The people factor: investigating the gown

While individual results are rarely of significance, a well-designed environmental monitoring programme signals conditions contributing to rises in microbial levels. Shifts in microbial trends can be due to ineffective cleaning, disinfection, faulty air handling systems, material and equipment transfer, and personnel-related issues.

The majority of contaminants dispersed into cleanrooms derive from personnel.¹ For this reason, environmental monitoring extends to people and, for aseptic processing areas, this includes plates taken on exit of the operator’s gown.² Special clothing designed for the clean environments is required because the human body creates its own micro-environment of potentially damaging particulate contamination. To be effective, clothing must:³

• Form a particulate barrier for the human micro-environment
• Allow freedom of movement and be comfortable
• Address any specialist requirement, eg, static dissipation
• Avoid being a significant particulate contributor itself.

Personnel monitoring is required under EU GMP Annex 1 and by the FDA guidance for aseptic filling, in relation to the aseptic processing of sterile drug products. Such monitoring focuses on the monitoring of gloved hands (where samples, via finger dabs, are taken during operations, especially following critical activities) and gown plate monitoring (where samples are taken on exit from the aseptic core, since the act of sampling compromises gown integrity). Such monitoring is particularly important when personnel are required to break the aseptic core and undertake an intervention.

Table 1: Gown plate results by location

Detecting contamination on the gown either indicates a concern with the practices of an individual operator or a problem with the gown itself. This paper looks at several aspects of gown wearing through a review of data collated over a one-year period. The data was studied for four considerations:

• Locations most likely to indicate contamination
• Differences between re-laundered and single-use gowns
• Variations of gowns when re-laundered
• Variations in efficiency of gowns when worn over time.

Analysis of these considerations concluded that: the top of the head is most likely to indicate contamination; there are no differences between re-laundered and single-use gowns; gowns re-laundered up to 50 times showed no significant differences; there is a slight rise in recorded counts when gown are worn for four hours or more. Importantly, these assessments relate only to the data sets they were drawn from, which relate to cleanrooms located in the south-east of England. Other variations may occur based on cleanroom type and geographical locale.

Cleanroom gowns

Gowns can be ‘reusable’ or single-issue. Reusable gowns are subject to washing (re-laundered), followed by packing and irradiation. Reusable cleanroom fabrics are manufactured using 100% continuous filament polyester and continuous filament polyester/carbon combination yarns to minimise particle shedding. Non-woven fabrics are constructed of a polyolefin fibre and used in disposable cleanroom garments. All cleanroom gowns are designed to act as filters, allowing air to pass through but to retain microorganisms. There is little difference between re-laundered and disposable gowns – the choice comes down to operator preference or company economics.

While the difference between gown types may not overly matter, there are a number of factors to consider when selecting a suitable gown. These include thickness, weight, flexibility, filtering properties, durability and comfort.⁴ Assessing these requires a review by the cleanroom manager supported by the microbiologist. Gowns worn in aseptic processing areas need to be sterile and they should only be worn for one session before being sent for re-laundering or disposal. Further to aseptic processing, cleanroom gowns are not worn over street clothes; instead operators strip down to their undergarments and don a polyester under-suit. Once the under and outer gown have been put on, gloves, facemasks and goggles are put on. Importantly, there should be no exposed skin.⁵

Table 2: Disposable and re-laundered gowns compared

Table 3: Comparison of gown data at start and end of re-laundering

Gown monitoring in aseptic processing areas

The monitoring of cleanroom gowns, for each staff member, on exit from aseptic processing areas is of great importance for assessing the risk to processes and products. This is because most contamination can be traced to humans working in cleanrooms. This is, in some way, evidenced from the association of microorganisms transient or residential to skin being the primary isolates from environmental monitoring in controlled environments (organisms like staphylococci, micrococci and corynebacteria). Personnel shed high numbers of skin cells, mostly as skin flakes, and even the best cleanroom garments cannot contain all human detritus (at least not as time progresses). The significance of this is that people are not only a source of contamination, but are also an agent for transferring contamination to locations that could pose a product risk.

To assess the likelihood of risks, locations on the gown are monitored through the use of agar contact plates. The locations selected will vary between organisations. Typical locations monitored include:

• The hood
• Left and right arms
• Torso
• Left and right leg.

It is also typical to sample the facemask. Facemasks control, to a degree, the risks associated with personnel coughing or sneezing, and the release of streptococcal and related organisms. Facemasks are not discussed further. Sampling typically uses a 55mm plate with TDA/SCDA media. The plate is pressed against the sampling locations for a specified time period (typically 3-5 seconds; the time selected should be qualified). For suit contact plate monitoring limits, EU GMP Annex 1 provides no guidance. Many practitioners apply the same limits as per finger dabs taken under EU GMP Grade B conditions (maximal value of 5CFU per plate).

Table 4: Comparison of data for standard gown wear time and maximum wear time

Assessing suit contact plate data

Data collected from suit contact plates not only informs about personnel in relation to specific batch activities, it can provide interesting information in relation to gown control. In relation to this, the author assessed 2,952 personnel sampling sessions (and by inference from the same number of gowns worn) across a 12-month period in relation to an aseptic processing facility in northern Europe. Five samples were taken from the suit (n=14,760). With the gown types, 952 of the samples were taken from disposable gowns and 2,000 from re-laundered gowns. The re-laundered gowns were at different stages of their re-use maximum (which was set at 50 cycles of re-use). The data was analysed against several measures of interest. These measures are not designed to be definitive but to provide a benchmark for other pharmaceutical organisations to compare their own findings, should they be minded to do so, against.

Examination 1: Does a worst-case location exist?

The data from the five locations, for the 2,952 gown monitoring sessions are shown in Table 1. This indicates that out-of-limits results are relatively rare; however, the location most likely to record an out-of-limits result and which also records the higher count is the hood (the covered head of the operator).

Examination 2: Differences between re-laundered and single-use disposable gowns

The data relating to re-laundered gowns (n=2,000) was compared to data from disposable gowns, with the outcomes given in Table 2. The data suggests, based on descriptive statistics, that the results obtained from re-laundered and disposable gowns are broadly similar and there are no apparent operational differences between them.

Examination 3: Variations in gowns when re-laundered

The policy of the organisation surveyed was that gowns can be re-laundered and sterilised up to 50 times (with this being controlled through a bar-coding system). The limit is intended to safeguard the gown integrity, because the number of wash cycles and doses of gamma radiation could adversely affect the weave of the gown). For the 2,952 gowns worn, 650 reached the maximum of 50 re-launders (the gowns were at different stages when the review began). A comparison of data (five samples per gown) for the start and end of the gown use is shown in Table 3, indicating no appreciable decrease in gown efficacy.

Examination 4: Decrease in gown effectiveness over time

The fourth examination looked at whether gown effectiveness altered over the length of time that the gown was worn. The policy in place during this study was that the gown could be worn for four hours, after which time it should be changed. This was in recognition of operator comfort and the length of time operators should spend in the area between breaks. On occasion, operators needed to stay in the area for longer, although there were only 25 occurrences. Here, the maximum time was seven hours. Table 4 presents a simple review of the data. Although limited, the data suggest a higher rate of out-of-limits results through increased gown wear time.

Summary

The data presented in this article has focused on gown use, and several aspects of gown use by operators working in an aseptic processing area have been compared. Although data was limited by being tied to one facility and only covering a one-year period, some inferences can be drawn. Examination 1 looked at five different locations to determine whether one location produced a higher proportion of out-of-limits results than another. The data here suggest that a sample of the hood produces more out-of-limits results and a higher mean count. This may relate to the head being one of the hotter regions of the body. There is also a possible connection, although one that would need to be explored separately, to a higher incidence of counts with people who exhibit male-pattern baldness or alopecia areata. Examination 2 compared some data for re-laundered gowns against disposable gowns and showed no apparent difference. The choice between gown types remains one of personal preference and business economics. Examination 3 considered the life-expectancy of re-laundered gowns. Here there are several measures that can be performed on re-laundered gowns, including microscopic examination and particle generation. There was no measurable reduction of efficiency in the gowns’ ability to retain microorganisms after 50 cycles of re-laundering and sterilisation. The final examination, number 4, looked at the length of time a gown (in this case all re-laundered gowns) can be worn for. Data was limited by the low number of occasions where the gown had been worn past four hours and the lack of available data as to how many times the gown had been re-laundered. Moreover, no measures were available for ambient temperature and humidity. Nevertheless, the data does suggest a difference and a potential decrease in efficiency. This may arise through increased operator perspiration, which could impact on the weave and hence the filtration efficiency of the gown. While further data is clearly needed, the data suggests that applying a limit to the length of time that a gown can be worn within an aseptic facility is an important contamination control measure. With each of the examinations it was unknown how well the operators undertook gowning (in terms of their gowning technique) and the extent of the activities they undertook (including the physicality of their actions). These factors can have a bearing on the overall counts obtained. This is overcome, to a degree, by the relatively high number of samples collected (almost 15,000), which will help normalise the data set. The aim of the analysis, and hence this paper, was to highlight the importance of gown control, especially in the context of personnel being the main source of contamination in the cleanroom. As the research presented demonstrates, control is not simply about donning the gown in an aseptic manner (important though this is), because good practices extend to the maximum wear time and the nature of the operations. While not definitive, the data could help cleanroom microbiologists to benchmark data from their own facilities and help to review environmental monitoring results.

About the author

DR TIM SANDLE’s primary role is Head of Microbiology at Bio Products Laboratory, a sterile products manufacturer. In addition, he is a tutor with the School of Pharmacy and Pharmaceutical Sciences, University of Manchester, for the university’s pharmaceutical microbiology MSc course, and a longstanding committee member of the pharmaceutical microbiology society Pharmig.

References

1. Hyde W. Origin of bacteria in the clean room and their growth requirements. PDA J Sci Technol. 1998;52:154-164.
2. Sandle T. Environmental Monitoring: a practical approach. In Moldenhauer, J. Environmental Monitoring: a comprehensive handbook. 2012. Volume 6, PDA/DHI: River Grove, USA, pp 29-54.
3. Ramstorp M. Microbial Contamination Control in Pharmaceutical Manufacturing. In Saghee MR, Sandle T, Tidswell
   E. (Eds.) Microbiology and Sterility Assurance in Pharmaceuticals and Medical Devices. 2011 Business Horizons: New Delhi. pp 615-701
4. Eudy J. Cleanroom garment selection. Controlled Environments. 2014;17(4):8-13
5. Sandle T, Vijayakumar R. Cleanroom Microbiology. 2014. DHI/PDA: Bethesda, MD, USA, pp 80-85.