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Agenda

The 2022 program has been announced!
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Take a look at the 2022 agenda, which features

  • Presentations from BD, The FDA, Eurofins Medical Device Testing, Thermo Fisher Scientific, Intertek, and many more!  Meet the 2022 Speakers >>
  • Sessions covering industry-leading topics, such as: Regulations and standards, extractions and analytical testing, impact assessments, study designs, poster session, te future of E&L, and more.

 

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

Registration & Welcome
Registration Open
Welcome and Opening Remarks
Ashli Speed, Conference Producer, Smithers  
Paul Cummings, General Manager, Analytical Services Medical Device Testing Smithers
Session I: Regulations and Standards
Industry Update on Major Changes, Challenges, and Innovations
USP Update
Abstract Coming Soon
EU MDR Update
Abstract Coming Soon
Networking Break
Challenges with receiving accreditation per ISO 17025,
Networking Lunch
Session II: Extractions and Analytical Testing
Evaluation of Optimal Extraction Conditions for Polypropylene, PBT Resins, and Chlorobutyl Rubber Elastomer – Using a Variety of Solvents and Extraction Conditions
Additional Speaker:
  • Gyorgy Vas, Ph.D., Business Technical Scientific Liaison,  Intertek Pharmaceutical Services
Polymers used in the pharmaceutical industry serving different purposes. They can be used as part of the packaging or delivery systems, part of the manufacturing process, and can be used as a medical device.The performance and the quality of the polymer play important role how those different functions are being fulfilled the expectation of the intended use. They must meet high level of purity standards in order to minimize the probability of harmful chemicals leaching out from the packaging or from the devices. Chemical safety assessment is one of the necessary steps to claim that the polymer is safe to use for pharmaceutical applications. Over the past decade, different standard setting organizations (USP, ISO) made significant efforts to guide the industry how those safety assessments should be performed, supporting higher chemical safety and lower patient exposure to potentially harmful chemicals. The chemical safety assessment should start with proper material characterization, using state of the art analytical methods, including different chromatography techniques hyphenated with mass-spectrometric detection. Since the polymers are mostly not compatible with direct analysis of those chromatography based techniques, an extraction step is required to perform the testing. The extraction can be based on solvent mediated or solventless technique. This paper presenting data sets for 3 different types of polymers (polypropylene, polyisobutylene and a rubber elastomer), using 3 different solvents and 3 different extraction techniques. The extracts were collected at different time points, and analyzed by GC-MS. There are significant differences were observed between the different extraction techniques and the different solvents.
Dr. Daniel Norwood | Executive Partner, SCIO Analytical & Senior Consultant, Smithers
Examination of Time/Temperature Solvent Variables on Extractables Profiles from Various Polymers (i.e., How much is too much?)
The purpose of an exaggerated extraction is to perform an extraction that is intended to result in a greater number/amount of extractables versus that which would be generated under the clinical conditions of use. In order to do this, some extraction solvents are employed which are not realistic in terms of contact with the materials, but instead are designed for the purpose of materials understanding and characterization. There are a number of reasons for this, but ultimately, in order to properly assess risk, one must completely understand the extractables "universe" for any material. However, it is also important to not to "cause deleterious effects to the materials (such as degradation) or the extractables profile" (ISO-10993-18-2020 Annex D). This presentation will explore the relationship of the exaggerated extraction to the clinical use scenario for medical devices, including how extraction conditions dictated in ISO-10993-12 for medical devices can create the possibility of inappropriate extractions and subsequent conclusions during risk assessment. A systematic approach was taken for multiple polymers using different extraction times/temperatures and subsequent analysis of extractables profiles for evidence of species attributed to degradation of materials. Optimal extraction times/temperatures (alternatives to those proposed in ISO-10993-12) will be discussed with the goal of open dialog on the subject. One specific scenario will also be explored regarding the appropriate solvent and extraction scenario to be used in order to simulate blood contact.
Alan Hendricker | Manager - Chemical Sciences, Becton Dickinson
Identification of Additives in Polymers from Single-use Bioprocessing Bags by Accelerated Solvent Extraction and Ultra-high Performance Liquid Chromatography Coupled with High-resolution Mass Spectrometry
Single-use technologies are increasingly used in biopharmaceutical manufacturing. Despite their advantages, these plastic assemblies draw concern because they are a potential source of contamination due to extractable and leachable compounds (E&Ls). Characterizing E&Ls from such materials is a necessary step in establishing their suitability for use. Therefore, there is an urgent need for sensitive methods to identify and quantitatively assess compounds in plastic materials. Accelerated solvent extraction (ASE) is a powerful technique that can be reliably used for this purpose. In this study, ASE followed by liquid chromatography and Orbitrap-based High Resolution Accurate Mass (HRAM).
Chris Shevlin | Scientific and Educational Affairs Manager, Thermo Fisher Scientific
Networking Break
Quantification of Chemical Characterization Data of Medical Devices: How can we Implement the use of Multiple Standards?
The concept of the analytical evaluation threshold (AET) provides a rationale for the appropriate reporting threshold for E&L screening while also addressing the uncertainty in the relative response of individual compounds in the identified data set. The uncertainty in the quantification of data generated using screening methods is based on the fact that not all compounds respond the same in a mass spectrometer. The AET calculation accounts for this uncertainty by employing an uncertainty factor (UF) based on a laboratory’s experimental data. Specifically, the UF is based on the relative response factors of authentic reference standards to the assays internal or external standard. In that past few years clients have been conveying to Eurofins that the FDA has recommended multiple reference standards be used for quantification of compounds in the retention time vicinity of said reference standard. This request seems counter to the AET concept and, since the FDA has provided little detail on how to implement this approach, raises a number of questions. 1. How does the AET apply (or not) to reference standards that are not used in the AET calculation itself? 2. Should class of compound be used in applying the different standards to the data set instead of retention time? 3. How does a laboratory treat unknowns or compounds only identified by class? 4. Does the use of multiple reference standards increase the certainty in the data?
Charles E Ducker | Group Leader, Eurofins Medical Device Testing
Understanding Extractables Profiles from Polymerization ChemistrY
At the US RAPRA 2021 conference, we explained the extractable profiles of LDPE, HDPE, polypropylene and ABS based on the polymerization reaction chemistry of these materials. In this presentation, we are going to explore the extractables profiles of other commonly used polymer materials in drug product packaging and manufacturing components, including butyl rubber, silicone rubber, PET, PBT and polycarbonate. We will provide the typical extractable compounds from those materials and explain how they are formed from their polymerization chemistry.
Benton Cartledge, Ph.D. | Senior Scientist, PPD Laboratories
Analytical Panel Discussion
Panelists Coming Soon
Networking Reception
Registration and Welcome
Registration Open
Welcome & Opening remarks
Session III: Impact Assessment of Extractables & Leachables
Medical Device Poisons: Extractables and Toxicological Assessment Down and Around the TTC
With the publication of ISO 10993-18:2020 and refreshed scrutiny of medical device extractables methodology, the diligence, transparency, and burden of these studies has increased tremendously. Laboratories are producing more, and better, data that needs to be evaluated for toxicological risk; it is not uncommon for some devices to produce several hundred or even thousands of compounds requiring assessment. Most typically, the majority of these compounds are at or near the TTC and it is not uncommon for them to lack full identification. This presentation proposes a risk-based approach to toxicological assessment of medical device leachables, focusing on those compounds with imperfect identification and concentrations near the TTC.
Dr. Matthew Jorgensen | Senior Extractables and Leachables Expert, Nelson Laboratories
In Silico Assessment of Biomolecule Reactivity with Leachables
Active pharmaceutical ingredients (APIs) which are comprised of biomolecules are being increasingly used as therapeutics. The novel application of such APIs has led to an emerging regulatory question concerning the potential interaction of biomolecule APIs with leachables. To address this question, experimental and computational approaches could be used within a framework which relies on the rapid and conservative screening potential of in silico methods upfront, followed by a more extensive evaluation of any concerning signals from the computational methods. To this end, a biomolecule reactivity in silico workflow was developed which presents the necessary stages for assessing the reactivity of a small molecule leachable with a biomolecule. In silico models which are relevant to the assessment of peptides, proteins and mAbs include a statistical model which predicts the reactivity classes of the Direct Peptide Reactivity Assay (DPRA) and a profiler which characterizes the potential interaction of the chemical with a nucleophile into different chemical domains (e.g., Michael acceptor, aromatic nucleophilic substitution, bimolecular aliphatic nucleophilic substitution, Schiff base, acyl transfer, and nonreactive. Assessment of the reactivity of leachables with nucleotide containing APIs can be supported by the application of direct acting mutagenicity alerts that were derived from an analysis of AMES data and an expert review.
Candice Johnson, Ph.D. | Research Scientist, Leadscope, Inc.
Combination Product Presentation per Brown/Stults
Impact Assessment Panel
Panelists Coming Soon
Networking Break
Session IV: Extractables and Leachables Study Designs – Best Practices
An Idea Whose Time Has Come – Learnings from Conducting Extractables & Leachables Risk Assessments According to USP <665>
The extractables and leachables, E&L, literature is now replete with several examples of unplanned sources of leachables in drug products. From pesticide treated shipping pallets to printed unit cartons of ophthalmic products, there are leachables migrating into drug products from unplanned sources. Typical E&L risk assessment focuses on the primary container closure or drug delivery system. Other potential sources have expanded to include secondary packaging for dosage forms such as eye care where the primary package is semi-permeable. USP <665> (draft) has attempted to expand the risk assessment process into both the bulk active and final dosage form manufacturing stages to identify & control potential sources of leachables. This talk will discuss application of a single risk assessment framework and several case studies to refine and simplify the framework.
Robert E. Malick | Principal Research Scientist II, Combination Products, Operations Science & Technology, Abbvie
Identifying Your Regulatory Risks Early is Key to Success
Complete Chemical Characterization as part of managing the risk in of your materials has taken front stage in recent years. Ever increasing expectations continue to drive regulatory questions. Anticipating these regulatory questions before you initiate your chemical characterization study is key to maximizing for success. With this presentation we will discuss the evolving expectations for chemical characterization studies to meet regulatory expectations and what you need to do to get it right the first time. The crucial elements for success we will cover are these: 1. Robust Study Design: Anticipate and address expectations from the start. 2. Instrumentation: Picking the right tools for the job. 3. Data Analysis: Putting in the time upfront means time saved in the end. 4. Expert Assessment: When assessing risk, experience matters.
Sandi Schaible | Senior Director, Analytical Chemistry and Regulatory Toxicology, WuXi AppTec
Impact Assessment Panel
Panelists Coming Soon
Networking Lunch
Session V: Poster Session
Posters Coming Soon
Session VII: Future Direction of E&L
To be Determined
To be Determined
Panel Discussion, Future Direction
End of Conference