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Natural Products
Registration

Azrina Hassan
Natural Products Unit
Section of Complementary and Alternative Medicines
Center for Product Registration
National Pharmaceutical Regulatory Agency, MOH
 OVERVIEW OF
NATIONAL
PHARMACEUTICAL
REGULATORY
AGENCY

2
 ORGANIZATION CHART OF NATIONAL
PHARMACEUTICAL REGULATORY AGENCY (NPRA)

Director
Regulatory Pharmacy

Deputy Director Deputy Director

Centre for Product Centre for Quality Control
Registration

Deputy Director
Deputy Director Centre for Organisational
Centre for Compliance & Development & Strategic
Licensing Planning

Deputy Director Deputy Director

Centre for Post Registration of Centre for Investigational New
Products Products

Executive Officer
Administration Centre 3
 LEGISLATIONS
SALES OF DRUG ACT 1952
Control of Drugs and Cosmetics Regulations (CDCR) 1984

Regulation 7(1)
No person shall manufacture, sell,
supply, import, possess or administer any product
unless:
(a) the product is a registered product,
and
(b) the person holds the appropriate licence*
required & issued under these Regulations.

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THE AUTHORITY

• The Drug Control Authority (DCA) as the

licensing authority (Regulation 3, CDCR 1984).

• National Pharmacy Regulatory Agency (NPRA)

as the secretariat to DCA is responsible for:
Product registration
Licensing (manufacture, import, wholesale)
Monitoring and surveillance activities.
 Registration

Surveillance Analysis

Regulatory
Component

Pharmacovigil
ance Licensing
PRODUCT CATEGORIES
1. NEW DRUG PRODUCTS (NDP)
- any pharmaceutical product that has not been previously registered in
accordance with the provisions of the CDCR 1984, e.g. Innovator product.

2. BIOLOGICS
- active substance is made by or derived from a living organism (plant, human, animal or
microorganism) and may be produced by biotechnology methods and other cutting-edge
technologies. This product imitates natural biological substances in our bodies such as
hormones, enzymes or antibodies.

2. GENERIC PRODUCTS
i) Scheduled Poison (Prescription Medicine)
ii) Non-Scheduled Poison (Non-Prescription Medicine - OTC)

4. COMPLEMENTARY & ALTERNATIVE MEDICINES (CAM)

i) Natural Product (Traditional Medicine & Homeopathy)
ii) Health Supplement

5. VETERINARY
 ORGANISATION CHART OF CENTER FOR
PRODUCT REGISTRATION

Director

Deputy
Director

VETERINARY REGULATORY
API
NEW GENERIC MEDICINES COORDINATION
SECTION
DRUG MEDICINES BIOLOGIC COMPLEMENTA SECTION SECTION
SECTION SECTION SECTION RY AND
ALTERNATIVE
MEDICINES
(CAM) SECTION

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ORGANISATION CHART OF COMPLEMENTARY
& ALTERNATIVE MEDICINE SECTION

Complementary and
Alternative Medicine
(CAM)

Natural Health
Products Supplement

Vitamin / Substances
Traditional Homeopathic Amino Acid derived from
Medicine Medicine / Enzyme / natural
Probiotics sources (eg.
Fish Oil, EPO)

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 REGISTRATION
REQUIREMENTS &
PROCEDURES

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 PHASES OF REGISTRATION
New Products Phase 1 Phase 2 Phase 3 Phase 4 Phase 5

Biotechnology Registration
Registration Registration
Registration Feb 2002 Registration
August 1985 Jan 1992
1988 (Cosmetics) August 2007
(Prescription (Natural
(OTC) Notification: 1 (Veterinary)
Drug) Products)
January 2010

Veterinary Products
Licensing
Licensing Licensing Manufacturers Licensing
Licensing
May 1987 1992 Importers Jan 2004
Jan 1999

Active Pharmaceutical Licensing

Ingredients
Wholesalers
Surveillance Surveillance Surveillance
July 2002 Surveillance
1990 1995 2004
Surveillance
1999

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 PURPOSE OF REGISTRATION

• Toensure that all natural products which

are registered with the DCA are evaluated
on Safety & Quality.

* For natural products efficacy is based on

the claimed benefits and documented use
as folk medicines based on philosophy of
the respective traditional medicines .

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 DEFINITION OF TRADITIONAL
MEDICINES

• Traditional medicine is defined as any product used in the practice of

indigenous medicine, in which the drug consists solely of one or more
naturally occurring substances of a plant, animal or mineral, or parts
thereof, in the unextracted or crude extract form and a homeopathic
medicines (CDCR 1984)

• It shall not include any sterile preparation, vaccines, any substance derived
human parts, any isolated or characterized chemical substances

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TRADITIONAL PRODUCTS THAT ARE

REQUIRED TO BE REGISTERED

Traditional medicine in pharmaceutical dosage form

with claims.
eg: pill, tablet, capsule, tea bag, powder
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PRODUCTS THAT DOES NOT REQUIRE

REGISTRATION
1. Extemporaneous medicine – prepared and
given directly to patient by traditional
practitioner.
2. Herbal medicine containing plants produced
only through drying, grinding or blending
(raw herbs).
3. A herbal preparation containing plants
normally taken as food and consumed as a
drink/beverage with no medicinal claim.
4. A preparation used for a cosmetic purpose
(eg. to whiten) shall be notified as a
cosmetic product.
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PRODUCTS THAT ARE NOT ALLOWED TO BE REGISTERED

1. Products containing herbal ingredients as listed under Poison Act
1952 (Eg. Foxglove leaf, Ephedra).
2. Products containing ingredient known or reported to cause any
adverse effect on humans. Eg: Stephania Tetrandra & Aristolochic
Acid Kidney dysfunction.
3. Products containing ingredients derived from human origin. Eg:
Crinis Carbonisatus = Carbonised human hair; Human Placenta (URI).
4. Products containing ingredients derived from prohibited /
endangered animal species. Eg: tiger bone, rhino horn, panggolin etc.
5. Products with the indication as listed in “List of Non Permissible
Indications according to Medicine Advertisement and Sale Act 1956”
(eg. diabetes, cancer, etc).
 CRITERIA FOR REGISTRATION

1) Applicant must be a locally incorporated company

and be authorized in writing by the product owner to
be the holder of the registration certificate
2) Product Registration Holder (PRH) responsible for
all matters pertaining to the registration of the
product

3) Product must satisfy registration criteria with

respect to safety, quality and claimed benefits.
FEES FOR NATURAL PRODUCTS REGISTRATION
Processing Fee (RM) Testing (RM) Total (RM)

500 700 1200

CLIENT CHARTER FOR NATURAL PRODUCTS

REGISTRATION
Category Duration (days)

Single active ingredient 116 working days

Two or more active ingredients 136 working days

Full Compliance to
With condition
Requirements
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 STATISTICS
582 565 578 590 569

600
467

500

400

300

200

100

0
2010 2011 2012 2013 2014 2015

Number of traditional products registered

Source: NPCB Statistics Department

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 EVALUATION OF NATURAL PRODUCTS

Incomplete
Screening
(Within 14 working days) Product
Registration
Holder (PRH)
Complete

Payment done by applicant Send Sample

Evaluation by the evaluator *Lab Analysis

(Testing within 30
working days –single
Incomplete ingredient/ 45 working
days – multiple
Checking by the Head of Unit/Section ingredients)

Complete
Incomplete

Product Evaluation Committee

Meeting
Approve REJECT
Incomplete Letter of rejection
Drug Control Authority Meeting to applicant

Approve
Notification via email Applicant can appeal through the
OR checking product Minister of Health for reviewing
Product is registered DCA’s decision. ( Within 14 days)
registration status via
NPCB website
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 EVALUATION OF NATURAL PRODUCTS

QUALITY CRITERIA
Compliance to Good Manufacturing Practice
(GMP)
IPQC, Finished products QC

COA of raw materials & finished products

Stability testing

Product freely sold in the country of origin

 EVALUATION OF NATURAL PRODUCTS

SAFETY CRITERIA
Does not contain banned ingredients

Warning statements/adverse effects on product label

Contains substances in allowable limits/dose
Limits for heavy metals, limits for microbial contamination, no adulterants

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 EVALUATION OF NATURAL PRODUCTS

Products Particulars Product Formula

Product Name
Product Description -Active
ingredient
-Ban item
-Excipient

Manufacturer
-CPP
_GMP
-Compulsory -CFS
labeling -Pack size
requirement -Type of
-Additional
container
Warning/
Precaution Labeling Packing Particulars
Requirement
Drug Registration Guidance Document

Appendix 5:
Guideline on
registration of
natural products

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 EVALUATION OF NATURAL PRODUCTS

COMMON REASONS FOR PRODUCTS REJECTION

Incomplete documentation
Excipient’s function/ limit was not supported
Issuing body for CFS/ GMP was not listed/ not accepted
Manufacturer produce dosage form which is not permitted
in its facility.
Same holder wish to register another product with same
formulation (not replacement product)
Fail lab testing
Applicant does not complete the correspondence within 6
months from date of dossier submission

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SECTION A: PRODUCT PARTICULARS
Fields Description
A1 Name of Product
A2 Product Description
A3 Dosage Form
A4 Name and Strength of Active and Excipient Substance
A5 Product Indication
A6 Dose / Usage instruction
A7 Contraindication
A8 Warning / Precaution
A9 Drug Interaction
A10 Side Effects / Adverse Reaction
A11 Signs of Overdose
A12 Storage Condition
A13 Shelf Life
A14 Therapeutic Code
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Examples of indication allowed

Traditionally used….……

GENERAL HEALTH MAINTENANCE / KESIHATAN AM

- for general health maintenance / for general well being
- for health and strengthening the body
BLOOD & BODY FLUID / DARAH & CECAIR BADAN
- for improving blood circulation
- to improve urination
- for improving bowel movement

BONE, MUSCLE AND JOINT / TULANG, OTOT & SENDI

- for strengthening muscle and bone
- for relieving muscular ache .
- for relieving waist ache and backache

SKIN AND EXTERNAL USE

- for symptomatic relief of pain and itch associated with insect
bites
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PAIN & FEVER / SAKIT AM & DEMAM

- to relieve / alleviate pain
- for relieving headache

COUGH & COLD

- to relief cough and cold
- to relief of nasal congestion

DIGESTIVE SYSTEM
- for relief of stomachache, mild diarrhea
- for relief of flatulence, stomach ache, mild diarrhea and
loss of appetite

WOMEN’S HEALTH / MEN’S HEALTH

- to relief menstrual pain, headache,
- to relief vaginal discharge
- for energy and men’s health/ for vitality
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SECTION B - PRODUCT FORMULA

B 1.1 Batch Manufacturing Formula

B 1.2 Attachment of Batch Manufacturing

B 2.1 Manufacturing process

B 2.2 Attachment of manufacturing

B3 In Process Quality Control

B 4 Attachment of Finished Product Specification Documentation

B5 Attachment of Stability Data Documentation

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SECTION C – PARTICULAR OF PACKING
C1 Pack Size

e.g. : 100 capsule

C2 Container Type/Container Type Description

E.g. : HDPE Plastic Bottle, Glass Bottle, Aluminum Blister Pack

C3 Barcode/Serial No.

C4 Recommended Distributor’s Price, RM

C5 Recommended Retail Price, RM

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SECTION D – LABEL AND PROPOSED PACKAGE INSERT

D1 Label (mock up ) for immediate container

D2 Label (mock up ) for outer carton

D3 Proposed package insert

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SECTION E –PARTICULARS OF MANUFACTURER/

IMPORTER / REPACKER / PRODUCT OWNER/STORE ADDRESS
E1 Product Owner

E2 Manufacturer

E3 Other manufacturer(s) involved

E.g.: Repacker

E4 Store Address
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SECTION F– SUPPLEMENTARY DOCUMENTATION
F1 Letter of Authorisation from Product Owner
F 2.1 Letter of Appointment of Contract manufacturer from Product Owner
F 2.2 Letter of Acceptance from Contract Manufacturer

F3 Is the Active Substance(s) Patented in Malaysia

F4 Certificate of Pharmaceutical Product (CPP)
F5 Certificate of Free Sale (CFS)
F6 Good Manufacturing Practice (GMP) Certificate
F7 Summary of Product Characteristics (Product Data Sheet – if any)
F8 Patient Information Leaflet ( PIL)
F9 Attachment of Protocol Analysis
F 10 Attachment of Certificate Analysis (Finished Product)
F 11 Attachment of Certificate of Analysis (Active Ingredient)
F 12 Other Supporting Document
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Example
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PRODUCT REGISTRATION NUMBER

• Registration number: MAL YYMMŠŠŠŠ@##

Code(@)
A: Scheduled Poisons
X: Non-scheduled Poisons (over the counter products)
T: Traditional Medicines
C: Contract Manufactured
E: Export Only
R: Repacked
S: Second source

• Validity period of registration – 5 years

• Renewal of product registration should be done not later than 6 month prior to
expiry of product registration
• Validity period of registration – 5
years M
• Surveillance programme P A
• Handling products complaints O R
• Pharmacovigilance – handling S K
ADR reports & safety reports
T E
T
 CHALLENGES

• Adulteration – with schedules poisons

• Detection of adulteration (analogues)
- require knowledge and skills in isolation, extraction &
purification
- The need to understand structural elucidation and
capable of interpreting analytical data
• Detection of marker compound to verify plant species in
natural medicinal products
• Research & development of testing methodologies –
require knowledge, skills & extensive technical expertise
• Claims – therapeutic (high) claims, new claims
 MEASURES TAKEN

• Pre & post market testing for adulterants

• Guideline for natural product with high claims
• Develop Malaysian Herbal Monograph (MHM) –
collaboration with other institutions
• Developing methodologies for detection of marker
compound in plant species
 Thank You
azrinahassan@npra.gov.my

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 Compedium Medicinal Plants Used In
Malaysia (Vol I & II)
REFERENCES Indeks Tumbuhan Ubat Malaysia

Chinese – English manual Of Common-

Used In Traditional Chinese Medicine
PDR For Herbal Medicine
Indian Materia Medica (Vol 1 & II)
Pharmacopoea Of The People’s Republic
of China
The Coloured Atlas of Chinese Materia
Medica Specified In Chinese
Pharmacopoeia
Encyclopedia Of Homeopathic
Pharmacopeia (Vol I. II & III) 40