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Overview on Drug QualityOverview on Drug Qualityand Drug Standardand Drug Standard
Sompol PrakongpanSompol Prakongpan,, Ph.D.Ph.D.
Faculty of Pharmacy, Mahidol UniversityFaculty of Pharmacy, Mahidol University26 March 201026 March 2010
Medicine Quality
Desired characteristics of product to ensure :
• Safety• Efficacy• Quality
Number of Drug-Quality Reports Receive
d by the FDA, 1999–2007
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.
USP and GlycerinUSP 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
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
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
Metal fragmentMetal fragment
Impacts of Low-Quality MedicinesImpacts of Low-Quality Medicines
? ? MEDICINE MEDICINE QUALITYQUALITY
MaterialsManufacturing
processPackagingTransportationStorage
condition Lack of therapeutic
effect Prolonged illness
Death Toxic and adverse
reaction Waste of limited
financial resources Loss of credibility
Determinants of Medicine QualityDeterminants of Medicine Quality Identity: Active ingredientIdentity: Active ingredient
Purity: Not contaminated with potentially harmful Purity: Not contaminated with potentially harmful
substancessubstances
Potency: Usually 90Potency: Usually 90––110% of the labeled amount110% of the labeled amount
Uniformity: Consistency of color, shape, sizeUniformity: Consistency of color, shape, size
Other Specifications: polymorph, particle size, chirality, dissolution, Other Specifications: polymorph, particle size, chirality, dissolution,
Bioavailability: Interchangeable products? Bioavailability: Interchangeable products?
Stability: Ensuring medicine activity for stated periodStability: Ensuring medicine activity for stated period
Identity, purity, potency, uniformity are defined in pharmacopoeias and stated in certificate of analysis (COA)
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 c
an target Monitor for counterfeit and substandard products Monitor the quality of imported drug products Provide information for compounding pharmacist
s
Thai PharmacopoeiaThai Pharmacopoeia
New generics : major consumptionNew generics : major consumption
Difference in standardDifference in standard and testing and testing methods among official pharmacopoeiasmethods among official pharmacopoeias
Thai formulary, herbThai formulary, herb
Biopharmaceuticals? Insulin, somatropin, Biopharmaceuticals? Insulin, somatropin, interferoninterferon
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.
Quality ChainQuality Chain
OperationOperation Good Practices (GGood Practices (GxxP)P)
R & DR & D GCPGCP
FormulationFormulation GFPGFP
RegistrationRegistration GRPGRP
ManufacturingManufacturing GMP/GLPGMP/GLP
StorageStorage GSPGSP
DistributionDistribution GDPGDP
DispensingDispensing GPPGPP
ConsumersConsumers Proper useProper use
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.
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.
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.
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.
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.
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.
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.
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
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
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 associ
ated with medicines• preventing harm to patients
Who Ensures Medicine Quality?Who Ensures Medicine Quality? Drug Drug
regulatory regulatory authorityauthority
DrugDrug TherapeuticsTherapeutics CommitteeCommittee
HospitalHospital procurementprocurement officeoffice
PatientsPatients
PhysiciansPhysicians and otherand other prescribersprescribers
PharmacyPharmacy (and dispensers)(and dispensers)
MedicineMedicineQualityQuality
Quality AssessmentQuality Assessment
COACOA– Identity, purity, potency, uniformity– Additional test: dissolution test, polymorph, Additional test: dissolution test, polymorph,
particulate matter, bacterial endotoxin testparticulate matter, bacterial endotoxin test
Company track record: responsibility, Company track record: responsibility, recall, defect, servicerecall, defect, serviceGMP/PICsGMP/PICsRaw materials: active, inactive ingredients, Raw materials: active, inactive ingredients, impurity, etcimpurity, etc
Thank YouThank You
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