The in vivoPig-a gene mutation assay is based on the endogenous X-linked Pig-a gene (phosphatidylinositol N-acetylglucosaminyltransferase, subunit A).
The Pig-a gene codes for an N-acetyl glucosamine transferase that is involved in the biosynthesis of Glycosyl phosphatidyl inositol (GPI) anchor for tethering a variety of mammalian cell surface protein markers. A single mutation in the Pig-a gene results in loss of the GPI anchor and the GPI-tethered protein markers and can be detected by fluorescent antibodies against the surface markers and flow cytometric analysis to quantify marker deficient cells.
The Pig-a assay has been evaluated internationally and the data generated to date indicate that it is sensitive, robust and has high reproducibility and transferability. With this in mind, Working Groups of the International Workshop on Genotoxicity Testing (IWGT) and HESI Genetic Toxicology Technical Committee (GTTC) have been working towards the development of an OECD testing guideline for performing the Pig-a assay in rodents, which will allow the Pig-a assay to be used for regulatory assessments in drug development.
Current guidance for the assessment of DNA reactive (mutagenic) impurities in pharmaceuticals (ICH M7(R1)) has already suggested the use of the Pig-a assay to investigate the in vivo relevance of in vitro mutagens (Ames positive).
Jim Whitwell Jim has a BSc (Hons) degree in Applied Biological Sciences from the University of Bristol. He has more than 25 years of experience in genetic toxicology and related fields and currently serves as Scientific Specialist and Subject Matter Expert for in vitro micronucleus assays within Genetic Toxicology.
His areas of expertise include in vitro and in vivo chromosome aberration and micronucleus assays, peripheral blood and flow in vivo micronucleus studies and non-standard assay designs (e.g. sister chromatid exchange and mechanistic mode of action investigations).
He is a member of several industry groups and has presented at industry conferences, as well authoring and co-authoring multiple publications in journals such as Mutation Research and Mutagenesis.
Darren Kidd Darren has a BSc (Hons) degree in Biological Sciences from the University of Plymouth and a PhD entitled “In Vitro Gene Mutation and Apoptosis” from the University of York. He has more than 20 years of experience as scientist, toxicologist and study director in laboratory research and currently serves as Lead Scientist for in vitro toxicology assays within Genetic Toxicology.
His areas of expertise include in vitro micronucleus, skin, ocular, phototoxicity and cytotoxicity assays, flow cytometric applications and mechanistic investigations.
He is member of several industry groups and has authored or co-authored dozens of posters, presentations and publications in journals such as Mutation Research, Toxicology in vitro, Genetic Toxicology and Environmental Mutagenesis, Methods in Molecular Biology and Mutagenesis.
Robert Smith Robert has a MSc in Biology from the University of York. He has over 15 years of experience within genetic toxicology at Covance from working in the laboratory on standard and non-standard genotoxicity assays and currently serves as a Study Director within Genetic Toxicology with emphasis on screening as well as investigative work and method development.
His areas of expertise include Ames, in vitro and in vivo chromosome aberration and micronucleus assays, in vivo Comet and MutaMouse, 3D skin micronucleus and fluorescence in situ hybridisation (FISH) assays.
He is member of several industry groups and is the current secretary of UKEMS. He has authored or co-authored publications in Mutation Research and Mutagenesis.
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Joint PSI, EFSPI & ASA BIOP Webinar: Estimands
PSI, the European Federation of Statisticians in the Pharmaceutical Industry (EFSPI) and the Biopharmaceutical Section of the American Statistical Association (ASA) are jointly organising a webinar on Estimands in Practice. Speakers from regulatory authorities (FDA and EMA) and industry will present on their experience on this topic to date.
Discover your potential by working as a Covance Senior Principal / Principal Biostatistician. You'll enjoy a varied role working for different sponsors across several therapeutic areas, leading projects and mentoring junior members of the department.
Biometrics at AstraZeneca provides the data that influences decisions on how we roll back the frontiers of science to bring life-changing medicines to the world. We are at the heart of design, analytics and interpretation of AstraZeneca’s portfolio.