WHO GMP Requirements

WHO Good Manufacturing Practice Requirements
Good Manufacturing Practice is the part of quality assurance that ensures that products are consistently manufactured and controlled to the quality standards appropriate to their intended use.

1. WHO GMP REQUIREMENTS DEEKSHITHA H S DEPARTMENT OF QUALITY ASSURANCE MPHARM 1 st SEMESTER 01-02-2022 1

2. INTRODUCTION According to FDA a drug is defined as adulterated if the methods used in its manufacture or processing ,Testing, Packaging , Storing did not conform to the GMPs As a result of this, GMPs were first established in June 1963. The concept was born in U.S.A Drugs being a very important component of health care system need special attention in regard to their Quality , Safety , efficacy. Final testing of the product cannot ensure the quality, safety, efficacy of a product . Therefore the concept of QC evolved and The development of QC resulted in GMPs. 01-02-2022 2

3. Many Indian drug manufacturers export pharmaceutical preparations to other member countries of WHO. Indian drug manufacturers as well as their technical personnel should be aware of the GMP guidelines prepared by WHO . These are referred to WHO GMPs GMP- GOOD MANUFACTURING PRACTICES . 3

4. Good manufacturing practices WHO defines Good Manufacturing Practices (GMP) as “that part of quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization. GMP covers all aspects of the manufacturing process: defined manufacturing process; validated critical manufacturing steps; suitable premises, storage, transport; qualified and trained production and quality control personnel; adequate laboratory facilities; approved written procedures and instructions; records to show all steps of defined procedures taken; full traceability of a product through batch processing records and distribution records; and systems for recall and investigation of complaints. 01-02-2022 4

5. Why GMP is important ? A poor quality medicine may contain toxic substances that have been unintentionally added. A medicine that contains little or none of the claimed ingredient will not have the intended therapeutic effect. Poor quality medicines are not only a health hazard, but a waste of money for both governments and individual consumers. GMP helps boost pharmaceutical export opportunities Most countries will only accept import and sale of medicines that have been manufactured to internationally recognized GMP. Governments seeking to promote their countries' export of pharmaceuticals can do so by making GMP mandatory for all pharmaceutical production and by training their inspectors in GMP requirements. 01-02-2022 5

6. GMP Benefits 01-02-2022 6 Helps to reduce observations raised on inadequate documentation practices. Ensures products are safe for humans. Helps Prevent and control contamination and cross contamination. Reduces the risk of mislabeling and adulteration. Promotes efficiency and reduces the cost of doing business.

7. Principles of GMP 1. Writing step-by-step operating procedures and work instructions. 2. Following written procedures and instructions at all times to prevent contamination, mix-ups and errors. 3. Documenting work accurately and in a timely fashion. 4. Proving that systems do what they are designed to do by validating equipment systems and processes. 5. Designing and constructing facilities and equipment. 6. Monitoring and maintaining facilities and equipment. 7. Defining, developing and demonstrating job competence. 8. Protecting against contamination and maintain a clean environment. 9. Controlling raw materials, components and product related processes. 10. Conducting planned and periodic audits. 01-02-2022 7

8. Principles 1&2 • Stress the importance of written procedure. • The best way to comply with GMP is to have well written procedures and carefully following them. • Give us the controls necessary to minimize the chance of contamination, mix-ups and Errors. 01-02-2022 8

9. Principle 3 Documentation is the key to operating a pharmaceutical company in compliance with GMP requirements. The system of documentation devised or adopted should have as its main objective to establish, monitor, and record "quality" for all aspects of the production and quality control. Several types of documents are needed to accomplish this. Standard operating procedures, specifications and master formulae Forms for recording data Identification numbers Labels 01-02-2022 9

10. Any document that can impact the quality of the product or product safety is treated as a controlled document. Examples of controlled document: Policies, SOPs, Specifications, MFR (Master Formula Record) The accuracy and content of these documents can be subject to review by regulatory bodies Including the FDA. 01-02-2022 10

11. Principle 4 Validation: Proactive proof that we can produce safe and effective products. Requires a series of tests to assure our systems do what we say they do. Gives meaning to documentation we make. Tells us written procedures are correct and our products are truly safe. 01-02-2022 11

12. Principle 5 &6 Key concern of principle 5&6: Avoid the possibility of contamination, mix-ups and errors in work place. Keeping certain areas such as cafeteria , restrooms and locker rooms separated from manufacturing area. Water, air, temperature and humidity should be controlled in order to avoid mix-ups and errors. 01-02-2022 12

13. Principle 7 • GMP requires competent personnel who perform the job right every time. • Personnel should be properly trained. • Company must have formal training program to assure each employee can competently preform assigned job. 01-02-2022 13

14. Principle 8 Focuses on cleanliness and requires us to constantly be on-guard to defend our product against contamination. Particular Contamination: Product has been made impure by any particle that does not belong in it. Examples: Dust, dirt, hair. B) Microbial contamination: Caused by microscopic organisms that are living organisms that exist on everything in environment that is not sterilized. Examples: Fungus, mold, bacteria and viruses. C) Cross Contamination: Occurs when traces of other materials, components and products adulterate or miss brand a product that we are currently manufacturing or testing. 01-02-2022 14

15. Principle 9 d processes. 01-02-2022 15 Material and Components • Satisfy our quality standards. • Upon receipt must be carefully examined for damage and contamination. • Certain components and materials must be sampled and tested to ensure that they meet the established identity, quality and purity. • After approval they are released to manufacturing and used on first in first out basis. Manufacturing Process • Master records that outline specifications and manufacturing procedures. • Individual batch or history records to help to document the conformance to master record. • Written schedules and procedures for cleaning and maintaining equipment. Packaging and Labelling • Inspect packaging and labeling area before each new batch is processed. • Packaging equipment is clean and the area does not contain any materials from previous run. Testing Supports all other areas of control. • Must be performed by qualified individuals. • Assures the safety, effectiveness and purity of product as they enter marketplace.

16. Principle 10 FDA has major responsibility to externally audit manufacturing operations to see if we are in compliance with cGMP regulation. FDA has the responsibility to protect the consumer and can recommend a recall product if a product is contaminated, miss-labeled or is not manufacture in compliance with cGMP regulations. Company has the responsibility to internally ensure the integrity of products. 01-02-2022 16

17. The Aim of GMP Key Provisions of GMP GMP General Provisions Building and facilities Equipment 01-02-2022 17 SAFE the product has the right ingredients . It is packaged as intended and correctly labelled in order to provide identification and safe use. PURE it is free of contaminants, foreign matter, chemicals and harmful microbes. EFFECTIVE Product requires the correct ingredients, the correct amount of ingredients and correct packaging to maintain the product stability over time. UNIFORM The product is manufactured consistently and will have the same quality between batches manufactured on different days.

18. Quality management Quality management in the drug industry is discussed in the WHO GMP for Pharmaceutical Products . In this document the following are presented: • The basic elements of quality management are: - an appropriate infrastructure or “quality system”, encompassing the organizational structure, procedures, processes, and resources; and - systematic actions necessary to ensure adequate confidence that a product (or service) will satisfy given requirements for quality. The totality of these actions is termed “quality assurance”. • The concepts of quality assurance, GMP, and quality control are interrelated aspects of quality management. They are of “fundamental importance to the production and control of pharmaceutical products”. 01-02-2022 18

19. QA encompasses all of the arrangements made to ensure that pharmaceutical products meet the quality required for their intended use. Although QA is not specified in all GMP documents, the WHO GMP guidelines present the principles of QA are to ensure that GMP and other regulatory codes (GLP - Good Laboratory Practice, and GCP - Good Clinical Practice) are respected; that responsibilities are clearly specified; all testing, controls, calibrations, validations, etc are performed as specified; that products are not sold before the correct authorizations have been obtained; that products are appropriately handled throughout their shelf-life; and that there is a procedure for self inspections (quality audit). 01-02-2022 19

20. Standard operating procedures (SOPs) Standard operating procedures (SOPs) are the detailed written instructions that specify how a test or administrative procedure is to be performed, or how a piece of equipment is operated, maintained and calibrated. They indicate exactly how things are done, and are kept current by review and approved revision on a predetermined schedule (usually annual), or when planned changes are made to the procedure or equipment and reagents used in the procedure. The original of a current version of an SOPs is maintained in a central file, and copies are distributed to the locations where the procedure is performed. The procedure for describing the writing, revising and approving of SOPs and the control of distribution of SOPs is one of the important quality assurance procedures. 01-02-2022 20

21. The term “change control” has recently been introduced to the vocabulary of pharmaceutical manufacturing and control. Although this is primarily a term for validation procedures, it may also apply to the control of the review and revision of SOPs for routine procedures. SOPs are used as a reference by the persons responsible for the performance, and are also used for training new operators in the performance of the procedure. Quality assurance procedures should be in place to ensure that SOPs are enforced and properly used. SOPs follow a scientific format, and are written with the view that they will be used by persons trained in the procedure. They should be specific instructions for each step in sequential order including the preparatory work which must be done before starting the main procedure, as well as instructions for recording and reporting the results. Usually the initial draft of an SOP is written by the person performing the procedure or by someone who knows the procedure well and must be written including the details and the time course of the tasks. Supervisors review the SOPs for completeness and content and QC or QA staff approve for regulatory compliance. 01-02-2022 21

22. When appropriate, formal data sheet or data record form is prepared for an SOP. This form is a parallel summary document with checklists, checkboxes, and blanks for all data to be recorded during the performance of the procedure. It also has spaces for signatures of the operator and other technicians who verify and countersign certain critical operations during the procedure. Finally, there is the space for the signature of the department supervisor who reviewed the completed data record form. Blanks and checklists ensure that the required data are collected, that nothing is overlooked and also provide the evidence that the procedure was performed according to the SOP. The datasheets also provide instructions for recording deviations to the procedure, for calculations or reporting requirements, for comparison of results with predetermined specifications, and the criteria for repeating procedures in cases where unacceptable results were obtained. 01-02-2022 22

23. Format for a standard operating procedure (SOP) Name of facility ________________________________________________page .......... of .......... SOP Number ________ Title _________________________________________________ Revision number ________ Written by ______________________________ Edited by __________________________ Authorization signature ________________________ Department _______ Date ___________ Effective date ____________________________________ Replaces ____________________ Purpose: WHY: Why is this procedure written. Why is it being performed. Scope WHEN: Indicate when this procedure needs to be performed. WHERE: Indicate where this procedure applies. Responsibility WHO: Who performs the procedure, who is responsible to see it is performed correctly. Materials and equipment WHAT: What is needed to perform the test. The list should be complete and specific. 01-02-2022 23

24. SOP Number : .......... Rev...........Name of facility ........................................... page .......... of .......... Short title: .................................................................................................. Procedure HOW: Clear concise, step by step instructions on how to perform the procedure. This should be written as instructions for the operator to follow, without a lot of theoretical background. A section on fundamental principles can be included if necessary. It should include: a) Preliminary steps that must be done before beginning the actual procedure. b) Safety considerations: Precautions for work with physical, chemical, or biological hazards (containment facility clothing, masks, hoods, goggles, gloves, clean up of spills etc.). c) The chronological instructions. It is useful to number the steps so that repeat steps can be referred to rather than making the SOP very long. d) Calculations: Explanations and sample of how to do any required calculations. Reporting WHAT NEXT: a) Indicate where the results should be recorded. b) Explain what to do if there are problems during the test. c) Indicate that deviations to the procedure must be approved and recorded. d) Identify the person to whom the final results should be reported. Reference documents: List other SOPs which directly affect or are relevant to this procedure. For example, the SOP for making a buffer used in the procedure, or the SOP for the operation of a piece of equipment used 01-02-2022 24

25. MASTER FORMULA Master formula: A document or set of documents specifying the starting materials with their quantities and the packaging, materials, together with a description of the procedures and precautions required to produce a specified quantity of a finished product as well as the processing instructions, including the in process controls. GMP documents from WHO and other countries all require that a Master Formula be prepared and approved for each batch size of every product manufactured. The format for the MF should be a formal document with the company name, product name, batch size, site of manufacture, a document number with revision number, and approval signatures and dates. Each page should be numbered and spaces should be provided to fill in the lot number of the batch and for approval signatures. The MF, and any revisions, must be approved, with dated signatures, by both Production and QA officials. 01-02-2022 25

26. GMP Categories Sale Premises Equipment Personnel Sanitation Raw Material Testing Manufacturing Control Packaging Material Testing Finished Product Testing Quality Control Department Records Samples Stability Sterile Products 01-02-2022 26

27. GMP The Govt of India amended the drugs & cosmetics rules, 1945 on 24th june 1988 and prescribed GMPs under Schedule M Schedule M has 2 parts, part 1 and part 2 GMP guidelines come under part1 The Schedule M has been revised and brought more less to the level of WHO GMP text 01-02-2022 27

28. WHO GMP ensures the following: Avoidance of Cross- Contamination Prevention of Mix-ups Provide Traceability Accountability of actions Responsibility Product Performance Guarantee 01-02-2022 28

29. Conclusion From the above discussion we can conclude that Pharmaceutical Industry is regulated by GMPs Good Manufacturing Practices must be followed GMPs ensure drug products are safe, pure and effective. Good Manufacturing Practice is Good Management Practice Get More Profit Give More Production 01-02-2022 29

30. References https://www.nne.com/services/good-manufacturing-practice/ https://www.who.int/medicines/areas/quality_safety/quality_assurance/gmp/en/ gmp-140930003330-phpapp02%20(1).pdf /goodmanufacturingpracticepritesh-160516130050.pdf 01-02-2022 30