1. Overview on Drug Quality and Drug Standard Sompol Prakongpan, Ph.D. Faculty of Pharmacy, Mahidol University 26 March 2010

2. Medicine Quality Desired characteristics of product to ensure : Safety Efficacy Quality

3. Number of Drug-Quality Reports Received by the FDA, 1999–2007

4. Background - 1990: 236 Children died in Bangladesh. - 1990: 40 Children died in Nigeria diethylene glycol. - - 1995: 88 Children died in Haiti - - 2006: 116 died in Panama - - 2009: 24 died in Bangladesh Paracetamol elixir, Cough syrup: Glycerol adulterated with diethylene glycol.

5. USP and Glycerin   Glycerin revision (official May 1, 2009) includes a Limit test for both Diethylene Glycol (DEG) and Ethylene Glycol (EG) at 0.10% each in the Identification test   Official monograph and reference standard information posted on the USPC website: http://www.usp.org/hottopics/glycerin.html

6. Types of Quality Problems mislabeled drugs inaccurate or unreadable product labels/labeling sterile containers or vials that are punctured or leaking packaging or product mix-ups abnormal odor or taste capsule leakage

7. Types of Quality Problems (Cont.) chipped, cracked, or splitting tablets tablet or capsule discolorations broken, cracked, or chipped syringes suspected product contamination vials with foreign floating objects or growth container closure defects leaking vials

8. Metal fragment

9. Impacts of Low-Quality Medicines ?MEDICINEQUALITY  Materials  Manufacturing process  Packaging  Transportation  Storage condition  Lack of therapeutic effect Prolonged illness Death  Toxic and adverse reaction  Waste of limited financial resources  Loss of credibility

10. Determinants of Medicine Quality  Identity: Active ingredient  Purity: Not contaminated with potentially harmful substances  Potency: Usually 90–110% of the labeled amount  Uniformity: Consistency of color, shape, size  Other Specifications: polymorph, particle size, chirality, dissolution,  Bioavailability: Interchangeable products?  Stability: Ensuring medicine activity for stated period Identity, purity, potency, uniformity are defined in pharmacopoeias and stated in certificate of analysis (COA)

11. Why is a Public Standard Important?   Assure a consistent approach to quality for pioneer and generic products   Assess the quality of drug products in commerce   Provide specifications that new manufacturers can target   Monitor for counterfeit and substandard products   Monitor the quality of imported drug products   Provide information for compounding pharmacists

12. Thai Pharmacopoeia New generics : major consumption Difference in standard and testing methods among official pharmacopoeias Thai formulary, herb Biopharmaceuticals? Insulin, somatropin, interferon

13. How is quality Assured? Quality Assurance (QA): The sum total of all arrangements made with the object of ensuring that medicinal products are of the quality required for their intended use.

14. Quality Chain Operation Good Practices (GxP) R & D GCP FormulationGFP RegistrationGRP ManufacturingGMP/GLP StorageGSP DistributionGDP DispensingGPP Consumers Proper use

15. Definitions (Continued…) Good Manufacturing Practice (GMP) GMP is that part of quality assurance which ensures that products are consistency produced and controlled to the quality, standard required for their intended use.

16. Basic Principle of GMP 1. Quality, safety and efficacy must be designed and built in the product. 2. Testing alone cannot be relied on to ensure quality. 3. Each step in the manufacturing process must be controlled to ensure that the final product within limits and specifications.

17. Basic Requirements for GMP Clearly defined and systematically reviewed processes. Critical steps validated. Appropriate resources: personnel, buildings, equipment, materials. Clearly written procedures. Trained operators. Complete records, failure investigations. Recall system. Complaint handling.

18. Why GMP compliance important? GMP aim to ensure that the product is made in a way that : Assure consistency of quality, batch-after- batch. Ensure that any change is only implemented after impact on quality is assessed. Ensure that record keeping ensure traceability of all action and therefore, verification of complaints.

19. Absence of GMP means: Batch-to-batch quality consistency is not assured. Changes may be implemented without consideration for impact on quality. Deficient record keeping make investigation impossible. Contamination by other products from poorly cleaned multipurpose equipments. Different purity, strength, efficiency, safety and quality. Production operation different from the filing at the authority. Poor control and traceability of production.

20. GMP compliance is expensive as GMP requires: Higher standard of facilities. Critical changes to procedure, equipment, raw material require validation Stability testing Bioequivalence Qualified staff.

21. Business impact: More cost Reduce speed Reduce flexibility GMP is very expensive Hence much temptation to forget GMP and take short-cuts. This can be eliminated by regulate INSPECTION.

22. GDP – Good Distribution Practices Organization and management Personnel Quality management Premises, warehousing and storage Vehicles and equipment Shipment containers and container labelling Distribution Transportation and products in transit

23. What are GPP’s? (Good Pharmacy Practices) Framework for standards to suit national situation and needs for pharmacy practice Goal to provide consistent, quality, pharmacy services Other Tools: – Pharmacist and Other Healthcare Provider Good Practice Guidelines for the detection and prevention of Counterfeit Drugs – Partnership for Safe Medicines

24. Pharmacovigilance Systems Relates to the detection, assessment, understanding and prevention of adverse effects of medical products – Reports from manufacturers, healthcare providers, and patients on the adverse effects Purpose: identifying new information about hazards associated with medicines preventing harm to patients

25. Who Ensures Medicine Quality?  Drug regulatory authority  Drug Therapeutics Therapeutics Committee Committee  Hospital procurement procurement office office  Patients  Physicians and other and other prescribers prescribers  Pharmacy (and dispensers) (and dispensers) MedicineQuality

26. Quality Assessment COA – –Identity, purity, potency, uniformity –Additional test: dissolution test, polymorph, particulate matter, bacterial endotoxin test Company track record: responsibility, recall, defect, service GMP/PICs Raw materials: active, inactive ingredients, impurity, etc

27. Thank You