First, GMP requirements for QC laboratory personnel in pharmaceutical factories
The quality control laboratory should be equipped with a certain number of management and inspection personnel with corresponding professional knowledge. The specific requirements are as follows:
(1) the person in charge of the department should have a college degree or above in medicine or related major, have practical experience in drug quality inspection management, be able to effectively organize, guide and carry out the business work of the department, make correct judgments and treatments on related problems in drug inspection in time, and be responsible for the inspection results.
(2) Drug inspectors shall undergo professional technical training and post assessment, have basic theoretical knowledge and practical operation skills, and be approved by the person in charge of enterprise quality before taking up their posts. Non-professional technicians and personnel without technical titles shall not engage in drug inspection. Drug quality inspectors with high biological activity, high toxicity, strong pollution, high sensitization and special requirements shall receive corresponding professional and technical training.
(3) Employees should have regular physical examinations and make records. When people are found to have diseases (such as infectious diseases and skin diseases). ) adversely affect the laboratory work, should be suspended or transferred from its work.
(4) The quality inspection laboratory shall arrange training and business training plans, train and assess personnel at all levels through various channels and forms, attach importance to the cultivation of technical backbones, make annual plans, and determine training objectives and training contents. Training and evaluation should be documented.
(5) Quality inspector files, including training materials, training certificates, job certificates, academic certificates, professional skills certificates, health examination materials, etc. , kept by the personnel department.
Second, GMP requirements for QC laboratory software
(1) The setting of inspection quality system shall include the following aspects and be documented:
A) Quality assurance of inspection process (such as implementation of inspection procedures, inspection basis and standard operating procedures, writing, inspection and audit of records and reports, processing of experimental data, issuance of reports, etc.). );
B) Quality assurance of test environment and instruments and equipment;
C) Quality assurance of reference materials, experimental animals and reagents;
D) technical quality assurance of inspectors, etc. There should be a clear classification responsibility system in the quality inspection guarantee system to ensure the quality of the whole process of drug inspection, and to ensure the accuracy and reliability of various reports such as drug inspection, standard review and establishment of new drug inspection methods.
(2)QC laboratory should set up a quality supervisor to re-examine and handle the inspection, inspection, experimental records, unqualified drugs or inspection results under suspicious circumstances.
(3) In order to improve the quality of inspection work and ensure the reliability of inspection data, all inspection operations in QC laboratory (use of instruments and equipment, inspection techniques and methods, animal experiment procedures, preparation and management of reagents and liquid medicines, etc.). ) should be expressed in the form of SOP, and the defined SOP should be clear, definite, coherent and easy to understand, and used in the experimental field. The formulation and revision of SOP shall be carried out according to the prescribed procedures, and the original records of formulation and revision shall be kept.
(4) Before the development of new products, the drafting of analytical methods for drug quality standards, the change of pharmaceutical production methods, the change of preparation components and the revision of original analytical methods, or the introduction of other analytical methods for drug quality standards, methods should be verified. Before the start of verification, a verification scheme should be formulated for the verification object, and submitted to the verification committee or other verification management institutions for approval before implementation. The verification content should at least include accuracy, precision, specificity, detection limit, quantitative limit, linear range and durability index. In the process of implementation, the verification record should be filled in carefully, and the verification report issued should be submitted to the verification Committee or other verification management institutions for approval before it takes effect. Verification scheme and records (including printed original data, etc.). ) and reports should be filed in a unified way.
(5) The management system of experimental reagents should include procurement, preparation, consistency inspection, effectiveness management, use record filling, identification of articles in bottles, and account management of reagents in and out of storage.
(6) The quality control of standard and reference materials shall conform to the relevant provisions of China Pharmacopoeia and China Biological Products Regulations, and a corresponding management system shall be formulated, which shall be implemented by special personnel. There must be records in and out of the account.
(7) Laboratory management system should include laboratory work system, safety system, inspection and sample retention system, cleaning and sterilization system, bacterial virus species and cell strains management system, experimental reagent, test solution and titration solution quality management system, drug standard substance management system, measurement management system, precision instrument management system, experimental animal management system, confidentiality system, error accident management system, etc.
(8) Management of inspection records and reports. Inspection records are the original basis for issuing inspection reports. Must be written in blue-black ink or carbon pen, so that the records are original, the data are true, the handwriting is clear and the information is complete. The signature of personnel shall be in full name. The original records shall be filed by page number, and the contents shall not be disclosed privately. The inspection report is a technical appraisal of drug quality, which should be complete in information, clear in handwriting, standardized in language and clear in conclusion, and kept for a long time according to the specified time (one year after the expiration date of the product, at least three years without expiration date), and its format should be printed in a unified and standardized manner.
(9) File management. The quality control laboratory should be equipped with necessary facilities to ensure the integrity and safety of files, so as to archive the whole set of inspection data after all inspection work is completed.
(10) Self-inspection Qc laboratories should regularly or irregularly check the implementation of the quality assurance system of each laboratory, and write inspection records, including date, purpose, content, implementation, suggestions and opinions, names of inspectors, etc. Report any major problems in time.
Three, GMP requirements for QC laboratory hardware
(1) laboratory scale and layout requirements
1) laboratory scale (including building area, room function setting, etc. ) should adapt to the requirements of inspection function to meet the needs of various experiments. Rooms and areas with different functions should be clearly distinguished, emergency lighting and alarm devices should be set up, and reasonable disaster avoidance routes should be considered.
2) The laboratory should be completely separated from the production area, and the environment should be clean, ventilated, bright and quiet, and away from noise, vibration and pollution sources.
3) The following areas in the laboratory should be physically isolated and arranged separately: the receiving area and the storage area for inspection samples; Receiving and storage areas for reagents and standards; Clean the washing area; Special operation area; General analysis experimental area; Aseptic laboratory; Sample observation room (including accelerated stability laboratory); Data processing and data storage area; Office; Personnel room (locker room and lounge).
4) The laboratory should be equipped with a special or dual-purpose sampling room suitable for inspection requirements, and the cleanliness level of the sampling room should be the same as that of the production feeding area; If sampling is not carried out in the sampling room, there should still be measures to prevent pollution and cross-pollution, such as using sampling carts.
5) The storage area of the laboratory should be suitable for the properties of the stored materials, such as flammability, toxicity, corrosiveness and confidentiality.
6) Biological verification, microbial limit inspection and radioisotope verification shall be conducted in a separate room.
7) Instruments and equipment with special requirements for dust prevention, humidity, temperature and vibration should be placed in a special instrument room.
8) Laboratory animal rooms should be strictly separated from other areas.
(2) Requirements for laboratory facilities
1) The pipelines in the laboratory should be arranged neatly, with safety management measures and alarm, emergency and first aid facilities. Laboratories used for testing radioactive drugs, bacteria and vaccines shall have corresponding safety protection facilities.
2) According to the needs of experimental safety, eye washing devices for accidents and accident shower places shall be set in convenient places.
3) 3) The design requirements of QC sterile operation room are the same as those of sterile product production site. When local 100-level measures are adopted, the environment should meet the requirements of 10,000-level cleanliness, and at the same time, relative positive pressure or negative pressure should be maintained according to the needs of the inspected products, and the cleanliness should be monitored regularly; Cleaning facilities and buffer room shall be provided when entering the aseptic operation room; The laboratory should have good lighting conditions and equipment to control temperature, humidity and other indicators.
4) The cold storage of the laboratory should be strictly managed, and the stored items should be partitioned and clearly marked. The thermometers used for monitoring should be qualified by metrological verification and reasonably arranged.
5) Animal experimental facilities and conditions (including building facilities, environmental conditions, noise, feed, etc. ) should meet the grade requirements of experimental animals used for verification, meet the corresponding national standards, and meet the special requirements of drug verification; Experimental animals used for drug testing should have quality certificates and indeed meet the quality standards stipulated in the certificates.
6) The instrument room should have facilities to prevent static electricity, vibration, humidity or other external factors from interfering with the normal use function of the instrument; The power supply used by the instrument should ensure constant voltage, sufficient capacity and good special grounding wire.
7) The sampling room shall be equipped with an air purification system to prevent pollutants from spreading and staying when the container is opened, with cleaning and disinfection sampling tools and tools for opening and closing the container again, and with signs or seals indicating that the container has been sampled.
8) There is a sample holding room that meets the sample holding requirements.
9) The quality inspection laboratory shall be equipped with "three wastes" protection and treatment devices.
10) install a well-ventilated toxic gas cabinet for chemical analysis, and the wind speed when it is opened shall not be lower than 0.40 and s.
(3) Requirements for experimental instruments and equipment
1) The types, quantities and parameters of the instruments and equipment selected by the quality control laboratory should meet the needs of the drug inspection work undertaken, with necessary spare parts and accessories. The measuring range, precision, accuracy and resolution of the instruments can cover the requirements of the standard technical indicators of the tested drugs.
2) Compulsory measuring instruments and equipment can only be put into use after they have passed the measurement by the national legal measuring units, and they are regularly verified and labeled as qualified.
3) Precision instruments should be managed by special personnel and checked regularly. Unqualified, repaired and inspected instruments should have obvious status marks and be handled in time. Instrument users should pass the examination before operation, and the use of precision instruments should have a use registration system.
4) Experimental equipment and instruments should not interfere with each other and should be considered in layout (for example, ovens and refrigerators, centrifuges and balances should be arranged separately).
5) The experimental instruments and equipment shall be affixed with the equipment number, qualified verification label and working status mark, which is convenient for use and management.
(4) Requirements for experimental reagents
1) laboratory reagents shall be purchased, stored and used according to the management regulations, and classified storage facilities that are light-proof, heat-insulated and easy to use shall be provided as required.
2) The outsourced and self-made experimental reagents should be packaged in containers that meet the requirements and labeled in obvious places. The contents of the label shall include the name, specification or concentration of the reagent, purchase date and manufacturer (or preparer, preparation date and preparation specification number), expiration date, use and storage conditions, etc. , and increase security when necessary; The standard document number, opening date and signature of the person in charge should be added to the benchmark standard; For titrant, the calibration date and the factors used should also be indicated.
The above is the answer given by Siegel Laboratory Design and Construction Company, thank you!