| Injection is a dosage form of injecting directly into human, which is usually with larger dosage. Injection can be classified into terminally sterilised processes and aseptic preparerations according to the productive technology. The sterile guarantee level of the aseptic preparerations is only 1/103-/109 of that of the terminally sterilised processes. Since there are many microbiological contamination factors during the production of the aseptic preparerations, therefore, high quality risks exist in the clinical practice.The current study takes the 5ml injection produced by aseptic preparerations as an example, and uses Shewhart Control Chart, Pie Chart and Histograms to monitor the microbiological contaminations introduced by environments, personnel, materials, water for injection, compressed air, nitrogen during production. We hope to find a high microbiological risk factor by performing risk assessment on each factor through Failure Mode Effects Analysis, Risk ranking and filtering. We then perform risk control by taking measures,The validity of the measures is sufficent to further decrease the risk of the quality of the aseptic preparerations and ensure the secure pharmacy of patients.This article was composed of the following eight parts:The results analysis of the microbiological and airborne particulate monitoring in clean zone; The results analysis of the personal microbiological monitoring; The results analysis of microbiological monitoring in materials; The results analysis of microbiological monitoring in water for injection; The results analysis of the microbiological and airborne particulate monitoring in the compressed and nitrogen; The Meta-analysis of the average results of monitoring data of the microbes in each factor; The risk analysis of microbes in each factor; Suggestions and measures.1. The results analysis of the microbiological and airborne particulate monitoring in clean zoneBy the microbiological and airborne particulate monitoring at rest in different room include a grade 100000 zone, a grade 10000 zone, a aseptic grade 10000 zone, a grade 100 zone, and by the microbiological monitoring in operation in different room in a aseptic grade 10000 zone and a grade 100 zone.The results are then analyzed according their grades through Shewhart Control Chart to calculated the average value of X, the standard deviation 8 and the control line X±38 of the static microbes and airborne particles at rest in different rooms in different clean zones, respectively, and those of microbes in operation in different rooms in a aseptic grade 10000 zone and a grade 100 zone. We find that each testing result is fall within the control line from the Shewhart Control Chart.We then perform a comparative analysis through Histograms of the microbes and airborne particles at rest in the critical rooms in each clean grades and find that①the testing results of the static the microbes and airborne particles have correspondence with the grades of the clean zones;②the testing results in different grades of clean zones have large differences:the best result is in a grade 100 zone, followed by the aseptic grade 10000 zone and grade 100000 zone.2. The results analysis of the personal microbiological monitoringBy microbiological monitoring on the surface of the personal gloves, sleeves, elbows, forehead and a face mask by successive 20 batchs of production in a aseptic grade 10000 zone and a grade 100 zone. The results are then summarized and analyzed by Shewhart Control Charts. The average values of x are calculated to be 1.50,1.25,1.55,1.15,1.15 CFU/plate for a aseptic grade 10000 zone,0.70,0.55,0.60,0.50,0.45 CFU/plate for a grade 100 zone, while the standard deviation 8 are calculated to be 0.51,0.44,0.51,0.59,0.37 CFU/plate for a aseptic grade 10000 zone and 0.47,0.51,0.50,0.51,0.51 CFU/plate for a grade 100 zone. We find that the testing result in a grade 100 zone is obviously better than that in a aseptic grade 10000 zone, and the face mask is better than others. Each testing result in within the control line.3. The results analysis of microbiological monitoring in materialsBy microbiological monitoring in A, B and C injections in successive 30 batchs, The results are analysis by using Shewhart Control chart. The average values of X, the standard deviation 8, and x+3δfor A, B and C injections are calculated to be 1.57,1.31,2.37 CFU/100ml,1.01,0.81,1.03 CFU/100ml and 4.59,3.73,5.47 CFU/100ml, respectively. We find difference of the quantity of microbes between the A, B and C injections:the testing data of A is best while C is worst. All testing results fall within the control line except several points in A and C injections.4. The results analysis of microbiological monitoring in water for injectionWe firstly monitor the microbes in the outlet, point of use 1,2,3 and inlet of the system of the water for injection weekly and then summarized and analysis the data obtained in a whole year by Shewhart Control Chart. For the outlet, point of use 1,2 3 and inlet, the average values of X, the standard deviationδ, and X+3δare calculated to be 0.10,0.12,0.12,0.14,0.18 CFU/100ml,0.31,0.33,0.33,0.35,0.39 CFU/100ml and 1.02,1.12,1.12,1.20,1.36 CFU/100ml, respectively. The testing result obtained (from the outlet in the best while that obtained from the inlet is the worst from the calculated results and the variation trend of data.5. The results analysis of the microbiological and airborne particulate monitoring in the compressed and nitrogenWe firstly monitor the microbes and airborne particles in the using points of washing bottle 1,2, filling 1,2, filtration of the compressed air and monitor the microbes and airborne particles in the using points of filling 1,2 of the nitrogen monthly, and then summarize and analysis the data obtained in a whole year by Shewhart Control Chart. We find that the values of the average X, standard deviationδand X+3δare all calculated to be 0 CFU/m3, indicating that the values of the microbes and airborne particles in each using point are stable.6. The Meta-analysis of the average results of monitoring data of the microbes in each factorThe monitoring data of microbes introduced by the environment of the clean zones, personnel contamination, materials, water for injection, compressed air and nitrogen during the aseptic prepareration firstly averaged and summarized. We then analyze the data by pie chart and conclude that the proportions of the microbes introduced by personnel contamination in operation (in containing a aseptic grade 10000 zone and a grade 100 zone), materials, the environments and water for injection are 46%,42%,9% and 3%, respectively, while that of the compressed air and nitrogen is zero.7. The risk analysis of microbes in each factorThe Risk ranking and filtering are performed on the collected data by Failure Mode Effects Analysis and conclude that the influence of each risk factor on the microbes in injections produced by aseptic preparations from small to large is compressed air, nitrogen, materials, water for injection, air in a aseptic grade 10000 zone, air in a grade 100 zone, personnel contamination with according Risk Priority Number of 2,3,8,9,19,32 and 252.8. Suggestions and measuresIn order to minimize risks of microbiological contamination of aseptic preparerations. Much depends on the skills, training and attitudes of personnel involved. The measures should be adopted as follows:①Setting personnel rules in aseptic room and training the aseptic operating skill and consciousness;②Adopting aseptic isolator technology;③Validation of aseptic processing need a process simulation test using a nutrient medium to verify the measures for reducing the contamination introduced by personnel.ConclutionAmong various microbiological risk factors in the production of aseptic preparations of injection, materials, compressed air and nitrogen belong to low risk factors, air in a aseptic grade 10000 zone, air in a grade 100 zone and water for injection belong to medium risk factor, while personnel contamination belong to high risk factor.Adopting aseptic isolator technology can effectively reduce the microbiological contamination introduced by personnel.It is effective in controling microbiological risk by making use of risk management process and tools and ways in the production of aseptic preparations of injection and can cover the Shortage of GMP in quality control tools and ways. |
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