Elemental Extractables for Medical Devices
The International Organization for Standards (ISO) describes the requirements for medical device biocompatibility testing in great detail in their well-established guidance ISO 10993: Biological evaluation of medical devices. Part 18 of this guidance, “Chemical characterization of medical device materials within a risk management process” specifically outlines the requirements for extractable studies, including assessment of elemental extractables by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). You can learn more about ISO 10993 here or learn more specifically about ISO 10993-18 and chemical characterization studies.
EKG has a validated ICP-MS method for ISO 10993-18 extractions. The method analyzes up to 62 elements, with validated limits of detection as low as 10 ppt (0.01 ng/mL).
Elemental Impurities for Pharmaceuticals
Based on ICH Q3D guidelines, the United States Pharmacopoeia (USP) has published general chapters <232> “Elemental Impurities — Limits” and <233> “Elemental Impurities — Procedures”. These chapters describe the elemental impurities testing necessary to evaluate pharmaceutical products for elevated concentrations of elements that are of significant toxicological concern.
EKG has written more extensively about ICH Q3D, USP 232, and USP 233 here.
Elemental Analysis Case Studies:
Learn more about any of the individual case studies below by following the provided link!
Meeting challenging detection limits in IV bags:
Because of the large daily dosages delivered by IV bags, and the high salt matrices of these solutions, IV solutions can present challenging detection limits. EKG Labs was asked to evaluate elemental impurities in IV bags containing uniquely high densities of salt and a 2 L/day dosage limit and successfully met the challenge!
Syringe discoloration investigation:
A client was receiving complaints about drug product discoloration in pre-filled syringes in a clinical setting. After testing control syringes and their discolored syringes, EKG found elevated levels of copper and zinc. EKG conducted a brief accelerated extraction study to expose the drug to a brass fitting present in the syringe and confirmed that the brass fitting was the source of the discoloration. EKG Labs was able to expedite the testing to get our client the answers they needed to resolve the issue as quickly as possible.
Elemental impurities in cell culture media:
Inorganic salts in cell culture media help maintain pH, retain the osmotic balance, and regulate membrane potential. However, it is generally understood that elemental impurities are ubiquitous in biologically-derived cell culture media. Trace metals have been shown to negatively impact the efficiency of cell culture media, which can be incredibly costly. EKG obtained a variety of commercially available cell culture media and found significant concentrations of elemental impurities.
ICP-MS analyses were also featured in the following medical device extractable case studies:
Assessment of lead in an inhalation device atomizer
No elemental impurities in a nasal cannula extraction
An ICPMS at EKG Labs
Elemental Testing at EKG Labs
EKG Labs provides elemental impurity testing services to the pharmaceutical and medical device industries. Using our state-of-the-art ICP-MS, EKG Labs is capable of detecting elemental impurities down to an analytical parts-per-trillion level. We have a validated ICP-MS method for ISO 10993-18 extractable studies that can analyze over 60 elements. EKG Labs can perform USP compendial and ICH testing for any or all of the elements listed in USP 232 and/or ICH Q3D.
We have experience demonstrating precise recovery even in most challenging matrices and can extract or digest your unique sample as necessary. EKG Labs can also develop and validate a risk-based, product-specific method in order to monitor one or more targeted elements. At EKG Labs we work with you to provide a customized solution to your impurity identification and analysis needs.
About EKG Labs
EKG Labs is an analytical service provider for the pharmaceutical and medical device industries. Our wide variety of analytical services support product development, regulatory filings, and analytical chemistry investigations. EKG Labs is now a part of the Infinity Laboratories group, a powerful network of state-of-the-art testing facilities that are FDA registered, ISO 17025 accredited, and DEA licensed. With an enhanced focus in the areas of chemical and microbiological sciences, we support pharmaceutical and medical device manufacturers. Our goal is to go Beyond Testing and become a partner in the success of our customers.
Some of our services include: