establishing a unique analytical strategy.

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References

  1. M. Abdollahpour-Alitappeh, M. Lotfinia, T. Gharibi, J. Mardaneh, B. Farhadihosseinabadi, P. Larki, B. Faghfourian, K. S. Sepehr, K. Abbaszadeh-Goudarzi, G. Abbaszadeh-Goudarzi, B. Johari, M. R. Zali, and N. Bagheri, J. Cell Physiol., 2019, 234, 5628.

    Article  CAS  PubMed  Google Scholar 

  2. J. M. Lambert and A. Berkenblit, Annu. Rev. Med., 2018, 69, 191.

    Article  CAS  PubMed  Google Scholar 

  3. R. Lyon, Drug Discov. Today Technol., 2018, 30, 105.

    Article  PubMed  Google Scholar 

  4. A. Beck, V. D’Atri, A. Ehkirch, S. Fekete, O. Hernandez-Alba, R. Gahoual, E. Leize-Wagner, Y. Francois, D. Guillarme, and S. Cianférani, Expert. Rev. Proteomics., 2019, 16, 337.

    Article  CAS  PubMed  Google Scholar 

  5. K. Todoroki, T. Yamada, H. Mizuno, and T. Toyo’oka, Anal. Sci., 2018, 34, 397.

    Article  CAS  PubMed  Google Scholar 

  6. US Food and Drug Administration (FDA), Guidance for Industry—Monoclonal Antibodies Used as Reagents in Drug Manufacturing, https://www.fda.gov/media/72408/download.

  7. US Food and Drug Administration (FDA), Assay Development and Validation for Immunogenicity Testing of Therapeutic Protein Products—Guidance for Industry, https://www.fda.gov/media/77796/download.

  8. Y. Matsuda, V. Robles, M-C. Malinao, S. James, and B. A. Mendelsohn, Anal. Chem., 2019, 91, 12724.

    Article  CAS  PubMed  Google Scholar 

  9. F. Debaene, A. Boeuf, E. Wagner-Rousset, O. Colas, D. Ayoub, N. Corvaïa, A. Van Dorsselaer, A. Beck, and S. Cianférani, Anal. Chem., 2014, 86, 10674.

    Article  CAS  PubMed  Google Scholar 

  10. L. N. Le, J. M. R. Moore, J. Ouyang, X. Chen, M. D. H. Nguyen, and W. J. Galush, Anal. Chem., 2012, 84, 7479.

    Article  CAS  PubMed  Google Scholar 

  11. D. Firth, L. Bell, M. Squires, S. Estdale, and C. McKee, Anal. Biochem., 2015, 485, 34.

    Article  CAS  PubMed  Google Scholar 

  12. M. Källsten, R. Hartmann, K. Artemenko, S. B. Lind, F. Lehmann, and B. Bergquist, Analyst, 2018, 143, 5487.

    Article  PubMed  Google Scholar 

  13. Y. Matsuda, C. Clancy, Z. Tawfiq, V. Robles, and B. A. Mendelsohn, ACS Omega, 2019, 4, 20564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. P. D. Senter and E. L. Sievers, Nat. Biotechnol., 2012, 30, 631.

    Article  CAS  PubMed  Google Scholar 

  15. H. Tilly, F. Morschhauser, N. L. Bartlett, A. Mehta, G. Salles, C. Haioun, J. Munoz, A. I. Chen, K. Kolibaba, D. Lu, M. Yan, E. Penuel, J. Hirata, C. Lee, and J. P. Sharman, Lancet Oncol., 2019, 20, 998.

    Article  CAS  PubMed  Google Scholar 

  16. Z. Tawfiq, N. C. Caiazza, S. Kambourakis, Y. Matsuda, B. Griffin, J. C. Lippmeier, and B. A. Mendelsohn, ACS Omega, 2020, 5, 7193.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. K. Yamada, N. Shikida, K. Shimbo, Y. Ito, Z. Khedri, Y. Matsuda, and B. A. Mendelsohn, Angew. Chem., Int. Ed., 2019, 58, 5592.

    Article  CAS  Google Scholar 

  18. Y. Matsuda, K. Yamada, T. Okuzumi, and B. A. Mendelsohn, Org. Process Res. Dev., 2019, 23, 2647.

    Article  CAS  Google Scholar 

  19. S. O. Doronina, B. E. Toki, M. Y. Torgov, B. A. Mendelsohn, C. G. Cerveny, D. F. Chace, R. L. DeBlanc, R. P. Gearing, T. D. Bovee, C. B. Siegall, J. A. Francisco, A. F. Wahl, D. L. Meyer, and P. D. Senter, Nat. Biotechnol., 2003, 21, 778.

    Article  CAS  PubMed  Google Scholar 

  20. G. T. Hermanson, “Bioconjugate Techniques”, 3rd ed., 2013, Elsevier, London, 240–246.

  21. S. Fekete, J.-L. Veuthey, A. Beck, and D. Guillarme, J. Pharm. Biomed. Anal., 2016, 130, 3.

    Article  CAS  PubMed  Google Scholar 

  22. V. D’Atri, R. Pell, A. Clarke, D. Guillarme, and S. Fekete, J. Chromatogr. A, 2019, 1586, 149.

    Article  PubMed  Google Scholar 

  23. Title 21 CFR Part 58 Good Laboratory Practice for Nonclinical Laboratory Studies, 18 February 2004.

  24. B. Stump and J. Steinmann, Methods Mol. Biol., 2013, 1045, 235.

    Article  PubMed  Google Scholar 

  25. D. E. Shafer, J. K. Inman, and A. Lees, Anal. Biochem., 2000, 282, 161.

    Article  CAS  PubMed  Google Scholar 

  26. J. C. Han and G. Y. Han, Anal. Biochem., 1994, 220, 5.

    Article  CAS  PubMed  Google Scholar 

  27. Y. Matsuda, M. C. Malinao, V. Robles, J. Song, K. Yamada, and B. A. Mendelsohn, J. Chromatogr. B, 2020, 1140, 121981.

    Article  CAS  Google Scholar 

  28. S. Sakamoto and I. Hamachi, Anal. Sci., 2019, 35, 5.

    Article  CAS  PubMed  Google Scholar 

  29. K. Tsuchikama and A. An, Protein & Cell, 2018, 9, 33.

    Article  CAS  Google Scholar 

  30. K. Maruyama and M. Kanai, Chem. Lett., 2019, 48, 1421.

    Article  CAS  Google Scholar 

  31. C. L. Becker, R. J. Duffy, J. Gandarilla, and S. M. Richter, Methods Mol. Biol., 2019, 2078, 237.

    Google Scholar 

  32. Y. Zhang, S. Zhou, X. Chang, and X. Tao, Anal. Sci., 2019, 35, 1291.

    Article  CAS  PubMed  Google Scholar 

  33. M. K. Sharma, P. Dhakne, S. NN, P. A. Reddy, and P. Sengupta, Anal Sci., 2019, 35, 1069.

    Article  CAS  PubMed  Google Scholar 

  34. Y. Matsuda, M. Leung, T. Okuzumi, and B. A. Mendelsohn, Antibodies, 2020, 9, 16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors wish to thank our colleagues from Ajinomoto Bio-Pharma Services, Inc., as follows: Mr. Shawn Littrell and Mr. William Wittbold for technical assistance for GLP study; Dr. Wen Chen and Mr. Keenan Moi for technical assistance with the ADC analysis; Mr. David Correa, Mr. Steve Folio, Mr. Darwin Richardson, Mr. Bert Barbosa, and Dr. Tatsuya Okuzumi from Ajinomoto Co., Inc. for many helpful discussions and suggestions in this study.

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Authors and Affiliations

  1. Ajinomoto Bio-Pharma Services, 11040 Roselle Street, San Diego, CA, 92121, United States

    Zhala Tawfiq, Melody Jane Alfonso, Colin Clancy, Veronica Robles, Monica Leung & Brian A. Mendelsohn

  2. Ajinomoto Co., Inc., 1-1 Suzuki-cho, Kawasaki, Kawasaki, Kanagawa, 210-8681, Japan

    Yutaka Matsuda

Authors
  1. Zhala Tawfiq
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  2. Yutaka Matsuda
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  3. Melody Jane Alfonso
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  4. Colin Clancy
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  5. Veronica Robles
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  6. Monica Leung
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  7. Brian A. Mendelsohn
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Correspondence to Brian A. Mendelsohn.

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Tawfiq, Z., Matsuda, Y., Alfonso, M.J. et al. Analytical Comparison of Antibody-drug Conjugates Based on Good Manufacturing Practice Strategies. ANAL. SCI. 36, 871–875 (2020). https://doi.org/10.2116/analsci.19P465

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  • DOI: https://doi.org/10.2116/analsci.19P465

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