For the transformation of starting material into the product is needed API synthesis, which involves multiple reaction steps, including reagents, intermediates, catalysts, solvents and others. As a result, low levels of by-products may appear in API as impurities. This impurity may have toxicity, incl. carcinogenicity and genotoxicity, what may cause mutations, potentially leading to cancer. Due to this fact and focusing on ensuring safety of public health is critical to identify, monitor, analyse and control genotoxic impurities and strive to their minimum level. This has led to the crucial need in the development and improvement of analytical methods.
The Genotoxic Impurities in Pharmaceuticals Summit 2019 is focusing on overcoming challenges and barriers, sharing knowledge, strategies, best techniques and new methodologies in GTI predictions, analysis and control during the drug development process, overview and practical implementation of GTI guidelines and regulations (ICH M7 and ICH Q3D), risk assessment, exposure limits calculation and predictions' empowerment through in silico.
08:00 Registration and Welcome Coffee
08:30 Opening Address from the Chairman
08:40 ICH M7 and extractables & leachables: understanding control, analysis and regulations of E&L.
Andrew Feilden,
Director Analytical Sciences, Bicycle Therapeutics, Shawbury, United Kingdom
09:15 Speed Networking
09:55 Examples of use of ICH M7 in early and late drug development including pediatrics.
Dr. Lutz Mueller,
Toxicology Project Leader – Distinguished Scientist, F. Hoffmann-La Roche Ltd., Basel, Switzerland
10:30 ICH Q3D: safety assessment of elemental impurities in topical drugs. The challange in defining the appropriate scenario of exposure.
Carla Landolfi, ERT,
European Registered Toxicologist (ERT) R&D, Head of WEP Toxicology - Preclinical Development, Angelini, Pomezia, Italy
11:05 Morning coffee and networking break
11:35 Screening and control of genotoxic impurities – An analytical approach.
A variety of process materials and reactive compounds are involved in the synthesis of pharmaceutical products. As a consequence, residues of such compounds and related degradation products can later be found as drug impurities in API and final formulation Some of those impurities are known to be mutagenic with the potential to cause adverse effects on the human body even when only present at trace level concentrations.
The detection, quantification and evaluation of such impurities is important but can be very challenging since matrix effects often discriminate these compounds. In many cases the route of synthesis allows to predict potential impurities. However, in other cases unexpected genotoxic compounds may be an issue since predictability is limited due to complexity of processes and formulations.
In our presentation we highlight the analytical challenges and propose possible solutions:
Case studies and examples
Dr. Stefan Heck,
Business Development Manager Pharma DACH, Intertek (Schweiz)AG, Freiburg, Germany
12:10 Characterization and quantitation of genotoxic impurities using a single platform. The Valsartan case.
To ensure patient safety, regulatory agencies have put in place guidelines which mandate the identification and profiling of impurities in APIs and formulated drug products and sets thresholds at which these impurities must be reported.
The Valsartan case, has shown the need for the implementation of the state of the art technology in the QC/QA laboratories. A creation of a fast, high throughput, robust, and reproducible analytical technology and method (e.g., LC-MS) is critical for increased confidence in impurity identification, detection, and quantification in pharma research to increase the safety of the end product. This critical information speeds drug candidate development from IND-enabling studies to NDA.
In our presentation we show how the combination of the speed, sensitivity and resolution on the latest QTOF technology can help to solve the questions related to the characterization and quantiation of impurities, with a system and solution that:
Axel Besa,
Business Development Manager, SCIEX, Dortmund, Germany
12:45 Business lunch
13:50 ICH Q3D: elemental impurities- an insider’s perspective.
Anja Slikkerveer, MD, PhD, ERT,
Scientific Director Translational Science, Astellas Pharma Europe BV, Hague, Netherlands
14:25 What to do if you need to do to propose a regulatory change to a ICH Q3D Elemental Impurity Control Threshold or PDE Limit.
Lance Smallshaw BSc(Hons) PhD EurChem CSci CChem FRSC,
Regulatory Intelligence and External Advocacy (Quality Analytical and Pharmacopoeia), UCB Biopharma sprl., Wallonia, Belgium
15:00 Afternoon coffee and networking break
15:30 Strategies for assessment of impurities and E&Ls.
Prof. Dr. Johannes Harleman
Independent Consultant, , Darmstadt, Germany
16:05 Use of the Bacterial Reverse Mutation (Ames) Test to Evaluate Impurities.
Leon F. Stankowski,
Senior Scientific Director, Genetic and In Vitro Toxicology, Charles River Laboratories, Chicago, USA
16:40 Challenges calculating compound-specific exposure limits.
Patricia Parris,
Project Toxicologist (RIA Safety), AstraZeneca, Royston, United Kingdom
17:15 Panel Discussion
17:40 Chairman’s closing remarks and end of day one
19:00 Business dinner
08:00 Registration and Welcome Coffee
08:30 Opening Address from the Chairman
08:40 Assessment and control of potential mutagenic impurities to comply with ICH M7.
Dr. M. Vijay Reddy,
Senior Principal Scientist in the department of Genetic Toxicology, Merck & Co., Inc., USA
09:15 Genotoxic Impurity Controls post ICH M7: BMS Work Practices for Assessing and Controlling GTIs.
The development and execution of Genotoxic Impurity control strategies has become a regulatory requirement for all phases of development.
With the issuance of ICH M7 sponsors now have clear guidance on the strategies which will be required to meet these expectations.
BMS has an aligned process which uses the principles in ICH M7 to define these control strategies.
This presentation will review GTI examples from the BMS portfolio which highlight these different control strategies.
Rodney Parsons,
Executive Director, Chemical and Synthesis Development, Bristol-Myers Squibb, Philadelphia, USA
09:50 Morning coffee and networking break
10:20 Retrospective assessment of the process for mutagenic impurities is also discussed using “free data” to verify purging.
Mike Urquhart,
Scientific Director, GlaxoSmithKline, Stevenage, United Kingdom
10:55 Control of toxic impurities in pharmaceutical products.
Tom van Wijk,
Principal Scientist, Analytical Science and Technology Team lead Pharmaceutical analysis, Abbott Healthcare Products B.V., Weesp, The Netherlands
11:30 Best practice for dealing with conflicting computational predictions for mutagenicity.
Raphael Nudelman, Ph.D., ERT,
Senior Director Impurity Expert, Teva Pharmaceutical Industries Ltd., Israel
12:05 Business lunch
13:05 In silico assessment of genotoxic impurities under the ICH M7 guideline (best practice in industry).
Dr. Joerg Wichard,
Pharmaceuticals Division / Genetic Toxicology BLN, Bayer AG, Berlin, Germany
13:40 Interactions of Leachables with Biopharmaceuticals: Combined In-Silico and Experimental Model to Monitor the Potential Impact on Quality and Safety of Therapeutic Proteins.
Koen Nuyts , Ph.D.,
Study Director, Nelson Labs Europe, Antwerp, Belgium
Ank Reumer, Ph.D.,
Study Director Pharma Services, Nelson Labs Europe, Leuven, Belgium
14:15 Chairman’s closing remarks and end of day one
14:25 Afternoon coffee and networking break
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Abbott Healthcare Products B.V. - Alkaloid AD - Angelini - Astellas Pharma Europe BV - AstraZeneca - Bayer AG - Bristol-Myers Squibb - Charles River Laboratories - Cipla Limited - Elanco Animal Health - Elpen Pharmaceutical Co.Inc. - Eurofarma labs - F. Hoffmann-La Roche Ltd - Fresenius Kabi Deutschland GmbH - GlaxoSmithKline - Intertek (Schweiz) AG - Lhasa Limited - Merck & Co., Inc. - Nelson Labs Europe - S-IN Soluzioni Informatiche Srl - SCIEX - Smithers Rapra Ltd. - Teva - Teva Pharmaceutical Industries Ltd. - ToxMinds BVBA - UCB Biopharma sprl. - Others