What Does “Good” Extractable and Leachable (E&L) Testing Really Mean?

In the world of medical devices, combination products and pharmaceutical products, extractables and leachable (E&L) testing is often viewed as a regulatory checkbox. But for those of us who’ve spent decades in the trenches of chemical characterization, we know that “good” E&L isn’t just about meeting minimum requirements—it’s about solid data to support a risk assessment to protect patients, enable innovation, and build trust.

So, what does good E&L look like?

Good E&L testing is grounded in robust analytical chemistry. That means:

Extraction studies using solvents and conditions to exaggerate use. The solvents might look very different if you are extracting a container closure (vial) or if you are extracting a permanently implanted medical device. Regardless, regulators are going to want to understand why the solvents and conditions you selected are justified based on the risk profile of your product.  Extraction conditions that are too gentle will likely result in missed compounds, under reported concentrations and regulatory scrutiny.

Alternatively, extraction conditions that are too aggressive will likely result in an extraction profile with degradation products that don’t accurately represent the worst-case profile of your device.  The extraction step is the most important part of the study, if this step isn’t executed correctly the rest of the study is at risk.

Next up is the analytical instrumentation.  In today’s world it’s going to be difficult if not impossible to provide data appropriate for a toxicological risk assessment without using mass spectrometry.  A comprehensive E/L study will include at a minimum the following analytical techniques (other analytical techniques may be necessary depending on the device materials and risks):

·       Headspace Gas Chromatography with Mass Spectrometry (HS-GC-MS) for volatile organic compounds

·       Direct Inject Gas Chromatography with Mass Spectrometry (GC-MS) for semi-volatile organic compounds

·       Liquid Chromatography with High Resolution Mass Spectrometry (e.g. LC-MS, LC-HRMS, LC-QTOF) for non-volatile compounds. High resolution mass spectrometry is a sophisticated (and expensive!) mass spectrometer that is used to measure the exact mass of atoms/molecules with the ability to separate compounds that are very close in mass.  Commonly used detectors are Time of Flight (TOF) and Orbitrap.  This is a non-negotiable first step in identifying compounds.

·       Inductively Coupled Plasma (ICP) typically with Mass Spectrometry (ICP-MS) or with Optical Emission Spectroscopy (ICP-OES) for element compounds. Just because metallic compounds aren’t part of the device doesn’t mean that the device doesn’t contain elements.  Elements are common in additives and colorants.

Analytical methods must be sensitive enough to detect trace-level compounds and, together with the extraction parameters and sample preparations techniques like concentration, be capable of meeting or exceeding the Analytical Evaluation Threshold or AET (see ISO 10993-18).

The final and often most tedious step is data interpretation, aka compound identification. Comprehensive identification strategies, not just peak hunting, are not optional, they are the expectation to meet the requirements of toxicological risk assessment. It’s not enough to run the extract through the instrument and pick the top library match. Good E&L demands thoughtful design, deep chemical insight, and a commitment to uncovering what others might miss (impurities, residuals and contamination).

Whether you’re navigating ISO 10993-18, USP <1663>/<1664>, or FDA guidance, good E&L testing:

•            Uncovers not only the expected but also the unexpected.

•            Supports risk assessment with clear and comprehensive data

•            Stands up to scrutiny from regulators, auditors, and stakeholders

It’s not just about checking boxes—it’s about telling a defensible story.

Great chemical characterization doesn’t happen in a vacuum. It’s Client-Focused and Collaborative. It’s built on:

•            Clear communication between chemists, toxicologists, and sponsor

•            Tailored study designs that reflect product use, materials, and patient exposure

•            Strategic enough to support global submissions

· Responsive service that adapts to changing timelines and priorities 

Good E&L is a partnership. It’s about helping clients make informed decisions, not just delivering data.

At Bonded in Science, we believe chemical characterization should be more than a regulatory hurdle—it should be a strategic asset. I can help you navigate the torturous E&L landscape—With over 35 years of experience in analytical chemistry, pharmaceutical and medical device testing, I help clients turn complexity into clarity, and regulatory expectations into sound decisions. I don’t work for the laboratories; I work for you!

If you need help gaining a deeper understanding of what E/L studies mean for your product, decoding E/L study proposals, evaluating laboratories —or just want to talk chemistry—I’d love to connect.