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Another post from me from my series of blog posts I am hoping to make on the topic area of Extractables & Leachables (E&L). In this one I thought I would talk about Extractable Studies, and why there seem to be so many different kinds.
On my website there is a definition of what an extractable is and what is an extractable study. It says,
Extractable Studies: Chemical analysis / testing that exposes a sample of the container closure system or manufacturing system part to a selected solvent system or conditions that either simulates the product formulation or aggressively extracts (but not destructs) the material at accelerated conditions in order to inform the potential for leachables under normal use. Therefore, extractables are the substances which are removed from the container closure or manufacturing material during studies. Extractable studies therefore can be used as a tool to assess risk from leachables.
I hope that you find it useful but there are many different reasons for conducting an Extractable Study and that is why perhaps people have come up with several different terms;
Controlled Extraction Study, Accelerated Extractable Study, Simulated Leachable Study, etc.
What I wanted to clarify is that these are all extractable studies. That is, they are designed studies - designed by people like me.
They may or may not be good fits to what patients might receive when they take the medicine, that depends on the study and to a certain extent the drug product and how easy it is to model it. They do take experience and skill to get right.
I would say there are five main uses for extractable studies:
Material Selection: When you first start a project, someone has to make a decision on what materials you are going to include either in your manufacturing process or container closure or device.
This choice will hopefully be made on the basis of knowledge and understanding rather than a random one!
One way to get that is through an Extractable Study. These type of studies should allow you to select one component / material compared to another, and the design of the study should compliment that. It does not necessarily require a study which models leaching but you might aim to do that.
This would depend on your project needs. This might mean a range of different studies each designed to measure a different attribute which is important; Safety, Quality or indeed another project attribute such as security of supply, or cost.
Extractable Studies to demonstrate "potential" leachables: These type of studies aim to predict leachable in the drug product but can also vary widely from very much worst case to closely matched to leachables, both from a what and how much is detected.
Careful selection of conditions can tune these studies to reflect the requirement.
You will often see this Venn diagram illustrating how Leachables are a sub-set of Extractables. More recently people have been careful to draw the diagram with the leachable area not quite overlapping the extractable one. This is to remind people that extractable studies may or may not be a complete predictor of leachables. Some leachable can not be detected with one material extractable study (more on that in another post I think)
Extractable studies which are part of development of suitable leachable methods:
Clearly to develop an appropriate leachable method (perhaps a future blog post) you must know (if at all possible) the kinds of substances which you need to analysis for. Leachable methods are time consuming to develop. Picking the right method for the job is made a lot easier if you know what to look for, using the output from an extractable study aids in this development.
Extractable methods as quality control methods: These are a sub-set of other extractable methods, in that they could be the same or different from previously described ones. They are designed to be operated in conjunction with a specification and acceptance criteria. Therefore they must be robust and reproducible
The final main type is where they replace leachable studies all together: It is not always possible to develop a leachable method (See my presentation on 13th November at Smithers E&L conference in London).
In these circumstances, extractable methods have to be suitable to replace the leachable method. That is, they need to be quantitative and they need to have been validated so demonstrate they can replace leachable studies.
Hope you enjoy this post: Contact me at Jason.Creasey@MavenEandL.com if you need further help. Also keen you hear if you think these blogs are useful, and any ideas or topic you wish me to write about in a future blog please let me know.
Next one I am thinking about...Top Ten Mistakes in Leachable Study Design