Đề tài 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 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. 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. 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 ASEAN GMP 10 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 Government policies towards GMP implementation 22 Vietnam GMP guidelines 24 Major challenges faced by firms towards implementing GMP 24 Government's responsibilities in supporting firms’ GMP compliance 30 Conclusions and Recommendations 31 Conclusions 31 Recommendations 32 To firms 32 To government 39 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 List of local pharmaceutical manufacturers and 55 their relevant data55 Circular 12 BYT-QD providing a guide 64 for implementing ASEAN GMP G. Interviewees 67 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 CHAPTER 1 INTRODUCTION 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. Production General Quality control Personnel Self-inspection Premises Handling of complaint and recall Equipment Documentation Sanitation Figure 1.1: Ten major contents of GMP 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: F 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. F 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. 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. 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 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. Methodology 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: Describe general concepts of Quality Assurance in Pharmaceutical Industry From Internet, books, journals Theoretical Review Review ASEAN GMP From Internet, books, journals Compare GMP vs. ISO From Internet, books, journals Review and describe the current situations of pharmaceutical industry in Vietnam, focusing on GMP compliance Actualities of pharmaceutical industry and GMP Implementation in Vietnam From secondary data, available at the Drug Administration of Vietnam Find out challenges faced by firms in implementing GMP Personal interviews Recommen- -dations For firms, for government, and for further studies Figure 1.2: Research framework of this paper 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. 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: medicinal products are designed and developed in a way that takes account of the requirements of GMP and GLP (Good Laboratory Practices); production and control operations are clearly specified and GMP adopted; managerial responsibilities are clearly specified; arrangements are made for the manufacture, supply and use of the correct starting and packaging materials; all necessary controls on intermediate products, and any other in-process controls and validation are carried out; the finished product is correctly processed and checked, according to the defined procedures; 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; 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 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. Quality Assurance in Pharmaceutical Industry Quality Assurance of Pharmaceutical products GPP Good Pharmacy Practices GDP Good Distribu-tion Practices GSP Good Storage Practices GLP Good Labora-tory Practices GMP Good Manufac-turing Practices Quality Assurance of Clinical Therapy GPP Good Prescri-bing Practices GCP Good Clinical Practices 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)? 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. 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. 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: 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. 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. 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. 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 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. Hardware Consistent and quality- met production processes Quality ensuring & controlling systems Software 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 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) 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 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: Figure 2.4: Comparison of GMP and ISO 9000 series standards Source: Carl Goodier, 1999 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 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, 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. 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. 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 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, local producers cut prices below cost, causing product dumping, serious profit losses and a price war in the marketplace. In 1999, the pharmaceutical sector is home to some 20 state-owned enterprises, more than 100 local producers and 180 liability limited companies (including joint-ventures, joint-stock and 100 per cent foreign-owned companies). Generally, the sector is performing poorly. In 1996, its total sales revenues were only equal to those of one or two enterprises of other sectors. With a seriously degraded material base and outdated technology, the entire sector operates unprofitably and inefficiently. Almost all drug-stores and ware-houses are inadequate for the preservation and sales of medicines. Many stores have been cited by the Ministry of Health for not following safety conditions. To respond to the local and export demands for pharmaceuticals, more than a few enterprises have boldly joined hands with foreign producers. To the end of the year 1999, there are 21 foreign-invested drug production projects licensed by the Ministry of Planning and Investment with 11 joint-ventures, nine wholly foreign-invested companies and one business co-operation contract. Seven have started production, but report modest results. The Vietnam Pharmaceutical Corporation alone has five foreign-invested projects, but only Sanofi Pharma Vietnam (SPV) has turned a profit. A list of local pharmaceutical manufacturers and their relevant data can be found in the appendix E. Current demand for pharmaceuticals is U.S.$0.8 - 1 billion in 2000 and should rise to U.S.$1 - 1.5 billion in 2005. This is viewed as both a challenge as well as an opportunity for the development of the pharmaceutical sector. With such actualities, the government’s role is needed to establish a sound market with a sound competition to ensure to quality of pharmaceuticals as well as to guide and support the local pharmaceutical manufacturers in reinforcing their production capabilities in order to lessen the imported drugs quota and promote exportation. Governmental policies towards drug quality management: Prior to September 1996, no formal drug policy existed, creating an over-abundance of product and sub-standard imports. However, some tougher regulations were promulgated, aimed at protecting domestic production and the general populace, focus on pricing, license registration, distribution and patent and trademark protection, such as: In an effort to protect local production and encourage on-shore foreign production, the government banned 62 drugs from importation and is to be considering additional 50 compounds for elimination. Comprehensive dossiers (as lengthy as ten books) are required in English and Vietnamese. Product licenses may be granted for one to five years, causing companies to begin the renewal process soon after licenses are registered. Only three state-owned importers are able to distribute to hospitals, reducing any competitive channel advantage previously gained. While the Ministry of Health has created new policies against counterfeit products, few have been enforced, under cutting potential sales and the perceived effectiveness of successful foreign brands. Importers face a cloud of uncertainty as the Ministry of Health legally able to reduce and control quantities and types of product licensed for importation. (M. Doyle, 1999) In October 1996, the government established the Vietnam Pharmaceutical Management Department in an effort to restore order to the pharmaceutical and cosmetic industries. Also in 1996, the Vietnamese government took steps to eliminate sub-standard drugs from entering Vietnam and began enforcing stricter guidelines for importers. As a result of new regulations, several Thai and Indian pharmaceutical companies have been forced out of the country and others (primarily generics) are under scrutiny. Besides, Vietnam Pharmaceutical Management Department, along with the Ministry of Commerce, had the authority to grant or cancel pharmaceutical and cosmetic import and export licenses and were in charged of the implementation of the national drug policy. Before 1997, Vietnam operated with no official policy on the manufacturing, distribution or selling of pharmaceuticals. In 1997, sixty-two drugs have been essentially banned from importation in order to support local production. The Ministry of Health announced that by January 1998 all imported drugs must have instructions on product use, dosage, and expiration dates printed in Vietnamese and inserted in packages, and a company's visa number must be printed on all packages. Drug advertising has come under scrutiny in 1998. Additionally, the Ministry of Health began inspecting local drug-producing plants and the quality of medicines on sale in pharmacies nationwide in August 1997. However, the government's policy projected a shortfall of domestic product to meet demand. While $20 billion is forecasted to be invested in the pharmaceutical industry in Vietnam between 1997 and 2010, domestic medicine manufacturing will probably meet only 50% of demand. Priority will be given to imported drugs, which cannot be produced locally. Though, importers need a Bill of Laden, Certificate of Authority and specific, individual licenses to bring product into Vietnam. To date, the government recognizes three standards of quality for drugs: International standards of the World Health Organization (WHO), ASEAN Good Manufacturing Practices (GMP) guidelines, and National Standard which followed lesser Indonesian and Thai standards. However, the government has never granted an international standard license and is eliminating consideration of national standard licenses while focusing more on GMP standards. To register product, a company needs a Certificate For Sale (CFS), GMP approval from the Ministry of Health and sample testing from five separate committees. It is imperative that all documentation be thorough and accurate. Medical dossiers must be prepared in English (or French) and Vietnamese, then notarized. Each product must be registered at a cost of $2000 per product form. Approvals may take six months to a year or more. Products are granted licenses for a specified length of time. Generally, three types of licenses are given depending on product’s types. A one-year license is given to product that is being produced with a Vietnamese joint venture. A three-year license is granted to product that is imported and not produced in significant amounts domestically. A five-year license may be given to product, which cannot be produced locally and is in demand. 3.2 Government policies towards GMP implementation First of all, does Vietnam need to enforce the GMP compliance in pharmaceutical industry? The listed reasons hereunder can lead to the answer of yes. For the nation’s benefits: GMP standards help improve and control the medicinal products’ quality as well as protect human’s health in Vietnam Enforcing GMP compliance can help prevent the manufacturing and selling of low-quality products, contaminated products, fake products and the like. It also benefits Vietnamese patients in using local-produced medicines. For firms’ benefits: For firms to penetrate their markets to other countries or to franchise from foreign pharmaceutical manufacturers, GMP compliance is required by the franchisers and host countries. In long term, GMP as other quality standards, can help save money by the “Do it right at the first time” principle. Firms will be able to achieve the optimal productivity, production process effectiveness by complying with GMP standards. The example of Dong Thap Pharmaceutical Company – a state-owned company that achieved ASEAN GMP certificate in June 1997 illustrates the benefits gained from investing on improving products’ quality. Dong Thap Pharmaceutical Company is a state-owned enterprise in Cao Lanh, Dong Thap province, headed by Ms. Tran Thi Dao since 1986. In 1987, Ms. Dao decided her company, a pharmaceutical importer for twelve years, could out-produce domestic drug manufacturers by focusing on quality. Her simple plan was to scrap most of the manufacturing equipment the company had bought but never used years earlier, salvage the rest, and add new equipment from Taiwan and China where she could and key parts from Germany where she had to. At first, the company just made two drugs as a subcontractor for a well-known company in Ho Chi Minh city. In 1990, she upgraded and expanded production to twenty drugs, this time marketing under the company's own name. The strategy succeeded, and Dong Thap Pharmaceutical Company became one of the few local drug companies whose products could compete with foreign imports. In 1998, sales revenues for Dong Thap Pharmaceutical Company were 200 billion VND (over USD 14 million) domestically, up five percent over 1997. Export revenues in its first full year of exporting were just under USD 1million. What has distinguished the company has been Dao's disdain for conventional wisdom and ability to persuade the Dong Thap provincial government to go along with her. The company's fortunes continued to improve when her success attracted European experts providing management expertise to Vietnam who provided on-site training for her 200 employees over three years. With additional management and equipment upgrades, the company received GMP certification in June, 1997, and a second, new production line is about to receive it as well. The company is about to produce 30 products under the trademark of a foreign pharmaceutical company and it hopes to establish it as a contract manufacturer for more foreign companies. (Source: U. S. Department of Commerce - National Trade Data Bank, November 3, 2000). To date, Dong Thap Pharmaceutical Company is one of the most well-known local and state-owned pharmaceutical manufacturers in Vietnam, in terms of successes in doing business and goodwill. Recognizing the importance and benefits of product’s quality, since September 1996, the Vietnamese Ministry of Health promulgated several decisions as well as official letters regarding GMP implementation and enforcement. However, it should be noticed that the aforementioned documents are not enforceable by law. These decisions as well as official documents are outlined hereunder, focusing on the general contents. On September 9th, 1996, the Ministry of Health issued the Decision 1516 BYT-QD on implementing ASEAN GMP, including: The requirement of ASEAN GMP implementation in all pharmaceutical manufacturing factories. The compliance of ASEAN GMP is one of the basic factors to be considered in applying for product registration and production permit. This decision is effective from the signed date, which is September 09th, 1996 On September 12th, 1996, the Ministry of Health issued the Circular 12 BYT-QD providing a guidance for implementing ASEAN GMP, covering the requirements of : Document set for applying for GMP approval The dissemination and training of ASEAN GMP Training of GMP inspectors and their required qualifications Inspection and result consideration procedures The entire content can be referred in the appendix F On January 14th, 1998, the Ministry of Health sent the letter No. 284/QLD on favorable conditions for GMP-approved pharmaceutical factories, addressing the privileges for the GMP-approved pharmaceutical manufacturers as following: Be allowed to print an additional sentence of “GMP-approved Company” in the label. Be granted some favors in manufacturing the exports. Be allowed to cooperate and to be franchised with major well-known pharmaceutical manufacturers in the world for some kinds of products. Be prioritized in participating in bidding both at national and international level, to supply pharmaceuticals for national health programs. Be favored in supplying the essential pharmaceuticals for hospitals as well as health programs, which funded by governmental funds or international aids. Be privileged in approving the production registration, including the pharmaceuticals belonging to the list of limited-granting products. On May 20th, 1999, the Ministry of Health sent the letter No. 3153/YT-QLD on Drug Registration for GMP-approved pharmaceutical factories, which outlines the favorable procedures for GMP-approved firms in applying for the product registration. Moreover, with the Decision No. 05/TDC-QD issued on January 04th, 1997 by Quality Measuring Standards Department belonged to the Ministry of Sciences, Technology and Environment, which relates to the publishing of the general guidelines for basic contents to implement GMP in food manufacturing factories, is an evidence of Vietnamese government’s consideration of the GMP’s importance, not only in pharmaceutical industry but also in food industry as well. 3.3 Vietnam GMP guidelines for pharmaceutical industry On September 9th 1996, Vietnam’s Ministry of Health issued the Decision No. 1516 BYT/QD which has decided to apply ASEAN GMP and requested all drug manufacturers to make their own plans for GMP implementation. However, the mentioned GMP is only guideline but not regulation. Vietnam GMP is basically built followed ASEAN GMP, however, it is only true for the general guidelines, while the practical and specific procedural guidelines are established for the appropriateness of the local circumstances. For detailed and specific requirements of Vietnam GMP, two key persons in Vietnam Ministry of Health can be contacted via the addresses given in the appendix G. 3.4 Major challenges faced by firms towards implementing GMP standards Up to the end of the first quarter of the year 2000, Vietnam has only 15 pharmaceutical factories that are recognized as meeting the ASEAN GMP standards, accounting 13.4% of total pharmaceutical manufacturers in Vietnam. (Ministry of Health at a Friday meeting in HCMC to review the implementation of GMP standards by drug factories nationwide on April 10th, 2000). These include eight all-local producers, and seven foreign-owned companies. In reaching the target of 100% GMP compliance in the year 2003, there must be some dramatic changes happened, both in companies’ efforts and government’s supports to overcome the existing challenges. Thus, before mentioning how to overcome those challenges, they must be addressed specifically. Hence, what are the challenges faced by firms in implementing GMP standards? The challenges faced by pharmaceutical manufacturers in Vietnam in attaining GMP compliance are divided into two groups of internal factors and external factors. 3.4.1 Internal factors Internal factors consist of three major sources mentioned hereunder, which are the financial shortage, the qualified-personnel shortage in terms of both GMP-relating as well as technical manpower, and finally the inconvenience or incapability of firms in accessing the needed information. Financial challenges According to the Dr. Quang, Vice Director of the Institute of Drug Quality Control, Ho Chi Minh city, Vietnam, approximately two million of U.S dollars per production line is needed for firm to spend on GMP implementation. That amount is a considering large amount for local pharmaceutical manufacturers, especially the small enterprises. Local pharmaceutical manufacturers’ revenues in 1999 are summarized in the graph hereunder. Figure 3.1: Local pharmaceutical manufacturers’ revenues in 1999 Note: Data collected from Vietnam’s Ministry of Commerce A list of firms and their relevant data can be referred in the appendix E From the above graph, there are only eight firms having the revenues exceeding two million of U.S.$, accounting less than 30% of total mentioned There are more smaller local pharmaceutical firms which are not included in the list due to two main reasons: Not directly produce drugs Too small compared to others local pharmaceutical manufacturers. There is only one firm having revenue exceeding ten million of U.S.$, that is the National Pharmaceutical Co. No.1. With revenues exceeding eight million of U.S.$, there is an additional company qualified. In general, assume that a company wanting to implement GMP (investment of two million U.S.$ per production line) needs to have revenue doubling the initiative investment on GMP, thus, there are only 4 companies qualified, accounting less than 20% of total considered local firms. Lack of qualified personnel Lack of GMP-trained personnel: In Vietnam, the number of persons who was properly trained of GMP is insufficient. Foreign-owned firms usually send their personnel abroad for GMP training while it is hard for state-owned companies to do so due to the limited financial budgets. According to the statistics of the Ministry of Health, up to the second quarter of the year 2000, there are only twenty local pharmacists trained formally by Australian trainers on GMP (Saigon Times, August 22nd, 2000). Besides, there are few officers of the Ministry of Health are trained on GMP and attended meetings relating to ASEAN GMP topics. Aside form those, many persons are trained locally and informally of general information about GMP for a short period. Thus, they are not qualified as key persons in promoting GMP implementation process. Lack of highly technical-skilled personnel: In GMP guidelines, there are many well-defined and rather strict requirements that need to be executed properly by qualified technical staffs, who are usually qualified pharmacists. As common actualities for firms around the world, it is quite difficult to be able to recruit the well-qualified personnel, and it is much harder to retain them. That reality is especially true for state-owned firms wherein the improper organizational rules or bureaucracy procedures still exist. Difficulties in Information Accessing: It is a common circumstance in Vietnam that firms, especially state-owned and small enterprises, face many obstacles and challenges in finding the necessary information for doing their businesses. It is even truer for searching the information relating to GMP as GMP is rather new in Vietnam for about four or five years. Usually firms are eager to implement GMP, however, they do not know what to do, where to commence, to what extent, and alike. In the guidelines, regulations, circulars All of the guidelines, regulations, circulars and the like can be found at the Vietnam Ministry of Health at the following address: 138A Giang Vo Street Hanoi, Vietnam Tel: (844) 8461525 Fax: (844) 8234758 alike, there is no specific detail guiding firms on a step-by-step basis towards implementing GMP. Though, this might be considered as an external factor. Nevertheless, it is included in internal factors for accentuating firm’s insufficient investment on maintaining and improving their intangible assets. Normally, at this moment, email is popular for firms. However, Internet and its robust information resources are still beyond major firms’ reach mainly due to the two reasons: there is no needed information available on the Internet, and the high Internet accessing fee. (Currently, the Internet accessing fee through phone line is approximately U.S.$ 1.5 per hour). 3.4.2 External factors Three main causes are believed to be factors that obstruct firms’ GMP-implementation capabilities. They are the lack of updated as well as the proper governmental policies towards encouraging firms’ GMP compliance, consumers’ behaviors and attitudes such as self-directing habits in buying medicines, plus their lacking of awareness of quality standards such as GMP standards, and finally the rivals’ effects such as unbalanced and unsound competition, price competition and the like. Governmental policies: Regulations as well as guidelines are issued laggardly, inconsistently and non-synchronously, bringing firms many obstacles and confusions in deciding what to do in implementing GMP standards. Referring to all of the issued guidelines, regulations, circulars and the like, which are relating to GMP, there is no specific guidance on how to successfully implement GMP standards or the listed pitfalls, key points in GMP implementation. Moreover, referring to session 3.2, it can be seen that there is nearly one and a half year lagged after the issuing of the requirement of GMP compliance in all pharmaceutical manufacturers, the privileges for GMP-complied firms was mentioned formally. Thus, firms have not many motives for implementing GMP that costs them significantly at the initial period. Lacking of clear favorable conditions reserved for GMP-complied firms as well as of a proper and effective mechanism for supplying the essential and necessary information for firms in order to encourage GMP compliance. As mentioned in session 3.2, the followings are the granted privileges for GMP-complied firms: Be allowed to print an additional sentence of “GMP-approved Company” in the label. Be granted some favors in manufacturing the exports. Be allowed to cooperate and to be franchised with major well-known pharmaceutical manufacturers in the world for some kinds of products. Be prioritized in participating in bidding both at national and international level, to supply pharmaceuticals for national health programs. Be favored in supplying the essential pharmaceuticals for hospitals as well as health programs, which funded by governmental funds or international aids. Be privileged in approving the production registration, including the pharmaceuticals belonging to the list of limited-granting products. (Note: the above favors for GMP-complied firms are entirely quoted from the letter No. 284/QLD issued on January 14th, 1998 by the Ministry of Health on favorable conditions for GMP-approved pharmaceutical factories). The ambiguousness of these favors are analyzed hereunder: Be allowed to print an additional sentence of “GMP-approved Company” in the label. What does it benefit the company while the local consumers are not aware of GMP quality standards? What does it benefit the local producers while doctors and pharmacists keep on recommending the premium-price or imported medicines to end-consumers for gaining higher commission? Be granted some favors in manufacturing the exports. Which favors are granted specifically? Tax-reduction? Prioritized in bidding? Allowed to franchise? However, the ultimate issue is that how to find markets for their exports? Does the government help GMP-complied firms find foreign markets for their products? Does this encourage firms to implement GMP if their focused market is local market? Be allowed to cooperate and to be franchised with major well-known pharmaceutical manufacturers in the world for some kinds of products. Actually, this mentioned favor is unnecessary, as the franchisers themselves always require their franchisees to have GMP-complied certificates. Be prioritized in participating in bidding both at national and international level, to supply pharmaceuticals for national health programs. Be prioritized to what extent? In this case, does price affect the final decision? It should be noticed that it is supplying medicines to funded national health programs, and there are much red tape and bureaucracies in funded national programs that may consider the price as the first priority in selecting the suppliers. Moreover, it is normal that GMP-complied firms may have higher production costs than non GMP-complied manufacturers at the first several years. Thus, GMP-complied firms surely loose their advantages in bidding for price-sensitive cases. Be favored in supplying the essential pharmaceuticals for hospitals as well as health programs, which funded by governmental funds or international aids. As in the previous analysis, to what extent and in which categories GMP-complied firms are favored? Be privileged in approving the production registration, including the pharmaceuticals belonging to the list of limited-granting products. Does it encourage all pharmaceutical manufacturers to implement GMP if their major and targeted products are just the general medicines? However, the Ministry of Health is on the process of banning non GMP- complied pharmaceutical manufacturers from producing any kinds of medicines. It means that GMP is going to be regulation in 2003. Moreover, with regards to the lack of a proper and effective mechanism for supplying the essential and necessary information for firms, there is no GMP-focused web-site now in Vietnam. In this IT era, Vietnam is surely capable to build database and web sites for GMP-related contents. However, it has not been done yet as the importance and usefulness of IT is not properly appreciated in governmental organizations. Consumers’ behaviors and attitudes: Consumers can be classified into two groups: end-users (patients) and influencers (doctors, pharmacists). End users: Consumers are usually influenced by the media advertisements due to lacking of professional knowledge in medicines. Therefore, the real quality is not as important as the advertised-quality in theirs buying decisions. This habit hinders pharmaceutical manufacturers to invest significantly on improving product quality by implementing GMP standards, as GMP-implementing execution requires huge financial and manpower investment. Moreover, the price sensitiveness is still most of Vietnamese’s character due to the low-income level and most of the individual consumer does not aware of GMP quality standards. Thus, it contributes to the indifferences of GMP-approved firms and non GMP-approved pharmaceutical manufacturers. Last but not least, up till now, fondness of imported goods is still the character of Vietnamese’s majority that hinders local firms’ potentials. Doctors and pharmacists: While the patients are the ultimate end-users, pharmacists and private or public doctors are usually key buyers and decision-makers. And normally their profit is directed related to the price, thus, premium-priced foreign products tend to be recommended to patients regardless of their quality. Rivals’ Influences Price competition from sub-standard generics, parallel imports, smuggled drugs and copycat products obstruct firms from investing capital on implementing GMP. Moreover, at the very first stage of GMP implementation, the production costs will be increased significantly. Unsound and unequal competitions among immature local pharmaceutical manufacturers and joint-ventures with giant worldwide corporations or financial-strong as well as technical-strong FDI companies in the conditions of lacking proper governmental ruling or guiding regulations. Without a proper support from the government, local firms may be kicked out of the market. 3.5 Government's responsibilities in supporting firms’ GMP compliance As written before, the Vietnamese government realized the importance of GMP compliance for pharmaceutical manufacturers, especially local firms in terms of: Supplying consumers with consistent and good quality medicinal products, as human’s health is greatly critical. Penetrating local firms’ markets into other countries to promote exports and reduce the import quota for drugs. Thus, with certain approaches, the government is on the process of encouraging firm’s GMP compliance, such as: Issued some decisions and regulations concerning the promotion of GMP implementation of pharmaceutical manufacturers throughout the country. Granted some privileges for GMP-approved firms in their production registration and cooperation with foreign pharmaceutical manufacturer corporations as well as participation in bidding. However, there is no specific guidance is built to help firms step-by-step successfully implement GMP standards and those granted privileges are vague and too general in meanings. Thus, further government’s efforts are obviously needed to improve the existing circumstances to meet the defined target of 100% pharmaceutical manufacturers meeting the ASEAN GMP standards in the year of 2003. The role of government is significantly important in Vietnam’s business environment, as it is still a “market economics with the guidance and monitor of the government”. Therefore, to increase the GMP-compliance ratio (number of GMP-approved firms to total number of pharmaceutical manufacturers in the country, which is less than 15% in the year 2000) and reach the 100% ratio, Vietnam’s government has to do the best in enforcing firms’ GMP-compliance while still support local firms in fostering their capabilities in doing their businesses. Some recommendations concerning the policies are mentioned in the next chapter. CHAPTER 4 CONCLUSIONS AND RECOMMENDATIONS 4.1 Conclusions With the on-going market globalization and the increasingly severe competition over the world, quality becomes the first priority in manufacturing firms in sustaining and developing. Also quality plays more and more important role in consumer’s buying decision. These are reasons why firms are trying to meet particular international-recognized quality standards including GMP standards system for pharmaceutical products. In most developed countries, GMPs have become regulations and some mutual recognition agreements have been established among them such as United States of America and European Union, Canada and European Union, Australia and European Union and the like. However, in Asian region, although there was a unique GMP guidelines called ASEAN GMP, in each country there is a national GMP standards system that is generally based on ASEAN GMP, and there is no mutual recognition for GMP-approved certificates among ASEAN members. In Vietnam, the Vietnam’s GMP is basically followed ASEAN GMP but with some additional specific measures and requirements that are suited to the local actualities. However, pharmaceutical manufacturers, especially local firms are facing many challenges in struggling to achieve GMP conformity due to many sources of factors including the immature capabilities and lack of proper, on-time supports and guidance from the government. Some typical examples of those are: The lacking of financial budget for GMP implementation (estimated at U.S.$ two million per production line) The shortage of qualified personnel in GMP-relating fields as well as technical fields The unavailability of necessary information for deciding what to do, how to do, to what extends, and the like in implementing GMP standards. The regulations as well as guidelines that are laggardly, inconsistently and non-synchronously issued lead to the confusions and troubles in firm’s GMP implementation. The lack of clearly distinctions in government’s favorable treatments between GMP-approved firms and non-GMP-approved companies that lessen firms’ willingness to achieve GMP certificates In summary, to be able to meet the defined target of 100% GMP-qualified pharmaceutical manufacturers in Vietnam in the year of 2003, more significant efforts from Vietnam’s government (Ministry of Health) are needed. This is the main objective of this research paper, for examining the existing challenges and recommending some considering points for both firms and the government to take into account when thinking of GMP-implementation and GMP-compliance promotion. 4.2 Recommendations Recommendations are made to firms, government, and to further studies. Recommendations to firms Pharmaceutical manufacturers should comply with GMP standards because of the reasons hereunder: In this fiercely competitive market, quality is crucial to firms’ survival and development. GMP helps build quality into firms’ products. GMP is recognized and enforceable by governmental authorizations, thus, firms have to comply with GMP sooner or later. Moreover, only with GMP-complied certificate, firms can penetrate their markets beyond local saturated market. Thus, how to overcome the aforementioned challenges in implementing GMP standards? The followings are some recommendations to firms: To overcome financial shortage: Merging together: As currently, almost every province in Vietnam has its own pharmaceutical manufacturer. These provincial firms usually have revenues less than one million U.S. dollar (from appendix E, there are 14 firms having revenues less than one million U.S.$, accounting more than 50% of the total considered firms). Thus, they themselves should think of merging together to be stronger in both human and financial capitals. If facing conflicts in merging together, firms can propose that solution to the upper level management (the government). This issue is also mentioned in the recommendations for government hereafter. Advantages: Be stronger in both human and financial capitals. Disadvantages: How to make the decisions relating to the location, facilities, personnel and alike. However, these challenges can be solved based on clear macro and micro strategies set by the government (in state-owned firms) or based on a clear business vision and win-win solutions set by all parties. Privatization (for state-owned firms only): In case that the government looses control or is incapable to control the merging, state-owned provincial firms may propose another solution that is privatization to become private companies or stock-based companies. Advantages: Have stronger motives in implementing GMP for their own competitive advantages. Also, they can collect more capital from employees, outsiders (in stock-based option), or from investors, new owners (in selling-out option). Disadvantages: May not be allowed by the government. Seeking governmental financial supports: Asking helps from the government for low interest rate loans aiming at encouraging GMP implementation (with the Ministry of Health’s appeal). However, before making the decision for taking any loan, small firms should consider carefully the potential benefits gained by implementing GMP, especially in the short term as the initial seems not too smoothly in terms of cost, sales and alike, such as whether they are sure to have new contracts, new markets when complied with GMP? If they are not sure and the prospective seems too gloomy, they should think of stepping out of the industry because GMP will become regulation sooner or later. To overcome the qualified-personnel shortage: GMP well-trained personnel: + Ask for helps from consultants, experts mainly from two sources: officers of the Ministry of Health, and well-trained GMP experts in foreign-owned firms who are Vietnamese nationals and willing to devote to the nation’s pharmaceutical industry. + Benchmark from other GMP-complied firms by establishing good relationship among rivals. + Cooperate for mutual benefits and build a GMP forum, may be virtual forum in the simplest form of a mailing list, to share and solve problems. + Try to send at least one key person per firm to be formally trained about GMP. The tuition may be less than one percent of the total investment on one production line when implementing GMP. However, the benefits seem far from expectations. It can help save time, save money by avoiding numerous mistakes that would occur during the implementing period. High qualified technical personnel: + Reconsider the human resource policies in terms of recruiting, compensation, rewarding and alike, to be able to recruit and retain the qualified technical staff. + Usually, firms want to employ experienced potential employees. However, experience needs a working environment to be built. Thus, firms should be willing to recruit fresh graduates and offer on-the-job training. By doing that way, firms will have qualified technical staff years later. + Also firms should cooperate with universities by giving students opportunities to practice at firms, granting top students scholarships if they are willing to work for the companies when graduated. Information Accessing: Firms should keep in mind the importance of knowledge and information and do not devaluate their roles in running a business successfully. Firms also need to be more active in finding and contributing useful information such as tactics, how-to-do advice for mutual benefits. Last but not least, if firms can overcome financial and personnel shortages, then, in the implementing process, they may still face mistakes. Thus, the following tactics are recommended for successfully and effectively implementing GMP. Ten principles of GMP implementation: (Kathy Constantine, 2000) Writing step by step procedures that provide a roadmap for controlled and consistent performance: Written procedures are essential to the consistent functioning of the company. When writing them, make sure that they are clear, concise, easy to understand, and logical. Having well conceived, well-written, and well-packaged procedures is the first step toward GMP compliance, and controlled and consistent performance. Carefully following written procedures to prevent contamination, mix-ups, and errors: The written procedure is the most valuable tool that one have at his or her disposal to ensure product quality. A written procedure is a well thought out plan to help one attain the consistent quality in his or her work. Written procedures are as important to the experienced veteran as they are to the newly hired employee. The written procedure is the key to ensure compliance with the GMP Regulations. Written procedures are the roadmap to quality. Promptly and accurately documenting work for compliance and tractability: Before any product is released to the market, a complete check of its records is made to make sure the product meets the quality standards. When receiving a customer complaint, the product history records become very important documents. They allow the responsible person to carefully examine each step of the manufacturing process to determine the seriousness of the complaint and decide what action should be taken. Proving that systems do what they are designed to do by validating work Do not totally believe in written procedures. Sometimes, employees do not properly follow written procedures. Thus, do the validating works periodically to ensure everything happen as expected. Integrating productivity, product quality, and employee safety into the design and construction of facilities and equipment GMP is a goal common to every food, drug, medical device and cosmetic manufacturer. The responsibility for achieving this important goal and making GMP a "productive lifestyle," not just a regulation is shared by many people in many different ways. For example, one of the personal GMP responsibilities is to carefully follow the written procedures. Another is to promptly and accurately document the works. And a third way to "stay on target" in meeting GMP responsibility is to properly maintain the facilities and equipment. This third GMP responsibility is very important to company productivity, employee safety and product quality. Four key points are suggested to be kept in mind as following: Provide Adequate Space - A lack of space in the manufacturing area can cause confusion in the work flow, and this could possibly have an adverse effect on company productivity. A lack of space can also cause unnecessary traffic in the work area which can endanger employee safety. And finally, a lack of space could affect the product quality by causing cross contamination of product components or mix-ups and errors in labeling and record-keeping. Control Internal Environment - Another important area that company must constantly maintain is the internal environment such as the air, water, lighting, ventilation, temperature and humidity in our plant. Written procedures and standards are developed to ensure the proper maintenance and control of company’s internal environment. The plant sanitation program is one example of the "built in" controls used to minimize the chance of contamination, mix-ups or errors in the manufacturing area. It is very important that everyone knows and understands his/her personal responsibility in complying with plant sanitation standards. Inspect and Maintain Equipment - The routine inspection and maintenance of equipment is another important factor in applying GMP to the workplace. The proper maintenance of equipment requires that certain indicators are frequently checked to make sure all equipment is operating properly. Keep Accurate Records - GMP requires that accurate records concerning each piece of major equipment are kept. The "equipment logs" tell such important information as: when the equipment was used, what it was used for, when it was cleaned, inspected or repaired, and who do it and how it was done. This important information helps control the proper use and maintenance of equipment and helps prevent contamination, mix-ups, and errors. Properly maintaining facilities and equipment It is important that the company has a maintenance schedule for buildings and equipment. The company should identify what areas require regular maintenance in order to prevent contamination, mix-ups, and errors, and write procedures prescribing the maintenance. Additionally, it is possible that an unexpected event (such as extreme weather) would cause deterioration of the facility and equipment and require emergency maintenance or repairs. These must be immediately completed before production can resume if the damage could potentially contaminate the products. It is everyone's responsibility to follow established maintenance schedules, and to be on the lookout for new evidence of necessary maintenance. By doing this firm can maintain its good image and stay profitable. Clearly defining, developing, and demonstrating job competence GMP requires that everyone be competent in his or her jobs. In addition, firm’s customers depend on firm’s employees’ competence. When someone buys one of firm’s product, they are putting their trust in firm’s ability to manufacture quality products. It is important to remember that competence takes on a different meaning for every person, depending on the jobs, duties, and responsibilities he or she has. Therefore, the challenge is to clearly identify, define, develop, and demonstrate the individual job competencies that relate to each employee’s job. How can one meet this challenge and do his or her job right the first time and every time? The followings are some recommendations: Identifying Your Job Competencies In order for employees to properly identify their job competencies, they must be specific. Don't let the list of "must knows" and "must dos" get too long. Try to limit the "must knows" to 16 specific areas, and the list of "must dos" should be kept to under 16 basic skill requirements. Defining and Developing Your Job Competencies Once the "must knows" and "must dos" have been identified, employee then need to properly define each one and begin to develop his or her competency in each area. Through education, employees can learn about a subject so they can understand the who, what, and why. Training teaches them the when, where, and how to perform their various job responsibilities. One of the most important things to remember as defining and developing the "must knows" and "must dos" is to be patient! No one is, or ever will be, totally competent in his or her job. Technology changes too fast and there is always room for improvement. Demonstrating Your Job Competence Employee must demonstrate his or her job competence every day by producing quality products in a safe and efficient manner. He or she must take his or her knowledge and skills and apply them in the "real world". Then and only then can he or she claim to be a competent employee. The job competence is critical to making GMP a "lifestyle" at a particular company. GMP needs competent people as well as every company needs those who know how to do the job right the first time and every time Protecting products against contamination by making cleanliness a daily habit When implementing a Plant Sanitation Program, an important question that usually be asked is - "How clean must we keep ourselves and our workplace?" The answer to this question is not that simple, mainly because the degree of cleanliness depends on the type of products manufacturing. Therefore, firm must design its Plant Sanitation Program to meet the standards of cleanliness necessary to insure the integrity of the specific product it manufactures. The fight against contamination is a constant battle -- requiring the ever-ending energy and attention. Building quality into products by systematically controlling components and product related processes such as manufacturing, packaging, and labeling, testing, distribution, and marketing Those who work in the food, drug, cosmetic and medical device industries know that the health and safety of their customers depend on the quality of their products. It is very important, therefore, that they must do their best to build quality into each product they produce. Recognizing that product quality is so important to the customers, companies need to ask themself two key questions: 1) What is Quality? and 2) How can we build quality into our products? The first question can be answered by defining quality as the absence of defects - defects which are most often caused by contamination, mix-ups, and errors. Since the best way to prevent contamination, mix-ups, and errors is to follow the guidelines of Good Manufacturing Practice, let's see how GMP can help answer the second question. Through GMP four critical areas can be identified in the manufacturingoperation where firm must establish effective controls to assure product quality. There are key elements in each of these critical control areas that help build quality into firm’s product mentioned hereunder. Control of Components. Check all of the components when they enter the plant to be sure they meet the purchasing specifications. All components must be tagged and stored in quarantine, sampled and tested according to your written procedures, and approved or rejected prior to release for manufacturing. Control of the Manufacturing Process. Company establishes records and procedures to assure product quality and uniformity. For each product it has master records that outline the specifications and manufacturing procedures, individual batch or history records, and written schedules and procedures for cleaning and maintaining equipment. Packaging and Labeling Controls. Since packaging and labeling are the areas where most mix-ups and errors occur, firm must be sure to: (i) assign a control number to each batch or lot to help trace the manufacturing history of each product, (ii) inspect the packaging and labeling areas before each new batch or lot is processed (this helps assure that the area does not contain materials from a previous run), and (iii) follow the written procedures and carefully document the works. Holding and Distribution Controls. Company controls for any contamination, mix-up, or errors that might have occurred during the manufacturing process by quarantining and testing the finished product before it is approved for release, establishing written procedures for handling and storing the products, and keeping well documented distribution records to help trace the shipment of the products should a complaint or problem arise. Moreover, remember that building in quality is the responsibility of everyone. Every person and every job in the company has a direct effect on the quality of products. Firm must constantly control for quality by doing jobs right the first time. Conducting planned and periodic audits GMP is a government regulation which establishes minimum standards that prevent firm’s products from being adulterated or misbranded. More important, GMP is the "lifestyle" at companies to achieve the three business goals of Company Productivity, Product Quality, and Employee Health and Safety. Now, how does the government know and how do firms know that they are achieving these goals of GMP? The answer is by conducting planned and periodic audits of the job performance. Besides external audits conducted by the authorization agencies, the company should conducts its own internal audit to evaluate how well it is living a lifestyle of GMP. Since everyone is ultimately responsible for GMP in the company, each employee should personally audit his or her own job performance every day. Let's review several of the key areas should be concerned with in conducting the personal audit. The following questions are designed to help employees audit their own job performance. Written Procedures Are there written procedures that provide me with a "blueprint" or "step by step instructions" for performing my job? Do I know and understand these procedures and do I carefully follow them? Do I regularly check my written procedures to make sure they are accurate and up-to-date? When I see an easier or better way to do my job, do I go ahead and deviate from my written procedures or do I discuss the change with my supervisor first? Job Competence Do I have the necessary education, training, or on-the-job experience to perform my assigned function? Have I identified and learned the "must knows" for my job? For example, do I know and understand the safety standards and regulations that apply to my job? Have I identified and acquired the necessary skills or "must dos" that specifically relate to my job? For example, do I keep accurate records and do I safely operate my equipment? Do I demonstrate my job competence by performing my job right the first time and every time? Documentation and Validation Do I carefully document my work by recording all necessary information immediately on the batch or history record? When and where a signature is required, do I sign my name legibly and inink? When the batch or history record requires it, do I mark down the date andthe time I started or completed the job? Do I validate my work by checking and double checking all critical operations to make sure there are no mix-ups or errors? Sanitation and Cleanliness Do I practice good personal hygiene? Do I always wear the proper clothing in the workplace? Do I wear the clothing properly? Do I keep my equipment and tools clean and store them in the proper manner? Do I quickly report any conditions in our plant or with our equipment that could be potential sources of product contamination? Maintenance of the Workplace Do I have adequate space in my work area to safely and effectivelyperform my assigned job? Do I minimize the chance of product contamination, mix-ups and errors by helping to control the Internal Environment of the plant? Do I perform routine maintenance on my equipment and do I check to seeif my measuring and testing equipment has been properly calibrated? Do I keep accurate equipment logs and do I promptly report any maintenance problems to the supervisor? Quality Control Do I carefully control the components used in the manufacture of our products? Do I pay close attention to the control numbers assigned to our product components and to the individual lot numbers assigned to our finished products? Do I know and understand what responsibility the Quality Assurance or Quality Control Department has for assuring Product Quality? Do I know and understand my responsibility to build quality into our products? Recommendations to government: With regards to firms’ financial shortage: Considers the option of merging or privatizing small state-owned firms. This issue should be included in setting strategies for pharmaceutical industry (should enrich firms’ capabilities, not enlarge them). Helps appeal the government (beyond the Ministry of Health’s authority) to grant low interest rate loans to pharmaceutical manufacturers, especially selected state-owned firms, in order to encourage the GMP implementation. Encourages state-owned firms to form joint ventures with foreign firms in order to be stronger in capital and production capabilities, especially in producing specialty drugs that are still imported presently. However, the government and the firms them