Specific Requirements For Manufacture of Oral Solid Dosage Forms



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 processes shall be provided. Filters shall be installed to retain dust and to 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 deviation shall be brought to the immediate attention of the Production and Quality assurance departments.
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 of lubricants leaking into the product from any part of the equipment’s.

Sifting, Mixing and Granulation: –

-Unless operated as a closed system, mixing, sifting and blending equipment shall be fitted with dust extractors or in a dedicated area for each operation.

-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 sensitising 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 minimises 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-limits 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 pharmacopoeial 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 quantity 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 of not greater than 30 minutes 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 minimise the risk of microbial growth. Their preparation and use shall be documented and recorded.

Filling of Hard Gelatin Capsule: –

-Empty capsules 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.


Packaging (Strip and Blister): –

-Care shall be taken when using automatic tablet and capsule counting, strip and blister packaging equipment to ensure that all ‘rogue‘ tablets, capsules or foils from packaging operation are removed before a new packaging operation is commenced. There shall be an independent recorded check of the equipment before a new batch of tablets or capsules is handled.

-Uncoated tablets shall be packed on equipment designed to minimise the risk of cross contamination. Such packaging shall be carried out in an isolated area when potent tablets or Beta-lactum containing tablets are being packed.

-The strips coming out of the machine shall be inspected for defects such as misprint, cuts on the foil, missing tablets and improper sealing.

-Integrity of individual packaging strips and blisters shall be subjected to vacuum test periodically to ensure leak proofness of each pocket strip and blister and records maintained.

Reference :-

Revised Schedule M4

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