Pharmaceutical enterprises clean plant supervision points
With the continuous development of China's pharmaceutical industry, the new version of the GMP March 1, 2011 onwards, the implementation of the plant, equipment and facilities more and more stringent requirements, the following for you to organize a number of pharmaceutical enterprises clean plant supervision points, the meeting you read!
1 clean room
1.1 air cleanliness regulations
According to the new version of the GMP regulations: air cleanliness level is divided into 4 levels: A, B, C, D level, the cleanliness of the air by the air purification facilities to ensure that the air, and the qualified air once sent to the clean room, can only be by the enclosure of the clean room to protect and maintain from contamination. Protection and maintenance of the clean room is not contaminated.
1.2 Clean room enclosure structure
(1) building enclosure structure of the material must be good airtight, in the temperature and humidity changes in the deformation of the smallest amount;
(2) structural decoration, the plate should be flat, smooth, not dusty, easy to clean, resistant to water, waterproof, easy to maintain, air flow or friction, no particles or shedding, to avoid glare, the light reflection system is suitable for 0.5mm, the light reflection system is suitable for 0.5mm. Light reflection system should be 0.6 ~ 0.8;
(3) clean room walls and ceilings, floors and other parts of the connection should be made into a curved, all R corners, rounded corners with aluminum alloy profiles, and have a reliable seal;
(4) the floor of the clean room should be a good overall integrity, smooth, wear-resistant, impact-resistant, not easy to accumulate static electricity, easy to remove dust and cleaning; (5) clean room doors and windows should be constructed Level and simple, not easy to accumulate dust, easy to clean and have good airtightness, the surface should be free of scratches, bruises. Windows are generally fixed double-glazed windows;
(6) All color plates in the clean room connection parts should be high-quality neutral silicone sealing, coated with dense, uniform, continuous, no tumor.
1.3 Clean room, enclosure supervision points
1.3.1 Material inspection
(1) Aluminum honeycomb and rock wool color steel plate: plate color difference should be relatively uniform, smooth appearance, thickness and weight up to standard, the thickness of the substrate selection of ≮ 0.5 mm; (2) clean room doors and windows: varieties, types of specifications, construction and profile thickness, size and airtightness are Meet the requirements; (3) self-leveling materials: brand, manufacturer, factory time, quality inspection reports should meet the requirements; (4) PVC flooring: review the thickness, color, water permeability and acid and alkali corrosion resistance of the quality inspection report.
1.3.2 Quality control checkpoints in the construction process
(1) Sheet lifting bars and air ducts, pipes, lamps and lanterns, air outlets and other lifting bars are installed separately, and should ensure that the corresponding bearing capacity.
(2) clean room compartmentalization line: the requirements of the red solution radiation locator line, according to the design drawings check the line, check the line through the next process into the laying of the upper and lower open rails, the installation of the ground rail. At the same time, the entire cleanroom partition system to provide continuous electrostatic grounding.
(3) should be partition wall and ceiling color plate splicing: first of all, the construction unit required to carry out the second design, issued by the second design plan, the map must be marked clean area high-efficiency air outlet number and size code, non-clean area air outlet number, room name. In the construction of the field to be confirmed before the large area is prohibited openings, plate seam uniform gap of 3 ~ 4 mm. exhaust or return air ducts, such as civil engineering columns need to be wrapped with color plates.
(4) self-flowing apron construction: the main construction of flatness and thickness to be measured, according to the drawings required to check, including the slope requirements with floor drains, and control the construction temperature is not less than 15 ℃.
(5) PVC flooring: color lines follow the direction of foot traffic, adhesion before the brush glue to be uniform, compaction shall not have bubbles, welding at the joints should be straight, high and low uniformity, there can be no leakage, leakage phenomenon.
(6) sealing: the gap between the wall plate adjusted evenly after gluing, the various pipelines into and out of the clean room plus decorative cover after glue seal, especially switches, sockets, door and window frames, air return, air diffuser peripheral, exhaust or return air clamping within the color plate must be glued sealing treatment, construction must be to ensure that the clean, neat and tidy after the construction.
2 Power Distribution System
The power distribution system mainly includes lighting, electricity, communication and fire protection, etc., the production area should have moderate lighting, visual operation area lighting should meet the operating requirements, lamps, switches and sockets, and other materials should be in line with the requirements of the use of the clean room, and at the same time to ensure that the sealing. In addition to meeting cleanliness, energy saving should also be considered. Clean power distribution system supervision points are:
2.1 Material inspection
(1) lighting fixtures selection of ceiling transparent cover purification lamps, switches selection of clean switches, sockets selection of clean sockets;
(2) electrical appliances, electrical material packaging should be intact, the appearance of the material should not be damaged, accessories, spare parts should be complete;
(3) electrical appliances, electrical material specifications, models should be consistent with the design requirements and national standards. (3) Electrical appliances, electrical material specifications, models should be in line with the design requirements and the relevant provisions of the current national standards for electrical products.
2.2 construction process inspection
(1) clean room switchboard (cabinet), control display panel (cabinet), switch box should be embedded installation, and the gap between the wall should be used to gas-tight construction;
(2) switchboard (cabinet), control panel (cabinet) of the access door should not be opened in the clean room, such as must be located in a clean room, should be for the disk, cabinet installation Airtight door;
(3) clean room power distribution system construction to meet the current national standards, "Building Electrical Engineering Construction Quality Acceptance Specification" (GB 50303) requirements, the materials used and construction should also meet the needs of the clean room;
(4) clean area power lines and non-clean area lines should be laid separately, the main work (production) area with auxiliary work (production) Area lines should be laid separately;
(5) the distribution panel of the metal frame and base steel must be grounded PE or zero PEN reliable;
(6) lighting power density current value should meet the design requirements, the main workplace of its purification area illumination is not less than 300 LX, purification area auxiliary studio, corridors, purification of personnel and materials purification room 150 ~ 200 LX, non-purification Office, instrument room and laboratory illuminance is not less than 300 LX, of which the power distribution room illuminance is not less than 200 LX;
(7) the installation of power outlets, facing the left side of the outlet should be connected to the zero line (N), the right should be connected to the phase line (L), the middle of the upper should be connected to the protective earth (PE);
(8) electrical piping within the clean room should be concealed, the piping material using non-combustible materials.
3 Ventilation and air conditioning
Filtering device is the main component of the realization of the means of purification. A clean production environment is necessary for the production of industrial gas, which is necessary to ensure the product yield and the reliability and long life of product quality.
3.1 Air purification
Clean room air purification treatment
Air filter classification: the first category of coarse, medium, sub-high-efficiency, high-efficiency and ultra-high-efficiency, filtered particle size of ?5 ?m, >1 ?m, <1 ?m, ?0.5 ?m, ?0.1 ?m; the second category of high-efficiency filtration efficiency is divided into A, B, C, D, efficiency of 99.4% and the efficiency of 99.4%, the efficiency of 99.2%, C, D, efficiency of 99.9%, 99.99%, 99.999%, 99.999% (particle size 0.1 ?m).
Filter settings: coarse filtration is set in the new air pre-treatment; intermediate filtration is used for high efficiency before the pre-filtration, to extend the life of high efficiency filters; high efficiency filters are located in the clean room, is to ensure that the key to cleanliness.
High-efficiency filters in the clean room, refers to the production process does not produce harmful substances, in order to save energy to maximize the use of return air. For high cleanliness level of unidirectional flow clean room using fresh air centralized processing plus FFU purification and air conditioning system. That is, composed of multiple fan filter unit equipment to achieve direct circulation of the clean room return air.
Frequency control fan: in the purification and air conditioning system due to changes in resistance to affect the air volume and the use of frequency control to achieve a fixed air volume or fixed pressure control, is through the high-efficiency filter pressure difference changes in control of frequency conversion devices, practice has proved that the system has a significant ` energy-saving effect.
3.2 Supervision points of clean air conditioning
3.2.1 Material inspection
3.2.1.1 Materials of ventilation ducts
(1) The materials, specifications, performance and thickness of metal ducts are in accordance with the design and current national standards. When there is no design provisions, should be implemented in accordance with the specification. And the corresponding factory inspection certificate;
(2) non-metallic duct material varieties, specifications, performance and thickness should be consistent with the design requirements and current national product standards. When there is no design, should be implemented in accordance with the specification. And have the corresponding factory inspection certificate. Non-metallic duct should provide fire and health testing certificate;
(3) fireproof duct materials, frame and fixed materials, sealing gasket must be non-combustible materials, their fire resistance level should be consistent with the design. Inspection Quantity: 10% by material processing batch number of sampling, should not be less than 5 pieces. Inspection method: check the quality certification documents, performance test reports, observation and inspection of the ignition test;
(4) composite air duct cover materials must be non-combustible materials, the internal insulation materials are also non-combustible or flame retardant B1 level, and harmless to the human body. According to the number of material processing lot of 10% random inspection, should not be less than 5 pieces. Inspection method: check the quality certification documents, performance test reports, observation and inspection of ignition test;
(5) galvanized steel surface shall not have cracks, scars and scratches and other defects, there should be galvanized crystalline pattern, there shall be no obvious oxidation, pinholes, pockmarks, skinning and plating defects such as fall off;
(6) galvanized sheet metal should have good plasticity, electrical conductivity, thermal conductivity and corrosion resistance, the surface shall not be less than five pieces. and corrosion resistance, the surface shall not have scratches and wear.
3.2.1.2 Duct insulation materials
Clean air conditioning ducts are mostly used rubber insulation, the procurement unit is required to issue manufacturers or testing department test reports, and check the thickness and fire rating is in line with the design requirements.
3.2.1.3 Supporting components
Check the static pressure box material, airtightness and rigidity, etc.; a variety of air valve airtightness and sensitivity; a variety of filters of the technical indicators, focusing on the inspection of the structure of the FFU or laminar flow hood unit, the static pressure box, the fan and the filter element whether it meets the requirements.
3.2.1.4 Equipment inspection
The main inspection equipment for the air conditioner and ozone generator, first of all, check whether the appearance is intact, and secondly, in addition to equipment to meet the appropriate qualification requirements, there should be packing lists, equipment manuals, product quality certificates and product performance test reports, and other random documents, imported equipment should also have a qualified document of the commercial inspection; and finally equipped with pieces of the inspection to be In line with the requirements (such as air-handling equipment table cooler without barbed phenomenon; filter installation seal and to facilitate maintenance, etc.).
3.2.2 Duct production and installation process quality pre-control
(1) duct materials, specifications, dimensions must meet the design requirements;
(2) duct nibble seam must be tight, no holes, half nibble distension cracks and other defects;
(3) weld is strictly prohibited to have a burn-through, leakage weld and cracks and other defects, and the longitudinal weld must be staggered;
(4) the duct is not allowed to be used for the production and installation process. >
(4) clean system ducts, fittings and static pressure box of all seams must be tight;
(5) clean system surface must be flat and smooth, prohibited transverse splicing seams and tube reinforcement frame or the use of convex rib reinforcement method;
(6) clean duct must be kept clean, free of grease and dust, etc., with a film sealing;
(7) ducts Appearance should be folded corner straight, arc uniform, two end surfaces parallel, no angle, surface concave and convex ≯ 5 mm, duct and angle steel flange connection is firm, the flap should be flat, close to the flange width should be ≮ 7 mm, and cut off the overlap, flap at the cracks and holes should be coated with sealant;
(8) duct flange hole spacing should be in accordance with the design requirements and the construction specification, welded firmly, welded at the welded seam is not set up screw holes, the screw holes have interchangeability. Screw holes have interchangeability. When used for level 5 and higher than level 5 cleanliness level occasions, angle steel flange bolt holes and fittings on the rivet hole distance should be ≯ 65 mm, level 5 or less should be ≯ 100 mm. rectangular flange corners should be set up with bolt holes, flange splicing joints should be avoided bolt holes. Bolts, nuts, gaskets and rivets should be galvanized;
(9) duct reinforcement should be firm, reliable, neat, properly spaced, uniform and symmetrical;
(10) galvanized sheet duct surface should be free of cracks and other defects, no damage to the surface of the air duct;
(11) tin insertion flange width should be the same, inserted into the ends of the firm and reliable;
(12) air ducts and Flange production size of the allowable deviation and inspection methods in accordance with the relevant norms;
(13) duct production and installation process, especially to control: rivets off, duct flange connection is not tight, flange flange leakage at the corners of the pipe connection with holes.
3.2.3 Duct installation should pay attention to the problem
In the duct through the need to close the fire, explosion-proof wall or floor, there should be a pre-embedded or protective casing, the thickness of the steel plate should be ≮ 1.6 mm. duct and protective casing, the application of non-combustible and harmless to the human body of the flexible material blocking, the surface should be finally decorative treatment. Inspection method: Verify the duct performance inspection report provided by the inspection organization, observe and inspect by comparison method or ignite the relevant material test, measure the wall thickness of the pre-buried pipe, and the wall thickness of the duct should be 10-20 mm from the inside of the flange side of the two ends of the pipe opening to test 4 points, and take the average value. Check the number: 20% of the number of random checks, not less than 1 system.
Duct installation must comply with the following provisions:
(1) the duct is strictly prohibited in other pipeline crossing;
(2) the delivery of flammable, explosive gases or installed in a flammable, explosive environment of the duct system should be a good grounding, the flange should be spanned across the wire. Through the living area or other production room must be tight, and shall not be set up interface. Conveyance of aerosol air containing biological aerosols that pose a disease risk to humans, there shall be no openings, must be openings or connections should be located in the negative pressure zone;
(3) outdoor risers are strictly prohibited from pulling the fixed cable in the lightning rod or lightning net;
(4) check the number of: 20% sampling by the number of, not less than 1 system.
3.2.4 duct segment leakage test
The system is implemented according to the design requirements, in a single branch system needs to be assembled after the leakage check, check after passing the leakage test, the test method can be according to the "Cleanroom Construction and Acceptance Specification" GB 5059?2010 Appendix A-A.2?Duct Segment Leakage Detection Methods? Carry out.
3.2.5 The installation of the ventilator should comply with the following provisions
(1) the model, specifications should be in line with the design, and its exit direction should be correct;
(2) the impeller rotation should be smooth, and should not be stopped every time to stay in the same position after stopping;
(3) fixed ventilator ground bolts should be tightened, and there are measures to prevent loosening.
Number of inspections: full number of inspections.
Inspection method: check according to the design drawings, observation and inspection.
Description: project site on the fan impeller installation quality and balance of the inspection, the most effective and rough method is to disk impeller, observe its rotation and whether it will stay in the same position.
3.2.6 Clean room test items
(1) temperature and humidity, differential pressure test;
(2) air volume test (the number of air changes);
(3) air filter leakage test;
(4) indoor air cleanliness level of the test;
(5) indoor bacterial planktonic and sedimentary bacterial detection;
The above test items can be referred to the "clean room construction and acceptance specification" GB 50591?2010 Appendix E.
4 clean pipeline
Clean pipeline is before and after the process equipment and equipment between the pipeline to transport high-purity liquid and high-purity gas. The pipeline material has certain special requirements to ensure that the gas and liquid in the delivery process is not contaminated, the pipeline is not corroded, then the process of the pipeline put forward clean requirements, especially the roughness of the inner wall of the pipeline to meet the requirements.
a) Surface roughness before polishing
b) Surface roughness after polishing
4.1 Introduction to clean pipeline
Clean pipeline has a pharmaceutical water system (purified water pipeline, pure steam pipeline, injection water pipeline), industrial media system (clean compressed air pipeline, vacuum pipeline, nitrogen, industrial steam pipeline, hot and cold media pipeline, etc.)
Pharmaceutical water systems involved in purified water piping, pure steam piping, water injection piping, clean compressed air piping and vacuum piping.
Purified water piping: material 316L stainless steel electropolished pipe, piping using automatic orbital protection welding, protective gas for 99.999% purity of argon, valves for the sanitary high-temperature diaphragm valves, welded or clamped connection, rock wool insulation, aluminum skin coating, clean room stainless steel skin coating.
Pure steam pipeline: material 316L stainless steel electropolished pipe, pipeline using automatic orbital protection welding, protective gas for 99.999% purity of argon; pipeline valves for the sanitary diaphragm valves, clamp connection, rock wool shell insulation, in the mezzanine with aluminum skin wrapped in stainless steel skin wrapped in the clean room.
Injection water pipeline: the material is 316L stainless steel inner electropolished pipe, the pipe is fully automatic orbital protection welding, protective gas for 99.999% purity of argon, the valve is sanitary high temperature diaphragm valve, welding or clamp connection. Rock wool insulation (? = 50), aluminum skin outside; clean room insulation thickness of 20 mm, stainless steel skin outside.
Clean compressed air piping and vacuum piping: the material is SUS304 stainless steel pipe, the pipeline using automatic orbital protection welding, the protective gas for the purity of 99.999% argon.
Valves, fittings and instruments on the process pipeline should be compatible with the material of the pipeline where they are located.
4.2 Pickling and passivation of clean pipelines
Pickling and passivation of clean pipelines mainly refers to pure water pipes, injection water pipes and pure steam pipelines, and its process: pure water cycle pre-rinse, lye cycle cleaning, pure water rinsing, pickling, pure water rinsing, passivation, pure water rinsing, discharging, disinfection.
4.3 Supervision of clean pipes
4.3.1 Material inspection
(1) clean pipe packaging: check for damage, pollution, water damage, etc.;
(2) whether the pipe appearance marking (material labeling, diameter and wall thickness, cleanliness level, roughness level, standard number, manufacturer labeling, etc.) is in line with the design requirements;
(2) pipe appearance marking (material labeling, diameter and wall thickness, cleanliness level, roughness grade, standard number, factory labeling, etc.);
(3) pipe appearance marking (material labeling, diameter and wall thickness, cleanliness level, roughness grade, standard number, factory labeling, etc.) whether the design requirements;<
(3) According to the relevant standards and factory material report to check the wall thickness and roughness;
(4) Random information: certificate of conformity, material report, imported materials, customs clearance procedures are complete.
4.3.2 Inspection during construction
(1) clean pipe stacking environment: should be placed indoors to avoid rain;
(2) clean pipe material environment: should be set up in the room can be sheltered from the rain, dust-free, closed;
(3) should have a special equipment for the material: including pipe cutter, mouth processor, etc., under the material must be blocked after the mouth of the pipe to transport to the welding site;
(4) random information: certificate of conformity, material reports, imported materials, such as customs procedures. Transported to the welding site;
(4) pipe welding before the requirement of sample test welding, test samples indicate the time, location, operator's name and welding parameters, samples sent to the supervisor for inspection at regular intervals;
(5) pipeline next to each weld to be affixed to the same format as the sample label and number;
(6) try to avoid hand-welding, flanges, clamps require a short pipe;
(7) welds should be ray detection, manual welding test rate of 100%, automatic welding test rate of 10%;
(8) according to the design requirements of the pressure test, pressure before the construction unit is required to report on the pressure program and safety measures;
(9) cleaning of pipelines: the construction unit is required to do the cleaning program, modification, approval of the implementation;
(10) clean Valves and fittings used indoors, in addition to meeting the process requirements, should be used to disassemble, cleaning, maintenance are convenient structural form.
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