Stability Test Standard Jan 06, 2023
In Stability Testing - An Overview, we look at Stability Testing Requirements - Chamber Selection, Validation Requirements, IQOQPQ and IPV Considerations.

In order to demonstrate the shelf life of a drug in a certain market, the manufacturer must store it at the relevant temperature and humidity for a specified period of time. This is done in what is also known as a stabilization chamber.

Regulatory agencies in each market, such as FDA in the US, HPRA in Ireland, specify the temperature and humidity conditions that should be used and how long samples should be stored, such as a minimum of 6 to 12 months. During this time, samples were tested and their potency and degradation measured and recorded. This is called a stability test.

The most common conditions are 25°C/60%RH. For new products, accelerated conditions may be 40°C/75%RH. Other conditions include 30°C/65%RH, 30°C/35%RH and 25°C/40%RH.

For products intended to be stored in a blood bank Refrigerator, another condition is 5°C ±3°C. For products intended to be stored in a refrigerator, the test condition is -20°C ±5°C.

ICH, the International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use, has developed rules for running stability tests. ICH Q1A states that during stability testing, conditions should be kept constant at ±2°C and ±5%RH.

Also, if these conditions are not met for more than 24 hours, the test may need to be extended, creating a lot of paperwork. If conditions deviate from ±2°C/±5%RH, even for a short period of time should be accounted for. Probably due to the door opening to "pull" the sample. Events like this are usually logged in the room log.

If no explanation is apparent, it may be necessary to seek assistance from a service engineer. In the event of a failure in the laboratory, a quick response from the supplier is required and although he should stock major spare parts, the auditor would also like to have some stocked on-site as well. It is also recommended to have redundancy, ie another room on site as a backup. The chamber must be fully validated and ready for use.

Photostability Test Chamber
To demonstrate shelf life under ambient light conditions, samples may be exposed to precise doses of UV and visible light in specially designed chambers. ICH Q1B specifies temperature control to prevent localized hot spots.

Surveillance and 21 CFR Part 11
Indoor conditions should be independently monitored. This usually requires temperature and humidity transmitters connected to the recording system. In the Photostability chamber temperature, UV and visible light intensities will be recorded.

This system must comply with the regulations of 21 CFR part 11 in the United States, whether it is a paper recorder or a computer system. 21 CFR Part 11 states that all related data collection and storage systems must be designed to prevent counterfeiting, corruption, untraceable alteration, or loss of data. In the case of computer systems, formal testing (IQOQ-Installation Qualification, Operation Qualification) should be performed to demonstrate compliance.

Stability chamber Qualification
Likewise, formal testing (IQOQ and PQ performance qualification) must be performed on new Stability chamber. During its useful life it should be maintained regularly (usually annual preventive maintenance service and calibration checks) and preferably mapped with several probes per year (IPV - Instrument Performance Verification).

PQ and IPV typically require at least one 24-hour surveillance run, empty, loaded, or both. During this run, conditions must be shown to remain within ±2°C, ±5%RH of the set point. Test equipment used for these tests must be traceably calibrated at least annually and meet the IQOQ standards of 21 CFR P11.

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