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Registration and Welcome
Opening remarks & Opening Speech
Session 1: New research and Case Studies of E&L and update on ISO10993-17:2023
E&L research and in vivo biological performance of implantable interventional medical devices E&L
1) Regulations and relevant standards that used in the Medical Device E&L Research Institute;
2) Current status and challenges of E&L research on implantable interventional medical devices;
3) From the perspective of extractables and leachables, discussing and Case sharing on the biological performance of implantable interventional medical devices in animals
Dr. Xiaoliang Wang | Deputy Director, Safety Evaluation Center, Sichuan Insitute for Drug Control (Sichuan Testing Center of Medical Devices)
Proper Calculation of the Uncertainty Factors and its Application to the Analytical Evaluation Threshold and for Quantitation
Tea Break and Networking
New concept and approach for toxicological risk assessment of the constituents of medical devices in ISO10993-17:2023
The new version of ISO10993-17 will be launched in September 2023. It is significantly different from the old version more than 20 years ago. This report will explain the principles and characteristics of the toxicological evaluation of the new version of device E&L as well as the differences and advantages compared with the old version.
Dr. Leshuai Zhang | Professor, Toxicologist, Soochow University
The Single Use System dilemma - a case study
Before implementation of single use systems (SUS) in the production a risk assessment, with regards to leachables and safety risk to patients, is needed. Several manufactures/suppliers of SUS have been involved in the BioPhorum E&L SUS initiative, where a process for generation of extractables data on their SUS components are described. As a result suppliers are providing extractables data on their main SUS, which can then be used directly in the risk evaluation process at the pharmaceutical companies. However, many pharmaceutical companies experiences a challenging supply situation and may therefore need to qualify back-up systems/components in case of shortage. The presentation will discuss the dilemma of using SUS from suppliers without extraction data or knowledge on E&L.
Further the presentation will describe a case, where a SUS component for a new drug product filling setup was to be implemented and since supplier extraction data was unavailable, an in-house extraction study was carried out. Abundant, unknown extractables proved a major challenge since they appeared in the leachables study in concentrations above the defined acceptance criteria. In addition to the identification work done by Liquid Chromatography with Ultra-Violet and Mass Spectrometric detection (LCUVMS), the presentation will include considerations about the challenge in handling exceeding low analytical evaluation thresholds (AETs) resulting from use of SUS with biological drug products.
Carsten Worsøe | Principal Scientist Extractables and Leachables, Novo Nordisk
A Chemical Characterization of Implantable Devices for Regulatory Satisfaction and the Differences and Applications of the New 2023 Toxicology Assessment
Long-term implantable polymeric devices require comprehensive chemical characterization studies. The first part to complete is an asymptotic extraction study, , which requires multi-method confirmation of how to determine the limit extraction level to be reached. The second part is to pay attention to the selection of simulation solvents, as unreasonable solvents can increase the list of extractable/leachable compounds, and the solvents need to be selected appropriately based on the risk of the device. The third part is to do a complete scan of leachables using comprehensive testing methods, the uncertainty factor is the most current regulatory concern. Finally, a toxicological assessment of the risky leachables should be done to evaluate the long-term risk of the device in vivo. The latest version of ISO 10993-17:2023, which has been significantly updated from the previous version, is used to draw conclusions on the toxicological evaluation of leachables
Chunxing Lin | Vice President, Milestone
Lunch break
Session 2: Medical Device
Biocompatibility Research and Case Analysis of Medical Mevices Utilizing Animal Tissues and Their Derivatives/Tissue Engineered Medical Products
This topic will introduce the biocompatibility research of medical devices utilizing animal tissues and their derivatives/Tissue engineered medical products, including the following four aspects: Product Definition, Relevant Regulations and Standards in China, Research Protocol Design (such as sample preparation, biocompatibility tests, immunotoxicology, etc.) and Case Analysis (such as animal derived typeⅠcollagen plant, 3D printed bioceramic scaffolds, etc.)
Zhai Zhichen | Director of the IBMD-TC, Guangdong Institute of Advanced Biomaterials and Medical Devices, Testing Center
Cope with the challenges- Application of concentration methods in LVP E&L study
Large-Volume Parenteral has developed rapidly in recent years, especially the potential market for therapeutic or nutritional varieties. However, as the tremendously raise of medicine usage by different therapeutic approach, a series of potential problems in E&L study have also been triggered. Fulfillment of the AET requirement is the huge challenge what we are going to tackle at the current stage. Concentration is a very direct processing method for sample enrichment, we will discuss the current situation of common enrichment method for E&L analysis.
Xiaowei Wang | Analytical Scientist , Fresenius Medical Care
Tea break and Networking
Session 3: Chemical characterization analysis and guidance
A comparative study of extractables/leachables with different extraction methods
The extractables/leachables analysis is the most convenient and effective means in chemical characterization, and its main research steps include the determination of extraction conditions, the establishment of AET, the development and verification of analytical methods, and the qualitative/quantitative extractables/leachables. Extraction conditions are the key to affect the test results. The report will review the extraction methods of common medical devices, and compare the effects of different extraction conditions on the qualitative and quantitative results of extractables/leachables.
Wang Heng | Senior Technical Director, WEIPU Medical Devices Division
Selecting the right surrogate standards for semi-quantitative concentration determinations of extractables in GC/MS: what the Nelson Database can learn us.
Panel Discussion: Research and analysis of E&L assessment reports
Haiyan Hong, Analytical & QC & Development manager, Asia at Saint-Gobain
Panelist: Wenjing Zhao, Biocompatibility Technical Manager at Fresenius
Prof. Zhang Leshuai, Professor, Soochow University
Carsten Worsøe, Principal Scientist Extractables and Leachables, Novo Nordisk Carsten Worsøe
End of Day one
Session 4: SUS & Pharm Packaging, Toxicological risk assessment and Testing
Assessment on compatibility and safety of labels for pharmaceutical packaging
Networking tea break
E&L identification and risk assessment for single-use systems used in biopharmaceutical manufacturing
Extractable study for the printed label on the plastic solution bag
When to Use Computational Models to Predict the Genotoxic and Carcinogenic Potential of E&L Compounds and How to Interpret the Predictions from the Models
Computational models are often used to predict the genotoxic and carcinogenic potential of extractable and leachable (E&L) compounds in the absence of experimentally derived data.   Notably, the ICH M7 and ISO/TS 21726 documents recommend the use of in silico models to predict the genotoxicity and carcinogenicity of impurities in pharmaceuticals and extractables from medical device materials, respectively.  This talk will provide practical advice on when to use computational models to predict the genotoxic and carcinogenic potential of E&L compounds and will provide guidance on how to interpret the model-derived results for the toxicological risk assessment of these compounds.
Ron Brown | Toxicologist, Risk Science Consortium, LLC & US FDA (Retired)
Lunch Break and Networking
Considerations for Extractables & Leachables and Introduction to State-of-Art 4040 Elastomer
Extractables and leachables (E&L) is a very popular and very important topic for the pharmaceutical industry. The is because if E&L are not assessed thoroughly and mitigated, they can cause serious adverse events compromising on safety and even causing deaths of patients if timely recalls are not made. In this session, I will focus on the elastomeric closures used for pharmaceutical applications as they are the primary closures in direct contact with the drug formulations. I will take a look at the elastomer types used for pharmaceutical applications and the various factors that may affect chemical compound migration to the drug which may potentially cause toxicity either as it is or in worst case, a reaction with the drug or its excipients, resulting in a chemical specie of safety concern. Therefore, it is necessary to perform E&L assessment based on the specific drug product and its intended application. From the rubber closure manufacturer’s perspective, I will share our groundbreaking approach, adopting Quality by Design (QbD) principles from raw material selection through to the final component manufacturing, to develop state-of-the-art 4040 elastomer, greatly reducing the risks from elastomeric E&L. 
Boo Jia Min | Technology Manager, AP , West Pharmaceutical Services Singapore Pte Ltd
Health risk assessment of Extractables and Leachables – things are not always what they seem
  • Extractables and leachables (chemical characterisation) studies are a requirement for both medicines and medical devices.
  • E&Ls can arise from containers and closure systems used for pharmaceuticals, from medical devices, and from packaging of both.
  • Uncertainties exist in the characterisation of the source, identity and quantity of E&Ls, which can impact the toxicological risk assessment.
  • This presentation will include several case studies of the toxicity assessment of E&Ls where these uncertainties were addressed. 

Chris Waine | Senior Toxicologist, bibra toxicology advice and consulting
Conducting leachable risk assessments via A modified FMEA process
End of Day Two