General case drug products are not the only medications that are adding environmental conditions to their studies. More conditions have
also been added to the stability study profiles of refrigerated drug products. Per ICH guidelines, long-term storage of refrigerated products should be 5 °C ± 3 °C for a minimum of 12 months.
The accelerated condition is 25 °C ± 2 °C/60% RH ± 5% RH for a minimum of six months (2). Outside the ICH guidelines, this
study setup may or may not be sufficient. While the long-term 5 °C ± 3 °C condition still applies, 30 °C ± 2 °C/65% RH ± 5%
RH or 30 °C ± 2 °C/75% RH ± 5% RH is now often used for accelerated stability studies (1). Overall, adding these conditions
provides a risk-based assessment for the product, especially if it is a biologic. With the required additional conditions
and samples, where does this leave a CRO?
To support global stability practices, fundamental basics must be put in place. The first is to have validated and qualified
stability chambers. A qualified and validated chamber must have the proper installation, with operational and performance
qualifications completed before sample placement occurs. As well as validated hardware, a compliant CRO needs the correct
standard operating procedures (SOPs) and quality control systems. This allows the flexibility to adapt chamber conditions
as required for handling a variety of product lines.
It is imperative to fully understand the scope of any study; that is, how many primary and retained samples will be received,
their storage conditions, and sample storage orientation. These conditions determine how much space a study will occupy and,
from a risk mitigation standpoint, provide insight into the conditions that must be replicated.
Risk assessment is also crucial to a stability program. For example, having multiple stability chambers under the same conditions,
or chambers with redundant temperature and humidity controls are approaches to mitigate effects of any mechanical failures.
This redundancy prevents study restarts or additional testing to ensure the product was not compromised during an excursion
or failure. A robust monitoring program is key and should assess temperature or humidity excursions. In collaboration with
a good general preventive maintenance schedule, this monitoring can prevent mechanical failures from being catastrophic.
Finally, a CRO should have a suitable laboratory information management system (LIMS) to monitor the stability program. The
LIMS should be able to track the progress of an entire study. The data collected include but are not limited to: recording
sample receipt, placement of samples into the chambers, interval pulls, and test results. For laboratory personnel, the stability
pull schedule should be readily available with information about the required conditions and tests. Tracking of turn around
metrics should also be possible. The LIMS system needs to generate reports on instrument conditions and/or sample results
as necessary. Although there are other aspects required for a stability program to ensure its integrity, without these basics,
the program is not likely to function optimally in a global regulatory environment.
Deni Jo Williams is a GMP project manager at MPI Research, State College, PA.
1. WHO, Stability Testing of Active Pharmaceutical Ingredients and Finished Pharmaceutical Products, Technical Report Series 953, Annex 2 (2009).
2. ICH, Q1A (R2) Stability Testing of New Drug Substances and Products (2003).