India-Schedule M Good manufacturing practices

What is Schedule M under Drugs and Cosmetics Act 1940?

Schedule M part of Drugs and Cosmetics Act 1940 deals with Good Manufacturing Practices for pharmaceuticals that should be followed by pharmaceutical manufacturing units in India. Schedule M guides on Good Manufacturing Practices regarding company premises, quality control system, quality check laboratories, production, cleaning of equipment, housekeeping, cross-contamination, and other related topics.

Schedule M-I: Deals with the requirements of factory premises for manufacturing of Homeopathic preparations.
Schedule M-II: Deals with the requirements of premises, plant, and equipment for manufacture of cosmetics.
Schedule M-III: Deals with the requirements of premises, plant, and equipment for manufacture of Medical devices.

Objectives

To help a manufacturer better recognize, investigate, and take appropriate planned action for manufacture of drugs and cosmetics.
To protect consumer and marketplace from exposure to any potentially harmful ingredients or practices.
To adopt strict, risk-based practices and procedures for their manufacturing facility with a good manufacturing practice facility registration.

Applicability

These practices are applicable to all manufacturers of drugs and cosmetics who have their manufacturing facility with a good manufacturing practice facility registration. The manufacturing facility should aim to ensure that all personnel concerned with the manufacture know the information necessary to decide whether or not to release a batch of drugs for sale and to create an audit trail for future reference which shall permit investigation of the history of any suspected defective batch.

Salient Feature:

Requirements for Construction of building under GMP for Premises and Materials in Schedule M-I
The factory building for manufacture of drugs should have measures like covered sewage and drain, public lavatory facilities, proper exhaust system for obnoxious odour, fumes, excessive dust, smoke and other chemical or biological emissions. Building should be temperature controlled. Adequate measures should be taken to prevent entry of insects, pests, birds, vermin, and rodents. Designing of the factory shall be such that it suits the manufacturing operations to permit production of drugs under hygienic conditions. They shall conform to the conditions laid down in the Factories Act, 1948.
Requirements for supply of waterunder GMP for Premises and Materials in Schedule M-I
Purified water is be used for all the operations except washing and cleaning operations. Potable water may be used for washing and cleaning operations. Water shall be stored in tanks, which do not adversely affect quality of water and ensure freedom from microbiological growth. The tank shall be cleaned periodically, and records must be maintained by the licensee in this behalf.
Requirements for disposal of wasteunder GMP for Premises and Materials in Schedule M-I
Disposal of sewage and effluents (solid, liquid and gas) from the manufacturing unit should be as per the guidelines of Environment Pollution Control Board. All biomedical waste should be destroyed as per the provisions of the Bio Medical Waste (Management and Handling) Rules, 1996. Records need to be maintained for all disposal of waste.
Requirements for warehousing areaunder GMP for Premises and Materials in Schedule M-I
Warehousing areas should be designed and adapted to ensure good storage conditions. They must be maintained clean, dry and within acceptable temperature limits. In special storage circumstances, temperature and humidity control mechanism should be adopted, monitored, and recorded. Storage areas should have appropriate housekeeping and rodent, pests and vermin control procedures and records maintained. Proper racks, bins and platforms shall be provided for the storage of materials.
Requirements for production areaunder GMP for Premises and Materials in Schedule M-I
The production area should be designed in uniflow manner and with logical sequence of operations. Production areas should install separate dedicated and self-contained facilities for production of sensitive pharmaceutical products like penicillin or biological preparations with live microorganisms, to avoid the risk of cross-contamination.
Quality Control requirements under GMP for Premises and Materials in Schedule M-I
Independent quality-control laboratories should be constructed. Separate areas shall be provided each for physicochemical, biological, microbiological, or radio-isotope analysis. Quality Control Laboratories shall be designed appropriately for the operations to the carried out inside them.
Requirements for ancillary areasunder GMP for Premises and Materials in Schedule M-I
Rest and refreshment rooms shall be maintained separate from other areas. These areas should not lead directly to the manufacturing and storage areas. Facilities for changing storing clothes and for washing and toilet purposes shall be easily accessible and adequate for the number of users. There shall be separate toilets for males and females, and it should not be directly connected with production or storage areas.
Requirements for health, clothing, and sanitation of workersunder GMP for Premises and Materials in Schedule M-I
The personnel handling Beta-lactam antibiotics shall be tested for Penicillin sensitivity before employment and handling sex hormones, cytotoxic substances, and other potent drugs. They shall be periodically examined for adverse effects of smoking, eating, drinking, chewing. Keeping plants, food, drink, and personal medicines shall not be permitted in production area. Employees with any kind of illness or abnormal health condition are instructed to report the same to their immediate supervisor so that appropriate action can be taken.
Requirements regarding raw materialsunder GMP for Premises and Materials in Schedule M-I
Under controlled temperature and humidity, separate areas should be defined adequately for materials under test, approved, and rejected with arrangements and equipment to allow dry, clean, and orderly placement of stored materials and products. The incoming raw materials should be quarantined immediately after receipt or processing.
Requirements for labels and other printed materialsunder GMP for Premises and Materials in Schedule M-I
All containers and equipment should have appropriate labels. Colour coding of labels should be used to indicate the status of a product. All labels for containers, cartons and boxes and all circulars, inserts and leaflets should be examined by the Quality Control Department of the licensee before the dispatch.
Quality assurance requirements under GMP for Premises and Materials in Schedule M-I
The finished product should be correctly processed and checked in accordance with established procedures. The company should ensure the quality of products required for their intended use. Every manufacturing establishment shall establish its own quality control laboratory manned by qualified and experienced staff. The area of the quality control laboratory should be divided into Chemical, Instrumentation Microbiological and Biological testing.
Product recall requirements under GMP for Premises and Materials in Schedule M-I
The company should devise a prompt and effective product recall system for timely information of all concerned stockiest, wholesalers, suppliers, up to the retail level within the shortest period. The licensee should make use of both print and electronic media in this regard. There should be an established written Standard Operating Procedure for effective recall of products distributed by the licensee. Recall operations should be capable of being initiated promptly to effectively reach at every level of each distribution channel.
Records to be maintained under GMP for Premises and Materials in Schedule M-I

Master formula records: There shall be Master Formula records relating to all manufacturing procedures for each product and batch size to be manufactured. These shall be prepared and endorsed by the competent technical staff. i.e. Head of production and quality control. It should include:
(a)  The name of the product together with product reference code relating to its specifications.
(b)  The patent or proprietary name of the product along with the generic name, a description of the dosage form, strength, composition of the product and batch size.
(c)  Name, quantity, and reference number of all the starting materials to be used. Mention shall be made of any substance that may 'disappear' while processing.
(d)  A statement of the expected final yield with the acceptable limits, and of relevant intermediate yields, where applicable.
(e)  A statement of the processing location and the principal equipment to be used.
(f)   The methods or reference to the methods, to be used for preparing the critical equipment including cleaning, assembling, calibrating, sterilizing.
(g)  Detailed stepwise processing instructions and the time taken for each step.
(h)  The instructions for in-process controls with their limits.
(i)    The requirements for storage conditions of the products, including the container, labeling and special storage conditions where applicable.
(j)    Any special precautions to be observed.
(k)  Packing details and specimen labels.
Batch packaging records: A batch packaging record shall be kept for each batch or part batch processed. It shall be based on the relevant parts of the packaging instructions and the method of preparation of such records shall be designed to avoid transcription errors.
Batch Processing Records: Batch Processing Record shall be maintained for each product. It shall be based on the relevant parts of the currently approved Master Formula. The method of preparation of such records included in the Master Formula shall be designed to avoid transcription errors.