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Pre Conference Masterclass - Monday 4th November 2024 Day One – Tuesday 5th November 2024 Day Two – Wednesday 6th November 2024
Toxicological Risk Assessment of Medical Device Materials
Selection of PoDs for TI derivation and toxicological risk assessment of medical device E/Ls
  • Health risk assessment of E/Ls typically involves comparing a tolerable exposure with an estimated exposure figure
  • The tolerable exposure (Tolerable Intake; TI) is dependent upon the choice of point of departure (PoD)
  • Ultimately, so is the margin of safety (MoS) for each E/L and conclusion on device safety
  • The presentation will discuss some of the factors affecting the choice of PoD including:
    • Choice of key study based on duration
    • Effect of study route on choice of key study
    • When study quality can impact on study choice
    • Way forward when study NOAELs vary
    • Should you choose a NOAEL or LOAEL as PoD?
    • Read-across v TTC – science v conservatism? 

Pete Watts | Toxicology Director, Bibra toxicology advice & consulting
Toxicological risk assessment on soluble and insolube fragments (particles) of product contacting materials
Reinhard Stidl, Senior Toxicologist, Safetree Consulting e.U.
Assessing sensitization hazards of extractables and Leachables
Erica Dahl, Senior Managing Toxicologist, SafeBridge Consultants, Inc.
Drinks and Panel Discussion
Peter Watts, Toxicology Director, Bibra toxicology advice & consulting
Reinhard Stidl, Senior Toxicologist, Safetree Consulting e.U.
Erica Dahl, Senior Managing Toxicologist, SafeBridge Consultants, Inc.
Registration and welcome refreshment
Chair’s opening remarks
SESSION 1: ANALYTICAL CHEMISTRY
Keynote: Analytical Assessment of Leachables in Biological Drug Products: Adapting FDA Insights for the EU Regulatory Landscape - tbc
Andrey Sarafanov, PhD | Principal Investigator, Center for Biologics Evaluation and Research, U. S. Food and Drug Administration
Low analytical evaluation thresholds in leachable screening: Challenges, potential solutions and alternative approaches
  • An explanation of the challenges experienced by companies in achieving Analytical Evaluation Thresholds
  • Presentation of alternative approaches when calculated AETs cannot be met
  • Presentation of case studies together with suggested alternative approaches to the challenges of a low Analytical Evaluation Threshold

Petra Booij | Investigator Trace Analysis Extractables and Leachables , GlaxoSmithKline
Challenges associated with E&L studies in the detection and identification of unknowns
  • Introduction to E&L Specialty at Novartis, scope and challenges
  • Role of GC-(Q-)TOF in High-Resolution Mass Spectrometry for compound Identification
  • Integration of Thermal Desorption-GC-MS for the analyses of volatile compounds

Céline Turminel | Expert Science & Technology, Novartis Pharmaceutical Manufacturing GmbH
A novel solvent depletion headspace GC/MS method for volatile extractables and leachables analysis
  • Accurate determination of volatile extractable/Leachable peaks using solvent depletion methodology
  • Increased sensitivity for high water soluble compounds
  • Ways to reduce the response factors variation of volatile extractables with different chemical structures

Mohinish Sahai | Group Leader, Laboratory Services, GMP, PPD, part of Thermo Fisher Scientific
Networking Break
Analysis of cohorts of concern – understanding and addressing emerging challenges associated with the assessment of special case compounds in E&L studies
Nick Morley | Principal Scientist, Element Materials Technology
Uncertainty factors & relative response factors: Combined models to correct detection & quantification bias in E&L studies
  • Identification of potentially concerning compounds is a challenge for E&L
  • Lower SCT/TTC values pair up with Uncertainty Factors (UFs) in order to overcome the limitations of the screening process i.e. semi-quantification
  • Lower thresholds result in diminishing returns and cannot solve the underlying issue
  • Taking into account Relative Response Factors (RRFs) directly improves the quality of E&L studies
  • The impact of UFs and RRFs can be shown by a simulation model

Davide Angelini | Extractables & Leachables – Project Leader, Eurofins BioPharma Product Testing Italy
PFAS in pharmaceutical products – a view on findings and potential relevance
Stephan Lebertz | Operational Laboratory Manager , SGS INSTITUT FRESENIUS GmbH
What could be the analytical approach in case of sustainable packaging?
  • Overview of Europe’s regulations and directives regarding sustainability, packaging and packaging waste management
  • Current regulatory requirements for pharmaceutical packaging and possible future scenarios
  • State of the art of E&L studies in pharmaceutical packaging
  • Recycled content and novel materials: sustainability impact on E&L studies

Margherita Monico | E&L Senior Project Manager, Mérieux NutriSciences Italia
Networking Lunch
SESSION 2: E&L CASE STUDIES & SINGLE-USE SYSTEMS
Process equipment related leachable compounds – 3 case studies
  • Case 1: Over sterilized filter, 3 days instead of 3 hours – process leachable compounds in the parenteral drug product
  • Case 2: Solid, white, 5 mm flakes in process equipment – effects on the parenteral drug products
  • Case 3: What is wrong with the process equipment? – PERL investigation continued as a rubber stopper related leachable analyses

Tarja Nurmi | Senior Expert, Extractables & Leachables, Bayer
The seemingly infinite chemical universe of extractables is actually smaller than you think
Roberto Menzel, Manager E&L laboratory, Sartorius Stedim Biotech
Evaluation of leachables in hospital pharmacy compounding: case studies
  • Swiss hospital pharmacies compound drug products in response to hospital practices and demands, to compensate for the lack of market availabilities e.g. drug shortages, or neonatal/paediatric population with specific needs. Ready-to-use or to-administer products are provided in prefilled plastic syringes, prefilled IV plastic bags and prefilled glass or plastic vials, which are stored long-term
  • One of the biggest issues in hospital pharmacy is the inappropriate selection of medical devices used in the compounding of drug products that could expose potentially harmful leachable compounds frail and/or vulnerable patients
  • As part of a PhD project, an analytical quality screening system by UHPLC-HRMS and a multi-functional database were set up for the identification and the semi-quantification of non-volatile leachable compounds in hospital pharmacy-prepared drug products
  • Several hospital pharmacy compoundings were assessed in terms of profiling of leachable compounds to establish their risk to patients. Endocrine disrupting properties were also assessed
  • A new E&L quality control concept in hospital pharmacy

William Bello | Analytical Pharmacist, Lausanne University Hospital
X-ray as alternative to Gamma irradiation: effect on extractables
  • Investigation towards the effect of X-ray irradiation on the extractables profile of rubber closures
  • Comparison of X-ray irradiation with gamma irradiation and their effect on extractables
  • Changes in the extractables profiles of rubber closures at the end of shelf life

Tine Hardeman | Manager Material Development Healthcare, Datwyler
Networking break
SESSION 3: REGULATIONS
USP E&L Initiatives: System suitability standard proposal path forward & new general chapter updates
Prabhakar Reddy, Ph.D., Director, Pharmaceutical Sciences,General Chapters and Complex Generics, USP 
FDA presentation tbc
Berk Oktem PhD DABT | Chemist, Center for Devices and Radiological Health, U.S. Food and Drug Administration
Chair’s conference summary
Networking Drink Reception
Registration & Welcome Refreshments
Chair's Opening Remarks
SESSION 4: TOXICOLOGY
Emerging toxicological issues and issues to product quality for the safety assessment of E&L compounds
  • ICH Q3E regulation scheduled to come into effect in 2026
  • Drivers of protein aggregation (e.g. silicone oil)
  • Adduct-forming interactions and immunotoxicology of sensitization
  • Deterministic versus probabilistic approaches
  • Regulatory endorsed adjustments for duration of exposure  

Kai Zwingenberger | Medical Director Global Quality, CSL Behring
Read across assessment for potential leachables without toxicological data
  • Computational tools can help identify appropriate surrogates with toxicological data for E&Ls with limited data
  • Top ranked surrogates can be selected to perform the read across toxicity assessment. 
  • A case study of an accepted regulatory response utilizing the read across assessment will be presented

Yana Chervona | Senior Principle Scientist, Drug Safety Team Lead, Pfizer
Toxicological risk assessment of E&L: medical devices and pharmaceuticals - trends and challenges
  • Regulatory guidelines and position papers 
  • Toxicological risk assessment of chemical constituents of medical devices
  • Parallels with toxicological risk assessment of E&L in pharmaceuticals

Alina Martirosyan | Sr. Scientific Manager Toxicology, B. Braun Melsungen AG
Networking Break
Assessing bioavailability for the derivation of permitted daily exposures (PDE) limits for extractables and leachables (E&L)
  • Bioavailability considerations are an important element of the permitted daily exposures (PDE) derivation supporting route-to-route extrapolation
  • A review of computational approaches for bioavailability assessments is presented
  • Discussion includes considerations for a fit for purpose estimation of bioavailability for E&L assessments

Candice Johnson, Ph.D. | Senior Research Scientist, Instem
Use of computational toxicology for the derivation of safety limits for data-poor E&Ls
  • Computational toxicology can aid the derivation of safety limits for data-poor extractables and leachables
  • In silico predictions can be used to assign a class, and a corresponding limit for genotoxic compounds, following the ICH M7 scheme
  • For data-poor E&Ls, a PDE limit can be derived with read-across
  • Justification of similarity within a read-across framework can be supported by computational models
  • Case studies of substances from the PQRI database will be provided

Christian Novello | Junior scientist – Toxicologist, Innovatune Srl
Toxicological risk assessment of a bag - medical device or primary packaging?
  • Novelization of EU MDR changed the classification of plastic bag containers
  • Commonalities and differences of the assessment of a PVC bag as either medical device or primary packaging
  • Toxicological risk assessment, extraction protocols, analytical evaluation thresholds, biocompatibility testing

Nina Macho | SeniorToxicologist, Octapharma
Networking lunch
SESSION 5: MEDICAL DEVICES & COMBINATION PRODUCTS
A CROs experience of designing the right 10993-18 chemical characterisations
  • Overcoming challenges faced when design: exhaustive, simulated and exaggerated extractables assessment.
  • Alignment of study design with ISO 10993-17
  • Practical considerations for selection of the right extraction power
  • Risk management of study design
Helen Lewis, Smithers MDT Limited
Discussion of various recent updates in regulatory expectations for medical device extractables testing, including: Exhaustive extraction with non-volatile residue testing, establishment of uncertainty factor (UF) databases/values and method performa
  • Medical Device Extractables
  • ISO-10993 Chemistry Extractables Testing
  • Case Studies
  • Mass Spectrometry
  • The Uncertainty Factor (UF)
  • Regulatory Expectations versus Reality

Alan Hendricker | Manager - Chemical Sciences, Becton Dickinson
Bridging regulatory and operational approaches in managing E&L challenges for dual-classified medical devices
  • Standards Integration: Covers key standards like ISO 14971 and ISO 10993, ensuring comprehensive safety evaluations
  • E&L studies focus: Stresses the importance of studies on extractables and leachables for identifying risks and predicting effects
  • Material selection and testing: Emphasizes careful material choice and ongoing tests to reduce risks and ease regulatory approvals
  • Regulatory: Highlights adaptive strategies for navigating regulatory challenges and improving compliance and safety

Francois Bianchi | Principal Consultant, Avisulting LLC
Case study: application of E&L chemical characterisation testing in the introduction of a constituent material change impacting several permanent implantable medical devices
  • Application of E&L chemical characterization testing to assess the constituent material change applicable to several EU and US marketed medical devices
  • Comparative chemical characterization study
  • Chemical data leveraged to mitigate the risks for systemic toxicity (subacute, subchronic and chronic), genotoxicity and carcinogenicity
  • Extraction conducted until exhaustivity in four different solvents to cover a broad range of polarities
  • Toxicological risk assessment performed on the resulting E&L profile of each final finished device that was impacted by the material change

Chiara Lorenzetto | Principal Consutant, Niu Consulting
Chair's closing remarks and end of conference

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EL-2024-agenda-10-7-2024
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