Pharmaceutical - Leachables

Leachables are defined as “compounds that leach from elastomeric, plastic compounds or coatings of the container & closure system as a result of direct contact with the formulation during the shelf-life of the product.”

The Identification of leachables & attribution to the contact component from which they originate is important because such species may react with the drug product or formulation ingredients, compromise the efficacy of the drug product or interfere with dosage consistency.

The European Agency for the evaluation of Medical Products (EMEA) Guideline states that “ It should be determined whether any of the extractables are also leachables present in the formulation at the end of the shelf life of the product or to the point equilibrium is reached if sooner.

Once the level of potential extractables has been determined (cf. CES) validated analytical methodology should be utilised to establish the accumulated level of the target species throughout the shelf life of the drug.

The biological risk posed by the accumulation of the species throughout the product’s shelf-life can be assessed.

A typical leachable study to monitor potential migratory chemical species throughout the shelf life of the product might be:

Time (months)	0	1	2	3	6	9	12	18	24	36
Real Time Data	x			x	x	x	x	x	x	x
Accelerated data		x	x	x	x	x	x

X - Leachable Testing

Depending on the levels & types of compounds detected, consideration should be given to including a test & limits for leachables in the drug product specification. If a correlation between extractable & leachable profiles can be established, control of leachables could be accomplished via testing & limits on extractables.