QCS-014 - Quality Operations Procedures for Pharmaceutical, API, and Biotechnology - page 73

SOP No. QCS-014.00 Effective date: mm/dd/yyyy
Approved by:
14.4.4.4 Product formula and/or Process change
Stability samples are required from the first product lot following a formula or manufacturing pro-
cess change which may have stability significance.
For example, a change in active ingredient excess would be a formula change having stability
significance.
14.4.4.5 Packaging materials
The testing should be carried out in the final packaging proposed for marketing. Additional testing
of unprotected drug product can form a useful part of the stress testing and pack evaluation, as can
studies carried out in other related packaging materials in supporting the definitive pack(s).
14.4.5 e valuation
A systematic approach should be adopted in the presentation evaluation of the stability information
which should cover, as necessary, physical, chemical, biological, and microbiological quality character-
istics, including particular properties of the dosage form (e.g., dissolution rate for oral solid dose forms).
An acceptable approach for quantitative characteristics that are expected to decrease with time
is to determine the time at which the 95% one-sided confidence limit for the mean degradation
curve intersects the acceptable lower specification limit. If analysis shows that the batch-to-batch
variability is small, it is advantageous to combine the data into one overall estimate and this can be
done by first applying appropriate statistical tests (e.g., p values for level of significance of rejection
of more than 0.25) to the slopes of the regression lines and zero time.
14.5 significant changes at the accelerated conditions
Significant changes at the accelerated conditions are defined as:
a. A 5% potency loss from initial assay value of a batch. All obtained values for all batches
should be combined and treated by appropriate statistical tests at 95% confidence limit.
b. Any specific degradation exceeding its specification limit.
c. Exceeding in its pH limits.
d. Dissolution exceeding the specification limits for 12 caps or tablets.
e. Failure to meet specifications for appearance and physical properties such as change in
color, phase separation, resuspend ability, delivery per actuation, caking, hardness, and so
on.
f. Microbiological specification limit.
g. The standard conditions for light affects certain preparations. It is important to observe
effects caused by their exposure to light.
14.6 stability Protocols/execution
After the product is selected, the stability officer will raise the protocol form and enter the
following:
1. Product name
2. Batch number
3. Shelf life
4. Reason for study