Which links in the production of drugs are prone to microbial contamination

Aseptic drugs mainly refers to the legal drug standards listed in the sterility check items in the preparation, mainly divided into sterile raw materials, final sterilized preparations, non-final sterilized preparations and so on. Used for aseptic dispensing powder needle sterile raw materials, non-final sterilized preparations and F value <8 final sterilized preparations, due to the final sterilization can not be achieved through the sterilization of microorganisms to achieve the purpose of complete killing, so the degree of sterility of the production process is directly related to the level of sterility of the drug. For example, if there is a single contamination in the production process, it is difficult to detect it in the final aseptic examination, and then it will flow to the market, which will cause great harm to the safety of medication. Therefore, analyze the factors of microbial contamination in the production process of sterile drugs, and targeted development of appropriate processes and methods, procurement of appropriate equipment and facilities, the use of appropriate materials and protective facilities, and the development of effective operating procedures to ultimately ensure the sterility of the product is particularly important.

The following from the production of sterile drugs, personnel, plant and facilities, equipment, materials, processes and other six aspects of the analysis of microbial contamination is easy to cause the factors.

1 personnel

People are the main source of contamination in the production of sterile drugs, the possibility of contamination due to the operation of personnel more than 70%. Clean room (area) should be limited to the region's production operators and approved personnel to enter, the number of personnel should be strictly controlled, to enter the clean room (area) of the temporary outsiders should be guided and supervised.

1.1 the number of aseptic operators: according to the analysis of the contamination of the personnel, as above, to determine the control of aseptic production area of the number of personnel is very important. In addition, the operating range of the aseptic operator should be standardized to minimize movement. The number of personnel should be verified to demonstrate that there is no impact on the relevant indicators of a sterile environment before being determined.

1.2 Entry of non-production personnel Non-production personnel, such as visitors, equipment maintenance personnel, quality inspection personnel, etc., due to the lack of professional microbiological knowledge, aseptic dressing requirements and aseptic operation requirements of the training, in the dressing and aseptic production area of the process of operation and so on is likely to bring microbial contamination of the aseptic production area. Therefore, non-production personnel should be strictly controlled to enter the aseptic production area, and if they need to enter, they should be strictly trained and led by the personnel in the aseptic production area, and be guided and monitored.

1.3 Qualification of personnel: For the operator of aseptic production area, it is recommended to choose the producer with patience and secondary school education or above (the control of aseptic production area requires strict requirements, and the operator needs to insist on following the SOP and related regulations for a long time).

1.4 Personnel training: as aseptic drugs, the most important thing that the personnel in the aseptic production area need is the training of microbiological knowledge, disinfection and sterilization knowledge, etc. Moreover, the training of aseptic dressing and aseptic operation is also very important.

1.5 Aseptic operator: the aseptic operation of personnel is very important, because there is a possibility of direct or close contact with the drug and bring microbial contamination.

The main risks that may exist in the aseptic operator are: ① Non-production personnel's awareness of aseptic operation is not strong and lead to contamination of the environment, equipment and drugs. ② The current aseptic protection devices can not guarantee the contamination brought about by the personnel themselves. ③Aseptic operators often touch gloves may contaminate the hands. ④ Aseptic operators do not disinfect in time or enter the 100-level operation area without disinfection ⑤ Aseptic operator's movement or action is too large and easy to bring the Egyptian, human excreta and microbial increase. (6) The aseptic operator may cross the dead space of the aseptic production area and be contaminated. (7) aseptic operator filling if the unsealed bottle mouth of the drug above the operation may lead to the human body or aseptic clothing contaminated microorganisms directly into the bottle of liquid medicine, etc..

2 plant and facilities

Aseptic environment is the production of qualified sterile drugs based on the guarantee, it is difficult to imagine a non-sterile production environment can consistently produce sterile products. Therefore, the aseptic production environment is critical, it is mainly related to the design of the aseptic production environment, layout, facility conditions, environmental disinfection, airflow conditions.