SCHEDULE M, Pharmaceutical Jurisprudence, 5th sem

Pharmaceutical Jurisprudence

1. SCHEDULE M Good Manufacturing Practices (GMP) requirements of factory premises, plant & equipment for pharmaceutical products

2. Good Manufacturing Practices (GMP) requirements of factory premises, plant & equipment for pharmaceutical products. SCHEDULE M PART I- GMP for premises & materials PART IA- Specific requirements for manufacture of sterile products, Parenteral preparations, Sterile ophthalmic preparations PART IB- Specific requirements for manufacture of oral solid dosage forms PART IC- Specific requirements for manufacture of oral liquids PART ID- Specific requirements for manufacture of topical product PART IE- Specific requirements for manufacture of metered dose inhalers PART IF- Specific requirements of premises, plant & materials for manufacture of API (bulk drugs) PART II – Requirements of plant & equipment

3. M1- Requirements of factory premises etc for homeopathic preparations M2- Requirements of factory premises for the manufacture of cosmetics M3- Requirements of factory premises for manufacture of medical devices

4. The basic responsibility of a manufacturer is to ensure the production of quality products. GMP regulations were introduced in the form of amended Schedule M in 1988. The Schedule M has been amended in a major way by the D & C ACT (8 th amendment) rules 2001 and embraces rules 71,74,76 and 78 under drugs and cosmetics 1945. "GMP" - A set of principles and procedures which, when followed by manufacturers for therapeutic goods, helps ensure that the products manufactured will have the required good quality.

5. GENERAL REQUIREMENTS 1.1 . LOCATION AND SURROUNDINGS: The factory building for manufacture of drugs shall be so situated that it avoids risk of contamination from external environmental including open sewage, drain, public lavatory or any factory which produces obnoxious odor , fumes, dust/ smoke chemical or biological emissions. 1.2. BUILDING AND PREMISES : Buildings shall be designed, constructed, adapted and maintained to permit production of drugs under hygienic conditions.

6. They shall conform to the conditions laid down in the Factories Act, 1948. The premises used for manufacturing, processing, warehousing, packaging, labeling and testing purposes shall be compatible with other drug manufacturing operations. A dequate working space shall be provided to avoid the risk of mix-up between different materials & avoid the possibilities of contamination and cross contamination. The premises should be designed / constructed / maintained to prevent entry of insects, pests, birds, and rodents. The production & dispensing areas are well lighted, effectively ventilated, with proper Air Handling Units.

7. The walls and floors of the areas shall be free from cracks and open joints to avoid accumulation of dust. 1.3. WATER SYSTEM: There shall be validated system for treatment of water so as to produce Purified Water conforming to IP specification. 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. Only Purified Water shall be used for all the operations however potable water may be used for washing & cleaning operation.

8. 1.4. DISPOSAL OF WASTE: The disposal of sewage and effluents shall be carried out in conformity with the requirements of Environment Pollution Control Board. All bio-medical waste shall be destroyed as per the provisions of the Bio-Medical Waste (Management and Handling) Rules, 1996.

9. 2. WAREHOUSING AREA  Adequate areas to allow orderly warehousing of various categories of materials. (racks, bins & platforms) Area shall be designed & adapted to ensure Good storage conditions. There shall be a separate sampling area for active raw materials and excipients Segregation shall be provided for the storage of rejected, recalled or returned materials or products. Highly hazardous, poisonous and explosive materials shall be stored in safe and secure areas. Rodents treatment (pest control) should be done regularly at least once in a year & record shall be maintained.

10. 3. PRODUCTION AREA : Separate dedicated and self-contained facilities shall be made available for the production of sensitive pharmaceutical products. ( biologicals & antibiotics) Production area shall be designed to allow the production preferably in uni -flow & with logical sequence of operations. Pipe works, electrical fittings & other such services lines shall preferably be identified by colors and the nature of the supply and direction of the flow shall be indicated .

11. 4. ANCILLARY AREAS Rest and refreshment rooms shall be separate from other areas & shall not lead directly to the manufacturing & storage areas . Facilities for changing, storing clothes and for washing and toilet purposes shall be adequate for the number of users. Maintenance workshops shall be separate & away from production area. Tools & spare parts for use in sterile area shall be disinfected before they are carried inside production area. Animal houses shall be isolated from other areas.

12. 5. QUALITY CONTROL AREA QC Lab shall be independent of the production areas. Separate areas each for physico -chemical, biological, microbiological or radio-isotope analysis. Adequate space shall be provided to avoid mix-ups & cross contamination. Sufficient & suitable storage space shall be provided for test samples, retained samples, reference standards, reagents and records. Separate instrumentation room with adequate area shall be provided for sensitive & sophisticated instruments.

13. 6. PERSONNEL Manufacturing/ testing shall be carried out under the direct supervision of competent technical staff. Personnel shall be suitably qualified & experienced. The licensee shall ensure that the personnel shall receive training appropriate to the duties & responsibility assigned to him. They shall be provided with regular in-service training.

14. 7. HEALTH, CLOTHING AND SANITATION OF WORKERS Prior to employment, all personnel, shall undergo medical examination and shall be free from tuberculosis, skin & other communicable / contagious disease. A periodically examination is carried out, records are also maintained Proper training shall be given to all employees to maintain personnel hygiene. No person showing at any time, apparent illness or open lesions shall be allowed to handle starting materials, packaging materials, in-process materials & drug products. Smoking, eating, drinking, chewing , food, drink and personal medicines not permitted in production, laboratory, storage area.

15. 8. MANUFACTURING OPERATIONS AND CONTROLS All manufacturing operations shall be carried out under the supervision of technical staff. Products not manufactured under aseptic conditions are required to be free from pathogens like Salmonella, E.coli etc. Precautions against mix-up and cross-contamination- Area shall be maintained at required levels of temperature, humidity & cleanliness by proper air handling system, pressure differential. Proper records and SOP there of shall be maintained. Processing of sensitive drugs and cytotoxic substances shall be done in separate areas.

16. 9. SANITATION IN THE MANUFACTURING PREMISES The manufacturing premises shall be cleaned and maintained in an orderly manner so that it is free from accumulated waste, dust or debris. A validated cleaning procedure shall be maintained. A routine sanitation program shall be drawn up which shall be observed & properly recorded. Production areas shall be well lit, particularly where visual on-line controls are carried out.

17. 10. RAW MATERIALS All raw materials shall be purchased from approved sources. Authorized staff shall examine each consignment of raw materials. All incoming materials shall be quarantined immediately after receiving or processing. All materials shall be stored in an orderly fashion – first in / first out principle. Labeling with the following information: Name of the product and the internal code reference and analytical reference number Manufacturer’s name, address and batch number The status of the contents (e.g. Quarantine, under test, released, approved, rejected) The manufacturing date, expiry date and re-test date .

18. 11. EQUIPMENT Equipment shall be located, designed, constructed, adapted to suit the operations and log book is maintained Equipment shall be calibrated and checked on a scheduled basis in accordance to SOP and maintain records. Effective cleaning & maintenance of equipments in order to prevent contamination, dust build up are routinely checked.

19. 12. DOCUMENTATION AND RECORDS Documentation is an essential part of the quality assurance system. Its aim is to define the specifications for all materials, method of manufacture and to control release of a batch of drug for sale. Documents shall be approved, signed, dated by appropriate & authorized persons. Whenever data is handled by electronic data processing systems, access shall be restricted by passwords.

20. 13. LABELS AND OTHER PRINTED MATERIALS Labels are necessary for identification of the drugs and their use. The Printing shall be done in bright colors and in a legible manner. The label shall carry all the prescribed details about the product. All containers and equipment shall bear appropriate labels. Prior to release, all labels for containers shall be examined by the QC Department. Records of receipt of all labeling and packaging materials shall be maintained and unused coded, damaged labels and packaging materials shall be destroyed and recorded.

21. 14. QUALITY ASSURANCE It is a wide-ranging concept concerning all matters that individually or collectively influence the quality of a product It shall ensure that: - The pharmaceutical products are designed and developed in a way that takes account of the requirement of GMP ,GLP and GCP. Adequate controls on starting materials, intermediate products, and other in-process controls, calibrations & validations are carried out. Products are released after authorized persons have certified.

22. 15. SELF INSPECTION AND QUALITY AUDIT It is for the assessment of all or part of a system with the specific purpose of improving it. The program is designed to detect shortcomings in the implementation of GMP and to recommend the necessary corrective actions. Self-inspections shall be performed routinely and on specific occasions. The team responsible for self-inspection shall consist of independent, experienced, qualified persons from within or outside the company who can evaluate the implementation of GMP objectively; all recommendations for corrective action shall be implemented. The procedure for self-inspection shall be documented indicating self-inspection results; evaluation, conclusions and recommended corrective actions with effective follow up program.

23. QUALITY CONTROL SYSTEM Every manufacturing unit shall establish its own QC laboratory manned by qualified & experienced staff. Quality control shall be concerned with sampling, specifications, testing, documentation, release procedures. SOPs shall be available for sampling, inspection & testing of raw materials, intermediates, packaging materials & bulk finished products. Materials are not released for use, nor products released for sale or supply until their quality has been judged to be satisfactory by the authorized person. Pharmacopoeia, reference standards, working standards, references spectra, other reference materials and technical books, as required, shall be available in the QC Laboratory

24. SPECIFICATIONS Specifications shall be available separately for raw materials, packaging materials, product containers & closures, in-process & bulk products & finished products. MASTER FORMULA RECORD There shall be Master Formula records relating to all manufacturing procedures for each product and batch size These shall be prepared and endorsed by head of production and quality control The master Formula shall include: the name of the product together with product reference code relating to its specifications 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.

25. Name , quantity, and reference number of all the starting materials to be used . A statement of expected final yield with acceptable limits. A statement of the processing location and the principal equipment to be used. Method used for the preparing the equipment including cleaning, assembling, calibrating , sterilizing. D etailed stepwise processing instructions and the time taken for each step. T he instructions for in-process control with their limits. T he requirements for storage conditions of the products, including the container, labeling and special storage conditions where applicable. A ny special precautions to be observed. P acking details and specimen labels.

26. PACKAGING RECORDS There shall be authorized packaging instructions for each product, pack size and type These shall include: Name of the product Description of the dosage form, strength, composition & pack size. Complete list of all the packaging materials required for standard batch size Reproduction of relevant printed packaging materials & specimens Special precautions to be observed Details of in-process controls with instructions for sampling

27. BATCH PACKAGING RECORDS A batch packaging record shall be kept for each batch or part batch processed Before any packaging operation begins, checks shall be made & recorded that the equipment & work stations are clear of the previous products & the equipment is clean & suitable for use. BATCH PROCESSING RECORDS There shall be Batch Processing Record for each product It shall be based on the relevant parts of the currently approved Master Formula The method of preparation of records included in the Master Formula shall be designed to avoid transcription errors

28. During processing, the following information shall be recorded at the time of each action is taken & the record shall be dated & signed by the person in-charge for the processing operations: