REGISTRATION PROCEDURE OF MARKETING AUTHORIZATION OF

MEDICINAL PRODUCT IN MALAYSIA

NAVEEN KADIAN*, MOHIT SAINI, MANAS TANDON

Address of Correspondence
Getwell Pharmaceuticals,
Plot No- 474, Udyog Vihar
Phase- V, Gurgaon - 122016
Haryana, India
Email naveen20.a@gmail.com

ABSTRACT
South East Asian pharmaceutical market is a strong and rapidly growing market. There are
several countries in south East Asia but only 10 countries are included in the ASEAN region.
Although regulatory environment among all ASEAN countries is similar but still requirements
and process of registration is varying among the countries of ASEAN region. ASEAN market is
having huge potential for those companies which are looking for fast expansion and this ASEAN
are expected to grow with a rate of 12.8% by the 2015. ASEAN market is basically depends
upon import of the pharmaceutical product in order to fulfill the public health need. Although
ACTD format is harmonized and mandatory from 2009 for all 10 countries but still every
country is differ in some local requirement such as Administrative data and labeling. The purpose
of this paper is to provide an overview on Drug registration requirement in Malaysia. Therefore
this review article will try to give easy understanding on dug registration requirement of
Malaysia i.e. safety aspects, documents required for registration, types of application review,
type of application, timeline for different type of application review, presubmission and post
registration requirement.
KEY WORDS: ASEAN, ACTD, DRGD, PPWG, Malaysia, Pharmaceuticals.

INTRODUCTION:
At present ASEAN consist of 10 countries (Indonesia, Malaysia, Philippines, Singapore,
Thailand Brunei Darussalam, Vietnam, Laos, Myanmar and Cambodia) was established on 8
August 1967 in Bangkok but initially when it was established it consist of only five original
member countries (Indonesia, Malaysia, Philippines, Singapore and Thailand) after that five
additional countries (Brunei Darussalam, Vietnam, Laos, Myanmar and Cambodia) joined
ASEAN. In 1999 a harmonization initiative was started among the 10 ASEAN countries. In 1997
ASEAN began with the harmonization of pharmaceutical standards when they felt the need to
establish a PPWG (Pharmaceutical product working group) during meeting in 1997 and a
proposal was given by Malaysia and supporting by other relevant bodies. Accordingly PPWG
held its first meeting in September 1999 with Malaysia as chair and Thailand as co-chair. After
the subsequent meetings PPWG developed the ACT, ACTD and its guideline. Reason for the
harmonization was there should be to harmonize quality guidelines that are valid for 10 countries
involved and co-operation between them. MALAYSIA is also one member of the ASEAN
countries and follows ASEAN guideline. Still every country is having their own registration
guidance. In this document we are going to discuss only drug guidance registration document
(DRGD). DRGD is discussing all requirements which are needed for the registration process of
the Product used in treatment, prevention, cure and diagnosis of the disease. The control of drug
and cosmetic regulation (CDCR) 1984 were promulgated under the Sale of Drug act 1952 and
DCA (Drug control Authority) is established under these regulations. This DCA is responsible
and working in such a way to ensure the Safety, Quality and Efficacy of the medicinal product
registration, licensing, inspection, quality control and post registration activities.
This DRGD shall be read in conjunction with the current laws and regulations together with
other relevant legislations, where applicable, governing pharmaceutical and natural products for
human use in Malaysia, which include but not limited to the following:
a) Sale of Drugs Act 1952;
b) Control of Drugs and Cosmetics Regulations 1984;
c) Dangerous Drugs Act 1952;
d) Poisons Act 1952;
e) Medicines (Advertisement & Sale) Act 1956;
f) Patents Act 1983;
g) Wildlife Conservation Act 2010 (Laws of Malaysia Act 716); and
h) International Trade in Endangered Species Act 2008 (Act 686).
Any enquiry on the registration of product may be submitted to the Secretary, Drug Control
Authority, National Pharmaceutical Control Bureau, Ministry of Health Malaysia, Jalan
Universiti, P.O. Box 319, 46730 Petaling Jaya, Selangor
The different phases of product registration are given as follows:

Malaysian DRGD divided registration of products into three types:

Registrable product: A drug or any substance used for medicinal purpose.

a) Pharmaceutical product containing scheduled poisons
b) Pharmaceutical product containing scheduled poisons
c) Natural products
Non-Registrable Product
a) Diagnostic agents
b) Medical device
c) Food
d) Sports nutrition
e) Raw herbs Used in Extemporaneous preparation
f) Insect repellants, insecticides, pesticides and paracitisides.
g) Detergents/disinfectants for domestic use
Exemption for products used in clinical trial and manufacturing samples for registration
a) Clinical trial Import license(CTIL)
b) Clinical trial Exemption (CTX and exemption) and exemption for
manufacturing sample for registration

Registration involves a step wise trend which is followed by every medicinal product:

The ASEAN common technical dossier (ACTD) which is using for the registration of a
pharmaceutical product for human use is an organization of the dossier which agreed upon the
ICHs CTD which is submitted to the regulatory authority for the drug product registration. It is
having different modules (Four) each consist of different information.
ASEAN CTD organized in Four modules described as follows:
Part I. Table of Contents, Administrative Data and Product Information
Part I contains initially the overall Table of Contents of the whole ACTD to provide basically the
information. Secondly, the next content is the Administrative Data where required specific
documentation in details is put together such as application forms, label, and package insert etc.
The last section of this part is Product Information where necessary information includes
prescribed information, mode of action, side effects etc.
A general introduction to the pharmaceutical, including its pharmacologic class and mode of
action should be included. Consist of following sections:
Section A: Introduction
Section B: Overall ASEAN Common Technical Dossier Table of Contents
Section C: Documents required for registration (for example, application forms,
Labeling, Product Data Sheet, prescribing information)

Part II. Quality Document

Part II should provide the Overall Summary followed by the Study Reports. The quality control
document should be described in details as much as possible and which consist of following
sections:
Section A: Table of Contents
Section B: Quality Overall Summary
Section C: Body of Data
Part III. Nonclinica1 Document
Part III should provide the Nonclinical Overview, followed by the Nonclinical Written
Summaries and the Nonclinical Tabulated Summaries. The document of this part is not required
for Generic Products, Minor Variation Products and some Major Variation Products. For ASEAN
member countries, the Study Reports of this part clinical may not be required for NCE,
Biotechnological Products and other Major Variation Products
if the Original Products are already registered and approved for market authorization in
Reference Countries. Therefore, the authority who requires specific Study Reports should ask for
the necessary documents. This part contains:
Section A: Table of Contents
Section B: Nonclinical Overview
Section C: Nonclinical Written and Tabulated Summaries
1. Table of Contents
2. Pharmacology
3. Pharmacokinetics
4. Toxicology
Section D: Nonclinical Study Reports
1. Table of Contents
2. Pharmacology
3. Pharmacokinetics
4. Toxicology
Part IV Clinical Document
Part IV should provide the Clinical Overview and the Clinical Summary. The document of this
part is not required for Generic Products, Minor Variation Products and some Major Variation
Products. For ASEAN member countries, the Study Reports of this part may not be required for
NCE, Biotechnological Products and other Major Variation Products if the Original Products are
already registered and approved for market authorization in Reference Countries. Therefore, the
authority who requires specific Study Reports should ask for the necessary documents.
The overall organization of Common Technical Dossier is presented on the following in Parts:
Section A: Table of Contents
Section B: Clinical Overview
Section C: Clinical Summary

1. Summary of Biopharmaceutics and Associated Analytical Methods

2. Summary of Clinical Pharmacology Studies

3. Summary of Clinical Efficacy

4. Summary of Clinical Safety
5. Synopses of Individual Studies
Section D: Tabular Listing of All Clinical Studies
Section E: Clinical Study Reports
Section F: List of Key Literature References

Types of application and their evaluation:

A separate application is required if product containing the same ingredient but made to different
specifications, in terms of strength/content of ingredient, dosage form, description etc.
or different manufacturer. In case of variants a maximum of five variants is acceptable in
registered product.

Every application for registration shall be accompanied with a processing and analysis fee,
as specified below:

Time Line for product registration:

If application is considered as satisfactory then a product registration number will be given by

the regulatory authority (i.e. MAL number).
If it is non-satisfactory then it will be rejected by the authority, In this case the applicant can
appeal within 14 days of the notification from the authority after that a period of 180 days from
the date of notice of appeal is given for submission of any additional information and
supplementary data and document for new drug product and biologics and a period of 90 days is
allowed for other categories of the product.
Pre-Submission of Application
Prior to submission of an application for product registration, applicant shall determine/
understand:
a) The category of the product (different product category requires different data);
b) Method of evaluation;
c) General and specific requirements;

d) Conditions applied;
e) Multiple applications;
f) Variants; and
g) Language.
Product registration process:
Flow of registration process:

Submission of application
Application
Rejected
Screening of Application
If Nonsatisfactory

Satisfacto

Evaluation of Application
Rejecte
d

Appeal
Regulatory Outcome
Post-Registration Process

Approved

REQUIREMENTS

FOR

REGISTRATION:
a) General requirements (either for full or abridged evaluation);
i) Full Evaluation;
(In accordance to ASEAN ACTD/ ACTR or ICH guidelines)
Part I - Administrative data and product information;
Part II - Data to support product quality (Quality Document);
Part III - Data to support product safety (Nonclinical Document); and
Part IV - Data to support product safety and efficacy (Clinical Document).

PRODUCT

b) Specific requirements according to category of product (biologics, health supplements and

natural products).
-Biologics
-Health Supplements
-Natural Products
Applicant shall comply with all requirements such as special condition for registration for
particular drug product, list of permitted and restricted substances, Labeling requirement and
guideline on patient dispensing pack of pharmaceutical product in Malaysia and all other
requirements.
Application of product registration shall be submitted via online quest system at
www.bpfk.gov.my. After submission application will go for the screening part and on the basis of
the complete and incomplete application it will be classify satisfactory and non-satisfactory
respectively. After screening it will go for first step of the evaluation known as initiation of the
review and then for correspondence in which application is send to the applicant if there s any
clarification of further r data is required in the application.

General Condition For Registration of Drug Product Under The Control Of Drug And
Cosmetic Regulation 1984:

Registration number
Product particular
Labeling
Product authentication
Indications, special conditions
Adverse reactions, complaints
Holder of registration certificate
Withdrawal from registration
Cancellation, suspension, amendment by the authority
Directives

Quality control documents and their requirement :

Documents to be submit via online quest system
Complete protocol analysis for the finished
product including preservative and diluents

Documents to be submit as hard copy

Certificate of analysis for active drug
substance (1 Batch) and recent batches of
finished product(3 different batches)
Summary of AMV which includes all the relevant Complete protocol of analysis for active
validation characteristics, its acceptance criteria drug substance and finished product.
and result.
Certificate of analysis for active drug substance (1 Complete testing method for the AMV
Batch) and recent batches of finished product (3
Complete result for the AMV with all
different batches)
relevant validation parameters, including
acceptance criteria and supporting raw
data. (e.g. chromatograms, spectrum etc)
POA (Protocol of analysis) should be written in Bahasa Malaysia which is included in general
requirement.
Specific requirements: The specific requirement for test method are based on type of test and
dosage forms of product and divided into the following category.
Category
Physical and performance tests
Quality test
Safety test

Types of Tests
Friability, Uniformity of weight, pH, Disintegrating test,
Dissolution test,
Identification test, Color test, FTIR, TLC, Content
Uniformity, Biological assay for antibiotics
Pyrogen test, Bacteria endotoxins Test, LAL test, Sterlity test,
Microbial Contamination Test, Mycrocystin Test

AMV (Analytical method development) document I one of the most important document which
required for DGRD. Analytical procedures which should be validated are given as follows:

a) Identification tests
b) Quantitative tests for impurities' content
c) Limit tests for control of impurities
d) Quantitative tests of the active ingredient in the sample (assay and dissolution)
e) Pyrogen or Bacterial endotoxin test
f) Sterility test
g) Microbial Contamination Test
h) Biological Assay of Antibiotics
i) Bacterial Endotoxin test
j) Microbial contamination test
k) Microbiological assay of antibiotics
Licensing and inspection:
After the drug registration licensing an inspection is also equally important part:
Inspection is usually conducted to ensure that whether a premises is comply with GMP (Good
manufacturing practices) and GDP(Good Distribution practices) guideline.
Licensing: Any company which wants to manufacture import and wholesale any registered
product should have respective license for the same. There is three types of license According to
Malaysian DRGD guidance:
a) Manufacturer license
b) Import license
c) Wholesaler license

For getting the any of the above type of license one should apply with Borang BPFK-413 and for
Application of the GMP certificate shall be submitted by filling Borang-420 Permohonan Sijil
Amalan Perkilangan Baik (APB) with a fee of RM 50.00.
Post registration process:
Registration is valid for the five years and application for renewal of product shall be done
within six month prior to the expiry of the validity of a product registration. The product
registration holder also withdraw the registration and he have to state the reason for the decision.
There are several amendments which applicable registered products such as:
Variation: variation shall follow the Malaysian Variation Guideline (MVG), NPCB is having all
right to request the all supporting document and variation approval letter from other regulatory
for all types of products. There is two types of variation classified in DRGD document one is
minor variation (Type-I) and second is major variations (Type-II).

Change in the manufacturing site (COS) classified as:

Types of manufacturing Site Changes
Type I
Change of manufacturing site with in Malaysia
Type II
Change in manufacturing site from foreign country to Malaysia
Type III Change of manufacturing site located outside Malaysia
Type IV Change of manufacturing site for sterile products
Type V
Change of manufacturing site in crisis situation

Change in product registration holder: Transfer of marketing authorization from existing

product holder to the another holder. For change in product registration holder there is several
conditions which has to be fulfil. After fulfillment of all condition the existing PRH shall submit
The following documents:
Application form BPFK-430.5
Borang Penyerahan Permohonan BPFK-)001
Processing Fee (Which is non-refundable and 500 for traditional product and RM 1000 for
poison or Non poison product and submitted in the form of bank draft/money order/postal order
payable to Biro Pengawalan Farmaseutical Kebangsaan)
New/ Additional indication: New /additional indication is defined as the which is not initially
approved for a registered pharmaceutical product. In Malaysia there are two type of evaluation
process for new/additional indication.
a. Full evaluation
b. Verification process
Post Marketing activities:
Phamacovigilance: It includes Adverse drug reaction (ADR) reporting and safety Updates.
Product registration holder is responsible to inform to regulatory authority of any serious adverse
reaction on the receipt of such report.
Post marketing Surveillance: It is the responsibility of PRH to ensure that al products are
comply with the standard and retirement of the authority and authority can take any necessary
action if any product is not conforming with te standard requirement in the form of Product

recalls and warnings. And it is the responsibility of the PRH to notify any product related
problem. All complaints received are investigated by NPCB.
Adulteration: If any registered product found to have been adulterated, the product license shall
cancelled and recall shall be done immediately of that particular batch or manufacturers license
can be revoked for six months for the first commitment of the offence and on second
commitment it shall be revoked for a year.

Reference:
1. National Pharmaceutical control Bureau, Introduction to DCA http://portal.bpkf.gov.my/
index.cfm?menuid=9
2. Malaysian regulatory guideline http://portal.bpfk.gov.my/index.cfm?&menuid=124&par
entid=82
3. Drug labeling in developing countries, http:/www.fas.org/ota/reports/9321.pdf.
4. Drug Registration Guidance document (DRGD) http://portal.bpfk.gov.my/index.cfm?
&menuid =137.
5. RanjithY, Manthan D Janodia*, Jagadish PC, K M Bhat, Swati Karande, N udupa,
" SCENARIO OF GENERIC DRUG REGULATIONS FOR ASEAN
COUNTRIES ", Inventi Impact: Pharmacy Practice , Vol. 2012 , Article ID" Inventi:ppp/174/12 " , 2012 [ cited 2013 Oct 25 ] Available From
http://www.inventi.in/Article/ppp/174/12.aspx.
6. The ASEAN common technical dossier http://www.medi-power.com/aseanguideline.pdf
7. The ASEAN common technical dossier, Quality module
http://www.pharmatutor.org/articles/registration-dossier-pharmaceuticals?page=0,1 .
8. The ASEAN technical dossier, Organization of the Dossier
http://www.hsa.gov.sg/publish/hsaportal/en/health_products_regulation/western_medicin
es/guidelines.html.