|
 Leachables
are defined as “compounds that leach from elastomeric,
plastic compounds or coatings of the container and closure
system as a result of direct contact with the formulation
during the shelf-life of the product.”
Identification
of leachables and 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
- Interfere
with dosage consistency
The
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 and types of compounds detected, consideration
should be given to including a test and limits for leachables
in the drug product specification. If a correlation between
extractable and leachable profiles can be established, control
of leachables could be accomplished via testing and limits
on extractables.”
Interested
in the details covered here, then why not contact us?
|
