1. CHEE 4401 Introduction to GMP

2. CHEE 4402 Objectives u Acquire basic knowledge of Good Manufacturing Practices (GMP) ä What are GMPs ? ä Why are they important ?

3. CHEE 4403 History of Food and Drugs Act u Government Authorities ä Canada: Health Canada Health Products and Food Branch (HPFB) ä USA: Food & Drug Administration (FDA) ä Europe: EC Directives

4. CHEE 4404 History u Food and Drugs Act u Food and Drug Regulations ä Division 2 : Good Manufacturing Practices u 1900s- Adulterated Food ä First purity laws enacted u 1930s- Sulfanilimide ä Drugs had to be proven safe u 1960s- Thalidomide ä Drugs had to be proven safe and effective through clinical trials

5. CHEE 4405 Why are GMPs important? u Government requirement u Ensure quality product u Reduce rejects, recalls u Satisfied customers u Maintain manufacturing consistency u Company image and reputation

6. CHEE 4406 Drugs u HPFB Definition: Any substance or mixture of substances manufactured, sold or represented for use in a) the diagnosis, treatment, mitigation or prevention of a disease, a disorder, an abnormal physical state or the symptoms thereof in humans or animals b) restoring, correcting or modifying organic functions in humans or animals c) disinfection in premises in which food is manufactured, prepared or kept u DIN u Label Claim

7. CHEE 4407 Food and Drugs Act u Establishment license u Site Reference File u HPFB Inspections

8. CHEE 4408 Production Goals u Safety ä Product is free of unwanted side effects when used appropriately by patient u Identity ä Product exactly matches the labelling and related documents u Strength ä Product has correct concentration, potency or therapeutic activity of active ingredient u Purity ä Product is free from contamination u Quality ä Product meets all standards, expectations; performs as claimed ä Product made consistently

9. CHEE 4409 GMP Categories u Sale u Premises u Equipment u Personnel u Sanitation u Raw Material Testing u Manufacturing Control u Quality Control Department u Packaging Material Testing u Finished Product Testing u Records u Samples u Stability u Sterile Products u Medical Gases

10. CHEE 44010 Sale C.02.003 u No distributor … and no importer shall sell a drug unless it has been fabricated, packaged/labeled, tested, and stored in accordance with the requirements of this Division

11. CHEE 44011 PremisesC.02.004 Equipment C.02.005 u Permits effective cleaning u Prevents contamination u Orderly conditions u Good state of repair

12. CHEE 44012 PersonnelC.02.006 u Appropriate education, training and experience u Sufficient number of people u Receive GMP training ä Initial and continuing training as relevant to job responsibilities

13. CHEE 44013 SanitationC.02.007 -.008 u Sanitation Program to prevent contamination ä Limit the sources and types of contamination »Cleaning procedures for facilities & equipment »Pest control »Environmental monitoring ä Documented evidence

14. CHEE 44014 SanitationC.02.008 u Hygiene ä Health and eye examinations ä Report adverse health conditions ä Clothing requirements »No direct skin contact with product »Wash hands »No jewelry or excessive makeup ä No smoking, eating, drinking, chewing, or keeping of plants in operations areas

15. CHEE 44015 Raw Material Testing C.02.009 -.010 u each lot or batch of raw material is tested u three objectives ä confirm the identity of the raw materials ä provide assurance that quality of the drug in dosage form will not be altered by raw material defects ä assure that raw materials have the characteristics that will provide the desired quantity or yield in manufacturing process

16. CHEE 44016 Raw Material, Packaging Material and Finished Product Testing u Samples of incoming materials are collected and tested before use u Approved test methods and specifications are used u Results must conform to specifications for release for use or sale u Transportation and storage records

17. CHEE 44017 Manufacturing Control C.02.011 u Written procedures are established and followed ä Master formulae, manufacturing order and packaging order u Critical processes are validated u 2nd person verification of activities u Quarantine system u Labelling requirements

18. CHEE 44018 Manufacturing Control C.02.012 u Recall Programme u Self-Inspection Programme u Ensure compliance with vendors/contractors

19. CHEE 44019 Manufacturing Control (contd) u Validation: the documented act of demonstrating that any procedure, process, equipment, material, activity, or system will consistently lead to the expected results »TPP 1998 Edition ä Design Qualification (DQ) ä Installation Qualification (IQ) ä Operational Qualification (OQ) ä Performance Qualification (PQ)

20. CHEE 44020 Quality Control Department C.02.013 - C.02.015 u Quality Control Responsibilities ä Testing of bulk components prior to use by production ä Testing of finished product prior to release for sale ä Stability program (in association with QA)

21. CHEE 44021 Quality Control Department C.02.013 - C.02.015 u Quality Assurance Responsibilities ä Ensure GMP compliance ä Review batch records, labels ä Release product, based on QC test results ä Authorize all master documents and SOPs ä Training, auditing ä Customer complaints ä Recall

22. CHEE 44022 Key Quality Terms u CHANGE CONTROL ä written procedure that describes the action to be taken if a change is proposed to facilities, etc. used in fabrication, packaging, and testing of drugs or any change that may affect quality or support system operation u DEVIATION ä Planned or unplanned temporary departure from an approved process, specification or procedure with the potential to impact product quality

23. CHEE 44023 RecordsC.02.020 - C.02.024 u Document all GMP activities u Use Good Documentation Practices (GDP) u Records must be readily available u Needed to prove activities were done

24. CHEE 44024 Good Documentation Practices u Documentation must be: ä permanent (black or blue ink) ä legible, clear, concise ä accurate ä timely ä consistent ä complete

25. CHEE 44025 Samples and Stability u Samples ä Retain samples of each lot of raw material and finished product for specified period of time u Stability ä Establish the length of time in which the product meets all specifications ä Monitor the drug for this period of time

26. CHEE 44026 Sterile ProductsC.02.029 u Sterile Products ä Packaged in separate enclosed area by trained personnel using method to ensure sterility

27. CHEE 44027 Summary u Pharmaceutical Industry is regulated by GMPs u Good Manufacturing Practices must be followed u GMPs ensure drug products are safe, pure and effective.