challenges of biological drug registrationinvietnam and suggesting for improving registration process in a local pharmaceutical company

HO CHI MINH CITY OPEN UNIVERSITY

UNIVERSITÉ LIBRE DE BRUXELLES
SOLVAY BRUSSELS SCHOOL OF
ECONOMICS & MANAGEMENT

MBQPM5

“NGUYEN NHU TRANG”

“CHALLENGES OF BIOLOGICAL DRUG
REGISTRATION IN VIETNAM AND SUGGESTING
FOR IMPROVING REGISTRATION PROCESS IN A
LOCAL PHARMACEUTICAL COMPANY”

MASTER FINAL PROJECT
MASTER IN BUSINESS QUALITY AND PERFORMANCE MANAGEMENT

Ho Chi Minh City
(2016)


HO CHI MINH CITY OPEN UNIVERSITY

UNIVERSITÉ LIBRE DE BRUXELLES
SOLVAY BRUSSELS SCHOOL OF
ECONOMICS & MANAGEMENT

MBQPM5
“NGUYEN NHU TRANG”

“CHALLENGES OF BIOLOGICAL DRUG
REGISTRATION IN VIETNAM AND SUGGESTING
FOR IMPROVING REGISTRATION PROCESS IN A
LOCAL PHARMACEUTICAL COMPANY”

MASTER FINAL PROJECT
MASTER IN BUSINESS QUALITY AND PERFORMANCE MANAGEMENT

Tutor: Jacques Martin

Ho Chi Minh City
(2016)


HO CHI MINH CITY OPEN UNIVERSITY

UNIVERSITÉ LIBRE DE
BRUXELLES
SOLVAY BRUSSELS SCHOOL OF
ECONOMICS & MANAGEMENT

MBQPM5
“NGUYEN NHU TRANG”

“CHALLENGES OF BIOLOGICAL DRUG
REGISTRATION IN VIETNAM AND SUGGESTING
FOR IMPROVING REGISTRATION PROCESS IN A
LOCAL PHARMACEUTICAL COMPANY”

MASTER FINAL PROJECT

MASTER IN BUSINESS QUALITY AND PERFORMANCE MANAGEMENT

Tutor: Jacques Martin

Ho Chi Minh City
(2016)

2


ACKNOWLEDGEMENTS
Firstly, I would like to acknowledge the support of Prof. Jacques Martin who gave me
strength, encouragement and his kind input and re-sharpening of my ideas.
Special appreciation is also expressed to all Drs and Professors from the Master In
Business Quality And Performance Management 5 program, for their professional advice
on data collection, review and methodology that truly supporting for final report writing.
I also extend my gratitude to DAV Officers, specifically the Director of the Drug
registration Department, Mr Chu Dang Trung, for approving for me to purse the data
collection and follow – up interview, and the whole Department of Medicines Registration
for their material support during data collection.
I extend my gratitude to pharmacist in-charge and evaluators for devoting their time
cooperation given during data collection.
I specially acknowledge the HL Pharma company, the Executive Management team, and
Head of R&D department, for accepting this work to be done supported me academically
and materially during this final report preparation.
I also extend my gratitude for the moral support and assistance from my colleagues in the
MBQPM5 class during times academically.
Finally, I would like to send my deep gratitude to my family for all of their supports and
encouragements.

4


ACCEPTANCE OF FINAL PROJECT REPORT FOR DEFENSE

Mr/Ms NGUYEN NHU TRANG’s final project report for the degree of Master in
Business Quality and Performance Management is officially accepted for defense.

On 14 April 2016

Dr. Jacques M.A. Martin
Academic Director
Master in Business Quality and Performance Management
Solvay Brussels School of Economics and Management – Ho Chi Minh City Open University


5


TABLE OF CONTENT
1 INTRODUCTION ................................................................................................................ 11
1.1 BACKGROUND............................................................................................................ 11
1.2 PHARMACEUTICAL MANAGEMENT SYSTEM .................................................... 12
1.3 HL PHARMA ................................................................................................................ 12
1.4 HISTORY OF REGISTRATION IN VIETNAM.......................................................... 13
1.5. GENERAL DESCRIPTION OF REGISTRATION PROCESSES .............................. 14
1.5.1 Drug regulation process ........................................................................................... 14
1.5.2 Key players and tasks in drug registration .............................................................. 15
1.5.3 Regulatory affairs department ................................................................................. 15
1.6 Drug registration process in HL Pharma ........................................................................ 16

PART 1: METHODOLOGY ................................................................................................... 18
Chapter 1 REGULATORY FRAMEWORK .......................................................................... 18
2.1 Legislative in harmonization trends ............................................................................... 18
2.1.1 ICH hamonization ................................................................................................... 18
2.1.2 ASEAN Harmonization strategy ............................................................................. 19
2.1.3 ASEAN Harmonization in Vietnam ........................................................................ 20
Chapter 2 METHODS AND MATERIALS ........................................................................... 21
3.1 Study Design .................................................................................................................. 21
3.2 Study participants .......................................................................................................... 21
3.3 Study Period ................................................................................................................... 21
3.4 Sampling technique ........................................................................................................ 21
3.4.1 For identification the challenges of medicines registration process in Vietnam ..... 21
3.4.2 To determine the need of good registration process in HL Pharma ........................ 22
3.5 Data Collection............................................................................................................... 22
PART 2: ANALYSIS AND REVIEW .................................................................................... 23
Chapter 1 RESULTS ............................................................................................................... 23
4 1 Socio-demographic information of participants............................................................. 23
4.2 Companies represented, and their number of biological products registered ................ 24
4.2.1 Companies represented. ........................................................................................... 24
4.2.2 Time taken for dossier registration approval ........................................................... 25

6


4.2.3 Time taken for dossier registration preparation....................................................... 25
4.3 Assessment of knowledge with regards to medicines registration................................. 26
4.4 Practice among DAV evaluators on medicines registration .......................................... 27
Chapter 2: ASSESSMENT OF CHALLENGES IN DRUG REGISTRATION
PROCESSAND REVIEW ....................................................................................................... 29
5.1 Challenges encountered by evaluators (21) ................................................................... 29

5.2 Challenges encountered by representatives of manufacturer (40) ................................. 31
6 REVIEW CURRENT QUALITY MANAGEMENT IN HL PHARMA. ........................... 32
6.1 GDP system in HL Pharma ............................................................................................ 32
6.2 Registration system in HL Pharma ................................................................................ 33
6.2.1 The current role of regulatory activities within HL Pharma ................................... 33
6.2.2 Improve the registration process ............................................................................. 34
7. CONCLUSION AND RECOMMENDATIONS ................................................................ 38
7.1 CONCLUSION .............................................................................................................. 38
7.2 RECOMMENDATIONS ............................................................................................... 38
REFERENCES ........................................................................................................................ 42

7


LIST OF ABRIVIATIONS AND/OR SYMBOLS
ASEAN Common technical dossier

ACTD

Balance scorecard

BSC

Drug administration of Vietnam

DAV

EMEA

Europe, the Middle East and

Africa countries

ICH

The International Conference
on Harmonisation

Good Distribution Practice

GDP

Good Storage Practice

GSP

Quality Management System

QMS

Regulatory affairs

RA

Research and development

R&D

8

LIST OF FIGURES, TABLES AND ANNEXES.
Figure:
Figure 1: Pharmaceutical Management system ....................................................................... 12
Figure 2: Reason of delay in DAV registration process .......................................................... 30
Figure 3 Reason of delay in registration process (encountered by Pharmacist-in-charge)..... 31
Figure 4: The plan–do–check–act cycle………...……………………………...………....34

Table
Table 1: ACTD harmonization in drug registration guidelines from 2009-2015 .................... 20
Table 2: Socio-demographic characteristics of medicine evaluators (n=21) ........................... 23
Table 3: Socio-demographic characteristics of pharmacists’ in-charge of pharmacies
(n=45)....................................................................................................................................... 24
Table 4: Local companies distribution in relation to companies represented, and dossiers
applications registered (n=25) ................................................................................................. 24
Table 5: Time taken for dossier registration preparation in HL Pharma. ................................ 26
Table 6: Proportion of evaluators’ knowledge assessment in relationship to the correct
responses .................................................................................................................................. 26
Table 7: Summary of responses to practice on medicines registration among evaluators ...... 28
Table 8: Challenges encountered by evaluators (n=21)........................................................... 29
Table 9: Challenges encountered by representatives of manufacturer (n=40) ........................ 31
Table 10: Assessment and overview of the current drug regulatory situation in the
company ................................................................................................................................... 35

Annex
Annex 1_Questionaires to Evaluators_Pharmacist.
Annex 2_DAV Regulatory_Process_VIETNAM.
Annex 3_2016-02 BSC_RA HL Pharma.
Annex 4_Estimated registration time.
Annex 5_Regulatory Roadmap 2016_Template
Annex 6_Proposed drug registration Procedure

9


Abstract
Total quality management is considered important in the competitive industry strategies at
the level of organizations on one hand, including Pharmaceutical industry. Quality
represents specific behavior for a group of consumers. It is becoming imperative for
businesses to supply goods and services of high quality to achieve a competitive advantage
in their markets (Amalia Venera, Todorut, 2012).
Dugs (Pharmaceutical finished products) are only authorized to circulate in the market
after being registered. The Drug administration of Vietnam (DAV) has been mandated by
the Vietnam Ministry of Health to ensure quality, safety and efficacy of medicines. Since
about 70% of medicines are imported from abroad, registration process contributes to the
availability of quality, safe and efficacious medicinal products in the country (Assembly,
2005). In this regard the registration process needs to be effective and should avoid
unnecessary delays in order to increase the variety of medicines registered in the country.
In order to distribute in Vietnam market, once approval granted, the imported medicines
must be also complied with some requirements in labeling, distribution legislation, and the
local pharmaceutical companies must also meet the required qualifications approved the
DAV (GDP – Good Distribution Practice; GSP – Good Storage Practice).
Study objective:
- The aim of this study is to identify challenges of biological drug registration process in
Vietnam and the impact of registration processes as independent variables on the
development of registration policies used in HL Pharma to identify the chance developing
appropriate registration system elements followed by these facilities.
-The final report also attempted to identify the realities and readiness of GDP/GSP
management in HL Pharmaceutical Trading Company (HL Pharma). These findings are
closely linked to the capacity of product supply and quality of product control to meet
customer requirements on product supply continuity.

10


1 INTRODUCTION

1.1 BACKGROUND
The first purpose of this study was to determine challenges faced by both DAV and local
pharmaceutical companies in biological drug registration. In Vietnam, medicine
registration is an official authorization or registration of a product by DAV for the purpose
of marketing or free distribution in the country after evaluation for safety, efficacy and
quality (Drug Administration of Vietnam, 2015). Hence, the objective of evaluation is to
ensure that before a medicine is placed on the market there is enough evidence that it has
been properly formulated, manufactured and adequately tested and meets the criteria of
safety, efficacy and quality.
A drug product registration dossier is a set of document that consists of data on
administrative, pharmaceutical, clinical and labeling of the product. The administrative
part gives preliminary information of that medicine, applicant and its manufacturer. The
quality part contains detailed information of the active pharmaceutical ingredient(s) (APIs)
used and finished pharmaceutical product whereas in ensuring medicines safety and
efficacy, these data are provided in the clinical part of the dossier 3
Quality has been recognized broadly as one of the key factors to success in the global
market for all kind of business. Quality is describe as products’ or services’ totality of
features and characteristics while quality system is "a set of interdependent processes that
function harmoniously, using various resources, to achieve the objectives related to
quality” (Juran, 1951). In pharmaceutical industry, the QMS lives in a dynamic business
environment characterized by acquisitions, portfolio changes, operational realignment,
manufacturing relocation, facility repurposing, restructuring, and workforce right-sizing.
The QMS also lives in a dynamic regulatory environment of the registration and
compliance requirements of global markets as well as inspections. Present day the biggest

challenge faced by the pharmaceutical organizations is to build up a quality system that
could focus on sustainability issues and assume that quality problems and regulatory noncompliances will be reduced as a result of the organized way of thinking, transparency,
documentation and continuous evaluation of Quality Management System (QMS). QMS
starts with recognizing that customers play a significant role in defining requirements as
inputs and monitoring of customer satisfaction is necessary to evaluate and validate
whether customer requirements have been met. As QMS is related to regulatory
compliance and continuous inspection readiness, it shall maximize benefit to the
organization by improving quality, increasing the yield, cutting costs due to quality failure,
and import alerts.
And as an effect, in drug registration process, the quality of registration dossier is key
factor for a successful registration.

11


From the applicant or manufacturer’ representative in Vietnam, not only the quality of their
registration dossiers but also the implementations of quality management system to ensure
product quality after registered become very important. Quality management is generally
referred to the identification and administration process of the activities in order to achieve
the quality objectives of the organization. The main purpose of the quality management is
to get competitiveness by improving quality performance (Deming, 1982; Garvin, 1988;
Steeples, 1992).
In order to improving quality performance constantly, quality system of HL Pharma must
properly maintain whereas the company has to develop, be self-motivated and develop for
better internal and external quality services persistently. While following consistently with
GDP/GSP guidelines issued by DAV, the company needs to ensure the compliance with
Manufacturer’ quality requirements applied for their registered products in Vietnam.

1.2 PHARMACEUTICAL MANAGEMENT SYSTEM
Managing medicines supply is basically organised into four functions which include

selection, procurement, distribution and use. In order to achieve its function there is a need
to have efficient management support. The entire cycle rests on policy and legal
framework that establishes and supports the public commitment to essential medicines
supply (MSH and WHO, 1997).

Figure 1: Pharmaceutical Management system
Source: Managing Drug Supply, 2nd Edition of 1997

1.3 HL PHARMA
HL Pharma is a diversified local healthcare company that specializes in imported medical
devices, pharmaceuticals. They also have imported food supplements and tent to reach to
cosmetic portfolio.

12


HL Pharma operates main business activities on doing marketing, trading for
pharmaceutical products in Vietnam. All importation activities are done by their thirdparties, a local Government’ company, this local company also does the service of
registrations of medical devices, import license for food supplements HL. Therefore, HL
Pharma plays only the key role as distributor for all of their devices and food supplement
products in Vietnam market. For pharmaceutical products, HL Pharma does the
registration and doing distribution in Vietnam. They also store products in their
warehouses, control the tender listing and selling to hospitals/pharmacies.
HL Pharma’ business segments are differentiated into 3 categories:
- The pharmaceutical products which is biological products, this segment consists of
recombinant and plasma based proteins to treat hemophilia and other bleeding disorders,
plasma based therapies to treat immune deficiencies. This segment comprised 68.4% of
total revenues.
- The food supplements segment consists of: nutrition products, infusion pumps, and
inhalation anesthetics, as well as products and services related to pharmacy compounding,

drug formulation and packaging technologies. This segment comprised 22.7% of total
revenues.
- The medical devices which has just been started from early 2015, consists of devices to
treat sore throat, asthma, ... This segment, together with some registration services to their
foreign’ partners, comprised ~ 8.1% of total revenues.
The company has a simply quality system which based on the requirements of their
foreign’ partners (the Manufacturers) and DAV GDP standards. Due to the different of
quality management for each type of products, they follow several sets of quality
requirements by each Manufacturer. They also have some basic processes that required by
local regulations in Good practice distribution, which will be studied and enhanced during
this final report.

1.4 HISTORY OF REGISTRATION IN VIETNAM
In Vietnam, drug registration is also known as marketing approval, marketing
authorization or product licensing.
In the last two decades, medicinal regulation had become more organized at international
and regional level for instance International Conference on Harmonization, ICH,
EUROPEAN, and ASEAN Agencies respectively. Since 1998, about fourteen guidelines
have been harmonized in the European Union, Japan and USA through the ICH and in July
2003 a Common Technical Document (CTD) that assists in medicine application among
the three regions was finally implemented (ICH, 2008). Nowadays, many medicines
regulatory authorities structure their dossier requirements along with WHO guidelines

13


which are very close to the CTD format in respect to their national settings as part of the
ASEAN harmonization initiative.
In 1990, the DAV embarked on a drug registration exercise. Before then, all drugs
imported into the country had not been subjected to a drug registration process. The

process has been a control measure to ensure that only drugs of proven quality, safety and
efficacy are licensed for importation into Vietnam.
The registration of drug was made under the Pharmaceutical Law, 2005. The Act provides
conditions under which a medicinal product may be registered in Vietnam that include the
availability of medicine to be of the public interest, safe, efficacious and of acceptable
quality, the premises and manufacturing operations should comply with the current GMP
requirements or any other requirements as may be prescribed by the authority. The
Registration guidelines were introduced specific requirements for each product category
such as chemical medicines, biological products, herbal medicines, food supplements and
medical devices.
In 2009, Vietnam was the 2nd authority in ASEAN region to partly require registration
dossier in ASEAN Common technical dossier (ACTD) which was still new and countryspecific requirements to EU countries. In early of 2015, DAV has changed the Drug
regulation guideline to fully allow ACTD template only, and to require the registration
companies to follow ASEAN Stability condition. Including in the 2015 Drug registration
guidelines (Drug Administration of Vietnam, 2015), DAV also sets a number of variations
required approval before implementation, this increase a significant number of registration
dossiers in maintaining a product license.
Currently, DAV has gained expertise and more knowledge of medicine evaluation. These
has led to changes in medicines registration requirements which has resulted in most of
dossiers submitted ending up in non-conformance, rejection or queried hence prolonged
registration time. The evaluation timeline can last from 14-18 months for chemical
products, and 18-24 months for biological products, while the Guideline saying that drug
licenses will be granted 6 months after submission of qualified and sufficient registration
dossier. The delay in registration has created more customer complaints and unavailability
of medicines within the medicines supply chain.

1.5. GENERAL DESCRIPTION OF REGISTRATION PROCESSES
1.5.1 Drug regulation process
A drug registration process generally covers the following areas:

• Pre-marketing assessment and evaluation of the quality, safety and efficacy of
a medicine, including compliance of manufacturing sites and processes with
Good Manufacturing Practice (GMP) standards

14


• Assessment and inspection of all components of the pharmaceutical supply
chain

• Maintenance of a register of available products, and post-marketing
surveillance activities, including random sampling of registered medicines for
quality control and pharmacovigilance

• Promotion, advertising and provision of medicines information.
All of these activities require an appropriate legislative framework. The precise nature and
scope of legislation, as well as models for drug regulatory frameworks, varies from setting
to setting.
1.5.2 Key players and tasks in drug registration
Drug regulation is an interplay between law and sciences, as well as between regulators
and the pharmaceutical manufacturers, with input and influences from patients and
medical/health professions. In addition, Drug regulatory authority of Vietnam (DAV)
interrelates with many other authorities active in the health sector, such as the Ministry of
Health and other health protection agencies.
DAV also needs to interact with politicians; apart from anything else, politicians need to be
persuaded of the importance of effective regulation in order to ensure that it is paid for at
an appropriate level. In general, effective drug regulation requires effective legislation and
administration, as well as a mechanism for control of the market and enforcement of
penalties for breaches of legislation that applies equally to both the public and private
sectors.

1.5.3 Regulatory affairs department
At the organization level, Regulatory affairs (RA) professionals play critical roles
throughout the healthcare product lifecycle, from concept through product obsolescence.
They provide strategic, tactical and operational direction and support for working within
regulations to expedite the development and delivery of safe and effective healthcare
products to individuals around the world. The Regulatory Affairs departments of
pharmaceutical companies ensure that their companies comply with all of the regulations
and laws concerning their business.
The Regulatory Affairs department is an important part of the organizational structure of
pharmaceutical companies. Internally it liaises at the interphase of drug development,
manufacturing, marketing and clinical research. Externally it is the key interface between
the company and the regulatory authorities (Bevan, 2009).

15


Regulatory Affairs department contributes essentially to the overall success of drug
development, both at early pre-marketing stages and at all times post-marketing.
At the late stage of product development regulatory professionals are responsible for the
submission of the registration dossier. It is their responsibility to provide the strategic
regulatory framework for the submission, to advise on procedures and formats, to collect,
evaluate and compile the scientific data and information on the product. They manage the
communication and negotiations with the authorities. They are accountable for
maintenance of marketing authorizations and are involved in the life-cycle management of
a product. In addition to handling regulatory submission, Regulatory Affairs leads labeling
compliance, and DAV listings and registrations, and acts as the official DAV
correspondent.
1.6 Drug registration process in HL Pharma
In both GDP / GSP guidelines, DAV has not identified any requirement on registration
process.

In all regulations related to the drug registration in Vietnam, no specific requirements have
been set for a Regulatory department, or a registration process in practical operation. Based
on current practice, the registration processes includes all sub-processes that ensure the
compliance in term of product specification in product registration, product quality control
and product information. As a result, HL Pharma has only a simple registration process as
a part of R&D processes. The main tasks of their regulatory activities related is to ensure
product licenses on time for drug supply continuity, and only 1 Pharmacist is assigned as
R&D Head who takes care for all related activities in registration management. These tasks
are not documented clearly and reviewed to see whether any risk to new drug registration
regulation.
Due to constantly increasing regulatory obligations and new DAV requirements as well as
the globalization of the pharmaceutical market, the demands and responsibilities of
regulatory departments for HL Pharma is becoming more and more compulsory and
complex.
Furthermore, starting from 1 Jan 2015, DAV issued a guideline to accept ACTD dossier
format only. This applies for both new drug registration and renewal registrations, effective
from 1 Jan 2015 and 1 Jan 2016 respectively. All of key existing biological products of HL
Pharma will be required renewal submission in 2017-2018. That’s the reason HL Pharma
needs to be ready for the country specific requirements and work with their manufacturers
to fulfill these changes in regulation while taking into account the continuity supply for
their medicines.
An example of this stringent requirement by local Health Authority is the normal storage
condition followed ASEAN region. Since Jan 2015, new applications for marketing
authorization are only accepted if they include either the results of stability studies at
16


ASEAN condition or an EMEA decision on a waiver by good justification and rational for
the different condition during registration evaluation. The specific storage condition
strategy must therefore be considered early on and built into the overall development plan

to avoid any delays in view of market access of the product. The EU manufacturers mostly
have their products stored at below 25oC while ASEAN countries require normal storage
conditions at not above 30oC. For biological products, DAV now accepts only a good
justification and rational for the different condition during registration evaluation. Without
rational in writing at timeline of submission, the dossier will be rejected by DAV after first
evaluation. Therefore, in addition, a close storage and delivery system to ensure
manufacturer’ storage condition to prove how HL controls the quality of their products,
their drug registrations can be results in withdrawal or pending approval of their registered
products in Vietnam market. This is also the critical need to re-assess and improve their
GDP compliance.

17


PART 1: METHODOLOGY
Chapter 1 REGULATORY FRAMEWORK

2.1 Legislative in harmonization trends
2.1.1 ICH hamonization
Harmonization of regulatory requirements was initiated by the European Community (EC),
in the 1980s, the EC moved towards the development of a single market for
pharmaceuticals. At the same time there were discussions between Europe, Japan and the
US on possibilities for harmonization. ICH is a unique undertaking that brings together the
drug regulatory authorities and the pharmaceutical industry of Europe, Japan and the
United States (K.Sparrow, 2000).
ICH provides various guidelines which are categorized into four category, Quality
guidelines, safety guidelines, efficacy guidelines and multidisciplinary guidelines. These
guideline give special concern for the patient population, large-scale human clinical trials
lasting up to one year can begin in the absence of completed carcinogenicity studies in
rodents. The major aim of ICH is to achieve greater harmonization in the interpretation and

application of technical guidelines for the registration of new active substances or products
obtained by biotechnology by its members; to improve the efficiency of global drug
development; to reduce redundant studies; and to improve pharmacovigilance activities
and quality assurance.
As of today, ICH has completed an important phase. Key guidelines are now being
implemented in the areas of Efficacy, Quality and Safety in the three ICH regions. The
organization has established a maintenance procedure to ensure that the guidelines
continue to reflect the latest scientific developments and best practice. These maintenance
activities are essential to the future of ICH, and to ensure that harmonization continues.
Several more ambitious guidelines are under development, such as Good Manufacturing
Practice (GMP) for Active Pharmaceutical Ingredients (APIs), Pharmacopoeias
Harmonization. The Common Technical Document and its electronic counterpart will be
available in less than two years, both set to change procedures for regulatory dossier
submission significantly. The organization has recognized the importance of making
available information on the ICH process and guidelines to non-ICH regions with the
establishment of the Global Cooperation Group. As well as making information available,
the group will act as a resource in the understanding, and even acceptance, of many of the
guidelines.
Drug Registration harmonization provide benefit for better health:
•

Regulatory harmonization offers many benefits to both regulatory authorities and
the pharmaceutical industry, and has a positive impact for the protection of public
health.

18


•

•

Through the development of harmonized guideline: streamline the regulatory
assessment process for new drug applications; reduce the development times and
resources needed for drug development; prevent duplication of clinical trials in
humans; and minimize the use of animal testing without compromising safety and
effectiveness.
To harmonize requirements in the drug registration process promotes quicker
access to medicines for patients.

2.1.2 ASEAN Harmonization strategy
ASEAN member countries have established the framework on economic cooperation for a
long time already. Since the 9th ASEAN Summit on 7th October 2004, the members have
agreed to integrate ASEAN countries to become ASEAN Economic Community (AEC)
with in 2020. The goals are to become single market and production base, and to promote
convenience and liberalization in the goods, services, investments and funds movement.
Because pharmaceutical product is among the healthcare sector, it is necessary to
accelerate the harmonization by assigning appropriate measures and definite time lines for
every procedure. Hence, for these matters, the roadmap of healthcare integration was set
up:
1. Study the feasibility of ASEAN Mutual Recognition Arrangement (MRA) in
Pharmaceuticals by 30th September 2005
2. Establish alert systems for under-standard and unsafe products by 31st
December 2005
3. Establish labeling standards by 31st December 2006
4. Implement ASEAN Common Technical Dossier (ACTD) by 31st December
2008
5. Promote medicinal drugs approval process by apply ASEAN-X principles after
full implementation of ACTD after 31st December 2008
6. Study the feasibility of Harmonization Placement System in Pharmaceuticals

into ASEAN market after 31st December 2009
7. Study the feasibility of Flexible Twinning System in mutual regulatory capacity
and resource development
From above listing, we can see that ASEAN leaders have agreed to proceed towards many
cooperation programs with specific time frames covering the strategy to establish ASEAN
single market to increase our negotiation power with other regions. Therefore, local
business sectors should keep up with those changes. At the same time, government
officials must strengthen their knowledge, skill, and comprehension to support ASEAN
agreements. In addition, all sectors, both public and private, must altogether work together
for benefits of our nation and us all.

19


2.1.3 ASEAN Harmonization in Vietnam
The initiation of ASEAN Pharmaceutical Harmonization have affected directly to the drug
registration system. The harmonization program focuses in 2 principles that are to promote
and support drug registration system, trade and cooperation in the region, and to eliminate
technical barrier to trade among ASEAN countries.
Vietnam Ministry of Health, by DAV, had decided to fully implement ACTD by 31st
December 2016 in response to ASEAN goal and government strategy to be actively
involved in the region. Below are summarized changes and implementation phrase for
adopting ACTD harmonization in drug registration guidelines from 2009-2015.

Drug
registration
requirements

Scope

Country
specific
requirements

1998-2009
Administrative
documents
Drug
product
specification

2009-2014
Administrative documents
Drug substance and drug
product section
Dossier format: either ICH
CTD or ACTD format.
Both renewal and From 1.1.2010 for new
new registration
registration, and 1.1.2012
No
differences for renewal registration
between
Applicable for chemical
Chemical
and medicines only.
biological
From
1.1.2017
for

products
biological.
Fully required to follow
without justification.

From 2015
Administrative documents
Quality and Clinical/Nonclinical section
Dossier format: ACTD
format only
ICH CTD is acceptable only
in case of new drug
substance entity.

Country
specific
requirements
where
applicable. This enhance
chance to accept evaluation
per quality risk management
based.
Applicants
are
required to provide strong
rational/justification.
Table 1: ACTD harmonization in drug registration guidelines from 2009-2015
Technical regulations in excess of what is necessary may become a technical barrier to
trade. In applying technical regulations, DAV has adopted an approach of using
international standards and practices and alignment with the WTO/TBT obligations, where

possible. Furthermore, DAV need to provide a Regulatory Practice Guide for regulators
and Applicants to assist in the preparation and adoption of efficient regulatory
arrangements that would improve the consistency and transparency of technical
regulations, thereby reducing barriers to trade.
As a result of this harmonization approach, the involvement of local business sectors,
especially small pharmaceutical companies would take into consideration. A significant

20


step up needs to be taken at particularly the national level but also regional level. It is
required small and medium-sized enterprises to get involved when it is not too late, i.e.
before the implementation phase of regulations is already impacting them. Pharmaceutical
companies need to look specifically all potential impact across, and to actively go out and
evaluate what this might be. This task may even be outsourced as interim option, and the
critical need to redesign the Registration management activities at HL Pharma.
Chapter 2 METHODS AND MATERIALS
3.1 Study Design
A descriptive cross sectional study design was used to collect data: Structured
questionnaires.
Study participants were interviewed through questionnaires in order to get the information
required to achieve study objectives.
GDP compliance will be evaluated by using checklist and recorded during warehouse
visiting. Historical audit results by DAV are also be reviewed and compared if applicable.
3.2 Study participants
The study involved drug registration evaluators from DAV, within and outside the Drug
registration department, and representatives of manufacturer and pharmacists‟ in-charge,
who also our partner in local industry, were kindly agreed to join the study. Other study
participants were Director of the Drug registration Department. Study participants were
interviewed through questionnaires in order to get the information required to achieve

study objectives.
Drug registration evaluators within DAV (25)
RA representatives of foreigner manufacturers (25): All of their imported products are
biological products.
And 45 pharmacists in-charge related to R&D including registration activities in above
local representatives.
3.3 Study Period
The study took about five months for its completion.
The study period includes proposal development in September 2015, data collection in
September to Dec 2015 and final report submission in Apr 2016.

3.4 Sampling technique
A convenient sampling technique was used to get the sample size due to the small number
of evaluators and pharmacies involved in medicines registration in the country. Study
participants who were willing and available during the survey at the study sites were
included.
3.4.1 For identification the challenges of medicines registration process in Vietnam

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A convenient sampling was used to get the sample size due to the small number of
evaluators and pharmacies involved in biological medicine registration in the country.
Study participants who were willing and available during the survey at the study sites were
included. Retrospective data of all applications received in the past two years was collected
(2014 and 2015).
3.4.2 To determine the need of good registration process in HL Pharma
Retrospective data of all applications prepared and submitted in the past 5 years was
collected (2009- 2014). The rationale for selecting this period was based on the fact that
the current Drug registration guidelines were reviewed in 2009, and in Jan 2015

respectively.
Factors that hinder smooth registration process were evaluated based on the number of
dossiers registered, queried or rejected.
3.5 Data Collection
- Using a questionnaire (Annex 1)
- Questionnaires were distributed and the information was required to set the date for
collection.
- Survey questions focused on the demographic data, training, work experience, knowledge
on medicines registration, views (challenges) and experiences in dealing with regulatory
requirements. The survey also included registration document template classification,
storage condition type.
- Face-to-face interview with responsible pharmacists in HL Pharma during warehouse
visiting.

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PART 2: ANALYSIS AND REVIEW
Chapter 1 RESULTS
4 1 Socio-demographic information of participants
Out of 25 targeted medicines evaluators, 24 of them filled the questionnaires which made
response rate of 96%. Among these 25 targeted pharmacies, only 21 could be enrolled in
the study (ensuring further follow-up after finalizing questionnaires) which made a
response rate of 84%. Respondents included medicines evaluators, representatives of
manufacturers and pharmacists‟ in-charge of the premises. The results for sociodemographic characteristics of medicines evaluators are summarized in Table 2 below.
Table 2: Socio-demographic characteristics of medicine evaluators (n=21)
Characteristics

Number

Percentage

Gender
Female
15
71.42%
Male
6
28.58%
Professional status
Pharmacist
10
47.62%
Medical Doctor
7
33.33%
Other
4
19.05%
Experience in medicines evaluation
0 – 1 year
12
57.14%
2 – 5 years
7
33.33%
6 – 10 years
1
4.76%
Above 10 years

1
4.76%
Main daily activity
Medicines Registration
12
57.14%
Officer Medicines Inspector
4
19.04%
Clinical Trial Officer
3
14.28%
Others*
2
9.52%
Attended regional training in
medicines evaluation
Yes
6
28.58%
No
15
71.42%
*includes lecturers, researchers and administrative employed evaluators
Out of 21 respondents, 15 (71.42%) were females while 6 (28.5%) were males with
majority (47.62%) of respondents being pharmacists, medical doctors (33.33%) and other
qualifications (19.05%). The high number of pharmaceutical – medicinal professional
related here reflects the essential competency for pharmaceutical industry, that a Pharmacy
or doctor degree is required.
Most evaluators 12 (57.14%) had experience of ≤ 1 year and 7 (33.33%) had worked for

more 2-5 years while only 2 evaluators (~8.5%) had experience of between 6 to 10 years.

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Taking into account the retrospective study period (about 5 years from starting 1st Drug
registration guideline per ACTD format and recent revised Guideline), it shows few
number of evaluators could experience the changes and challenges for new Drug
registration guideline. Among the 21 respondents, only 12 of them (57.14%) could be
categorized as medicine evaluators based on their main daily activity at DAV and job
description. Six (28.58%) respondents had attended training on dossier evaluation abroad.
Table 3: Socio-demographic characteristics of pharmacists’ in-charge of pharmacies
Characteristics
Gender
Female
Male
Experience in medicines evaluation
0 – 1 year
2 – 5 years
6 – 10 years
Above 10 years
Attended training in medicines Registration
Guidelines for Biological products.
Yes
No

Number (n=45)

Percentage

32
13

71.11%
28.89%

2
32
10
1

4.44%
71.11%
22.22%
2.23%

26
19

57.77%
42.23%

From Table 3 above, among the 45 ‟ in-charge” pharmacists who were interviewed, 32
were females and 13 were males. Only 2 of them had work experience of ≤ 1 year as
pharmacists‟ in-charge”. Forty ‟ in-charge” pharmacists had experience of between 2 to 10
years. Only one had more than 10 years working experience. Also, 26 ‟ in-charge”
pharmacists had received training on dossier preparation, indicating that most of the ‟ incharge” pharmacists had not undergone any training with regards to dossier preparation or
compilation related new requirements for Biological products.
4.2 Companies represented, and their number of biological products registered
4.2.1 Companies represented.

Table 4: Local companies distribution in relation to companies represented, and dossiers
applications registered (n=25)
Characteristics
Number
Percentage
Companies represented
0 – 5 manufacturers
20
80%
6 – 10 manufacturers
3
12%
Above 10 manufacturers
2
8%
Application of products registered
0-10
9
36%
11-20
12
48%
21-30
4
16%

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