Ted Heise, PhD, RAC | VP Regulatory and Clinical Services, MED Institute

In order to successfully assess the toxicological risk of an extractable, you first must identify it.  However, it is frequently the case that a definitive identification cannot be made.  In this presentation, defining what is meant by “unknowns”  and strategies for addressing unknowns will be discussed. 

Paul Cummings | General Manager E&L, Smithers

Gyorgy Vas | Technical Scientific Liaison, Intertek

Roger Pearson, PhD | President Analytical Services, Aspen Research Corporation

Alan Hendricker | Manager - Chemical Sciences, Becton Dickinson

Poster Sessions:

• Leadscope
• Boston Analytical
• Intertek
  • ​Anna Michelson, Research Scientist

• Bryan Kratzenmeyer PhD, Senior Manager Materials Science, Americas Field Marketing, Waters Corporation
• Andrew Leightner, Market Development Manager, Pharmaceuticals – Americas Field Marketing
• Jeffrey Dahl Ph.D., Application Scientist, Shimadzu Scientific
• Tim Stratton, Manager, Library Technologies, Thermofisher Scientific
• Dr. David Weil, Senior Application Scientist, Extractable and Leachable Analysis Expert, Agilent Technologies

Recently there have been a number of drug product recalls due to the unexpected presence of N-Nitrosamines. While in most of those cases, N-Nitrosamine formation occurred at the level of the drug substance synthesis and stability, it is well known and documented that some materials, used in primary packaging can also be a source for N-Nitrosamine contamination of the packaged drug product (e.g. older grade elastomers and nitrocellulose laminated blister foils). The unanswered question is: do we know everything about the materials of construction of a container closure system and their ability to generate N-Nitrosamines? When looking at the formation mechanism of N-Nitrosamines, it are secondary amines (and potentially tertiary amines) that are a precursor to N-Nitrosamine formation, together with a nitrosating agent (such as e.g. nitrite/nitrous acid). When evaluating the extraction profile of materials of construction, it is clear that secondary amines are often encountered as an extractable being present in the material. Should this raise a “red flag” for those materials in a N-Nitrosamine risk mitigation strategy, as one precursor for N-Nitrosamine formation is obviously present in the material? And what could be the consequence of these findings, both for the design of extractable and leachable studies, as well as in the assessment of the E/L-results? This presentation will give more insights on how an integrated approach for both the E/L-qualification as well as the N-Nitrosamine risk evaluation for a pharmaceutical container closure system could look like.

Ward D’Autry, PhD | Study Director , Nelson Labs Europe

Why the extractables profiles of low density polyethylene (LDPE) component and high density polyethylene (HDPE) component are so much different although both LDPE and HDPE are polyethylene? Why the extractables profile of polypropylene component are so much more complicate than polyethylene component although both are simple polyolefin material? This presentation explores the extractables profile of some common polymer materials and explains the extractables profiles from the polymerization chemistry.
Benton Cartledge, Ph.D. | Senior Scientist, PPD Laboratories

A review of the current regulatory expectations of heath authorities will be reviewed. The disconnects within various guidelines will be discussed. Different testing method from heath authorities and in public literature will be presented. Testing strategies based on risk management will be discussed along with the current status of E&L testing for nitrosamines
Atish Sen, PhD | Staff Scientist Analytical Sciences Inhalation Product Development, AstraZeneca

Abstract to come
Praneeth D Edirisinghe, PhD | Principal Scientist - Extractables, Leachables & Impurity Identification , Pfizer

This session is focused on the real-world application of extractable and leachable principles and guidelines – putting the theory into practice. It focuses on the different approaches taken by companies to understand the risk to patients. 

 In the absence of harmonized regulatory guidance, identification of appropriate safety thresholds can present a challenge. This session will focus on how working groups within ELSIE are using the E&L Safety Database to address areas of uncertainty in the current risk assessment process. Two use cases will be presented to introduce different applications for the ELSIE Safety Database to address potential uncertainty through an analysis of relevant E&L chemical space to derive a science based qualification threshold and general recommendations for safety assessment of sensitization potential in parenteral drug products. A brief update on the next phase of the ELSIE Database, the ELSIE Knowledge Base, will also be provided.
Brad Stanard, PhD, DABT | Director, EHS Product Stewardship, Ultragenyx Pharmaceutical Inc.

The FDA’s Pre-Market Tobacco Applications (PMTA) for electronic nicotine delivery systems (ENDS) requires extractables and leachables (E&L) studies. We will discuss the approach to E&L testing on vaping devices for E-Liquids, which presents unique challenges in E&L design. Data from multiple different devices for which these studies were performed in support of a PMTA application will be presented. 
Emma Leishman, Ph. D. | Manager, Advanced Analytics, Avomeen

This presentation will focus on the most prominent lessons learned in relation to the assessment of extractables / leachables in biological drug products in the past 10 years, including the importance to identify clearance steps, to design extraction protocols that are well-adjusted to the actual application, and to mind scaling factors during extrapolation of extractables in the drug product, for instance. Special focus will be put on extractables and therefore, potential leachables derived from chromatography resins and leachables in solvents that are used for lyophilized drug products. Despite best efforts, an E&L assessment for biologics may still contain uncertainty. Therefore, it is important to understand the uncertainty factors that are inherent to materials, extractable testing and toxicological threshold values and to balance any remaining risk with expert judgment, data from clinical studies and pharmacovigilance and ultimately, the benefit from the treatment with the biological drug product.
Alicja Sobańtka, PhD | Corporate Operational Excellence and Support, Octapharma

A significant difference in the leachables analysis of medical devices as compared to pharmaceutical packaging is the ability to utilize the actual use condition (drug product) for the analysis of pharmaceutical packaging. The use condition for many medical devices (biological environment) is difficult to simulate and therefore it has been common practice to use binary solvent mixtures (alcohol/water) to simulate the leachables condition. Recently, a number of potential concerns have been raised about the use of binary solvent mixtures such as preferential absorption of the more hydrophobic component of the solvent by the medical device. In this talk, we will review the issues related to the use of binary solvents as well as relay results showing a comparison of the extraction power of blood contrasted with saline and water/alcohol mixtures for a series of analytes relevant to blood contacting medical devices. In addition, a brief update will also be provided on the latest work on mitigating the need for uncertainty factors through a multidetector strategy as recently publications in a work entitled “An Analytical Strategy Based on Multiple Complementary and Orthogonal Chromatographic and Detection Methods (Multidetector Approach) to Effectively Manage the Analytical Evaluation Threshold (AET)
Kevin Rowland | Lab Manager, Jordi Labs

Chemical characterization (Extractable and Leachable Studies) per ISO 10993 has become an important component of biocompatibility testing for medical devices. A major revision of ISO 10993-18 “Chemical characterization of medical device materials within a risk management process” was recently published in the beginning of 2020. This presentation will focus on the analytical considerations of medical device extractable and leachable (E&L) studies per the new ISO 10993-18 chapter. Topics to be covered will include: 1. Understand the analytical testing requirements per the new ISO 10993-18. 2. How to design an extractable study of medical devices in terms of solvent selection, extraction conditions, setting the suitable analytical evaluation threshold (AET), etc. 3. Analytical case studies per common regulatory deficiency points on medical device E&L studies, including requirements on reference standards during semi-quantitation, spiked recovery, LC-MS ionization modes, analytical uncertainty factor, compound identification status, etc.
Dujuan Lu, Ph.D. | Manager/Global Leader-E&L, SGS

It has now been over a year since the revised ISO10993-18 guidance came out. This presentation covers the similarities and more significantly the differences between medicinal products and medical devices for chemical characterisation /extractable leachable testing. Key areas will be around limits and the design of extractable studies.
Dr. Andrew Feilden | European E&L Strategic Director, Hall Analytical

Potentially catastrophic biological threats exist which can place populations at considerable risk. These may represent either deliberate (e.g., counterfeiting, malicious intent, etc.) or unintentional (e.g., natural disaster, pandemic, etc.) events and necessitate extremely rapid assessment and review processes to deploy life-saving countermeasures with an acceptable and appropriately scaled benefit/risk ratio. Agencies such as the US FDA have developed cross-functional programs with pharma and non-pharma collaborators (e.g., DoD, DOE, EPA) and guidance (e.g., Emergency Use Authorization) to expedite development and deployment of drugs to treat life-threatening diseases and unanticipated, unmet medical needs.  However, the implementation of such efforts is not without significant technical challenges, such as development of rapid, robust and portable technologies for threat identification, simple and effective risk assessment processes for rapid development, storage, deployment and delivery of drug products and countermeasures, and ensuring supply chain integrity.  These processes are required to be agile and necessarily rely upon SUS and platform technologies (e.g., digital, rapid, reconfigurable manufacturing for small and moderate targeted therapeutic population needs).   Benefits and some technical and regulatory challenges with implementing accelerated development and deployment of countermeasures will be explored, and as well as the future direction of this rapidly evolving area.
Douglas Kiehl | Research Advisor, Eli Lilly and Company

Panelists:

• Diane Paskiet, Sr. Director Scientific Affairs, West Pharmaceutical Sciences
• Lee Nagao, ELSIE

Adapting and Thriving in the Face of Change: Navigating     the Challenges of an Evolving Landscape and Preparing for the Future of E&L
Chair: Paul Cummings