Extractables and leachables are compounds that can be extracted from the packaging containers or enclosed containers, manufacturing systems and medical equipment which can come in contact with the drug before it is administered to the patient. Extractables are generally compounds that in the presence of a solvent can be extracted from the container closure system. They can be organic and inorganic chemical compounds released from the surfaces of components used in the manufacture and storage of drug products and can vary in nature with respect to temperatures, solvents or surface exposure. Whereas leachables are the compounds that leach into the drug product formulation from the container closure system. They are organic and inorganic chemical components released from the surfaces of components used in the manufacture and storage of drug products under normal conditions.
The crucial part of the drug development programmes is to estimate the purity of the final end product and to validate the purity profile of the drug compound. But in recent times the impurities arising out of the manufacturing process and the degradation of the pharmaceutical product is assessed through migration of the mobile chemical species used during the manufacturing process and storage of pharmaceutical products.
Extractable and leachable (E&L) study:
Extractable and leachable studies are crucial part of the regulatory concerns and are important for consideration of parenteral biologics. The extractable and leachable study profile in general is observed and controlled as per the safety protocols as they can influence the biological product stability, quality, and efficacy. Over the last few years industrial procedures are equipped with best practices and guidance to address the issues regarding E&L studies. However, technical and regulatory challenges still persist because of the development of a large number of biologics and vaccines using novel modalities such as cell and gene therapy as well as primary packaging systems.
The best practices conducted and the case studies done are relative to the regulatory exercises. There has been increased focus on the components interactions, drug delivery systems, container closure systems and drug products to analyse the toxicological effects during the interaction.
Extractables and leachables are a crucial part of the drug product release owing to the safety, strength, quality, purity and efficacy of the drug compound. Leachable studies sometimes or in practice, identify all the components that were not observed during the extractables study but there is a congregation of the sets of extractable and leachable species.
Leachable components exists in the manufacturing process, filters, in the disposable or intravenous bags and syringes, tubing and primary packaging, container closure systems such as vials, caps, lids and foils, gasket and valves, springs, secondary and tertiary packaging, labels and adhesives and also inks and colourings. The part of leachable studies involve study of antioxidants and stabilizers, anti-static coatings, lubricants, slip agents and emulsifiers, dyes and colourants and vulcanizing agents, residual monomers, polymers and oligomer species, phthalates, nitrosamines and poly-aromatic hydrocarbons (PAHs)
For the evaluation of the safety of the drug product industries have formatted an advanced technology of validating the limits of leachable impurities called as Safety concern threshold limit (SCT). Safety concern threshold is the validated limit below which the dose of leachable components is not harmful or causes any carcinogenic side effects that would be of safety concern. Safety concern thresholds are affected by two factors such as route of administration and product packaging contact.
Management of extractables and leachables are critically important to pharmaceutical manufacturers and regulatory authorities for the safety and efficacy of the drug product formulations. Therefore testing is necessary for the identification of leachables to induce firm assessment of the potential impact of interactions between the packaging systems and the final dosage form.
