| 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 |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
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 |
Related Documents
:
|
1447685 - Stimulus recognition and the mere exposure effect. 20635315 - [does long-term asbestos exposure cause an obstructive ventilation pattern?]. 16012345 - Shift in the cochlear place-frequency map after noise damage in the mouse. 17274995 - Mother's timing and duration of corticosterone exposure modulate offspring size and nat... 21828755 - Monolithic gaas/ingap nanowire light emitting diodes on silicon. 10521625 - Three-dimensional motion analysis of upper limb movement in the bowing arm of string-pl... |
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 |
Affiliation:
|
Pharmaceutical Development Department, Centocor R&D, Inc., 145 King of Prussia Road, Radnor, Pennsylvania 19087, USA. qi@alderbio.com |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Antibodies, Monoclonal
/
analysis,
metabolism Excipients Humans Immunoglobulin G / analysis*, metabolism* Light Nitrogen Oxidation-Reduction Photolysis |
| Chemical | |
Reg. No./Substance:
|
0/Antibodies, Monoclonal; 0/Excipients; 0/Immunoglobulin G; 7727-37-9/Nitrogen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Pharmacokinetics of CPX-351 (cytarabine/daunorubicin HCl) liposome injection in the mouse.
Next Document: Ultrastructural characterization of the new NG97ht human-derived glioma cell line using two differen...