GOOD MANUFACTURING PRACTICES [GMP]

1. GOOD MANUFACTURING PRACTICES [GMP] Mr.B.BRAHMAIAH

2. WHAT IS GMP ? GOOD MANUFACTURING PRACTICE

3. What is GMP? • Good Manufacturing Practice is a set of regulations, codes, and guidelines for the manufacture of drug substances and drug products, medical devices, in vivo and in vitro diagnostic products, and foods. Fig.4 GMP handbooks for every industry

4. Public Involvement • 1905 - TheJungle by Upton Sinclair (BOOK) • Exposure of unsanitary Meat packing plants. • Increased Public awareness And involvement • Pure Food and Drug Act • False labeling became illegal

5. Good Manufacturing Practices Worldwide Enforcement • Good Manufacturing Practices are enforced in the United States by the FDA • In the United Kingdom by the Medicines and Healthcare Products Regulatory Agency • GMPs are enforced in Australia by the Therapeutically Goods Administration • In India by the Ministry of Health, multinational and/or foreign enterprises • Many underdeveloped countries lack GMPs

6. 1941 Initiation of GMP • Sulfathiaziole tablets contaminated with phenobarbital • 1941 - 300 people died/injured • FDA to enforce and revise manufacturing and quality control requirements • 1941 - GMP is born Fig- 1906 Certificate of Purity signed by doctor

7. 1962 Kefauver-Harris Drug Amendments • Thalidomide tragedy • Thousands of children born with birth defects due to adverse drug reactions of morning sickness pill taken by mothers • Strengthen FDA’s regulations regarding experimentation on humans and proposed new way how drugs are approved and regulated • “Proof of efficacy” law Fig -Kennedy signing the Kefauver –Harris Drug Amendments

8. 1976 Medical Device Amendments • 1972 and 1973 -Pacemaker failures reported • 1975 - hearing-Dalkon Shield intrauterine device caused thousands of injuries • Class I, II and III medical devices – based on degree of control necessary to be safe and effective Fig-President Gerald Ford signs the Medical Device Amendments

9. 1980 Infant Formula Act • 1978 - major manufacturer of infant formula reformulated two of its soy products • 1979 - Infants diagnosed with hypochloremic metabolic alkalosis • Greater regulatory control over the formulation and production of infant formula • Modification of industry’s and FDA’s recall procedures Fig-Parody on Infant Formula Act

10. Bhopal Gas Disaster • The Union Carbide Pesticide Plant in Bhopal, released 40 tons of Methyl Isocyanate (MIC) gas, killing between 2,500 to 5,000 people in the early hours of the morning. • The World’s worst Industrial Disaster

11. The gas being heavier than air, started entering into the homes of the unwary population. Many who panicked and ran out also got crushed in stampedes. • Around 500,000 were estimated to be exposed to the gas & around 20,000 have died as a result. Over 120,000 continue to suffer from the from the effects of the disaster.

12. Doctors and Hospitals were unaware of the nature of the Gas, nor were they informed of the proper treatment of the inhalation of MIC gas, being merely asked to give cough medicine & eye drops. • If they were informed about the same, proper treatment could have been instituted & a lot of lives could have been saved.

13. Red Page in Annals of Occupational Health • The Bhopal disaster brought into sharp focus the unprecedented potential of hazardous chemical release in terms of loss of life, health, injury and evacuation. • It created a compelling evidence to approach disaster management and chemical safety holistically. • The disaster brought in its wake, an era of restructuring and inducting new hazardous chemical control systems and procedures all over the world

14. A Time line of GMP • 1902 - Development of the Biologic Control Act • 1906 - Development of the Pure Food and Drug Act • 1938 - Federal Food, Drug and Cosmetic Act • 1941 - Initiation of GMP • 1944 - Development of Public Health Services Act • 1962 - Kefauver-Harris Drug Amendments released • 1963 - Establishment of GMPs for Drugs • 1975 - CGMPs for Blood and Components Final Rule • 1976 - Medical Device Amendments • 1978 - CGMPs for Drugs and Devices • 1979 - GLPs Final Rule • 1980 - Infant Formula Act is passed

15. What is GMP ? • GMP is that part of Quality assurance which ensures that the products are consistently manufactured and controlled to the desired Quality standards appropriate for intended use • "GMP"- A set of principles and procedures which, followed by manufacturers for therapeutic goods, helps ensure that the products manufactured the required quality.

16. WHY DO WE NEED GMP?

17. TYPES OF CONTAMINANTS • PARTICULATES Dust, dirt, paper, metal, fibers, etc. • MICROORGANISMS Bacteria, yeasts, molds • CROSS-CONTAMINATION Labels, cartons, foil, materials, etc.

18. SOURCES OF CONTAMINATION AIR , WATER, SURFACES, PEOPLE, PESTS

19. PEOPLE CONTAMINATION CAUSE HEH! HEH! HEH! • IMPURE • UNCLEAN • UNFIT FOR USE CONTAMINATION

20. CGMP REGULATION

23. 1. Quality management

24. Introduction • What is quality? Dictionary has many definitions: “Essential characteristic,” “Superior,” etc. Some definitions that have gained wide acceptance in various organizations: “Quality is customer satisfaction,” “Quality is Fitness for Use.”

25. Why Quality? Reasons for quality becoming a cardinal priority for most organizations: • Competition – Today’s market demand high quality products at low cost. Having `high quality’ reputation is not enough! Internal cost of maintaining the reputation should be less. • Changing customer – The new customer is not only commanding priority based on volume but is more demanding about the “quality system.”

26. What is a Quality Management System? • Required for planning and executing business processes • To meet customer requirements • Accredited to International Standards by a Registrar ISO 9001:2008 is an example

27. Quality levels • Organizational level 2. Process level 3. Individual job level

28. QUALITY IS A JOURNEY, NOT A DESTINATION

29. TQM • Total Quality Management is a management approach that originated in the 1950's and steadily became more popular since the early 1980's. • TQM, is a method by which management and employees can become involved in the continuous improvement of the production of goods and services.

30. 2. Quality Assurance • The sum total of the organized arrangements made with the object of ensuring that medicinal products are of the quality required for their intended use. “All those planned & systematic actions necessary to provide adequate confidence that an item or a facility will perform satisfactorily in service.”

31. 3. Quality control “Those quality assurance actions which provide a mean to control and measure the characteristics of an item, process or facility to established requirements.”

32. GENERAL PRINCIPLES • Each holder of a manufacturing authorization should have a QC Department • Independence from production and other departments is considered to be fundamental • Under the authority of an appropriately qualified and experienced person with one or several control laboratories at his or her disposal.

33. BASIC REQUIREMENTS Quality Control department should have : • Resources: • Adequate facilities • Qualified personnel • Approved written procedures • Tasks : • Sampling, inspecting, testing, • Releasingor rejecting • Monitoring • Objects : • Starting materials, intermediates, bulk, and finished products • Returned products • Environmental conditions

34. Quality Control System. • Quality control shall be concerned with sampling, specifications, testing, documentation, release procedures . Materials are not released for use, nor products released for sale or supply until their quality has been judged to be satisfactory. • QC lab should have qualified and experience staff. • QC lab. may be divided into Chemical, Instrumentation, Microbiological and Biological testing. • The QC department shall conduct stability studies of the products to ensure and assign their shell life . All records of such studies shall be maintained. • All instruments shall be calibrated and validated before adopted for routine testing. • Pharmacopoeia, reference standards, working standards, references spectra, other reference materials and technical books, as required, shall be available in the QC Laboratory.

36. Start • Intermediates • Bulks • Finished goods • Environment monitoring • Incoming materials • Water • Returned goods 2. Receiving 3. Sampling QC/QA Status 4. Test samples Lab Records 5. Review of batch record Release NO Meet specification 7. Non conformance or out of specification investigation Reject YES 6. Goods release 8. Goods Reject Release Reject End End QC WORK FLOW

38. 4. Sanitation & hygiene • Physical cleaning. • Chemical cleaning. • Thermal cleaning.

39. Reasons of cleaning • Pleasant and safe environment • Reduce contamination • Allow disinfection • Effective cleaning • What • How • Who • When • How much time is allowed for cleaning

40. Use of chemicals for cleaning • Bactericide - Destroys bacteria • Detergent - Removes grease and dust • Disinfectant - Reduce micro organism to a safe level • Sanitizer- Chemical that use both clean and disinfections • Sterilizer- Heat treatment

41. BASIC DESCRIPTION

42. OBJECTIVE The aim of sanitation and hygiene measures is to eliminate all potential sources of contamination and cross-contamination from all areas where the product quality is at risk.

43. BENEFITS For personnel : • To prevent contamination risk that effect personnel health For product : • To prevent contamination of the products • To maintain the high standard of product quality For company : • To save on cost, avoid reworks and rejects • To avoid consumer complaints • To avoid potential product recall For consumers : • To get safe and good quality product

44. HYGIENE SANITATION PERSONNEL HYGIENE

45. BASIC HYGIENE Personal hygiene will usually be the main element in the term “hygiene”; the reason being obvious. Bacteria causing diseases or spoilage may be carried and transmitted to surfaces and productby workers handling the drug products.

47. GENERAL REQUIREMENTS • All personnel working in direct contact with products shall conform to hygienic practices while on duty to the extent necessary to protect the product against contamination. The methods for maintaining cleanliness include, but are not limited to: • Wearing outer garments suitable to the operation in a manner that protects against the contamination. • Maintaining adequate personal cleanliness. • Washing hands thoroughly (and sanitizing if necessary to protectagainst contamination with undesirable microorganisms) • Maintaininggloves, if they are used in product handling, in an intact, clean, and sanitary condition. • Wearing, where appropriate, in an effective manner, haircap, beard covers, or other effective hair restraints.

48. GOOD PERSONNEL HYGIENE • Personnel must practice good personal hygiene. • Regular bathing every day • Brushing of teeth • Washing hands • Before entering the production area • After visiting the toilet • After eating • After smoking

49. Wet your hand with flowing water Use soap around your hand and fingers. If needed use brush to clean your nails Rinse your hand with flowing water Dry your hand with tissue or hand dryer at 320 – 600C. 6. Don’t touch anything. If can not be avoided, repeat step 1-5 HAND WASHING GUIDELINES

50. All authorized personnel entering the production areas should practice good personal hygiene including wearing of proper attire, suitable headwear and footwear. PROPER ATTIRE • To avoid cross contamination, personnel should not move between areas producing different products.