A lot of the information here is derived from ICH Guidelines. These can be found at www.ich.org. The purpose of stability testing is to demonstrate how packaged and unpackaged pharmaceutical product changes with time in different temperature, humidity and light conditions. Data is used to help establish product shelf life and storage conditions as well as whether further testing is necessary. Similar testing may also be carried out on other products such as cosmetics, pesticides and foods.

The main types of testing are long term – which aims to mimic conditions the product is likely to be exposed to through its normal life, and stress testing where the product is exposed to conditions likely to accelerate the normal aging process.

The conditions used for testing will depend on whether it is intended to store the product in ambient conditions or controlled conditions (e.g. cool 5°c or freezer -20°c). Where ambient conditions are to be used the climate of the intended region will also be taken into account.

The Chamber

The chamber needs to be capable of achieving consistently the appropriate conditions for the test. Consider: -

· Temperature control normally needs to be within 2°c of the set test temperature, at all times and in all parts of the chamber likely to be used for testing. Temperature mapping should be used to ensure this is the case.
· Test chambers should be built from tried and tested components to ensure reliability and backed up with service and emergency breakdown in your locality.
· Access should be controlled and chambers should be secure against unauthorised entry.
· Data gathered should be accurate and secure (21 CFR part 11 compliance)
o System should ensure authenticity, integrity and appropriate confidentiality.
o Individuals should not be able to repudiate the authenticity of records.
o There must be time-stamped audit trails of entries, modifications or deletions of data. (The time-stamp clocks must be accurate, reliable and tamper proof)
· Chambers must meet the requirements of the International Conference Harmonisation (ICH) for stability (Q1A) and photostability (Q1B).
Chambers should provide shelving to provide easy access to samples as well as sufficient room for air circulation and light penetration (photostability) so that conditions are properly maintained for all of the samples all of the time.

Humidity fluctuation and variation

Humidity fluctuation is the difference between the highest and lowest humidity at a given point in the chamber when running at a constant humidity set point. The fluctuation is a function of control – the dead zone between on and off of the humidistat, and the speed and accuracy of changes in humidity input or removal.

Humidity variation is the spatial difference between the highest and lowest relative humidity in the chamber at the same time. The relative humidity of a given volume of air with a fixed amount of water in it will change with temperature – humidity falls as temperature rises. As a consequence humidity variation is governed by temperature variation. (Unless there are changes to the absolute water content of the air. In most applications these are inconsequential.)

Opening doors, cooling coil defrosts, personnel and power failures can cause significant temporary disruptions to the humidity. These problems can be resolved but this must be done at the design stage.

Reducing Humidity

Water vapour in the air will condense on any surface colder than dew point. In chambers, refrigeration coils designed to capture condensate exploit this phenomenon. The amount of moisture removed will depend on the temperature of the coil and the proportion of air exposed to it.

If chamber humidity set points are below dew point, the refrigeration coil will freeze up (what ever the temperature set point!). The coil will then need to go through periodic defrost cycles that will result in short term disruptions to temperature and humidity control. If this is a problem it can be resolved by using two coils alternating between control and defrost.

For some situations it is better to use a dryer to remove humidity. Dryers use silica gel in a rotating wheel arrangement where initially chamber air is passed through the gel which absorbs moisture. As the wheel rotates the gel moves into a recharge sector where heat is used to drive off the absorbed moisture ready for its next pass through the chamber.

Raising humidity

Where humidity set points are high or where refrigeration coils used for temperature control are condensing too much moisture, it may be necessary to add water back in to the air. There are various ways to do this but using a water boiler has the advantages of ensuring the water is sterile and free from dissolved solids which could contaminate work and is also temperature neutral so will not disrupt fine temperature control.

In some situations it may be advantageous to use a fog or evaporative pad system that will cool and humidify at the same time.

This is the place to come for news, views and information. These will be in the form of short articles added on a regular basis. To get the ball rolling you will find below an article about the diverse uses of controlled environment chambers. Please let us know if you have any suggestions for future articles, or indeed other comments about the website.

Controlled Environment (CE) Chambers are used for a very wide range of purposes. In every case there is a requirement for the chamber to be able to reproduce a particular set of environmental conditions. Control may be simple as with steady state control of a single environmental component, complex with programmed variations of a number of components or anything in between.

In many cases the controlled environment is intended to replicate conditions found in nature or in man made environments. Plant scientists will seek to reproduce a particular climate with diurnal variations but without the randomness. This is to ensure that the work is repeatable and experimental error minimised. Similarly pharmaceutical stability chambers are designed to simulate the man made environments to which drugs and packaging are likely to be subject. Biotechnology uses CE rooms to produce the ideal environment for the production of various organisms, some of which may live naturally inside an animal, plant or their residues.

Climatic chambers are used to intensify the effects of natural conditions to determine quickly the probable life of a product. This may be done by rapid cycling of conditions or by the addition of aging agents such as salt spray. Seed and artefact stores demonstrate the converse situation, where the intention is to remove the conditions and changes in condition that cause aging, thereby extending life.

Chambers can also be used for physiological and medical reasons. Athletes may use chambers to reduce times required for acclimatisation prior to competing in an unfamiliar climate. Research may also be carried out under closely controlled and monitored conditions using running machines or static bikes so that the monitoring equipment can easily be attached to the athlete.

Isolation and quarantine chambers are used to contain potentially damaging substances or organisms such as pests, diseases and transgenics. They are also used to protect subjects from damage from the natural environment. They use special measures such as pressure differentials, air locks and drainage containment or treatment to achieve this.

CE chambers can be used to provide conditions for a particular process. Tissue culture is a process used to bulk up living cells and perhaps produce clones of organisms. It is commonly used to bulk up rare or new lines of plants, or indeed plants which are difficult to propagate by other methods. Similarly stem cell production is a tissue culture process. These are living processes, but not natural as they could not happen without special management.