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
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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
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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.
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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
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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
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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.
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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.
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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.
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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:
<http://www.ipec.org/newsjan.pdf>
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 http://www.fip.nl/pdf/gpp.pdf.
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.
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