Maintain cleanroom integrity to protect end-users
A clean environment is paramount when creating, testing or packaging medicines or other substances destined for human consumption or contact. Contamination can cause serious illness or even death. An environmental monitoring (EM) programme must demonstrate control over both viable and non-viable particles in critical areas. The methods used to achieve a contamination-free environment are the same regardless of industry or size of business.
The EU’s Good Manufacturing Practice (GMP) regulations provide for systems that ensure processes and facilities are controlled and maintained effectively. This means that EM programmes need to adhere to EU GMP best-practice. The 2022 revision of EU GMP Annex 1 further seeks to ensure the safety of end-users through stringent guidelines.
To ensure that the quality standards indicated by GMP Annex 1 are met, the air, personnel, surface areas, and specific areas of the cleanroom facility, all need to be monitored for microbial contamination. But what’s the best way to achieve and maintain a cleanroom, and the high standards set by Annex 1?
Choosing appropriate environmental monitoring methods
Understanding exactly what to clean and monitor, and where to focus these efforts, is the starting point to maintaining the integrity of your cleanroom. Both viable and non-viable particles can exist, and monitoring for both is important to understand the cleanliness – and thus safety – of your operation.
Non-viable particles that don’t contain living organisms can spread viable particles, so monitoring for these is critical to maintaining asepsis. Testing for viable particles includes methods for isolating bacteria, yeast and mould.
What and how to monitor in the cleanroom
Personnel: use contact plates and correct gowning procedures to minimise risk
People are the most significant source of contamination within a cleanroom. It’s essential to establish a specific routine that each staff member entering the cleanroom must follow. This could include doubling up on the use of personal protective equipment (PPE) and gowning, and minimising skin contact with the products, the cleanroom environment and facility.
To evaluate the effectiveness of the gowning process, monitor personnel by using contact plates. Contact plates are placed against areas of the body that could interact with sterile areas, and will indicate the presence of bacteria following a period of incubation.
Air: continuous monitoring, air samplers and settle plates
The air in the facility will be continuously controlled by HVAC systems. While parameters such as pressure, temperature and humidity may be continuously monitored, routine air sampling for both viable and non-viable particle counts will be conducted depending on the grade of room and operations. A selected volume of air will need to be sampled to identify any presence of such particles.
Real-time, continuous airborne microbial monitors such as Cherwell’s BAMS unit offer benefits of instantaneous alerts, meaning the potential to significantly reduce losses should contamination occur, ease of operation and useful data output for analysis. Machines such as BAMS use a laser to identify viable and non-viable particles in the air; this means there’s no wait time, no consumables, and no storage required for incubation of media plates. This combination of factors means such units are much more convenient and less labour intensive than traditional methods of air sampling.
Air samplers such as our range of SAS units draw a specific volume of air, which is passed over a media plate. Viable particles will “settle” on to the plate, and reveal the presence of any viable organisms following a period of incubation. Air samplers used for both viable and non-viable particle monitoring must be maintained and calibrated regularly to ensure optimum functionality and accuracy of results.
Settle plates are considered the standard passive air sampling method. These plates use Petri dishes that contain sterile growth media, typically Tryptone Soy Agar (TSA) or Sabouraud Dextrose Agar (SDA). The plates can be left exposed in the environment for up to four hours before their integrity becomes compromised. Take care when positioning settle plates, as they can easily be damaged or moved; settle plate stands can be used to help reduce these risks, and also ensure the plates are positioned appropriately, for example at working height but away from the work surface.
Although settle plates represent a low-cost monitoring method, accurately measuring contamination is almost impossible with this form of passive air sampling. A programme that includes real-time continuous monitoring such as that offered by BAMS, or a combination of both passive and active air sampling is therefore recommended.
Surfaces: two monitoring methods required for best results
Floors, walls and equipment must all be monitored and cleaned appropriately and regularly. Regular monitoring for viable particle counts should be implemented through use of contact plates, which will indicate the presence of contaminants following incubation.
Contact plates are used for surface monitoring, by preparing the culture media so that it protrudes above the sides of the dish. The plate is then pressed against the surface to be sampled; any contaminants present will stick to the media and become visible after incubation. Standardisation of this method can be achieved by using devices such as contact plate applicators.
Sterile swabs can also be used for the sampling and monitoring of surfaces. These are rubbed across the focus area, then transferred to a laboratory. The presence of microorganisms can be established through the sub-culturing on to culture media of any particles collected by the swab. This is common practice if the surface area to be sampled is not flat, or is difficult to reach.
Minimise losses, maximise production, protect consumers
Failure to adequately implement environmental monitoring of the cleanroom can have serious consequences for both end-consumers and your business. Using the appropriate method or combination of methods for effective monitoring can reduce risk.
A stringent environmental monitoring programme in line with GMP Annex 1 guidelines can not only reduce the likelihood of contamination, but also provide critical data to help identify areas of weakness. This will minimise potential losses arising from production outages, helping to maintain both output and industry reputation.
If you’d like to discuss the environmental monitoring solutions available from Cherwell, including our BAMS real-time continuous monitoring unit, air samplers, settle plates, contact plates, custom media and servicing, please contact our team on +44 (0) 1869 355 500.
