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 2021 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.
12:00 Registration
12:20 Opening Address
12:30 Regulatory Updates on Nitrosamine Impurities.
It has become mandatory to understand current regulations and recommendations by FDA, EMA, WHO and other authorities to implement adequate quality risk management principles to make science-based decisions to mitigate potential risks. Competent staff, sound knowledge and in-depth understanding of products and processes are critical when assessing potential risks to manufacturing processes to ensure that patient safety is adequately protected.
Vimal Sachdeva,
Technical Officer (Expert Inspector), World Health Organization (WHO), CH, Switzerland
13:00 Questions & Answers
13:10 Meeting the challenge of trace analysis of N-nitrosamines -The impact for the pharmaceutical industry.
Mark Harrison,
Principal Analyst, AstraZeneca, Sheffield, United Kingdom
13:40 Questions & Answers
13:50 Break
14:00 Risk Assessment of Nitrosamines in Pharmaceuticals: Not All Nitrosamines are Highly Potent.
Michelle Kenyon,
Associate research fellow in Drug Safety, Pfizer Global Research and Development, USA
14:30 Questions & Answers
14:40 Development of a Drug Product workflow for Nitrosamine Risk Assessments.
Mike Urquhart,
Scientific Director, GlaxoSmithKline, Stevenage, United Kingdom
15:20 Questions & Answers
15:30 Quantitative Analysis of In Vivo Mutagenicity Dose-Response Data for Risk Assessment and Regulatory Decision-making: A Case Study of Alkylnitrosamines.
Dr. George Johnson,
Associate Professor in the Institute of Life Science, Swansea University, United Kingdom
16:00 Questions & Answers
16:10 Break
16:20 Setting limits for nitrosamines that lack carcinogenicity data.
Raphael Nudelman, Ph.D., ERT,
Senior Director Impurity Expert, Teva Pharmaceutical Industries Ltd., Israel
16:50 Questions & Answers
17:00 Analytical Solutions for the Detection and Quantification of Nitrosamines Using Separations and Mass Spectrometry.
The analytical methodology applied for genotoxic impurity analysis needs to provide an appropriate level of sensitivity to meet the required detection limits and demonstrate good accuracy, precision, and reproducibility. In this work, we present robust analytical approaches for the detection and quantification of nitrosamine impurities using UV, MS and HRMS techniques. The performance and sensitivity of these methodologies are demonstrated by analyzing several nitrosamine impurities in drug substances and drug product formulations.
Margaret Maziarz,
Principal Scientist, Scientific Operations, Waters Corporation, Milford, MA, USA
17:30 Questions & Answers
17:40 PANEL DISCUSSION: 3 general suggestions for assessing positive response.
Dan Roberts,
Genetic Toxicologist and Flow Cytometrist, Charles River Laboratories, USA
18:40 Networking Hour
19:40 Closing remarks and end of day one
12:00 Registration
12:20 Opening Address
12:30 Continuing development of applied chemical knowledge for an in silico purge tool - Incorporating lessons from nitrosamines.
The impact of nitrosamines within drug substances has been felt widely across the regulatory landscape in the last few years. The application of chemistry knowledge within the risk assessment process for nitrosamines has been one of the subjects that has drawn interest from both industry and regulators. The in silico purge tool, Mirabilis, has therefore been adapting to reflect the lessons which have been learnt from the nitrosamine crisis, incorporating an understanding of both the risk of carry-over, and the risk of formation.
Dr. Michael Burns,
Principal Research Scientist, Lhasa Limited, United Kingdom
13:00 Questions & Answers
13:10 Assessment of potential mutagenic degradation products.
Tom van Wijk,
Principal Scientist, Analytical Science and Technology Team lead Pharmaceutical analysis, Abbott Healthcare Products B.V., Weesp, The Netherlands
13:40 Questions & Answers
13:50 Break
14:00 From in silico to in vivo assessment for mutagenicity of impurities.
Carla Landolfi, ERT,
European Registered Toxicologist (ERT) R&D, Head of WEP Toxicology - Preclinical Development, Angelini, Pomezia, Italy
14:30 Questions & Answers
14:40 A Journey for Risk Mitigation of Genotoxic Impurities in Pharmaceutical Products.
Jörg Freudenberger,
Manager Strategy & Global Business Development, Chemicals & Pharma, Intertek, Switzerland
15:10 Questions & Answers
15:20 Break
15:30 Handling mutagenic extractable and leachable compounds released from devices.
Genotoxic compounds can be released from some medical devices during their clinical use. The ISO 10993-17:2002 standard outlines steps to assess the risk posed by patient exposure to genotoxic compounds released from device materials. It is important to note; however, that the ISO 10993-17 standard is currently undergoing revision and the procedures for conducting a toxicological risk assessment of genotoxic compounds are likely to change following revision of the standard. This talk will outline the proposed changes to the ISO 10993-17 standard regarding methods to assess the risk posed by patient exposure to genotoxic compounds released from medical devices and will describe steps to mitigate the risk using risk management strategies. The talk will also briefly address how Carcinogenic, Mutagenic, and Reproductive (CMR) compounds will be handled in Europe under the new Medical Devices Regulation 2017/745/EU.
Ron Brown
Owner and Principal Toxicologist, Risk Science Consortium, LLC, USA
16:00 Questions & Answers
16:10 Can the Ames test adequately predict the carcinogenic potential of nitrosamines?
Mutagenicity data is a core component of the safety assessment data required by regulatory agencies for acceptance of new drug compounds, with the OECD-471 bacterial reverse mutation (Ames) assay most widely used as a primary screen to assess drug impurities for potential mutagenic risk. Previous literature reports indicated that the Ames test might not be sensitive enough to detect the mutagenic potential of N-nitrosamines in order to accurately predict a risk of carcinogenicity. To explore this hypothesis, public Ames and rodent carcinogenicity data pertaining to the N-nitrosamine class of compounds was collated for analysis. Here we present how variations to the OECD 471-compliant Ames test, including type of metabolic activation, solvent type and preincubation/plate incorporation methods, may impact the predictive performance for carcinogenicity. An understanding of optimal conditions for testing of N-nitrosamines may improve both the accuracy and confidence in the ability of the Ames test to identify potential carcinogens.
Rachael Tennant,
Senior Research Scientist, Lhasa Limited, United Kingdom
16:40 Questions & Answers
16:50 Networking Hour
17:50 Closing remarks and end of summit
To register to the summit as a Delegate, please provide the details below. Once the form is submitted, we will send you the official confirmation and the invoice for payment. In case of doubt, contact us at info@qepler.com.
*Please note, all participation packages, contains complete conference materials distribution after the event (Slides, list of participants, stream and video recording). You don't need to order an additional "Documentation Packages".
To register to the summit as a Delegate, Exhibitor or Sponsor, please provide the details below. Once the form is submitted, we will send you the official confirmation and the invoice for payment. In case of doubt, contact us at info@qepler.com.
*Please note, all participation packages, contains complete conference materials distribution after the event (Slides, list of participants, stream and video recording). You don't need to order an additional "Documentation Packages".
Please fill in the details below to get the latest news, discounts, early-bird rates, and upcoming annual details.
€395 - Documentation Package, includes complete conference materials.
Post-event presentations with video recording, slide decks, a list of participants, and other promotional materials.
*The presentation content is subject to speaker’s companies approval for distribution.
Abbott, NL - Amgen, USA - Angelini Pharma Spa, IT - Apotex Research Pvt Ltd, IN - AstraZeneca, UK - Bayer AG, DE - Bibra toxicology advice & consulting Ltd, UK - Boehringer Ingelheim Pharmaceuticals, Inc., USA - Bristol-Myers Squibb, USA - Charles River Laboratories Montreal ULC, CA - Charles River Laboratories, USA - Corteva, USA - CP Pharmaceuticals Ltd, UK - Egis Pharmaceuticals Plc., HU - European Environmental Mutagenesis and Genomics Society, UK - Exponent International Ltd, UK - Freyr Global Regulatory Solutions and Services, IN - FUJIFILM Corporation, JP - Gilead Sciences, USA - GlaxoSmithKline, UK - Hemogfarm AD, RS - Innovature Srl, IT - Intertek (Schweiz) AG, CH - King & Spalding, USA - Kirkland Consulting, UK - Lek d.d., SI - LEO Pharma, IE - Lhasa Limited, UK - Litron Laboratories, USA - Medichem Manufacturing (MALTA) Ltd., MT - Merck & Co., Inc., USA - Novartis GDD/CHAD, CH - Novartis, CH - Pall Corporation, USA - Pfizer Global Research and Development, USA - Pfizer, USA - Polpharma, PL - ProtoQSAR SL, ES - QACS, LTD., GR - Rentschler Biopharma SE, DE - Risk Science Consortium, LLC, USA - SafeBridge Regulatory & Life Sciences, CA - SafeBridge Regulatory and Life Sciences Group, USA - SE Tylose GmbH & Co. KG, DE - St. George's University, UK - Surface Measurement Systems Ltd., DE - Teva Pharmaceutical Industries Ltd., IL - Tofwerk, CH - ToxHub Srl, IT - ToxMinds BVBA, BE - UCB Biopharma SRL, BE - UCB Biopharma, BE - VERFORA, CH - Vertex Pharm, USA - Vertex, USA - VYNE, IL - Waters Corporation, USA - World Health Organization (WHO), CH - Yuria-Pharm LLC, UA - and others.
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
