I. Inspection and evaluation methods

1. According to the good manufacturing practice (revised 1998) and its appendices, in order to unify the standards, standardize the certification inspection and ensure the quality of certification work, the Evaluation Standards for GMP Certification Inspection of Drugs are formulated.

2. There are 225 2.GMP certification inspection items, including 56 key items (*) and 69 general items/kloc-0.

3, drug GMP certification inspection, when applying for certification, according to the drug GMP certification inspection items, determine the corresponding inspection scope and content.

4. During on-site inspection, the listed items and their contents shall be comprehensively inspected; Positive or negative comments should be made item by item. All incomplete and incomplete projects are called defective projects; If the key project is unqualified, it is called a serious defect; General unqualified items are called general defects. General defective items or other problems found in the inspection that seriously affect the quality of drugs are regarded as serious defects. Inspectors shall investigate and collect evidence and make detailed records.

5. Evaluation of results:

project

Serious defect general defect

0 ≤20% passed GMP certification.

0 20-40%

≤3 ≤20%

≤3 >20%

>3

Second, GMP certification and inspection items of drugs

Check the content of the clause.

* 030 1 whether the enterprise has established pharmaceutical production and quality management institutions and defined the responsibilities of institutions and personnel at all levels.

Whether 0302 is equipped with management personnel and technical personnel suitable for drug production, and has corresponding professional knowledge.

040 1 whether the person in charge of production and quality management of the enterprise has a college degree or above in medicine or related major and has experience in drug production and quality management.

0402 Does the person in charge of the production and quality management of the biological products manufacturing enterprise have the corresponding professional knowledge (bacteriology, virology, biology, molecular biology, biochemistry, immunology, medicine, pharmacy, etc.)? ) and rich practical experience to ensure that they perform their duties in production and quality management?

0403 Whether the person in charge of drug production and quality management of Chinese medicine preparation production enterprise has professional knowledge of Chinese medicine.

050 1 Whether the person in charge of the production management and quality management department has a college degree or above in medicine or related major and has practical experience in drug production and quality management.

* 0502 Whether the heads of production management department and quality management department hold concurrent positions with each other.

060 1 Whether the personnel engaged in drug production and operation have received corresponding professional and technical training.

0602 Whether the personnel engaged in API production have received relevant knowledge training on specific operations of API production.

0603 Whether the inspectors of Chinese herbal medicines and Chinese herbal pieces have been trained in relevant knowledge and have the skills to identify the authenticity, advantages and disadvantages of Chinese herbal medicines.

0604 Whether the personnel engaged in drug quality inspection have received corresponding professional and technical training.

070 1 Whether the personnel at all levels engaged in drug production are trained and assessed according to the requirements of this specification.

0702 Whether all personnel engaged in the manufacture of biological products (including cleaning personnel and maintenance personnel) have received professional (hygiene, microbiology, etc. ) and safety protection training.

080 1 Whether the pharmaceutical production environment of the enterprise is clean and tidy, whether the ground, road surface and transportation of the factory cause pollution to pharmaceutical production, and whether the overall layout of production, administration, living and auxiliary areas is reasonable; Interfere with each other.

090 1 whether the workshop is reasonably arranged according to the production process and the required air cleanliness level.

0902 Whether the production operations in the same factory and between adjacent factories interfere with each other.

100 1 Whether the plant has facilities to prevent insects and other animals from entering.

1 10 1 Whether the inner surface of the clean room (area) is smooth, crack-free, tightly connected, free of particle shedding and resistant to cleaning and disinfection.

1 102 whether the junction between the wall and the ground of the clean room (area) is bent or other measures are taken.

1 103 whether the clean room (area) is equipped with sanitary tools that are convenient for cleaning and disinfection, whether the storage location causes pollution to the products, and whether the use area is limited.

165438+

1 105 whether there is a picking workbench for cleaning medicinal materials in the workshop, and whether the surface of the workbench is smooth and not easy to fall off.

Whether the production area of 120 1 has an area and space suitable for the production scale.

1202 Whether the workshops for extracting, concentrating, steaming, frying and baking Chinese herbal medicines and Chinese herbal pieces are suitable for their production scale.

1203 if the quality inspection of intermediate products of APIs has cross-influence with the production environment, is the inspection place set in the production area?

Whether the storage area of 1204 has an area and space suitable for the production scale.

1205 are there any measures to prevent the storage of materials, intermediate products and products to be inspected from errors and cross-contamination?

1206 whether the factories and facilities that produce and store inflammable, explosive, toxic and harmful substances of APIs comply with the relevant provisions of the state.

130 1 whether all kinds of pipes, lamps, tuyeres and other public facilities in the clean room (area) are easy to clean.

140 1 whether the illumination of clean room (area) meets the production requirements and whether the workshop has emergency lighting facilities.

* 150 1 Whether the air entering the clean room (area) is purified as required.

1502 whether the air in the clean room (area) is monitored as required, and whether the air monitoring results are recorded and archived.

1503 if the purified air in the clean room (area) can be recycled, do you take effective measures to avoid pollution and cross-contamination?

1504 whether the air purification system is cleaned, repaired and maintained as required and recorded.

* 160 1 whether the connection parts of windows, ceilings, pipes, tuyeres, lamps and lanterns with walls or ceilings in the clean room (area) are sealed.

1602 whether adjacent rooms with different air cleanliness levels have devices for indicating pressure difference, and whether the static pressure difference meets the requirements.

1603 whether the doors and windows of the workshop for the production of non-traumatic external traditional Chinese medicine preparations and their special preparations can be sealed, and whether there are good dehumidification, ventilation, dust removal and cooling facilities when necessary.

1604 whether the doors and windows of the factory building where pure medicinal materials and dry paste directly used as medicine are used for batching, crushing, mixing and sieving can be sealed and have good ventilation and dust removal facilities.

170 1 whether the temperature and relative humidity of the clean room (area) meet the requirements of the pharmaceutical production process.

180 1 whether the pool and floor drain in the clean room (area) are contaminated with drugs, 100 whether the floor drain is installed in the clean room (area).

190 1 whether there are measures to prevent cross-contamination when people and materials enter and leave clean rooms (areas) with different air cleanliness grades.

*190210,000 clean rooms (areas) whether the transmission equipment used passes through the lower area.

* 1903 whether buffer facilities are set between clean room (area) and non-clean room (area) and clean room (area)

Whether the direction of people flow and logistics is reasonable.

*200 1 Whether independent factories and facilities and independent air purification systems are used to produce highly allergic drugs such as penicillin, whether the sub-packaging room is kept at a relative negative pressure, whether the exhaust gas discharged from the sub-packaging room is purified to meet the requirements, and whether the exhaust port of the sub-packaging room is far away from the air inlets of other air purification systems.

* Whether the production areas of β -lactam structural drugs and other drugs were strictly separated in 2002, using special equipment and independent air purification system.

*2 10 1 whether the production workshop of sex hormone contraceptives is separated from other pharmaceutical production workshops, whether it is equipped with an independent dedicated air purification system, and whether the gas emission is purified.

*2 102 Whether the production of hormones and anti-tumor chemicals uses the same equipment and air purification system as other drugs; When it is inevitable, whether to take effective protective measures and necessary verification.

*220 1 Whether the processing or filling of production strains and non-production strains, production cells and non-production cells, virulent and attenuated viruses, dead and live viruses, products before and after detoxification, live and inactivated vaccines, human blood products and preventive products are carried out in the same production workshop at the same time.

*2202 Whether the storage of production strains and non-production strains, production cells and non-production cells, virulent strains and attenuated strains, dead strains and live strains, products before and after detoxification and live and inactivated vaccines, and human blood products and preventive products are strictly separated.

*2203 Whether the handling and filling of different kinds of live vaccines are separated.

* Whether the 2204 virulent microorganism working area maintains a relative negative pressure with the adjacent area, whether there is an independent air purification system, and whether the discharged air is recycled.

*2205 Whether the operating area of spore fungus products keeps relative negative pressure with adjacent areas, whether there is an independent air purification system, whether the exhausted air is recycled, and whether special equipment is used to operate spore fungus products until the inactivation process is completed.

*2206 Whether the air purification system and other facilities meet the special requirements of the operation involving high-risk pathogenic factors in the production process of various biological products.

*2207 Whether the equipment used in the production of biological products in some living organisms is special and whether it is carried out in an isolated or closed system.

* 2208 BCG production workshop and tuberculin production workshop are strictly separated from other product production workshops, and BCG production equipment should be dedicated.

*2209 Whether anthrax, Clostridium botulinum and Clostridium tetanus products are produced in the corresponding special facilities.

22 10 equipment is dedicated to the production of sporozoites. When processing a product, whether to concentrate production, whether to produce only one product in stages in a certain facility or a set of facilities.

*22 1 1 Whether the workshops and facilities producing biological products have potential pollution to raw materials, intermediates and finished products.

* Whether the production and verification of 2212 polymerase chain reaction reagent (PCR) are carried out in a separate building to prevent cross-contamination caused by aerosol formed during amplification.

*22 13 whether there are protective measures and facilities that meet the corresponding regulations when using positive samples to produce testing reagents such as human immunodeficiency virus.

*22 14 Whether the seed batches and cell banks used for production are specially reserved under the specified storage conditions, and whether only designated personnel are allowed to enter.

*22 15 whether the products made of human blood, human plasma or animal organs and tissues use special equipment and are strictly separated from the production of other biological products.

*22 16 biological products (such as monoclonal antibodies and recombinant DNA products) produced by closed system biological fermentor can be produced at the same time in the same area.

*22 17 all kinds of inactivated vaccines (including recombinant DNA products), toxoid and cell extracts can be used alternately with other aseptic products in the same filling room and filling freeze-drying facilities after inactivation or disinfection. However, after repackaging the product, it must be cleaned and disinfected effectively, and whether the cleaning and disinfection effect is verified regularly.

*22 18 Whether the pathogenic microorganism operation is carried out in a specific area and whether the relative negative pressure is maintained.

*22 19 Whether there is an independent air purification system in the bacterial (virus) operation area and the sterile (virus) operation area, and whether the air in the pathogen operation area is recycled.

*2220 Whether the air from pathogens with Grade II or above risk is discharged through the sterilization filter, and whether the performance of the filter is checked regularly. Whether there are effective disinfection facilities for discharged pollutants when using materials containing more than two pathogens to produce products.

222 1 Whether the production operation area and equipment for processing living organisms are easy to clean and remove pollution, and can withstand fumigation and disinfection.

230 1 Whether the production operations such as pretreatment, extraction, concentration, washing or treatment of animal organs and tissues are strictly separated from the preparation production.

Whether there are good ventilation, dust removal, smoke exhaust and cooling facilities in the steaming, frying and baking workshops of Chinese herbal medicines.

Whether the extraction and concentration workshops of Chinese herbal medicines and Chinese herbal pieces have good ventilation and facilities to prevent pollution and cross-contamination.

Whether there are effective dust removal and exhaust facilities for the screening, slicing and crushing of 2304 Chinese herbal medicines.

240 1 whether to use return air in the air purification system of clean room (area) where non-sterile drugs produce a lot of dust after dust collection treatment. Whether the operating room with large dust production maintains relative negative pressure in the same area as the air cleanliness level of non-sterile drugs.

250 1 Whether the dry air, compressed air and inert gas in direct contact with drugs have been purified and meet the production requirements.

260 1 Whether the storage area is kept clean and dry, and whether lighting and ventilation facilities are installed. Whether the temperature and humidity control in the storage area meet the storage requirements should be monitored regularly as required. Whether there are measures to prevent pollution and cross-contamination when sampling.

270 1 Clean room (area) Whether the air cleanliness level of weighing room or material preparation room meets the production requirements, whether there are dust collection facilities and measures to prevent cross-contamination.

Whether 280 1 laboratory, Chinese medicine specimen room and observation room are separated from the production area.

Whether the biological test and microbial limit test are carried out in different rooms.

290 1 Are instruments and meters with special requirements placed in special instrument rooms, and are there facilities to prevent static electricity, vibration, humidity or other external factors?

300 1 Whether the laboratory animal room is strictly separated from other areas, and whether the laboratory animals conform to the relevant provisions of the state.

*3002 Whether the animal house and quality inspection animal house used for the production of biological products are separated from the product production area.

*3003 Whether the feeding management requirements of animals used in biological products conform to the Regulations on the Management of Experimental Animals.

3 10 1 Whether the design, selection and installation of equipment meet the production requirements, whether it is convenient for cleaning, disinfection or sterilization, whether it is convenient for production operation and maintenance, and whether it can prevent errors and reduce pollution.

3 102 Whether the capacity of sterilization cabinet is suitable for production batch, and whether the sterilization cabinet has automatic monitoring and recording device.

3 103 Whether the piping systems, valves and ventilation filters used in the production of biological products are easy to clean and sterilize, and whether the closed containers (such as fermentors) are sterilized by steam.

320 1 Whether the surface of equipment in direct contact with drugs is smooth, flat, easy to clean or disinfect, corrosion-resistant, and does not chemically change with drugs or adsorb drugs.

Whether the surface of insulation layer of equipment in 3202 clean room (area) is smooth, bright and clean, and whether particles fall off.

3203 Whether the surfaces of tools and containers in direct contact with Chinese herbal medicines and Chinese herbal pieces are neat, easy to clean and disinfect, and not easy to fall off.

Whether 3204 equipment, containers, pipes, valves, pumps, etc. Whether high-quality corrosion-resistant materials are used in contact with the liquid medicine, and whether the connection (welding) ports are minimized in the installation of pipelines.

3205 Whether the filtering equipment absorbs the components of liquid medicine and releases foreign substances, it is forbidden to use filtering equipment containing asbestos.

Whether lubricants and coolants used in 3206 equipment pollute drugs or containers.

330 1 Whether the main fixed pipes connected with the equipment are marked with the name and flow direction of the materials in the pipes.

Whether the preparation, storage and distribution of 340 1 purified water can prevent the breeding and pollution of microorganisms.

* Whether the preparation, storage and distribution of 3402 water for injection can prevent microbial breeding and pollution, whether the exhaust port of the storage tank is equipped with a hydrophobic sterilization filter that does not remove fibers, and whether the storage is kept above 80℃, above 65℃ or below 4℃.

*3403 Whether the materials used for storage tanks and pipelines are non-toxic and corrosion-resistant, whether the design and installation of pipelines avoid dead corners and blind pipes, and whether the cleaning and disinfection cycles are specified for storage tanks and pipelines.

*3404 Whether the water for injection for the production of biological products is used within 6 hours after preparation; Sterilize within 4 hours after preparation and use within 72 hours.

Whether the design, installation and maintenance of 3405 water treatment and its supporting system can ensure that the water supply meets the set quality standards.

350 1 Whether the use scope and accuracy of instruments, meters, measuring tools and weighing instruments for production inspection meet the requirements of production inspection, whether there are obvious conformity marks and whether they are calibrated regularly.

360 1 Whether the production equipment has obvious status marks.

Whether the 3602 production equipment is regularly repaired and maintained. Whether the operation of equipment installation, repair and maintenance affects the product quality.

Is there a filtering device at the air inlet of the non-sterile drug drying equipment and an air backflow prevention device at the air outlet?

Whether articles and equipment that pollute pathogens in the production of biological products are separated from unused sterile articles and equipment, and clearly marked.

370 1 Whether the production and inspection equipment has a record of use, repair and maintenance, and whether it is managed by a special person.

380 1 Whether the management system of material procurement, storage, distribution and use has been formulated.

3802 Whether raw and auxiliary materials are stored separately according to varieties, specifications and batch numbers.

*390 1 Whether the material meets the drug standards, packaging material standards, biological product regulations or other relevant standards shall not have adverse effects on drug quality.

3902 Whether raw materials and auxiliary materials are sampled and tested by batch.

*3903 Whether the imported raw materials, Chinese herbal medicines and Chinese herbal pieces have the drug inspection report of the port drug inspection office.

400 1 Whether the Chinese herbal medicines are purchased according to the quality standards, whether the origin remains relatively stable, and whether the purchased Chinese herbal medicines and Chinese herbal pieces are recorded in detail.

Whether each package of 4002 Chinese herbal medicines and Chinese herbal pieces is clearly marked, indicating the name, specification, quantity, place of origin and date of receipt (production).

4 10 1 Whether the materials are purchased from qualified units and put into storage as required.

420 1 Whether the materials to be inspected, qualified and unqualified are strictly managed.

*4202 Whether the unqualified materials are stored in the special area, whether there are obvious signs that are easy to identify, and handle them in time according to relevant regulations.

430 1 Whether the materials, intermediate products and finished products with special requirements are stored according to the specified conditions.

4302 Whether solid raw materials and liquid raw materials are stored separately, whether volatile substances avoid polluting other substances, whether the processed pure medicinal materials use clean containers or packaging, and whether the pure medicinal materials are strictly separated from unprocessed and processed medicinal materials.

*440 1 Whether narcotic drugs, psychotropic drugs and toxic drugs (medicinal materials) are inspected, stored and kept according to regulations.

* Whether the strain 4402 is inspected, stored, kept, used and destroyed as required.

When using animal-derived raw materials for biological products, detailed records should be made, including at least the animal source, animal breeding and feeding conditions and animal health status.

4404 Whether the animals used for vaccine production are clean animals or above.

Whether the original seed batch, main seed batch and working seed batch system are established for 4405 production strains.

Whether the seed batch of 4406 has complete information on original source, characteristics identification, subculture pedigree, single pure microorganism, production and culture characteristics, optimal preservation conditions, etc.

Whether the original cell bank, primary cell bank and working cell bank system have been established for 4407 production cells.

Does the 4408 cell bank system include: the original source of cells (karyotype analysis, tumorigenicity), population doubling number, passage pedigree, whether cells are single purified cell lines, preparation methods, optimal preservation conditions, etc.

4409 Whether inflammable, explosive and other dangerous goods are accepted, stored and kept according to regulations.

*44 10 Whether there are special warehouses or counters for toxic medicinal materials and precious medicinal materials respectively.

44 1 1 Whether there are obvious specified marks on the outer packaging of toxic medicinal materials, inflammable and explosive medicinal materials, etc.

450 1 Whether the materials are stored according to the specified service life, and whether they are reinspected according to the regulations after expiration; Whether to reinspect in time in case of special circumstances during storage.

*460 1 Whether the drug labels and instructions are consistent with the contents, styles and words approved by the drug supervision and administration department. Whether the drug packaging printed with the same content as the label is managed according to the label.

* Whether the 4602 label and instruction manual are printed, distributed and used after being audited by the quality management department.

470 1 Whether labels and instructions are kept and collected by special personnel.

Whether 4702 labels and instructions are stored in the counter (warehouse) according to varieties and specifications, whether they are distributed according to batch packaging instructions, and whether they are collected according to actual requirements.

Whether the 4703 label is counted and issued shall be checked and signed by the receiver. Whether the sum of label usage, damage and remaining quantity is consistent with the collected quantity.

4704 Whether the damaged labels or residual labels with batch numbers are destroyed by special personnel, whether there are records, and whether there are records of distribution, use and destruction.

480 1 Whether the enterprise has sanitary measures to prevent pollution and various sanitary management systems, and whether the person in charge is responsible.

490 1 Is the workshop cleaning regulation formulated according to the requirements of production and air cleanliness level, and does the content include: cleaning methods, procedures, intervals, cleaning agents or disinfectants used, cleaning methods and storage locations of cleaning tools?

Is the 4902 equipment cleaning regulation formulated according to the requirements of production and air cleanliness level, and does the content include: cleaning methods, procedures, intervals, cleaning agents or disinfectants used, cleaning methods and storage locations of cleaning tools?

Is the 4903 container cleaning regulation formulated according to the requirements of production and air cleanliness level, and does it include: cleaning method, procedure, interval time, cleaning agent or disinfectant used, cleaning method and storage location of cleaning tools?

500 1 Whether unproductive articles and personal sundries are stored in the production area, and whether the wastes in production are handled in time.

5002 contains high-risk pathogens such as cholera, mouse vaccine, HIV, hepatitis B virus, etc. , whether the suspected contaminated items are disinfected on the spot, whether they are disinfected separately, and whether they can be moved out of the work area.

5 10 1 Whether the setting of changing rooms, bathrooms and toilets has adverse effects on clean rooms (areas).

Whether the material of 520 1 work clothes meets the requirements of production operation and air cleanliness grade shall not be mixed. Whether the texture of clean work clothes is smooth, does not generate static electricity, and does not shed fibers and particles.

Whether the style and wearing method of 5202 sterile work clothes can cover all the hair, beard and feet and prevent the human body from falling off.

5203 Whether the work clothes used in different air cleanliness grades are cleaned and sorted, disinfected or sterilized if necessary, and whether the work clothes cleaning cycle is formulated.

Whether the clean work clothes in the area above grade 5204 100000 are washed, dried, sorted and sterilized in the clean room (area) as required.

Whether 530 1 Clean room (area) is limited to the production operators and approved personnel in this area, whether the number of personnel is strictly controlled, and whether temporary outsiders are guided and supervised.

5302 Whether the staff (including maintenance and auxiliary personnel) who enter the clean area regularly carry out training and assessment on basic knowledge of hygiene and microbiology and clean operation.

5303 During the production day of biological products, production personnel shall not go from the area where live microorganisms or animals are operated to the area where other products or microorganisms are operated without clearly defined decontamination measures.

Whether the personnel irrelevant to the production process enter the vaccine production control area and wear sterile protective clothing when entering.

Whether the personnel engaged in the production and operation of biological products are separated from the animal breeders.

540 1 whether the personnel entering the clean room (area) wear makeup and accessories, whether they directly touch drugs with their bare hands,/whether the operators in the clean room (area) of kloc-0/00 operate with their bare hands, and whether their hands are disinfected in time under inevitable circumstances.

Whether 550 1 clean room (area) is disinfected regularly; Whether the disinfectant pollutes equipment, materials and finished products, and whether the disinfectant varieties are changed regularly to prevent drug-resistant strains.

560 1 Do drug producers have health records, and do producers who have direct contact with drugs have physical examinations at least once a year? Whether patients with infectious diseases and skin diseases and those with wounds on the body surface are engaged in the production of direct contact drugs.

Whether the operators and managers of biological products production, maintenance, inspection and animal feeding are vaccinated and have regular physical examinations.

5603 Do people suffering from infectious diseases, skin diseases, skin injuries and potentially adverse effects on the quality of biological products enter the production area for operation or quality inspection?

*570 1 whether the enterprise conducts drug production verification, whether it establishes a verification team according to the verification object, puts forward verification projects, formulates verification schemes, and organizes their implementation.

* Does the verification content of 5702 pharmaceutical production process include air purification system, process water system, production process and its changes, equipment cleaning and changes of main raw and auxiliary materials?

*5703 Does the verification of key equipment and sterile drugs include sterilization equipment, liquid medicine filtration and filling (sub-packaging) system?

Whether to revalidate 580 1 after a period of production.

590 1 Whether to write a verification report after the verification work is completed shall be reviewed and approved by the person in charge of the verification work.

600 1 Whether the data and analysis contents in the verification process are archived in the form of documents, and whether the verification documents include verification schemes, verification reports, evaluations and suggestions, approvers, etc.

640 1 Whether the management system of document drafting, modification, review, approval, cancellation, printing and storage is established.

6402 Whether the file distributed and used is the currently approved text. In addition to filing for future reference, whether invalid and expired documents appear on the job site.

Whether the document 650 1 is formulated as required.

*660 1 whether there are production process regulations, post operation methods or standard operating procedures, whether they are changed at will, and whether they are changed according to the prescribed procedures if necessary.

Whether the 6602 biological products are produced in strict accordance with the Regulations of China on Biological Products or the process approved by National Medical Products Administration.

Whether to check the material balance of 670 1 product. If the material balance exceeds the specified limit, the reason should be found out, and the normal products can be treated only after reasonable explanation and confirmation that there are no hidden dangers of quality accidents.

Whether the precious and toxic medicinal materials and Chinese herbal pieces needed in the production of 6702 traditional Chinese medicine preparations are monitored and recorded according to the regulations.

680 1 Whether to create mass production records. Whether the batch production records are timely, clear, true in content and complete in data, and signed by operators and auditors.

Whether the production records of batch 6802 are kept clean and tidy shall not be torn up or altered at will. If the batch production record is filled in incorrectly, is it changed according to the regulations? Whether the batch production records are filed according to the batch number and kept for one year after the expiration date of the drug; Whether the batch production records of drugs without expiry date are kept for three years.

Whether the production record of 6803 API is traceable or not, its batch production record at least starts from the refining process of crude products.

* 690 1 Whether the drugs are divided into production batches according to regulations and the production batch number is compiled.

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