ASSURING SAFETY OF T/CM PRODUCTS:

THE MALAYSIAN EXPERIENCE

Abida Syed HaqNational Pharmaceutical Control BureauMinistry of Health Malaysia

TRADITIONAL MEDICINES In 1994, about 4000 dietary supplements and

herbal products available in the USA. Today, it is estimated that there are over

29000 herbal and other natural products are available in the USA

In Malaysia, >9000 traditional medicines registered by the Drug Control Authority for use

Malaysian Drug Registry

Cosmetics1757

Prescription Drugs

8891 (33%)

OTC6576 (24%)

Traditional Medicines

9693 (36%)

Prescription Drugs OTC Traditional Medicines Cosmetics

TRADITIONAL MEDICINES (TM)

Generally used as health supplements and for

the treatment of benign, self limiting

conditions

Occasionally used to self treat serious illnesses

Products are widely advertised over the

Internet and through the mass media

“IT IS NATURAL, THEREFORE IT IS SAFE”

Common misnomer Impossible to ensure that all medical

interventions including traditional medicines are entirely risk-free

Numerous reports of adverse effects associated with the use of TM

Unlike pharmaceuticals, TM continue to be marketed unless, or until, proven to be unsafe

SAFETY ISSUES - MALAYSIA Products marketed with unsubstantiated

claims Adverse drug reactions e.g. Noni juice Continued presence of unregistered

products Adulterated products Counterfeit

SAFETY ISSUES - MALAYSIA Product registration withdrawn

Aristolochic Acid Kava-kava Magnolia officinalis Adulteration

Steroids Fenfluramine Sibutramine Sildenafil Phenylpropanolamine

SAFETY ISSUES - US FDA

In the past, no evaluation of herbals done Now, taking a new approach – evaluation

on available information being done to facilitate regulatory decisions being made

Products under study Chapparal, chromium picolinate,

glucosamine, melatonin, saw palmetto and shark cartilage

FACTORS AFFECTING SAFETY Intrinsic factors

Inherent toxicity, adverse effects due to overdosage, interactions, underlying risk factors

Extrinsic factors Quality defects, misidentification, contamination,

adulteration, mislabeling, improper storage

PRODUCT SAFETY Systems have to be put in place to ensure

safety of all products Responsibility of the

Manufacturers Product owners Regulatory authority Practitioners Retailers Consumers

Mission

To have only safe traditional medicines which comply with set standards of quality available in Malaysia.

Vision

To be a world leader in the production of safe traditional medicines which are of quality

POLICIES & STRATEGIES Legislation

In Malaysia, all medicinal products including traditional remedies must be registered before they can be manufactured, imported, sold

Governed by Sale of Drugs Act Control of Drugs and Cosmetics Regulations Poisons Act Medicines Advertisement Act

POLICIES & STRATEGIES Regulatory

All products are evaluated for quality & safety Paper and laboratory evaluation

Adherence to Good Manufacturing Practices All products subjected to surveillance Monitoring of adverse drug reactions Monitoring of labels, information leaflets Control of advertisements

POLICIES & STRATEGIES Education

Manufacturers Good knowledge of plant nomenclature

Labeling of ingredients using scientific names

Botanical verification and identification of starting materials

Quality control and quality assurance procedures Integrity and self-regulation

POLICIES & STRATEGIES Education

Practitioners of conventional medicines Basic knowledge on traditional medicines Break away from situation of “don’t ask, don’t

tell” Monitoring and reporting of adverse reactions

Public Using products in accordance to intended use Be forthcoming with information

NATIONAL SURVEILLANCE PROGRAM

Ideally, all marketed products should undergo surveillance

Criteria for surveillance Registered, marketed products which have never

been tested Products previously found to have failed lab

analysis Manufacturers identified by GMP inspectors to

have problems “Tip-offs”/suspicious products

NATIONAL SURVEILLANCE PROGRAM

Quality standards Microbial/ fungal Limit Tests Testing of toxic heavy metal contamination

i.e. lead, mercury, arsenic Detection of adulterants/ undeclared drugs

Adverse drug reactions monitoring Local International

Year No. of Traditional Medicines Tested

Failure Rate No. of Product

Recalls

2000 1014 173

(17.06%)

97

(9.56%)

2001 652 157

(24.07%)

85

(13.03%)

2002(Jan-Aug)

784 151

(19.26%)

56

(7.14%)

NATIONAL SURVEILLANCE PROGRAM

Ref: National Pharmaceutical Control Bureau

NATIONAL SURVEILLANCE PROGRAM

Year No. of Traditional Medicines Tested

No. Failed MLT

No. Failed Heavy

Metal Limits

2000 1014 57

(5.62%)

30

(2.95%)

2001 652 35

(5.36%)

37

(5.67%)

2002

(Jan-Aug)

784 68

(8.67%)

19

(2.42%)

Ref: National Pharmaceutical Control Bureau

Strengths Good regulatory system Compulsory testing as part of the

registration procedure Post-marketing Surveillance System for investigating product complaints Adequate laboratory testing facilities for

surveillance samples

Strengths Implementation of Good

Manufacturing Practices for all manufacturers of traditional medicines

QUALITY SAFETY ISO 9002 certified quality system PIC/S Certification A good pharmacy enforcement unit

EVALUATION & REGISTRATION

SURVEILLANCE

GMP & LICENSING

PHARMACY ENFORCEMENT

SAFETY ISSUES

PUBLIC

Weaknesses Poor compliance to GMP by some

manufacturers Inadequate finished product

testing by manufacturers Lack of standardisation of “active”

ingredients Security/tamper-proof packaging

systems

Weaknesses Underreporting of adverse reactions

by health professionals, consumers No reporting of adverse reactions by

traditional medicine practitioners Inadequate availability of

information adverse reactions of ingredients interactions with pharmaceuticals contraindications

Opportunities Increasing knowledge on the use of

traditional medicines by health professionals

Regular dialogues with traditional medicine practitioners

More stringent regulatory requirements to ensure the quality of starting materials, formulations used

Global partnership with WHO, other regulatory and health authorities

THREATS

Complacency Unscrupulous manufacturers and

traders “Supply and Demand” for

unregistered products

THE PARADIGM SHIFT Evidence on efficacy – inefficacy is also a

safety issue Evidence on the safety of products and

therapies used – not sufficient to just believe that it safe

Need to have a system for assuring product safety

Better quality control of products – underdosing, overdosing, contamination, adulteration are all safety issues

THE WAY FORWARD Increased surveillance - by regulators,

industry Improved safety monitoring System for identifying unregistered/ counterfeit products Good knowledge base – information

hub In-house laboratory testing by

manufacturers

It is an uphill task, but….

…we have already got a head start!