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Recent technological advancements may have put cleanroom monitoring into a state of flux.
Cleanroom monitoring is an industry that some reports estimate will be valued at as much as $7.1 billion by 2028 (1). In spite of that massive projected value proposition, however, many questions remain regarding the current (and future) state of the industry. How are recent advances affecting the field? What upcoming changes should we be aware of? Is the industry stable or in flux?
To learn more about the current state of cleanroom monitoring, recent advances in the field, and potential upcoming changes that might impact the industry, Pharmaceutical Technology spoke with the Alex McDaniel, Environmental Monitoring Program manager, Element; Joe Mundell, chief research officer, Sonicu; and Stephen Tierney, president, XiltriX North America.
When taken together their perspectives provide insight not only into the current state of cleanroom monitoring, but also into changes that may be cresting over the horizon. Topics of discussion include the current state of cleanroom monitoring, recent advances in the industry, upcoming changes, and more.
PharmTech: Broadly speaking, can you share your thoughts on the current state of cleanroom monitoring? Would you say it is in flux, or a relative state of stability?
McDaniel (Element): Over the course of the past six years, it has been apparent the current state of cleanroom monitoring is always seemingly in flux. As the industry works to align the methodology, frequency, and validation of a formal environmental monitoring (EM) program, many applicable guidance documents and standards are undergoing revision. This includes USP [United States Pharmacopeia] General Chapter <797> (2), which is (hopefully) nearing the finish line of its long overdue revision. An increased frequency of surface sampling within the cleanroom suite is anticipated in the USP <797> revision, in addition to changing the organism identification requirements to be more pragmatic to delivering patient care.
In the current good manufacturing practices sector, the EU Annex 1 revision will emphasize the increasing need for a contamination control strategy, whereas the current version lacks specificity on this. A more consistent and patient-focused approach to EM will be embraced by the industry, as the Annex 1 revisions will impact cleanroom monitoring, especially as it relates to an enhanced focus on conducting a risk assessment of the activities within the facility.
Mundell (Sonicu): Cleanroom technology is rapidly evolving as more healthcare and life science customers migrate to the cloud and demand mobile-first solutions that are always on and can be accessed from anywhere. Moreover, clients are looking for monitoring solutions that both integrate with and serve as a multiplier for their BMS/BAS [building management system/building automation system] systems.
PharmTech: Can you discuss some of the most recent advances in cleanroom monitoring? What makes these technologies fundamentally different from those that came before?
Tierney (XiltriX): Some of the recent advances in cleanroom monitoring would be continuous particle counting and measurements, such as volatile organic compounds (VOCs), becoming more and more ‘the norm’. Technologies never fundamentally change because it’s evolution, not revolution. Legislation and regulation would not be able to keep up if it were the latter.
[Increasingly] sensors [are being seen] in a single system. For example, analog magnehelic differential pressure sensors can now be digitally integrated into an [environmental monitoring system] alongside a room’s conditions and particle counters, as well as the equipment stored inside.
McDaniel (Element): Rapid microbiology has garnered a great deal of interest, yet it remains an unknown quantity and certainly does not look to unseat conventional microbiological testing methods in the near future. The turnaround time for traditional incubation of viable media is its primary pain point, as it takes a minimum of (roughly) a week to 10 days, depending on duration of media dual incubation conditions. This does not include the time microbial identification and reporting takes. Rapid test methods allow for quicker batch release and insight into the state of microbial control, as firms can receive insight into potential growth of bioburden much sooner (some within minutes or hours).
Fundamentally, the validation process for this is not necessarily as straightforward as traditional methods. Guidance documents like USP <1223> Alternative Microbiological Methods (3) are a good starting point to consult when considering validation of this system. The data comparison is not ‘apples to apples’, as the rapid method employs the use of technologies like ATP [adenosine triphosphate] bioluminescence and viability staining to detect the presence of viable organisms. Rapid forms can cover a wide range of assays, from bioburden of raw materials to sterility confirmation, water monitoring, and active air sampling. However, it is important to ensure that rapid methods are of equal or better quality than traditional testing.
PharmTech: Has there been any recent changes in what customers want in their environmental monitoring systems? If so, how has the industry changed to accommodate it?
Tierney (XiltriX): Data security is continuously becoming more stringent every year. Since the pandemic, life science facilities have been in greater need of remote accessibility; to have full insight into everything going on in a facility, no matter where the staff are located. [Facilities’ operators] want their electronic management systems more integrated with other critical systems like LIMS [laboratory information management system], building management systems, electronic lab notebooks, batch records, asset management, [and so on].
McDaniel (Element): Along with automation, clients are asking for trended data from their monitoring projects. While trending is a wide-ranging regulatory requirement, it is currently performed via a very manual process. To produce better reports that feature trended data as a standard inclusion, [Element implements and uses] LIMS.
Compressed gas testing is also more frequently requested in the industry. Including secondary points, such line drops within the building that are not routinely monitored, can provide a holistic diagnosis of how the entire system is performing versus a fragmented approach of selecting only certain locations. [It is expected that there will be a] significant increase in this [request] moving forward, especially in terms of validating a previously installed system.
Within the next several years, the momentum will likely swing towards systems that can provide continuous and automated sample collection during a production run. Some processes are still performed in a very manual way and require a great deal of human intervention, from differential pressure monitoring, temperature, and humidity data, or non-viables. Some manufacturers of monitoring devices are also developing viable particle counting units to provide real-time data of colony forming unit (cfu) counts with the use of laser technology similarly used for non-viable particle count testing.
PharmTech: As the EU GMP Annex 1 revisions edge closer to publication, what changes, if any, will this make to environmental monitoring specifically? If we’re anticipating significant change, what future-proofing (if any) are you seeing in customer orders?
McDaniel (Element): There is an increased onus on manufacturers to implement and document a contamination control strategy and a vigorous risk assessment within the pharmaceutical quality system. Manufacturers may need to completely overhaul their program to include additional sampling locations if a formal monitoring program was not previously established, or the original program was not updated to reflect current processes or was based upon previous facility designs. An increase in EM performance qualifications conducted on existing cleanroom areas to align with an updated and more modern approach to the documented risk assessment [is expected].
Given the push to take a comprehensive look at processes to identify failure points and consequences of those failures in the upcoming Annex 1, using the failure mode and effects analysis (FMEA) tool has worked out well for clients looking to future-proof their risk assessments.
PharmTech: Do you have any final thoughts on the topic that you can share with our readers?
Mundell (Sonicu): [A] greater attention from larger healthcare systems to include air pressure differential and humidity as well as O2, CO2, and VOCs [is being witnessed]. Infection control experts are driving the conversation as part of their risk management focus while construction firms are being consulted on both new build and retrofit projects to work collaboratively on these projects. [Additionally, a] significant demand relative to pre-COVID [is being seen] and [this is] expected to continue accelerating.
McDaniel (Element): [From personal experience, it is apparent that] critical gaps within an operation may not be identified until it is too late. Downtime can be eliminated, back-end costs reduced, and production lines will stay in operation if those within the industry tasked with maintaining compliance to these standards establish documented protocols in partnership with a subject matter expert (SME) and team of microbiologists.
As professionals, [there is] a responsibility to seek out continual education, as well as educate others in the industry. Establishing a partnership with a collaborative organization with a consultative team invested in teaching others is vital to staying on top of these dynamic requirements—and that is only the beginning. Selecting a firm that has a robust scope of service offerings and quality procedures that can look at processes, provide a gap analysis, establish methods to help mitigate contamination control before it becomes problematic, and even assist in validating a cleaning and disinfection program is a gamechanger when the FDA walks through the door.
Grant Playter is the Assistant Editor at Pharmaceutical Technology.