Stability tests are conducted to establish how the quality of a drug substance or drug product varies with time under the influence of a range of environmental factors. Recommendations for storage conditions, re-test periods and shelf lives are established from analysis of the data collected and it is therefore essential that the artificially simulated test conditions are accurate, stable and repeatable.

For world-wide stability testing, the world is divided into four climatic zones for which storage conditions have been established on the basis of data collected for a number of cities in the relevant zone.

Climatic Zone Temperature Humidity

I - Temperate 21°C 45%

11 - Mediterranean 25°C 60%

111 - Hot Dry 30°C 35%

1V - Hot Humid 30°C 70%

Climatic Zone 1 is established as being prevalent in covering EC, USA and Japan.

Long term testing is conducted for at least 12 months and often up to 5 years,at the designated conditions. Accelerated testing can be carried out at a temperature at least 15°C above the relevant temperature along with the appropriate relative humidity for that temperature. There is also the possibility of an intermediate test to provide a more severe thermal challenge than the long term test. In summary, for Climatic Zone 11, the conditions are as follows:

Test Temp Humidity Period

Long term
25°C ±2°C >60% ±5% > 12 months

Intermediate
30°C ±2°C >60% ±5% > 6 months

Accelerated
40°C ±2°C 75% ±5% 6 months

Large scale testing naturally requires large scale test chambers and it is generally accepted that the larger the physical space, the more difficult it is to maintain an even temperature and humidity.

Temperature deviations are traditionally defined as Variation (a temperature change across space) and Fluctuation (a temperature change over time).

Fluctuation is a function of the temperature controller, but with modem electronic thermostats this can be measured in fractions of a degree and is therefore not the most critical factor.

Variation is a function of the basic design of the chamber and is determined by such things as the overall volume and shape, air flow, insulation, positioning of heaters, coolers, etc.

Humidity differs from temperature in that it is the fluctuation at the control point that is of most concern, rather than the variation across the chamber. Humidity sensors are not as inherently accurate as temperatures sensors but control accuracy of ±3%RH is now achievable with electronic sensors.

The overall size and shape of a chamber are typically determined by the product load specified and is therefore fixed. With regard to air flow it is generally accepted that a laminar type system will result in minimal temperature variation, however the cost overhead involved in producing a large cabinet or room to this design is usually prohibitive. Some form of internal ducting is essential and where possible, the conditioned air should be made to travel through the workspace and not just re-circulate around a point. The air flow may appear perfect in an empty room but when the shelves are fully loaded the whole temperature/humidity profile may change.

Adequate insulation not only helps to minimise temperature variations but is a significant factor in running costs over the life of a cabinet. The balance between heating and cooling should be maintained at a sensible level. Modem techniques are increasingly energy efficient, for example steam humidifiers that are typically rated at 3 kW and over, can be replaced with low voltage ultrasonic systems which do not input heat to the chamber.

Finally, a few words about any potential supplier. Ensure that the manufacturer is willing to perform a validation run (with traceable instruments) prior to delivery or hand over. Enquire about any Quality Systems that the manufacturer may have and whether those systems have been assessed by a third party auditor. Specifically with regard to BS 5750, is the registration to Part 1 - Specification for Design, Development, Production, Installation and Servicing, or just Part 2 - Specification for Production and Installation. If there is any doubt ask to see the Scope of Registration document.

Ensure that the manufacturer has previous experience, ask for details of similar installations, take up any references that are offered. Insist that the manufacturer appoints a Project Manager to be your point of contact and with whom you can establish a working relationship.

Remember that the simplest way to achieve a successful outcome to a project is to specify the requirements correctly in the first place and then stick to the agreed specification.

Vindon Scientific Limited - Tel:.+44(0)1457.876616..Fax:.+44(0)1457.871355 Registered in England No. 878160