Pharmaceutical clean room environment monitoring questions
2016-09-05 16:26:28
1. Q: purified water system and water for injection systems, ultraviolet disinfection regularly whether it? If not, what methods should be used?
A: "Good Manufacturing Practice (revised 2010)," requires companies to deal with purified water, water for injection pipeline cleaning and disinfection, and sterilization methods no way mandatory. Factors ultraviolet disinfection more, such as ultraviolet wavelength, intensity, exposure time, the water layer thickness, difficult to control, can be used as an adjunct to disinfection.
Water for injection and purified water disinfection system has multiple ways, for example: purified water system can be pasteurized or sterilized pure steam, water for injection may be pure steam sterilization or hot water sterilization. The UV merely assisted approach can be extended sterilization cycle, but the effect is very limited.
Enterprises can identify specific disinfection and sterilization equipment according to their own situation as well as the sterilization cycle, and its fully verified. However, under normal circumstances, it does not recommend water purification systems and water for injection system using only UV disinfected regularly this way.
2. asked to monitor the clean area, dome cameras each wash clean is not clean, and cleaning dead ranged very unsanitary environmental protection, is there even a good cleaning method?
A: clean room for clean area D and production of clean area dedicated camera, dedicated camera clean area is peacekeeping far Tektronix for the special use of the environment clean area, clean room, specifically for the pharmaceutical, electronics factory, hospital operating room, food factory like clean area / clean room / clean room development of special webcam. The camera can seamlessly embed color plate installation, flat circular outer surface and color steel flush, no health corners, easy to clean and easy to disinfect. The camera can key processes, key positions sentinel surveillance for 24 hours. Use the camera in conjunction with peacekeeping far Tektronix OPCMES software enables monitoring of clean areas alarm events associated with video clips. Clean areas as pharmaceutical companies manufacturing site, the environment, dress, movement of persons and other strict rules and requirements. The camera can not fully monitor the operation of the clean room staff through a single hemisphere, the state will not be able to run critical equipment, real-time operation monitoring point. How to clean areas remote offsite key positions, real-time monitoring of critical equipment fixed?
To achieve multi-point monitoring operation between the clean area, under the existing technical conditions, the need to increase the number of clean room surveillance cameras. Dome camera mounted on the ceiling, the installation position is too high, clean up is not convenient, and the presence of health corners, increasing the workload of cleanroom cleaning and acceptance.
Clean area dedicated camera embedded solve the problem. Embedded clean area dedicated camera mounted on the clean area color steel wall by embedding color plate installed, the installation height from the ceiling about
40-60cm. The camera plane flat panel, after embedding color plate, color plate camera plane and plane flush, wipe clean the wall using the wall while achieving clean the camera. Meanwhile, the camera's flat panel zero health corners, in clearing the place does not exist.
Pharmaceutical cleanroom area
3. Q: What is the basis for monitoring standards and drug manufacturers clean room air cleanliness of the environment parameter is? "Good Manufacturing Practice (revised 2010)," is not clearly defined technical standards for clean room, for example: ventilation frequency, temperature, humidity, etc., then the third party should be in clean room cleanliness level testing to confirm what kind of standard?
A: "Good Manufacturing Practice (revised 2010)," Article 42 states: "The plant should have proper lighting, temperature, humidity and ventilation, to ensure the production and storage of product quality and performance is not directly related to equipment or indirectly affected. " Enterprises should be combined product and process characteristics to determine the temperature and humidity range of clean areas.
Cleanroom technology standard, China has more than GB are involved, such as: "The pharmaceutical industry clean plant design specifications" (GB50457-2008), "clean room construction and acceptance" (GB
50591-2010) and the like. Suspended particles, planktonic bacteria detection method for settling microbe can refer GB / T16292-2010, GB / T16293-2010, GB / T16294-2010 etc. GB.
ISO14644 standard for cleanroom technology also has a strong reference value, in addition to the State Food and Drug Administration Drug Certification Center organized the compilation of "Drug GMP Guide" also lists a number of requirements, such as the number of ventilators
D-level dynamic standards: 6-20 times / h; C-level dynamic standards: 20-40 times / h; grade B standard Dynamic: 40-60 times / h and the like.
4. Q: regulatory requirements in key operations for dynamic monitoring of microorganisms, whether bacteria floating in the whole process requires dynamic monitoring?
A: According to Good Manufacturing Practices Appendix a sterile pharmaceutical provisions of Article 11 shall microbial dynamic monitoring, assessment sterile production of microbiological status. There settling bacteria, quantitative planktonic bacteria sampling air and surface sampling (eg swab method and the contact plate method) and other monitoring methods. Dynamic Sampling should avoid adverse impact on the clean area. Finished batch record review should include the results of environmental monitoring.
The emphasis here is to produce a sterile environment must be monitored to assess the microbiological status of the dynamic, the dynamic monitoring of the whole process did not request. Pharmaceutical production and quality management specification also provides a "dynamic sampling should avoid adverse impact on the clean area." Enterprises to cope adopt monitoring methods and procedures for evaluation. In particular, taking into account the planktonic bacteria sampling procedures and related intervention may be critical airflow areas affected. Therefore, the key operation dynamic monitoring of microbes, planktonic bacteria do not need the whole dynamic monitoring.
5. Q: pharmaceutical raw materials for production equipment (a single species) when performing cleaning validation, do you need to detect the residual amount of the active ingredient? No visible residue by visual material as the standard is feasible?
A: "Good Manufacturing Practice (revised 2010)," Article 143 stipulates: cleaning methods should be validated, confirmed that the cleaning effect, in order to prevent contamination and cross-contamination.
Cleaning validation should consider the use of equipment, cleaning agents and disinfectants used, the nature and limits of the sampling methods and sampling location and the corresponding recovery, residues, residue testing method sensitivity factors.
Cleaning Validation single species raw material drug production process equipment from a risk perspective, the active ingredient of special equipment on residual subsequent production quality is not affected. Cleaning validation focuses confirm the presence of related impurities (degradation products, reactants) residues, the residue is able to ensure the safety and effectiveness of drugs.
If a single species for the production of special equipment, should be a comprehensive assessment of drug (or intermediate) on the nature of the related equipment, whether there are impurities produced high activity, the impurities present in the residual standard cleaning methods can achieve the like. Under normal circumstances, the need for cleaning validation testing by sampling way to prove, not only visually no visible residue as an indicator.
No visible residue visual material often used as a standard for each measurement after the cleaning behavior.
6. Q: The specification states that "air cleanliness level of the sampling area should be consistent with production requirements." How to understand "is consistent with production requirements," it is consistent with the material to be used in a production environment is consistent with the material itself or production environment?
A: The complete requirements for pharmaceutical production and quality management practices as "Article 62 should normally be a separate sampling area material air cleanliness level of the sampling area should be consistent with production requirements as in other regions or other means of sampling should. possible to prevent contamination or cross-contamination. "
Good Manufacturing Practice requirements are introduced in order to control pollution in the sampling process and the risk of cross-contamination. From a risk perspective, sampling conditions and the sampled material production conditions are not consistent with an enlarged risk of contamination and cross-contamination, so air cleanliness level of the sampling area shall not be less than the sampled material will be used in production conditions are acceptable of.
7. Q: Clean level Bottle non terminally sterilized small volume injections, potting, how to divide the ingredients? Between their accessibility and its clean room production operation level must be the same as you? Such as the operating room is a Class A Class B under the background, it is between the auxiliary class B can it?
A: For each process step of non-terminally sterilized small volume injections should be at what level of cleanliness, Article XIII of GMP Annex 1 gives an example of non-terminally sterilized small volume injections bottle can be located in D grade, potting in the B-class a-class background, may be formulated or sterile filtration of liquid products in the C grade, sterile ingredients should be at a-level grade B background. Sterile drug production operating environment can refer to the sample selection.
It should be noted that the layout of the core area should be reasonable to minimize the auxiliary function rooms, such as the need to set up an auxiliary room, should minimize its impact on the core area. Specifically cleanliness level utility room should be determined based on the characteristics in the room of operation or stored materials and appliances.
8. Q: I will be concentrated and dilute with a small volume injection with large capacity injection feature on the C-class area, improve the level of cleanliness with concentrated, it is feasible?
A: feasibility, need to consider whether the impact of the concentration step with dilute with due process can be accepted, whether the measures can be taken to reduce the possibility of contamination and cross-contamination. For example, the concentration distribution process may use a lot of materials, dust generation, can cause contamination or cross-contamination (activated carbon weighing, preparation, etc.). Enterprises should consider the possibility of taking measures to ensure that will reduce the risk of dust contamination or cross-contamination to acceptable levels.
9. Q: The specification does not mention "disinfectant rotation," Does it mean that the disinfectant can not rotate?
A: Good Manufacturing Practices Appendix I of sterile drugs Article 43: "It should be in accordance with the rules of the clean area cleaned and disinfected under normal circumstances, the use of more than one kind of disinfectants should not be used. UV disinfection alternative to chemical disinfection should be regular environmental monitoring, timely detection and contamination tolerant strains. "
Although pharmaceutical production and quality management specification does not dictate the use of disinfectants must be rotated, but the company actually made more scientific requirements. Enterprises have often been carried out in accordance with the requirements of a disinfectant rotation, and the rotation of disinfectants to clean areas using disinfecting effect do research. The newly revised drug GMP requirements for enterprise environmental monitoring data for statistical analysis, and to determine at least a class on how to use disinfectant, and ultimately ensure the effectiveness of disinfectants in a clean area.
10. Q: Compliant between clean area and non-clean areas, different levels of pressure between the clean area should be not less than 10 kPa, if the production of A-grade core area, the core production area from A to non-clean area whether there will be at least 40 Pa pressure difference? How to achieve?
A: Yes. By Professional Institute of the air purification system design, on this basis, through the rational allocation of difference with the air supply and return air ventilation frequency different levels of cleanliness to meet this requirement.
A: "Good Manufacturing Practice (revised 2010)," requires companies to deal with purified water, water for injection pipeline cleaning and disinfection, and sterilization methods no way mandatory. Factors ultraviolet disinfection more, such as ultraviolet wavelength, intensity, exposure time, the water layer thickness, difficult to control, can be used as an adjunct to disinfection.
Water for injection and purified water disinfection system has multiple ways, for example: purified water system can be pasteurized or sterilized pure steam, water for injection may be pure steam sterilization or hot water sterilization. The UV merely assisted approach can be extended sterilization cycle, but the effect is very limited.
Enterprises can identify specific disinfection and sterilization equipment according to their own situation as well as the sterilization cycle, and its fully verified. However, under normal circumstances, it does not recommend water purification systems and water for injection system using only UV disinfected regularly this way.
2. asked to monitor the clean area, dome cameras each wash clean is not clean, and cleaning dead ranged very unsanitary environmental protection, is there even a good cleaning method?
A: clean room for clean area D and production of clean area dedicated camera, dedicated camera clean area is peacekeeping far Tektronix for the special use of the environment clean area, clean room, specifically for the pharmaceutical, electronics factory, hospital operating room, food factory like clean area / clean room / clean room development of special webcam. The camera can seamlessly embed color plate installation, flat circular outer surface and color steel flush, no health corners, easy to clean and easy to disinfect. The camera can key processes, key positions sentinel surveillance for 24 hours. Use the camera in conjunction with peacekeeping far Tektronix OPCMES software enables monitoring of clean areas alarm events associated with video clips. Clean areas as pharmaceutical companies manufacturing site, the environment, dress, movement of persons and other strict rules and requirements. The camera can not fully monitor the operation of the clean room staff through a single hemisphere, the state will not be able to run critical equipment, real-time operation monitoring point. How to clean areas remote offsite key positions, real-time monitoring of critical equipment fixed?
To achieve multi-point monitoring operation between the clean area, under the existing technical conditions, the need to increase the number of clean room surveillance cameras. Dome camera mounted on the ceiling, the installation position is too high, clean up is not convenient, and the presence of health corners, increasing the workload of cleanroom cleaning and acceptance.
Clean area dedicated camera embedded solve the problem. Embedded clean area dedicated camera mounted on the clean area color steel wall by embedding color plate installed, the installation height from the ceiling about
40-60cm. The camera plane flat panel, after embedding color plate, color plate camera plane and plane flush, wipe clean the wall using the wall while achieving clean the camera. Meanwhile, the camera's flat panel zero health corners, in clearing the place does not exist.
Pharmaceutical cleanroom area
3. Q: What is the basis for monitoring standards and drug manufacturers clean room air cleanliness of the environment parameter is? "Good Manufacturing Practice (revised 2010)," is not clearly defined technical standards for clean room, for example: ventilation frequency, temperature, humidity, etc., then the third party should be in clean room cleanliness level testing to confirm what kind of standard?
A: "Good Manufacturing Practice (revised 2010)," Article 42 states: "The plant should have proper lighting, temperature, humidity and ventilation, to ensure the production and storage of product quality and performance is not directly related to equipment or indirectly affected. " Enterprises should be combined product and process characteristics to determine the temperature and humidity range of clean areas.
Cleanroom technology standard, China has more than GB are involved, such as: "The pharmaceutical industry clean plant design specifications" (GB50457-2008), "clean room construction and acceptance" (GB
50591-2010) and the like. Suspended particles, planktonic bacteria detection method for settling microbe can refer GB / T16292-2010, GB / T16293-2010, GB / T16294-2010 etc. GB.
ISO14644 standard for cleanroom technology also has a strong reference value, in addition to the State Food and Drug Administration Drug Certification Center organized the compilation of "Drug GMP Guide" also lists a number of requirements, such as the number of ventilators
D-level dynamic standards: 6-20 times / h; C-level dynamic standards: 20-40 times / h; grade B standard Dynamic: 40-60 times / h and the like.
4. Q: regulatory requirements in key operations for dynamic monitoring of microorganisms, whether bacteria floating in the whole process requires dynamic monitoring?
A: According to Good Manufacturing Practices Appendix a sterile pharmaceutical provisions of Article 11 shall microbial dynamic monitoring, assessment sterile production of microbiological status. There settling bacteria, quantitative planktonic bacteria sampling air and surface sampling (eg swab method and the contact plate method) and other monitoring methods. Dynamic Sampling should avoid adverse impact on the clean area. Finished batch record review should include the results of environmental monitoring.
The emphasis here is to produce a sterile environment must be monitored to assess the microbiological status of the dynamic, the dynamic monitoring of the whole process did not request. Pharmaceutical production and quality management specification also provides a "dynamic sampling should avoid adverse impact on the clean area." Enterprises to cope adopt monitoring methods and procedures for evaluation. In particular, taking into account the planktonic bacteria sampling procedures and related intervention may be critical airflow areas affected. Therefore, the key operation dynamic monitoring of microbes, planktonic bacteria do not need the whole dynamic monitoring.
5. Q: pharmaceutical raw materials for production equipment (a single species) when performing cleaning validation, do you need to detect the residual amount of the active ingredient? No visible residue by visual material as the standard is feasible?
A: "Good Manufacturing Practice (revised 2010)," Article 143 stipulates: cleaning methods should be validated, confirmed that the cleaning effect, in order to prevent contamination and cross-contamination.
Cleaning validation should consider the use of equipment, cleaning agents and disinfectants used, the nature and limits of the sampling methods and sampling location and the corresponding recovery, residues, residue testing method sensitivity factors.
Cleaning Validation single species raw material drug production process equipment from a risk perspective, the active ingredient of special equipment on residual subsequent production quality is not affected. Cleaning validation focuses confirm the presence of related impurities (degradation products, reactants) residues, the residue is able to ensure the safety and effectiveness of drugs.
If a single species for the production of special equipment, should be a comprehensive assessment of drug (or intermediate) on the nature of the related equipment, whether there are impurities produced high activity, the impurities present in the residual standard cleaning methods can achieve the like. Under normal circumstances, the need for cleaning validation testing by sampling way to prove, not only visually no visible residue as an indicator.
No visible residue visual material often used as a standard for each measurement after the cleaning behavior.
6. Q: The specification states that "air cleanliness level of the sampling area should be consistent with production requirements." How to understand "is consistent with production requirements," it is consistent with the material to be used in a production environment is consistent with the material itself or production environment?
A: The complete requirements for pharmaceutical production and quality management practices as "Article 62 should normally be a separate sampling area material air cleanliness level of the sampling area should be consistent with production requirements as in other regions or other means of sampling should. possible to prevent contamination or cross-contamination. "
Good Manufacturing Practice requirements are introduced in order to control pollution in the sampling process and the risk of cross-contamination. From a risk perspective, sampling conditions and the sampled material production conditions are not consistent with an enlarged risk of contamination and cross-contamination, so air cleanliness level of the sampling area shall not be less than the sampled material will be used in production conditions are acceptable of.
7. Q: Clean level Bottle non terminally sterilized small volume injections, potting, how to divide the ingredients? Between their accessibility and its clean room production operation level must be the same as you? Such as the operating room is a Class A Class B under the background, it is between the auxiliary class B can it?
A: For each process step of non-terminally sterilized small volume injections should be at what level of cleanliness, Article XIII of GMP Annex 1 gives an example of non-terminally sterilized small volume injections bottle can be located in D grade, potting in the B-class a-class background, may be formulated or sterile filtration of liquid products in the C grade, sterile ingredients should be at a-level grade B background. Sterile drug production operating environment can refer to the sample selection.
It should be noted that the layout of the core area should be reasonable to minimize the auxiliary function rooms, such as the need to set up an auxiliary room, should minimize its impact on the core area. Specifically cleanliness level utility room should be determined based on the characteristics in the room of operation or stored materials and appliances.
8. Q: I will be concentrated and dilute with a small volume injection with large capacity injection feature on the C-class area, improve the level of cleanliness with concentrated, it is feasible?
A: feasibility, need to consider whether the impact of the concentration step with dilute with due process can be accepted, whether the measures can be taken to reduce the possibility of contamination and cross-contamination. For example, the concentration distribution process may use a lot of materials, dust generation, can cause contamination or cross-contamination (activated carbon weighing, preparation, etc.). Enterprises should consider the possibility of taking measures to ensure that will reduce the risk of dust contamination or cross-contamination to acceptable levels.
9. Q: The specification does not mention "disinfectant rotation," Does it mean that the disinfectant can not rotate?
A: Good Manufacturing Practices Appendix I of sterile drugs Article 43: "It should be in accordance with the rules of the clean area cleaned and disinfected under normal circumstances, the use of more than one kind of disinfectants should not be used. UV disinfection alternative to chemical disinfection should be regular environmental monitoring, timely detection and contamination tolerant strains. "
Although pharmaceutical production and quality management specification does not dictate the use of disinfectants must be rotated, but the company actually made more scientific requirements. Enterprises have often been carried out in accordance with the requirements of a disinfectant rotation, and the rotation of disinfectants to clean areas using disinfecting effect do research. The newly revised drug GMP requirements for enterprise environmental monitoring data for statistical analysis, and to determine at least a class on how to use disinfectant, and ultimately ensure the effectiveness of disinfectants in a clean area.
10. Q: Compliant between clean area and non-clean areas, different levels of pressure between the clean area should be not less than 10 kPa, if the production of A-grade core area, the core production area from A to non-clean area whether there will be at least 40 Pa pressure difference? How to achieve?
A: Yes. By Professional Institute of the air purification system design, on this basis, through the rational allocation of difference with the air supply and return air ventilation frequency different levels of cleanliness to meet this requirement.
