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Environmental monitoring of sterile fluid production facilities
Journal of Hospital Infection (1982) 3, 201-207
Letters to the Editor Sir, Environmental
monitoring
of sterile
fluid
production
facilities
I read with interest the leading article by Dr Gillett (1981), concerning the production of sterile fluids in hospital pharmacies. However, there are several points raised in the article, which require further comment. Firstly, I would like to dispel the idea that the intervention of the Medicines Inspectorate has seriously jeopardized the manufacture of sterile fluids in hospitals. On the contrary this intervention has brought about a long needed stream-lining and rationalization of the products made. Consequently, products which can be made more efficiently and cheaper by the pharmaceutical industry with their superior facilities are, on the whole, no longer manufactured in hospitals. Those manufacturing units which remain in hospitals are more and more concentrating on specialist products. The fact that fewer manufacturing units are now in operation means that the staff who work in these units are now more specialized, better trained and possessing a greater expert&e in the production of sterile fluids. The second point worth commenting upon is the statement of Dr Gillett that ‘it is the failure to provide such facilities which has led to the closure of these departments’, Most hospital pharmacy departments have a small inexpensive manufacturing facility, where small numbers of specialist items are made up on a named patient basis or for a particular clinic on a particular day. Large-scale manufacturing in hospitals is now more centralized. These units are initially expensive, but very quickly pay for themselves by being more efficient and requiring fewer staff than several smaller units. However, there can surely be no compromise on facilities in units where products are not terminally sterilized, but are manufactured aseptically by filtration. Regarding the extent of environmental monitoring which is carried out in hospital pharmacies, first of all I would be interested to know the source of the figures for the West n4idlands Region, since no such figures are available to the Quality Controllers in the West Midlands Region and as far as I am aware no detailed survey has been carried out to compile such figures. Consequently, I would question their accuracy. Even if we accept those figures, 22,000 specimens in one year in the largest region in the country, where there are several sterile manufacturing units, is not a large number and considering that approximately 60 per cent of these specimens (Dr Gillett’s figures) are settle plates, then it is a small effort, divided between several laboratories, for the sake of safety. A breakdown of the environmental monitoring in the West Birmingham Health District, where there are two manufacturing units, one for sterile products and one for non-sterile products (for which it is desirable to keep the levels of contamination to a minimum), reveals that in 1981, there were 952 settle plates, 968 contact plates and 194 swabs taken in the sterile laboratory. There were also 392 201
202
Letters
to the Editor
settle plates in the laminar flow cabinet sited in the non-sterile laboratory. Other microbiological monitoring included 192 viable counts on still water and filtered and unfiltered bulk solutions. The total amount of time spent in microbiological monitoring was very small compared to the amount of time spent in chemical testing of raw materials and products and was small compared to the amount of time spent on thermocouple testing of sterilizers and performing sterility tests. If anything it is the actual sterility tests which are the most time-consuming aspect of microbiological control of pharmaceuticals. It could be argued that if the environment, the in-process controls, the final sterilization procedure and the closure efficiency are carefully monitored, then the sterility test is merely a formality. In the West Birmingham Health District, we would be very concerned about a genuine failed sterility test. In 1981, we performed 474 sterility tests and had 11 failures all of which passed on a retest and were consequently attributed to contamination by the operator. The microbiological monitoring we perform gives us the confidence that our production facilities are of a suitable standard. Furthermore, the results can give us a great deal of information such as, where the areas of higher contamination risk are, whether our cleaning procedures are adequate, whether our air filtration system and laminar flow cabinents are functioning properly. It is worth noting that about half of the settle plates taken were for the monitoring of laminar flow cabinets. We have on one occasion been able to pick up a leaking filter very quickly by this method and it is our experience that, contrary to the findings of Whyte, Bailey and Hodgson (1979~~)the integrity of the HEPA filter makes a great deal of difference to the numbers of airborne microbial particles in a laminar flow cabinet. In summary then, I feel that the case against expensive sterile production units and time-consuming and expensive environmental monitoring is somewhat overstated. In the long-term, the expense is low compared to the cost of buying these products from the pharmaceutical manufacturers, made under special licence. The time-consuming monitoring is not so time-consuming as has been implied and the cost of materials for monitoring is minimal. Set against these disadvantages are the advantages. The need to install costly air filtration systems has meant better air conditioning for staff working in sterile fluid production units, has led to a rationalisation of sterile fluid production and has given pharmacists greater confidence in the products they make. Furthermore, although there is an argument to the contrary (Whyte, Bailey and Hodgson, 19793), it is my experience that the improvements in manufacturing facilities have greatly reduced the levels of particulate contamination in sterile fluids. I remember not so many years ago making water for irrigation in a prefabricated hut and having to discard 60 per cent of every batch because of gross particulate contamination, which could only have come from the manufacturing environment. Once an air filtration system is installed the advantages of monitoring it are obvious. Continuous monitoring acts as an early warning of a malfunction and monitoring can highlight problem areas.
Letters
203
to the Editor
Since the introduction of the Guide to Good Pharmaceutical Manufacturing Practice (HMSO, 1977), the record for the manufacture of sterile fluids in hospitals has improved greatly and although it may be argued that the standards set are unnecessarily high, it can also be argued that one contaminated bottle is one too many. It is better to be safe than sorry. Dudley Road Hospital, Birmingham
T. Deeks
References Gillett, A. P. (1981). Production of sterile fluids in hospital pharmacies. Journal of Ilospital Infection 2, 113-l 15. HMSO (1977). Guide to Good Pharnuzceutical Manufacturing Practice. HMSO, London. Whyte, W., Bailey, P. V. & Hodgson, R. (1979~). Monitoring the causes of clean room contamination. Manufacturing Chemist and Aerosol News, September, pp. 65-81. Whyte, W., Bailey, P. V. & Hodgson, R. (19796). The sources of contamination in bottles of infusion fluid. The Pharmaceutical Journal 223, 173-174.
Sir, Incidence
of nosocomial
infections
in the University
Hospital,
Jeddah
Since the opening of this 166-bedded hospital four years ago, the infection control committee has monitored hospital-acquired infection. The type of infection and organisms isolated were recorded. Table I shows that over a 12 month period 181 out of 5386 (3.4 per cent) patients were infected: 60 per cent of those infections were in the surgical or neonatal departments. Table II shows that the most common infections were of surgical wounds and the urinary tract. Gram-negative bacilli and Staphylococcus aureus were the most frequent isolates. (Tables I and II overleaf.) The overall infection rate is fairly low and the type of infection is similar to that found in many other countries (e.g. Centres for Disease Control, 1981). However, infections with pseudomonas were rather high, and these were particularly common in intensive care patients. We feel our infection rate is reasonably satisfactory especially when we take into consideration the various constraints we had to face trying to establish and maintain infection control of a new general hospital in this rapidly developing country. King Abdulaxiz University Hospital, PD. Box 6615, jfeddah, Saudi Arabia
M. A. Kassimi P. Leonard
Reference Centres for Disease Control (1981). National Sunzwzary, 1978. Issued March 1981.
Nosocomial Infections Study Report Annual
Letters to the Editor Sir, Environmental
monitoring
of sterile
fluid
production
facilities
I read with interest the leading article by Dr Gillett (1981), concerning the production of sterile fluids in hospital pharmacies. However, there are several points raised in the article, which require further comment. Firstly, I would like to dispel the idea that the intervention of the Medicines Inspectorate has seriously jeopardized the manufacture of sterile fluids in hospitals. On the contrary this intervention has brought about a long needed stream-lining and rationalization of the products made. Consequently, products which can be made more efficiently and cheaper by the pharmaceutical industry with their superior facilities are, on the whole, no longer manufactured in hospitals. Those manufacturing units which remain in hospitals are more and more concentrating on specialist products. The fact that fewer manufacturing units are now in operation means that the staff who work in these units are now more specialized, better trained and possessing a greater expert&e in the production of sterile fluids. The second point worth commenting upon is the statement of Dr Gillett that ‘it is the failure to provide such facilities which has led to the closure of these departments’, Most hospital pharmacy departments have a small inexpensive manufacturing facility, where small numbers of specialist items are made up on a named patient basis or for a particular clinic on a particular day. Large-scale manufacturing in hospitals is now more centralized. These units are initially expensive, but very quickly pay for themselves by being more efficient and requiring fewer staff than several smaller units. However, there can surely be no compromise on facilities in units where products are not terminally sterilized, but are manufactured aseptically by filtration. Regarding the extent of environmental monitoring which is carried out in hospital pharmacies, first of all I would be interested to know the source of the figures for the West n4idlands Region, since no such figures are available to the Quality Controllers in the West Midlands Region and as far as I am aware no detailed survey has been carried out to compile such figures. Consequently, I would question their accuracy. Even if we accept those figures, 22,000 specimens in one year in the largest region in the country, where there are several sterile manufacturing units, is not a large number and considering that approximately 60 per cent of these specimens (Dr Gillett’s figures) are settle plates, then it is a small effort, divided between several laboratories, for the sake of safety. A breakdown of the environmental monitoring in the West Birmingham Health District, where there are two manufacturing units, one for sterile products and one for non-sterile products (for which it is desirable to keep the levels of contamination to a minimum), reveals that in 1981, there were 952 settle plates, 968 contact plates and 194 swabs taken in the sterile laboratory. There were also 392 201
202
Letters
to the Editor
settle plates in the laminar flow cabinet sited in the non-sterile laboratory. Other microbiological monitoring included 192 viable counts on still water and filtered and unfiltered bulk solutions. The total amount of time spent in microbiological monitoring was very small compared to the amount of time spent in chemical testing of raw materials and products and was small compared to the amount of time spent on thermocouple testing of sterilizers and performing sterility tests. If anything it is the actual sterility tests which are the most time-consuming aspect of microbiological control of pharmaceuticals. It could be argued that if the environment, the in-process controls, the final sterilization procedure and the closure efficiency are carefully monitored, then the sterility test is merely a formality. In the West Birmingham Health District, we would be very concerned about a genuine failed sterility test. In 1981, we performed 474 sterility tests and had 11 failures all of which passed on a retest and were consequently attributed to contamination by the operator. The microbiological monitoring we perform gives us the confidence that our production facilities are of a suitable standard. Furthermore, the results can give us a great deal of information such as, where the areas of higher contamination risk are, whether our cleaning procedures are adequate, whether our air filtration system and laminar flow cabinents are functioning properly. It is worth noting that about half of the settle plates taken were for the monitoring of laminar flow cabinets. We have on one occasion been able to pick up a leaking filter very quickly by this method and it is our experience that, contrary to the findings of Whyte, Bailey and Hodgson (1979~~)the integrity of the HEPA filter makes a great deal of difference to the numbers of airborne microbial particles in a laminar flow cabinet. In summary then, I feel that the case against expensive sterile production units and time-consuming and expensive environmental monitoring is somewhat overstated. In the long-term, the expense is low compared to the cost of buying these products from the pharmaceutical manufacturers, made under special licence. The time-consuming monitoring is not so time-consuming as has been implied and the cost of materials for monitoring is minimal. Set against these disadvantages are the advantages. The need to install costly air filtration systems has meant better air conditioning for staff working in sterile fluid production units, has led to a rationalisation of sterile fluid production and has given pharmacists greater confidence in the products they make. Furthermore, although there is an argument to the contrary (Whyte, Bailey and Hodgson, 19793), it is my experience that the improvements in manufacturing facilities have greatly reduced the levels of particulate contamination in sterile fluids. I remember not so many years ago making water for irrigation in a prefabricated hut and having to discard 60 per cent of every batch because of gross particulate contamination, which could only have come from the manufacturing environment. Once an air filtration system is installed the advantages of monitoring it are obvious. Continuous monitoring acts as an early warning of a malfunction and monitoring can highlight problem areas.
Letters
203
to the Editor
Since the introduction of the Guide to Good Pharmaceutical Manufacturing Practice (HMSO, 1977), the record for the manufacture of sterile fluids in hospitals has improved greatly and although it may be argued that the standards set are unnecessarily high, it can also be argued that one contaminated bottle is one too many. It is better to be safe than sorry. Dudley Road Hospital, Birmingham
T. Deeks
References Gillett, A. P. (1981). Production of sterile fluids in hospital pharmacies. Journal of Ilospital Infection 2, 113-l 15. HMSO (1977). Guide to Good Pharnuzceutical Manufacturing Practice. HMSO, London. Whyte, W., Bailey, P. V. & Hodgson, R. (1979~). Monitoring the causes of clean room contamination. Manufacturing Chemist and Aerosol News, September, pp. 65-81. Whyte, W., Bailey, P. V. & Hodgson, R. (19796). The sources of contamination in bottles of infusion fluid. The Pharmaceutical Journal 223, 173-174.
Sir, Incidence
of nosocomial
infections
in the University
Hospital,
Jeddah
Since the opening of this 166-bedded hospital four years ago, the infection control committee has monitored hospital-acquired infection. The type of infection and organisms isolated were recorded. Table I shows that over a 12 month period 181 out of 5386 (3.4 per cent) patients were infected: 60 per cent of those infections were in the surgical or neonatal departments. Table II shows that the most common infections were of surgical wounds and the urinary tract. Gram-negative bacilli and Staphylococcus aureus were the most frequent isolates. (Tables I and II overleaf.) The overall infection rate is fairly low and the type of infection is similar to that found in many other countries (e.g. Centres for Disease Control, 1981). However, infections with pseudomonas were rather high, and these were particularly common in intensive care patients. We feel our infection rate is reasonably satisfactory especially when we take into consideration the various constraints we had to face trying to establish and maintain infection control of a new general hospital in this rapidly developing country. King Abdulaxiz University Hospital, PD. Box 6615, jfeddah, Saudi Arabia
M. A. Kassimi P. Leonard
Reference Centres for Disease Control (1981). National Sunzwzary, 1978. Issued March 1981.
Nosocomial Infections Study Report Annual