• All forms of environmental sampling, except active air sampling, can be done in "background" aseptic filling rooms (Grade B) without significant risk to process or product. Only in the most compact filling rooms is the presence of a QA microbiologist for a few minutes in each shift likely to be significantly disruptive to air flows or operational disciplines. It should be remembered that the QA microbiologist is a fallible mortal from whom contamination may arise. Particular care should be taken with active air samplers that their exhaust air is not directed towards areas where product or product-contact components are exposed.
A comprehensive set of monitoring locations should be developed from:
- past experience of where contamination has actually been found
- opinion of where contamination may most likely occur
- knowledge of the locations where the highest nonviable particulate counts were obtained in validation.
All of these locations need not be monitored for every batch of product manufactured or on every monitoring occasion. A planned or randomized matrix approach may be taken. All locations should be carefully monitored over a reasonable period (e.g., weekly for a facility that is in frequent or constant operation). There should be data from each location for every day in the working week (e.g., monthly), and from each location at the beginning, the middle and the end of each working day (e.g., quarterly).
• Grade A areas are specifically protected to a high degree because the work done or the materials exposed in these areas is of particular risk. Monitoring should as far as possible avoid being intrusive. The best time to do any monitoring in these areas is at the end of the working period or shift. This is also supported by the as-yet unproven concept that microbiological contamination may, over a period of time between cleanups, build up in these areas.
Swabs should be reserved for difficult-to-clean areas. This means they are almost bound to be both intrusive and disruptive. Any traces of moisture or swab material (e.g., cotton) left behind in niches, nooks, crannies and roughened areas of filling equipment could end up damaging the product more than the value obtained from the data.
Most active air samplers will disrupt protective air-flow patterns and are therefore both intrusive and disruptive. The Sartorius MD-8 sampler can be adjusted to take an isokinetic sample and, although still intrusive, it may be used in laminar flow-protected areas with less disruption than other active air samplers.
The least intrusive and nondisruptive sampling method is the settle plate, which can only sensibly be used as a "real-time" monitor. The author's view is that the value of settle plate data does not outweigh the risk to the process of intruding into operational point-of-fill Grade A aseptic areas or into stopper hoppers, etc. This type of activity may be necessary to provide the data expected by European regulators. It is less risky to place settle plates in laminar flow units that may be used to protect autoclave off-load stations, storage cabinets, etc., and the practical value of settle plates in these areas should not be discounted. The settle plates should be set out at the time when work is done in these protected areas. Other physical monitors should be quite adequate to demonstrate that the equipment is performing as intended when personnel are not present.
As with the Grade B areas, a comprehensive list of Grade A monitoring locations should be developed. The most obvious location is at point-of-fill. Others may be on the stopper hoppers, forceps used for collecting samples or freeing jams, steriliser off-load stations, etc. Each filling room is unique and should have its own list prepared.
Locations that are only monitored at the end of the working period should preferably be monitored at the end of every working period. Settle plates used in laminar air-flow stations should be set out on every occasion of use as is normal in sterility testing laboratories. Operational personnel may set them out but it is probably in the best interests of "checks and balances" for microbiological QA personnel to retrieve them. Isokinetic active air samples may be monitored on a matrix basis with the same systematic or randomized coverage as recommended for Grade B areas. Other active air samples and swabs should be taken at the end of each working period but before the area and equipment are cleaned down.
Personnel working in Grade A and Grade B areas should be checked at the end of their work periods. Monitoring should be done in the change rooms. Glove prints should be done on each operator at the end of every shift. If the standards of training, disinfection, glove quality, discipline and supervision are high, the counts from glove prints are most likely to be 0 cfu, and the laboratory workload for counting and identification will therefore be low. It is best that microbiological QA supervise glove printing. Results relate back to the individual and doubtless some sensitive individuals would, if unsupervised, be tempted to take nonroutine steps to criticism, no matter how sensitively and objectively this may be offered. More complex garment monitoring may be done less frequently on a matrix basis but still covering all operators.
The program of personnel monitoring should include the personnel from microbiological QA who are responsible for environmental monitoring. Engineering and other personnel who may have reason to enter Grade A and Grade B areas should also provide, at the very least, glove prints.
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