Contaminant tests for compressed gases

Compressed gases are used widely in pharmaceutical production facilities. A variety of different gases can be introduced into the process at various stages of a product’s manufacture for different reasons. Common gases, such as air and nitrogen, are often injected upstream into cleanroom environments or processes, or act as barriers in the production of Active Pharmaceutical Ingredients (API). Nitrogen is also used in processing tanks.

Applications can vary but include, for example, the use of compressed air to remove vials or plastic containers that fail automated quality inspection tests on the line, ie check weighing or the positioning of labels.

First released in 1991 and updated in 2001, ISO 8573 contains several parts that, when implemented together, help in maintaining a particle-free compressed gas for cleanroom environments. Table.1 lists the different parts making up the standard. The following text outlines why it is such an important standard and how it contributes to a particle-free environment in pharmaceutical production facilities both downstream and upstream.

Downstream

A compressor is used to compress gases based on the law of ideal gases: p = nRT/V (the more gas, the higher the pressure). They use motorised suction techniques to pull a gas into a closed tank.

Compressors used in pharmaceutical applications should be 100% oil-free and manufactured to ISO 8573 CLASS 0 standards. To gain certification to the Class 0 standard the compressor must successfully pass strict testing by a qualified external laboratory. The TÜV (Technische Überwachungs Verein) a technical monitoring association based in Germany was the first independent laboratory to certify a compressor as Class 0 in 2006, and this is now widely used in the pharmaceutical, medical device, semiconductor, food and beverage industries.

The removal of water vapour and particulates:

The compressor, by nature of its function, introduces water vapour into gas lines. Once the compressed air is released and regulated it condenses and water vapour is formed. It is critical that this vapour is removed before it enters the cleanroom or process area, as it is entering a controlled environment and water vapour under warm conditions in gas lines provides an ideal breeding ground for bacteria.

Class 0 compressors have built-in dehumidifiers and particle filtration systems to remove bacteria to levels of 0.01?m, and therefore eliminate these problems.

Upstream

Testing the compressed gas line:

External testing by a qualified company with certified equipment, as well as in-house testing, should be carried out routinely.

Frequently, the testing for viable and non-viable particles is commonplace but testing for humidity (ISO 8573-3) is not so common, yet should be included in the testing to verify that water vapour (if the gas is air) or humidity is not present. If it is present it could influence the sizing of particles detected on a particle counter. This can occur because the vapour can attach to the particle having the effect of making the diameter of the particle appear larger to the particle counter. Also with an air sampler, water vapour could affect viable particles and their ability to incubate and could also influence the growth of bacteria in the gas line.

Testing for non-viable particles using a particle counter:

When testing a compressed gas line using a particle counter, ISO 8573-4 should be followed. The particle counter must have a diffuser attached. This prevents the sensor inside the particle counter from being damaged by diffusing the high pressure and maintaining desirable flow conditions that ensure the velocity of particles entering the particle counter are within the operating limits of the particle counter.

The gas tested must have its flow rate on the particle counter calibrated so that the offset (as opposed to ambient conditions) takes into consideration the gas being tested. Some gases, such as oxygen, may present hazardous conditions, such as explosive atmospheres. The manufacturer must always be contacted to verify compatibility of gases for health and safety reasons. The pressure should always be higher in relation to the flow rate of the particle counter, otherwise there is a risk of ambient air being pulled through the diffuser by the particle counter, making the test invalid. A sample of 1m3 is required. Compressed gas line pressure should be regulated to 1 bar as outlined in the standard. Particle counters operate between at 28.3 LPM or 50 LPM depending on model.1 bar may not be sufficient on particle counters with higher flow rates, normally 2.5 bar is enough pressure to prevent contamination of ambient air through the diffuser. The diffuser should be matched with the flow rate of the particle counter and air temperature should be 20°C.

Testing for viable particles using an active air sampler:

ISO 8573-7 should be followed when monitoring for viable particles. The air sampler should be fitted with a diffuser capable of maintaining laminar flow conditions so that particles pass through the sample head in a controlled flow; any disruptions would have a negative effect on the impaction of the particle on to the contact plate media, which could render the particle non-viable or the particle could bounce off the contact plate.

A 1m3 sample is required. The sample must contain an adequate label for identification and be incubated as outlined in the standard. Prior to sampling, both the sample head and diffuser must be sterilised.

Normally, after correct sampling and with the expectation that the compressor is functioning correctly, no colony forming units (CFUs) should be observed once the sample has been incubated. If CFUs are present they must be identified and the source of contamination should be found.

On the compressor side, filters should be checked or replaced if necessary. Dehumidifiers also need to be examined to ensure correct function. A dew point test upstream should suffice. All valves and connection points along the gas pipe should be visibly checked and leak tested.

Test reports

Once the sample data has been collected for viable and non-viable particles a test report is required. Each test report should contain the following information:

• Details of the compressor, including make, model number and classification.
• Details of the particle counter, air sampler, manometer including model number, serial number and calibration certificate number.
• Flow rate, sample time, volume of sample, pressure, temperature and humidity.
• Observation of any other contaminants (oil/water).
• Description of the point at which samples were taking.
• Actual sample data average concentration of particles/CFUs per m3.
• Diameter of non-viable particles tested with number of particles found at that size.
• Identification of CFU (bacteria and fungi).
• Date of test.
• Name of person who carried out tests.