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

th 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 themselves should be careful in negotiating and monitoring as well as learning in forming the joint ventures. As it is a common situation in Vietnam that almost joint ventures are going to be wholly foreign-owned companies as a result of the immature management knowledge and skills of Vietnamese parties. With regards to firms’ GMP personnel shortage: Funds can be collected from fees for consulting, approval, auditing services conducted by departments belonged to the Ministry of Health, that are almost free now. Comparing to ISO 9000 consulting service that is normally U.S.$15 – 20 thousands per company (conducted by local consulting firms), thus, assume that there are ten companies asking for consulting services in a year, the fund can be added U.S.$200,000. This fund will be managed and used by the Ministry of Health, probably a particular GMP-related department. Then, that department will have the responsibility to conduct GMP training for representatives from local pharmaceutical firms. The training fee may be collected also or can be subsidized by the aforementioned fund. Building information sources: With the aforementioned fund, the Ministry of Health can send more key persons to be trained formally and that will be consultants to help firms in implementing GMP standards. A web site can also be build and made it a virtual GMP forum and database that are freely accessed by firms. The important point is that “What are there on the web site?” It is suggested at least the followings should be there on the web site: A mailing lists of GMP consultants, officers, experts in firms and the like, A database comprising all the guidelines, circulars issued by the Ministry of Health concerning GMP, and Tactics, pitfalls, best practices posted by consultants, officers, experts in firms that are collected during their working experiences. Policy making: Policies can be better made with feedback from the influenced persons such as firms. It can be easily done by posting the potential policies online and asking feedback from concerning people. One additional critical point is that, the policy makers should try to get rid off the negative habit of issuing too general and vague official documents by having them read by their targeted persons before issuing. After reading, if those persons still can not understand exactly and specifically what mentioned in the documents, then, these documents should be revised and rewritten. Granting privileges for GMP-complied firms: Currently, those privileges granted to GMP-complied firms are presented hereunder: 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. However, they are too vague and ambiguous and thus, are recommended to be revised as followings: Be prioritized in participating in bidding both at national and international level, to supply pharmaceuticals for national health programs. It is suggested that the first condition to be considered in allowing firms to take part in bidding for supplying medicines to any programs is GMP-compliance. Aside from those, some additional privileges are recommended such as: 100% tax-cut for local firms in the GMP implementing period, then, 25% tax-cut when complied with GMP. Control import quota for medicines that can be produced by local GMP-complied firms in order to reserve the local market for them. That is, the amount to be imported equals the forecasted annual consumption amount minus the production capabilities of local GMP-complied manufacturers in a particular year. Moreover, for some certain drugs that are produced much better in terms of quality and productivity by GMP-complied firms, they can be allowed to go to market only with an additional sentence of “GMP-approved Company” in the labels. Consumer education: Educating the community through the media, hospitals, health-care programs about the GMP awareness. Considering the application of the other g-P such as GPP (Good Pharmacy Practices), GCP (Good Clinical Practices) and GPP (Good Prescribing Practices). Supporting local pharmaceutical manufacturers: Controls the licenses for establishing wholly foreign-owned pharmaceutical manufacturers, especially when their intended products can be produced by local GMP-complied firms. Plans and executes stricter battles towards fake drugs, illegally imported medicines. Controls the import quota and encourage exports. Grant favors for local GMP-complied firms in supplying drugs for national programs, hospitals and alike. That is, foreign suppliers will be considered only if local suppliers are incapable to supply these medicines. Recommendations to further study Due to the limited time allowance, some interesting extents are not included in this paper. Thus, it is recommended for further studies. These issues are: Mutual recognition of GMP certifying in ASEAN region: How to build a unique GMP standard for ASEAN members that satisfies all members and suitable to the local actualities in ten countries? If a unique GMP standard for ten countries of ASEAN can not be achieved, then, how to establish the agreement between the national GMP registrars to obtain to mutual recognition for GMP certificates? Quantitative research on benefits gained when implemented GMP Conducting research on some or all GMP-approved pharmaceutical manufacturers in Vietnam, for example, in terms of finding out the quantitative benefits gained by complying with GMP standards, such as percentage increase in revenues, percentage saving in re-production or contaminated drugs, and the like. REFERENCES Carl Goodier, 1999. Thai Code of GMP for Cosmetics. Azimuth Company Ltd., Thailand Dr. Cao Minh Quang and Dr. Dang Van Giap, 2000. Good Manufacturing Practices for Pharmaceutical Products. Ministry of Health, Vietnam Dra. MSc. Andajaningsih, 1996. ASEAN Good Manufacturing Practices guidelines. Health Publisher, Vietnam 1997 M. Doyle, 1999. Vietnam Drugs and Pharmaceuticals. U.S. and Foreign Commercial Service. Dann M. Michols, 2000. Risk Classification of GMP Observations. Canada. David Hoyle, 2001. ISO 9000:2000 – A significant change for Quality Management Consultants? Transition Support Ltd., IEE Dr. Ludwig Huber, National Healthcare Organizations and Authorities with Impact on Analytical Laboratories, 2000 James D. Destefani, 1997. A Current Good Manufacturing Practices (CGMP) primer. U.S FDA John Rushing, 1999. Prerequisite Programs and Good Manufacturing Practices (GMPs). U.S Kathy Constantine, 2000. Good Manufacturing Practices - The Quest For Quality. National Nutritional Foods Association Northwest Region Kenneth R. Foster, Ph.D., PE and Jordan D. Haller, MD, 1998. Regulation of Medical Devices and Drugs. Philadelphia Maureen Breitenberg, 1993. More questions and answers on the ISO 9000 standard series and related issues. NISTIR, Gaitherburg. OECD, 1999. Quality Assurance and GLP. Paris U.S FDA, Good Manufacturing Practice (GMP) Requirements Quality System (QS) Regulation Information, 2000. U.S FDA, Lists of Documents that Describe The U.S. Pharmaceutical GMP Regulatory System, 2000. W.Fred Hooten. A brief History of FDA Good Manufacturing Practices, 1996 APPENDIXES A. ASEAN GMP ASEAN GMP Guidelines (Extracted from ASEAN GMP Guidelines, the third draft in 1996, by Dra. MSc. Andajaningsih) General Provisions The GMP for drugs is aimed to ensure that products are consistently manufactured to meet specified quality appropriate to their intended use. It is concerned with all aspects of production and control. General Principles In the manufacturing of drugs, overall control is essential to ensure that consumers receive drugs of high quality. Haphazard operations cannot be tolerated in the manufacture of products intended to save life or to restore or to preserve health It is not sufficient that the finished product passes testing protocols, but quality must be built into each stage of the production process. Sole reliance should not be placed on any test for assurance of quality. All products should be manufactured under carefully controlled and monitored conditions. The good practices given in this guidelines should be considered as flexible guidelines with the objective of ensuring that the products are of the nature and quality intended; whenever necessary, they may be adapted to meet individual needs, provided that established standards of product quality are still achieved. Definition, which gives some explanations of specific terms Personnel There should be an adequate number of personnel of all levels having knowledge, skill and capabilities relevant to their assigned functions, in good mental and physical health to be able to execute their duties professionally and properly. Moreover, these personnel should have the attitudes to achieve the goal of GMP. Organization, Qualification and Responsibilities Mentioning the requirements for organizational structure of the company, the required qualifications of some kinds of managers and personnel’s responsibilities. Typical examples are outlined hereunder: The organizational structure of the company shall be such that the production and the quality control are headed by different managers, neither of whom shall be responsible to the other. Each should be given full authority and facilities necessary to execute his or her duties effectively. Neither should have any interests outside the manufacturer’s organization that prevent or restrict their devotion to the assigned responsibilities or which may be considered to entail a conflict of personal or financial interest. The production manager should be a qualified pharmacist and he or she should have other responsibilities in order to share with the quality control manager and the person responsible for engineering relating to quality. The quality control manager should be a qualified pharmacist as well. Moreover, he or she should clearly define the field of work and the method of deputizing for his or her absence. The responsibilities placed on any one employee should not be so extensive as to cause risk to the achievement of quality. Training Training in GMP should be on a continuing basis and with adequate frequency to assure that employees remain familiar with the GMP requirements relevant to their functions. Records of personnel training in GMP should be maintained and the effectiveness of training programs should be assessed periodically. Premises The premises for manufacturing should be of suitable size, design, construction and location to facilitate proper operation, cleaning and maintenance. The individual areas should be adequate so that any risk of confusion, cross-contamination and other mistakes that could adversely affect the quality of drugs could be avoided. Equipment Equipment used in manufacturing of drug products should be of appropriate design and construction, adequate size and suitably located in order that the quality designed into each drug product can be assured and reproducible on a batch-to-batch production basis and to facilitate its cleaning and maintenance. Under this item, three sub-items are mentioned as following: Design and Construction Installation and Location Maintenance Written procedures should be established and followed for maintenance of equipment. A written record of major equipment maintenance and use should be included in individual equipment logs which also identifies the date, time, product, strength and batch or lot number of each batch processed. Sanitation and Hygiene High level of sanitation and hygiene should be practiced in every aspect of manufacturing drug products. The scope of sanitation and hygiene covers personnel, premises, equipment and apparatus, production materials and containers, and anything that could become a source of contamination to the product. Potential sources of contamination should be eliminated through an integrated comprehensive program of sanitation and hygiene. Personnel, which outlines some requirements relating to the hygiene assuring including the instruction of washing hands and changing clothes before entering production areas. Premises Sinks should be excluded from sterile areas. If installed in sterile areas, they should be of a suitable quality, equipped with overflow protection device, and be supplied with water of at least potable quality. Waste materials should not be allowed to accumulate. It should be collect in suitable receptacles for removal to collection points outside the buildings and disposed of safety and in a sanitary manner at regular and frequent intervals. Rodents, insecticides, fumigating agents and sanitizing materials should not be permitted to contaminate equipment, raw materials, packaging materials, in-process materials or finished products. Equipment, emphasizing that record of cleaning, sanitizing, sterilization and inspection prior to use should be maintained. Qualification and Validation of Sanitation and Hygiene Procedures In all instances, the sanitation and the hygiene procedures should be validated and periodically assessed to ensure that the effectiveness of the operation meets the requirements. Production Production should follow defined procedures known to be capable to provide assurance of consistency yielding drug products, which conform to their intended specifications. Starting Materials All incoming, out-coming and remaining materials should be recorded. The record should contain information on supplies, batch or lot number, date of receipt or issuance, date of release and date of expiry if any. Each delivery or batch of starting materials should be assigned a reference number, which will identify the delivery or batch throughout storage and processing. All rejected starting materials should be conspicuously identified, placed separately and should be destroyed or returned to the supplier as soon as possible. Process Validation emphasizes that all production procedures should be properly validated. Contamination The presence in a drug product of any chemical or microbiological contaminant, which may have the potential to adversely affect the patient’s health or impair the therapeutic activity of the product, is unacceptable. Batch and Lot Numbering System that guides how the batch and lot numbers are assigned. Weighing and Dispensing For any weighing or measuring operation two persons should independently verify the correctness of the identity and amount of weighed or measured materials. Returns Processing All required in-process controls should be accurately recorded at the time of performance. Sterile Products The processing of sterile products requires three kinds of rooms of different environment, from a room consisting of two separate areas each for removing outer garments and for wearing sterile clothing, to the strictest hygienically conditioned room that meets the predefined hygienic criteria. Some specific requirements relating to the personnel’s clothing, premises, equipment, processing, approaches of sterilization, and the like. Packaging, mentioning: Pre-coding of components, Line clearance, In-process control, Operating practices, and the like. Recovered Materials Returned Goods Finished Product Quarantine and Delivery to Finished Stock Control Record for Shipment of Drug Products Storage of Starting Materials, Intermediates, Bulk Products and Finished Product Contract Manufacture Quality Control Quality control is an essential part of GMP to provide assurance that the products will be consistently of a quality appropriate to their intended use. The involvement and commitment of all concerned at all stages are mandatory towards the achievement of this quality objective from the starting of manufacturing to the distribution of the finished product. An independent quality control unit should be established. General Provisions Control Laboratory The Good Laboratory Practices is included in this part, mentioning the following items: Premises Personnel Equipment Reagents and Culture Media Reference Standards Specifications and Testing Procedures Records of Analysis Retained Samples Validation The quality control unit should conduct the following validation tests: Validation of assay procedures Calibration of instruments Control of Starting Materials, Intermediate, Bulk and Finished Products, including: Specifications Sampling Test requirements Environment control In-process control Packaging control Re-testing of approved materials Reprocessing Quality Control Evaluation on Production Procedures The quality control unit should participate in the development of the master processing procedure and master packaging procedure for each batch size of a drug product to assure uniformity from batch to batch manufactured. Any changes and adjustments in the master processing procedure or master packaging procedure should have quality control approval prior to execution in production. Production Record Review Stability Study A stability-testing program should be designed to assess the stability of characteristics of drug products and to determine storage conditions and expiration date. The written program should be followed and included: sample size test intervals based on statistical criteria for each attribute examined to assure estimate of stability; storage conditions; reliable, meaningful and specific test method; testing of the product in the same packaging form in which the product is marketed; and testing of the product for reconstitution before and after it has been reconstituted. Product Complaints Records of complaints and their handling should be made and include the following information name, dosage form, package form and batch number; date, place of occurrence, name and address of complaint; and nature of complaints in detail; The product complaint records should be maintained for a specific period Returned Goods Vendor Rating, addresses that all the established suppliers should be evaluated periodically. Self Inspection The purpose of self-inspection is to evaluate the manufacturer’s compliance with GMP on all aspects of production and quality control. The self-inspection program should be designed to detect any shortcoming towards the implementation of GMP and to recommend the necessary corrective actions. Self-inspection should be performed routinely. A team consisting of personnel who can evaluate the implementation of GMP objectively should be appointed. The procedure and record for self-inspection should be documented. Five sub-items hereunder are included: Item for Self-Inspection, including personnel, premises, storage of starting materials and finished products, equipment, production, quality control, documentation, and maintenance of building and equipment. Team of Self-Inspection Management should appoint a team of self-inspection consisting of at least three members who are experts in their own fields and familiar with GMP. The members of the team may be appointed from inside or outside the company. Coverage and Frequency of Self-Inspection Self-inspection may be conducted by part of unit depending on the company requirements. However, a complete self-inspection should be conducted at least once a year. Self-Inspection Report, mentioning the three following sub-parts: self-inspection report, evaluation and conclusion, and recommended corrective actions. Follow-up Action Handling of Product Complaint, Product Recall and Returned Drug Products Product Complaint and Report A product complaint and report may relate to the quality, adverse reaction or other therapeutic effect of the product, thus, all complaints and reports should be thoroughly investigated and evaluated. And there should be a follow-up action after investigation and evaluation of the complaint and report are completed. Product Recall A product recall is a process of withdrawing one or more batches or all of a certain product from market distribution. And a product recall is instituted following discovery of a quality defect or if there is a report of serious adverse reaction of a drug product which may cause health risk. Returned Drug Product The manufacturer should establish a procedure for holding, investigating and analyzing the returned drug product and deciding whether the product may be reprocessed or should be destroyed after a critical evaluation made. Procedure for Handling Returned Drug Product, including the following steps: identifying and recording the quality of returned drug product; holding the product in quarantine; investigating, test and analysis of the product by quality control; critical evaluation before the management decides whether the product may be reprocessed or not, and additional test for a requirement of the reprocessed product Handling of Rejected Returned Drug Products Returned drug products that can not be reprocessed should be destroyed. A procedure for destruction is outlined which includes precautionary measures to prevent pollution of the environment and misuse of the material or product by unauthorized persons. Documentation The handling of returned drug product and the follow-up actions should be documented and reported. If the product is to be destroyed, the documentation should include a certificate of destruction, which is dated and signed be the persons performing and witnessing the destruction. Documentation Documentation in any manufacturing process is a part of management information system, which include specifications, procedures, methods and instructions, reports and records and other documents which are required for planning, organizing, controlling and evaluating the activities of drug manufacturing. General Provisions Specifications, which cover specifications for raw materials, packaging materials, intermediate products, bulk products and finished products. Production Documents, mentioning Master production documents, which contain the production formula of a product in its dosage form and strength irrespective of the batch size. Master processing procedures, which are documents form that copies are made for use in the processing of individual batches of product. Master packaging procedures, which are documents form that copies are made for use in the packaging of individual batches of product Batch processing records, and Batch packaging records Quality Control Documents The documents required in quality control are: Quality control procedures and test methods as the procedure for sampling is a very important document in quality control, and Records of analysis and test report noticing that the records of stability test results are usually presented separately. A test report may take the form of certificate of analysis. Warehouse and Distribution Documents The storage and distribution of drug products should be documented. The most important documents in this area are inventory card and distribution record. Inventory card contains record of the quantity received, issued and balance stock of the starting material, intermediate product, bulk product and finished product at any time. It is recommended to use different color of inventory card for each group of product. Moreover, the inventory card should be a tool for the application of first-in-first-out principle. Deviation from this principle should be for a short term and only when approved by an authorized manager. Record of Distribution of Finished Product, covering the following details: name and address of consignee; delivery order date and number; name, dosage form and strength of the product; quantity delivered; product batch number; expiration date where applicable, and special storage requirements or precautionary measures to handle the product. Documents for Maintenance, Cleaning and Monitoring of Manufacturing Areas and Equipment Documents for Handling of Product Complaints, Product Recall, Returned Drug Products and Destruction of Drug Products Documents for Specific Equipment Procedure and Record of Self-Inspection Guidelines and Records of Personnel Training on GMP B. A typical Organizational Structure of GMP-approved firm Plan Manager Secretariat & Administrative Financing & Accounting Quality Manager Production Manager Sales Manager Quality Assurance R&D Dept. Production Technical Services Materials Management Distribution Marketing - Quality Control - Validation - Stability - Production Dept. - Registration - Workshop 1 - Workshop 2 … - Technical Utilities - Maintenance - Purchasing - Warehouse - Pro-Introducing Network - Retailed Network - Advertisement - Medical Representatives C. ASEAN and other National GLP and GMP Authorities Australia Australian Department of Health P.O. Box 1 00 Woden, A.C.T 2606 TGA – Therapeutic Goods Administration URL: Burma Director_General Department of Health Ministry of Health 36 Theinbyu Street Rangoon Cambodia No. 128 Kampuchea Krom Boulevard Phnom Penh Telephone: (855-23)426 841 Canada Drugs Directorate Health Protection Branch Health and Welfare Canada Tunney’s Pasture Ottawa ON K1A 0L2 URL: China Bureau of Drug Administration Ministry of Public Health 44 Hou Hai Bei Yan 100725 Beijing Europe Eudra (European Drug Regulatory Authorities Network) URL: Indonesia Jalam HR Rasuna Said Kav 4 - 9 Jakarta URL: Japan Pharmaceutical Affairs Bureau Ministry of Health and Welfare 1-2-2, Kasumigaseki, Chiyoda-ku Tokyo 1 00 URL: Malaysia National Pharmaceutical Control Laboratory Ministry of Health Malaysia P.O. Box 319 46730 Petaling Jaya, Selangor Philippines Department of Health URL: Singapore Director, Medical Services Ministry of Health Palmer Road Singapore 2 Ministry of Health URL: Thailand Secretary-General of Food & Drug Administration Ministry of Public Health Devevesm Palace Bangkok II Ministry of Public Health URL: United Kingdom Department of Health Medicines Control Agency (MCA) Market Towers 1, Nine Elms Lane London SW8 5NQ URL: United State of America Food and Drug Administration Center for Drugs and Biologics 5600 Fishers Lane Rockville MD 20857 URL: Vietnam Ministry of Health URL: D. Web-sites relating to some of GMP regulations EU GMP Guidelines URL: FDA’s Current GMP in Manufacturing, Processing, Packaging, or Holding of Drugs URL: FDA’s Current GMP in for Finished Pharmaceuticals URL: Key National and International Standards, Laws, Regulations and Guidelines URL: GMP Institute – A Division of ISPE – A link to many useful web address related to GMP URL: E: List of local pharmaceutical manufacturers and their relevant data 1. English name: 2-9 PHARMACEUTICAL ENTERPRISE Vietnamese name: XI NGHIEP DUOC PHAM 2-9 Address: 136 Ly Chinh Thang Street, District 3 Location: HO CHI MINH city Phone: 84-8-441953 Fax: 84-8-224408 Capital: 14369 Mil.VND Labour: 547 Revenue: 25403 Mil.VND Branch: Production of chemicals and articles thereof Activity: Medicines producing and trading. 2. English name: 3-2 PHARMACEUTICAL ENTERPRISE Vietnamese name: XI NGHIEP DUOC PHAM 3-2 Address: 10 Cong Truong Quoc Te Street Location: HO CHI MINH city Phone: 84-8-230512 Capital: 9718 Mil.VND Labour: 500 Revenue: 26345 Mil.VND Branch: Production of chemicals and articles thereof Activity: Production of and trading in medicines 3. English name: BINH THUAN PHARMACEUTICAL AND MEDICAL MATERIALS CO. Vietnamese name: CONG TY DUOC, VAT TU Y TE BINH THUAN Address: 114 Nguyen Hoi Street, Phan Thiet Town Location: BINH THUAN province Phone: 84-4-21691 Capital: 1039 Mil.VND Labour: 203 Revenue: 6376 Mil.VND Branch: Production of chemicals and articles thereof Activity: Import, export pharmaceutical products, production of medicines. 4. English name: DISTRICT 5 PHARMACEUTICAL ENTERPRISE Vietnamese name: XI NGHIEP CHE BIEN DUOC QUAN 5 Address: 99 Luong Nhu Hoc Street, District 5 Location: HO CHI MINH city Phone: 84-8-559615 Capital: 3118 Mil.VND Labour: 87 Revenue: 914 Mil.VND Branch: Production of chemicals and articles thereof Activity: Producing and processing pharmaceutical products. 5. English name: DISTRICT 8 PHARMACEUTICAL CO. Vietnamese name: CONG TY DUOC PHAM QUAN 8 Trade Name: EDPHARCO Address: 30-32 Phong Phu Street, District 8 Location: HO CHI MINH city Phone: 84-8-550908 Capital: 2515 Mil.VND Labour: 81 Revenue: 10657 Mil.VND Branch: Production of chemicals and articles thereof Activity: Producing and trading in medicines. 6. English name: DONGTHAP PHARMACEUTICAL CO. Vietnamese name: CONG TY DUOC PHAM TINH DONG THAP Trade Name: D.P.f IMEXPHARM Address: 4 30/4 Road, Cao Lanh Town Location: DONG THAP province Phone: 84-67-51620 Capital: 4512 Mil.VND Labour: 181 Revenue: 95975 Mil.VND Branch: Production of chemicals and articles thereof Activity: Manufacture and trade in pharmaceutical products. 7. English name: CUULONG PHARMACEUTICALS AND MEDICAL MATERIALS CO. Vietnamese name: CONG TY DUOC VA VAT TU Y TE CUU LONG Trade Name: PHARIMEXCO Address: 150 14/9 Road, Vinh Long Town Location: VINH LONG province Phone: 84-70-22533 Fax: 84-70-22779 Capital: 7965 Mil.VND Labour: 378 Revenue: 121000 Mil.VND Branch: Production of chemicals and articles thereof Activity: Producing and trading in medicines. 8. English name: HATAY PHARMACEUTICAL CO. Vietnamese name: CONG TY DUOC PHAM HA TAY Address: 80 Quang Trung Street, Ha Dong Town Location: HA TAY province Phone: 84-34-24432 Capital: 2921 Mil.VND Labour: 205 Revenue: 13016 Mil.VND Branch: Production of chemicals and articles thereof Activity: Manufacturing and trading in pharmaceutical. 9. English name: HATHANH PHARMACEUTICAL CO. LTD Vietnamese name: CONG TY TNHH DUOC PHAM HA THANH Address: 103 K 10 A Bach Khoa Ward Location: Ha Noi; Phone: 691891 Capital: 200 Mil.VND Labour: 17 Revenue: 727 Mil.VND Branch: Production of chemicals and articles thereof Activity: Production of curative medicines. 10. English name: HOABINH PHARMACEUTICAL UNITED ENTERPRISE Vietnamese name: XI NGHIEP LIEN HOP DUOC HOA BINH Address: Dong Tien Sub-district, Hoa Binh Town Location: HOA BINH province Phone: 84-52187 Capital: 942 Mil.VND Labour: 254 Revenue: 3210 Mil.VND Branch: Production of chemicals and articles thereof Activity: Produce and trade in pharmaceutical products and medical equipment. 11. English name: NAMHA PHARMACEUTICAL UNITED ENTERPRISE Vietnamese name: XI NGHIEP LIEN HOP DUOC NAM HA Address: 228 Han Thuyen Street, Nam Dinh City Location: NAM HA province Phone: 84-35-49408 Capital: 1930 Mil.VND Labour: 222 Revenue: 5120 Mil.VND Branch: Production of chemicals and articles thereof Activity: Producing and trading in drugs of all kinds. 12. English name: NATIONAL MEDICINAL MATERIALS CO. NO.2 Vietnamese name: CONG TY DUOC LIEU TRUNG UONG 2 Trade Name: PHYTOPHARCO Address: 34 Nguyen Hue Street, District 1 Location: HO CHI MINH city Phone: 84-8-295752 Capital: 6400 Mil.VND Labour: 105 Revenue: 11055 Mil.VND Branch: Production of chemicals and articles thereof Activity: Production of medicines. 13. English name: NATIONAL PHARMACEUTICAL CO. NO.1 Vietnamese name: CONG TY DUOC PHAM TRUNG UONG 1 Address: Giap Bat Street, Dong Da District Location: HA NOI Phone: 84-4-643327 fax: 84-4-641366 Capital: 42411 Mil.VND Labour: 202 Revenue: 143877 Mil.VND Branch: Production of chemicals and articles thereof Activity: Production and trading in medicines. 14. English name: NATIONAL PHARMACEUTICAL ENTERPRISE NO.2 Vietnamese name: XI NGHIEP DUOC PHAM TRUNG UONG 2 Address: 9 Le Thanh Tong Street Location: HA NOI Phone: 84-4-256291 Capital: 13936 Mil.VND Labour: 705 Revenue: 42240 Mil.VND Branch: Production of chemicals and articles thereof Activity: Production of pharmaceutical products. 15. English name: NATIONAL PHARMACEUTICAL ENTERPRISE NO.24 Vietnamese name: XI NGHIEP DUOC PHAM TRUNG UONG 24 Trade Name: MEKOPHAR Address: 397/5 Ly Thuong Kiet Street Location: HO CHI MINH city Phone: 84-8-550363 fax: 84-8-290084 Capital: 17625 Mil.VND Labour: 547 Revenue: 86219 Mil.VND Branch: Production of chemicals and articles thereof Activity: Production of medicine. 16. English name: NATIONAL PHARMACEUTICAL ENTERPRISE NO.25 Vietnamese name: XI NGHIEP DUOC PHAM TRUNG UONG 25 Trade Name: UPC25 Address: 120 Hai Ba Trung Street, District 1 Location: HO CHI MINH city Phone: 84-8-295046 Capital: 15813 Mil.VND Labour: 514 Revenue: 45005 Mil.VND Branch: Production of chemicals and articles thereof Activity: Production of medicine. 17. English name: NATIONAL PHARMACEUTICAL ENTERPRISE NO.26 Vietnamese name: XI NGHIEP DUOC PHAM TRUNG UONG 26 Address: 343D Hung Vuong Street, District 6 Location: HO CHI MINH city Phone: 84-8-757043 fax: 84-8-752048 Capital: 10265 Mil.VND Labour: 381 Revenue: 24129 Mil.VND Branch: Production of chemicals and articles thereof Activity: Production of medicine. 18. English name: PHARMACEUTICAL TECHNOLOGY DEVELOPMENT CO.-HOCHIMINH CITY Vietnamese name: CONG TY KY NGHE PHAT TRIEN DUOC TP HO CHI MINH Address: 19 Nguyen Van Troi Street Location: HO CHI MINH city Phone: 84-8-440106 Capital: 8336 Mil.VND Labour: 165 Revenue: 40667 Mil.VND Branch: Production of chemicals and articles thereof Activity: Manufacture of medicines. 19. English name: SOCTRANG PHARMACEUTICAL UNITED ENTERPRISE Vietnamese name: XI NGHIEP LIEN HIEP DUOC SOC TRANG Address: 105 Hai Ba Trung Street, Soc Trang Town Location: SOC TRANG province Phone: 84-79-20512 Capital: 1800 Mil.VND Labour: 71 Revenue: 7231 Mil.VND Branch: Production of chemicals and articles thereof Activity: Produce and trade in pharmaceutical products 20. English name: SONLA PHARMACEUTICAL CO. Vietnamese name: CONG TY DUOC PHAM SON LA Address: Chieng Le Sub-district, Son La Town Location: SON LA province Phone: 84-22-52340 Capital: 1759 Mil.VND Labour: 133 Revenue: 2096 Mil.VND Branch: Production of chemicals and articles thereof Activity: Manufacture and trading in pharmaceutical products. 21. English name: THAIBINH PHARMACEUTICAL UNITED ENTERPRISE Vietnamese name: XI NGHIEP LIEN HIEP DUOC THAI BINH Address: Km 4 Highway 10, Thai Binh Town Location: THAI BINH province Phone: 84-36-31162 fax: 84-36-36497 Capital: 3813 Mil.VND Labour: 439 Revenue: 14624 Mil.VND Branch: Production of chemicals and articles thereof Activity: Produce and trade in pharmaceutical products. 22. English name: THANHHOA PHARMACEUTICAL ENTERPRISE Vietnamese name: XI NGHIEP DUOC PHAM THANH HOA Address: Quang Trung Street, Thanh Hoa Town Location: THANH HOA province Phone: 84-37-52282 Capital: 1167 Mil.VND Labour: 231 Revenue: 3557 Mil.VND Branch: Production of chemicals and articles thereof Activity: Medicines production. 23. English name: TUYENQUANG PHARMACEUTICAL UNITED ENTERPRISE Vietnamese name: XI NGHIEP LIEN HOP DUOC TUYEN QUANG Address: Tan Quang Street, Tuyen Quang Town Location: TUYEN QUANG province Phone: 84-27-22553 Capital: 1446 Mil.VND Labour: 211 Revenue: 3063 Mil.VND Branch: Production of chemicals and articles thereof Activity: Produce and trade in pharmaceutical products - medical equipment. 24. English name: YENBAI PHARMACEUTICAL ENTERPRISE Vietnamese name: XI NGHIEP DUOC PHAM YEN BAI Address: Minh Tan Sub-district, Yen Bai Town Location: YEN BAI province Phone: 84-29-52525 Capital: 694 Mil.VND Labour: 114 Revenue: 1485 Mil.VND Branch: Production of chemicals and articles thereof Activity: Medicines production. 25. English name: VIETNAM NATIONAL PHARMACEUTICAL ENTERPRISE NO.1 Vietnamese name: XI NGHIEP DUOC PHAM TRUNG UONG 1 Address: 160 Ton Duc Thang Street Location: HA NOI Phone: 84-4-254561 Capital: 12605 Mil.VND Labour: 537 Revenue: 51883 Mil.VND Branch: Production of chemicals and articles thereof Activity: Medicines production. 26. English name: VIETNAM NATIONAL PHARMACEUTICAL ENTERPRISE NO.3 Vietnamese name: XI NGHIEP DUOC PHAM TRUNG UONG 3 Address: 103 Dien Bien Phu Street Location: HAI PHONG city Phone: 84-31-42576 Capital: 3549 Mil.VND Labour: 259 Revenue: 6581 Mil.VND Branch: Production of chemicals and articles thereof Activity: Medicines production. 27. English name: VINHPHU PHARMACEUTICAL ENTERPRISE Vietnamese name: XI NGHIEP DUOC PHAM VINH PHU Address: Dong Da Sub-district, Vinh YEN Town Location: VINH PHU province Phone: 84-21-61233 Capital: 1631 Mil.VND Labour: 203 Revenue: 4654 Mil.VND Branch: Production of chemicals and articles thereof Activity: Pharmaceutical production and trading. Summary: Name Capital VND mil. Capital USD mil. Revenue VND mil. Revenue USD mil. Labor 2-9 PHARMACEUTICAL ENTERPRISE 14369 1.03 25403 1.81 547 3-2 PHARMACEUTICAL ENTERPRISE 9718 0.69 26345 1.88 500 BINH THUAN PHARMACEUTICAL AND MEDICAL MATERIALS CO. 1039 0.07 6376 0.46 203 DISTRICT 5 PHARMACEUTICAL ENTERPRISE 3118 0.22 914 0.07 87 DISTRICT 8 PHARMACEUTICAL CO. 2515 0.18 10657 0.76 81 DONGTHAP PHARMACEUTICAL CO. 4512 0.32 95975 6.86 181 CUULONG PHARMACEUTICALS AND MEDICAL MATERIALS CO. 7965 0.57 121000 8.64 378 HATAY PHARMACEUTICAL CO. 2921 0.21 13016 0.93 205 HATHANH PHARMACEUTICAL CO. LTD 200 0.01 727 0.05 17 HOABINH PHARMACEUTICAL UNITED ENTERPRISE 942 0.07 3210 0.23 254 NAMHA PHARMACEUTICAL UNITED ENTERPRISE 1930 0.14 5120 0.37 222 NATIONAL MEDICINAL MATERIALS CO. NO.2 6400 0.46 11055 0.79 105 NATIONAL PHARMACEUTICAL CO. NO.1 42411 3.03 143877 10.28 202 NATIONAL PHARMACEUTICAL ENTERPRISE NO.2 13936 1.00 42240 3.02 705 NATIONAL PHARMACEUTICAL ENTERPRISE NO.24 17625 1.26 86219 6.16 547 NATIONAL PHARMACEUTICAL ENTERPRISE NO.25 15813 1.13 45005 3.21 514 NATIONAL PHARMACEUTICAL ENTERPRISE NO.26 10265 0.73 24129 1.72 381 PHARMACEUTICAL TECHNOLOGY DEVELOPMENT CO.-HOCHIMINH CITY 8336 0.60 40667 2.90 165 SOCTRANG PHARMACEUTICAL UNITED ENTERPRISE 1800 0.13 7231 0.52 71 SONLA PHARMACEUTICAL CO. 1759 0.13 2096 0.15 133 THAIBINH PHARMACEUTICAL UNITED ENTERPRISE 3813 0.27 14624 1.04 439 THANHHOA PHARMACEUTICAL ENTERPRISE 1167 0.08 3557 0.25 231 TUYENQUANG PHARMACEUTICAL UNITED ENTERPRISE 1446 0.10 3063 0.22 211 YENBAI PHARMACEUTICAL ENTERPRISE 694 0.05 1485 0.11 114 VIETNAM NATIONAL PHARMACEUTICAL ENTERPRISE NO.1 12605 0.90 51883 3.71 537 VIETNAM NATIONAL PHARMACEUTICAL ENTERPRISE NO.3 3549 0.25 6581 0.47 259 VINHPHU PHARMACEUTICAL ENTERPRISE 1631 0.12 4654 0.33 203 Circular 12 BYT-QD providing a guide for implementing ASEAN GMP Ministry of Health No.: 12/BYT-QD SOCIALIST REPUBLIC OF VIETNAM Independence – Freedom – Happiness Hanoi, September 12th, 1996 CIRCULAR GUIDANCE FOR THE IMPLEMENTATION OF ASEAN GMP GUIDELINES On September 9th, 1996, The Ministry of Health issued the Decision No.: 1516/BYT-QD relating to the implementation of ASEAN GMP guidelines in Vietnam. In order to help pharmaceutical manufacturers in Vietnam execute the aforementioned Decision, the Ministry of Health guides some following specific points: Purposes, Executors, Documents, and Requirements: Purposes: Vietnam was an official member of ASEAN, Vietnam’s pharmaceutical industry has many common points with the region’s pharmaceutical industries. Starting implementing ASEAN GMP in order to gradually improve Vietnam’s pharmaceutical industry, improve the local drugs’ quality, improve the health-care for the community and help Vietnam’s drugs penetrate the regional as well as international markets. Executors: Organizations who are allowed to produce pharmaceutical products Organizations who are designed, built, expanded, renovated production lines to produce drugs The aforementioned organizations are those who produce materials as well as finished products originating from pharmaceutical-chemicals, biological products or pharmaceuticals, and prepared by modern technologies (modern medicine manufacturers). Documents: ASEAN GMP Guidelines, the newest version ASEAN Manual for Inspection of GMP, newest version Requirements Strictly, continuously, execute from low level to high level, from simple to complicated. Suitable for each executor with considering to each organization’s capability Commencing applying registration and inspection regulations from the signed date. Target of 100% pharmaceutical manufacturers meet GMP requirements in 2003. General Regulations Organizations who are allowed to produce pharmaceutical products Institute studying ASEAN GMP Guidelines and related documents issued by the Ministry of Health. Establish the executive plan Register with the Ministry of Health to be inspected and certified ASEAN GMP – compliance periodically. Organizations who are designed, built, expanded, renovated production lines to produce drugs after the effective date of the Decision No.: 1516/BYT-QD relating to the implementation of ASEAN GMP guidelines in Vietnam: Have to submit to the Ministry of Health the draws of designing, expending, and renovating the production lines that meet the ASEAN GMP standards. Have to register to the Ministry of Health to be inspected the ASEAN GMP periodically. Only after being approved by the Ministry of Health, the new production lines are allowed to operate. Inspection applications Inspection Application form of ASEAN GMP The attached documents including: Organization’s training documents relating to GMP Location map of firm Production layout map Production line layout map List of produced products List of firm’s equipment, facilities GMP Internal audit record Three copies are required to be sent to Drug Management Division, Ministry of Health. Report procedures when inspected Pharmaceutical manufacturers have to report with maps, digraphs, and short data relating to the required issues when inspected. Inspected firms are responsible for planning a shortcoming-overcome plan for the pointed-out shortcomings, then submit to the inspectors within two months. Execution Educating, training relating to ASEAN GMP The Ministry of Health (Drug Management Division), Health Divisions are responsible for organizing training classes relating to GMP knowledge for all pharmaceutical manufacturers. Pharmaceutical manufacturers are responsible for studying, training of GMP regulations and standards for all employees with suitable knowledge concerning their jobs. Training GMP Inspectors The Ministry of Health (Drug Management Division) organizes the training for GMP inspectors. The training has to be conducted continuously. Each pharmaceutical manufacturer must have at least one personnel who equipped with GMP inspection training. Basic qualifications of GMP Inspectors University-graduated pharmacists who have experiences in production as well as drug management. Trained with GMP inspection Detail-oriented and honor personalities Have working approaches but strictly commit to regulations, be able to point out firm’s shortcomings and recommend persuadable approaches to overcome mistakes. Good health, without infectious diseases. Inspection and Processing the Results After receiving all necessary documents for GMP inspection application from the firms, the Drug Management Division prepares the schedule and commences the inspection. If more than two months from receiving the documents but could not inspect, then, the Drug Management Division has to issue the formal document explaining the reasons. Periodically inspect for GMP standards for each two years, except the irregular cases due to the firm’s or Ministry of Health’s requirement. Inspection records must be signed by firm’s manager and inspection-team leader and produced to three copies: one copy for the firm, one for the inspection team, and the last for sending to the approval committee of the Ministry of Health. After two months from the inspection date, firms have to submit the reports presenting to methods and time to overcome the defined shortcomings according to GMP standards mentioned in the inspection record. If later than two months without receiving the reports from firms, inspection team has to report to the approval committee for making the decision. With regards to firms who do not correct or are not able to correct the mentioned mistakes, depending on the levels, inspection-team leader is authorized to ask the approval committee and the Ministry of Health to remove partly or completely the product registrations which firms are producing. The Ministry of Health grants the GMP-certificates for pharmaceutical manufacturers who implement well the regulations, standards and the requirements of the inspection team. Head of Minister of Health Prof. Dr. Le Van Truyen G. Interviewees Ph.D. Phar. Pham Thi Binh Minh Head of Drug and Cosmetic Practice Management Division Drug Administration of Vietnam Ministry of Health Office: 138A Giang Vo Str. Hanoi, Vietnam Tel: (844) 8461525 Fax: (844) 8234758 Email: minhdung@fpt.vn Ph.D. Phar. Cao Minh Quang Vice Director of Institute for drug Quality Control Ministry of Health Office: 200 Co Bac Str., District 1 Ho Chi Minh City, Vietnam Tel: (848) 8367356 Fax: (848) 8367900 Email: phmdrquang@hcm.vnn.vn