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Agenda

Registration & welcome refreshments
Chair's opening remarks
Session 1 - E&L hot topics
What's hot in E&L? Latest feedback from Smithers' E&L series in US, China and Europe
Panel discussion: Addressing the key knowledge gaps - what is the availability and status of guidance to address them?
  • Opportunities for harmonization:
    • Expectations of ICH Q3E status and preparation for implementation
    • Learnings and successes of USP and ISO10993 updates
    • Opportunities for further harmonization and potential challenges
    • Dealing with analytical uncertainty and safety assessments
  • Workflow, supply chain & speed to market
Chair: Carsten Worsøe, Principal Scientist Extractables and Leachables, Novo Nordisk, Denmark

Panellists:
  • Jason Creasey, Managing Director, Maven E&L
  • Thomas Egert, Analytical Development, Boehringer Ingelheim Pharmaceuticals
  • Alicja Sobańtka, Corporate Operational Excellence and Support, Octapharma
  • Michael Creese, Manager E&L Consultants, Smithers, UK
  • Dr Cheryl Stults, Principal, C&M Technical Consulting
Session 2: E&L for medical devices
Similarities and differences between chemical characterisation of medical devices and medicinal products
Networking break
Chemical characterisation of medical devices - from a Notified Body perspective*
  • Chemical characterisation with special interest in classification, chemical extraction and subsequent analysis of extracts
  • Certification and quality expectations for analytical laboratories performing the tests per ISO10993 17 and 18
  • Are solvents recommend for biologocail testing relevant as solvents for chemical characterisation or should other solvents be used?]
  • E&L from packaging of non-solid medical devices

Dr. Christina Reufsteck | Biocompatibility Expert, TUV SUD Product Service GmbH
Extractables and leachables journey for medical devices - planning for uncertainty, including regulatory and market considerations
Case studies, including regulatory questions from FDA and EU notified bodies, will be shared.
 
Sandi Schaible | Senior Director, Analytical Chemistry and Regulatory Toxicology, WuXi AppTec
Panel: Adapting to the new reality of chemical characterisation of devices
Chair: Carsten Worsøe, Principal Scientist Extractables and Leachables, Novo Nordisk, Denmark

Panellists:
  • Paolo Pescio, Senior Scientific Director – Europe, Eurofins Medical Device Testing
  • Andrew Feilden, European E&L Strategic Director, Hall Analytical
  • Dr Christina Reufsteck, Biocompatibility Expert, TüV Süd Product Service GmbH
  • Sandi Schaible, Senior Director, Analytical Chemistry and Regulatory Toxicology, WuXi AppTec
Networking lunch
Session 3: Modelling of E&Ls
Extractables goes in-silico: The Extractables Management and Calculation Tool ExSim
  • Extractables management for SUS with an IT tool
  • Extrapolation of extractables to SUS geometry and dimensions
  • Forecast of extractables for SUS

Dr Armin Hauk | Principal Scientist, Sartorius Stedim Biotech GmbH
The future role of Mass Transport Modelling in support of leachable risk management
  • Why Mass Transport Modelling?
  • Predicted information in a leachables risk management framework - dimensions of risk and their interplay
  • Possibilities, challenges & limitations for the evolution of the E&L regulatory- and industry landscape
Joint presentation with Jason Creasey, Managing Director, Maven E&L
 
Thomas Egert | Analytical Development, Boehringer Ingelheim Pharmaceuticals
Networking break
Session 4: Toxicological safety assessments of E&Ls
Development of non-mutagenic TTC values for parenteral L&E substances: An ELSIE initiative*
Framework for sensitisation assessment of extractables and leachables in pharmaceuticals*
Panel discussion
Chair: Ron Brown, Toxicologist, Risk Science Consortium, LLC

Panellists:
  • Robert E. Malick, Principal Research Scientist II, Combination Products, Operations Science & Technology, Abbvie **
  • Dr. Thomas Broschard, Head of Chemical Toxicology, Biopharma, Merck Healthcare KGaA
  • Dr Cheryl Stults, Principal, C&M Technical Consulting

 
Ron Brown | Toxicologist, Risk Science Consortium, LLC & US FDA (Retired)
Chair's day one summary and closing remarks
Networking drinks reception
Registration & welcome refreshments
Chair's opening remarks
Session 5: E&L case studies
Tailoring of standardised SUT/SUS extractables protocols for the First Disc Stack Single-Use Separator
Industry protocols describe the best practices for performing Extractables studies on Single Use Technologies (SUT), for example, those published by the BioPhorum Operations Group (BPOG) and the current drafts of the Unites States Pharmacopeia (USP) <1665> and <665>. However, these industry protocols do not describe testing protocols for new types of SUT, such as a Single-Use Separator Insert – which should be considered as a quite large and complex SU system.

This case study describes how E&L risk assessments were conducted for the first to market disc stack SU separator to direct testing requirements. The presentation will describe how the risk assessment process, conditions of use, industry protocols and analytical knowhow were used to successfully develop an appropriate testing strategy. The lessons and observations learnt will help support the design of E&L strategies for new large and complex types of SUT.

Joint presentation with Michael Creese, Manager of Project Management - E&L and Chemical Analysis, Smithers
 
Dr. Martin Wåhlander | Senior Specialist - Materials and Coatings, Alfa Laval
An impurity detected in a stability study: Did we miss anything in our E&L risk assessment?*
Extractable and leachable (E&L) testing are required to identify substances that can or will migrate into the drug substance or drug product during the manufacturing process, storage and administration to assess the risk for patients being exposed to these substances. Stability testing is required to provide evidence on how the quality of a drug substance or product varies over time. E&L testing and stability testing can be run in parallel, but the conditions and detection techniques used for screening can be different. Although stability testing focuses on the quality of the drug substance or product by investigating the degradation products, it can occur that compounds are detected which are leachables.

In this case study an unknown compound was detected during stability studies using LC-UV which could not be linked to a degradation product and was suspected to be a leachable. The question was raised if the unknown compound could be linked to extractables or leachables and if there was a potential risk for patient safety and drug product quality. E&L studies require complementary analytical techniques to screen for a wide range of compounds and the experimental design needs to be considered and stability studies can be set-up differently.

This case study shows challenges in identification when using complementary techniques and discusses uncertainty in identification of leachables.
 
Petra Booij | Senior Scientist, PDS-CMCA-SFC-Trace Analysis and E&L, GlaxoSmithKline
The necessity of extractable & leachable qualifications for lyophilised drug products: some fallacies addressed
When selecting and qualifying the Primary Packaging for lyophilized drug products, one of the obvious questions is “how deep should one go into the E/L-qualification process of a lyo-container”. As the drug product is in a solid state, it is expected that the interaction between the lyophilized drug product and the components of a lyo-container will be low. This is also reflected in the USP<1664> Monograph on Leachables and the EMA Guideline on “Plastic Immediate Packaging Materials” (2005). However, the mechanism of interaction between the lyo-cake and e.g. the rubber stopper (when considering a lyo vial) are not always fully understood. The interaction mechanism is based upon “outgassing” of the rubber stopper, where the lyo cake acts as an adsorbent. Not only can this lead to substantial accumulation of the volatile and semi-volatile leachable compounds onto the lyophilized drug product, it may also induce chemical reactions between the leachables and the drug product, i.e. when the adsorbed leachables show electrophilic properties.
 
Dr. Piet Christiaens | Scientific Director, Nelson Labs NV
How to address USP 665/BPOG in an easy tool for the end user?
Interpretation of the current USP 665 draft and existing BPOG documentation
•             Creation of a simple and easy to use tool for the end user to define the risk level
•             Automatic selection of the necessary testing requirements based on the risk level identified
•             Example with two SUS and a final container (vials)

Joint presentation with Etienne Michel, Global Quality Expert, GSK Vaccines

 
Marine Lepoutre | Global Subject Matter Expert, Extractables & Leachables, GSK Vaccines
Networking break
Session 6: Analytical chemistry
Agreement of a method standard for non-volatile analysis for extractables
  • Current approaches to Non-Volatile Analysis
  • How LCMS and other detection systems are selective in detection and why is this a problem
  • Why current non-volatile detection systems are bias and introduce errors into quantitation
  • Why it is important to move forward and establish a standard
  • Suggestions on what a standard would look like and what would it cover

Jason Creasey | Managing Director & Principal Consultant, Maven E&L Ltd.
Comprehensive use of high-resolution accurate mass LC/MS analysis in leachable studies*
According to USP <1664>, the analytical methods used for leachables studies 'must be subject to complete validation using industry-accepted validation practices' as well as 'capable of characterizing targets as well as new (or unspecified) leachables'. This requires validated LC/MS methods for quantification of specified targets which have been detected in the previously performed extractables study. This presentation will demonstrate the benefits and advantages of high-resolution accurate mass LC/MS in leachables studies in order to obtain comprehensive quantitative and qualitative information about the studied formulation.


Joint presentation with Ulli Hohenester, Senior Scientist, Solvias AG
 
Heike Schafer-Grebe | Senior Scientist, Solvias AG
Networking lunch
Qualitative extractable and leachable testing
The initial determination of extractables compounds is often done by high resolution mass spectrometry using ToF MS in Information Dependent Acquisition (IDA) mode. If compounds are present at low levels, or chromatographically coelute with other compounds, they may be missed. Here we present a SWATH acquisition method, that when coupled with an extractables and leachables focused compound library, will provide greater confidence that extractable compounds are not missed during analysis. Extractables samples were prepared using different conditions specified in the USP guidelines. A ExionLC system (SCIEX) with a Phenomenex 150x2.1mm, 1.6u Luna Omega C18 column was used for separation. Data was acquired on a X500R QTof system (SCIEX) operated in SWATH mode, scanning from 100 to 1100 m/z. Data was using both targeted library searching and non-targeted peak finding. The MS/MS library contains high resolution, full scan spectra for compounds known to be present in many types of packaging and handing materials. The ability to compare high resolution MS/MS spectra for acquired data with library spectra for known compounds added confidence to identification.
 
Ernst Bouvin | Sales Specialist, SCIEX
Obstacles to identification and quantification of extractables - lessons learned from the past 10 years of E&L assessment in biologics
Challenges and lessons learned in the study of extractables and leachables in opthalmic drug products*
  • Discussion on the regulatory environment, including PQRI recommendations
  • Key lessons learned in 20 years of studying E&L in ophthalmic drug products
  • Case studies

Christopher T. Houston, PhD | Senior Principal Scientist & Group Leader, Bausch + Lomb
Chair's conference summary and closing remarks

Download E&L Europe 2021 Agenda

*These speakers will be presenting remotely due to COVID-19 travel restrictions.