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The 2023 agenda has been announced! Take a look at the program, which features expert speakers from SGS, the FDA, Intertek, Solvias, Novo Nordisk, GSK, PPD, SafeBridge, Sartorius, and more, covering important industry topics such as medical devices, tox evaluation, material selection, single use, study designs, and more!   


Please click on the dates below to see each day's program!

Registration and Continental Breakfast
Registration and Continental Breakfast
Welcome and Opening Remarks
Ashli Speed, Conference Producer, Smithers 
Session I: E&L Industry Present and Future
< Session Description >
This session will update delegates on E&L regulations as well as discuss the future of the industry.
Medical Device Chemical Toxicological Risk Assessments: Applying Toxicological Principles to Meet the Challenge. Part II
Development and Application of USP Extractables and Leachables Standards: An Insiders View from the Outside
Expectations in the EU MDR from a Biological Safety Perspective
The talk will give an understanding of why the MDR was developed and focus on the biological safety and chemistry related requirement in MDR
• Background to MDR - what triggered it?
• Focus areas related to biological safety
• Specific requirements compared to ISO 10993-1
• Substance based devices - what are they and how to assess them
• Experiences of notified bodies' expectation
Lina Burman | Senior Scientific Officer, Limulus Bio AB/Inc
Networking Coffee Break
New Version of ISO 10993-17: Potential impacts to Chemical characterization for Medical Devices

The new International Organization for Standardization ISO 10993-17: Toxicological Risk Assessment of Medical Device Constituents is essential for the evaluation of toxicological hazards of extractable/leachable chemicals detected in from medical device extracts. The new ISO 10993-17 is currently in the final draft phase and vastly different to the first version which was published in 2002 and last revised in 2012. The document is now in its final draft phase and thought to be published at the end of this summer. Along with the major changes presented in the new standard, more toxicological evaluation tools are offered to decrease the burden of assessing the toxicological risk of chemicals extracted from medical devices. This presentation will provide a brief overview of the new standard and also evaluate the potential impacts to chemical characterization for medical devices (ISO 10993-18).

Sarah Campbell, PhD, DABT | Principal Toxicologist, Nelson Labs
Speaker Roundtable: Relation to Combination Products
Moderator: Cheryl Stults, Principal, C&M Technical Consulting

  • Alan Hood, Research Toxicologist, FDA
  • Lina Burman, Senior Scientific Officer, Limulus Bio AB
  • Sarah Campbell, PhD, DABT, Nelson Labs
  • Daniel Norwood, Ph.D. | Principal Consultant, Feinberg Daniel Norwood & Associates Pharma Consulting
Session II: Extractbles and Leachables Study Designs
Case Studies and Regulatory Expectations in Extractables and Leachables Testing of Medical Devices and Combination Products
Chemical characterization per ISO 10993-18 has become an important component of biocompatibility testing for medical devices. The Extractables and Leachables (E&L) study designs of pharmaceutical/biopharmaceutical products typically follow USP <1663> / <1664> and PQRI guidance, while chemical characterization of medical devices follows ISO 10993-18. Although the E&L analytical testing methodologies are similar, there are some differences in terms of study designs. This presentation will overview the differences and similarity of E&L requirements between medical devices and pharmaceutical products. Several case studies related to recent regulatory expectations on the extractables and leachables testing of medical devices and combination products will be discussed.
Key Points:
  • Differences and Similarity on E&L study designs between ISO 10993-18 (Medical Device) and USP <1663> / <1664> (Drug Product).
  • Case studies related to recent regulatory expectations on the extractables and leachables testing of medical devices and combination products

Dujuan Lu, Ph.D. | Manager/Global Leader-E&L, SGS Health Sciences
Reporting Analytical Data for Regulatory Submissions: A CRO Perspective on Implementing the BP4NTA Study Reporting Tool in the Healthcare Industry
Analytical data packages are an essential part of the CMC (Chemistry and Manufacturing Control) section of US FDA (United States Food and Drug Administration) NDA (new drug application) submissions for pharmaceuticals and biologics. In many cases, the biocompatibility assessment for medical devices and E&L testing of pharmaceutical packaging systems also requires analytical testing to be performed and reported. Based on the quality of the data presented, the regulatory review team makes an informed decision about the safety of the drug product or the medical device. If the submission is incomplete or does not support the safety assessment of the product, additional data may be required, which often delays product approval. Study sponsors must decide between optimizing the amount and quality of the data in the filing packages to save costs upfront, which may delay the approval process versus taking the more conservative approach of providing detailed information, investing more upfront, and minimizing the risk of delays.
Gyorgy Vas | Research Fellow, Intertek Pharmaceutical Services
Networking Lunch (Included)
A Comparative Study of Electron Spray Ionization (ESI) LC/MS versus Atmospheric Pressure Chemical ionization (APCI) LC/MS on Extracts of Medical Devices
In the last few years, the Analytical Chemistry approaches to characterize extracts of Medical Devices – In line with the new ISO 10993-18:2020 Standard – has grown considerably. Biocompatibility assessments, based on (experimental) Chemical Characterization of Medical Devices is now one of the standard approaches for a number of toxicological end points. While there is no strict “official guidance” on the selection and use of analytical methodologies, instrumentation and detection technologies, it is clear that LC/MS is one of the standard techniques that needs to be included in such an evaluation to inspect the extracts for Non-Volatile Organic Compounds. However, there has been an ongoing debate on whether to use ESI or APCI as ionization technique in LC/MS. At the moment, Regulatory Authorities are inclined to support ESI based MS as the only detection of choice. While there may be some validity in the selection of ESI for polar and semi-polar extracts, based upon available literature and theoretical considerations, the choice of ESI is harder to justify when analyzing non-polar extracts. Nelson Labs has a vast experience in using both ESI and APCI in the analysis of material extracts for a wide range of extraction solvents, which allows us to compare the experimental outcome of an ESI analysis with the outcome of an APCI analysis for a broad range of materials extracted with extracts of varying polarity. The outcome of this comparative study will be discussed in this presentation and conclusions on the best scientific approaches going forward, will be given
Philippe Verlinde PhD | LC/MS-Expert, Nelson Labs Europe
Extractables & Leachables Case Study for Over-the-Counter Nicotine Transdermal Patches
Additional Presenter: Will Parker, Director of E&L , Boston Analytical

Transdermal patches are used to incorporate the active ingredient of the drug into the circulatory system through the skin. Transdermal products have gained popularity in the industry due to their ease of use; however, they present unique leachables concerns compared to traditional drug products.  Transdermal products incorporate a backing layer, release liner and storage pouch that all can serve as sources of leachables to the patient during the administration of the transdermal patch. The U.S. Food and Drug Administration (FDA) Guidance for industry has categorized transdermal patches as a packaging type with a high concern associated with the route of administration. The FDA has specifically requested leachables studies be performed for transdermal patch products, which include methodologies that mimic skin-contact during typical usage including exercise conditions. Over-the-counter nicotine patches were selected as an interesting case due to the need to keep them applied for 18-24 hours per day for upwards of 8 weeks. Design of suitable leachables studies that mimic “in-use” conditions can be challenging. Herein, we propose a skin-contact simulation study based on the single-side extraction to mimic the skin-contact under conditions of exercise in the worst-case clinical usage. In this study, a special customized extraction vessel is applied to perform the single-side extraction without extracting the backing layer. A full submersion extraction is also compared to the one-sided extraction to highlight key differences. A sweat simulation solvent is used to mimic the extracting power of sweat under conditions of exercise. The resulting extracts were analyzed as appropriate for volatiles, semi-volatiles, non-volatiles, and metals with gas chromatography/mass spectrometry (GC-MS), liquid chromatography/mass spectrometry (LC-MS) and inductively coupled plasma mass spectrometry (ICP-MS) to provide comprehensive leachables profiles.  Example data and the study outline will be presented.
Eric Hill | Director of STS, Boston Analytical
Session III: Challenges in Identification and Quantification of Extractables
A reliable method using a UHPLC/UV/CAD/MS multidetector platform for routine quantification of extractables and leachables in common medical and pharmaceutical-grade plastics.
A well-characterized in-house method for extractables and leachables quantification and for MS library data generation was used with common medical- and pharmaceutical grade-plastics. Three orthogonal detectors, LCMS, UV and charged aerosol detector (CAD), facilitated analysis of analytes with diverse chemical natures. An inverse gradient strategy was implemented and further refined with an in-line mixer and with optimized gradient delay times. A previously published method was used for determining whether analytes present as non-volatile or semi-volatile in the CAD. The approach minimizes inter-analyte response factor variation and increases quantitative accuracy, thereby minimizing the uncertainty factor used to set analytical evaluation thresholds. One case study is presented in which a single quadrupole MS would match compound masses and relative retention times with an in-house library. Disadvantages of the inverse gradient in the MS, such as adduct formation or worse limits of detection, were not observed. The goal was to find the most efficient and cost-effective strategy to meet key requirements in E&L studies of potentially harmful substances. Authors: Xiaochun Yu#, Katherine Lovejoy‡, Mauro De Pra‡, Carolin Kraus‡, Basant Soliman‡ #PPD® Laboratories, GMP Labs, a part of Thermo Fisher Scientific, Middleton, Wisconsin, USA, Presenting Author ‡Thermo Fisher Scientific, HPLC Factory Site, Germering, Germany
Sven Hackbusch | Senior Application Scientist, Thermo Fisher Scientific
Maximizing identification rates in E&L studies with state-of-art HRAM-GC/MS and HRAM-LC/MS/MS technology
Within E&L studies, regulative bodies now demand that number of unknown compounds in E&L investigations is minimized, ideally until there are no unknowns in drug products above the safety concern threshold.  Although it is clearly not possible to always achieve these expectations, technological developments (namely HRAM-LC/MS/MS with Orbitraps or Q-ToFs) has widely facilitated achieving ID ratios > 95% in LC/MS screening. The presentation demonstrates structure confirmation of a series or trifluoro-propylated silicones with a molecular weights above 2000 Da, in an extract of a CSTD device, by using HRAM-GCMS with EI/CI ionization.
Dr. Karl Abele | Team leader HRAM Mass Spectrometry , Solvias AG (Switzerland) Solvias LLC (Boston, USA)
Networking Coffee Break
Session IV: Single Use
“The Single Use 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
How to implement USP 665 requirements before 2026
The goal will be to present a lifecycle approach of our existing park of single-use, based on leachable risk, to ensure a compliance for the effectivity date of the USP in 2026.
  • Management of existing items, lifecycle and retrospective approach
  • Management of new items created between 2021 and 2026
  •  Ensure full compliance for items after 2026
  • Quid of Chinese pharmacopea ?

Marine Lepoutre | Global Subject Matter Expert for GSK Vaccines, GSK Vaccines
Extractables Evaluation X-ray or Gamma Irradiated SU Components and Materials
Sartorius initiated a comprehensive qualification program for X-ray irradiated SU equipment. One main working package is to investigate extractables profiles of components sterilized by gamma or X-ray irradiation technologies. The presentation will summarize recently published results of various tested polymers used in Single-Use devices. Recommendations and possible hurdles in the design of a comparison study are outlined. This information is essential in order to assess if the data obtained can be used for a qualitative or quantitative comparison. For this purpose, a definition for equivalence is presented and relevance on the process qualification and safety margins is shown. The talk will close with the question what actions should be done if a unique peak is detected for one of the irradiation modalities?
Dr. Roberto Menzel | Manager Extractables Group, Sartorius Stedim Biotech
Session Speaker Q&A
Networking Reception
Registration and Continental Breakfast
Registration and Continental Breakfast
Session V: Medical Devices
Designing E/L studies with the Risk Assessment in Mind
Regardless of what type of extractable or leachable study is being conducted or what product is being tested (medical device, combination product, single-use system, container closure), one thing is consistent. The study should be designed with the risk assessment in mind.
  • Importance of the Risk Assessment and overview of the process
  • Key inputs for the Risk Assessment and how they relate to the E/L study
  • Essential components of an E/L Study

Sandi Schaible | Senior Director, Analytical Chemistry and Regulatory Toxicology, WuXi AppTec Medical Device Testing
Roundtable on Perspectives on Exhaustive Extraction moderated by Lee Nagao
  • Lee M. Nagao, Ph.D., Senior Director, Science, Regulation & Policy, ELSIE
  • Cheryl Stults, PhD, Principal, C&M Technical consulting LLC
  • Dennis Jenke, Chief Executive Scientist, Triad Scientific Solution
  • Ron Brown, Toxicologist, Risk Science Consortium, LLC (Retired US FDA)
Networking Coffee Break
Session VI: Material Selection Impact on Extractables Profiles
Overcoming Challenges Associated with E&L Testing of Flexible Plastic Formulations Used in Medical Devices & Pharmaceutical Manufacturing
Flexible polymer formulations are instrumental for use as materials of construction in medical devices, single use components in manufacturer of drug substances and packaging of pharmaceuticals. However, performing extractable and leachable (E&L) studies on these flexible test articles can be challenging. E&L analysis of flexible plastics commonly leads to a higher number of extractables detected compared to rigid plastics due to the higher levels of additives and higher glass transition temperatures. There is an increased propensity for extractables to migrate from these softer plastics.
This presentation will focus on case studies which highlight some of these challenges from materials such as polyvinylchloride, polyurethane, ethylene-vinyl acetate, thermoplastic elastomers & fluorinated ethylene propylene with an emphasis on how the different plasticizers used can affect the extractable profile.
Sam Albeke | LC Manager, Element
Understanding Extractables Profiles from Polymerization Chemistry
At the US Smithers 2021 and 2022 conference, PPD explained the extractable profiles of LDPE, HDPE, polypropylene, ABS, butyl rubber, silicone rubber, PET, PBT and polycarbonate based on the polymerization reaction chemistry of these materials. In this presentation, we are going to explore the extractables profiles of other polymer materials commonly used in medical devices, including Polyoxymethylene (POM), Polyurethane, Polyamide and Cyclic olefin copolymer (COC). We will provide the typical extractable compounds from those materials and explain how they are formed from their polymerization chemistry
Eric Hansen | Sr. Scientist Extractables/Leachables, Development and Validation, PPD, Part of Thermo Fisher Scientific
Session VII: Tox Evaluation
The ELSIE Knowledge Base: A Novel Research Tool to Advance Collaboration on Safety and Extractables Evaluation
The Extractables and Leachables Safety Information Exchange (ELSIE) is a consortium of bio/pharmaceutical and medical device companies with the aim of sharing knowledge and information on and advancing the science and regulation of leachables and materials quality. ELSIE recently launched its "Knowledge Base" (KB), a database designed in consultation with subject matter experts to share and store safety and extractable study data and assist experts and nonexperts in understanding key aspects of E&L evaluation. We will present the technical capabilities and design of the KB with an invitation to the community to include their extractable and safety data in the KB.
James M. Vergis, Ph.D. | Principal, ELSIE Secretariat
CHemical RISk calculators (CHRIS): Regulatory tools for assessing medical device leachables
Physics-based mass transport models are tools that can provide more clinically relevant exposure estimates for leachable substances in polymeric medical device components.  However, there are inherent challenges with parameterization, validation, and implementation of these models and the level of regulatory acceptance can be uncertain.  Therefore, we have developed the CHemical RISk calculators (CHRIS), which are a collection of web-based applications intended to facilitate the widespread use of these models in regulatory submissions.  This presentation will cover the following topics:
* Types of regulatory tools and hierarchy of regulatory acceptance
* Mass transport models for exposure estimation
* Models for E&L testing
* CHemical RISk calculators (CHRIS) case study
David M. Saylor, Ph.D. | Research Materials Engineer, Division of Biology, Chemistry, and Materials Science, US Food and Drug Administration
Networking Lunch (Included)
Towards Good Read Across Practice in Medical Device Risk Assessment
With increasing chemical characterization requirements for identifying extractable compounds above analytical evaluation thresholds, read-across can be a powerful risk assessment tool to fill data gaps and evaluate safety. However, structural similarity is not enough to adequately justify a read across approach. In addition to documenting similarities between target and surrogate compounds related to chemical structure, reactive functional groups, and other relevant physicochemical properties, special consideration should be made for respective toxicokinetic and metabolic profiles. In silico methods can be useful for addressing data gaps related to physicochemical properties and hazard potential. Several predictive toxicology tools are available for such purposes, though should not be used as a "black box," and expert judgment may be required in evaluating the confidence and reliability of any predictions. This presentation will provide an overview of lessons learned from read across applied in other regulatory contexts, useful tools for filling data gaps and justifying read across approaches, as well best practices in accounting for uncertainty in such approaches. Lastly, a case study will be presented applying the concepts of good read across practice in identifying and justifying the suitability of proposed analogue compounds for the purposes of a read across risk assessment
Joel M. Cohen, Sc.D., DABT | Senior Toxicologist , Gradient
Methodology for Toxicological Evaluation of Leachables and Extractables into Drug Products
A health-based toxicological risk assessment is the overall goal of conducting extractables and leachables studies. This assessment must be performed on all compounds found in the final drug product at concentrations above the analytical evaluation threshold (AET) by a qualified toxicologist. As there are no specific guidance documents on toxicological assessments, we will present a scientifically defensible stepwise approach of how to assess these compounds. Additionally, a case-study toxicological assessment will be presented.
Mac Taylor D.V.M., DABT | Managing Toxicologist, SafeBridge Regulatory Life Sciences Group
Networking Coffee Break
Using expert knowledge-based and statistical in silico models to predict the toxicity potential of extractables and leachables
Extractables and leachables need to be assessed for their toxicological safety, whether they are found in pharmaceutical products or medical devices, with the major toxicity endpoints of concern being mutagenicity, sensitisation, and systemic toxicity. This study sought to investigate the role that in silico models, including expert systems and various statistical models, could play in predicting the mutagenicity and sensitisation potential of E&Ls as part of a wider risk assessment. Nearly 800 E&L chemical structures were collected from the published ELSIE and PQRI datasets, and publicly available mutagenicity and sensitisation data was located for these wherever possible. This reference data was used to assess the performance of various expert knowledge-based and statistical in silico models, and combinations thereof, for these endpoints. Two existing in silico models (expert knowledge in the form of structural alerts in Derek Nexus and a statistical self-organising hypothesis network model in Sarah Nexus) were applied to predict the bacterial mutagenicity of E&Ls. These models, when used in combination but before any expert review were applied, showed excellent performance with a sensitivity of 75% and specificity of 94% . This approach is already recommended within the ICH M7 guideline for the assessment of potentially mutagenic impurities, and this study shows that the same approach can be applied to accurately predict the mutagenicity of E&Ls. For the sensitisation endpoint , expert knowledge (in the form of skin sensitisation structural alerts in Derek Nexus) was used to predict hazard with a sensitivity of 73% and a specificity of 85%. A novel workflow has been designed which combines this expert knowledge with a statistical model (a k-nearest neighbours model in Derek Nexus) and threshold-based default predictions to predict dermal sensitisation potency. This approach was able to predict whether E&Ls were strong/extreme sensitisers, weak/moderate sensitisers, or non-sensitisers with an overall accuracy of 71%. As the science involved in the toxicological risk assessment of extractables and leachables advances, in silico approaches are expected to play an increasingly important role. This is especially pertinent in the context of the upcoming ICH Q3E guideline, which is hoped will bring much-needed clarity and international harmonisation to this area. This study analysed various expert knowledge-based and statistical in silico models and has shown that different combinations of models are well placed to help assess the mutagenicity and sensitisation potential of E&Ls moving forwards.
Charles Modlin | Principal Scientist, Lhasa Limited
Characterizing extractables and leachables chemical space to support in silico toxicological hazard assessments
In silico tools play an increasingly important role in the toxicological evaluation of extractables and leachables (E&L). It is useful to understand the chemical space defined by E&L chemicals in order to identify procedures and principles governing the use of these tools. The Extractables and Leachable Safety Information Exchange (ELSIE) Consortium and the Product Quality Research Institute (PQRI) have published datasets of E&L chemicals. The combination of the datasets resulted in 783 structures which were used to perform chemical structure-based clustering that allowed a description of the E&L chemical space. 74% of the chemical classes identified in the combined dataset included examples from both ELSIE and PQRI and the most populated classes included linear and branched alkanes, carboxylic acid derivatives (esters and carboxylic acids) and aliphatic alcohols. In silico models that predict bacterial mutagenicity and potent dermal sensitizers were used to assess potential hazards associated with E&L. Approximately 9% (69 out of 783) of chemicals were flagged as potential mutagens and around 3% (25 out of 783) were flagged as potent dermal sensitizers. These observations support previous findings that there is a low prevalence of potent dermal sensitizers in the E&L chemical space. Additionally, this presentation will describe a collaborative effort to determine the feasibility of setting class-based limits for E&L chemicals.
Candice Johnson, Ph.D. | Senior Research Scientist, Instem
Speaker Q&A
  • James M. Vergis, ELSIE Secretariat - Faegre Drinker Biddle and Reath, LLP, Director Science, Research, & Innovation
  • David M. Saylor, Ph.D., CDRH, FDA
  • Dr. Joel Cohen, Principal, Gradient
  • Mac Taylor D.V.M., DABT, Managing Toxicologist for SafeBridge Regulatory Life Sciences Group
  • Charles Modlin, Principal Scientist, Lhasa Limited
  • Candice Johnson Senior Research Scientist Instem 
Closing Roundtable: Topic TDB
Advisory Board
End of Event