What is extractables testing?
Extractables and Leachables Testing is an analysis of potentially harmful materials that could be administered to a patient with a drug or device. Toxicological assessments may then be made, to quantify a patient’s exposure to each chemical and gauge the level of risk posed by these materials.
What is a Leachables?
Leachables are chemical species that make their way into the product under normal product, application or storage conditions. There is generally an overlap such that the leachables involved may be classified as a subset of the extractables.
What are leachable impurities?
– Compounds that leach into the drug product. formulation from the container closure as a. result of direct contact with the formulation.
How do you test for leachables?
Detecting extractables and leachables: using the right tests Semi-volatile organic compounds —typically performed using GC-MS or high resolution accurate mass (HRAM) GC-MS. Non-volatile organic compounds —typically performed HRAM LC-MS/MS. Elemental impurities (metals) —typically performed ICP-MS.
What are organic extractables?
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.
What is extractable study?
The extractables study identifies species from manufacturing components (where applicable) and the packaging system that could migrate into the pharmaceutical product upon storage under normal conditions.
What is E&L testing?
E&L testing (Extractables and Leachables) is conducted on plastic products to determine the small molecules which are released from a polymer system including antioxidants, surfactants, slip agents, plasticizers, acid scavengers, crosslinking agents, lubricants, residual monomers and oligomers.
What is E and L testing?
How do you calculate an AET?
Determine estimated AET by converting SCT (0.15 µg/day) to units relative to an individual OINDP (e.g, µg/canister, µg/gram component, etc.) Estimate position of SCT on the particular extractables/leachables profile. This is the Estimated AET.
What is aet toxicology?
Definition of AET. “The AET is defined as the threshold at or above which an OINDP pharmaceutical development team should identify and quantify a particular extractable and/or leachable and report it for potential toxicological assessment.”
What is aet extractable?
The AET is defined as the threshold at or above which a chemist should begin to identify a particular leachable and/or extractable and report it for potential toxicological assessment. • The AET is developed during extractables studies and is applied to both extractables and leachables.
What is SCT in pharma?
Safety thresholds (SCTs) have been proposed for patient exposure to many of the individual chemicals that might be identified in these studies. Generally, the investigational equipment used by an analytical chemist reports chemicals found in concentrations of PPM or PPB.
Is there an overlap between extractables and leachables?
There is often an overlap between extractables and leachables, meaning leachables are intended to be a subset of the extractables. Stability leachable studies are carried out to understand leachables which migrate under simulated environmental conditions.
Which is the best definition of a leachable?
Leachable: Chemical species that migrate from a packaging/delivery system, packaging component, or packaging material of construction into an associated drug product formulation under normal conditions of use or during accelerated drug product stability studies. Leachables are typically a subset of extractables or are derived from extractables.
How are leachable studies used in extractable studies?
Extractable studies can also be used as a baseline to ensure SUS consistency over time. Leachable studies determine the chemical compounds that migrate from SUS into process solutions and characterize possible adsorption and/or absorption of process fluid (under normal process conditions).
What is the SCT for an extractable and leachable?
•SCT: Safety Concern Threshold is defined as the threshold below which a leachable would have a dose so low as to present negligible safety concerns from carcinogenic and non-carcinogenic toxic effects. The safety concern threshold (SCT) for extractables and leachables has been defined as 0.15 µg/day.