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Agenda

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Registration and Welcome
Registration
Opening remarks & Opening Speech
Session 1: 2024 guidelines and E&L case Study
The application requirements for EXTRACTABLE AND LEACHABLE studies from the point of pharmaceutical companies Current E&L regulatory Of FDA.EMA.NMPA and case studies of E&L deficiencies
Tea Break and Networking
Equivalence Research and Case Analysis of pharmaceutical packing
  • Regulations and relevant standards used in Equivalence Research, purpose and significance of Equivalence Research on pharmaceutical packing;
  • The basic idea of equivalence research;
  • Explain how to conduct research on the equivalence of pharmaceutical packaging through case analysis.

Xiaocong Pu | Senior Engineer, Sichuan Medical Device Testing Center
Session 2: characterization and evaluation of Medical devices
Read across and its application in product evaluation
The new version of ISO10993-17 provides a simplified approach to the toxicological assessment of medical devices and the evaluation requirements for allowable limits related to drug cleaning validation are becoming increasingly strict. These will inevitably make use of the read across method. Read-across is used in the absence of toxicological data for the substance being assessed, utilizing similar substances or substances within the same group to fill in its toxicological characteristics, and conservatively obtaining the toxicological characteristics and thresholds of the substance being assessed, in order to better complete the product risk assessment work. This lecture will introduce the concept of read across and existing regulations, as well as its application in the evaluation of products.

Dr. Leshuai Zhang | Professor, Toxicologist, Soochow University
Lunch break
Practical Issues Associated with Extractables Testing of Medical Devices
It is a well-known saying that “the devil is in the details.” As authoritative texts associated with the chemical characterization of medical devices generally present concepts and generalities and lack details, sponsors seeking to design and implement extraction studies for medical devices occasionally struggle to establish critical experimental details that are scientifically sound, practical, and regulatorily compliant.
 This presentation provides insights into several of these critical experimental details, addressing concepts that include:
• The “It all comes out at Once” Paradox
• Exhaustive Extractions as a Source of Kinetic Release Data
• Predicting Exhaustive Extractions with a Minimum Number of Extraction Steps
• A Protective Approach to Quantitation and Managing the AET
• What number and types of extraction solvents are appropriate?

Dennis Jenke | Chief Executive Scientist, Triad Scientific Solutions
Regulatory Requirements and Evaluation Methods for Materials of Concern (MOC) in Medical Devices
Medical device companies are compelled to adhere rigorously to the legal and regulatory frameworks of their targeted markets to safeguard environment and human well-being. The evaluation and understanding of Materials of Concern (MOC) specifications within these laws and regulations emerge as critical imperatives for such companies. These imperatives necessitate comprehensive consideration throughout the phases of material selection, development, manufacturing, distribution, and reprocessing processes. By doing so, companies can effectively facilitate market entry and ensure conformance with pertinent legal stipulations. This report will present the legal and regulatory requirements for materials of concern across various international domains like EU MDR hazardous substances, EU REACH, EU POPs, EU Battery, California Proposition 65 list, etc. The report will also share the assessment strategies in terms of supplier declarations, raw material composition analysis, finish-product testing, disclosure requirements, standards compliance, and periodic review.

Jingwen Shi | Chemical Scientist , Medtronic China R&D Center
Challenges and Approaches in the Chemical Characterization of Absorbable Medical Devices
Unlike traditional medical device implants, resorbable medical device implants produce different morphologies and degradation products at different implantation time points, so how to scientifically conduct chemical characterization to avoid underestimating or omitting the leachables risk of the product becomes particularly important. This presentation will focus on the difficulties in chemical characterization of this type of products, and will provide targeted thoughts and ideas to discuss with the participants.
 
Xiaolong Rong | Technical director of Chemistry Laboratory, WuXi AppTec
Tea break and Networking
A CROs experience of designing the most appropriate E&L study – a collaborative approach
  • Understanding the requirements of the client
  • Alignment of study design to appropriate regulatory bodies
  • Practical considerations
  • Risk management of study design

Dr. Candice Bellis | Project Manager, Smithers
Biological Evaluation of Innovative Medical Devices-Regulatory Science Research and Practice
The Advantages of Chromatographic Endpoint Determination in Exhaustive Extractions of Medical Device E&L Studies
Performing an exhaustive extraction as defined by ISO 10993-18:2020 is a common regulatory expectation for medical device E&L studies that has a crucial impact on study design and corresponding results. The typical method for exhaustive endpoint determination is based on measuring non-volatile residue gravimetrically. However, the standard provides an open opportunity to determine the exhaustive endpoint using other techniques. When the E&L data are intended to be toxicologically evaluated in alignment with ISO 10993-17, exhaustive extractions performed using a chromatographic approach provides more relevant data. Data generated using a chromatographic approach will be used to outline the advantages over the NVR approach from a toxicological risk assessment perspective.
• Definition and regulatory framework for exhaustive extraction based on ISO 10993-18
• Advantages of the chromatographic approach for exhaustive endpoint determination
• Non-Volatile Residue determination vs chromatographic approach
• ISO 10993-17 based toxicological evaluation using daily exposure vs. exhaustive extraction
Tim Petermann | Principal Chemist, Obernburg Laboratory Services, NAMSA
End of Day one
Session 3: Pharm packaging and extractables study

How to Properly Design and Execute E/L studies for liquid oral dosage forms
Improving the Accuracy of your E&L Testing
E&L studies can have many sources of uncertainties. These arise from issues with extraction and analysis. An incomplete extraction (low temperatures, short times, etc.) will skew the results towards underestimation of extractables. Analytical uncertainties which result from analytical detection, analytical identification, and analytical quantitation of extractable will adversely affect extractables results.. These same uncertainties might also cover leachable analysis. Lack of validated, qualified/verified analytical procedures might result in reported amounts that are less than that of the true value which will cause an improper assessment of risk. Uncertainty due to un-defined or ill-defined chemical structure may lead to incorrect toxicological risk assessments. Lack of certified reference standards will cause errors in determination of amounts and confirmation of identification. Uncertainty in undefined detector response, i.e., relation between response and concentration, will significantly change extractable determination. All these issues will be discussed and steps to lower uncertainties in extractables be recommended.

Atish Sen, PhD | Director, Analytical Sciences Inhalation Product Development, AstraZeneca
Nitrosamines in flexible plastic packaging materials for large volume parenterals
Nitrosamine impurities are one of cohort of concerns that regulatory authorities focus on. For large-volume injections, the maximum daily dosage is extremely high, resulting in extremely low detection limits for nitrosamines. To address this key point, we have successfully developed an analytical method for nitrosamines in parental packaging materials. Nitrosamines have been found in extractable studies of multiple materials. Therefore, for a scientific assessment of nitrosamines, the industry needs to work together to promote the update of regulations..

Weichun Yang | Global Laboratory Head & Senior Director, Fresenius
Networking tea break
Label – an important part of extractables & leachables testing
Requirements from regulatory bodies concerning detection, identification, and quantification of extractable and leachable compounds in pharmaceuticals are getting increasingly rigorous. These stricter requirements are due to many documented cases of contaminants leaching from packaging and causing potential or real risk to human health. Leachables originating from label components and printing inks, were in the past sometimes overlooked, but are now very much in scope of the extractables and leachables studies. Label stock supplier can support the brand owners in their E&L studies by providing extraction data and more detailed information of the chemical composition of label materials.
Paavo Sillanpää | Global Senior Manager Business Development, Pharma , UPM Raflatac
Session 4: SUS and E&L testing
Development of a ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry method (UPLC-QTOF-MS) for identification and detection of oleamide in pharmaceutical labels
Labels are a widely used type of pharmaceutical packaging for recognition and classification of various information. Although the pharmaceutical labels are not in direct contact with drugs, there may still be compatibility problems between them. Unknown chemical migration may pose a potential risk to patients. In order to ensure the quality and safety of drug products, it is necessary to analyze extractables and leachables in label materials. In this study, oleamide was found in pharmaceutical labels for the first time. For the separation and identification of oleamide, we combine high performance liquid chromatography (HPLC), ultra-performance liquid chromatography-quadrupole time-of-flight mass (UPLC-Q-TOF-MS) and nuclear magnetic resonance (NMR) spectroscopy. Then, a quantitative UPLC-MS/MS method with high sensitivity and resolution was developed and validated. Finally, the safety assessment of oleamide was conducted to verify whether the labels posed a toxicological risk.
Peilin Fu | R&D Center Director, Shenyang Sinqi Pharmaceutical
Assessing the Substitutability of Packaging Systems and SUS Suppliers through E&L Testing
Amid the downturn of the international economic cycle and the advancement of government centralized procurement policies, the strategy of supplier substitution for packaging systems and single-use systems (SUS) is gaining increasing attention. - E&L testing to obtain the extractable profiles and conducting targeted testing, tailored to the needs of drug development. For instance, testing for extractables/leachables that may interact with therapeutic proteins, and the potential cytotoxicity of antioxidant degradation products. - Research design for risk management ensures that extraction or simulated extraction tests represent the characteristics of various formulations, necessitating comprehensive yet undistorted extraction. Overly exaggerated extraction could lead to the presence of significant unknown extractables, posing a major challenge. - Systematically and scientifically assessing the chemical and toxicological equivalence of materials to gain regulatory approval. - Exploring differences in laboratory test practices to reduce unnecessary duplicate testing. By cooperating between manufacturers and contract research organizations (CROs), solve the problems faced by pharmaceutical companies in test practices and reduce unnecessary repeated testing. - Case studies will demonstrate how E&L testing can assess the equivalence and substitutability of domestically sourced packaging materials and components.
Dr. Yi Zhang | Principal Scientist, Guangzhou E/L laboratory
Lunch Break and Networking
Impact of Experiment design and Analysis on the Extractables and Leachable Profile
Filters and single-use system are widely utilized in pharmaceutical manufacturing processes, often made of various polymers with additives. These materials and their degradants have the potential to leach into the drug product. To identify and evaluate these potential leachable, extractables studies are performed by using clean test solvents under worst- case conditions, but the design of extraction and method have an impact on the extractables. Such as, the design of autoclave intensity on the extractables Profiles of the Filters Flushed Post.
Zhaodi Zhang | E&L Lab Manger , Cytiva Fast Trak™ Validation Services
Assessing biologic/toxicologic effects of extractables from plastic contact materials for advanced therapy manufacturing using cell painting assay and cytotoxicity screening
The differences between Advanced Therapy Medicinal Products (ATMP) and traditional biopharmaceutical products create new challenges for extractables and leachables (E&L) assessments. These issues are particularly important considering the increasing reliance on single-use systems (SUS). While SUS extractables data can serve as a basis for assessing ATMP applications, there are significant opportunities to improve assessment tools for exposure estimation and toxicological evaluation. In ATMP applications cells or viruses are the therapeutic product and a patient exposure estimation for leachables must consider both the liquid phase and the therapeutic biological material. We tested forty-five commonly found extractbales and processing aids in a highthroughput screening cell-painting assay using a human cell line. Results showed that most compounds did not create a response in the > 550 cell features analyzed. Only three candidates were found to show an effect in this assay, including the antioxidant degradant bDtBPP, known to be detrimental to cell growth. Further, a concept is developed that allowes to model process equipment-related leachables (PERLs) exposure in an ATMP production environment. In summary, cell-based products' exposure to PERLs is expected to fall far below critical effective concentrations. Nonetheless, avoiding materials of construction containing extractables with a known detrimental effect to cells is advisable.

Dr Armin Hauk | Principal Scientist, Sartorius Stedim Biotech GmbH
Cumulative effect vs Lego mode: How to simplify extractable approach
The goal will be to present how to manage the cumulative effect and to explain which simplifications can be implemented for extractable studies and patient exposure scenario:
•             Why extractable studies are not always representatives?
•             How to deal with cumulative effect described in regulations?
•             The concept of Lego approach to simplify cumulative evaluation?
•             How to use of digital tool to support approach and simplify patient exposure scenario and toxicological evaluation?

Marine Lepoutre | Global Subject Matter Expert for GSK Vaccines, GSK Vaccines
End of Day Two