1. Potential Contamination of Drug Production by Personnel
As we all know, in the production of sterile drugs in each element, people are the biggest pollution source. As people are the most active factor, and mechanical sterilization and disinfection measures cannot be implemented. Therefore, the control of human contamination has become a key issue for the sterile pharmaceutical industry. Table 1 lists some data on the potential risks posed by people to drug production.
Table 1 Data of human related microorganisms | |
The body part | Data of microorganisms |
Hair\Scalp | 15million/cm² |
Oral | 1-100million/ml |
Nose-Throat(secretions) | 1million-10million/ml |
Covered skin(black) | 500-1000/cm² |
Area of sweat glands(underarm) | 24million/cm² |
Hands | 100-6000/cm² |
Finger tip of the finger | 20-100/cm² |
Feet | 100-1000/cm² |
Gastric contents | 1000-10000/g |
Small intestine contents | 1000-1million/g |
Large intestine contents | 100million-10billion/g |
Rectum contents | 100billion/g(=10%-20% of excrement) |
2. Requirements of GMP For Personnel Purification in Aseptic Production Clean Area
Regarding sterile products, there are two production processes for sterile products, one is the sterilization process and the other is the aseptic process. Whether pharmaceutical enterprises use sterilization process, or use aseptic process to produce drugs, people are the biggest potential pollution source of drugs. Therefore, for personnel’s dressing change procedures, is also the focus of GMP in various countries.
From the GMP standards of various countries on changing clothes for people engaged in aseptic drug production, drug regulatory agencies of various countries, for how to avoid personnel pollution, how to scientifically design the changing procedure, how to verify the effectiveness of the procedure, how to monitor the controlled state of the changing procedure, are very concerned.
3. Key Points in The Design of Changing Procedure in Clean Area of Aseptic Production
3.1 Material selection and quality evaluation of clean clothes
Because people can not be disinfected and sterilized like materials and products. Therefore, wearing appropriate clean clothes has become the main means of controlling pollution brought by people. For the material of clean clothes used by pharmaceutical enterprises,GMP (revised in 2010) requires that the clothes should be sterilized one-piece clothes, without shedding fibers or particles, and can retain particles emitted by the body.
The fabrics used in work clothes are generally made of repeatable materials and disposable materials. Reusable textile fabrics are made from fibers woven by spinning. Single-use materials are usually made of nonwovens. The processing of nonwovens is a one-step process that does not require spinning and weaving.
Since the 1970s, manufacturers have applied triple resistance treatments to fabric surfaces to reduce the penetration of blood and fluids. Considering that washing will gradually destroy the treatment layer of the surface of the fabric, the washing method and frequency are stipulated to ensure that the performance of the fabric meets the requirements after each washing.
In China’s pharmaceutical industry, most of the early clean clothes are polyamide filament. Now polyester filaments are mainly used at home and abroad. With the continuous improvement of the industry’s requirements for the antistatic performance of clean clothes, high clean clothes emerge at the historic moment, which requires friction voltage less than 300V, and has good washability. At present, the quality control of clean clothes in the pharmaceutical industry in China is mainly based on YYT0506.1-8 to control product quality.
3.2 Design of changing process
At present, Chinese aseptic pharmaceutical enterprises have different design schemes for A/B region personnel access channels. However, the following basic principles should be followed:
◆ The area and space of the changing channel can meet the maximum flow of people through at the same time, can not be too narrow.
◆ Personal coat shall not be taken into the locker room leading to level B or C clean area. A spacious and safe dressing room shall be set at the entrance of personnel and equipped with a locker.
◆ Every employee shall change his/her sterile work clothes every time when he/she enters the A/B clean area; or change it at least once. But the monitoring results should be used to demonstrate the feasibility of this method. This requires aseptic workshop laundry equipment, whole clothing space and clean clothing sterilization equipment can meet the requirements of maximum production load. In addition, if the pharmaceutical enterprises provide aseptic clean clothes for each shift once, and can be reused in a shift, it is necessary to set up a hanger in the personnel exit channel, to ensure that the clean clothes are temporarily stored in the way of suspension after the personnel exit, to avoid the contamination of the surface of the clean clothes in the process of stripping.
◆ Gloves should be disinfected frequently during operation, and masks and gloves should be replaced when necessary. As it is not practical to change masks in class B area, it is recommended that a mask and glove changing area be set up in the last changing room of the changing access channel. A stainless steel bench can be used instead.
◆ Changing rooms should be designed in accordance with air lock mode to separate the different stages of changing clothes and avoid microbial and particulate contamination as far as possible.
◆ There should be enough ventilation in the dressing room. The static level of the rear section of the dressing room shall be the same as that of the corresponding clean area. For this requirement, it is generally required that the cleanliness level of the sterile clothing changing room should reach GRADE B.
◆ If necessary, the changing room entering and leaving the clean area can be set up separately. If the pharmaceutical company has separate access and exit channels for sterile dressing, the distribution channel and the recovery method after use of clean clothes should be considered . In this case, clean clothes entering A/B area can only be used once.
◆ In general, washing facilities can only be installed in the first stage of changing clothes.
◆ It is recommended that the changing channel be set separately according to gender. Although some companies may have the same gender of employees entering the A/B area, it is better to separate them by gender in view of the possibility that there may be different genders in external official inspectors, temporary maintenance personnel and verification personnel.
Based on the above principles, it is suggested that the pharmaceutical industry should design the changing channel for personnel entering the A/B area according to the following flow chart.
3.3 Personnel training and assessment
Because of the complexity of personnel’s dressing changing procedures for entering the level A/B area of aseptic pharmaceutical plants, personnel’s dressing changing training is also a basis for ensuring successful verification of the procedures. Pharmaceutical companies should develop specific, detailed and explicit written changing procedures and train relevant personnel (including aseptic operation personnel, QA monitoring personnel, QC sampling personnel, maintenance personnel and relevant supervisors). In order to achieve good training results, pharmaceutical companies can adopt a variety of flexible training methods such as human demonstration, trainees drill, video changing clothes, centralized learning and so on. In short, solid and effective dressing training is the basis for successful verification of dressing procedures.