Just as trace-level and impurity analysis require case-by-case adjustments to methodology, extractables and leachables methods, in their current state, are not universal.
In the case of pharmaceuticals, for instance, each dosage form, container closure system (CCS), and drug delivery system(DD) exhibit their own unique composition, some of which are at the ppm (parts per million) level.
There are many challenges when developing routine extractables and leachables methods, such as:
Extractables profiles, when conducted early in the product development process, usually begin with the same general parameters for preparation and analysis. However, for individual sample types, parameters will need adjustments that are specific enough that require the methods to be potentially only one-time use. These methods for extractables profiles may not be transferrable from one packaging system to another.
Chemical profiles in extraction studies can lead to further studies in order to determine if additional development is required so leachable studies can be evaluated. Material selection is, therefore, paramount to the progress of analysis. However, because forming a reliable baseline affects the rest of the method development, materials must undergo selection specific to the product.
One of the chief goals of a routine extractables and leachables screening method should be to find a way that ensures the product, when it goes to market, is safe for consumer’s usage. The safety concern threshold (SCT) is the standard to which analysts hold product formulas to ensure safe use by consumers.
Routine methods can be used during the later stages of product development to monitor inhalation and parenteral product leachables during registration stability studies. Such methods help identify known compound quantities and detect new chemical species, which contributes to a robust report usable to analyze and improve safety of products.
Leachables do not typically appear in drug products at a significant level for weeks (sometimes months) after production. To accurately control leachables levels, compounds must be extracted from CCS materials as part of routine analytical tests. From the information made available through such tests, the development of an appropriate routine extractables test becomes possible.
By examining the correlation between extractables and leachables levels, specific information on extractables provides superior control over leachables.
Experts are now implementing routine methods where possible and searching for new ways to utilize routine methods to accomplish tasks that currently require modification of existing methods or the development of unique methods. Through continued method development focused on current challenges, extractables and leachables methods are likely to become more global over time. For more information about extractables and leachables testing, visit our service page.