MEDICAL DEVICES The journey of extractables


and leachables Aspen Research Laboratories is a contract research organisation known for its superior understanding of materials science, engineering and analytical testing. Its experienced and highly qualified team of scientists collaborates with pharma, medical device manufacturers, single-use suppliers, packaging companies and many other industries to solve challenges and expedite product development.


for its intended use. An extractable is defined as a substance – organic and inorganic chemical entities – that is released from a medical device or material of construction when the medical device or material is extracted using laboratory extraction conditions and vehicles (solvents). A leachable is defined as a substance that is released from a medical device or material during its clinical use (ISO 10993-18:2020) or as foreign organic and inorganic chemical entity that is present in a packaged drug product, because they have leached into the packaged drug product from a packaging/delivery system, packaging component or packaging material of construction under normal conditions of storage and use, or during accelerated drug product stability studies (USP 1663 and 1664). In the extractables testing field, there are no hard and fast rules as to what the extracting solvents to use are or what the times and temperatures of the extractions must be. There are, however, guidance documents and ISO standards that help direct appropriate testing. Given that the results of the testing are used in regulatory submissions for approval of medical devices and drug products, it is imperative that studies are designed to yield results that can be used to determine if the device or drug product is safe for the intended use.


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Designing the extractables study As a contract analytical chemistry laboratory, Aspen Research Laboratories’ clients come to it to not only


78 | Outsourcing in Clinical Trials Handbook


xtractables and leachables testing is done primarily to help ensure that a medical device or pharmaceutical packaging is safe


perform testing, but also to help advise on designing the study along with performing the analyses involved in the study. This article journeys through an extractables study from initial design through results and on to a leachables study, discussing some of the initial bases for the extractions used, the analytical techniques used and some of the terms found in the vernacular of extractables and leachables testing. The first step in any extractables study design


is to assemble as much information as possible about the materials of construction, the dosages (if applicable), information about the drug excipients and – if there is a device – the device design. The study in question involved a medical device used to mix and administer drugs, which was not an implantable. The materials used in the fluid path of the assembled device were high-density polyethylene, polyisoprene rubber and stainless steel. A wide variety of mixtures of solvents are used as carriers for drugs used with the device, and the most severe dosage would be 36 devices used over a four-day period. All this information, and guidance documents from the FDA and ISO 10993-12 – and input from a toxicologist that one should assume 20µg/day of any compound would be considered safe – was used to propose the details of the extractables study.


A twofold leachable screening study The purpose of the study was twofold. The first was to develop methods in the drug product vehicles to demonstrate that the extractables could be detected. The second was to qualify methods for an accelerated leachables study.


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