The new version of the Good Manufacturing Practice for Drugs has strengthened the quality control of the production process, requiring standardized quality monitoring operations in the production process to ensure that all production links of the product are effectively controlled. Quality supervision and management personnel must strengthen the production process and before and after production. Quality control and management to ensure drug quality.

1 Pre-production monitoring

First of all, in terms of production hardware, the production environment must comply with regulations, and the temperature, humidity, and pressure difference in the operation room should meet the production process requirements; the clean area is regularly monitored and meet the requirements. The operating procedures for each position are the current version, and the batch records of products prepared for production and the equipment usage records are complete. For example, the production environment in general areas requires that factory buildings, equipment, containers, utensils, tools, floors, doors, windows and other surfaces should be clean and dust-free, and that there should be no mice, flies, insects and other rodents in the factory building. In addition to the requirements of the general area production environment, the clean area production environment should also meet the corresponding pharmaceutical requirements at the clean area level. The clean area temperature: 18℃-26℃; relative humidity: 45%-65%. The pressure difference between clean areas and non-clean areas, and between clean areas of different levels, should be no less than 10 Pa. The pressure difference between clean rooms (areas) with different air cleanliness levels should be greater than 5 Pa, and should be recorded for each shift. A clean room (area) with a high air cleanliness level requires a relatively positive pressure to an adjacent clean room (area) with a low air cleanliness level, which is recorded for each shift.

In terms of personnel requirements, production personnel must be qualified to work, and their clothing, personal hygiene and operating behavior must meet the requirements. Taking oral preparations as an example, the hands of staff in the clean area must be disinfected with 75% ethanol. The work clothes and masks in the clean area are cleaned and then disinfected and sterilized (100°C, 40 minutes drying and sterilization), and the storage time should not exceed 24 hours. The floor drain in the clean area should be cleaned every day. Disinfectant should be added to the floor drain after cleaning. The disinfectant should be stored in the floor drain for no more than 24 hours.

The process water meets the process conditions, and the monitoring results meet the requirements. For example, purified water for oral preparations is required to test the pH, conductivity (conductivity ≤ 5 μs/cm), ammonia, and chloride of the purified water every two hours. The test results should meet the purified water quality standards. Purified water samples should be taken and sent every month. The quality department conducts full inspection of the project. If the production is stopped for more than three days, the tank must be removed for cleaning; the purified water storage tank must be removed for cleaning at least every 3 months. When cleaning, first clean and scrub with 0.5% sodium carbonate, then rinse the storage tank thoroughly with drinking water and purified water. The pH, ammonia, chloride, and conductivity of the last clean water should be tested to meet the purified water quality standards. Disinfection of purified water storage tanks and pipeline systems can be pasteurized once a week, with the water temperature controlled above 80°C and circulated for two hours.

Before production, the production site should be cleared in accordance with the relevant management procedures for site clearance, have a clearance certificate and be within the cleaning validity period; no materials, documents, tools or tools unrelated to the products to be produced should be left on site. etc.; status identification is complete, correct and clear. The production personnel of each process shall conduct inspections according to the pre-production inspection list of each process in the batch record, double-check, and the quality supervision and management personnel will sign to allow entry into the production stage after confirming that they are qualified.

2 Production process control

During the production process, quality supervision and management personnel should monitor the production site, environment, materials, production equipment, process parameters, personnel operations, etc. The production equipment is required to be in a cleaned state and within the cleaning validity period, and the equipment is in a normal state within the confirmation or verification validity period to ensure that production conditions always meet the production process requirements. Weighing, batching, and feeding should all be reviewed by an independent reviewer. Material labels should be filled in and pasted in a timely manner to correctly indicate material information and quantity. For example, when picking up materials, the workshop production supervisor will notify the workshop material clerk to collect the inspected raw materials and auxiliary materials from the warehouse according to the batch production instructions. The workshop material clerk checks the incoming materials from the warehouse one by one. If they are correct, they receive the materials and hand them over to the production operator. Before the preparation operation, the operator should check the name, batch number, and inspection report of the raw and auxiliary materials one by one according to the product process card and batch production instructions, check the appearance quality of the raw and auxiliary materials, and calculate and review the input amount, and then the quality supervision and management personnel will review it.

Quality supervision and management personnel should check whether the status signs of rooms, equipment, etc. are consistent with the products being operated in the operation room at the production site, and whether the batch record content is consistent with the on-site content. Whether the production operation process and parameter control comply with the process procedures, whether the production process meets the requirements of batch records and job operating procedures, and whether production personnel fill in batch records and other records correctly and in a timely manner, and fill in compliance with the requirements. The process requirements for materials and intermediate products entering and leaving the temporary storage room are correct, the handover procedures are complete, and the quantity of materials received and distributed is correct, which should be reviewed by two people; the labels and status of the materials should be complete and correct, and placed neatly and orderly.

3 Monitoring the end of production

After the production process is completed, each process should clear the production site and equipment in a timely manner according to the clearance procedures. After the site is cleared, the quality supervision and management personnel will check the effectiveness of the site clearance. If qualified, they will sign the original and copy of the "Cleaning Certification" at the specified locations.

Quality supervision and management personnel should check the material balance and yield rate after the completion of the production process. The results should be within the specified limits. It is required that the flow of materials and intermediate products in and out of the temporary storage room is correct, the handover procedures are complete, and the quantity Correct, there is double review. Material labels and status identification are complete and correct, and placed neatly and orderly.

After the batch production is completed, any unused packaging materials with batch numbers printed on them should be destroyed and recorded in a timely manner after material balance; unqualified products or remaining process products should be identified in a timely manner and kept or destroyed in accordance with regulations; production waste should be timely and in accordance with procedures. Clear out the production area.

4 Monitoring of company production areas

On-site quality supervision and management personnel should also regularly monitor company production areas, including sanitary ware rooms, container temporary storage rooms, and mold storage Check somewhere else. The mold storage room mainly checks whether the issuance and withdrawal records of molds are filled in timely, whether molds are inspected regularly according to regulations, whether lubricating oil meets corresponding specifications, and whether various hoses are clean and stored according to regulations. The sanitary ware room mainly checks whether the sanitary ware to be used with a specified validity period is within the validity period, whether other sanitary ware stored in the sanitary ware room is clean, and whether the disinfectant stored in the sanitary ware room is within the validity period.

5 Outer packaging production monitoring

Inspect packaging materials before use. Check the material code, product name, batch number and quantity of the packaging materials one by one according to the batch packaging records. For those with printed words Packaging materials should also be checked to see if the text content, patterns, specifications and dimensions of the packaging materials are clear and correct. When replacing the packaging materials with a new batch number, the above content should be re-checked. The production personnel of each process shall conduct inspections according to the pre-production inspection list of each process in the batch packaging record. Double-check, the packaging team leader and the on-site quality will confirm that they are qualified and write it on the batch record. The signature authorizes entry into production. For the printing of cartons, bottle labels and steel knife boxes, the operator prints qualified samples as required. After submitting them to the packaging team leader for review, the on-site quality supervision and management personnel are notified for the first inspection. The on-site quality supervision and management personnel sign on the batch record after passing the inspection. Then production started.

In short, doing a good job in the monitoring and management of key projects in the pharmaceutical production process and standardizing the quality monitoring operations of the pharmaceutical production process can ensure that the quality of each production link of the pharmaceutical is effectively controlled and the product quality is guaranteed.