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Exclusive Podcast Interviews Predictive Toxicology Thought Leaders

• How to Ensure High Levels of Good Clinical Practice - We Ask Merck
  
  Amer Alghabban, Head of the GCP Auditing Group at Merck Serono, joins Helen Winsor from Pharma IQ, to talk about the implementation of GCP and effective auditing of clinical trials. First he discusses where he thinks the main challenges are in ensuring high levels of GCP, as well as the technologies and solutions Merck employs.
  
  He also discusses whether quality-based risk management is something that will provide benefit when auditing. Next, Alghabban discusses the application of electronic data capture, the main challenges in satisfying regulatory criteria during audits, how first time approval can be assured and Merck’s approaches.
  
  Listen to Podcast
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• The Potential of Stem Cell Models for Safety Testing
  
  "We have established the hESCreg database on hESC s (EC FP6). We’re also currently involved in ESNATS (EC FP7) to develop hESC for use in drug discovery and toxicology studies. And finally, there are some new EC FP7 projects, Toxbank and Screentox, supporting data co-ordination of the current EC stem cell projects co-founded by COLIPA (Toxbank) and we are developing protocols for use of iPSC lines in routine toxicology screening (Screentox)", said Dr. Glyn Stacey, Director of the UK Stem Cell Bank.
  
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• Generating Metabolically Active Hepatocytes from Pluripotent Stem Cells
  
  Dr Dave Hay, Principal Investigator at the MRC Centre for Regenerative Medicine, joins Pharma IQ to discuss the challenges and potential of metabolically active hepatocytes, covering the following areas:
  
  • Insights into polymer screening to identify culture matrices which can regulate cell phenotypes.
  • How to achieve stability using a novel polymer matrix.
  • How high through-put polymer screening can be applied to enhance the stability of stem cell models.
  • The future development of stem cell use in predictive toxicology.
• Pre-Clinical Toxicity: Avoiding Common Mistakes in Early Development
  
  Dr. Mitchell Friedman, Director of Toxicology at Takeda Pharmaceuticals, discusses pre-clinical toxicity and avoiding common mistakes in early development so as to secure patient safety and better ROI.
  Listen to Podcast

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Further Reading - Exclusive Articles

The need for predictive toxicology
"The next hurdle for acceptance of mitochondrial impairment as an important cause of tissue toxicities is to establish tighter linkages between in vitro models and clinical outcomes. Some of this will be accomplished by correlative studies demonstrating relative toxicities for various drug classes in both in vitro and in vivo models, including the clinic," explained James A Dykens, Lisa D Marroquin and Yvonne Will in their report entitled Strategies to reduce late-stage attrition due to mitochondrial toxicity.

• Late stage trial success and the cost of failure
  Late stage drug attrition accounts for a significant amount of the cost of developing a new drug and failure can often have a major impact on the organisation creating it. It is estimated that the total cost of development of an innovative drug is in excess of $800 million (£518 million) and so it is more important than ever to… read more
• The importance of predictive toxicology
  It is imperative that pharmaceutical companies get it right when bringing a new product to market and this includes employing correct methodologies through the trial process. The failure of late-stage clinical trials accounts for a large proportion of the cost of development, which is why it is vital for companies to… read more
• Pharma IQ Article - InterMune calls off high dose trials after toxicity concerns
• Research Article Development of an In Vivo GeneMutation Assay Using the Endogenous Pig-A Gene
• Evaluation of Macaca mulatta as a model for genotoxicity studies
• Nirmala Bhogal, Rita Seabra and Michelle Hudson examine methods to limit the level of animal testing in clinical research
• Regulatory and scientific barri ers to the safety evaluation of medical nanotechnologies
• Published MUTGEN401662 Vasily Dobrovolsky
• Drug induced mitochondrial dysfunction: An emerging model for idiosyncratic drug toxicity
  By Dr James A. Dykens, Associate Research Fellow, Drug Safety R&D, Pfizer

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2011 Presentations

	Laszlo Urban, Preclinical Safety ProfilingNIBR, Cambridge, Ma. presents: How To Mitigate Cardiac Toxicity During Lead Selection And Lead Optimization? Major cardiac ion channel and non-ion channel targets associated with drug-related cardiotoxicities Application of assays and in silico tools for risk assessment and mitigation Predictive value of in vitro assays and associated follow-up tests for clinical adverse reactions Critical evaluation of the strategy and methodologies that can be employed to mitigate cardiac toxicity Click here to download Laszlo Urban presentation
	Frank W Bonner, Stem Cell for Safer Medicines (SC4SM) presents: Exploring the Potential of Stem Cell Assays in Predictive Toxicology Testing What are the important issues challenging the pharmaceutical industry? Why do we need improved predictive toxicology assays in drug development? What are the prerequisites for successful exploitation of stem cell assays? SC4SM Predictive Toxicology consortium: progress and plans Emerging opportunities Click here to download Frank W Bonner presentation
	Glyn Stacey, NIBSC-HPA presents: UK Stem Cell Bank: Supporting the Development of Stem Cell Models for Safety Testing. The UK Stem Cell Bank and its relationship with the industry Scientific and technical activity: supporting the development of effective, efficient and accurate stem cell assays EU and international projects: how they will impact the utility of stem cells in safety testing Click here to download Glyn Stacey presentation
	David R Jones, Expert Scientific Assessor (Pharmacotoxicologist), Licensing Division, Medicines and Healthcare products Regulatory Agency (MHRA), UK presents: Predictive Toxicology A Regulatory View The Role of the MHRA Regulatory Guidelines Scientific Advice Future Perspectives Click here to download David R Jones presentation

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Past Presentations

• Dr Paul Hastwell, Senior Scientist, GlaxoSmithKline presents:
  Application and Impact of Early Genotoxicity Assessment and Predictive Toxicology at GSK
  
  • Review of the need for reliable and predictive assays that can be used early in drug development
  • Approaches: In silico methods and genotoxicity methods including implementation of the GreenScreen in routine screening
  • Benefits of employing early Predictive Toxicology – reducing late stage drug attrition and missed opportunities
  
  Click here to download Dr Hastwell presentation
• Dr James Dykens, Associate Research Fellow, Drug Safety R&D at Pfizer presents:
  In Vitro Methods- Optimising Cell Models for Detecting Drug Induced Mitochondrial Dysfunction
  
  FOCUS POINT:
  Many drugs have ‘off-target’ deleterious effects on mitochondrial function. These effects have been underappreciated because many cell and animals models fail to report them. But new assays and animal models have been developed that do detect drug- induced mitochondrial dysfunction. These data support a new model of idiosyncratic drug toxicity…
  
  Click here to download Dr Dykens presentation
• Dr Mitchell Friedman, Director of Toxicology, Takeda Pharmaceuticals presents:
  Predicting Success/Failure: common mistakes in discovery and development
  
  FOCUS POINTS:
  • Mistakes to avoid in choosing compounds from discovery
  • Mistakes to avoid in early development
  • Case studies that illustrate pharmaceutical folly
  • Dealing with toxic assets
  
  Click here to download Dr Friedman presentation
• Dr Vasily N. Dobrovolsky from the Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research presents: An In Vivo Gene Mutation Assay for Hazard Identification and Risk Assessment: The Pig-A Story
  
  Mutation is involved in cancer onset and progression. Regulatory authorities require thorough characterization of all new drugs for mutagenicity. Cost efficient high throughput approaches are needed for better predicting genotoxic hazards that may impact on human health. A new model for detection of in vivo mutation in the endogenous Pig-A gene of cells in peripheral blood is a sensitive tool for use in screening and identification of potential mutagens during preclinical safety evaluations and in early clinical trials. The following topics are covered:
  
  • Limitations of the current ICH battery of genotoxic tests for safety assessment
  • Design of a novel high throughput model for detection of in vivo gene mutation
  • Laboratory animals - background and induced Pig-A mutation in rats and monkeys
  • Human PIG-A model - results from healthy and exposed Populations
  Click here to download Dr Dobrovolsky presentation

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