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