The challenges for implementation of good manufacturing practices by local pharmaceutical manufactures in vietnam

THE CHALLENGES FOR IMPLEMENTATION OF GOOD MANUFACTURING
PRACTICES BY LOCAL PHARMACEUTICAL MANUFACTURES IN VIETNAM
by
Duong To Dung (Ms.)
A research report submitted in partial fulfillment of the requirements
for the degree of Master of Business Administration.
Examination Committee Dr. Do Ba Khang (Chairman)
Dr. N. Ramachandran
Dr. Sang-kon Lee
Nationality: Vietnamese
Previous degree: Bachelor of Chemical Engineering
Bachelor of Computer Sciences Engineering
HCMC University of Technology
Ho Chi Minh City, Vietnam
Scholarship Donor: Government of Switzerland
Asian Institute of Technology
School of Management
Bangkok, Thailand
March, 2001
i
Acknowledgement
First of all, I would like to express my deep gratitude to Dr. Do Ba Khang, who is my
advisor for this research paper, for his kindness and willingness as well as valuable comments
and advice that help me well in conducting this paper. Moreover, I am also greatly indebted to
Dr. Cao Minh Quang and Dr. Pham Thi Binh Minh, who are chief officers of Vietnam’s
Ministry of Health for their whole-hearted supports and helps in giving me the necessary and
beneficial knowledge and data concerning Vietnam’s pharmaceutical industry. Besides, I truly
appreciate the enthusiastic contribution of Dr. Sang-kon Lee and Prof. N. Ramachandran, who
are extremely willing to give me helpful advice for improving this research paper.
Secondly, without the loves and sacrifices of my parents, I could not be here to have a
chance of conducting this research. Thus, it is my full pride to show my everlasting gratitude to

them.
Thirdly, my acknowledgement is included here to the government of Switzerland, who
granted me the scholarship for finishing my MBA at AIT.
And finally, I would like to send my thanks to all of my teachers as well as friends, who
make my life - not only in AIT but everywhere - more valuable and enjoyable.
ii
Abstract
Good Manufacturing Practices (GMP) guidelines or regulations for pharmaceutical, food,
cosmetic, and some other industries aim at ensuring that products are consistently produced and
controlled to the quality standards appropriate to their intended uses and as required by the
marketing authorizations or product specifications.
In pharmaceutical industry, GMP is the most fundamental element of Quality Assurance
and internationally recognized. Basic standards of GMP have been published by the World
Health Organization (WHO). Nevertheless, many multi-national companies normally work to
the more demanding standards of GMP imposed by regulatory agencies in the European Union
and the United States Food and Drug Administration (FDA) as well as their own internal or
national GMP guidelines.
In most developed countries, GMP has become force of law, while in Vietnam, GMP
guidelines that based on ASEAN GMP guidelines are not enforceable. Therefore, putting GMP
into regulation is the concern of Vietnam’s Ministry of Health, as there are existed constraints
relating to the current local circumstances as well as local pharmaceutical manufacturers’
capabilities.
Thus, this research identifies and describes the challenges and difficulties faced by
pharmaceutical manufacturers, especially local firms in Vietnam towards implementing GMP.
These challenges can be classified into two categories: internal factors and external factors.
Internal factors comprise the financial shortage, qualified-personnel shortage and inability in
information accessing. External factors include government lagged and inappropriate policies,
customer attitudes and behaviors, and rivals’ influences.
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Table of Contents

Chapter Title Page
Title Page i
Acknowledgement ii
Abstract iii
Table of Contents iv
List of Abbreviations v
1. Introduction 1
2. Theoretical Review 6
2.1 Quality Assurance in Pharmaceutical industry 6
2.2 ASEAN GMP 10
2.3 GMP in comparison with ISO 9000 series 12
2.4 Pros and cons in implementing quality standards 17
3. Pharmaceutical Industry and GMP implementation in Vietnam 19
3.1 Overview of pharmaceutical industry in Vietnam 19
3.2 Government policies towards GMP implementation 22
3.3 Vietnam GMP guidelines 24
3.4 Major challenges faced by firms towards implementing GMP 24
3.5 Government's responsibilities in supporting firms’ GMP compliance 30
4. Conclusions and Recommendations 31
4.1 Conclusions 31
4.2 Recommendations 32
4.2.1 To firms 32
4.2.2 To government 39
4.2.3 To further studies 42
5. References 43
6. Appendices
A. ASEAN GMP 44
B. A typical Organizational Structure of GMP-approved firm 51
C. ASEAN and other National GLP and GMP Authorities 52
D. Web-sites relating to some of GMP regulations 54

E. List of local pharmaceutical manufacturers and 55
their relevant data55
F. Circular 12 BYT-QD providing a guide 64
for implementing ASEAN GMP
G. Interviewees 67
iv
List of Abbreviations
GMP Good Manufacturing Practices
WHO World Health Organization
FDA U.S Food and Drug Administration
GLP Good Laboratory Practices
GSP Good Storage Practices
GDP Good Distribution Practices
GPP Good Pharmacy Practices
Good Prescribing Practices
GCP Good Clinical Practices
SOP Standard Operating Procedures
FIP International Pharmaceutical Federation
CFR Code for Federal Regulations
v

CHAPTER 1
INTRODUCTION
1.1 Background
Facing the increasingly fierce competition and rapid globalization trend, companies
around the world have to ensure their products’ quality by complying with some types of
quality assurance standards or regulations, which are internationally or globally recognized.
In pharmaceutical, food, cosmetic, and some other industries, the Good Manufacturing
Practices (GMP) regulations are mostly used.
• What is GMP?

In pharmaceutical industry, GMP is a quality assurance system for ensuring that
products are consistently produced and controlled according to quality standards, and it is
designed to minimize the risks involved in any pharmaceutical production that cannot be
eliminated through testing the final product. Those main risks are:
- Unexpected contamination of product, causing damage to health or even death.
- Incorrect labels on containers, which could mean that patients receive the wrong
medicines.
- Insufficient or too much active ingredients, resulting in ineffective treatment or
adverse effects.
GMP covers all aspects of production, from starting materials, premises and
equipment, to the training and personal hygiene of staff. Detailed, written procedures are
essential for each process that could affect the quality of the finished product.
Furthermore, there must be systems to provide documented proofs that correct
procedures are consistently followed at each step in the manufacturing process - every
time a product is made. The figure hereunder illustrates the ten major components of
GMP.
Figure 1.1: Ten major contents of GMP
1
General
Personnel
Premises
Equipment
Sanitation
Production
Quality control
Self-inspection
Handling of complaint and recall
Documentation
• Why GMP?
Two levels are mentioned hereunder as the reasons for implementing GMP standards:

the macro level relating to the national policies and benefits, while the micro level
concerns the firm’s benefits.
- Macro level:
 Economic aspects:
+ Most countries will only accept import and sales of medicine that have been
manufactured to internationally recognized GMP.
+ Governments seeking to promote their countries’ export of pharmaceuticals can
do so by making GMP mandating for all pharmaceutical production.
 Social and humane aspects:
+ Implementation of GMP is an investment in good quality medicine, that helps
improve the health of individual patients as well as the community in terms of patient
safety, recovery times and the like.
- Micro level (firm-level):
+ Making poor quality products does not reduce costs. In the long run, it is more
expensive in finding mistakes after they have been made than preventing them in the
first place and first time. GMP is designed to ensure that mistakes do not occur, thus,
helps firms reduce production costs significantly in the long term.
+ Making and distributing poor quality medicines leads to loss of credibility for
everyone: both public and private health care as well as the manufacturers. GMP
helps firms build their credibility through producing quality products.
In Asian region, many countries have not enforced the GMP compliance of
pharmaceutical manufacturers while merely encourage them to implement the GMP
guidelines for their own competitive advantages. Moreover, there is not a mutual recognition
for national GMP guidelines and regulations among members of ASEAN, which is a
considering obstacle to the pharmaceutical market opening process in the region.
In Vietnam, the Drug Administration formed in August 1997 is responsible for
establishing the GMP guidelines and granting the GMP - compliance certificates. However,
these certificates are effective only in Vietnam, as they are not recognized in other countries.
From 30 October to 1 November, 2000, there is a meeting of ASEAN members in Hanoi –
Vietnam, relating to pharmaceutical issues, includes a discussion of approaches to the mutual

recognition of ASEAN GMP certificates in the region. However, this issue is out of this
research’s scope, hence, it is not mentioned in detail herein.
2
1.2 Problem Statement
As aforementioned, the ongoing challenges faced by Vietnam’s Ministry of Health are:
• How to establish or amend GMP guidelines and regulations, which are both
appropriate to the domestic conditions and agreed with ASEAN GMP guidelines, that
will become the regulations in the near future.
• What can the government do to promote pharmaceutical firms’ GMP compliance.
• What can the government do to support and reinforce the domestic pharmaceutical
firms’ capabilities in order to sustain and develop in the on-going boundless market.
1.3 Objectives
In this research paper, the following objectives are supposed to be attained:
• To review the general concepts of quality assurance as well as ASEAN GMP
guidelines for pharmaceutical industry.
• To compare GMP standards and ISO 9000 series of standards
• To present a broad view of the current situation of Vietnamese pharmaceutical
industry and GMP compliance of pharmaceutical companies in Vietnam
• To outline pharmaceutical manufacturers’ difficulties and constraints relating to the
GMP compliance in Vietnam
• Based on external benchmarking and internal auditing, to propose recommendations
to:
- Firms for overcoming the challenges and successfully implementing GMP
- Government for promoting pharmaceutical firms’ GMP compliance
1.4 Scope of study
This research paper focuses only on the GMP guidelines and regulations for
pharmaceutical industry in general, as well as the GMP implementation situations in
Vietnam, which concentrated on finding out both internal and external challenges faced by
firms in the process of obtaining GMP conformity.
1.5 Methodology

3
This research is conducted based on three critical tasks:
• Theoretically reviewing the quality assurance in pharmaceutical industry in
general,
• Data collecting about Vietnamese pharmaceutical manufacturers in terms of
revenues, GMP compliance, labor forces, capitals as well as the Vietnamese
government’s policies towards firms’ GMP conformity, and
• Finally, basing on the collected information, recommendations are made to firms,
government (Ministry of Health) and further studies.
The research methodology framework is presented in the following diagram:
Figure 1.2: Research framework of this paper
4
From Internet, books, journals
From Internet, books, journals
From Internet, books, journals
Describe general concepts of Quality
Assurance in Pharmaceutical Industry
Review ASEAN GMP
Compare GMP vs. ISO
Theoretical
Review
From secondary data, available at the
Drug Administration of Vietnam
Review and describe the
current situations of
pharmaceutical industry in
Vietnam, focusing on GMP
compliance
Personal interviews
Find out challenges faced by

firms in implementing GMP
Actualities of
pharmaceutica
l industry and
GMP
Implementatio
Recommen-
-dations
For firms, for government, and for
further studies
1.6 Overview
The entire research paper is divided into four chapters as the following:
Chapter 1: presents a general overview of the background information, current problems,
objectives and scope of the research study as well as the methodology for conducting this
research paper.
Chapter 2: discusses briefly the quality assurance concept in pharmaceutical industry and
ASEAN GMP guidelines. A comparison of GMP versus ISO 9000 series standards is
included as well. Last but not least, some pros and cons of quality standards are also
considered.
Chapter 3: outlines the actualities of pharmaceutical industry in Vietnam in terms of
market structure and governmental policies. Moreover, the GMP compliance in Vietnam, as
well as governmental policies relating to GMP implementation is also included. Aside from
those, the internal and external challenges faced by firms in implementing GMP are also
presented.
Chapter 4: presents the recommendations to firms for overcoming the challenges and
better practicing in implementing GMP standards. Also the recommendations to government
for speeding up the GMP compliance of pharmaceutical manufacturers are addressed.
5
CHAPTER 2
THEORETICAL REVIEW

2.1 Quality Assurance in Pharmaceutical Industry
Quality assurance in pharmaceutical industry is a broad concept embracing research and
development through manufacturing, quality control, storage and distribution, to the
information provided to the prescribers and the patients. It is the sum total of the organized
arrangements made with the objective of ensuring that medicinal products are of the quality
required for their intended use. Quality assurance therefore incorporates GMP plus other
factors illustrated by 5g-P principle mentioned hereafter.
According to Kathy Constantine (2000), the system of quality assurance appropriate for
the manufacture of medicinal products should ensure that:
i. medicinal products are designed and developed in a way that takes account of the
requirements of GMP and GLP (Good Laboratory Practices);
ii. production and control operations are clearly specified and GMP adopted;
iii. managerial responsibilities are clearly specified;
iv. arrangements are made for the manufacture, supply and use of the correct starting
and packaging materials;
v. all necessary controls on intermediate products, and any other in-process controls
and validation are carried out;
vi. the finished product is correctly processed and checked, according to the defined
procedures;
vii. medicinal products are not sold or supplied before a qualified person has certified
that each production batch has been produced and controlled in accordance with
the requirements of the marketing authorization and any other regulations relevant
to the production, control and release of medicinal products;
viii. satisfactory arrangements exist to ensure, as far as possible, that the medicinal
products are stored, distributed and subsequently handled so that quality is
maintained throughout their shelf life; and
ix. there is a procedure for self-inspection and (or) quality audit which regularly
appraises the effectiveness and applicability of the quality assurance system.
The figure hereunder is the 5g-P principle or 5gxP principle developed by WHO in 1998
(GMP – Good Manufacturing Practices, GLP – Good Laboratory Practices, GSP – Good

Storage Practices, GDP – Good Distribution Practices, and GPP – Good Pharmacy Practices)
in quality assurance for pharmaceutical products (Cao Minh Quang, 2000). To ensure the
quality of medicinal products from the starting materials through many other processes or
stages, to the consumer, a good and cooperative relationship is needed between the
manufacturer, whole-sellers, pharmacists and the like. Hence, the focus on only GMP while
neglecting other four good practices (GLP, GSP, GDP, and GPP) is ineffectual to the
product’s quality. The brief concepts of the other four good practices are explained
hereunder.
6
Quality Assurance in Pharmaceutical Industry
Figure 2.1: 5g-P Principle in Quality Assurance of Pharmaceutical products
Source: Dr. Cao Minh Quang, 2000.
It should be noticed as well that the quality assurance of clinical therapy (including Good
Clinical Practices and Good Prescribing Practices) is not less important than the 5g-P
principle in quality assurance of pharmaceutical products in offering the best services to the
patients.
• What are the other four Good Practices (GLP, GSP, GDP, and GPP)?
a. Good Laboratory Practices: GLP regulations set forth in either Title 21 Code for U.S.
Federal Regulations (CFR) Part 58, Title 40 CFR Part 160 or Title 40 CFR Part 792.
GLP conditions are required for conducting studies that support or are intended to
support applications for research or marketing permits for products regulated by the FDA
or the Environmental Protection Agency (EPA). It is a method to ensure that the quality
and integrity of data generated in the course of a study are adequate to meet the Federal
requirements. In brief, a study is in compliance with GLP regulations when it has a sound
protocol, qualified personnel to run the study, standard operation procedures, proper and
adequate facilities, calibrated and maintained equipment, fully retrievable raw data and
overviewed by all independent quality assurance officer. Pharmaceutical manufacturers
are required that all non-clinical studies submitted for the development of a new drug to
be conducted under GLP conditions.
7

Quality Assurance of Pharmaceutical products
GMP
Good
Manufac-
turing
Practices
GLP
Good
Labora-
tory
Practices
GSP
Good
Storage
Practices
GDP
Good
Distribu-
tion
Practices
GPP
Good
Pharmacy
Practices
Quality Assurance of Clinical Therapy
GCP
Good
Clinical
Practices
GPP

Good
Prescri-
bing
Practices
b. Good Storage Practices: it is not an enforceable regulation at this moment, however, it is
now been considering by drug administrations in many countries. For instance, in Vienna
FIP (International Pharmaceutical Federation) Congress 2000, from 26 to 31 August
2000, Good Storage Practices is one of the topics discussed. The following is an
illustration of the GSP guidelines for storing and handling vaccines.
- Designate one person within each clinic or office to coordinate storage and
documentation of vaccines.
- Provide information to all personnel handling vaccines regarding appropriate storage
and documentation practices.
- Check all vaccine shipments for any evidence of heat damage upon receipt; check
cold chain monitor cards if appropriate.
- Routinely check all refrigerators or freezers to ensure proper working order.
- Place a thermometer in the refrigerator and maintain a daily log of refrigerator
temperatures to document compliance with manufacturers' recommendations.
- Avoid storing any food in the same area with vaccines.
- Store vaccines in an area away from refrigerated or frozen medications to avoid
confusion.
- Do not store vaccines in the refrigerator door shelf where temperature fluctuations
may be greater.
- If possible, store bottles of chilled water in refrigerators and ice in freezers to
minimize temperature fluctuations in the event of brief electrical power outages.
- Perform a monthly inspection of opened and unopened vials for out-of-date vaccines.
- When opening or reconstituting a vial, note the date and time it was prepared; check
the manufacturer's recommendations for storage of reconstituted vaccines.
- Perform a "shake test" for products containing tetanus toxoid; if the product has been
allowed to freeze, an insoluble precipitate will form in clumps that cannot be

dissolved with vigorous shaking of the vial.
c. Good Distribution Practices: as GSP, GDP is not a regulation. Moreover, there is no
official GDP guidance. However, it is one of the issues to be considered by drug
administrations as the quality of drugs depends significantly on the way they are
distributed. For example, quality of pharmaceutical products can be badly affected on the
way they are transported due to the under-qualified hygienic transportation means. It is
also currently considered by IPEC (International Pharmaceutical Excipients Council
Europe) that can be referred to by accessing to the following web site:
< />d. Good Pharmacy Practices: in 1993 FIP produced international Good Pharmacy Practice
guidelines in order to raise the quality of pharmaceutical care provided by pharmacists.
These have been, or are in the process of being adopted by many countries around the
world. Recent minor changes have been included in consultation with WHO and these
guidelines were adopted by WHO in 1997. The details can be found at the following web
site />Aside from those four good practices in quality assurance of pharmaceutical products,
the other two good practices in quality assurance of Clinical Therapy are also briefly
presented herein.
8
e. Good Clinical Practices: FDA guidelines for GCP are explained in 21 CFR part 54.
These guidelines require among other things, a complete written protocol that describes
in details the design of the study, and methods for selection of subjects, collection and
statistical analysis of the data, and the like. GCP guidelines are followed by drug
companies in many clinical studies needed for new drug applications.
f. Good Prescribing Practices: established in 1994 by WHO due to the following reasons:
Bad prescribing habits lead to ineffective and unsafe treatment, exacerbation or
prolongation of illness, distress and harm to the patient, and higher cost. They also make
the prescriber vulnerable to influences, which can cause irrational prescribing, such as
patient pressure, bad example of colleagues and high-powered salesmanship. Later on,
new graduates will copy them, completing the circle. Changing existing prescribing
habits is very difficult. Thus, good training is needed before poor habits get a chance to
develop. GPP includes four parts hereunder:

Part 1: The process of rational treatment: Rational treatment requires a logical approach
and common sense that includes many other components, such as specifying the
therapeutic objective, and informing the patient.

Part 2: Selecting drugs: This section explains the principles of drug selection and how to
use them in practice.

Part 3: Treating the patients

Part 4: Keeping up-to-date: To become a good doctor, and remain one, he or she also
needs to know how to acquire and deal with new information about drugs. This section
describes the advantages and disadvantages of different sources of information.
For further references, the detailed information can be found at this web-site
< />• Drug Quality
For other products, the quality can be evaluated as “good”, “beautiful”, or “excellent”,
and these evaluations are vague and immeasurable, while the quality of drug is defined
clearly and specifically as the following:
- correct identification,
- correct content,
- without contamination or damage,
- right packages,
- right label, and
- intact container.
The following figure shows an illustration of drug quality concept.
9
Effectiveness Safety
Applicable
Satisfactory quality
Meet the
specifications

Homogenous Stable
Figure 2.2: Illustration of Drug Quality
Source: Dr. Cao Minh Quang, 2000.
2.2 ASEAN GMP
ASEAN GMP is developed almost ten years after the first GMP was published by WHO.
Therefore, it is more useful to introduce briefly about the other famous and former GMP
such as WHO GMP, U.S. GMP before mentioning ASEAN GMP.
2.2.1 Introduction of other GMPs
• WHO GMP:
The first World Health Organization (WHO) draft text on good manufacturing
practices (GMP) was prepared at the request of the Twentieth World Health
Assembly (resolution WHA20.34) in 1967 by a group of consultants. It was
subsequently submitted to and was accepted by the Twenty-first World Health
Assembly under the title "Draft requirements for good manufacturing practice in the
manufacture and quality control of drugs and pharmaceutical specialties".
Then, the first GMP text published by WHO was revised in 1975. In the 1980s
and early 1990s, several national and regional drug regulatory authorities issued or
revised guidelines reflecting the ongoing elaboration of the concept of GMP. In
addition, the WHO Certification Scheme on the Quality of Pharmaceutical Products
Moving in International Commerce was extended in 1988. Together, these
developments necessitated an update of the existing guidelines on GMP published by
WHO.
Revised and expanded GMP guidelines were prepared during 1989–90, approved
by the WHO Expert Committee on Specifications for Pharmaceutical Preparations in
late 1990 and published by WHO in 1992. Part One of these revised and expanded
guidelines sets out the philosophy and essential elements of GMP while Part Two
10
deals with good practices in production and quality control. These two parts together
represent the "core" of the GMP guidelines published by WHO.
• U.S. GMP

GMP regulations in the United States of America were developed by the FDA in
1975 and issued in the U.S. Code of Federal Regulations Chapter 21. The GMP
regulations were revised and updated in 1978 and became official and were
enforceable by law in March 1979. These regulations present the minimum
requirements to be met by pharmaceutical industry for the manufacturing, processing,
packaging, and storage of human and veterinary drugs.
2.2.2 ASEAN GMP
The ASEAN GMP guidelines were developed and were adopted by the Fifth Meeting
of Technical Cooperation on Pharmaceuticals in 1984. The first edition, which consisted
of general and practical guidelines, was revised in 1993.
The second edition of ASEAN GMP guidelines consisted of ten chapters, namely
General Provision; Personnel; Premises; Equipment; Sanitation and Hygiene;
Production; Quality Control; Self Inspection; Handling of Product Recall, Product
Complaint and Returned Drug Products; and Documentation.
In accordance with the report of Thirteenth Meeting of the ASEAN Working Group
on Technical Cooperation on Pharmaceuticals in 1994, Indonesia as the coordinating
country on GMP has established a team to revise the second edition.
The third edition was published in 1996 and the fourth or the latest edition of GMP
guidelines is available at the Eighteenth Meeting of Technical Cooperation on
Pharmaceuticals held in Hanoi at the end of October 2000. The detailed ASEAN GMP
can be found in appendix A.
In general, irrespective of different GMP sources, they all have the common basis as
mentioned hereunder:
• Hardware: infrastructure system
• Software: Standard Operating Procedures (SOP) system, and
• The system of ensuring and controlling the quality.
11
Hardware
Quality ensuring & controlling systems
Consiste

Figure 2.3: GMP concept
A typical organizational structure of GMP-complied firm is illustrated in appendix B.
Also in appendix C, the list of ASEAN and other national GLP and GMP authorities can be
found. While in appendix D, some web-sites relating to some of GMP regulations are
addressed.
2.3 GMP in comparison with ISO 9000 series of standards
The two standards have common grounds, and the implementation of both standards will
provide a good balance between management systems required for consistency and specific
system requirements relating to the manufacturing which are essential for the control
processes. Even though both documents make indirect reference to product requirements and
standards, the two are in effect system standards, which do not mention any specific details
of product quality control elements of the products being manufactured.
The ISO 9000 Quality Management Systems series of standards are series of standards
which have been developed for the control of management processes in a broad range of
industries which include airlines, banks, engineering firms and manufacturing (including
drugs, food and cosmetics). The implementation of this standard may provide more than
enough control for industries where quality is less critical. However for industries where
quality is paramount in preserving or maintaining human life, such as the manufacturing of
medicinal products, medical devices and cosmetics, nuclear applications, and aerospace,
these common control systems do not provide enough information for the standardization of
acceptable manufacturing methods for the relevant sector. In this context, GMP is required.
With regards to the lawful issue, ISO 9000 series of standards is not required by federal
or governmental authorizations. ISO 9000 series of standards is optional for companies to
implement for their own sakes. While GMP regulations are or will be required by federal or
governmental authorizations. Pharmaceutical manufacturers have to implement GMP
standards to be allowed to produce medicinal products. Moreover, ISO 9000 series of
standards are recognized internationally as it is the standards developed by ISO
(International Standard Organization) and it is not varied in different countries. However,
there is not only one GMP standard but many national, regional GMP standards that lead to
the non mutual recognition among them.

According to Carl Goodier (1999), the most important factor of ISO 9000 series of
standards is commitment while that of GMP is documentation. As ISO 9000 series of
standards focus on achieving the optimal productivity, effectiveness and efficiency of the
production processes and they require a continuous monitor, involvement and commitments
of the management. However, in GMP standards, the main factor is documentation as the
targeted industries for GMP are pharmaceutical, food, and cosmetic industries which are all
relating to human’s health. Thus, an extreme carefulness is needed in every stage of the
12
Software
production process, and documentation can help well in establishing the SOPs and tracking
back in case of some failures happened.
Regarding to the registrars, there is the difference between the two quality standards as
well. Quality system registration or approval involves the assessment and periodic audit of
the adequate of a manufacturer’s quality system by a third party, known as a quality system
registrar. When a particular company’s quality system conforms to the registrar’s
interpretation of an ISO 9000 or other appropriate standard, the registrar issues that company
a “certificate of registration”. Note that the company’s quality system but not an individual
product is registered. Consequently, quality does not imply product conformity to any given
set of requirements. While conformity assessment, as in the case of GMP standards, a more
comprehensive term, is the systematic evaluation of a product, process, or service to
determine to what extent to which it complies with specified requirements. Conformity
assessment activities include quality system registration, product or service testing and
certification, laboratory, certification body or quality system registrar accreditation.
While in the case of GMP standards, the third parties are belonged to the Ministries of
Health or Federal Agencies while the third parties (registrars) for ISO 9000 series of
standards are non-governmental organizations. In 1989, the Registrar Accreditation Board
(RAB)
1
was established as an organization to develop a program to evaluate the quality of
services offered by ISO 9000 series of standards registrars.

In general, a company that obtained ISO 9000 series of standards certificate can not be
sure that its products are met the quality requirements. A certificate of meeting ISO 9000
series of standards just ensure that the company achieves the effectiveness in controlling the
production processes and other processes in running its business. While if a company is
certified with GMP compliance, it ensures that the company’s products are met the
predefined quality requirements.
Key comparison points: GMP and ISO9000 series
• Scope:
1
Information on the RAB program is available from:
RAB
611 East Wisconsin Ave.
P.O. Box 3005, Milwaukee, WI 53202
Phone: 414-272-8575; Fax: 414-765-8661
13
The above figure explains clearly the common area and other individual areas in
terms of scope between GMP standards and the ISO 9000 series of standards. According
to the figure, GMP focuses more on the system or process requirements, either specific
or general requirements, while less focus on total involvement as ISO 9000 series of
standards. One more critical point is that GMP mentions more about safety and
environment issues as it is used for industries relating to human’s health.
• Physical and Mental health of employees
Although ISO 9000 does not specifically address the physical and mental health of
employees, it does mention the identification and use of suitable resources, and if
physical and mental health were an important parameter of quality control, then it would
be considered as a requirement. For instance, the physical and mental health of
commercial pilots and personnel assembling and dismantling nuclear weapons would be
considered as an important part of quality control in such industries. The effects of this
part of the GMP standards are far reaching in the sense that there would have to be
periodic assessment of these characteristics of personnel who are subjected to this clause.

• Hygiene and cleanliness of employees and environment
As could be expected hygiene and cleanliness is considered a critical element in the
operation of a drug, food and cosmetic manufacturing plant. Some of the critical points
mentioned are washroom cleanliness, use of protective clothing, shoes, gloves, caps and
14
Figure 2.4: Comparison of GMP and ISO 9000 series standards
Source: Carl Goodier, 1999
masks where required to reduce the risks of contamination. There is also mention of the
selection of equipment, production facilities and finishes to ensure that they are easy to
clean, do not retain contamination and induce contaminants such as machine lubricants
into the produced products. Such requirements are also mentioned in ISO9000 under
clause 4.9 and 4.15.2 of the standard (Carl Goodier, 1999), although it is less specific
than the code of GMP on this issue.
• Environment Protection & Safety of personnel
This requirement in the code of GMP is not a compulsory item of ISO9000 as the
specific focus of ISO9000 is to ensure that products produced meet the requirements of
the customer and are delivered on time. Polluting the environment or lack of safety of
employees would not be of a concern to ISO 9000 unless it was specified as a contractual
requirement by the customer. This requirement of the code of GMP would therefore be
moving toward a Total Quality Management (TQM) type of requirement where other
considerations are brought into perspective rather than just product quality and customer
satisfaction. This requirement would impose further complications to the implementation
of the code as it implies that the persons implementing the code and the persons
assessing companies against the code should have a clear understanding of national
environmental and safety acts and practices.
• Documentation
ISO 9000 series of standards have a general approach to the documentation in the
organization, and the corner stone of the standards is that procedures and records are
generated where they are required by the standards, and where they are necessary for the
control of the processes in the organization. In addition to the requirements of ISO 9000,

the code of GMP goes deeper into the types of documentation required in an organization
wishing to meet the requirements and the type of information to be conveyed in the
documentation.
• Heavy emphasis on complaint handling.
There are several portions of the GMP standards, which define the necessity of
recording and acting on customer complaints, which is critical for damage or liability
limitation and customer satisfaction. Similar to the code of GMP, there are several
portions of ISO 9001, which mention the handling of customer complaints, however
there is a strong emphasis on the prevention of complaints by the definition and control
of process characteristics and ensuring that personnel are suitably trained for allocated
tasks. ISO 9001 contains also a clause "Preventive Action" (4.14.3.) (Carl Goodier,
1999) that is considered as a very important part of the standard as it specifically
addresses problem prevention.
• Additional ISO 9000 series requirements
In general terms, the Code of GMP heavily leans towards production control and
quality inspection, thus, it is therefore less emphasis on staff related functions compared
with ISO 9001 topics such as management structures, management responsibility, design,
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R&D (Research and Development) control, documentation control, purchasing controls,
and statistical techniques.
• Implementation
Although the implementation of the code of GMP could follow a similar method
utilized with implementation of ISO9000, there are some elements of the code, which
would require some further attention for companies wishing to implement the code.
For instance, the requirement to procure and utilize equipment as well as facilities
that can be adequately maintained and operated from a hygienic perspective, would
require an extensive assessment of suppliers capabilities to ensure the delivery of
equipment or the design of the facilities in accordance with the requirements of the code
of GMP. This may require the education of suppliers to allow them to meet these more
stringent requirements, and potentially the removal of certain suppliers from the approved

suppliers list if they are not capable of meeting the requirements as spelt out in the code.
• Potential Future Trends
Since the worldwide spread quality management systems there has been a concerted
effort by the international community to standardize on the essential control elements of a
good quality management system, which resulted in the development of the ISO 9000
Quality Management Systems series of standards. In addition to this, there has been an
extensive drive by ISO 9000 certification bodies world-wide to standardize on their
understanding of the implementation of the standards, and methods of assessing its
implementation.
Therefore, the most cost effective and comprehensive solution for implementing the
code of GMP would be to merge the various standards on Environmental Management
Systems (ISO 14000), Safety Management Systems, and Quality Management System
(ISO 9000) together with the code of GMP into one management system which can be
applied to the entire organization. As these standards have many common points which
are required for effective control of the defined parameters, which may differ per
standard, the development of separate stand alone systems will not aid an organization
with long-term quality improvement objectives, and could only be considered as a short
term solution.
As many organizations have difficulty with the implementation of ISO 9000 in its
raw format, so the simultaneous implementation of all of the above standards and codes
may prove too complex for most organizations, and could possibly result in the failure of
implementation. It is suggested that the development of a common base from which the
other standards and codes could be attached to at a later stage. As ISO 9000 could be
considered as a base system for all the above mentioned standards and codes, it would be
an appropriate vehicle to form the foundation of the system, upon which the other
requirements could be attached later, further building the system into its required final
format.
The following table presents an overview of the common points and the differences of the
two standard systems.
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Table 2.1: Common points and the differences of GMP and ISO 9000 series of
standards
Common features of GMP and ISO 9000 series standards
• Implementation of both standards will provide a good balance between management
systems required for consistency and specific system requirements relating to the
manufacturing which are essential for the control processes
Differences
GMP ISO 9000 series of standards
• For industries where quality is paramount
in preserving or maintaining human life
• Focus more specifically on: physical and
mental health of employees, hygiene and
cleanliness of employees and
environment, environment protection &
safety of personnel, complaint handling,
and the like
• Be or will be a force of law
• Non-mutual recognition over the world
• First established in 1967 by WHO
• Most important factor is documentation
• Certified by Drug Administration
Agencies
• Issued by WHO, FDA, national drug
administrations
• For the control of management processes
in a broad range of industries
• These issues (refer to the left) are
mentioned generally
• It is not a lawful regulation
• Globally recognized

• Established in 1987 by ISO
• Most important factor is commitment
• Certified by the non-governmental
registrars
• Issued only by International Standard
Organization
2.4 Pros and cons of implementing quality standards
Standards can be politicized, or unduly influenced by special interests, especially when
written into laws and regulations. This can give certain producers or health care providers a
monopoly, which drives up prices and which can make products unaffordable to those whom
would otherwise have the means to buy them. In the extreme case, they can cause a product
to be removed from the market, even when it is quite safe. This deprives consumers of the
opportunity to benefit from the product and can be financially devastating to producers who
have invested in its production.
However, some standards provide clear benefits at little cost because they serve an
obvious need, are well established and straightforward, are less controversial, and are
therefore easier to establish. These include things like dissolution standards and the inclusion
of lot numbers and expiration dates on product labels. These standards seem extremely
simple and commonsense, however, they help very well in making production and
controlling much more effective and efficient.
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The following table addresses the general pros and cons of quality standards.
Table 2.2: Pros and cons of quality standards
Pros Cons
• Well-developed and broadly accepted
standards provide an easy way of
determining if a product is beneficial and
safe.
• They also ensure that a product is
manufactured to an acceptable level of

high quality.
• Some standards provide clear benefits at
little cost because they serve an obvious
need, are well established and
straightforward, are less controversial, and
are therefore easier to establish
• Help firms save money with the quality
principle of “do it right at the first time”
• They can be inflexible and force
producers to make products a certain
way when other options are just as good,
sometimes better, than what a standard
dictates.
• If adopted into law, they become even
harder to change, either to meet the
demands of the marketplace or to reflect
new scientific knowledge
• Standards can be politicized, or unduly
influenced by special interests,
especially when written into laws and
regulations
• Require firms to spend more on
consultants, external auditing,
certifications and the like.
With regards to GMP regulations, the pros of them can be outlined as following:
• Help ensure the medicinal products’ quality to protect human’s health.
• Help save money on contaminated products that would be destroyed.
• Help pharmaceutical manufacturers to penetrate their markets to other countries
However, GMP implementation also bring some cons mentioned hereunder:
• Requires firms to invest largely at the initial stage in terms of financial as well as

personnel resources
• Deepens the gap between developed and developing countries as developed countries
set their own GMPs and do not recognize others’ GMP certificates without the
persuasive and clear evidence that the other GMP standards are under-qualified.
• Non-unified GMPs bring the new issue of mutual recognition that is considered by
many countries and regions.
CHAPTER 3
PHARMACEUTICAL INDUSTRY
AND GMP IMPLEMENTATION IN VIETNAM
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3.1 Overview of pharmaceutical industry in Vietnam
According to M. Doyle (1999), in 1998, the Vietnamese drug and pharmaceutical
market was modest at an estimated $325 million. However, it has shown continuous
growth on a year-on-year basis. Per capita spending on pharmaceuticals is believed to be
$4.25, representing a 21% growth in the past two years and triple the per capita spending
rate of a decade ago. While the per capita consumption of pharmaceuticals by Americans
or Japanese is more than U.S.$300 per year, Singaporeans - $45 per year and Indonesians
- $10 per year.
There are approximately 10,000 pharmaceutical products legally sold in Vietnam to
6000 pharmacies, 900 hospitals or clinics, and thousands of private doctors. The
pharmaceutical market is fragmented and highly competitive, with most major
international pharmaceutical companies operating in Vietnam, and most of these
companies have representative offices. Imports account for 85% of all dollar sales.
Domestic production is limited and losing ground to imports. Furthermore, the market is
poorly regulated for production and distribution.
Specialty drugs represent 70% of the market and are the best prospect for
importation. The government recognizes domestic production cannot meet demand in
specialty drugs and, therefore, are likely to grant most favorable conditions to importers.
Generic product accounts for half of all unit sales. They are produced domestically and
imported from Western and Asian countries.

According to the above reference, foreign imports account for roughly 85% of all
dollar sales and 70% of unit sales while locally made product accounts for approximately
15% of dollar sales and 30% of unit sales. It is estimated that nearly 2500 products are
currently imported and more than 7500 products are made domestically. Generally, local
products do not meet international standards and may not meet ASEAN GMP quality
standards.
The Vietnamese government stated it plans to raise investment in healthcare from the
current 3% of budget to 5% by the year 2000 and 8% by 2020, with the intent to decrease
the rate of infectious diseases, raise health conditions, reduce infant mortality and
prolong life expectancy. Drugs that treat epidemic-prone diseases (malaria, encephalitis,
tuberculosis, AIDS, etc.) and common environmental illnesses (diarrhea, dysentery,
respiratory, etc.) will be in demand. Additionally, preventative healthcare (e.g. vitamins,
condoms) and childhood treatments (e.g. nutritional supplements) will rise in importance.
Domestic manufacturers produce topical creams, generic antibiotics, analgesics, anti-
inflammatory, respiratory and cardiovascular pharmaceuticals, and specialty drugs to a
small extent. The government has stated interest in producing basic medicines, such as
painkillers, cold medicine, vitamins and antibiotics. However, foreign manufacturers
consider locally produced drugs sub-standard. Price-oriented rather than quality-oriented,
local producers are known to use lower quality raw materials, reduce active ingredients
and alter the overall composition of formula, in order to maintain a given price. In 1997,
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