With the fast paced evolution of single use technologies for pharmaceutical processing, there are many topics and questions that are becoming increasingly relevant as technology evolves. Chief among them are questions about extractables and leachables. How do we test for them? Is this the best way to test for them? How do we quantify and standardize on acceptable levels? This post will focus on the L & E’s (or E & L’s, depending on who you talk to), what the difference between the two are, and why this is such a big deal in single use technology today.
To begin, an extractable is a chemical entity, both organic and inorganic, that will extract from the components of a process system into a solvent under controlled conditions (usually extreme conditions not encountered in a process). This means high heat, pressure, or even multiple sterilization cycles. It also mean strong acids and organic solvents. Extractables are important because they help us to identify potential leachable.
Leachables, on the other hand, are chemical entities, both organic and inorganic, that migrate from components of a system into a drug product over the course of the system’s life. Leachables can sometimes be found in final drug product, usually in trace level relative to the active pharmaceutical ingredient (API).
So now that we know what E & L’s are and the difference between the two, why is this such a big deal in single use systems today? Well, as single-use systems have been widely adopted for upstream biopharmaceutical processing and have been proven effective process and economic system models, interest has been growing to integrate these technologies with downstream processing. As we get closer to the final drug, FDA and internal quality control becomes more intense. This gets people asking about things like extractables and leachable profiles.
These concerns have prompted a battery of validation studies by both the end users and suppliers of single use components. Most single use component suppliers will now have full profiles of each of their products on hand and available to distributors and end users.
End users are doing validation testing as well. Each of manufacturer does something different from their competitor. They make different products, use different solvents, or autoclave at different temperatures, which means they can’t use “stock” testing to see if it is going to impact there product. Each product- and process- is unique.
The variability and attempts to in the characterize extractables and leachables in the most accurate and robust way is what is driving the discussion today. There is currently no specification or guidance documents by an approval agency that mandates testing protocols or set levels that manufacturers must comply with. Additionally, plastic process component manufacturers are asking questions of both regulators and end users as to why extractables and leachables are so important in single use applications, while stainless systems are seemingly grandfathered in. What do you think you might be able to pull out of a stainless system after hundreds and hundreds of steam and aggressive chemical cycles? The answer? Nobody is really sure because we haven’t done the testing.
While this debate is likely to continue to loom over the industry until there is a guidance document or standard for testing and acceptable levels, the industry as a whole has taken steps to better characterize the products that are being used in process today. For questions about the extractables and leachable profiles for your process component, contact a Holland Sales Engineer today.