Extractables and leachables: what plastic might release into a medicine
A medicine bottle must add nothing to what it holds. To make sure, the industry asks two questions in turn: what can be pulled out of this plastic, and what is actually found in the product?
By Tecmom editorial team · 2 min read
Two words, two questions
Extractables are the substances that can be drawn out of a pack in the laboratory, under deliberately harsh conditions: aggressive solvents, high temperature, long duration. The aim is to find what could come out.
Leachables are the substances that actually pass from the pack into the medicine, under normal storage and use. The aim is to find what really comes out. Leachables are generally a subset of extractables, or substances derived from them.
Why two steps
The extractables study maps the possibilities: additives, manufacturing residues, degradation products. It then allows the right substances to be looked for in the medicine, at the right levels, instead of searching blindly.
The leachables study checks, over the shelf life, what has actually migrated. Results are assessed toxicologically: a substance that passes in a tiny amount does not weigh the same as a substance of concern.
When regulators expect it
The European Medicines Agency's guideline on plastic packaging organises these studies according to the nature of the product: liquid and semi-solid forms are the most exposed, since a solution touches the whole wall for its whole shelf life. The FDA guidance on container closure systems also weighs the route of administration: concern is highest for injectables and inhaled products, high for eye drops, lower for oral forms.
For a dry form, a tablet in a bottle, the interaction is far more limited. See primary packaging.
What the packaging maker brings
An extractables study only makes sense if the material does not change from one lot to the next. That is what raw material control, traceability and the change control required by ISO 15378 guarantee. See what the standard requires and pharmaceutical packaging.
Extractables say what could happen; leachables, what does. Between the two lies the whole safety case of a primary pack: knowing what to look for, and proving it is not found at levels of concern.
Glossary
- Extractables
- Substances that can be drawn out of a pack under harsh laboratory conditions.
- Leachables
- Substances that migrate from the pack into the product under normal conditions.
- Toxicological assessment
- Analysis of the risk from a substance according to its amount and nature.
- Change control
- The rule that forbids changing, unilaterally, an item that is part of a medicine's file.