Extractables are defined as organic and inorganic contaminants such as plasticizers, elastomers, oligomers, dyes, elemental impurities etc. that can be extracted from the surfaces of packaging components under extreme conditions such as elevated temperature and pressure or with exposure to organic solvents.
Leachables are defined as organic and inorganic contaminants that can be released from the surface of container closure systems under standard storage conditions.
Extractables and leachables (E&Ls) may be inherently toxic and can contaminate the drug product. To ensure the safety and efficacy of drug products there has been an increase in regulatory measures to monitor and control extractables and leachables in pharmaceuticals, drug delivery systems, and biomedical devices.
The enhanced regulatory standards necessitates pharma industry to develop sensitive and accurate analytical methods to detect, identify, and quantitate extractables and leacheables in drug product, as per U.S. FDA 21 CFR 211.94(a) and European Commission Directive (2001/83/EC).
Extractables and leachables represent contaminants from a broad range of structural categories, covering inorganics (elemental impurities Hg, Pb, Cd, As, etc…), organics (PAHs, Nitrosamines, Azo Dyes, Vulcanizing Agents, Phthalates, antioxidants, Elastomers, Stabilizers, etc…) with a wide range of molecular weights and physico-chemical properties.
No single analytical technique in the study of extractables and leacheables can be used for all categories of compounds. As a result, testing for extractables and leachables is achieved by complementary use of a variety of analytical techniques, as shown below:
Dalton Pharma Services offers consultation services and customized testing capabilities for determining extractables and leachables on container closure systems.
There has been a significant amount of regulation and guidance for industry for extractables and leachables study, with a large percentage of the requirements established over the last few years.
Extractable and leachable studies are essential for the identification and quantitation of toxic leachable impurities that can migrate from pharmaceutical container closure systems, process equipment and packaging, resulting in adulterated products. Extractable and leachable study is an important and essential parameter, especially for high risk sterile Parenteral and Ophthalmic Drug Products.
A successful Extractable and leachable study using validated analytical methods assures that the quality of drug product is not compromised in container closure system; ensuring patient safety.