This article focuses on 5 different aspects of GMP requirements for tablet shops.
The main contents of GMP are suitable to plant facilities, good technical equipment, and storage, and transportation conditions, trained and qualified staff, qualified raw and auxiliary materials, verified production methods in a hygienic environment, reliable quality control, and production of high-quality products.
According to the general requirements of GMP, the implementation of GMP in tablet workshops mainly includes 5 aspects: plant, equipment, personnel, production management, and quality management.
The Plant
Plant environment
(1)The main roads in the plant area are smooth, the road surface is level, there are no piles of materials, and no plants producing flakes are planted in the green area around the production plant.
(2) The plant area basically achieves four noes: no stagnant water, no weeds, no garbage, and no mosquito and fly breeding ground.
(3) The overall layout of the plant is reasonable, and the production area is separated from the administrative, living, and auxiliary areas.
(4) The clean area is far away from railroads, docks, airports, and other major roads, and the distance between it and the major roads with frequent traffic is more than 50m.
(5) The production plant is far away from the area emitting dust, smoke, and corrosive gas. Can not be far from the plant should be built in the air pollution of the upwind side.
(6) the production of penicillin and cephalosporins, contraceptive drugs plant should be strictly separated from other drug production plants, and the plant should have an independent air conditioning system so that the exhaust gas after purification treatment. This type of drug production equipment should be dedicated.
(7) production of hormones, and anti-tumor chemicals should use special equipment, equipment closed; the plant should be equipped with dust and dust-catching facilities.
Plant layout
(1) plant area should be appropriate to the scale of production, there is enough space for equipment and materials.
(2) plant according to the production process and the required clean level of reasonable layout, human flow, logistics with the appropriate self-purification facilities, flow in a reasonable direction, equipment and process requirements have to adapt to the auxiliary rooms and areas, the purification level, and production conditions.
(3) Storage has enough space and sampling facilities consistent with the production cleanliness level. Storage area is kept clean, well-ventilated, fireproof, moisture-proof, insect and rodent-proof, mold and chemical pollution. According to the need to have facilities to control temperature, humidity, etc., and set up special warehouses or cabinets for narcotic drugs, psychotropic substances, toxic drugs, and dangerous goods.
(4) set up the production of places suitable for testing, each test room according to the test requirements set up dust, shock, moisture, purification, and other facilities.
Plant facilities
(1) clean area of the ground, ceiling, and wall surface should be flat, and smooth, with no particles, no mold, and can withstand cleaning and disinfection. Plant clean area (room) wall and wall, wall and ceiling, wall and ground connection should be curved.
(2) Clean area doors, windows and ceilings are well sealed, and there are measures to prevent animals, dust, or dust from entering. The connection between the clean area and the general production area should have buffering facilities.
(3)The dry pipes of water, electricity, and process pipelines in the clean area are concealed and through the wall, and the pipes in the floor and ceiling should be sealed.
(4)There should be fewer floor drains in the clean area and measures to avoid pollution.
(5) Clean areas should be equipped with alarm devices, fire can be timely alarm.
Air purification regulation
(1)The clean air cleanliness level and the number of air changes in the clean area should meet the requirements of GMP, and the room with high dust production should keep the relative negative pressure with other areas of the same level.
(2)The air filter should be inspected, cleaned, and replaced according to the regulations, and records should be kept.
(3) The temperature and relative humidity of the clean area should be adapted to the requirements of the production process, with the control temperature at 18℃~24℃ and the relative humidity at 45%~65%.
(4) clean area and general production area should be positive pressure between and maintain ≥ 4.9Pa pressure difference, clean area has a device to detect the pressure difference.
The equipment
Selection and design
(1) equipment should meet the scale of drug production and process requirements.
(2) equipment and piping materials do not react chemically with the material. The inner wall of the equipment and pipes in contact with the drug solution should be smooth, flat, easy to clean, corrosion-resistant, and non-toxic.
(3) Tablets should be dispensed using mechanical equipment.
(4) weighing, dosing, crushing, sieving, mixing, pressing, coating, and other production facilities or production equipment should be dust-catching devices or isolation measures to prevent cross-contamination.
(5) The equipment itself is well sealed, and can effectively avoid transmission friction generated by foreign objects brought into the drug
Equipment installation
(1)The transfer equipment shall not cross the clean room of different cleanliness levels.
(2) Fixed pipeline should have a conspicuous sign, indicating its contents and flow direction.
(3)The surface of the equipment and the pipeline insulation layer is flat and smooth, and no particulate matter is shed.
(4) The storage tank of distilled water and deionized water is airtight, and the exhaust port should be equipped with a filter.
Equipment management
(1) The main equipment and pressure vessels should be established files, and the content is complete.
(2) The development of equipment operating procedures and strictly enforced.
(3) Equipment numbering, status identification, and setting up a person responsible for maintenance.
(4)The equipment is kept intact, running normally, without running, bubbling, dripping, leaking, dirty, loose, messy, rusting, lacking, etc.
(5) No overload operation of production equipment.
(6) Develop a maintenance system for major equipment and specify the maintenance cycle.
(7) There are maintenance and overhaul records.
(8) There is a system for mold management and strict implementation, and the use of the ledger is established.
(9) Develop cleaning procedures for equipment and stipulate that no fiber or particulate matter is shed.
Instruments and scales
(1)The scope of application and precision of instruments, meters, gauges, scales, etc. used in production and quality control should meet the requirements of production and quality control.
(2) measuring instruments according to the prescribed calibration period calibration, there should be the use of records.
(3) the establishment of measuring instruments ledger and precision instrument files.
Equipment verification
(1) indicate the date of calibration, and the establishment of calibration records, measuring instruments should be calibration records, and precision instruments should be used to record.
(2) new equipment in the production run before the installation, operation, and verification of performance.
(3) There are provisions for equipment revalidation, according to the characteristics of the equipment to develop the validation cycle, the equipment should be validated after major repairs or changes in key parts.
The Personnel
Basic personnel requirements
(1) quality management department personnel: ① quality management responsible person should have college (or equivalent) or above, be engaged in drug quality management for more than 3 years, the ability to make the right judgment and deal with the actual problems in production quality management; ② operators engaged in drug quality inspection should have high school (or equivalent) or above, subject to professional training and assessment, and hold an induction certificate; ③ drug production Quality management personnel should have a high school education or above, engaged in drug production for more than 3 years, have some practical experience.
(2) manufacturing department personnel: ① drug production department should be responsible for the college (or equivalent) or more and have more than 3 years of experience in pharmaceutical production management engineers and technicians: ② workshop technology should have the title of an engineer or above, secondary school or above, and production experience in engineering and technical personnel as; ③ preparation, granulation, tablet pressing workers should have more than high school education degree, after job training, inspection and qualified to work; ④ operators should have more than junior high school education, and professional training, examination and qualified to work.
Personnel training
(1) Develop staff training plan, regularly train staff on GMP, professional basic theory, and practical operation at different levels, conduct assessment and establish training and education files.
(2) Train maintenance staff and auxiliary staff on clean area management, hygiene knowledge, GMP basics, etc.
Production Management
Material management
(1) Do not use packaging materials produced by enterprises without a production license.
(2) There are raw and auxiliary materials, packaging materials, and finished products quality standards, and approved, with the implementation date and unified code, according to the prescribed standards for procurement.
(3) raw materials, auxiliary materials and packaging materials in direct contact with the drug should be fixed supply units, and the establishment of the supply unit files.
(4) materials according to the different nature of classification, partitioned by batch storage. Neat cargo space, a library to use shelves or pads, there are cargo schematics. Goods stored strictly distinguish between pending inspection, qualified or unqualified.
(5) highly allergenic drugs, toxic drugs, narcotic drugs, psychotropic substances, etc. should be stored in accordance with the provisions.
(6) The warehouse shall issue the material with the inspection report and the material receipt filled by the material unit, and both parties shall check and sign when receiving the material.
(7) According to the stability of the material storage period, more than the storage period according to quality standards after re-inspection and release, except for the drugs specified in the expiration date.
(8) Sales records are kept until one year after the expiration date of the drug, and at least three years for sales records without the expiration date.
Production process management
(1) deionized water prepared in the production process, distilled water storage, and transport pipelines should be cleaned and disinfected regularly according to regulations.
(2) Different varieties or different specifications of the same variety of product replacement, should be thoroughly cleaned and have clearing records.
(3)When replacing products of the same variety or different batch numbers of the same specification, the remnants of the previous product should be cleaned and recorded.
(4) into the clean area of raw materials in the buffer zone to remove the outer packaging or packaging cleaning process.
(5) Containers containing raw and auxiliary materials and semi-finished products should be cleaned in accordance with the process requirements, and containers, screens, and molds should be checked before and after the use of their cleanliness and integrity to prevent foreign objects mixed and cross-contamination.
(6) Check and verify the product name, batch number, expiration date, label, packing list, packing weight, and packing quantity on the packaging line, which should be in accordance with the physical.
Cleanliness and hygiene
(1) According to different cleanliness levels develop a sanitation management system, regular inspection, and have records.
(2)The waste or garbage transfer station should be far away from the production area, and no bathroom or toilet should be set up in the clean area.
(3) Establish cleaning procedures for facilities, equipment, and containers of different cleanliness levels and have cleaning records.
(4) Establish environmental monitoring systems for different cleanliness levels, and regularly monitor temperature, humidity, differential pressure, wind speed, suspended particles, and live microorganisms, with monitoring records.
(5) Work clothes according to the clean level to develop a cleaning cycle, different clean levels of work clothes, and shoes should be washed separately, not mixed put.
(6) The staff in the clean area receive regular personal hygiene education, develop personal hygiene standards and inspection system, and have records.
(7) Clean area operators do not wear watches and ornaments and do not wear makeup.
(8) The clean zone equipment cleaning validity period and disinfection validity period are stipulated as follows.
①Equipment: disinfection before production, monthly replacement of disinfectant, daily disinfection, cleaning validity period of 3 days.
②Rags: cleaning validity 3 days, disinfection 2 times a week, disinfection method is soaked for 3 minutes.
③Mop: disinfected 2 times a week, disinfection method is soaking for 3 minutes, disinfectant is changed once a month.
④Disinfectant: valid for 72 hours.
⑤Production containers: disinfection before production, cleaning validity 3 days, disinfectant replaced once a month.
⑥Clean area sanitary tools: disinfection time 3 minutes, purified water rinsing 2 minutes, cleaning validity 3 days.
(7) Clean area work clothes: cleaning is valid for 3 days.
⑧Telescopic ladder: disinfection once a week, cleaning validity 3 days.
⑨ Clean area floor drains daily cleaning, daily disinfection, the disinfectant dosage of 100ml (0.2% benzalkonium bromide, 75% ethanol.
Quality control
Quality inspection agencies and personnel
(1) An independent quality management department should be set up.
(2) Quality management department should be equipped with sufficient quality inspection personnel and full-time quality management personnel.
(3) quality management department set up quality inspection agencies, workshops set up inspection rooms (groups), and production teams set up inspection posts as needed.
Quality inspection
(1) inspection department and workshop laboratories with the necessary testing instruments and devices, test instrument precision, and stability should meet the test requirements, there are records of use.
(2) standards, controls, test bacteria, titration solution, standard solution, there is a person responsible for the custody and distribution.
(3) there is a sample observation management system, sampling procedures, and methods, and approved by the relevant departments. There are special sampling tools and containers, containers should be clean and dry. Sampling to fill out the sampling records, the records are complete.
(4) There is a person in charge of the test and observation of the sample, there are test and observation records and quality stability analysis, and there is a written summary at the end of the sample. Abnormal quality changes during the observation of retained samples, should fill out a notification form to report the person in charge, and notify the relevant departments. Samples with expiration dates are retained until 1 year after the expiration date, and samples without expiration dates are kept for at least 3 years.
