What are Extractables and Leachables Studies?
Extractables and leachables (E&L) studies are in-depth analytical investigations of the chemical interactions between a medical device and a drug product or the human body itself. The primary purpose of an E&L investigation is to identify any potential chemicals derived from the interaction of the constituent parts and then to determine the impact to human health and/or drug efficacy that those chemicals pose. This identification is an extractables/leachables profile. Organizations that seek to provide guidance for medical device E&L studies include the FDA, ICH, and ISO.
What are Extractables?
Extractables are substances in a medical device which can be “pulled out” using stressing conditions such as strong solvents, elevated temperatures, and/or increased surface area. Substances observed in this stage are characterized and identified per FDA guidelines and further evaluated by a toxicologist to determine if the substance is a potential hazard. Common extractables include plasticizers, surfactants, processing aids, degradants, and other materials.
What are Leachables?
Leachables are substances in the medical device that leach or “come out” under normal conditions of exposure over the natural lifespan of the product. Sources of leachables are potentially numerous and can include anything from residual manufacturing solvents to ink and adhesives from labels of secondary packaging material. FDA guidelines monitor known extractables and leachables to ensure human exposure levels do not exceed appropriate safety limits.
The International Organization for Standards (ISO) guidance ISO 10993: Biological evaluation of medical devices describes the expectations for medical device extractables testing (a part of the “chemical characterization” of medical devices) in a subsection of the larger document and within the broader scope of medical device testing. You can read an in-depth discussion of this guidance, practical considerations, and information on updates to this guidance on our ISO 10993 Chemical Characterization page.
At EKG Labs we specialize in chemical characterization of medical device materials for regulatory filings. Our medical device extractables and leachables program is constructed around ISO 10993-12 (sample preparation) and ISO 10993-18 (chemical characterization). We routinely carry out exhaustive extractions (assessed by gravimetric analysis), simulated-use extractions, accelerated aging studies, and leachable studies—all per ISO 10993 guidance. Extraction solutions are typically evaluated, depending on solvent utilized, by LC-MS, GC-MS, and ICP-MS. The end report of an extractable study will list detected compounds and their in-sample concentrations.
Extractables and Leachables Studies at EKG Labs
Understanding the complex chemical interactions in medical device materials is critical to designing a proper extractables and leachables program. Our team has years of experience working with diverse pharmaceutical products and a variety of medical device materials including polymers, metals, ceramics, and composites. In addition to these raw materials, we understand how to characterize ancillary chemicals associated with device production such as plasticizers, fillers, additives, cleaning agents, and release agents. We are prepared to flag any materials which need further toxicological evaluation or analysis. The head of our analytical team, Dr. Allen Kesselring, is known throughout the medical device development industry for designing and managing large E&L programs. EKG has also been recognized as a Top Medical Device Testing and Certification Company.
We can perform E&L analytical studies with the ultimate goal of submitting data for FDA review and approval. Our capabilities include:
- Full scale GMP analytical extractables and leachables programs
- ISO 10993 Chemical Characterization
- Method Development
- Method Validation
- Chemical Characterization
- Impurity Identification
- Elemental Impurities Analysis
Extractables and Leachables Analytical Techniques at EKG Labs
- Chromatographic Characterization – HPLC, LC/MS, GC/MS, GC/FID, GC/TCD, GPC/SEC
- Spectroscopy Characterization – ICP-MS, NMR, MS, PXRD, TF-XRD, UV-Vis, FTIR, Raman
- Extraction Techniques – Soxhlet, Reflux, Immersion, Agitation