Development of a microflow digital imaging assay to characterize protein particulates during storage of a high concentration IgG1 monoclonal antibody formulation

Journal of Pharmaceutical Sciences

Volumn 99, Issue 8, 2010, Pages 3343-3361

  Wuchner, Klaus ^a,b   Büchler, Jochen ^a,b   Spycher, Rene ^a,b   Dalmonte, Paul ^a,c   Volkin, David B ^a,c,d  

^a 3210 Merryfield Row   (United States)

^b University of Kansas ^*  (Switzerland)

^c NONE   (United States)

^d UNIVERSITY OF KANSAS   (United States)

Author keywords

Aggregation; IgG; Infrared microscopy (ATR FT IR); Microflow digital imaging (MDI or MFI); Monoclonal antibody; Protein stability; Scanning electron microscopy energy dispersive X ray spectrometer (SEM EDX); Subvisible particles; Visible particles

Indexed keywords

IMMUNOGLOBULIN G1; IMMUNOGLOBULIN G; MONOCLONAL ANTIBODY; PARTICULATE MATTER; PROTEIN;

ARTICLE; DIGITAL IMAGING; DRUG FORMULATION; DRUG STABILITY; DRUG STORAGE; FOURIER TRANSFORM MASS SPECTROMETRY; MICROSCOPY; PARTICLE SIZE; QUALITATIVE ANALYSIS; SCANNING ELECTRON MICROSCOPY; CHEMISTRY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IMMUNOLOGY; INFRARED SPECTROSCOPY; MEDICINAL CHEMISTRY; PARTICULATE MATTER; PEPTIDE MAPPING; PHOTOMETRY; SPECTROMETRY;

ANTIBODIES, MONOCLONAL; CHEMISTRY, PHARMACEUTICAL; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DRUG STABILITY; DRUG STORAGE; IMMUNOGLOBULIN G; MICROSCOPY, ELECTRON, SCANNING; NEPHELOMETRY AND TURBIDIMETRY; PARTICLE SIZE; PARTICULATE MATTER; PEPTIDE MAPPING; PROTEINS; SPECTROMETRY, X-RAY EMISSION; SPECTROSCOPY, FOURIER TRANSFORM INFRARED;

EID: 77955101936     PISSN: 00223549     EISSN: 15206017     Source Type: Journal    
DOI: 10.1002/jps.22123     Document Type: Article

References (46)

1. Carpenter JF, Randolph TW, Jiskoot W, Crommelin DJA, Middaugh CR, Winter G, Fan Y, Kirshner S, Verthelyi D, Kozlowski S, Clouse KA, Swann PG, Rosenberg A, Cherney B. 2009. Overlooking subvisible particles in therapeutic protein products: Gaps that may compromise product quality. J Pharm Sci 98:1201-1205.
2. Shire SJ, Shahrokh Z, Liu J. 2004. Challenges in the development of high protein concentration formulations. J Pharm Sci 93:511-516.
3. Trevino SR, Scholtz JM, Pace CN. 2008. Measuring and increasing protein solubility. J Pharm Sci 97:4155-4166.
4. Mahler H, Friess W, Grauschopf U, Kiese S. 2009. Protein aggregation: Pathways, induction factors, and analysis. J Pharm Sci 98:2909-3934.
5. Rosenberg AS. 2006. Effects of protein aggregates: An immunologic perspective. AAPS J 8:E501-E508.
6. Swann PG, Tolnay M, Muthukkumar S, Shapiro MA, Rellahan BL, Clouse KA. 2008. Considerations for the development of therapeutic monoclonal antibodies. Curr Opin Immuno 20:493-499.
7. Shankar G, Shores E, Wagner C, Mire-Sluis A. 2006. Scientific and regulatory considerations on the immunogenicity of biologics. Trends Biotechnol 24:274-280. (Pubitemid 43853075)
8. Mukovozov I, Sablijc T, Hortelano G, Ofosu FA. 2008. Factors that contribute to the immunogenicity of therapeutic recombinant human proteins. Thromb Haemost 99:874-882.
9. Sharma B. 2007. Immunogenicity of therapeutic proteins. Part 1: Impact of product handling. Biotechnol Adv 25:310-317.
10. Sharma B. 2007. Immunogenicity of therapeutic proteins. Part 2: Impact of container closures. Biotechnol Adv 25:318-324.
11. Sharma B. 2007. Immunogenicity of therapeutic proteins. Part 3: Impact of manufacturing changes. Biotechnol Adv 25:325-331.
12. Philo JS. 2009. A critical review of methods for size characterization of non-particulate protein aggregates. Curr Pharm Biotechnol 10:359-372.
13. Bond MD, Panek ME, Zhang Z, Wang D, Mehndiratta P, Zhao H, Gunton K, Ni A, Nedved ML, Burman S, Volkin DB. 2009. Evaluation of a dual-wavelength size exclusion HPLC method with improved sensitivity to detect protein aggregates and its use to better characterize degradation pathways of an IgG1 monoclonal antibody. J Pharm Sci [Epub, DOI 10.1002/jps.22034].
14. Tyagi AK, Randolph TW, Dong A, Maloney KM, Hitscherich C, Carpenter JF. 2009. IgG particle formation during filling pump operations: A case study of heterogeneous nucleation on stainless steel nanoparticles. J Pharm Sci 98:94-104.
15. Brorson K, Phillips J. 2005. Defining your product profile and maintaining control over it, Part 4. Bioprocess Int 3:50-54.
16. Narhi LO, Jiang Y, Cao S, Benedek K, Shnek D. 2009. A critical review of analytical methods for subvisible and visible particles. Curr Pharm Biotechnol 10:373-381.
17. Groves MJ. 1993. International concerns over particulate matter contamination. In particulate matter - Sources and resources for healthcare manufacturers. Buffalo Groves, IL: Interpharm Press. pp. 223-236.
18. Barber TA. 2000. Visible inspection of injectables and devices. In control of particulate metter contamination in healthcare manufacturing. Denver, Colorado: Interpharm Press. pp. 229-274.
19. Akers MJ, Larrimore DS, Guazzo DM. 2003. Particulate matter testing. In parenteral quality control: Sterility, particulate, and packaging integrity testing. 3rd edition, Revised and Expanded, New York: Marcel Dekker, Inc. pp. 197-280.
20. Knapp JZ, Kushner HK, Abramson LR. 1981. Particulate inspection of parenteral products; an assessment. PDA J Pharm Sci Technol 35:176-185.
21. Knapp JZ, Kushner HK. 1982. Particulate inspection of parenteral products: From biophysics to automation. PDA J Pharm Sci Technol 36:121-127.
22. Borchert SJ, Abe A, Aldrich DS, Fox LE, Freeman JE, White RD. 1986. Particulate matter in parenteral products: A review. PDA J Pharm Sci Technol 40:212-241.
23. Chi EY, Krishnan S, Kendrick BS, Chang BS, Carpenter JF, Randolph TW. 2003. Roles of conformational stability and colloidal stability in the aggregation of recombinant human granulocyte colony stimulating factor. Protein Sci 12:903-913.
24. J Pharm Sci 92:256-274.
25. Chi EY, Krishnan S, Carpenter JF, Randolph TW. 2003. Physical stability of proteins in aqueous solution: Mechanism and driving forces in nonnative protein aggregation. Pharm Res 20:1325-1336.
26. Chi EY, Weickman J, Carpenter JF, Manning MC, Randolph TW. 2005. Heterogeneous nucleation-controlled particulate formation of recombinant human platelet-activating factor acetylhydrolase in pharmaceutical formulations. J Pharm Sci 94:256-274.
27. Doyle BL, Pollo MJ, Pekar AH, Roy ML, Thomas BA, Brader ML. 2005. Biophysical signatures of noncovalent aggregates formed by a glucagonlike peptide-1 analog: A prototypical example of biopharmaceutical aggregation. J Pharm Sci 94:2749-2763.
28. Liu J, Nguyen MDH, Andya JD, Shire SJ. 2005. Reversible self-association increases the viscosity of a concentrated monoclonal antibody in aqueous solution. J Pharm Sci 94:1928-1940. (Pubitemid 41551477)
29. Kiese S, Pappenberger A, Friess W, Mahler HC. 2009. Equilibrium studies of protein aggregates and homogeneous nucleation in protein formulation. J Pharm Sci 99:632-644.
30. Sukumar M, Doyle BL, Combs JL, Pekar AH. 2004. Opalescent appearance of an IgG1 antibody at high concentrations and its relationship to noncovalent association. Pharm Res 21:1087-1093.
31. Eckhardt BM, Oeswein JQ, Yeung DA, Milby TD, Bewley TA. 1994. A turbidimetric method to determine visual appearance of protein solutions. J Pharm Sci Tech 48:64-70.
32. Li B, Flores J, Corvari V. 2007. A simple method for the detection of insoluble aggregates in protein formulations. J Pharm Sci 96:1840-1843.
33. Huang CT, Sharma D, Oma P, Krishnamurthy R. 2009. Quantitation of protein particles in parenteral solutions using microflow imaging. J Pharm Sci 98:3058-3071.
34. Sharma DK, Oma P, Pollo MJ, Sukumar M. 2009. Quantification and characterization of sub-visible proteinaceous particles in opalescent mAb formulations using micro-flow imaging. J Pharm Sci [Epub, DOI 10.1002/jps.22046] (submitted).
35. Wen ZQ. 2007. Raman spectroscopy of protein pharmaceuticals. J Pharm Sci 96:2861-2878.
36. Das T, Nema S. 2008. Protein particulate issues in biologics development. Am Pharm Rev 11:52-57.
37. Torraca G, Wen ZQ. 2005. Forensic investigation of biopharmaceutical manufacturing incidents by light microscopy, FTIR microscopy, scanning electron microscopy and energy dispersive X-ray spectrometry. Microsc Microanal 11:1224-1225.
38. Sharma DK, King D, Moore P, Oma P, Thomas D. 2007. Flow microscopy for particulate analysis in parenteral and pharmaceutical fluids. Eur J Parent Pharm Sci 12:97-101.
39. European Pharmacopeia, monograph 20920, 6th Edition 2009 (6.5).
40. Qi P, Volkin DB, Zhao H, Nedved ML, Hughes R, Bass R, Yi SC, Panek ME, Wang D, Dalmonte P, Bond MD. 2009. Characterization of the photodegradation of a human IgG1 monoclonal antibody formulated as a high-concentration liquid dosage form. J Pharm Sci 98:3117-3130.
41. Ritter N, Advant SJ, Hennessey J, Simmerman H, McEntire J, Mire-Sluis A, Joneckis C. 2004. What is test method qualification? Bioprocess Int 2:32-47.
42. Chalikian TV, Totrov M, Abagyan R, Breslauer KJ. 1996. The hydration of globular proteins as derived from volume and compressibility measurements: Cross correlating thermodynamic and structural data. J Mol Bio 260:588-603.
43. Andersson KM, Hovmöller S. 2000. The protein content in crystals and packing coefficients in different space groups. Acta Crystallogr D Biol Crystallogr 56:789-790. (Pubitemid 30454085)
44. Quillin ML, Matthews BW. 2000. Accurate calculation of the density of proteins. Acta Crystallogr D Biol Crystallogr 56:791-794.
45. Fischer H, Polikarpov I, Craievich AF. 2004. Average protein density is a molecular-weight-dependent function. Protein Sci 13:2825-2828.
46. Cooper EA, Knutson K. 1995. Fourier transform infrared spectroscopy investigations of protein structure. In physical methods to characterize pharmaceutical proteins. New York: Plenum Press. Pharmaceutical Biotechnology 7:101-143.