Dry powder therapeutic mAb formulations with enhanced temperature stability

Willa Gebbie, Katrina Davidson, Johann Partridge, Jan Vos, Barry Moore

Research output: Contribution to conferencePoster

Abstract

Purpose. There is an increasing demand for differentiated strategies for formulating and delivering mAb in particulate form. The aim of this study was to investigate methods for optimising protein-coated microcrystal (PCMC) formulations of a human monoclonal antibody. PCMC technology provides a novel method of stabilising these important biopharmaceuticals in the form of dry powders.
Methods. Human monoclonal antibody coated microcrystals were prepared by coprecipitation of an aqueous mixture of PBS buffered human monoclonal antibody and concentrated glycine into propan-2-ol. The standard formulation contained mAb buffer salts and glycine and the effect of including potential precipitation stabilizing additives (PSA) was investigated e.g. Glu, Arg.
Following coprecipitation, the PCMC particles were filtered and air-dried to form free-flowing dry powders. Protein integrity was assessed by comparing optical clarity of the reconstituted formulations, protein concentration by UV spectroscopy and monomer content by size-exclusion chromatography, using a Tosoh TSKgel G3000 SWXL 7.8 mm ID x 30 cm column.
Results. The measured protein loadings were found to be within 5% of the target protein loading for all formulations. However, the optical clarity of reconstituted PCMC prepared with optimal PSA was significantly better. Protein particulates could be observed in reconstituted standard samples, whilst PCMC utilising PSA, such as Glu, Arg, were optically clear and free of particulates. Consistent with this, measurement of the degree of monomer conservation following coprecipitation showed that material produced without PSA generally had monomer retention of less than 90% whilst optimised samples incorporating
PSA resulted in >98% of monomer conservation.
Conclusion. Human monoclonal antibodies can be readily formulated using PCMC technology by incorporating precipitation stabilizing additives (PSA). PCMC coprecipitation leads to finely-divided dry powders, which can be rapidly reconstituted back into aqueous, to release the monoclonal antibody in monomeric form.
LanguageEnglish
PagesM1032
Publication statusPublished - 21 Jun 2009
Event2009 AAPS National Biotechnology Conference - Seattle, United States
Duration: 21 Jun 200924 Jun 2009

Conference

Conference2009 AAPS National Biotechnology Conference
CountryUnited States
CitySeattle
Period21/06/0924/06/09

Fingerprint

Powders
Temperature
Proteins
Monoclonal Antibodies
Therapeutics
Glycine Agents
Technology
Glycine
Gel Chromatography
Spectrum Analysis
Buffers
Salts
Air

Keywords

  • protein-coated microcrystals
  • PCMC
  • precipitation stabilizing additives
  • PSA
  • dry powder biopharmaceuticals

Cite this

Gebbie, W., Davidson, K., Partridge, J., Vos, J., & Moore, B. (2009). Dry powder therapeutic mAb formulations with enhanced temperature stability. M1032. Poster session presented at 2009 AAPS National Biotechnology Conference, Seattle, United States.
Gebbie, Willa ; Davidson, Katrina ; Partridge, Johann ; Vos, Jan ; Moore, Barry. / Dry powder therapeutic mAb formulations with enhanced temperature stability. Poster session presented at 2009 AAPS National Biotechnology Conference, Seattle, United States.
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title = "Dry powder therapeutic mAb formulations with enhanced temperature stability",
abstract = "Purpose. There is an increasing demand for differentiated strategies for formulating and delivering mAb in particulate form. The aim of this study was to investigate methods for optimising protein-coated microcrystal (PCMC) formulations of a human monoclonal antibody. PCMC technology provides a novel method of stabilising these important biopharmaceuticals in the form of dry powders. Methods. Human monoclonal antibody coated microcrystals were prepared by coprecipitation of an aqueous mixture of PBS buffered human monoclonal antibody and concentrated glycine into propan-2-ol. The standard formulation contained mAb buffer salts and glycine and the effect of including potential precipitation stabilizing additives (PSA) was investigated e.g. Glu, Arg.Following coprecipitation, the PCMC particles were filtered and air-dried to form free-flowing dry powders. Protein integrity was assessed by comparing optical clarity of the reconstituted formulations, protein concentration by UV spectroscopy and monomer content by size-exclusion chromatography, using a Tosoh TSKgel G3000 SWXL 7.8 mm ID x 30 cm column.Results. The measured protein loadings were found to be within 5{\%} of the target protein loading for all formulations. However, the optical clarity of reconstituted PCMC prepared with optimal PSA was significantly better. Protein particulates could be observed in reconstituted standard samples, whilst PCMC utilising PSA, such as Glu, Arg, were optically clear and free of particulates. Consistent with this, measurement of the degree of monomer conservation following coprecipitation showed that material produced without PSA generally had monomer retention of less than 90{\%} whilst optimised samples incorporatingPSA resulted in >98{\%} of monomer conservation.Conclusion. Human monoclonal antibodies can be readily formulated using PCMC technology by incorporating precipitation stabilizing additives (PSA). PCMC coprecipitation leads to finely-divided dry powders, which can be rapidly reconstituted back into aqueous, to release the monoclonal antibody in monomeric form.",
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Gebbie, W, Davidson, K, Partridge, J, Vos, J & Moore, B 2009, 'Dry powder therapeutic mAb formulations with enhanced temperature stability' 2009 AAPS National Biotechnology Conference, Seattle, United States, 21/06/09 - 24/06/09, pp. M1032.

Dry powder therapeutic mAb formulations with enhanced temperature stability. / Gebbie, Willa; Davidson, Katrina; Partridge, Johann; Vos, Jan; Moore, Barry.

2009. M1032 Poster session presented at 2009 AAPS National Biotechnology Conference, Seattle, United States.

Research output: Contribution to conferencePoster

TY - CONF

T1 - Dry powder therapeutic mAb formulations with enhanced temperature stability

AU - Gebbie, Willa

AU - Davidson, Katrina

AU - Partridge, Johann

AU - Vos, Jan

AU - Moore, Barry

PY - 2009/6/21

Y1 - 2009/6/21

N2 - Purpose. There is an increasing demand for differentiated strategies for formulating and delivering mAb in particulate form. The aim of this study was to investigate methods for optimising protein-coated microcrystal (PCMC) formulations of a human monoclonal antibody. PCMC technology provides a novel method of stabilising these important biopharmaceuticals in the form of dry powders. Methods. Human monoclonal antibody coated microcrystals were prepared by coprecipitation of an aqueous mixture of PBS buffered human monoclonal antibody and concentrated glycine into propan-2-ol. The standard formulation contained mAb buffer salts and glycine and the effect of including potential precipitation stabilizing additives (PSA) was investigated e.g. Glu, Arg.Following coprecipitation, the PCMC particles were filtered and air-dried to form free-flowing dry powders. Protein integrity was assessed by comparing optical clarity of the reconstituted formulations, protein concentration by UV spectroscopy and monomer content by size-exclusion chromatography, using a Tosoh TSKgel G3000 SWXL 7.8 mm ID x 30 cm column.Results. The measured protein loadings were found to be within 5% of the target protein loading for all formulations. However, the optical clarity of reconstituted PCMC prepared with optimal PSA was significantly better. Protein particulates could be observed in reconstituted standard samples, whilst PCMC utilising PSA, such as Glu, Arg, were optically clear and free of particulates. Consistent with this, measurement of the degree of monomer conservation following coprecipitation showed that material produced without PSA generally had monomer retention of less than 90% whilst optimised samples incorporatingPSA resulted in >98% of monomer conservation.Conclusion. Human monoclonal antibodies can be readily formulated using PCMC technology by incorporating precipitation stabilizing additives (PSA). PCMC coprecipitation leads to finely-divided dry powders, which can be rapidly reconstituted back into aqueous, to release the monoclonal antibody in monomeric form.

AB - Purpose. There is an increasing demand for differentiated strategies for formulating and delivering mAb in particulate form. The aim of this study was to investigate methods for optimising protein-coated microcrystal (PCMC) formulations of a human monoclonal antibody. PCMC technology provides a novel method of stabilising these important biopharmaceuticals in the form of dry powders. Methods. Human monoclonal antibody coated microcrystals were prepared by coprecipitation of an aqueous mixture of PBS buffered human monoclonal antibody and concentrated glycine into propan-2-ol. The standard formulation contained mAb buffer salts and glycine and the effect of including potential precipitation stabilizing additives (PSA) was investigated e.g. Glu, Arg.Following coprecipitation, the PCMC particles were filtered and air-dried to form free-flowing dry powders. Protein integrity was assessed by comparing optical clarity of the reconstituted formulations, protein concentration by UV spectroscopy and monomer content by size-exclusion chromatography, using a Tosoh TSKgel G3000 SWXL 7.8 mm ID x 30 cm column.Results. The measured protein loadings were found to be within 5% of the target protein loading for all formulations. However, the optical clarity of reconstituted PCMC prepared with optimal PSA was significantly better. Protein particulates could be observed in reconstituted standard samples, whilst PCMC utilising PSA, such as Glu, Arg, were optically clear and free of particulates. Consistent with this, measurement of the degree of monomer conservation following coprecipitation showed that material produced without PSA generally had monomer retention of less than 90% whilst optimised samples incorporatingPSA resulted in >98% of monomer conservation.Conclusion. Human monoclonal antibodies can be readily formulated using PCMC technology by incorporating precipitation stabilizing additives (PSA). PCMC coprecipitation leads to finely-divided dry powders, which can be rapidly reconstituted back into aqueous, to release the monoclonal antibody in monomeric form.

KW - protein-coated microcrystals

KW - PCMC

KW - precipitation stabilizing additives

KW - PSA

KW - dry powder biopharmaceuticals

UR - http://abstracts.aaps.org/published/ContentInfo.aspx?conID=19420

UR - http://formulation.org.uk/index.php?option=com_content&view=article&id=279&Itemid=223

M3 - Poster

SP - M1032

ER -

Gebbie W, Davidson K, Partridge J, Vos J, Moore B. Dry powder therapeutic mAb formulations with enhanced temperature stability. 2009. Poster session presented at 2009 AAPS National Biotechnology Conference, Seattle, United States.