Schedule M-Jurisprudence

This presentation consists of information related to Schedule M, a topic under #Drug_and_Cosmetics_Act. This presentation could be beneficial for the sake of the seminar in #Pharmaceutical_Jurisprudence for pharmacy students.

1. Schedule-M Pharmaceutical Jurisprudence BP-505 T Saiyam Agarwal 1701450047 B. Pharm 3 rd Year

2. Contents :- Introduction History Schedule M Parts Part I Part II References

3. Introduction:- The Drugs and Cosmetics Act , regulates the manufacture and sale of drugs and cosmetics through licensing so that these are manufactured, distributed and sold only by qualified person. The quality of drug formulations is the sole responsibility of the manufacturer. He has to ensure the production of desired quality formulations and their stability until, the formulation reaches the consumer across the retail l counter.

4. History:- In 1937, in Europe there were 107 deaths caused by the use of diethylene glycol in a sulfanilamide elixir. Sulfanilamide was an anti-infective sulfa drug. The manufacturer developed an elixir using diethylene glycol as the solvent. No toxicity tests were performed on the diethylene glycol. The deaths resulted from the solvent in the elixir. In 1937, the FDA had no authority to ban the use of any unsafe drug products. In order to remove the drug product from the market, the FDA claimed that the drug was misbranded because it was labeled as an elixir. By definition, an elixir had to contain alcohol and this drug product did not contain alcohol. [3]

5. Cont. … So in order to ensure production of quality drug formulation it was made necessary on the part of the manufacturer to follow well established and ethical approach involving different operations of manufacture. These approaches were amended in Schedule M under Drugs and Cosmetics Act 1940, Rules 1945. Cosmetics are although a luxury item, they may contain some ingredients the constant use of which might prove to be harmful and hence need control. To have a check on such operations the Central and State Drugs Control authorities are established. [1]

6. W hat exactly Schedule M is ? Schedule M /Good Manufacturing Practices (GMP) are minimum standards used in the manufacturing process that assure that the product meets requirements of safety, identity, strength, quality, and purity. If a product does not meet these requirements the product may be considered adulterated or misbranded by FDA. Manufacturers are required to register with the Food and Drug Administration (FDA) and their manufacturing process is described in the new drug application. The FDA attempts to inspect manufacturers every 2 years. [3]

7. Cont.… The Schedule M has again been amended in a major way by the Drugs and Cosmetics(8 th Amendment) Rules, 2001 w.e.f. 11 th December 2001. These rules shall not apply to the manufacturers who are presently licensed to manufacture drugs for the period up to the 31 st Dec. 2003. This period has been allowed intentionally so that the manufacturers could equip themselves to meet the newly imposed stringent requirements. To achieve the main objectives, each licensee shall evolve appropriate methodology, systems and procedures, which shall be documented and maintained for inspection and reference. The manufacturing premises shall be used exclusively for production of drugs and not for any other manufacturing. [1]

8. Parts of Schedule M Part I deals with GMP relating to factory premises and materials. Part II deals with requirement of plant and equipment.

9. Part-I – GMP for premises and materials General Requirements :- Good location and surroundings, well designed and constructed buildings suitable for manufacturing. P roper water system and proper disposal of wastes. Warehousing Area :- Area shall be designed and adapted to ensure good storage conditions. C lean, dry and maintained within acceptable temperature limits. S hould be provided with proper racks, bins and platform for storage of products, machines and equipment part. [1]

10. Ancillary Areas :- Rest and refreshment room, washroom and toilets, etc. shall be separate from other areas. Shall not lead directly to the manufacturing and storage areas. Instructions for cleaning and disinfection should be properly mentioned. Production Area :- Area i.e., designed for uniflow production. There should be adequate space for equipment and materials and movement of personnel to avoid cross- contamination. [1]

11. Quality Control Area :- The laboratories must be independent of the production areas. They should be divided into separate sections for physiochemical, biological, microbiological and radioisotope analysis. The design of laboratories should be in such a manner that mix-ups and cross-contamination can be avoided. Personnel :- Every manufacturing/testing should be conducted under direct supervision of well trained and qualified technical staff. Every personnel should be provided with regular in-service training. [1]

12. Health, Clothing and Sanitation of workers :- Workers engaged in manufacturing shall observe a high level of personnel hygiene. Prior to employment all personnel shall undergo medical examination and shall be free from TB, skin and other communicable contagious diseases. Manufacturing operations and controls :- All manufacturing operations and all the critical step in the process relating to selection, weighing and measuring of raw material at various stages should be performed under the supervision of approved technical staff. Products not prepared under aseptic conditions are required to be free from pathogens like Salmonella, Escherichia coli., Pyocyanea etc. [1]

13. 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, debris and other similar material. A routine sanitation program shall be drawn and observed and recorded. Raw Materials :- All raw material shall be purchased from approved sources under valid purchase vouchers, possibly from the producers directly. Only raw materials which have been released by the QC Department and which are within their shelf life shall be used. All the containers of raw materials shall be placed on the raised platforms/ racks and not directly on the floor. [1]

14. Equipment :- Equipment shall be located, designed, constructed, adapted and maintained to suit the operations to be carried out. The design and layout of equipment shall aim to minimize the risk of errors. Each equipment shall be provided with a logbook, wherever necessary. Documentation and records :- It is an essential part of the QA system and, as such shall be related to all aspects of GMP. Its aim is to define the specifications for all materials, methods 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 of a drug for sale and to provide an audit trail that shall permit investigation of the history of any suspected defective batch. [1]

15. Labels and other printed materials :- The labels shall carry all the prescribed details about the product and shall be printed in bright colors and in a legible manner. All containers shall bear appropriate labels. Different color coded labels shall be used to indicate the status of a product e.g. under test, approved, passed, rejected. Self inspection and audit :- The manufacturer shall constitute a team of independent, experienced, qualified persons from within or outside the company who can audit objectively the implementation of methodology and procedures evolved. The procedure for self-inspection shall be documented indicating self-inspection results. [1]

16. Quality Control System :- Detailed instructions for quality control of raw materials and finished product; quality control for packaging and labeling; adequacy of storage, qualitative examination of returned products. Specifications :- Specifications shall be available separately for raw materials and packaging materials, product and closures, in-process and bulk-products, finished products. [1]

17. Master Formula Records (MFR) :- Licensee should maintain records relating to all manufacturing procedures for each product and batch size to be manufactured. It also includes patent or proprietary status; name of formulation along with generic name if any; name, quantity, and reference number of starting materials; strength; dosage form; description; identification; composition; statement of processing location; step-wise processing instructions; requirements for storage conditions; packaging details, etc. Batch Packaging Records :- It is based on relevant parts of packaging instructions. Transcription errors to be avoided; packaging equipment clean; planned packaging operations and proper maintenance of packaging records. [2]

18. Batch Processing Records (BPR) :- BPR for each product; clean equipment; name of product; number and batch being manufactured; dates and time of commencement of operation; initials of operator of different steps of production; batch number; amount of product obtained; note on any deviation from master formula; addition of any recovered or reprocessed material. Standard Operating Procedures (SOPs) and Records :-SOP and records for receipts of each delivery of raw, primary and printed packing material; sampling; instrument and equipment; quarantine and storage; batch numbering; testing, records of analysis; equipment assembly and calibration; maintenance; cleaning and sanitation; personnel; pest control; complaints, and recalls made and returns received. [2] x------ Part-I------x

19. Part-II Specific requirements of plant and equipment T his includes information related to space/area and equipment that are required for manufacturing of different dosage forms like external preparations, oral liquid preparations, tablets, powders, capsules, surgical dressings, ophthalmic preparations, pessaries and suppositories, inhalers, repacking of drug & pharmaceuticals, parenteral preparations. [1]

20. External Preparations :- It covers ointments, emulsions, lotions, solutions, pastes, creams, dusting powders and other identical preparations. Minimum area: 30 square meters for basic installation and 10 square meters for ancillary area. Requirements: mixing and storage tanks, jacketed kettles of different types, electric mixer, planetary mixer, colloid mill, triple roller mill, liquid and tube filling equipment, etc. Powders :- Area: Minimum 30 square meters; additional room for actual blending. Requirements: Disintegrator, electric mixer, sifter, SS vessels and scoops of suitable sizes, filling equipment, weighing balance, etc.

21. Oral Liquid Preparations :- It covers syrups, elixirs, emulsions and suspensions. Minimum area: 30 square meters for basic installation and 10 square meters for ancillary area; Requirements: SS mixing and storage tanks, jacketed kettles of different types, electric stirrer, electric colloidal mill, emulsifier, filtration equipment, bottle filling machine, cap sealing machine, de-ionizer or water distillation unit, clarity testing unit, etc. Surgical Dressings :- Area: Minimum 30 square meters for basic installation; for medicated dressing additional room required. Requirements: Rolling, staining, cutting, folding and pressing machines; mixing tanks, hot air oven, steam sterilizer, work tables, etc.

22. Repacking of Drugs and Pharmaceuticals :- Area: Minimum 30 square meters for basic installation. Exhaust system be provided in case of operations involving floating particles. Requirements: Weighing, measuring and filling equipment; powder disintegrator, electrically operated powder sifter, electric sealing machine, SS scoops and vessels, etc. Inhalers :- Area: Minimum 25 square meters for basic installation. Requirements: Mixing, graduated delivery and sealing equipment.

23. References Jain NK, “A textbook of Forensic Pharmacy”, published by Vallabh Prakashan, Delhi, 8 th Edition 2014, page no 48, 79-103. Kokate CK, “Textbook of Forensic Pharmacy”, published by Pharma med press, Hyderabad, edition 2008, page no. 78-88. Feinberg Debra B., Pharmacy Law Textbook and Review, published by Mc Graw Hill Medical, New York, 2008 edition, Page no. 7, 75. www.shutterstock.com/search/gmp/ www.pharmapress.com/browse-by-subject/laws-and-ethics

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