Earlier I have shared you the GMP Requirement for Pharmaceutical plant premises & Equipment’s. There are various modules of GMP which I will share one after another & today’s module is Production.
General Requirements :
The handling of materials and products, such as receipt, quarantine, sampling, storage, labeling, dispensing, processing, packaging and cleaning should be done in accordance with written procedures or instructions (Standard Operating Procedure) and, where necessary, recorded.
Deviation from instructions or procedures should be avoided as far as possible and If deviations occur, they should be in accordance with an approved procedure. The deviation shall be raised and approved and the required Corrective and Preventive action shall be taken.
Yields and reconciliation of quantities should be carried out at different stages of Manufacturing and packing to ensure that there are no discrepancies outside acceptable limits.
Operations on different products should not be carried out simultaneously in the same room or area as there are the chances of mix up or cross-contamination.
During manufacturing and packing the major items of equipments, the rooms, packaging lines being used should be labelled or otherwise identified with an indication of the product or material being processed. The labelled should contain Material name or product name, Batch number, Stage of manufacturing, done by, checked by and date etc to avoid mix-up.
Access to production premises should be restricted to authorized personnel.
In-process controls are usually performed within the production area.
Prevention of cross-contamination and bacterial contamination during production :
When dry materials and products are used in production, special precautions should be taken to prevent the generation and spreading of dust. Provision should be made for proper air control (e.g. supply and extraction of air and dust extraction system).
Contamination of a starting material or of a product by another material or product must be avoided.
Cross-contamination should be avoided by taking appropriate technical or organizational measures, for example: (a) carrying out production in dedicated and self-contained areas (which may be required for products such as penicillins, live vaccines, live bacterial preparations and certain other biologicals); (b) conducting campaign production (separation in time) followed by appropriate cleaning in accordance with a validated cleaning procedure; (c) providing appropriately designed airlocks, pressure differentials, and air supply and extraction systems; (d) minimizing the risk of contamination caused by recirculation or reentry of untreated or insufficiently treated air; (e) wearing protective clothing where products or materials are handled; (f) using cleaning and decontamination procedures of known effectiveness; (g) using a “closed system” in production; (h) testing for residues; (i) using cleanliness status labels on equipment.
Measures to prevent cross-contamination and their effectiveness should be checked periodically according to SOPs. Production areas where products are processed should undergo periodic environmental monitoring (e.g. for microbiological and particulate matter, where appropriate).
Processing or Manufacturing operations :
Before any processing operation is started, steps should be taken to ensure that the work area and equipment are clean and free from any starting materials, products, product residues, labels and documents which are not required for the current operation.
Line clearance should be taken before starting of any activity for the respective areas and equipments where batch processing shall be carried out.
For Line clearance Refer : https://pharmaceuticalupdates.com/2019/02/06/line-clearance-procedure-in-pharmaceuticals/
Any necessary in-process checks and environmental controls should be carried out and recorded during activity and at regular intervals.
Defective equipment should be withdrawn from use until the defect has been rectified. After use, production equipment should be cleaned without delay according to detailed written procedures and stored under clean and dry conditions in a separate area or in a manner that will prevent contamination.
Production equipment should be thoroughly cleaned according to a fixed schedule or after product to product change over or batch to batch change over or based upon validity of Cleaned equipment or Dirty equipment’s.
Balances and other measuring equipment of an appropriate range and precision should be available for production and control operations and should be calibrated according to a fixed schedule i.e. Calibration and daily Verification of weighing balances, Calibration of In process checks instruments like Disintegration tester, Friability, LOD apparatus, Vernier caliper, Hardness and Thickness Tester, leak test apparatus .
The cleaning, usage and preventive maintenance details shall be mentioned in the respective equipment logbooks separately which shall content Date, Product name, Batch number, cleaning or usage activity start time, End time, activity done by, checked by and type of cleaning or preventive maintenance etc. Any significant deviation from the expected yield should be recorded and investigated.
Pipework, light fittings, ventilation points and other services should be designed and sited to avoid the creation of recesses that are difficult to clean. As far as possible, for maintenance purposes, they should be accessible from outside the manufacturing areas.
Water sampling should be done at a regular interval or as per scheduled in production area
Measuring, weighing, recording, and control equipment and instruments should be serviced and calibrated at prespecified intervals and records maintained. To ensure satisfactory functioning, instruments should be checked daily or prior to use for performing analytical tests. The date of calibration and servicing and the date when recalibration is due should be clearly indicated on a label attached to the instrument.
Repair and maintenance operations should not present any hazard to the quality of the products.
Packaging operations :
When the packaging is going to start particular attention should be given to minimizing the risk of cross-contamination and mix ups. Different products should not be packaged in close proximity unless there is physical segregation or an alternative system that will provide equal assurance.
Before packaging operations are begun, steps should be taken to ensure that the work area, packaging lines, printing machines and other equipment are clean and free from any products, materials or documents used previously and which are not required for the current operation. The line clearance should be performed according to an appropriate procedure and checklist, and recorded.
The name and batch number of the product being handled should be displayed at each packaging station or line.
Normally, filling and sealing should be followed as quickly as possible by labelling. If labelling is delayed, appropriate procedures should be applied to ensure that no mix ups or mislabelling can occur.
The correct performance of any printing (e.g. of code numbers or expiry dates) done separately or in the course of the packaging should be checked and recorded. Attention should be paid to printing by hand, which should be rechecked at regular intervals.
Before start of packing activity the Specimen proof like Foil carton, leaflet, label etc should be checked by both production and Quality assurance and same shall be preserved along with batch record Regular online control of the product during packaging should include at a minimum checks on: (a) the general appearance of the packages; (b) whether the packages are complete; (c) whether the correct products and packaging materials are used; (d) whether any overprinting is correct; (e) the correct functioning of line monitors. Samples taken away from the packaging line should not be returned.
Any significant or unusual discrepancy observed during reconciliation of the amount of bulk product and printed packaging materials and the number of units produced should be investigated and recorded before batch release to market.
Upon completion of a packaging operation, any unused batch-coded packaging materials should be destroyed and the destruction recorded.
The excess printed packing materials like Aluminum foil, PVC/PVDC can be returned to warehouse with material return note.
Production records should be reviewed as part of the approval process of batch release and any deviation or failure of a batch to meet production specifications should be thoroughly investigated. The investigation should, if necessary, extend to other batches of the same product and other products that may have been associated with the specific failure or discrepancy.