All pharmaceutical actives and products are legally required to have a number
of parameters checked prior to, and post, approval. The purpose is to examine
how the quality of the substance or product varies with time, under environmental
conditions. Temperature, humidity and light are conditions typically assessed,
also the shelf life and recommended storage conditions need establishing. Uniformity
of quality needs examining between different production batches.
The stability testing requirements for a new drug substance and product are
covered in the core ICH guideline Q1A. There are subsequent guidelines that
describe specific testing requirements, e.g. Q5C covers the stability testing
requirements of Biotechnological / Biological products.
To satisfy the regulators that the development drug is safe to be used in Phase
I clinical trials certain data is required.
At this stage, the drug in development will have been formulated and a dose
route chosen that is most appropriate to the clinical trial. Several other things
need to be covered:
- The regulators need to be aware of how the active ingredient has been produced
and the location of manufacture
- Proof needs to be provided that the active is stable from manufacture to
completion of formulation at the intended storage conditions
- Some analytical methods need to have been developed and validated for the
active and specificity to detect any degradation products
- Some stability data is required that at least covers the dosage period used
in the clinical trial
- A proposed dosage form will be required, e.g. capsules
- The formulation has to be stable in the containers to be used during the
trial and over the dosing period
- Limited stress data is necessary to support any excursions from the storage
conditions, during usage to support any requirement to reject the test material.
The active will also require some stability data on a single batch. Storage
stability data should be at 25oC at 60% RH and cover the length of the trial.
A stability indicating assay, appearance check, moisture content and effect
of pH on dissolution will be required. If extension of the storage period is
necessary then accelerated storage stability studies should be performed. The
data generated can also be used for batch release later in development.
The formulation will require stability data on maximum and minimum strengths
to be used in clinical trials. Data needs to be at intended storage conditions
for a duration that covers the trial. Limited data on photostability is also
worth consideration. As with the active the formulation requires some stability
indicating assays, an appearance check, moisture content check and the dissolution
profile will be required.
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