What are Extractables and Leachables Studies?
Extractables and leachables (E&L) studies are in-depth analytical investigations of the chemical interactions between:
- a container closure and a drug product or pharmaceutical formulation
- a drug delivery system and a drug product or pharmaceutical formulation
- an implantable medical device and the human body
- between different materials comprising a medical device
- manufacturing components and finished products
- other component interactions relevant in the pharmaceutical or medical device industries
The primary purpose of an E&L investigation is to identify any potential chemicals derived from the interaction of 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 E&L studies include the FDA, ISO, ICH, BPOG, and USP.
What are Extractables?
Extractables are substances in a device, manufacturing component, or container closure system 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 that leach or “come out” under normal conditions of exposure over the natural lifespan of a 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.
Read More About Specific E&L Guidances
- ISO 10993 Chemical Characterization
- Medical devices
- USP General Chapters 1663 and 1664
- Pharmaceutical packaging/delivery systems
- USP 661, USP 661.1, USP 661.2, and USP 661.3 (now USP 665)
- Plastic pharmaceutical packaging
- Polymeric manufacturing components and systems
- BPOG Extractables and Leachables
- Single-Use Systems (SUS) in biopharmaceutical manufacturing
Extractables and Leachables Studies at EKG Labs
Understanding complex chemical interactions is critical to designing a proper extractables and leachables program. EKG has years of experience designing and managing large E&L programs. We routinely perform E&L analytical studies with the ultimate goal of submitting data for FDA review and approval. EKG Labs is familiar with guidance from organizations such as the FDA, ISO, ICH, BPOG, and USP. Our capabilities include:
- Full scale GMP analytical extractables and leachables programs
- Method Development
- Method Validation
- Material 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
EKG Labs Case Studies
- Medical Devices