2018 Programme

Day one - Tuesday 11 September

Day one

  1. Registration and morning refreshments

Training morning

  1. An introduction to E&L

    Led by Dr. Andrew Feilden, Chemistry Operations Director and Dr. Dan Norwood, Senior Consultant, Smithers Rapra

    A morning of in-depth training on extractables and leachables testing. 

    Includes a 30-minute networking break. 

    Topics to be discussed include:

    • Introduction to extractables and Leachables
      • Definitions
      • Chemical entities (chemical diversity)
      • Sources
    • Regulatory environment
      • Regulatory guidances
      • Best practices
      • Standards
    • Threshold Concept
      • Safety based thresholds
      • Analytical threshold (AET)
    • Extractables assessment
      • Basic principles
      • Generating the extract
        • extracting solvents
        • extraction techniques and conditions
      • Characterizing the extract
        •  identification of extractables
        • quantitation of extractables
    • Leachables assessment
    • Simulation studies
    • Extractable elements
  2. Networking lunch

Regulatory landscape, expectations and protocol insights

  1. Chair’s opening remarks for conference

    Dr. Andrew Feilden | Chemistry Operations Director of Smithers Rapra

  2. Welcome remarks from our Platinum Sponsor

    Baiba Cabovska | Senior Manager of Waters Technologies, USA

  3. The Product Quality Research Institute: almost two decades of progress on extractables and leachables

    Dr. Daniel Norwood | Executive Partner of SCIO Analytical & Senior Consultant at Smithers Rapra, UK

    The Product Quality Research Institute (PQRI) is an organisation based in the United States whose purpose is to facilitate collaborative work between scientists from industry, academia and government which is focused on problems and issues of concern to pharmaceutical development and the regulatory science of pharmaceutical development.  Since 2001, PQRI has facilitated the activities of two working groups related to the issue of extractables and leachables in pharmaceutical products.  The first of these groups (2001-2006) focused on inhalation drug products, which are considered to be of the highest risk based on both leaching potential and route of patient administration.  The second group (2008-present) extended the work of the first group to parenteral and injectable drug products.  This presentation will discuss the mission and organisation of PQRI, and summarise the achievements of both working groups.  In addition, possible future activities of PQRI related to the issue of extractables and leachables will be considered.

  4. USP strategy for pharmaceutical materials used in packaging, medical devices and manufacturing systems

    Dr. Dennis Jenke | Chief Executive Scientist of Triad Scientific Solutions, UK

    Pharmaceutical applications of polymers including packaging, medical devices and manufacturing equipment. Consistent with its mission to insure the safety and quality of pharmaceuticals, the United States Pharmacopeia has historically included monographs for plastic, glass and elastomeric materials intended for pharmaceutical packaging (but indiscriminately used in other applications).  In general, these monographs share a common emphasis in terms of addressing extracted substances, as it through the action of the extracted substances that the quality and safety of pharmaceutical products are impacted by packaging, devices and manufacturing equipment.

    As the scientific understanding of extractables and leachables has evolved, especially in the area of supporting analytical chemistry, a point was reached where the existing USP chapters no longer met the high standard of good science and a systematic effort was undertaken by the USP to re-invent relevant monographs involving glass, plastic and elastomeric materials, and considering both chemical and biological characterization.  Additionally, the drafting of  new monographs on new materials (e.g., metallic materials) and new applications (manufacturing equipment, medical devices) have been, are being, or will be drafted.

    The purpose of this presentation is to provide an overview of the USP efforts in this area, focusing on the harmonized methodology that the USP has used to revise its whole approach to the topic of the safety and applicability of materials used in pharmaceutical applications.      

  5. Networking break

  6. Moving from words to actions: putting the regulations to practice

    Dr. Cheryl Stults | Principal of C&M Technical Consulting, Dr. Dan Norwood | Senior Consultant of Smithers Rapra and Dr. Dennis Jenke | Chief Executive Scientist of Triad Scientific Solutions

    Regulatory guidance and guidelines generally focus on the big picture, largely enumerating general concepts and strategies but rarely providing detailed tactical directions or instructions.  Thus, a certain degree of translation is required to convert regulatory concepts into compliant experimental designs and laboratory practices.  In this presentation, the regulatory guidelines discussed in this morning’s Workshop will be interpreted for and applied to three important and challenging classes of pharmaceutical products; inhaled drug products, large-volume parenteral products and combination drug-device products.   Key practical challenges in meeting the regulations will be identified and practical solutions to these challenges will be considered.          

  7. Q&A Panel: Digging deeper into the different regulations and protocols and how to put them into practice

    Following all that you have heard in the training and the afternoon presentations, take this opportunity to ask your questions about the regulations and protocols, featuring CNPPA, Smithers Rapra, Baxter, Triad Scientific Solutions and more

    Panelists include:

    Yonghua Gao, Deputy Secretary General, China National Pharmaceutical Packaging Association

    Weichun Yang, Sr. Scientist II,  Baxter Suzhou R&D Center (China)

    Dr. Andrew Feilden, Chemistry Operations Director, Smithers Rapra

    Dr. Dennis Jenke, Chief Executive Scientist, Triad Scientific Solutions

    Dr. Cheryl Stults, Principal, C&M Technical Consulting

    Dr. Dan Norwood, Senior Consultant, Smithers Rapra

  8. Chair's closing remarks

    Dr. Andrew Feilden | Chemistry Operations Director of Smithers Rapra

  9. Evening networking reception

Day two - Wednesday 12 September

Day two

  1. Delegate sign-in and morning refreshments

  2. Chair’s opening remarks

Packaging systems

  1. Should the experimental design for a variety of medical and pharmaceutical product types be the same?

    Weichun (Wes) Yang | Senior Scientist II of Baxter, China

    There is often a desire by companies to standardise the experimental design for Extractable and/or Leachable studies. Whilst this may result in increased efficiencies, it is a strategy that does NOT have patient safety at the centre of it and therefore is high risk from a regulatory acceptance point of view. A generic experimental design applied to a diverse range of products is unlikely to focus the resource in the areas that present the greatest risk for different product types.

    Customising the experimental design for different product types ensures the specific risks associated with different product types are well understood and suitably qualified from a toxicological perspective. Take, for example, the experimental design for the stopper used in a pre-filled syringe should be different to the stopper in a lyophilized product. A range of scenarios will be provided to emphasise the need to customise the experimental design, and highlight the disservice a patient receives from inductry if a “one size fits all” approach is applied with no thought given to whether the specific risks associated with the product have been addressed.

  2. Detection and identification of leachables in vaccine from plastic packaging materials using UPLC-QTOF MS with self-built polymer additives library

    Dr. Zhenxia Du | Professor, Center of Analytical Chemistry and Testing of Beijing University of Chemical Technology, China

    In this work, a library containing 300 polymer additives was built. The library contained the additives information on their names, formulas, structures, retention times, fragments, classifications, origin, and corresponding MSE and MSMS spectra. The reliability of the library construction processes was demonstrated by a system stability and suitability test. Identification parameters of library application, such as mass error, retention times, fragments, and isotope pattern, were evaluated. Leachables in real vaccine and the intermediates were identified using automatic library searching. With the library, leachables were identified quickly and automatically. In principle, this library could be used effectively in any QTOF MS under the same acquisition conditions. In addition, the element composition, ChemSpider search, and mass fragment tools could help elucidate the structures of compounds that could not be identified by searching the self-built library. The results indicate that this method is a promising approach for fast screening assays of leachables from plastic packaging materials.

  3. Networking break including Poster Session

    Attend the Poster Session in the exhibition hall to find out about cutting-edge E&L science and put your questions to the authors. See the confirmed posters here: https://www.eandl-conference.com/china/poster-session.

Enabling science in E&L

  1. An overview of the extractables and leachables study in China due to an escalating stringency in the regulatory requirements

    Lynn Yao | Scientific Affairs Manager, China of West Pharmaceutical Packaging (China) Co., Ltd.

    Extractables and Leachables (E&L) study of pharmaceutical packaging components offer an insight of the potential risk to patient safety. Both pharmaceutical companies and regulatory agencies have rising concerns regarding E&L. CFDA is no exception. As a result, increasing requirements for E&L study and safety evaluation are expected for the drug submission. This is demonstrated by the several relevant guidelines for compatibility study issued by CFDA since 2012. The purpose of this presentation is to provide an overview of the China relevant requirements, clarify the responsibilities of packaging suppliers and pharmaceutical companies as well as the compatibility study focused in the E&L study. The presentation will share some case studies from a packaging supplier’s perspective.       

    • Overview of the China Technical Guideline
    • Safety & Toxicity requirements per CFDA’s Directive 155
    • General approach of E&L study
    • Safety Risk Assessment - responsibilities of packaging suppliers and pharmaceutical companies
    • Case study (unknown’s identification, impact of steam and gamma processing on Extractable profile)
  2. Targeted screening for E&L by using ion mobility LC-MS

    Baiba Cabovska | Senior Manager of Waters Technologies, USA

    Globally, much legislation exists to try to mitigate exposure to these components, which results in a significant demand for rapid, accurate, and reliable analytical methodologies. One such method is targeted screening using LC-MS techniques. The targeted screening starts by creation of a scientific library. Typically, in identification of compounds, retention time, accurate mass, and fragmentation ion information is used. However, if different chromatographic methods are used, the retention times will vary. If the compound is present at trace levels, the fragments might be absent. In this work, we will demonstrate how the inclusion of collisional cross section (CCS) values, acquired using ion mobility-mass spectrometry, can provide increased confidence in compound identification. In addition, the comparison of library generated CCS values obtained using different chromatographic conditions and over different sites is considered.

  3. A comprehensive analytical workflow for the qualitative assessment of extractables and leachables

    Jimmy Chan | LCMS Manager (South & West China), Agilent Technologies (China)

    We will present a comprehensive analytical strategy for the qualitative assessment of extractables. The strategy  consists of non-specific scouting techniques (FT-IR, UV-Vis) followed by more specific LC/MS, GC/MS and ICP-MS analysis. Our methodology  allows for the fast identification of E&L’s as well as rapid comparisons between different samples using automated feature finding and differential analysis. A high-resolution LC/MS database with 1000+ common E&L compounds and 350+ MS/MS spectra is useful for quickly identifying knowns and performing early risk assessment.  The analytical methodology  with be illustrated with several relevant application examples.

    • A comprehensive GC/MS and LC/MS workflow for the qualitative analysis of extractables from component extracts will be presented
    • The workflow allows comparing chemical features extracted from multiple components from the same system, looking at composition changes as a function of extraction conditions, or looking at differences in abundance of extracted chemicals across different samples
    • The presented workflow also provides for a convenient way of visualizing the large volume of data arising from these experiments and to facilitate presentation of results.
    • For the reference compounds in our database, retention time matching provides and additional level of confirmation besides MS and MS/MS data
    • The database also contains information on CAS number, Chemspider ID, IUPAC name, English and Chinese synonyms, classification (best ionization method, compound type, ELSIE etc.), safety information, EU regulation, SWISS ordinance, deleted CAS, and some other reference information.
  4. Networking lunch

  5. Presentation of ‘E&L China Poster of the Year 2018’

    Dr. Andrew Feilden | Chemistry Operations Director of Smithers Rapra

    Find out which of the onsite Posters the Advisory Board deems worthy of being called 'Poster of the Year' and hear from the author on that they have presented.

    If you haven't already had the chance to see the winning poster, you will be able to do so in the final break. 

Manufacturing systems

  1. Using extractables data for scaling and cumulative calculations of single-use systems

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

    Sartorius Stedim Biotech (SSB) provides extractables data of single use systems (SUS) used in biopharmaceutical industry to support the material safety assessment. Firstly, the extractables approach of SU components implemented at SSB is presented. Secondly, it is well accepted to perform scale-up and scale-down calculations of E/L data for SU devices, such as bags, tubing and filters, or even perform a cumulative calculation (so called “component approach”) for SU assemblies. We want to raise awareness that the underlying physical and chemical effects lead to limitations of such an approach for short term contact applications, such as filtration, and long term applications such as storage of a drug product in a bag or container closure system. We will discuss these two cases by giving illustrative examples. SSB has tested the scientific basis for a scale-up concept and a component approach for sterile filters when used in short term applications. Data on applicability and limitations of a scaling and the component are presented in the third part.

    • A standardized extractables concept for SU components
    • Physical and chemical effects during extraction with short term contact applications, such as filtration, and long term applications such as storage of a drug product in a bag or container closure system 
    • Experimental data for the use of a scale-up concept and a component approach for sterile filters when used in short term applications 
  2. Large-scale assessment of extractables and leachables in single-use bags for biomanufacturing

    Kyle D'Silva | Pharma & Biopharma Manager of Thermo Fisher Scientific

    Single-use technologies (SUTs) have emerged for use as production bioreactors for therapeutic proteins. Despite advances in SUTs a significant concern exists regarding the risk of release of potentially toxic or inhibitory extractables and leachables (E&Ls) substances. These E&Ls may detrimentally affect cell viability or productivity during upstream processing operations or may persist during downstream processing and represent a risk to the patient if remaining in the final drug product. Characterizing E&Ls from such materials is a necessary step in establishing their suitability for use in biomanufacturing processes. In this study, 34 plastic films from single-use bags (SUBs) for cell cultivation were extracted with incubated at small-scale under accelerated-aging conditions that represented working conditions of use. The resulting extracts were characterized by several chromatographic and mass spectrometric analytical techniques, including both LC and GC high resolution accurate mass MS to establish the corresponding E&Ls profiles.

    • Collaboration with 7 leading biopharmaceutical manufacturers
    • Evaluation of 5 brands of single use bioprocess materials
    • Over 1500 individual sample analyses using ICP-MS, HRAM LC-MS/MS, HRAM GC-MS/MS and GC-MS
  3. Interpreting BPOG extractables data to support qualification and safety risk assessment for effective adoption of single-use systems in drug manufacturing processes

    Queenie Gai | Extractable Lab Supervisor – BioReliance Validation Services, China of Merck Chemicals (Shanghai) Co., Ltd., China

    A successful adoption of single use technology in a Biopharmaceutical process largely relies on the confidence in selection of such materials for the process. An extractables profile generated by carefully choosing the solvent streams and the extraction conditions to broadly model the product and the process conditions with the right analytical strategy is an important step in the process qualification.

    This presentation will focus on the extractables data generated by adopting the BioPhorum Operations Group (BPOG) protocol as a baseline testing strategy as applied to the single use technology. The discussion will include the next step of skillfully applying the extractables data obtained to a specific process, followed by a systematic risk based safety assessment achieved through comparison to known permissible daily exposure (PDE) thresholds. The various stages in the risk assessment process will be demonstrated through case studies for single-use components used in typical drug manufacturing processes

  4. Networking break

Medical devices

  1. Major revisions to ISO 10993 - Importance of extractables and leachables data and their evaluation in the safety assessment of medical devices

    Dr. Albrecht Poth | Senior Toxicologist of Dr. Knoell Consult GmbH

    The three major standards to evaluate the biological safety of medical devices, ISO 10993-1, -17, -18 are going to be revised. The revision of ISO 10993-1 “Evaluation and testing within a risk management process” will include additional requirements to be evaluated and only the chemical characterization including the derivation of extractables and leachables data will be mandatory, while other toxicological endpoints will only be evaluated within the toxicological risk assessment. A major revision will be made on ISO 10993-18 to incorporate the technical and scientific experience developed during the last 10 years of its publication, including a more detailed description of experimental requirements for the investigation of extractables and leachables and a revision of the stepwise chemical characterization process, including the setting of the analytical evaluation thresholds (AETs) in alignment to agreed toxicological safety factors. Based on that new risk assessment approaches will be included in a revision of ISO 10993-17 dealing with the establishment of allowable limits for leachable substances.

  2. Product equivalency for medical devices. Case studies for biodegradable and permanent implantable devices

    Gyorgy Vas, Ph.D. | Technical Scientific Liaison of Intertek

    Toxicological equivalency of a medical device is well defined by ISO 10993-18 and the toxicological risk assessment requires extensive chemical testing. Any significant changes in the product manufacturing process must to be evaluated and data must be presented for toxicological equivalency to a clinically established product. Case studies will be presented to show analytical evaluation of implantable medical devices. Case 1: Analytical data will be presented for evaluating the effect of a manufacturing site change for a biodegradable implantable device Case 2: Analytical evaluation process will be presented for a permanent implant. Method validation aspects will be discussed .

  3. Chair's closing remarks and close of E&L China 2018