Document Detail

Characterization of the photodegradation of a human IgG1 monoclonal antibody formulated as a high-concentration liquid dosage form.
MedLine Citation:
PMID:  19009595     Owner:  NLM     Status:  MEDLINE    
The photodegradation of a human IgG1 monoclonal antibody has been examined in a high concentration (100 mg/mL) liquid formulation. It was observed that a yellowish color is generated when the formulation is exposed to intense and prolonged light exposure, and this discoloration occurs along with a loss in bioactivity. Extensive analytical characterization was performed to determine light induced degradation pathways that occur during exposure to intense light of ICH photodegradation conditions. It has been shown that the monoclonal antibody undergoes a combination of physical and chemical reactions under these conditions, including covalent aggregate formation, fragmentation at the hinge region, oxidation of Trp, His, and Met residues, and deamidation of Asn residues. Oxidation of Trp 94 and deamidation of Asn 93, located in the light chain CDR region, correlates with loss of bioactivity under these conditions. A series of formulation experiments were performed to elucidate the impact of the extent of light exposure, oxygen, protein concentration, and solution pH on the photostability of the formulation. Results demonstrated that photodegradation of the IgG, after intensive light exposure, can be prevented by proper secondary packaging. In addition, it is also shown that a high concentration, liquid dosage form of a human monoclonal antibody is stable upon exposure to the ambient light conditions encountered during routine manufacturing, long-term storage, and administration with proper design of formulation conditions, the primary container as well as the secondary package.
Pei Qi; David B Volkin; Hui Zhao; Michael L Nedved; Robert Hughes; Ryan Bass; Sun C Yi; Mark E Panek; Dana Wang; Paul Dalmonte; Michael D Bond
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  98     ISSN:  1520-6017     ISO Abbreviation:  J Pharm Sci     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-04     Completed Date:  2009-10-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3117-30     Citation Subset:  IM    
Pharmaceutical Development Department, Centocor R&D, Inc., 145 King of Prussia Road, Radnor, Pennsylvania 19087, USA.
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MeSH Terms
Antibodies, Monoclonal / analysis,  metabolism
Immunoglobulin G / analysis*,  metabolism*
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Excipients; 0/Immunoglobulin G; 7727-37-9/Nitrogen

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