E&L USA 2019 Poster Presentations

The Poster Session at E&L US gave the opportunity for industry and academic experts to share their technical research, testing results and latest case studies with an audience of E&L professionals from across the supply chain.

The posters were a prominent part of the exhibition hall to ensure that delegates have plenty of opportunity to visit. The posters were on display throughout the event, with a dedicated 'Poster Session' taking place during the conference where we asked authors to stand by their posters to allow attendees to answer questions and give comments on the information presented.

2019 E&L USA Poster Session

The Poster Session at E&L US will give the opportunity for industry and academic experts to share their technical research, testing results and latest case studies with an audience of E&L professionals from across the supply chain.

  1. The Development of a Library of Plastics Additives for Identifications of Extractables

    Yizhong Wang, Ph.D. | Project Director of Avomeen Analytical Services

    Peipei Hu, Ph.D., Alexis Langtry, Yizhong Wang Ph.D., and Andrew C. Kolbert, Ph.D. 
    Avomeen Analytical Services, 4840 Venture Drive, Ann Arbor, MI 48105

    In the pharmaceutical industry, it’s important to identify extractables and leachables from pharmaceutical packaging and container closure systems for patient safety and submissions to regulatory authorities.  Many of the substances reported are additives that provide a variety of technical effects to the polymer formulations. To facilitate the identification of extractables, we have acquired and compiled data on hundreds of examples across seven major categories of polymer additives including accelerants, antioxidants, antidegradants, bisphenol analogues, cross-liners, plasticizers, and UV stabilizers.  Common methodology using using HPLC, LC-MS, and GC-MS was established and will be presented as well as data across some of the major categories.  Examples of the use of the library in identifying unknowns in extractables and migration studies will be presented.

  2. In Silico Protocols for Mutagenicity as well as Sensitization and Irritation

    Candice Johnson, Ph.D. | Research Scientist of Leadscope, Inc.

    Candice Johnson, Dave Bower, Kevin Cross, Scott Miller, Pat Quigley, Glenn Myatt
    Leadscope, Inc., Columbus OH

    In silico methods play an important role in the toxicological evaluation of extractables and leachables. Frameworks for the in silico assessments of DNA-reactive mutagenicity as well as sensitization and irritation are presented. The frameworks are flexible and can provide endpoint predictions for a single test (eg. skin sensitization prediction based on the Local Lymph Node Assay (LLNA)) or for a test battery through an integrated approach to testing and assessment (IATA). The use of an IATA incorporates knowledge of structure-activity relationships along adverse outcome pathways (AOP), and assesses the weight of evidence from relevant effects and mechanisms. The frameworks are central parts of protocols that are being developed for assessing the toxicological endpoints. Each protocol outlines standardized procedures to conduct the in silico assessments of its dependent endpoint. A cross-industry consortium proposed a general strategy for the development of the protocols with the aim of improving the transparency and reproducibility of in silico assessments.

    • Protocols are defined for the in silico evaluation of genetic toxicity as well as sensitization and irritation
    • Relevant effects and mechanisms are arranged into a hazard assessment framework • Rules and principles are defined for deriving an overall assessment
    • The protocols aim to improve the transparency and reproducibility of in silico assessments
    • Protocols are under development for repeated dose toxicity, organ-system toxicity, environmental and neurotoxicity  
  3. Extraction Techniques Comparison for an Optimized Study. Accelerated Solvent Extraction, Microwave and Soxhlet Evaluation

    Diego Zulkiewicz Gomes | Analytical Development of Aché Laboratórios Farmacêuticos

    Extractables and leachables are of great concern in the pharmaceutical industry, considering that chemical entities with toxicological potential can be released from a container closure system (CCS), packaging components and/or processing equipment into a drug product, affecting the product quality, and in some cases reflecting in risk for the patient. Currently in Brazil, the regulatory agency (Anvisa) have no specific document that guide industries to what is really needed in an E&L study. The lack of information and harmonization brings up the necessity for scientific research to delineate best practices in a case-to-case approach. Taking as starting point important guidelines, like PQRI, that is already recognized by the scientific community, and USP General Chapters 1663 and 1664, we propose a comparison with different extraction techniques in a nasal suspension spray product. The traditional Soxhlet extraction, that take many hours to perform an efficient extraction is compared with microwave extraction and Accelerated Solvent Extraction (ASE), which may reflect in time saving in routine industry application and also a better understanding of CCS – Drug product interaction.

    • Extraction Techniques 
    • Accelerated Solvent Extraction (ASE)
    • Microwave
    • Soxhlet
  4. How to Use Extractables Data for Material Safety Evaluation of Sterile Filters

    Ina Pahl | Senior Scientist Device Technologies, Research & Development of Sartorius Stedim Biotech GmbH

    Ina Pahl*+, Roberto Menzel*, Armin Hauk*, Samuel Dorey**

    *Sartorius Stedim Biotech GmbH, August-Spindler-Straße 11, 37079 Göttingen, Gemany
    +phone: 0049 551 3082 241

    ** Sartorius Stedim FMT S.A.S., Avenue de Jouques, CS91051, ZI des Paluds, 13781 Aubagne Cedex, France

    Sartorius Stedim Biotech (SSB) provides complete extractables data for SU components such as storage bags, tubing or sterilizing grade filters obtained e.g. from pure ethanol and water extracts using state-of-the-art analytical methods such as (headspace) GC-MS, LC-HRMS, HPLC-UV, and ICP-MS. The extractables are identified and quantified using standard compounds, if available. The source of the identified compounds can be derived from the material of construction. This set of data allows users to perform a material safety assessment of the SU components, e.g. during the installation qualification phase of the biopharmaceutical process.

    This poster presents exemplarily how extractables data from the supplier can be used for the material safety assessment of sterilizing grade PESU filters. Toxicological information available from literature for selected extractables compounds is combined with the extractables data and assessed.

    With our approach we are able to provide state-of-the-art extractables profiles with almost no unknowns and therefore risk assessment is possible straight forward.

  5. Solvent Selection in Chemical Characterization of Medical Devices

    Joshua Young, PhD | Senior Study Director of NAMSA

    With the recent release of ISO 10993-1:2018, and the highly anticipated revision to ISO 10993-18, chemical characterization testing has skyrocketed to the forefront of necessary information for toxicological evaluation of medical devices. With increased scrutiny on the necessary threshold limits needed for chemistry data, the study design for an effective extractables characterization must include careful assessment of the extraction solvents and the anticipated material interactions.

    This presentation aims to explore several common methods of assessing the appropriateness of extraction solvent-polymer pairings by providing case studies which demonstrate the effectiveness of these approaches.

    • Solvent Selection
    • Polarity
    • Chemical Characterization
    • Medical Devices
  6. Optimization of Reference Standards: Strategy for Simple, Reliable, and Robust Workflow for E&L Analysis

    Naga D Koduri, PhD | Senior Chemist of American Preclinical Services

    Regulatory guidance (ISO 10993) on E&L analyses for medical devices are well documented. These guidance documents do not provide clear direction about analytical methodologies, they only provide recommendations for identification and quantification of E&L compounds. LCMS and GCMS are commonly used platforms to provide a complete picture of non-volatile, semi-volatile, and volatile E&L compounds from complicated extracts and samples with high matrix background. Selection of suitable reference standards is an integral part of E&L compound quantification using LCMS and GCMS. It is a challenging process to select the correct internal standards for semi-quantitative analysis of unknown E&L compounds because of their variable responses from MS detectors. Also, the sample preparation, data analysis, and processing methodology used can have a significant impact on the results. In this presentation we will review our proposed approach for streamlining the selection and analysis of reference standards in LCMS and GCMS characterization of medical devices. We will also demonstrate the semi-automated data analysis and identification workflows using ThermoFisher’s Compound Discoverer Software.

    1. Optimization of various classes of polymeric materials (industry polymer additives and preservatives) as reference standards.
    2. Showcasing how multiple standard selection create impact on the number of compounds determined to be above AET.
    3. Demonstration of automated Semi-qualitative analysis of E&L data using extracted ion (XIC) in presence of complex matrix background.
    4. Demonstration of simple and reliable automated compound identification using Thermo’s Compound Discoverer software.
  7. Assessment of Patient Exposure to Leachables from Lyophilized Drug Formulations Following Reconstitution, Storage, and Administration via Polymeric Packaging/Delivery Systems

    Steve Zdravkovic | Senior Research Scientist of PPD Laboratories

    It has been demonstrated that lyophilized drug formulations have an increased propensity to leach substances from the rubber stoppers comprising their primary packaging system. Unfortunately, patient exposure to leachables originating in lyophilized drug products is not known. To that end, the goal of this study was to assess patient exposure to these leachables after reconstitution, storage, and administration of the lyophilized drug. To achieve this goal, several leachables present in two commercial lyophilized drug products were quantified after contact with PVC and non-PVC medication bags as well as an infusion set for durations of 15 minutes to 7 days at refrigerated and/or ambient temperature. This study’s results showed that the bag’s material of construction and the drugs formulation did not impact the mass of the leachables administered. Conversely, the mass of each leachable administered to the patient was reduced or eliminated as the contact duration with the IV bag and the temperature increased. However, for shorter contact durations, refrigerated storage, and/or higher molecular weight compounds, the patient would be exposed to a majority of the leachables.

    • The results obtained in this study have shown that the mass of each leachable that would be introduced to the patient was reduced, or eliminated altogether, after exposure to a secondary/tertiary storage/delivery system.
    • However, the rate and magnitude of the mass administered as a function of time was not equivalent for each leachable.
    • Furthermore, it was demonstrated that in some cases an appreciable mass of the leachable present in the vial would be administered to the patient.
  8. Solubility of Common Extractable Compounds and Model Solvent Choice

    Michelle Kolodziejski | Principal Chemist of Eurofins BioPharma Product Testing

    Solubility is a critical parameter when evaluating potential extractables and/or leachables. Since most polymer additives are engineered to allow solubilization in the polymer mix, many show poor solubility in aqueous solutions. This solubility is a limiting factor when predicting potential leachables that may be introduced into a drug product formulation if the appropriate extraction solvents are not chosen. In order to provide solubility profiles, 14 common extractable compounds were evaluated for solubility in 11 common extraction solvents. Visual observation was utilized to determine the point of insolubility over a range of approximately 2 µg/mL to 2000 µg/mL. Solubility profiles were compared with particular focus on partition coefficient (logP) values. In addition, the solubility profiles for isopropanol:water, ethanol:water, and ethylene glycol monobutyl ether:water mixtures were compared to the profiles for 0.1% polysorbate 80 (PS80) and 1% PS80 solutions to determine if these solvents would be useful alternatives to this problematic solution.

    • Solubility profiles for 14 compounds that include several phenolic antioxidants, a phosphite antioxidant, a nylon monomer, fatty acids, and a fatty acid amide.
    • Comparison charts to quickly judge relative solubility and how they will impact the observed extractables.
    • Compound solubility in extraction solvents containing PS80 vs. alternative extraction solvents.
    • Discussion of logP as a rough indicator of solubility in aqueous solutions 
  9. Evaluation and Comparison of Sample Preparation Techniques and Analytical Instrumentation for Extractable Testing

    Anna Michelson, Ph.D. | Scientist in Trace Organic Labs of Intertek

    Anna Michelson, Gyorgy Vas, Louis Fleck, John Duett, Nan Zhang, Jacquelyn Cali
    Intertek Pharmaceutical Services, Whitehouse, NJ

  • Candice Johnson, Ph.D.

    Research Scientist Leadscope, Inc.

    Candice Johnson, Ph.D. is a Research Scientist at Leadscope, Inc. She is working alongside an international consortium to develop in silico protocols for the assessment of skin sensitization, respiratory sensitization, and skin irritation/corrosion.

    One of the aims of her work is to present a harmonized strategy for integrating in silico assessments of biological pathways which are relevant to each of the aforementioned endpoints. She is particularly interested in approaches used to derive a confidence measure in integrated assessments.

    Dr. Johnson’s experience includes developing dose-response models and computational methods for environmental mixture assessments.

  • Naga D Koduri, PhD

    Senior Chemist American Preclinical Services

    Naga D Koduri received his PhD in Organic Chemistry from the University of Tulsa. Starting in April of 2018, he is working as a Senior Chemist involved in developing workflows for generating quality data for E&L projects analyzing various medical devices and SUS at American Preclinical Services, LLC (APS), Minneapolis, MN.

    The team at APS designs and generates high quality analytical data needed to qualify the use of medical devices and SUS. Dr. Koduri has 3+ years of experience in E&L analysis.

  • Michelle Kolodziejski

    Principal Chemist Eurofins BioPharma Product Testing

    Michelle Kolodziejski is a Research Fellow at Eurofins Lancaster Laboratories with over 30 years of laboratory experience. Michelle earned a B.S. in Biophysical Environmental Studies from Northland College and a Masters in Analytical Chemistry from Illinois Institute of Technology. Michelle has been involved with Extractables/Leachables testing for over 14 years. Her expertise includes method development and validation, extractables screening, and comprehensive peak identifications.

  • Anna Michelson, Ph.D.

    Scientist in Trace Organic Labs Intertek

    Anna is a Scientist in the Trace Organics Lab at Intertek.

  • Ina Pahl

    Senior Scientist Device Technologies, Research & Development Sartorius Stedim Biotech GmbH

    Ina Pahl is chemist and started with Sartorius Stedim Biotech in 1997. She is senior scientist in the department of Bag Technology where she works in a team whose tasks are to develop and perform extractables studies, and evaluate the results thereof. The data are used to provide customer information on extractables data for the assessment of material safety of single-use components. She has published in the field of analytical chemistry, extractables data of single use components, sensors, and fundamentals of membranes. Ina is active member of DECHEMA and ELSIE.

  • Yizhong Wang, Ph.D.

    Project Director Avomeen Analytical Services

    Dr. Yizhong Wang has years of experience developing, implementing, and optimizing analytical methods, as well as performing validation/verification for developed, optimized, and transferred analytical methods under cGMP conditions per FDA, USP, and ICH guidelines for pharmaceutical products. Dr. Wang has planned and executed extractable and leachable testing for pharmaceutical packaging and delivery systems by GC/LC and peripheral analytical techniques. He is an expert in LC-MS/MS quantitative analysis, as well as GC, HPLC, UV, and IR analysis. Yizhong’s breadth of experience extends beyond analytical chemistry and includes organic chemistry and organic synthesis.

  • Joshua Young, PhD

    Senior Study Director NAMSA

    Joshua Young, PhD serves as NAMSA’s Senior Study Director based in Toledo, Ohio (USA). In his current position, Dr. Young manages and oversees specialized studies for standard and atypical chemical analysis needs. In total, he has 12 years’ experience in the analysis of small molecules and the chemical evaluation of medical devices for biological safety.

    Joshua earned his Bachelor’s degree in chemistry from the University of Michigan and his PhD in Chemistry from the University of Toledo.

  • Steve Zdravkovic

    Senior Research Scientist PPD Laboratories

    Steve Zdravkovic is a Senior Research Scientist at PPD, Inc. in Middleton, WI.  For the past 12 years, Steve has been responsible for the design and execution of all aspects of an Extractable/Leachable program associated with a wide range of pharmaceutical manufacturing, packaging, and delivery systems, with a focus on extractable and leachable screening studies utilizing mass spectrometry.  

    In addition to these responsibilities, Steve has also performed research on various issues in the Extractable/Leachable field resulting in the publication of 6 first-author papers in respected peer reviewed journals over the past 5 years.

  • Diego Zulkiewicz Gomes

    Analytical Development Aché Laboratórios Farmacêuticos

    Great experience in analytical techniques, with focus in mass spectrometry. I worked in a research institute for 6 years helping industries to find solutions in different problems involving production, product quality or search for innovation. In the last 2 years, I'm part of the pharmaceutical world, also acting in R&D, helping to apply new technologies and, with a scientific approach, helping attending new regulatory needs. I graduated and completed my master degree in chemistry.