schedule-m PART I GOOD MANUFACTURING PRACTICES FOR PREMISES AND MATERIALS

According to the schedule M guidelines

Construction of building;

The factory building(s) for manufacture of drugs shall be so situated and shall have such measures as to avoid risk of contamination. Including open sewage, drain, public lavatory or any factory which produces disagreeable or obnoxious, odor, fumes, excessive soot, dust, smoke, chemical or biological emanations. Building(s) should be air conditioned where prescribed for the operations and dosage forms. The designed / constructed / maintained to prevent entry of insects, pests, birds, vermin and rodents. The building(s) used for the factory shall be designed, constructed, adapted and maintained to suit the manufacturing operations so as to permit production of drugs under hygienic conditions. They shall conform to the conditions laid down in the Factories Act, 1948 (63 of 1948).

Water supply

Water (as per the specifications of Pharmacopoeia) shall only be used for all the operations except washing and cleaning operations where potable water may be used. 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 maintained by the licensee in this behalf.

Disposal of water ;

Disposal of sewage and effluents (solid, liquid and gas) from the manufactory shall be in conformity with the requirements of Environment Pollution Control Board (EPCB). All bio-medical waste shall be destroyed as per the provisions of the Rio Medical Waste (Management and Handling) Rules, 1996.

Production area;

The production area shall be designed to allow the production preferably in uni-flow and with logical sequence of operations. In order to avoid the risk of cross-contamination, separate dedicated and self-contained facilities shall be made available for the production of sensitive pharmaceutical products like penicillin or biological preparations with live microorganisms.

Quality control;

Quality-Control Laboratories shall be independent of the production areas. 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 he carried out in them.

Ancillary area

Rest and refreshment rooms shall he separate from other areas. These areas shall 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. Toilets separate for males and females, shall not be directly connected with production or storage areas.

Warehousing area

Adequate areas shall be designed to allow sufficient and orderly warehousing of various categories of materials and products like starting and packaging materials intermediates bulk and finished products, products in quarantine released, rejected, returned or recalled machine and equipment spare parts and change items.

Health clothing and sanitation of workers

The personnel handling Beta-lactam antibiotics shall be tested for Penicillin sensitivity before employment and those handling sex hormones, cytotoxic substances and other potent drugs shall he periodically examined for adverse effects Smoking. Eating, drinking, chewing or keeping plants, food, drink and personal medicines shall not be permitted in production. All employees shall be instructed to report about their illness or abnormal health condition to their immediate supervisor so that appropriate action can be taken.

Manufaturing operations and controls

The contents of all vessels and containers used in manufacture and storage during the various manufacturing stages shall be conspicuously labeled with the name of the product, batch no, batch size and stage of manufacture. Each label should be initialed and dated by the authorized

technical staff.

Raw materials

There shall be adequate separate areas for materials "under test", "approved ", and "rejected" with arrangements and equipment to allow dry, clean and orderly placement of stored materials and products, wherever necessary. Under controlled temperature and humidity. All incoming materials shall be quarantined immediately after receipt or processing. All materials shall be conditions and in an orderly fashion to permit hatch segregation and stock rotation by a 'first in/first expiry' - 'first-out' principle.

Documentation and records

Documentation is an essential part of the Quality assurance system and, as such, shall be related to all aspects of Good Manufacturing Practices (GMP). Its aim is to define the specifications for all materials, method of manufacture and control, to ensure that all personnel concerned with manufacture know the information necessary to decide whether or not to release a batch or drug for sale and-to provide an audit trail that shall permit investigation of the history of any suspected defective batch. Records and associated Standard Operating Procedures (SOP) shall be retained for at least one year after the expiry date of the finished product. Data may be recorded by electronic data processing systems or other reliable means, but Master Formulae and detailed operating procedures relating to the system in use shall also be available in a hard

copy to facilitate checking of the accuracy of the records.

Labels and other printed materials

All containers and equipment shall hear appropriate labels. Different color coded labels shall be used to indicate the status of a product (for example under test, approved. passed, rejected). Prior to release, all labels for containers, cartons and boxes and all circulars, inserts and leaflets shall be examined by the Quality Control Department of the licensee.

Quality assurance

It is the totality of the arrangements made with the object of ensuring that products arc of the quality required for their intended use. The finished product is correctly processed and checked in accordance with established procedures. Every manufacturing establishment shall establish its own quality control laboratory manned by qualified and experienced staff. The area of the quality control laboratory may be divided into Chemical, Instrumentation Microbiological and Biological testing.

Specifications

For the various raw materials and packaging materials, containers, closures and finished products various specifications should be written on the labels and should be maintained in the records.

(a) The designated name of the product and the code reference

(b) The formula or a reference to the formula and the pharmacopoeial reference

(c) Directions for sampling and testing or a reference to procedures

(d) A description of the dosage form and package details

(e) The qualitative and quantitative requirements. With the acceptance limits for release

(f) The storage conditions and precautions where applicable, and

(g) The shelf-life.

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' in the course of 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 he 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.

Reference samples

Each lot of every active ingredient. in a quantity sufficient to carry out all the tests except sterility and pyrogens or Bacterial Endotoxin. Test shall be retained for a period of 3 months after the date of expiry of the last batch produced from that active ingredient.

Product recalls

A prompt and effective product recall system of defective products shall be devised for timely information of all concerned stockiest, wholesalers, suppliers, up to the retail level within the shortest period. The licensee may make use of both print and electronic media in this regard. There shall be an established written procedure in the form of Standard Operating Procedure for effective recall of products distributed by the licensee. Recall operations shall be capable of being initiated promptly so as to effectively reach at the level of each distribution channel.

Sterile products, being very critical and sensitive in nature, a very high degree of precautions, prevention and preparations are needed. Dampness, dirt and darkness are to be avoided to ensure aseptic conditions in all areas. There shall be strict compliance in the prescribed standards especially in the matter of supply of water, air, active materials and in the maintenance of hygienic environment. Air Handling Units for sterile product manufacturing areas shall be different from those for other areas. Critical areas, such as the aseptic filling area, sterilized components unloading area and change rooms conforming to Grades B, C and D respectively shall have separate Air Handling Units The filling operations shall take place under Grade A conditions which shall be demonstrated under working of simulated conditions which shall be achieved by providing Laminar Air flow work stations with suitable HEPA filters or isolator technology. There shall be a written environmental monitoring program and microbiological results shall be recorded. Recommended limits for microbiological monitoring of clean areas "in operation" are given.

Posted in: schedule-m