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Microbes aren't your only threat: the risks of environmental monitoring

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Microbes aren’t your only threat: the risks of environmental monitoring

Abstract

The process of Environmental Monitoring in Microbiology labs is open to a range of risks which threaten the integrity of data - particularly for labs using paper, Excel and other legacy systems. Such risks in the Pharmaceutical and healthcare industries can have consequences from heavy fines and suspension of licences to the endangerment of a human life. By moving to a paperless system, these dangers can be significantly reduced.

Problem Statement

In the highly regulated world of Pharmaceuticals, Environmental Monitoring is essential for patient safety. The process, however, is not without risks of its own; in labs using paper and Excel or other legacy systems, despite your best efforts there are numerous actions that can cause risks to your lab, from heavy fines to even something as priceless as a patient’s life.

Background

Environmental Monitoring process and risks

The medicines produced in Pharmaceutical cleanrooms must be free of contaminants, to prevent exposing patients to particles which are not part of the intended composition of the medicine (1). The level of purity for a product varies depending on its pharmaceutical class; for example, orally administered chemical pharmaceuticals often have a high limit so as such, can be manufactured in cleanrooms of a lower grade. For injected medicines, even small quantities of contaminants are unacceptable, in which case a grade A cleanroom - which is sterile - is appropriate. Environmental Monitoring is used to assess the sterility of a cleanroom, to ensure that acceptable limits - set according to the grade of the cleanroom by regulatory bodies - are not breached, providing increased assurance as to the quality of products sent to patients.

Whilst for the above reasons Environmental Monitoring is essential, there are risks associated with the process, particularly for labs using excel or other legacy systems, which can lead to a lack of validity in data. If this is the case, a lab cannot be sure if limits are breached, putting patients in danger.

Figure 1 shows the stages of Environmental Monitoring for a typical lab. The first two stages – setting out and labelling plates – are carried out in the cleanroom, and particularly in labs with a high throughput, are open to association errors. Often in these environments there is pressure on staff to be productive, enhancing the risk that piles of plates get mixed and so a plate could be set with the incorrect label. In this event, the data collected from the plates is inaccurate.

Figure 1: The process of environmental monitoring

The plates are then sent to the lab which, depending on the facility, may be external. When the lab receives the plates, they should transcribe the data on the labels before incubation. There are several risks at this first transcription stage; many labs transcribe onto paper, which is not a permanent record. At every transcription stage, there is naturally a risk of human error, but when paper is used this is increased due to a lack of legibility. Furthermore, paper records can easily get misplaced. These breaches of the ALCOA+ principles of data integrity - as shown in Figure 2 - mean that even at this early stage, the data may not be trustworthy.

Figure 2: The ALCOA+ Principles

The next stage for the plates should be incubation, however, some facilities incubate plates before they record the data on the plate labels. If this is the case, data integrity is further reduced as plates could be lost before the data is recorded, meaning there is no evidence that they were received. This is particularly an issue if the plate would have indicated a limit breach, which would as a result have been missed.

Once the data has been recorded and plates incubated, the plates are then read. There are two main risks at this stage; firstly, a count risk which could have consequences especially in grade A environments, as if underestimated - which is particularly a risk should the count be on the border of being acceptable - there could have been a limit breach. The second risk is confusion; identifying the limit for the specific area the plate is associated with is heavily reliant on human memory. Particularly if there is high throughput, there is a possibility that breaches could be missed due to confusion as to what the limit is.

A way to minimise the risks associated with reading plates is through second checking. Whilst this should be standard practice, it doubles resource for the lab and as such is not always carried out. Second checking can be blind, where the second person checking the plates is not aware to what the first person had read. Alternatively, the second checker may be aware of what was initially recorded and may simply check that they agree. Blind checking is preferable as it reduces bias and therefore increases reliability of results. In some labs, photos of the plates may be taken. Whilst this is useful, there are risks of the photo being poor quality due to lack of controlled lighting. Furthermore, should the photo be downloaded from a device there is a possibility of a labelling risk, where the wrong image may be associated with a record.

The next stage is recording data. This second transcription stage is open to the same issues as the first, but also has risks of its own such as association through recording data from a plate onto the wrong piece of paper. When the plates have been read and the number of growths confirmed, they may be discarded if there were no growths to investigate, or they may again be incubated if further investigation is required. Investigations should be thorough and promptly identify the root cause of contamination (2). However, this is a challenge for labs using legacy systems who lack access to the relevant information in a timely manner. As a result, taking action may be delayed, or even in some cases no action may be taken as by the time any conclusions are drawn, the underlying event(s) has long passed and conditions have changed to the extent that a conclusion based on old information may be out of date.

The next stage involves transcribing the data again from paper to Excel or a similar system. Like previous transcription stages, this is open to an array of errors. Data is not attributable to the individual who originally recorded the data. Handwriting from the paper could be illegible and so recorded incorrectly. Data is not contemporaneous as it would not correspond with the original time data was recorded. By using paper, the data is not original. Multiple transcriptions decrease accuracy of the data and on Excel an audit trail is not able to be created. Due to the nature of the large excel files, there is a risk of the file crashing, meaning data is not enduring, available and potential data losses make the file incomplete. Therefore, at this point every one of the ALCOA+ principles could have been breached.

In addition to the breach of the ALCOA+ principles, on Excel like systems it is very easy to enter information onto the wrong line or tab. If there are high volumes of plates, this process is time consuming and monotonous and so there is increased risk of human error. If there is a backlog, there is also a risk that the paper may be lost, but there could also be delays in transcribing the data due to its time-consuming nature, holding back any investigations and trending.

The final stage is trending; this relies on the ability of staff to be able to identify and understand trends and be competent with Excel or the system used. There are also limitations with the tool, for example, to predict future trends making the lab reactive. If a trend is identified, due to the numerous errors discussed above there is a lack of trust in the data, so they are often ignored.

Consequences

Whilst an awareness of the risks themselves is important, understanding the consequences is even more so. Internally, QC labs require much resource but are often seen by the wider business as lacking value. Limited insight and responsiveness to the business needs due to information not being readily available contributes to this view, resulting in pressure from senior executives to enhance performance. In fact, studies suggest as many as 39% Quality professionals name economic performance as their main goal for 2020, even above compliance (3). However, for labs using legacy systems with multiple time-consuming transcription stages, this will prove a difficult goal to achieve.

Externally, consequences may be more severe. It is suggested that the number of warning letters and statements of non-compliance with GMP citing data integrity alone has tripled since 2013 (4); as a result, labs face increasing external scrutiny, heavy fines and in some circumstances, temporary suspension of manufacturing licenses or even licence removal. Ultimately though, the consequences stretch far beyond impact to business; by being unable to identify breaches and react to trends means that patient safety is at risk. In extreme circumstances, contamination could result in a patient becoming seriously ill, or even death. Minimising errors and risks are therefore of upmost importance.

Solution

Risk-reducing Environmental Monitoring software such as Microgenetics SmartControl modernise labs by removing the use of manual data entry, paper and Excel spreadsheets, helping labs to become compliant with GMP and maintain the ALCOA+ principles of data integrity. Figure 3 shows the Environmental Monitoring process with SmartControl.

Figure 3: The environmental monitoring process with SmartControl is more efficient that legacy systems (compare to figure 1), whilst maintaining the ALCOA+ principles.

Through minimising manual data entry, the risk of transcription errors is reduced making it easier for data to be correct upon first entry. Entering a sample takes 5 seconds and notification of limit breaches is instant, saving time throughout the Environmental Monitoring process which could otherwise be used to second-check plates or innovate.

SmartControl also comes equipped with a photobooth - a high resolution 4k photo capture device with controlled lighting, to ensure good quality of photos of every plate. These photos are stored on the cloud along with the data, making the original records and any subsequent amends easily accessible to multiple users and providing an audit trail.

SmartControl is able to carry out in-depth analysis of data captured in minutes, allowing labs to better understand their results and identify trends. In addition, SmartControl also offers machine learning tools, where it can conduct automated deep analysis of your data, uncovering previously hidden trends and enabling labs to be pro-active rather than reactive.

To see a summary of Environmental Monitoring risks and how SmartControl can help, download our free PDF.

Conclusion

Whilst Environmental Monitoring is important in a lab to ensure the sterility of a manufacturing facility, the process is open to a number of risks in labs using legacy systems such as paper and Excel. Such risks result in a lack of adherence to the ALCOA+ principles of data integrity, and therefore open the lab to consequences from external scrutiny and heavy fines to possible patient harm. To prevent this, there are software solutions such as Microgenetics SmartControl, developed in line with GMP Annex 11 and MHRA data integrity guidance. Such solutions remove the paper from labs, reduce manual transcription and therefore minimise the overall risk.

References

  1. World Health Organisation (2012) Environmental Monitoring of Cleanrooms in Vaccine Manufacturing Facilities: points to consider for manufacturers of human vaccines [PDF]
  2. Gupta. R (2014) Role of Environmental Monitoring and Microbiological Testing During Manufacture of Sterile Drugs and Biologics, American Pharmaceutical Review [Online]
  3. Hamilton. M.J New report indicates fewer pharmaceutical industry quality professionals believe compliance is the top goal compared to 2018, and most believe data will impact performance Biospace [online]