Air sampling has become increasingly important for pharmaceutical manufacturing procedures. John Cobb, Biotrace International, offers World Pharmaceutical Frontiers insights on current developments.
When a sterile pharmaceutical product is manufactured in a controlled area or cleanroom, an accurate measurement of the bioburden (viable bacteria, yeast, moulds and spores) is essential. Alert and action levels need to be appropriate to the classification of the area. The air quality adjacent to critical areas is the most significant indication of a product’s contamination risk.
Active air sampling entails that air in a cleanroom is sampled kinetically during a manufacturing process. This is done continuously in a controlled way by counting the number of viable or living organisms per cubic metre of air. Passive sampling, however, is used to measure organisms which have dropped onto surfaces. This is assessed by other means (settle plates and contact plates).
When a batch of sterile products is manufactured in a controlled area, it must meet certain sterility criteria to be released. The raw materials and finished products require sampling and need to be sterile. In addition, the environment and the people working in it must fulfil the standards required for the controlled area. This environmental monitoring is the basis of parametrically releasing pharmaceuticals.
There is also a requirement to test sterile gas lines regularly for the absence of viable organisms. This includes the frequently applied compressed air and nitrogen lines for driving processes and inertly packing products.
Innovative samplers
‘Air trace environmental slit-to-agar impaction samplers are used for active air sampling,’ John Cobb explains, ‘as part of an environmental monitoring programme in a critical area or cleanroom.’ The accuracy of the calibrated airflow rate and sampling of air are fundamental in meeting the regulatory requirements to control these types of critical areas (ISO 14698-1).
‘Air trace compressed gas slit-to-agar impaction samplers can be used anywhere a sterile gas line is present,’ Cobb continues. These gas lines are found in cleanrooms, in hospitals, in bottling and brewing plants and so on. All sources of compressed gas need to be tested routinely for the absence of contamination. All gas lines should be fitted with in-line bacterial block filters, but sampling still needs to be performed to check the integrity of the system.
A calibrated, known volume of environmental air (in the air trace environmental sampler) or compressed gas or air (in the air trace compressed gas sampler) is drawn through a precision cut slit, which increases the velocity sufficiently to impact any viable particles which may be present onto the agar surface of a 140mm petri dish immediately downstream of the slit. This dish revolves at a known rate (which may be adjusted). Therefore, after incubation the numbers of organisms grown per chosen volume of air or gas (typically per cubic metre) can be counted.
This method is known as slit-to-agar impaction and is the preferred method of regulatory authorities all over the world. The main advantage of this method is the accuracy and reproducibility of its results, which allows for validation against the international standard ISO 14698-1 for the control of cleanrooms and critical areas.
Other designs of samplers may produce turbulence in a critical area, may desiccate or damage viable organisms during sampling, or may not have sufficient sampling velocity to collect an appropriate percentage of organisms present. ‘Both Biotrace samplers, Air Trace Environmental and Air Trace Compressed Gas, can be calibrated for accuracy of performance traceable to International Standards. A major advantage of Air Trace Environmental is that it has been third party validated by the MHRA for the physical efficiency of all viable particle sizes encountered,’ Cobb says.
Future sampling
Even though various real-time rapid methods have been considered for both environmental monitoring and compressed gas testing, there is no current move away from the classical microbiological method of growing, counting and identifying contaminating organisms. This is particularly important for trend analysis of isolated organisms, when resistant or persistent contaminants can be assessed and eradicated at source.
Human intervention is the main cause of contamination in cleanrooms and other critical areas. ‘Current thinking about the operation of a cleanroom used for the sterile manufacture of products includes minimising human intervention by using an increased level of robotics’. Cobb suggests. However, continuous active air sampling throughout an entire production run will be required to check for any possible contamination by ingress of undetermined origin.
The AIR trace environmental slit-to-agar impaction sampler has been designed for continuous use during a production run, with minimal human intervention when a plate is changed. This is achieved because the user is able to vary the speed of the agar plate’s rotation, which is central to its testing method. This may be a compromise to compensate for the absence of human intervention, but at least it is minimised to a more acceptable level.
Asked about innovations Biotrace International is currently working on, Cobb says: ‘We cannot go into detail on our current developments, as all projects are confidential and cannot be discussed until launch. However, the company is committed to staying at the forefront of new technologies and is continually looking to improve and develop its products in line with customer requirements.’