Extractables potential leachables

Leachables in orally inhaled and nasal drug products (OINDP) are compounds which are present in the drug product due to leaching from container closure system components. Extractables are compounds that can be extracted from OINDP device components, or surfaces of the OINDP container closure system when in presence of an appropriate solvent(s) and/or condition(s). Leachables are often a subset of, or are derived directly or indirectly from, extractables. Extractables may, therefore, be considered as potential leachables in OINDPs. Some leachables may affect product quality and/or present potential safety risks, therefore regulatory guidance has provided some recommendations regarding the analysis and toxicological safety assessment (i.e., qualification) of such compounds. 

Complete information is important in order to assist in the initial selection of container closure components, design laboratory extraction studies for components, and to establish a linkage, or correlation, between potential leachables (i.e., extractables) and observed leachables in a particular drug product. Such a correlation is required by regulatory guidances for certain dosage forms. ... 

These results indicate that alkalinity and the rate of release of alkalinity plays a major role in the release of heavy metals from stabilized/solidified hazardous wastes. The U.S. EPA EP-Toxicity Test is not adequate to evaluate the potential leachability of these wastes because the large buffering capacity of the fixed waste causes the extraction to be performed at a high pH where heavy metals are generally least soluble. It is important to determine the buffering capacity... 

We have shown that polymeric stabilizers, polymeric ultraviolet stabilizers, and polymeric antioxidants are effective in retarding photooxidation and thermal oxidation in polymers. Polymeric stabilizers are not volatile, not extractable or leachable, and do not provide the undesirable characteristics of toxicity, potential carcino-... 

Exposiue to or contact with even minute amounts of potential leachables in medical devices or biomaterials can result in allergic or sensitization reactions. Sensitization tests estimate the potential for contact sensitization of medical devices, materials, and/or their extracts, are usually carried out in guinea pigs, and should reflect the intended route (skin, eye, mucosa) and nature, degree, frequency, duration, and conditions of exposure of the biomaterial in its intended clinical use. Emphasis is placed on utilizing extracts of the biomaterials to determine the irritant effects of potential leachables. Intracutaneous (intradermai) reactivity tests determine the localized reaction of tissue to extracts of medical devices, biomaterials, or pros-theses in the final product form. Irritation and intracutaneous tests may be applicable where determination of irritation by... 

The observed level of a given leachable at the end of drug product s shelf life was less than or equal to the potential level of the qualitatively correlated extractable as measured in appropriate container closure components (i.e., quantitative correlation). 

If the drug is in contact with any part of the device during its storage or use, the developer will need to understand the potential for extractables from the device components to leach into the medicinal product over time. A study should be designed to understand the potential for leachables, taking into account many considerations including the following ... 

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