Linked Life Data

20229596

Source:http://linkedlifedata.com/resource/pubmed/id/20229596

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2010-6-28
pubmed:abstractText
The development of a Microflow digital imaging (MDI) method to detect and monitor protein particulates in a high concentration IgG1 monoclonal antibody formulation is presented. The MDI assay was optimized and qualified as a characterization assay in terms of accuracy and precision of particle size and number using polystyrene standards (5-300 microm) and protein particles (2 to >100 microm). The stability profile of a 90 mg/mL IgG1 formulation stored at 2-8 degrees C and -70 degrees C for up to 18 months was then investigated. The MDI assay results showed improved sensitivity to detect subvisible particulates (>or=5 microm) compared to conventional light obscuration detection, presumably due to the translucent nature of the protein particles. For evaluation of visible protein particles (>70 microm), a good overall correlation was observed for MDI, inverted microscopy and visual assessments. Long-term stability data for a high concentration IgG1 monoclonal antibody formulation demonstrated an accumulation of protein particles in certain size categories with a concomitant increase in the overall particle size distribution over time. The weight amount of protein particulates in the IgG1 formulation was measured experimentally as approximately 0.022% (approximately 20 microg/mL) after storage at 2-8 degrees C for 16 months. Similar results were obtained by calculation from the MDI particle data indicating a low level of protein particulates by weight. The nature and composition of the protein particulates formed during storage were further characterized by a combination of inverted microscopy, FTIR microscopy, and SEM-EDX. Particulates were identified as protein with silicone, although some particles also contained other elements such as aluminum. The combination of MDI results and protein characterization studies have provided an enhanced understanding of protein particulate formation during long-term storage of a high concentration IgG1 monoclonal antibody formulation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1520-6017
pubmed:author
pubmed:copyrightInfo
(c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association
pubmed:issnType
Electronic
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3343-61
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Development of a microflow digital imaging assay to characterize protein particulates during storage of a high concentration IgG1 monoclonal antibody formulation.
pubmed:affiliation
BioPharmaceutical Development and Marketed Product Support, Centocor R&D, Inc., Schaffhausen, Switzerland. kwuchne1@its.jnj.com
pubmed:publicationType
Journal Article