Hi welcome to another in my occasional blogs on topics relating to extractables and leachables found in pharmaceuticals and medical devices .
This one is around a topic which I have a bit of a love / hate relationship with, and like any relationship of that kind I find myself returning to it time and time again trying to seek "enlightenment".
So a quick introduction to what is an EXTRACTABLE. An extractable is a chemical substance what is derived from an extractable study (sometimes called extraction study - and many other variants - don't get me started on that!!). But it was the subject of one of my 1st blogs here
An extractable study is a scientific investigation (or should be) into a material which is part of either packaging, delivery system or manufacturing process. A material which may or may not be a source of inorganic or organic substances which leach from the materials. That process of leaching may contaminate a drug product or medical device and lead to patient exposure.
So extractable studies are designed, and thus extractables can vary with that design.
This is a key point - since they are designed they are subject to all kinds of influences.
Here are a few:
• Opinion - Almost all well meaning, but invariably some contradictory
• Guidance Documents - a variety have been published, hopefully they are clear and unambiguous but they will nearly always leave gaps (filled with opinion)
• Regulatory Standards- See guidance documents, interestingly almost all are labelled as guidance.
• Best practice - This one is interesting, is this an oxymoron? Does this become a carrot (a reward, or something you should consume because you are told it is good for you) or a stick (to support you or beat you with) - How's that for a group of mixed metaphors? Best practice can easily slip into dogma and doctrine, which does not sit particularly comfortably with something suppose to be a scientific study.
• Scientific principles - hopefully this is the one that directs the study and its outputs
So you have spent some time defining extractable / extractable studies. What should we do with them?
Hopefully by now, you can see that extractables should come with a label. That label would perhaps read, "Do you know how I got here?".
Because it is highly likely those extractables are very much linked to the design.
That is, it is the design of the study and all the opinion and scientific principles which support it, which will define the extractable and how it then be used. Since that design will impact not only what extractables are detected, but also what is identified and what quantities are calculated. It is tempting to believe all extractables are created equal, but to misquote George Orwell's Animal Farm:
Some extractables (and Extractable Studies) are created more equal than others.
Here are some potential extractable study designs outlines:
A study to quantitatively estimate the content of substances present in a sample material
A study to explore qualitatively what substances are within a sample material
A study to predict leaching from the sample material under conditions similar to use of the material as a manufacturing part (or packaging, or delivery device, or medical device)
A study to aid in the development of a analytical procedure (setting limits of detection, establishing detector response characteristics, refining sampling, refining separation)
A study to provide a comparison between materials to allow a business choice
A study to meet a published regulatory standard (not best practice!)
A study to predict toxicity and patient safety
So you can see that we are asking a lot from our humble extractable and moreover, it is highly unlikely this can be achieved from a single design. But many many times I have seen groups and individuals expecting that.
The reasons for that are complex and perhaps I will write another blog around that.
For now, I would ask you to comment and question your extractable labels and think deeply next time you plan a extractable study to ensure you get the results and extractables you deserve and expect.