Register Today!


The 2024 Agenda has been announced! 

Meet the speakers from The U.S. Food and Drug Administration, West Pharmaceutical Services, Inc., Eli Lilly, Baxter Healthcare, Instem, WuXi AppTec, Nelson Labs, Cambridge Polymer Group, Element, GSK, ToxServices LLC, Octapharma, Intertek Pharmaceutical Services, and More.



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

Registration Opens
Breakfast sponsored by Labcorp
Welcome and Opening Remarks
Ashli Speed, Conference Producer, Smithers
Session I: Digital Transformation in Pharma and Potential Impact of the Assessment of E&L Compounds
< Session Description >
The future of healthcare delivery in the US and internationally is being led by the digital transformation of Pharma. This session will explore the digital transformation of Pharma and its potential impact on the assessment of E&L compounds.
Pharma 4.0/5.0, FDA/FRAME and Digital Twins: Exploring the Digital Event Horizon and Enabling Digital Transformation in Pharma
Digital transformation is driving and defining the disruptive and transformative roadmap for more expedient operations, product development, advanced manufacturing, supply chain and lifecycle management across multiple disciplines and industries. For the pharmaceutical industry, establishment of a digital transformation framework is increasingly aligned with principles consistent with the extrapolation of Industry 4.0 to pharmaceutical manufacturing and operations, with the objective of optimizing production and augmenting current workforce with automation and digital manufacturing operations.  This presentation will discuss the FDA/FRAME initiative, digital twins and cross-collaborative partnerships as primary enablers for advanced manufacturing and digital transformation in pharma.
Douglas Kiehl | Research Advisor, Eli Lilly and Company
Technology in the World of E&L: How Far Have we Come and How Far Can We Go?
Technology is constantly developing and evolving around us, changing and improving the way in which we perform tasks in every aspect of our lives. The world of Extractables and Leachables is no exception: the technology that we use across various areas of the discipline is constantly undergoing further innovations and developments, advancing the ways in which we work.

Over the past decade, particularly over the last few years, the world has seen massive developments in Artificial Intelligence which has already been adopted by a wide and varied range of fields. Therefore it’s important to consider how, and to what extent, AI technology can be implemented within the discipline of Extractables and Leachables: what are the benefits and what are the potential pitfalls that need to be considered when adopting AI into the E&L world.
Dr. Amy Johnson | Principal Scientist, Medical Device Testing, Smithers
Panel: Challenges with Enabling Digital Transformation in Pharma
Establishment of a digital transformation roadmap is aligned with principles consistent with the extrapolation of Industry 4.0 to pharmaceutical manufacturing and operations, with the objective of optimizing production and augmenting current workforce with automation and digital manufacturing operations.  Since many aspects of this broad transformation inevitably impact E&L testing, expectations and data supporting advanced manufacturing, packaging and smart drug delivery systems, this panel will discuss these concepts and impact on the future of E&L and related areas.

  • Candice Johnson, Ph.D., Senior Research Scientist, Instem
  • Dr. Amy Johnson, Principal Scientist, Medical Device Testing, Smithers
Networking Break Sponsored by WuXi AppTec
Session II: Challenges Associated with the Chemical Characterization for Medical Devices
< Session Description >
Medical device manufacturers face significant challenges when conducting a chemical characterization of a device. This session will provide practical advice on how to conduct a chemical characterization of a medical device and will focus on developing strategies that will be accepted by regulatory agencies.
The differences between ISO 10993 (Medical Device) and USP <1663> and <1664> (Combination Drug Product): A Path to Approval-The Regulatory Journey of a Combination Product
U.S. regulatory approval is rarely smooth sailing for any medical product and for combination products the journey can be filled with unexpected detours if you are not properly prepared. Understanding the regulatory landscape before you develop your test plan can get you to your destination on time. We will walk through: • Why understanding the primary mode of action is important • How a presub meeting can set you on a clear path • What are the differences between USP and ISO methods when it comes to Extractable/Leachable testing • When to apply USP<1663>/USP<1664> and/or ISO 10993 parts 17 and 18 in your test plan Finally, we will navigate a combination product case study and explore some of the hidden pitfalls encountered during the journey.
Sandi Schaible | Senior Director, Analytical Chemistry and Regulatory Toxicology, WuXi AppTec Medical Device Testing
The Impact of Physico-Chemical Properties of Extractable Compounds on their Analytical Responses: An Evaluation of GC/MS Response Data
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. However, one of the aspects that is under constant debate is how to make a non-targeted analysis – to detect and identify a broad set of compounds – sufficiently protective or quantitative allowing a subsequent reliable toxicological risk analysis. While authorities indicate that a number of surrogate standards (eg 3 for GC/MS, 5 for LC/MS) should be used with varying retention times or functional groups to assist in the quantification of the detected extractables, little or no guidance is given on the selection criteria on which surrogate to select to quantify a detected compound. In a first step to address this issue, Nelson Labs has evaluated over 2700 compounds of which the analysis of authentic standards provided relative response values in GC/MS. GC/MS was selected first because the methods developed in GC/MS often show a more standardized chromatographic and MS-settings and is considered as the “work horse” in E/L testing. Conclusions in GC/MS could also lead to guidance on how to optimize the orthogonal and complementary non-targeted analysis methodology (combining different chromatographic techniques and detectors) for low responding GC/MS compounds could be well defined.  The database of over 2700 compounds was evaluated against a number of physico-chemical properties such as 
  • boiling point
  • molecular weight
  • retention time
  • LogKow
While several of these parameters show to have an excellent inter-correlation (eg Boiling Point versus LogKow; LogKow versus retention time…), when it comes to impacting the GC/MS-responses of compounds, there is one correlation that stands out: The correlation between LogKow and the associated response measured in GC/MS. A detailed evaluation of this correlation could allow either a differentiated approach in the use of responses for compounds detected in GC/MS or it even would allow selecting surrogate standards in a more scientific way. The strategy on how this correlation could be used in actual E/L-studies will be presented.
Dr. Jan Baeten | Sr. Scientist – Technical Advisor, Nelson Labs
A Comparative Study of Extraction Techniques in E&L Testing
In the recent push for an analytical approach to medical device safety, reliable leaching and extraction methods have become critical to the success of the approach. For many medical devices, exhaustive extraction conditions, with reference to ISO 10993-18:2020, are expected by regulators to fully characterize the risk posed by chemical substances. Per the standard, exhaustive extraction is intended to allow capture of all compounds that might be of concern, while not damaging the device’s material. These conflicting demands make the choice of conditions harder than it may seem and has led to substantial increases in the time and cost required to develop new products and to clear regulatory hurdles when changes are made to existing products. Typically, exhaustive extraction requires multiple rounds of extraction at 50 C for 72 hours until exhaustion has been reached based on gravimetric determination of non-volatile residue (NVR) content. However, alternative extraction techniques may provide a more rapid and cost-effective approach towards obtaining an extractables profile for risk analysis. In this presentation, we compare the extractables profile obtained from a medical device component by several different extraction techniques, as determined by NVR analysis, LCMS, and GCMS. This information provides the context for a discussion on when an alternative extraction technique may allow medical device manufacturers to reduce the E&L testing burden.
Becky Bader | Associate Director of Chromatography, Cambridge Polymer Group
Case Study: Migration of PFAS from Fluoropolymers used as Single-Use Processing
Components in the Manufacture of Cell & Gene Therapy Products In the rapidly advancing field of Cell & Gene Therapy (CGT) manufacturing, the use of single-use processing components is integral for efficiency and flexibility. Fluoropolymers, such as FEP, have been commonly used as materials of construction for these components and commonly known for being inert. However, concerns have emerged regarding the potential migration of Per- and Polyfluoroalkyl Substances (PFAS) from fluoropolymer contact materials into therapeutic products. When PFAS are detected in E&L studies, they require thorough investigation to ensure the safety and efficacy of CGT products.This presentation will dive into a case study for the identification of PFAS from a commonly used single-use material, FEP. The case study will cover factors influencing migration, potential impacts on patient safety and regulatory feedback received with regards to PFA detection in CGT E&L studies. This presentation seeks to facilitate a collaborative dialogue within the CGT community, fostering awareness, and encouraging the development of industry-wide standards to ensure the continued success and safety of Cell & Gene Therapy products.

Co-presenter: Crystal Russo, Associate Director MSAT, Bluebird Bio  
Sam Albeke | LC Manager, Element
Networking Lunch
Session III: Medical Device Manufacturers Case Studies and Panel: The Trials and Tribulations of Chemical Characterization
< Session Description >
In the session, we will hear from four experts in the medical device industry and their specific experiences with chemical characterization and subsequent submissions for regulatory acceptance. The focus of the session will be case studies of real life scenarios as well as a panel for open Q&A.
From Hurdles to High-Fives: Navigating towards EU MDR Compliance
In this presentation, the impact that EU MDR has brought to the E&L world will be discussed, as well as the efforts required to sustain market access for Acute Solutions and Renal Care medical devices provided by Baxter to millions of patients. This presentation will also highlight the challenges that EU MDR has placed on the medical device industry, as well as provide hints on E&L testing strategies for EU MDR.  At a high-level, the long journey that EU MDR represents to manufacturers will be demonstrated with specific examples and case studies of deficiencies received by different notified bodies and how Baxter has turned hurdles into high-fives. Lastly, the presentation will provide an insight to what the post-MDR world might look like in terms of change controls driven by the constant challenges in the current uncertain global supply chain environment.
Rodrigo Feliciano, PharmD, PhD | Extractables and Leachables / Materials Science – Senior Manager, Renal Care, Baxter International Inc.
Proposed Revisions to ISO 10993-1: Renewed Guidance Recommendations Illustrated Through a Case Study Using a True Risk Assessment Approach for The Biological Safety Evaluation of a Hemodialyzer.
This presentation will cover a brief overview of biological risk assessment requirements per the current edition of ISO 10993-1 (2018) and what’s on the horizon for revisions to this guidance document. The highlight of this presentation will be an exceptional case study of an externally communicating, circulating blood contact device where the submission strategy necessitated the use of a true risk assessment approach due to an unfavourable outcome in the biological testing. Importantly, this case study will illustrate the limitations of chemical characterization through extractables and leachables studies. Key takeaways of this presentation will be the following: 1) Datasets providing evidence for the biological safety evaluation are not evaluated in isolation, 2) Biological safety evaluations should always be driven by a true risk assessment approach and 3) Proposed revisions to ISO 10993-1 will encourage the implementation of risk management principles to support medical device safety narratives.
Crystal D’Silva | Senior Manager - Preclinical Toxicology, Baxter International Inc.
Speaker Roundtable: Perspectives on E&L Experiences With Chemical Characterization
  • Descriptions of challenges and overcoming challenges with chemical characterization
  • Scientific solutions other manufactures may have used when submitting chemical characterization data, and or toxicological risk assessment
  • The opportunity to ask questions of experts in the medical device industry
  • Sheri Krajewski Senior Global Product Marketing Manager, Biological Evaluation of Medical Devices, NAMSA 
  • Nicole Soucy, Director of Global Toxicology and Biocompatibility, Boston Scientific
  • Anthony Ragheb, Senior Vice President, Cook Research Incorporated
  • Rodrigo Feliciano, PharmD, PhD, Extractables and Leachables / Materials Science – Senior Manager, Renal Care, Baxter International Inc.
  • Crystal D’Silva, Senior Manager - Preclinical Toxicology, Baxter International Inc.
Networking Break
Session IV: Pharma and CRO Collaboration
< Session Description >
Collaborations between manufacturers and contract research organizations (CROs) can help to resolve issued faced by manufacturers by leveraging the considerable expertise of CROs across a wide range of drug delivery systems and devices. These collaborative efforts can promote uniformity in analytical chemistry practices and improve data quality by taking a broad view of issues that are not typically possible for any single manufacturer to address.  This session will explore efforts to facilitate collaborations between Pharma and CROs to address issues of mutual interest in the chemical analysis and safety assessment of E&L compounds.
CHemical RISk calculators (CHRIS): Interlaboratory Study for Extraction Testing of Medical Devices
We have been developing physics-based models to provide an accurate and relatively facile means of predicting the extracted amount of chemicals found in extraction testing conducted in aggressive environments and translating these results to a more clinically relevant context (CHemical RISk calculators (CHRIS)).  However, confidence in the model output will be dictated by uncertainty in not only the model parameters, but also the model input.  Therefore, as part of these efforts, we conducted an interlaboratory study (ILS) with the goal of establishing the repeatability (variation within laboratories) and reproducibility (variation among laboratories) in quantitation of medical device extractables, which were present as bulk additives.  This presentation will cover the study design, analyses of the resulting data based on ASTM E691-21 "Standard Practice for Conducting an Interlaboratory Study to Determine the Precision of a Test Method", and potential implications of observed intra- and inter-laboratory variability.
David M. Saylor, Ph.D. | Research Materials Engineer, Division of Biology, Chemistry, and Materials Science, US Food and Drug Administration
Results of the ELSIE Lab Practices Sub Team's Surveys for Understanding Intra-Lab Method/Procedure Variations for the Execution of Extractable Screening Studies
Anecdotally, it’s been stated that the results obtained from extractable screening studies performed at different laboratories will be inconsistent in the qualitative and/or quantitative profiles reported to at least some degree. Such inconsistencies have been hypothesized to be attributable to differences in the methods and procedures used to generate and evaluate the data in these studies. To that end, ELSIE has formed a working group whose purpose is to investigate the extent of alignment, or lack thereof, between laboratories and ultimately work towards ways to improve consistency in the data generated on an inter-laboratory basis. To investigate this in more detail, the working group surveyed a large number of CRO and pharmaceutical (sponsor) companies in order to better understanding variations in methods and lab practices used between labs. This presentation will discuss the data obtained from these surveys, highlighting areas where labs are or are not well aligned for key method/procedural aspects including surrogate standard selection, uncertainty factor determination and usage, system suitability parameters, and relevant methodology variables.
Steve Zdravkovic | Research Scientist II, Baxter Healthcare
Panel facilitated by ELSIE: Aligning Critical Aspects of the Execution of Extractable Screening Studies Between Labs with the Goal of Improving the Consistency and Quality of Data Produced
Aside from anecdotal evidence suggesting a lack of alignment in the execution of extractable screening studies between labs, the recent ELSIE survey on this topic highlighted notable areas where labs were indeed not well aligned. This panel discussion will provide the participants and the audience a chance to weigh in on the topic of how to achieve better alignment between labs, concerns with alignment, and suggestions as to how this may be best achieved.

  • Steve Zdravkovic, Research Scientist II, Baxter Healthcare
  • Elizabeth Ebitson, Principal Scientist, Pfizer
  • Ravi Kaja PhD Senior Principal Scientist, USP
  • Edwin Jao, Division Director, Center for Drug Evaluation and Research, U. S. Food and Drug Administration
  • Joshua Young, FDA CDRH
Poster Sessions
Networking Reception
Registration Opens
Session V: Regulatory Expectations
< Session Description >
This session will explore how standards and guidance documents are used for this process and will provide an update on recent changes to the standards that impact the way that the safety assessment of E&L compounds is conducted.
Analytical Assessment of Leachables in Biological Drug Products: FDA Approach and Experience in Reviewing Information
Biological drug products (biologicals; such as therapeutic proteins, vaccine-, gene-, and cell therapy-based) are produced via multi-step processes involving multiple materials contacting intermediates and sourcing numerous leachables into final drug products (DP). Such steps involve (i) purification of intermediates using chromatography, centrifuging, dialysis, filtering, and filling in final container closure system, etc., (ii) shelf-life storage and (iii) in-use hold of DP. The respective contact materials involve chromatography resins, filtering/dialysis membranes, tubing, collecting bags/tanks, gaskets, valves, final container closure systems, etc. By these, the assessment of leachables risk in biologics is the most challenging compared to other types of DPs. However, current guidances are generally focused on assessment of the leachables only from single manufacturing components, scored to be high-risk for leachables, and by this, underestimate other components scored to have the lower risk. Following these directions, manufacturers typically perform the assessments only for the high-risk components and by this, underestimate the contribution of other materials to the overall (cumulative) leachables profile in final DP. Other typical issues involve (i) non-validation of analytical methods, resulting in ambiguity in Analytical Uncertainty Factor (AUF) used for calculation of the Analytical Evaluation Threshold (AET; reporting limit in an assay), (ii) missing the assessment of elemental (ionic) leachables, or (iii) incorrect leachables study design; altogether also resulting in potential underestimation of the leachables risk. These issues usually cause multiple back-and-forth communications between the FDA and Sponsor during the applications’ (BLAs and supplements) review, typically ending up with post-marketing requirements (PMR) and putting an unnecessary burden on both sides. This presentation overviews an FDA approach and experience in reviewing information for analytical assessment of leachables, including examples of the review cases and found issues, aimed to reduce the efforts of both sides in the review process and facilitate proper evaluation of the leachables risk, and also used in preparation of the current ICH Q3E guidance draft. 
Andrey Sarafanov, PhD | Principal Investigator, Center for Biologics Evaluation and Research, U. S. Food and Drug Administration
Extractable and Leachable Risk Assessment for a Pharmaceutical Manufacturing Train Utilizing USP <1665> and <665>
Catalent has a systematic process in place to incorporate E&L risk assessments in its pharmaceutical manufacturing train. The primary goal of this process is to ensure product safety and compliance with USP <1665> and <665> throughout all stages of manufacturing. This systematic approach involves an initial assessment, identification and quantification of risks, and the assignment of characterization levels to develop a robust risk mitigation strategy. Catalent uses risk dimension scores and clinical mitigation factors to evaluate the risk of leachables in systems used in the manufacture of pharmaceutical products. A case study will illustrate the application of the USP <1665> and <665> framework to perform an E&L manufacturing risk assessment and how this can support drug sponsors in obtaining regulatory approval.  
Vicki Ward | Sr. Manager, Analytical R&D, Catalent
Speaker Q&A
Networking Break
Session VI: Practical Application of Approaches to Assessment Safety of E&L Compounds: Part I
< Session Description >
This session will explore the practical challenges associated with the safety assessment of E&L compounds and will propose methods to address these challenges.
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
Design Principles for Extractables Studies of Combination Products
The use of medical devices in combination products has increased greatly in the past 15 years and is expected to continue to increase for the foreseeable future. This has been bolstered by an industry push to fill a demand for patients to have access to at-home therapies with the use of on-body-wearable and self-dosing technologies. Companies that decide to use devices like these to deliver their drugs have plenty to consider with regards to extractables, leachables, and the overall chemical safety of their product. A strong understanding of the risks that leachables may pose during the use of a combination product first requires thoughtful and informed design of extractables studies as a starting point, with the appropriate application of industry guidance. However, there are two main sources of guidance for drug-device combinations. First is USP <1663> Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems, which is primarily applied to drug primary packaging (container closure systems). Second is ISO 10993 Biological evaluation of medical devices, and in particular parts 12 and 18 which speak to the design of studies and proper chemical characterization of medical devices. Although there are some basic principles shared between these two sources, there are distinctions that must be understood so that the design of the extractables study starts you on the path of success in your extractables and leachables program. Presented here is a review of these principles and an ideal design of an extractables study of a combination product composed of a drug stored in a cyclic olefin copolymer (COP) cartridge inside a wearable device that is adhered to the skin. The drug is delivered subcutaneously over a short period of time through polymer tubing and a stainless-steel needle.
Will Parker | E&L Technology Manager, West Pharmaceutical Services
Networking Lunch
Session VII: Practical Application of Approaches to Assessment Safety of E&L Compounds: Part II
< Session Description >
This session will continue to explore the practical challenges associated with the safety assessment of E&L compounds and will propose methods to address these challenges.
Unique Challenges in Tolerable Intake Derivation for Medical Device Extractables
ISO 10993-Part 17 requires a toxicological risk assessment of medical device extractables or leachables, one component of which is the establishment of a tolerable intake (TI). The TI is based upon available toxicological data together with a calculated composite modifying factor. Although establishment of TIs can be straightforward, particularly if the substance has an existing USP or ICH PDE, in some cases unique medical device use conditions necessitate novel approaches to TI identification. We will present case studies that illustrate the unique challenges that can be associated with, for example, development of short-term inhalation TIs for elemental impurities, calculation of appropriate UFs for route-to-route extrapolation, and use of read-across for extractables or leachables with limited toxicological data.
Jennifer Ator | Principal Toxicologist, ToxServices LLC
Extractables and Leachables Assessments in Pre-Filled Syringe (PFS) Drug Products
The unique design of Pre-Filled Syringes (PFS) can results in a number of leachables from the container closure system (CCS) components and their processing. PFS are used for parenteral drug administration. Therefore, health authorities (HA) expects leachables documentation on the drug product side. Since PFS can also be device health authorities would expect documentation for a combination drug product combining the device documentation (ISO 10093, direct patient expose) with the drug product documentation (leachables, indirect exposure according to ISO 10993). This presentation will describe sources for leachables in the PFS including leachables that has a potential to interact with biologics drug products. The presentation will also describe leachables documentation and assessments for PFS as a combination drug product.
Carsten Worsøe | Principal Scientist Extractables and Leachables, Novo Nordisk
Interactions of Extractables / Leachables with Therapeutic Proteins - Assessment Strategies and Case Study
In addition to posing toxicological risks, extractables / leachables may interact with therapeutic proteins potentially altering their efficacy in an undesirable way. While many extractables / leachables exhibit protein binding alerts based on their chemical structure, the underlying reactions in a drug product matrix can only take place under certain conditions. For example, an SN2 reaction is inhibited in aqueous media. A simple assessment can help derisking a number of extractables / leachables in this regard. N-(3-(Dimethylamino)propyl)methacrylamide in addition to form- and acetaldehyde, two prominent extractables from irradiated single-use materials, were tested for reactions with the human derived coagulation factor IX. While no reaction with N-(3-(Dimethylamino)propyl)methacrylamide was observed, despite its alert for protein binding via Michael addition, formaldehyde was found to colvalently bind to lysine in two different peptides of the protein, starting at a concentration of 10 µg/mL. The clotting activity of FIX spiked with 500 µg/mL of formaldehyde dropped by more than half. The activity of the FIX spiked with acetaldehyde began to drop at already 50 µg/mL and continued to drop with increasing concentrations of acetaldehyde. The concentrations of form- and acetaldehyde that triggered a non-acceptable drop in the clotting activity did not correlate to the corresponding toxicological safety limits. It is concluded that some leachables may indeed react with- or modify therapeutic proteins, potentially causing an undesired pharmacological effect. Such effect may be captured by adequate product quality test methods. The results obtained in this case study indicate a concentration dependent effect.
Alicja Sobańtka PhD | Head of Corporate Material Qualification , Octapharma
Coffee Break
Evaluation of Complex E&L Data Packages. Using Science, Expertise, and Common Sense to Streamline Data Processing and Enhance Efficiency.
E&L testing is very often complicated by combination of complex matrices and extremely low-level detection requirements, particularly in the case of large volume parenterals or large size implantable devices. Based on the current regulatory standards and industry best practices it is required to use complimentary (and often orthogonal) analytical techniques, to evaluate volatiles, semi-volatiles and non-volatiles in various sample extracts. Elemental impurity testing is more straightforward and less complex, as finite numbers of elemental impurities existing and listed in the standards, allowing well defined targeted approach for testing. The situation is more complex for organic impurities as the potential number of targets are in a range of 10,000-100,000 analytes, which usually requires either a large number of targets on a defined list or use a non-targeted data processing. This presentation will focus on case studies, illustrating how data obtained from different type of analytical instrumentations can be used as complimentary information, empowering the scientist to make more confident decisions regarding identification and quantitation, and providing evidence for the suitability of the analytical methods used for the testing.
Gyorgy Vas | Research Fellow, Intertek Pharmaceutical Services
Speaker Q&A
Closing Remarks