Genotoxic compounds can be released from some medical devices during their clinical use.  The ISO 10993-17:2002 standard outlines steps to assess the risk posed by patient exposure to genotoxic compounds released from device materials.  It is important to note; however, that the ISO 10993-17 standard is currently undergoing revision and the procedures for conducting a toxicological risk assessment of genotoxic compounds are likely to change following revision of the standard.  This talk will outline the proposed changes to the ISO 10993-17 standard regarding methods to assess the risk posed by patient exposure to genotoxic compounds released from medical devices and will describe steps to mitigate the risk using risk management strategies.  The talk will also briefly address how Carcinogenic, Mutagenic, and Reproductive (CMR) compounds are handled in Europe under the new Medical Devices Regulation 2017/745/EU.
Presented by Ron Brown, Toxicologist at Risk Science Consortium

Ron Brown is a toxicologist with 35 years of experience in regulatory toxicology and risk assessment.  He recently retired from the US FDA and currently directs a small company, Risk Science Consortium, LLC, that provides consultation and training in toxicological risk assessment and computational toxicology.  At the FDA, Ron was the senior toxicologist responsible for developing and reviewing toxicological risk assessments of extractable and leachable (E&L) compounds from medical devices.  While at the FDA, he served in a number of leadership roles in standards development organizations.  At the international level, he served for many years as convener of ISO TC194 WG11 which is responsible for the development and revision of the ISO 10993-17 standard, Biological evaluation of medical devices-Part 17: Establishment of allowable limits for leachable substances.  At the national level, he represented the United States as an expert on ISO TC194 WG11 and served as co-chair of the AAMI Biological Evaluation Committee.  Prior to his position at the US FDA, Ron served as a Senior Associate at the ILSI Risk Science Institute.  He is founding member and former President of the Medical Device and Combination Products Specialty Section of the Society of Toxicology and former President of the Dose-Response Specialty Section of the Society for Risk Analysis.

On the Origin of Extractable Species

The Universe of Extractables (and potential leachables) is extremely diverse. The reason for this is that there are many different types of materials being used in the construct of a Container/Closure system or Medical devices, all with a different formulation, polymerization, processing and manufacturing. The impurities profile of a material is typically composed of compounds that were intentionally added to a material to protect the material during production or during its life cycle or to increase performance or functionality. In this case, we are talking about polymer additives, such as anti-oxidants, slip agents, acid scavengers, clarifying/nucleating agents, colorants, UV stabilizers, adhesives, etc…
However, there is even a longer list of compounds that are present in a material that were not intentionally added. These compounds have typically been introduced during the production process of the material or component, or they are the result of ageing of the material. Typical examples are solvent residues, cleaning residues, catalyst residues, oxidation/degradation compounds of the polymer, oxidation/degradation compounds of the polymer additives, polymer oligomers, etc…
The presentation will give an overview – for the most common materials used in the construct of container/closure systems or medical devices – of the main classes of compounds that are often detected in extractable studies and will explain why they are there, what their functions are (in case of the intentionally added substances) or what their sources are or how they have been formed (in case of unintentionally added substances).
Understanding the composition of a material and what the impact is on the extractables profile is an important and necessary first step in performing a proper evaluation of data and for a subsequent risk assessment. In addition, a good understanding of the material composition allows one to “fine tune” the analytical methods to guarantee that all compounds were properly picked up in the screening methods, guaranteeing the broad detection of extractable compounds and an associated correct identification.
Presented by Piet Christieans, PhD, Scientific Director at Nelson Labs

Sponsored by Nelson Labs
Nelson Labs, A Sotera Health company, is the leading, global provider of lab testing and expert consulting services. We perform microbiological and analytical laboratory tests across the medical device, pharmaceutical, and tissue industries. The company is regarded as a best-in-class partner with a strong track record of collaborating with customers to solve complex problems. We have over 700 scientists, technicians, and service specialists who diligently perform more than 700 rigorous tests in 13 global laboratory locations.
Based in Belgium, Nelson Labs Europe specializes in providing premium Extractables & Leachables testing services to the pharmaceutical and medical device industries. We also support pharmaceutical companies across the globe in developing worldwide compliance testing strategies to qualify container/closure applications and pharmaceutical production equipment from an Extractables & Leachables perspective.