Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
3.
Bioanalysis ; 3(9): 1001-6, 2011 May.
Article in English | MEDLINE | ID: mdl-21545348

ABSTRACT

"Good people are good because they've come to wisdom through failure" - William Saroyan. Since the Crystal City III conference considerable effort has been spent defining what constitutes appropriate incurred sample reanalysis analysis. While what to do, such as the number of samples and acceptance criteria, is becoming generally recognized, it is important to step back and examine as a community what we are learning by this exercise. Through discussions with colleagues throughout the industry who specialize in macromolecule analysis, it was clear most incurred sample reanalysis testing passes without issue, but in some cases there are lessons to be learned. We thank all who would share, in confidence, their failures as well as their investigations so as a community we can learn. We would suggest scientist can be substituted for people in the quote from William Saroyan.


Subject(s)
Artifacts , Biological Assay , Macromolecular Substances , Solvents/analysis , Specimen Handling/methods , Drug Stability , Drug Storage/standards , Guidelines as Topic , Humans , Macromolecular Substances/analysis , Macromolecular Substances/chemistry , Problem Solving , Quality Control , Reference Standards , Reproducibility of Results , Time Factors , Validation Studies as Topic
4.
J Pharm Biomed Anal ; 48(5): 1282-9, 2008 Dec 15.
Article in English | MEDLINE | ID: mdl-18977625

ABSTRACT

Application of research-grade diagnostic kits in clinical drug development has grown commensurate with the increased interest in utilization of biomarkers as drug development tools. Since novel biomarkers are frequently macromolecular, immunoassay methodology comprises the 'technology-of-choice' for biomarker quantification. In particular, commercial research-grade immunoassay kits are appealing for use in biomarker quantification during clinical phase drug development because of their ready availability, ease of operation and perceived convenience. However, bioanalytical validation issues arise often during the application of commercial kits, as GLP regulatory-compliant application places greater demands on kit design and performance. In this review, we have used the receptor activator of nuclear factor kappaB ligand (RANKL) as a model system to offer some insights into the challenges that can be encountered in the application of 'research-grade' diagnostic kits in support of clinical drug development. Currently only a few assays are available commercially for the determination of circulating concentrations of sRANKL. Of these, two immunoassay designs have been most often. The first design employs human osteoprotegerin to capture unbound sRANKL from serum and, thereby, provides a measure of circulating free concentrations. In contrast, the other common assay design first involves preincubation of serum samples with human osteoprotegerin to convert the free fraction of sRANKL to the osteoprotegerin-bound complex. The bound fraction is subsequently captured by an anti-osteoprotegerin antibody. In both immunoassay designs, detection is accomplished with an anti-sRANKL enzyme conjugation system. In this report we review these sRANKL immunoassay designs critically from the perspective of their potential suitability as drug development biomarker tools. In addition, analytical challenges relevant to the application of these 'research-grade' diagnostic kits for regulatory-compliant determination of sRANKL concentrations are discussed.


Subject(s)
Biomarkers/blood , Drug Design , Reagent Kits, Diagnostic/statistics & numerical data , Receptor Activator of Nuclear Factor-kappa B/blood , Humans , Immunoassay , Osteoprotegerin/blood , RANK Ligand/blood , Reproducibility of Results , Research , Solubility
SELECTION OF CITATIONS
SEARCH DETAIL
...