GENERAL:
- The processing of dry materials and products creates problems of dust control and cross-contamination. Special attention is therefore, needed in the design, maintenance and use of premises and equipment in order to overcome these problems. Wherever required, enclosed dust control manufacturing systems shall be employed.
- Suitable environmental conditions for the products handled shall be maintained by installation of air-conditioning wherever necessary. Effective air extraction systems, with discharge points situated to avoid contamination of other products and professes shall be provided. Filters shall be installed to retain dust and protect the factory and local environment.
- Special care shall be taken to protect against subsequent contamination of the product by particles of metal or wood. The use of metal detector is recommended. Wooden equipment should be avoided. Screens, sieves, punches and dies shall be examined for wear and tear or for breakage before and after each use.
- All ingredients for a dry product shall be sifted before use unless the quality of the input material can be assured. Such sifting shall normally be carried out at dedicated areas.
- Where the facilities are designed to provide special environmental conditions of pressure differentials between rooms, these conditions shall be regularly monitored and any specification results brought to the immediate attention of the Production and quality Assurance Department.
- Care shall be taken to guard against any material lodging and remaining undetected in any processing or packaging equipment. Particular care shall be taken to ensure that any vacuum, compressed air or air-extraction nozzles are kept clean and that there is no evidence lubricants leaking into the product from any part of the equipment.
SIFTING, MIXING ANG GRANULATION:
- Unless operated as a closed system, mixing, sifting and blending equipment shall be fitted with dust extractors.
- Residues from sieving operations shall be examined periodically for evidence of the presence of unwanted materials.
- Critical operating parameters like time and temperature for each mixing, blending and drying operation shall be specified in a Master Formula, monitored during processing, and recorded in the batch records.
- Filter bags fitted to fluid-bed drier shall not be used for different products, without being washed in-between use. With certain highly potent or sensitizing products, bags specific to one product only shall be used. Air entering the drier shall be filtered. Steps shall be taken to prevent contamination of the site and local environment by dust in the air leaving the drier due to close positioning of the air-inlets and exhaust.
- Granulation and coating solutions shall be made, stored and used in a manner which minimizes the risk of contamination or microbial growth.
COMPRESSION (TABLETS):
- Each Tablet compressing machine shall be provided with effective dust control facilities to avoid cross-contamination. Unless the same product is being made on each machine, or unless the compression machine itself provides its own enclosed air-controlled environment, the machine shall be installed in separate cubicles.
- Suitable physical, procedural and labeling arrangements shall be made to prevent mix up of materials, granules and Tablets on compression machinery.
- Accurate and calibrated weighing equipment shall be readily available and used for in-process monitoring of Tablet weight variation. Procedures used shall be capable of detecting out-of-limit Tablets.
- At the commencement of each compression run and in case of multiple compression points in a compression machine, sufficient individual Tablets shall be examined at fixed intervals to ensure that a Tablet from each compression station or from each compression point has been inspected for suitable pharmacopeial parameters like appearance, weight variation, disintegration, Hardness, friability and thickness. The results shall be recorded as part of the batch documentation.
- Tablets shall be de-dusted, preferably by automatic device and shall be monitored for the presence of foreign materials besides any other defects.
- Tablets shall be collected into clean, labeled containers.
- Rejected or discarded Tablets shall be isolated in identified containers and their quality recorded in the Batch Manufacturing Record.
- In-process control shall be employed to ensure that the products remain within specification. During compression, samples of Tablets shall be taken at regular intervals to ensure that they are being produced in compliance with specified in-process specification. The Tablets shall also be periodically checked for additional parameters such as appearance, weight variation, disintegration, hardness, friability and thickness and contamination by lubricating oil.
COATING (TABLETS):
- Air supplied to coating pans for drying purposes shall be filtered air and of suitable quality. The area shall be provided with suitable exhaust system and environmental control (temperature, humidity) measures.
- Coating solutions and suspensions shall be made afresh and used in a manner, which shall minimize the risk of microbial growth. Their preparation and use shall be documented and recorded.
FILLING OF HARD GELATIN CAPSULES:
Empty Capsule shells shall be regarded as drug component and treated accordingly. They shall be stored under conditions which shall ensure their safety from the effects of excessive heat and moisture.
PRINTING (TABLETS AND CAPSULES):
- Special care shall be taken to avoid product mix-up during any printing of Tablets and capsules. Where different products, or different batches of the same product, are printed simultaneously, the operations shall adequately be segregated. Edible grade colours and suitable printing ink shall be used for such printing.
- After printing, Tablets and Capsules shall be approved by Quality Control before release for packaging or sale.
PACKING OPERATION:
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 labeling. If labeling is delayed, appropriate procedures should be applied to ensure that no mix-ups or mislabeling 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.
- Special care should be taken when cut labels are used and when overprinting is carried out off-line, and in hand-packaging operations. Roll-feed labels are normally preferable to cut labels in helping to avoid mix-ups. On-line verification of all labels by automated electronic means can be helpful in preventing mix-ups, but checks should be made to ensure that any electronic code readers, label counters, or similar devices are operating correctly. When labels are attached manually, in-process control checks should be performed more frequently.
- Printed and embossed information on packaging materials should be distinct and resistant to fading or erasing.
- Regular on-line control of the product during packaging should include at least 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.
- Products that have been involved in an unusual event during packaging should be reintroduced into the process only after special inspection, investigation and approval by authorized personnel. A detailed record should be kept of this operation.
- 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, satisfactorily accounted for, and recorded before release.
- Upon completion of a packaging operation, any unused batch-coded packaging materials should be destroyed and the destruction recorded. A documented procedure requiring checks to be performed before returning unused materials should be followed if uncoded printed materials are returned to stock.