April 2023 Table of Contents TABLE OF CONTENTS ............................................................................................................................... 2 FIGURES ...................................................................................................................................................... 3 TABLES ........................................................................................................................................................ 3 ABBREVIATIONS ........................................................................................................................................ 4 ACKNOWLEDGEMENTS............................................................................................................................. 5 INTRODUCTION ........................................................................................................................................... 8 VALUE ADDITION OF THE PROJECT ............................................................................................................... 8 VIETNAM COUNTRY PROFILE .................................................................................................................. 9 BRIEF COUNTRY CONTEXT .......................................................................................................................... 9 THE IMPACT OF COVID-19........................................................................................................................ 13 NATIONAL IMMUNIZATION PROGRAM AND VACCINE DELIVERY ..................................................... 14 THE NATIONAL EXPANDED PROGRAM ON IMMUNIZATION ............................................................................. 14 VACCINE DELIVERY AND DISTRIBUTION ...................................................................................................... 17 DISTRIBUTION AND STORAGE OF COVID-19 VACCINES ............................................................................... 18 VACCINE PROCUREMENT ....................................................................................................................... 19 PROJECTED VACCINE REQUIREMENTS ....................................................................................................... 21 ROBUSTNESS OF EXISTING AEFI AND PHARMACOVIGILANCE SYSTEMS........................................................ 22 VACCINE REGISTRATION REGULATORY SYSTEMS ........................................................................... 23 APPLICABILITY OF REGIONAL HARMONIZATION POLICY ................................................................................ 25 DOMESTIC VACCINE MANUFACTURING CAPACITY ........................................................................... 26 COMMERCIAL PRODUCTION OF VACCINES .................................................................................................. 28 COVID-19 VACCINE MANUFACTURING CAPACITY....................................................................................... 31 INCENTIVES FOR DOMESTIC MANUFACTURE OF VACCINES .......................................................................... 32 PATENT REGISTRATION AND INTELLECTUAL PROPERTY............................................................................... 35 SWOT ANALYSIS OF VIETNAM’S POTENTIAL IN THE VACCINE VALUE CHAIN .............................. 36 CONCLUSION ............................................................................................................................................ 39 REFERENCES ............................................................................................................................................ 40 ANNEX 1. LIST OF AGENCIES INTERVIEWED ....................................................................................... 43 2 Figures Figure 1. Vietnam population trends, 2016-2021 .......................................................................................... 9 Figure 2. Age pyramid in Vietnam as of April 2020 .................................................................................... 10 Figure 3. Population distribution by gender and urban/rural ....................................................................... 11 Figure 4. Mortality trends by category, 2016-2020 ..................................................................................... 12 Figure 5. Leading causes of mortality, 2018 ............................................................................................... 12 Figure 6. COVID-19 cases per day, 2021-2022.......................................................................................... 13 Figure 7. Vaccination coverage in children under one year of age, 2019-2021 ......................................... 14 Figure 8. Vaccination coverage in Vietnam, 2009-2020 ............................................................................. 17 Figure 9. Sources of COVID-19 vaccines ................................................................................................... 21 Figure 10. Number of severe events, 2018-2021 ....................................................................................... 23 Figure 11. Vietnam’s AEFI surveillance system.......................................................................................... 23 Figure 12. Procedure for marketing authorization of new, domestically-manufactured vaccines .............. 24 Figure 13. Vaccine developers and manufacturers in Vietnam .................................................................. 26 Figure 14. Proportions of vaccines supplied to various markets by state-owned companies .................... 27 Figure 15. Current and existing maximum manufacturing capacity of domestic vaccines, by company (as of 2021) ................................................................................................................................................. 30 Tables Table 1. NEPI current vaccination schedule ............................................................................................... 15 Table 2. Summary of cold chain system upgrading and support provided by GAVI .................................. 18 Table 3. Quantity of NEPI vaccines procured, 2017-2021.......................................................................... 19 Table 4. Estimation of vaccine quantity and budget, 2021-2025 ................................................................ 22 Table 5. Current commercialized vaccines in Vietnam and their platform technologies ............................ 28 Table 6. COVID-19 vaccines in Vietnam .................................................................................................... 32 Table 7. Subprojects funded under the National Program for the Development of Vaccines for the Prevention of Human Diseases .................................................................................................................. 35 3 Abbreviations AEFI Adverse event following immunization AFP Acute flaccid paralysis BCG Bacille Calmette-Guerin CCE Cold chain Equipment CDCs Centers for Disease Control and Prevention cGMP Current Good Manufacturing Practice CHC Commune Health Centers cMYP Comprehensive Multiple Year Plan DAV Drug Administration of Vietnam DCVMN Developing Countries Vaccine Manufacturers Network DI&ADR Drug Information and Adverse Drug Reactions Monitoring DPT Diphtheria, Pertussis, Tetanus EMA European Medicines Agency EVFTA EU-Vietnam Free Trade Agreement EVMA Effectiveness Vaccine Management Assessment FDA Food and Drug Administration FIC Fully Immunized Children GAVI Global Alliance for Vaccines and Immunization GBT Global Benchmarking Tool GMP Good Manufacturing Practice HPV Human Papilloma Virus ICH International Council for Harmonization IP Intellectual property IPV Inactivated Polio Vaccine JE Japanese Encephalitis MOH Ministry of Health MR Measles-rubella NEPI National Expanded Program for Immunization NIHE National Institute of Hygiene and Epidemiology NRA National Regulatory Agency ODA Official development assistance OPV Oral Polio Vaccine PI HCM Pasteur Institute in Ho Chi Minh city PI Nha Trang Pasteur Institute in Nha Trang city R&D Research and Development TIHE Tay Nguyen Institute of Hygiene and Epidemiology UNICEF United Nations International Children's Emergency Fund WHO World Health Organization 4 Acknowledgements The Vietnam case study was prepared by a team led by Dr. Le Phuong Mai with Dr. Tran Dieu Linh and Dr. Tran Thi Mai Hung. The report benefited from the overall leadership of Mr. Christophe Lemiere (Practice Leader, Human Development) and Dr. Ronald Mutasa (Practice Leader, Human Development) and from technical inputs provided by Dr. Ramana Gandham (Technical Advisor/former Lead Health Specialist), Dr. Andreas Seiter (Technical Advisor/ Industry Expert), Ms. Nguyen Thuy Anh (Senior Operations Officer), Mr. Giles Newmarch (Senior Investment Officer, IFC), Ms. Ridhi Gupta (Investment Officer, IFC), Ms. Erin Sowers (Consultant), Ms. Zinaida Korableva (Operations Analyst). The information contained in this report draws heavily from interviews and consultations conducted with Vietnam government officials and private sector representatives, including Prof. Nguyen Dang Hien (Director, Polyvac), Dr. Do Tuan Dat (Director, VABIOTECH), Mr. Nguyen Xuan Nghia, (Vice Director, IVAC), Dr. Tran Thi Nghia (Director, DAVAC). The leadership and guidance of NEPI and the National Institute of Hygiene and Epidemiology are greatly appreciated. The Vietnam case study is part of a larger regional study with the following components: global desk review, private sector landscape analysis, economic analysis, and country deep-dive case studies. Partnership and collaboration with the ASEAN Secretariat under the leadership of Dr. Ferdinal Fernando and Ms. Jennifer dela Rosa, the UK Foreign, Commonwealth and Development Office, and the Global Financing Facility for Women, Children and Adolescents was essential to the successful completion of the study. Logistics support was provided by Nga Thi Anh Hoang and Mae Myat Moe. The cover and report layout were designed by Kayleigh Ghiot. This report benefited from the valuable comments of peer reviewers Dr. Matthew Downham (Director, CEPI), Ms. Zeynep Kantur (Manager, IFC), Dr. Lombe Kasonde (Senior Health Specialist), and Dr. Kayla Laserson (Deputy Director, Bill and Melinda Gates Foundation). The overall technical guidance provided by Daniel Dulitzky (Regional Director for Human Development), Farid Fezoua (Global Director, IFC) and Aparnaa Somanathan (Practice Manager, Health, Nutrition and Population) is gratefully acknowledged. 5 Executive Summary Vietnam ranks third in population size among ASEAN member states, with a population of 98.5 million in 2022. The Vietnam has a well- public health system in Vietnam is overseen at the central level by the Ministry of Health, while established domestic provincial and municipal authorities are vaccine responsible for health care service delivery at the local level. Preventive health services, manufacturing including vaccines in the National Expanded industry that fully Program on Immunization (NEPI), are provided free of charge at public health supplies all but two centers. Vietnam’s NEPI currently includes vaccines to protect children against 11 vaccines in the NEPI. diseases, with several new vaccine introductions planned or currently underway. Vietnam reported its first case of COVID-19 In 2021, Vietnam was recognized by WHO in January 2020, and the Government took as having a fully-equipped National quick action to contain disease spread Regulatory Authority (NRA) at Maturity through strict community quarantine and Level 3, able to ensure the safety and social distancing measures. These initial efficacy of vaccines produced and used COVID-19 restrictions impacted delivery of in the country. Nine public institutions and routine immunization services for children for a two private companies are involved in period of time and led to an overall reduction vaccine R&D, of which four public and both in health seeking behavior, resulting in private companies are capable of vaccine reduced vaccine coverage rates and a slight manufacture. The two private companies are reemergence of several vaccine-preventable exclusively focused on producing COVID-19 diseases, including measles and diphtheria. vaccines, while the four public institutions COVID-19 vaccines began arriving in Vietnam have manufactured vaccines for sixteen in February 2021, allowing the country to begin vaccine-preventable diseases over the vaccinating priority populations; by April 2022, years, of which fourteen are being produced eligibility had expanded to include everyone at commercial scale. Many of these vaccines over the age of 5, leading to a coverage rate of are the product of technology transfer 87 percent of the population. Coverage rates arrangements, which speaks favorably of the for NEPI vaccines have also seen relationships Vietnamese vaccine improvements. manufacturers have built with external partners, but also indicates a limitation in Vietnam has a well-established domestic domestic vaccine R&D capacity. There is vaccine manufacturing industry that fully also a heavy reliance on traditional supplies all but two vaccines in the NEPI. manufacturing technologies within these Vaccines are procured by the Ministry of public institutions. It is noted that, in addition Health at the central level with funds assigned to vaccines for endemic and/or tropical by the Government. Prices of domestic diseases, two of the four public companies vaccines are set by the Ministry of Finance, are also developing and/or producing though they have not been adjusted since COVID-19 vaccines. 2008. Vaccine requirements are estimated on an annual basis, from which purchase orders are created for domestic manufacturers while national open bidding is applied for imported vaccines. Vietnam faces challenges with vaccine delivery, as many areas are remote and hard-to-reach, and upkeep and replacement of cold chain equipment remain a constraint. 6 Despite producing adequate supply for the NEPI, none of the vaccine manufacturers in Vietnam have reached The Government of maximum production capacity due to: (1) export limitations, as most vaccines Vietnam has taken a have not been pre-qualified by WHO, and number of steps (2) preference to purchase imported vaccines among higher-income recently to build and populations. A substantial Government strengthen the investment would be required to help companies meet pre-qualification standards, domestic vaccine including to modernize and/or upgrade equipment and technology and train staff to manufacturing industry. use it while maintaining good manufacturing practice (GMP) standards. The Government of Vietnam has taken a number of steps recently to build and strengthen the domestic vaccine manufacturing industry through preferential tax policies, low-interest loans and tax waivers, and making land available for facility expansion. However, manufacturers interviewed for this study described a crucial need for a long-term, comprehensive, and adequately-funded strategy and implementation plan for domestic vaccine development including competitive pricing policies in order to ensure investment efficiency and build vaccine security. 7 Introduction COVID-19 has had a devastating effect on the ASEAN region, which has recorded over 27 million cases of the virus. Despite rapid development of a range of COVID-19 vaccines using innovative technologies, access to these vaccines has been a challenge, with manufacturing mostly concentrated in the US and Europe for high-value mRNA vaccines, and China and India for traditional platforms and high-volume production. Countries with domestic COVID-19 vaccine manufacturing capacity prioritized domestic vaccine requirements over foreign needs, putting countries with limited production capabilities at a disadvantage. ASEAN countries, which on the whole have made fairly limited investments in research and development of vaccines and biologicals, were highly dependent on imports, resulting in heightened vulnerability during COVID- 19 surges. Despite the existence of an established framework for ASEAN coordination on vaccines, there has been minimal coordination between member states to collectively procure COVID-19 vaccines. Consequently, ASEAN countries have experienced a common set of challenges in navigating the complex global vaccine market to ramp up COVID-19 vaccination. Leaders of ASEAN member states have recognized the need for the region to be self-sufficient in vaccine research and manufacturing to effectively address future pandemics and build regional vaccine security. ASEAN must build regional capacity to develop, test efficacy, and scale up manufacture of vaccines, building on existing country-level strengths and avoiding duplication. While some evidence on regional vaccine manufacturing capacity for ASEAN exists, there has been limited research on the technical, operational, financing and strategic partnership opportunities that exist in the region and might be leveraged to advance regional vaccine security. To address this knowledge gap, the United Kingdom Foreign, Commonwealth and Development Office (UK FCDO) and the World Bank initiated the ASEAN Vaccine Development and Manufacturing Research Project. This project complements the ASEAN Vaccine Security and Self-Reliance (AVSSR) Initiative and the Coalition for Epidemic Preparedness Innovations (CEPI) 2021 plan, and supports the November 2019 declaration of ASEAN leaders on regional vaccine security and self-reliance. Value Addition of the Project This regional analytical activity will contribute to knowledge on the technical, operational, and financial viability and strategic partnership required among ASEAN countries to strengthen coordinated investments on the vaccine value chain. The ASA has three major activities: i) A deep-dive public sector technical assessment of country and regional level vaccine security, including gaps and opportunities across the value chain from R&D to last mile distribution; ii) A private sector value chain analysis covering upstream and downstream aspects of vaccine manufacturing; and iii) An economic analysis examining the feasibility of coordinated investments across countries to leverage comparative advantage in specific aspects of the vaccine value chain. 8 Five ASEAN members states—Indonesia, Malaysia, Philippines, Thailand and Vietnam—were engaged to conduct detailed analyses of their country’s current vaccine system, including current processes related to procurement and distribution, manufacturing capabilities (current or potential), and regulatory systems related to domestic vaccine registration and production. The country teams also consulted with high-level stakeholders from government, regulatory agencies, academia, private sector and civil society to identify relative strengths and critical weaknesses in each country’s technical and human resource capacity to respond to vaccine manufacturing needs in the future. The results of those analyses and consultations make up the succeeding country profiles. Finally, a high-level policy dialogue was facilitated in late-2022 to explore regulatory, financing and institutional reforms required to address the identified challenges to regional vaccine manufacture. Vietnam Country Profile Brief Country Context According to the Vietnam General Statistics Office, the population of Vietnam was 98,510,000 at the end of 2021, making it the 15th most populated country in the world and the 3rd among Association of Southeast Asian Nations (ASEAN) member states, behind Indonesia and the Philippines. The population density of Vietnam was 311 people per square kilometer in 2020, behind only Singapore and the Philippines in the East Asia and Pacific region, and substantially higher than the regional average of 96 persons per square kilometer. Figure 1. Vietnam population trends, 2016-2021 99,000.00 98,000.00 97,000.00 96,000.00 95,000.00 94,000.00 93,000.00 92,000.00 91,000.00 90,000.00 89,000.00 2016 2017 2018 2019 2020 2021 WHOLE COUNTRY Source: General Statistics Office of Vietnam, 2021. 9 Figure 2. Age pyramid in Vietnam as of April 2020 Male Female Source: General Statistics Office of Vietnam, 2021. Vietnam has a young population, with a median age of 32.5 years and more than 90 percent of the population under the age of 65 (UN Population Division, 2022a). The fertility rate in Vietnam has been consistent over the past 10 years and is currently at 2 births per woman (UN Population Division, 2022b). Life expectancy is 75 years, also consistent over the past 10 years. Females accounted for 50.1 percent of the population in 2021, and their distribution among rural and urban areas is similar to that of males. According to the 2020 census, 35.4 million people, or 36.4 percent of the population, live in cities, while 61.8 million people, or 63.6 percent of the population live in rural areas (GSO, 2021) (Figure 3). 10 Figure 3. Population distribution by gender and urban/rural 100% 90% 80% 70% 63.3% 64.0% 60% 50% 40% 30% 20% 36.7% 36.0% 10% 0% Male Urban Rural Female Source: General Statistics Office of Vietnam, 2021. Mortality statistics over the past 20 years show a reduction in deaths due to communicable diseases and injuries in Vietnam and an increase in deaths due to non-communicable diseases, a trend that aligns with the economic growth of the country. Non-communicable diseases, including cardiovascular disease, stroke and diabetes, accounted for more than 70 percent of deaths in Vietnam in 2020, a figure relatively unchanged over the past five years (Figure 4), though indicative of a dramatic shift from the late 1990s when more than 50 percent of deaths were attributed to communicable diseases and injuries. In 2018, about a third of deaths were attributed to cardiovascular diseases and 19 percent of deaths were the consequence of cancers (Figure 5). The average mortality rate for adult females in 2020 was 75 deaths per 1000 population, while the mortality rate for males was more than double the female rate, at 186 deaths per 1000 population (UN Population Division, 2022c). The infant mortality rate has been dropping steadily over the past decade to a rate of 16.7 deaths per 1000 live births in 2020. Infant mortality is higher among males than females (18.9 deaths per 1000 live births for males versus 14.4 for females) as is the under- 5 mortality rate (24.4 for males versus 17.2 for females in 2020) 1. 1 United Nations Inter-Agency Group for Child Mortality Estimation 11 Figure 4. Mortality trends by category, 2016-2020 Communicable 80 diseases 70 Non-communicable 60 Accident, Injury, 50 poisoning 40 30 20 10 0 2016 2017 2018 2019 2020 Source: Vietnam Ministry of Health, 2019. Figure 5. Leading causes of mortality, 2018 Source: World Health Organization, 2018. Since the late 1980s, the health care system in Vietnam has been a mixed public-private system. The public system is overseen at the central level by the Ministry of Health; provincial and municipal authorities are responsible for health care service delivery at the provincial, district and commune levels. Preventive health services—including vaccines in the National Expanded Program on Immunization (NEPI)—are provided at public health centers free of charge. At provincial levels, people’s committees are responsible for allocating financial and human resources to support service delivery, while local governments work with MOH to ensure professional competency of providers (Duc-Cuong et al., 2010). Social health insurance was 12 introduced in Vietnam in 1992 and as of 2018 covers 87 percent of the population (WHO, n.d-a). Low income households, ethnic minorities, children under 6 and elderly adults over 80 years of age are fully covered via government subsidy. The Impact of COVID-19 Vietnam reported its first case of COVID-19 in January 2020, but quick and decisive action by the government to contain the spread of the disease through community quarantine and social distancing measures resulted in a relatively low burden of disease in the early months of the pandemic. However, later waves of infection impacted the country more severely (Figure 6), and by July 2022, a total of 9.98 million cases of COVID-19 and over 43,000 deaths had been reported. The average fatality rate is about 0.40 percent, and cases and deaths per 100,000 are 10,333 and 45, respectively. 2 COVID-19 vaccines began arriving in Vietnam in February 2021; soon thereafter, vaccine dissemination began among priority groups. Eligibility soon expanded to all adults over age 18, followed by young adults age 12-17 by November 2021, and children age 5-11 in April 2022. Though initial uptake was slow, vaccination rates increased dramatically by December 2021, resulting in a coverage rate of 70 percent of the total population. As of December 2022, the WHO reports that nearly 85 million people in Vietnam are fully vaccinated, or 86 percent of the population (WHO, n.d.-b). Figure 6. COVID-19 cases per day, 2021-2022 Source: National Technology Center for COVID-19 Pandemic Control. https://covid19.ncsc.gov.vn/graph Routine immunization services were temporarily suspended for three weeks in April 2020 when the government enacted strict, nationwide community quarantine and social distancing measures, putting as many as 100,000 mothers and newborns at risk of missing prenatal and postnatal care visits and immunization services, and threatening the vaccination status of as many as 420,000 children under the age of one. A study conducted by UNICEF in 2020 showed that 44 percent of study participants with children reported difficulty accessing child health care services compared 2 General Department of Preventive Medicine, Ministry of Health, Vietnam. https://ncov.vncdc.gov.vn 13 to the pre-pandemic period. In addition, the number of children under the age of 5 receiving immunizations in commune health centers decreased by nearly 75 percent in 2020, due to both the suspension of services as well as fear of infection. Thirteen provinces reported a more than 10 percent reduction in Measles-Rubella (MR) coverage, while seven reported a similar reduction in coverage for Diphtheria-Pertussis-Tetanus 4 (UNICEF, 2020). Vaccination rates did not rebound in 2021: according to a report of the National Expanded Program for Immunization (NEPI), vaccination coverage in children under the age of one in 2021 was nearly 10 percent lower than in 2020 (Figure 7). The suspension of immunization services and reduction in health seeking behavior coincided with the re-emergence of vaccine-preventable diseases in provinces throughout Vietnam. During the first quarter of 2020, over 2,100 suspected cases of measles were identified, of which 770 cases were sampled and 617 of those (80 percent) were positive. New diphtheria cases have also been detected in the Central Highlands and Southern and Central regions, taking the total number to 126 infections and three deaths since June 2020 (UNICEF, 2020b; UNDP, 2020). The COVID-19 pandemic also affected planned NEPI activities, including those to introduce new vaccines and to maintain and/or increase coverage rates to at least 95 percent. Substantial effort was required to strengthen missing doses during the pandemic, especially in the hardest hit provinces. However, the country has made recent strides to bring vaccination rates back to pre- pandemic levels through targeted outreach (WHO/UNICEF, 2021). Figure 7. Vaccination coverage in children under one year of age, 2019-2021 100% 97.3% 96.30% 94.2% 96.8% 95.4% 95.40% 94.30% 87.9% 89.10% 89.40% 87.8% 87.1% 82.2% 89.0% 80.4% 83.2% 80% 79.10% 79.9% 77.3% 72.90% 69.4% 60% 2019 2020 2021 Source: (i) WHO/UNICEF, 2021. Vietnam: WHO and UNICEF estimates of immunization coverage, 2020 revision. (ii) NEPI, 2021. Annual Report of the National Expanded Immunization Program in 2020. National Immunization Program and Vaccine Delivery The National Expanded Program on Immunization 14 The National Expanded Program on Immunization (NEPI) in Vietnam is overseen by the National Institute for Hygiene and Epidemiology, while program management is decentralized to four regional EPI offices, 63 Provincial Centers of Disease Control, and 704 District Health Centers. Immunization services are integrated into the health service delivery model of commune health centers (CHCs) and are normally provided in sessions for 1-3 days per month, supplemented by mobile health teams in remote areas and immunization campaigns. Outreach sessions are carried out at the village level in the hardest-to-reach communes (about five percent of CHCs nationwide). Vietnam currently operates a “dual system” for vaccinations, with NEPI immunizations provided for free at public health centers and non-EPI fee-for-service or paid vaccines available in health facilities across the country. Approximately 42 imported vaccines are available in Vietnam, including vaccines in the NEPI schedule that are produced abroad; these are generally purchased by higher income families who favor imported vaccines over those produced domestically. Vietnam’s NEPI currently protects children against 11 diseases: tuberculosis (BCG), hepatitis B (HepB); polio (OPV and IPV); diphtheria, pertussis, tetanus (DPT); pneumonia and meningitis (Hib); measles-rubella (MR); and Japanese Encephalitis (JE) (Table 1). Future program priorities include: achieving measles elimination by 2023; increasing the immunization coverage rate to 95 percent at the district level, and later at the commune level; introducing new NEPI vaccines into the national schedule, i.e. rotavirus, pneumococcal, HPV, influenza vaccines, before 2030; strengthening the NEPI cold chain system in the next five years, especially in isolated areas; and increasing the local budget for NEPI, especially for the procurement of new vaccines. Vietnam has a strong history of domestic vaccine production. Nearly all vaccines used in the routine immunization program are produced domestically, except for DTP-HepB-Hib and IPV vaccines, which are imported. In addition, Vietnam has also produced cholera and typhoid vaccines, which at one time were administered in high-risk areas, though they are no longer included in the NEPI. In June 2015, WHO formally certified Vietnam as having a fully-equipped national regulatory authority (NRA) that ensures the safety and efficacy of vaccines produced and used in the country. This certification confirms that Vietnam’s NRA is compliant in all areas required for regulatory oversight of vaccines, including: overall system framework; marketing authorization and licensing; post-health centers, which are further networked by a system of village health workers; marketing surveillance, including for adverse events following immunization (AEFI); lot release; laboratory access; regulatory inspections of manufacturing sites and distribution channels; and authorization and monitoring of clinical trials. Table 1. NEPI current vaccination schedule Vaccines DPT- No Age Measles- BCG HepB HepB- OPV IPV Measles DPT JE Rubella Hib 1 st Birth 1 Birth dose dose 15 2 1st 1st 2 months dose dose 3 2nd 2nd 3 months dose dose 4 3rd 3rd 4 months dose dose 5 IPV 5 months dose 9 6 1st dose months 18 Booster 7 2nd dose months dose 1 – 5 3 8 years doses Source: National Expanded Program on Immunization. www.tiemchungmorong.vn. Prior to the COVID-19 pandemic, Vietnam had reached high vaccination coverage nationally, with more than 90 percent of children under the age of one protected from the most dangerous vaccine-preventable diseases. There was a temporary dip in coverage in 2018 when Vietnam switched manufacturers for one of the NEPI vaccines, resulting in a temporary vaccine shortage, though the vaccine dropout rate has recently improved (Figure 8). The results of the 2018 NEPI appraisal showed no significant difference between boys and girls in access to vaccination, though geographic disparities in vaccine coverage were identified. The report listed 12 disadvantaged districts in 9 provinces where full immunization coverage was below 80 percent, and 142 districts with DTP3 coverage below 80 percent. In addition, specific challenges were noted for increasing vaccination rates among populations living in remote mountainous areas as well as those living in industrial parks with dense populations. Population fluctuations in urban areas also create difficulties with vaccine follow-up (GAVI, 2018). 16 Figure 8. Vaccination coverage in Vietnam, 2009-2020 100 90 80 70 60 50 40 30 20 10 0 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 BCG DTP1 DTP3 Pol3 IPV MCV1 HepBB Hib3 Source: Vietnam Ministry of Health. www.tiemchungmorong.vn/vi Vaccine Delivery and Distribution Despite national successes, challenges remain in vaccine delivery. The remarkable achievement of the NEPI in meeting the Government’s requirements for childhood vaccinations has unfortunately resulted in a reduced investment in the program, and the current immunization budget is very low compared to previous periods. NEPI has not been included in national target programs since 2020, leading to budget reductions from the national to the local level and low disbursements in some provinces and districts. Though NEPI vaccines are provided for free to children at public health centers, government health insurance covers health treatment only and not broader preventive health services. Structural changes in the organization of preventive medicine systems at the provincial and district levels, which were initiated nationwide in 2015, have negatively affected NEPI personnel. At the provincial level, CDCs were established by merging Preventive Medicine Centers, HIV/AIDS Control Centers and Communication Centers, among others. At the district level, Health Centers and District Hospitals were merged into one entity. These reforms aimed to increase efficiency and improve health care equity, but they also resulted in a high turnover of NEPI staff at all levels, as many well-trained and experienced staff resigned or took early retirement (GAVI, 2018). An Effective Vaccine Management Assessment (EVMA) conducted in 2019 identified the need to improve cold chain capacity within provinces and districts by replacing aging equipment and modernizing the cold chain system to accommodate new vaccines, including for rotavirus. From 2003 to 2012, NEPI received support for improving the cold chain system from the Luxemburg Development Corporation, including support for the procurement, delivery, installation and maintenance of over 5500 refrigerators; the organization also provided technical assistance 17 through a technical advisor to NEPI. During this time, NEPI also established a new maintenance system at the regional and provincial levels, through which technicians were trained in corrective maintenance and NEPI staff were trained in preventive maintenance. Despite regular maintenance, cold chain equipment must be upgraded and replaced as technology improves, and in 2017, GAVI provided support to procure new, more modern refrigeration units. These units have been provided to under-resourced and/or hard-to-reach districts and communes throughout the country. World Bank has also provided support to MOH to grow grassroots support for health services; some of the areas targeted under this program have also received new cold chain equipment. The progress of CCE replacement is summarized in Table 2. Table 2. Summary of cold chain system upgrading and support provided by GAVI TCW3000 units to be replaced at both provincial and district level stores 1,158 units RCW50EG units to be replaced at commune health centrers 3,988 units CCE replacement supported by CCEOP1 and CCEOP2 (GAVI-funded) 2019 2020 2021 2022 Total onwards CCEOP1 240 units of 350 units of 0 0 590 units of TCW4000AC TCW4000AC TCW4000AC CCEOP2 0 0 182 units of 386 units of 586 units of TCW4000AC TCW4000AC TCW4000AC 873 units of 0 1000 units of 1,873 units HBC80 HBC80 of HBC80 Source: NEPI, 2019 (b). Vietnam operates a 5-tier vaccine supply chain system that consists of one national store, four regional stores, 63 provincial stores, 712 district stores, and 11,160 commune health centers (CHC). Each CHC is an immunization point, though NEPI vaccines are not stored in CHCs except in very remote communes. Domestically-manufactured NEPI vaccines are distributed to national or regional stores, depending on location3; from there they are delivered to provincial stores on a bi- monthly basis, and then to district and commune stores on a monthly basis. Though the frequency of deliveries is defined, the number of deliveries is sometimes higher than planned due to storage capacity and supplier constraints. Expansion of cold chain capacity at all levels may help to ameliorate this situation. Distribution and Storage of COVID-19 vaccines Two notable achievements of the COVID-19 vaccination campaign in Vietnam are the participation of the military and the contribution of private sector. In order to assist the overburdened health care workforce, the government assigned the Ministry of Defense to support the transport of vaccines from the airport to national storage facilities at the National Institute of Hygiene and Epidemiology/Pasteur and the MAY Cosmetics Pharmaceutical Joint Stock Company, and 3 Over 50 percent of locally-manufactured vaccines are distributed directly to regional stores, enabling the national store to manage stock of locally manufactured vaccines for distribution to the Northern region only. 18 eventually to provincial storage facilities. Moreover, the eight military regions also established their own vaccine storage warehouses with GSP standard, which are equipped with 157 positive refrigerators, 56 deep refrigerators, and 560 cold boxes. The Truong Hai Thaco company donated 63 refrigerated trucks for receiving and storing COVID-19 vaccines and transporting them to provinces; the trucks were distributed between military regions. At the end of the campaign, all trucks and cold chain equipment will be transferred to health centers in provinces and cities throughout the country. In addition, as discussed previously, Vietnam has received considerable support from international donors to improve the cold chain infrastructure required for COVID-19 vaccines. The support includes ultra cold temperature freezers, and modern, high-functioning refrigerators and cold boxes. When they are no longer needed for pandemic response, the equipment will be distributed within all levels of the health care delivery system. Vaccine Procurement In Vietnam, NEPI at the central level is responsible for purchasing all vaccines and immunization materials with funds assigned by the central Government; local governments (or people’s committees) allocate the budget for NEPI operations at the province-level. As previously stated, most vaccines in the NEPI are manufactured domestically, including: BCG (TB), Hepatitis B (Gene- HBvax); Polio (bOPV); Diphtheria-Pertussis-Tetanus (DPT); Tetanus (TT); Tetanus, Diphtheria (Td); Measles (MVVAC); Measles-Rubella (MRVAC); and Japanese Encephalitis (JEVAX). Two vaccines are not produced domestically but rather imported by trading companies and provided to NEPI: DPT-Hep-Hib vaccine (Combi-Five), which has been imported from India since 2018; and IPV, which has been provided by Sanofi via UNICEF/GAVI grant since 2017, an arrangement that will continue until the end of 2022. The quantity of vaccines procured from 2017 to 2021 is shown in Table 3. Prices of domestic vaccines are determined by the Ministry of Finance; they are based on the prices of essential inputs—such as materials and vials—and other indirect costs, and have not been adjusted since 2008. Following an annual estimation of vaccine requirements, purchase orders are generated for domestically-manufactured vaccines, while national open bidding is used for imported vaccines, which are procured via public or private companies that meet qualification criteria4. For the procurement of syringes and safe boxes that are not included among vaccine delivery materials supplied by UNICEF (for GAVI-funded injectable vaccines) but instead provided by local enterprises, national competitive bidding is conducted in each province and supplies are paid for by the local authority. Table 3. Quantity of NEPI vaccines procured, 2017-2021 4 Qualification criteria is specified in the Circular 36/2018/TT-BYT and Decree 54/2017/NĐ-CP. 19 Vaccine 2021 2020 2019 2018 2017 BCG - 3,000,000 3,400,000 3,400,000 2,500,000 DPT 500,000 2,000,000 4,000,000 4,000,000 3,600,000 OPV - 11,000,000 8,000,000 7,000,000 7,000,000 IPV 3,500,000* 4,393,800* 2,078,000* 2,783,200* Measles 500,000 2,500,000 3,000,000 3,000,000 3,200,000 TT 1,500,000 5,000,000 5,000,000 4,000,000 3,500,000 Hepatitis B - 2,400,000 1,600,000 1,500,000 2,200,000 JE 1,500,000 3,000,000 3,500,000 4,139,870 4,380,000 DPT-Hep-HiB 2,000,000 4,000,000 5,085,700 5,479,700** Meals – - 3,200,000 5,542,700 6,399,380 2,500,000 Rubella Budget from Government 5,111,652.17 10,348,608.70 15,901,990.74 15,928,478.26 12,481,885.22 (USD)*** * Fully supported by GAVI ** Partly supported by GAVI ***Exchange rate: 1 USD=23,000 VND Source: NEPI, 2018-2021. From the beginning of the COVID-19 vaccine campaign through end-March 2022, Vietnam received over 217 million doses of COVID-19 vaccine, of which nearly 62 million (28 percent) were via the COVAX facility, 32 million (15 percent) as donations from other countries (including the United States, Australia and Germany), and 123 million (57 percent) through Vietnam government direct procurement agreements with manufacturers according to emergency regulations.5 Specifically, the Ministry of Health either purchased vaccines directly from manufacturers, including AstraZeneca and Pfizer, or purchased back vaccines from other governments. Every step in the contract signing process was closely monitored by the central government. Government funding for the purchase of COVID-19 vaccines and supplies as of end-January 2022 was over 14 trillion VND (US$ 626 million) (WHO, 2022). 5 Government Resolution No. 168/NQ-CP. Dated 31-12-21. 20 Figure 9. Sources of COVID-19 vaccines Source: WHO, 2022. COVID-19 in Vietnam Situation Report 86. Projected Vaccine Requirements The Vietnam Government is committed to introducing new vaccines into the national immunization schedule, a commitment that is reflected in the 2016-2020 Health Sector Plan, the 2016-2020 Comprehensive Multiple Year Plan (cMYP), and the Resolution of the Vietnam Communist Party on strengthening and improving health care and protection of the people in the new context. In August 2022, MOH proposed and the central government approved the introduction of the rotavirus vaccine in 2022 6, pneumococcal vaccine by 2025, HPV vaccine by 2026 and seasonal influenza vaccine by 2030. It also approved the initiation of HPV vaccination for girls aged 12-25 years from 2022-2025 if provinces can allocate local government budget (Ministry of Health, 2015). Table 4 shows the projected number and funding of vaccines in the immunization program through 2025 (data provided by NEPI). 6 The introduction of this vaccine is still awaiting budget approval as of December, 2022. 21 Table 4. Estimation of vaccine quantity and budget, 2021-2025 Vaccines 2021 2022 2023 2024 2025 Total Hepatitis 18,205,230 22,793,540 22,941,550 23,237,570 23,533,590 110,711,480 B BCG 7,867,800 10,123,800 10,236,600 10,349,400 10,462,200 49,039,800 DPT-VGB- 133,000,000 170,450,000 172,200,000 174,300,000 176,400,000 826,350,000 Hib OPV 43,235,500 44,246,200 44,751,550 45,256,900 45,762,250 223,252,400 IPV * 124,080,000 125,490,000 126,900,000 376,470,000 Measles 27,083,360 31,903,280 32,362,320 32,706,600 33,050,880 157,106,440 DPT 9,994,000 12,920,000 13,072,000 13,224,000 13,376,000 62,586,000 Measles - 29,934,450 40,933,620 41,351,310 41,908,230 42,325,920 196,453,530 Rubella JE 61,968,560 64,935,140 65,759,190 66,418,430 67,242,480 326,323,800 Tetanus 7,877,450 11,649,750 11,782,890 11,916,030 12,071,360 55,297,480 Doses of vaccines (TT) Rota** 13,254,205 26,776,959 41,865,069 57,716,240 72,681,336 212,293,809 Tetanus- 17,889,460 18,085,330 18,281,200 18,477,070 18,672,940 91,406,000 Diphtheria (TD) Budget 16,100,435 19,774,679 26,029,725 27,000,020 27,933,867 116,838,727 (USD)*** * GAVI donated IPV in 2021 (126,9 mil VND) and 2022 (124,08 mil VND); ** Rota is proposed to be introduced in 2022; *** Exchange rate: 1 USD = 23,000 VND Source: NEPI Robustness of Existing AEFI and Pharmacovigilance Systems Vietnam established an AEFI surveillance system in 2002 to reduce vaccine-related risk, detect early to mitigate and prevent potential errors, and build community awareness of the signs and symptoms of adverse events and reporting protocols. The development of the surveillance system has had a significant impact on the implementation of the vaccination program. In October 2012, an increasing number of serious adverse effects related to pentavalent vaccine were reported, leading to the temporary suspension of the vaccine. Responding to the events, the NEPI implemented a nationwide training program in injection safety and strengthened provincial AEFI committees. These efforts resulted in improved coverage rates in the following years. The number of severe AEFI cases from 2018 to 2021 is shown in Figure 10. In July 2016, the Vietnam Government issued Decree No. 104/2016/ND-CP on vaccination, which provided general guidance for safety in vaccination and established a ministerial and provincial advisory council to investigate and evaluate the occurrence of serious injuries resulting from vaccines. The decree stipulated that the number of common and serious adverse reactions should be monitored, collected, and reported periodically and promptly at each level of the healthcare 22 system. Case-based surveillance for AFP/polio, measles, rubella, and neonate tetanus has been implemented nationwide with WHO support. Over time, program data collection has improved and been converted into an electronic system. This system has been gradually integrated into a National Immunization Information System, which also includes data on health outcomes. AEFI events are reported through this system as well. The General Department of Preventive Medicine (GDPM) within MOH is responsible for recording AEFIs with detailed causes and distribution as shown In Figure 11. Figure 10. Number of severe events, 2018-2021 35 30 25 20 15 10 5 0 2018 2019 2020 1st Quarter - 2021 Vaccine-related Coincidental Unknown Source: Ministry of Health Vietnam. https://vncdc.gov.vn/hoat-dong-nra-nc5644.html Figure 11. Vietnam’s AEFI surveillance system AEFI Committee/NRA GDPM Central Hospitals IHEs/Pasteur Institutes Provincial Hospitals CDCs District Hospitals DHCs Village Health Workers CHCs Source: Ministry of Health Vietnam. https://vncdc.gov.vn/hoat-dong-nra-nc5644.html Vaccine Registration Regulatory Systems 23 In April 2021, WHO announced that Vietnam’s National Regulatory Authority (NRA) for vaccines, which is housed within the Drug Administration of Vietnam (DAV), reached maturity level 3 of 4 according to the WHO Global Benchmarking Tool (GBT) 7 (WHO, 2021b). Vietnam’s NRA was certified in eight of the nine functions of regulating vaccines, indicating the existence of stable, well-functioning and integrated regulatory processes and the fulfillment of criteria to ensure the quality, safety and effectiveness of vaccines distributed in Vietnam. The scope of this evaluation included all types of vaccines that were authorized for sale in Vietnam, excluding COVID-19 vaccines, which have not yet been authorized for sale. The Ministry of Health issued circular No. 32/2018/TT-BYT in November 2018, which gave guidance on marketing authorization of drugs and medicinal ingredients. The key steps to grant marketing authorization are the same for all domestically-manufactured vaccines (Figure 12). Authorization holders and/or manufacturers are required to submit licensing dossiers to DAV containing legal, administrative, and technical documents and risk management plans using either the ASEAN Common Technical Dossier or the Common Technical Document defined by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). Once DAV receives the appropriate dossier, the documents therein are sent to validation officials or units assigned by MOH. Following their review, DAV either rejects the application (with a written explanation), proposes acceptance, or requests additional comments from the Advisory Board specific to vaccine and biological marketing authorization, which was established by Decision 2885/QD-BYT in 2018. This consultation results in either acceptance or rejection. Figure 12. Procedure for marketing authorization of new, domestically-manufactured vaccines Source: Circular No. 32/2018/TT-BYT dated 12-11-18 on marketing authorization of drugs and medicinal ingredients The effective period of marketing authorization for new vaccines is 3 years. Authorization holders must submit reports on the safety and efficacy of registered vaccines to the National Center for Drug Information and Adverse Drug Reaction Monitoring (DI&ADR) every 6 months during the effective period and when applying for renewal of the marketing authorization. Although a general registration protocol is applied to all vaccines, the level of detail of market authorization dossiers can be simplified—and the time for validation shortened—in certain cases. Articles 34 and 35 in circular No. 32/2018/TT-BYT stipulate that drugs serving urgent needs for national defense/security, epidemic control and/or disaster relief may be eligible for a fast-track validation process, while drugs manufactured in factories that periodically undergo GMP 7 Level 3 represents the minimum target for most NRAs to reach and indicate the existence of a stable, well-functioning and integrated regulatory system. Level 4 NRAs exceed this required standard and represent regulatory systems operating at advanced level of performance and continuous improvement. 24 inspection by the DAV are eligible for a simplified validation process. Furthermore, Decision 3659/QD-BYT from August 2020 issued guidelines on research, clinical trials, marketing authorization, and the use of COVID-19 vaccines. This decision reinforced the DAV’s authority to exempt certain phases of clinical trials based on the recommendation of the Advisory Board, while still ensuring safety and efficacy for consumers. It specified that dossiers for quick validation of COVID-19 vaccines must include data from clinical trial phases 1 and 2 only and an interim assessment of phase 3 on safety and immunogenicity (Ministry of Health, 2020). This same circular also specified different requirements for market authorization dossiers for vaccines under technology transfer agreements and secondary packaging in Vietnam. For vaccines undergoing secondary packaging in Vietnam, the authorization holder and the manufacturer must complete the technology transfer within five years from the issuance date of the marketing authorization. Additionally, a technology transfer progress report must be submitted by the authorization holder within 3 years of marketing authorization issuance. 8 Applicability of Regional Harmonization Policy As described above, circular no. 32/2018/TT-BYT stipulates that authorization holders or manufacturers are required to use the ASEAN Common Technical Dossier or the Common Technical Document of the ICH for registration of pharmaceuticals for human use. Moreover, exemption of one or more clinical trial phases before marketing authorization is also applied to vaccines approved by the US FDA or EMA based on the reduced clinical documents they require. These regulations demonstrate the international integration policies of the Vietnam Government and its interest in creating favorable conditions for the import of vaccines from other countries as well as the export of vaccines to the world market. 8 Circular no. 32/2018/TT-BYT dated November 12, 2018 on marketing authorization of drugs and medicinal ingredients. 25 Domestic Vaccine Manufacturing Capacity Vietnam has known expertise in vaccine research and production meeting international standards (MOH, 2021), and is one of several ASEAN nations with domestic vaccine manufacturing capacity. Nine public institutions and two private companies located in Hanoi, Khanh Hoa, Lam Dong and Ho Chi Minh have been involved in vaccine R&D, of which four public and two private entities are capable of vaccine manufacture (Figure 13). The four state-owned companies—VABIOTECH, POLYVAC, IVAC, and DAVAC—produce vaccines against a variety of infectious diseases, including cholera, rubella, measles, hepatitis B, and tetanus. On the other hand, the two private manufacturers—Nanogen, a Vietnamese biopharmaceutical company, and VinBioCare, part of the Vingroup Company—are singularly-focused on producing COVID-19 vaccines, and their products are still undergoing the market authorization process. All of the manufacturers except for one, which is currently in the process of undergoing performance qualification, have complied with the WHO-cGMP (current GMP) standards as certified by DAV. In addition, among the six vaccine manufacturers, VABIOTECH and POLYVAC are current members of the Developing Countries Vaccine Manufacturers Network (DCVMN), while IVAC was a member of DCVMN until 2008. Figure 13. Vaccine developers and manufacturers in Vietnam VINBIOCARE IBT POLYVAC NIHE VABIOTECH IVAC IPHCM DAVAC NANOGEN In the last ten years, sixteen vaccines have been researched and developed by the above institutions to combat the following diseases: (1) live attenuated anthrax, (2) conjugate typhoid Vi conjugate, (3) measles, (4) rotavirus; (5) measles-rubella; (6) norovirus virus-like particle (VLP); (7) influenza A/H5N1, H1N1, H7N9; (8) seasonal flu; (9) rabies in cell culture; (10) inactivated polio; (11) EV71; (12) dengue; (13) Hib; (14) HPV; (15) 5-in-1 (DTaP-HepB-Hib); and (16) Japanese 26 Encephalitis (JE). Vaccines under the technology transfer track were also executed. Fourteen of the vaccines listed above have gone on to be commercially produced; the remaining two were limited by insufficient resources and investment for mass production. For example, to achieve large-scale production, a manufacturer must build and/or upgrade the manufacturing premises, hire sufficient staff, and establish quality and management systems for cGMP and marketing authorization, among others. To do this, manufacturers need financing and, more importantly, legal framework supports from authorities. Nine of the eleven vaccines included in the NEPI schedule are manufactured domestically. POLYVAC and IVAC vaccines are mainly provided for NEPI (90 percent and 44 percent, respectively), while those from VABIOTECH are mainly included among public paid vaccines (70 percent). DAVAC only produces one type of vaccine (typhoid vaccine), which is available exclusively by purchase. The proportions of vaccines supplied to the different markets by the four state- owned companies are described in Figure 14. Figure 14. Proportions of vaccines supplied to various markets by state-owned companies 9 Input materials for both upstream and downstream manufacturing processes of the four state- owned companies—including ingredients, excipients, vials and stoppers—are either purchased from foreign countries or domestic suppliers, or produced on-site, while diluents are all produced on-site where applicable. Domestic manufacturers have faced some challenges with regards to 9 Information provided by manufacturers during in-depth interviews. 27 imported materials, including a dependence on foreign suppliers, material shortages faced during the COVID-19 pandemic, and delays in import approval processes. Commercial Production of Vaccines WHO estimates that 95 percent of vaccine doses produced each year are manufactured in 25 countries, including Vietnam, which is also the fourth country in Asia to produce MR vaccine after Japan, India and China. Of the fourteen vaccines that are commercially produced in Vietnam (Table 5), 11 are products of technology transfer, including Japanese encephalitis (technology transfer from Biken Institute of Japan through WHO); Hepatitis B (technology transfer from Kitasato Institute, Japan through WHO); oral cholera (technology transfer from SLB institute, Sweden), and diphtheria-tetanus-pertussis (UNICEF support). The reliance on technology transfer indicates a limitation in vaccine research and development in Vietnam. Another limitation stems from the use of traditional technologies in vaccine manufacture, including LAV, recombinant and attenuated/inactivated platforms, rather than newer, more advanced platforms like mRNA and DNA. Table 5. Current commercialized vaccines in Vietnam and their platform technologies Company/ Partnership R&D No. Platform Technology Production stage capabilities 10 Vaccines POLYVAC 1 Live, attenuated from primary monkey Not applicable Capacity to bOPV (Polio) switch from kidney cell culture traditional 2 Rotavin- M1 Not applicable platform Live, attenuated from Vero cell culture (Rotavirus) technology 3 JICA and Kitasato vector to mRNA Live attenuated from chicken embryo Whole Daiichi Sankyo manufacturing technology MVVAC (Measles) cell culture (technology transfer) containing AIK-C measles strain Vaccine process (e.g., Covid-19) Company 4 Live, attenuated (technology transfer) JICA and Kitasato MRVAC (Measles- containing AIK-C measles and Daiichi Sankyo Rubella) Takahashi Vaccine Rubella vaccine strains Company VABIOTECH 5 SLB institute, Capacity to mORCVAX Sweden switch from Inactivated (technology transfer) (Cholera) traditional Whole platform 6 JEVAX (Japanese Inactivated, from mouse brain WHO and Biken manufacturing technology to Encephalitis) (technology transfer) Institute of Japan process cell-based (e.g., 7 Gene-HBvax Green Cross, JE, Rabies, Recombinant (technology transfer) (Hepatitis B) South Korea Dengue, EV71, 8 Havax (Hepatitis A) Inactivated from cell culture Not applicable Influenza etc.) 10 R&D capabilities reflect the perspectives of the manufacturing companies themselves which were shared during in-depth interviews. 28 Company/ Partnership R&D No. Platform Technology Production stage capabilities 10 Vaccines or recombinant (e.g., Hib) platform; develop polyvalent/com bination vaccines IVAC 9 IVACFLU-S Inactivated, fragment, embryonated WHO Capacity to (Influenza) chicken eggs (technology transfer) switch from traditional 10 Human Institute, platform Hungary and technology to National Institute cell-free Td (Tetanus, Inactivated, fermented (technology for Public Health vaccines (e.g., Diphtheria) transfer) and the pertussis) Environment (RIVM), Netherlands Whole 11 DTP (Diphtheria, Inactivated, fermented (technology UNICEF manufacturing pertussis, tetanus) transfer) process 12 BCG (TB) Live, lyophilized (technology transfer) UNICEF 13 Human Institute, Hungary and National Institute Inactivated, fermented (technology for Public Health TT (Tetanus) transfer) and the Environment (RIVM), Netherlands DAVAC 14 National Institutes Develop of Health (NIH), polyvalent/ Typhoid Vi USA Whole combination Fermented, purified (technology Polysaccharide manufacturing vaccines based transfer) (Typhoid) process on current platform technology Although vaccine production facilities and equipment were originally planned and built for high- capacity production, none of the vaccine manufacturers in Vietnam have reached maximum production capacity, except for HAVAX for Hepatitis A; this is due to low domestic demand and export limitations (Figure 15). Low domestic demand may be influenced by the preference for imported vaccines among urban, high-income populations who access a choice of vaccines through the paid vaccination service. Regarding exports, currently only IVAC exports the tetanus vaccine to Laos and Cambodia in small quantities (approximately 0.1 percent of total production). The majority of vaccines manufactured in Vietnam are not exported because they have not been prequalified by the WHO, leading to a lack of international buyers. Moreover, vaccines that are 29 not WHO prequalified are ineligible for purchase by UNICEF, further limiting the export market for Vietnam vaccines. Figure 15. Current and existing maximum manufacturing capacity of domestic vaccines, by company (as of 2021) 11 35,000,000 30,000,000 Doses per year 25,000,000 20,000,000 15,000,000 10,000,000 5,000,000 0 JEVAX (Japanese Encephalitis) Td (Tetanus, Diphtheria) Rotavin- M1 (Rotavirus) DTP (Diphtheria, pertussis, MVVAC (Measles) Gene-HBvax (Hepatitis B) TT (Tetanus) BCG (TB) bOPV (Polio) IVACFLU-S (Influenza) Havax (Hepatitis A) mORCVAX (Cholera) Typhoid Vi Polysaccharide MRVAC (Measles – Rubella) (Typhoid) tetanus) POLYVAC VABIOTECH IVAC DAVAC Vaccine manufacturers Existing capacity Maximum capacity In the near future, in addition to the four state-owned companies that have been producing vaccines for many years, the two private companies VinBiocare and Nanogen have the greatest potential to become commercialized vaccine manufacturers. Currently, their vaccines are still in the process of obtaining market authorization: Nanogen’s COVID-19 vaccine Nanocovax is aiming to complete Phase 3 by March 2023, while VinBiocare’s VBC-COV19-154 vaccine has finished phase 3b of clinical trials (see Table 6, below). Although these companies are exclusively focused on COVID-19 vaccines at present, there is a possibility for expansion to other vaccines in the future. In-depth interviews with vaccine manufacturing companies revealed that the four state-owned companies have sufficient human resources, infrastructure, and equipment for their maximum manufacturing capacity, but likely not enough capacity in those areas to upgrade or expand to new technologies or vaccines. Personnel are trained and specialized for each production line and/or stage, though additional training, infrastructure and/or equipment would be required if the companies developed or received transfer of new technology. The government gave land to state-owned companies to build production facilities, but the budget to upgrade and update these premises is very limited. On the other hand, private companies have had to incur upfront costs investing in land, infrastructure and equipment before their products were authorized to sell. 11 Information provided by manufacturers during in-depth interviews. 30 Developing vaccines using new platforms requires substantial resources and comes with a high risk of failure. This results in high barriers to entry for private companies in vaccine manufacturing. However, the biggest concern among manufacturers is the lack of a long-term comprehensive strategy for domestic vaccine development, which has led to inefficiency in investments in vaccine R&D, including in human resource capacity building, infrastructure upgrading, and GMP maintenance. COVID-19 Vaccine Manufacturing Capacity There are currently seven COVID-19 vaccines under development or production in Vietnam. Of these, three were researched and developed domestically (Nanocovax, Covivac, and Covinvac), two were technology transfers from abroad (VBC-COV19-154, SARS-CoV-2 Spike Protein, and COVID-19 DNA Vaccine), and one was filled and packaged in Vietnam (COVID-19 vaccine Sputnik V) (MOH, 2022). None of these vaccines have been approved for marketing authorization. Differing from other types of domestically-produced vaccines, COVID-19 vaccines employ more modern technologies such as viral vector and mRNA and DNA technology (Table 6), with which domestic manufacturing companies have limited experience. Additionally, companies have struggled to complete phase 3 clinical trials because the number of eligible subjects enrolled in clinical trials is very low due to the high rate of COVID-19 immunization throughout the country (nearly 100 percent). The cost of conducting clinical trials in other countries is prohibitively high. 31 Table 6. COVID-19 vaccines in Vietnam Vaccine Company Production Stage Manufacturing Technology Progress capacity platform Nanocovax Nanogen The entire 20-30 million Recombinant, Completed Phase Pharmaceutical production doses/year, protein subunit 3a CT in August Biotechnology process (both scaling up to vaccine 2021. Planning to JSC. upstream and 100 million complete entire downstream) doses/year phase 3 by March 2023 and undergo the process for licensing marketing authorization. Covivac Institute of The entire 6 million Viral vector, Completed Vaccines and production doses/year, cultured on phase 2 CT in Medical process (both scaling up to 30 embryonic December 2021 Biologicals (IVAC) upstream and million chicken eggs downstream) doses/year Covinvac VABIOTECH The entire 30 million Recombinant Completed production doses/year baculovirus preclinical trial in process (both March 2021 upstream and downstream) VBC-COV19- VinBiocare, The entire 100-200 million mRNA amplifying Completed 154* Vingroup production doses/year phases 3a and 3b process (both in December upstream and 2021 downstream S-268019 VABIOTECH and The entire Recombinant Ongoing phase 3, vaccine** AIC Group production protein expected process (both ------ (Baculovirus completion date upstream and Expression December 2023 downstream) Vector System) Sputnik V VABIOTECH Filling and 60 million Adenovirus viral First lot packaging of bulk doses/year, vector completed since products scaling up to 2021. However, 100 million distribution plan doses/year for finished vaccine will be decided by Russia. * Technology transferred from Arcturus Therapeutics, USA ** Technology transferred from Shinogi company, Japan. Source: Vietnam COVID-19 vaccine portal. Incentives for Domestic Manufacture of Vaccines The Government of Vietnam has made a strong commitment to build and strengthen domestic vaccine manufacturing capacity. In October 2021, a decision of the National Priority Science and 32 Technology Program "Research and Production of Human Vaccines by 2030" was approved by the Government. The objective of the program is to study and master the technology of producing vaccines for human use, improve the capacity of domestic vaccine research and vaccine manufacturing, and build readiness to address emerging epidemics. The program aims for 100 percent of domestic vaccines to meet international standards, including all vaccines in the NEPI, and to gradually bring Vietnamese vaccines to the international market. In addition, it aims to grow vaccine manufacturing capacity in Vietnam by calling for a mastery of technology required to produce 10 types of vaccines with actual production of at least 3 types of vaccines by 2025, and a mastery of the technology to produce 15 types of vaccines with actual production of at least 5 types of vaccine by 2030. To achieve the above goals, key tasks of reviewing, amending, and supplementing legal regulations, and promoting research, experimentation and licensing for the use of domestic vaccines have been initiated. Specific policies related to vaccine use in a pandemic situation were also addressed. The program also promotes research and application of new, advanced, and traditional technologies—prioritizing mRNA technology, recombinant protein technology, and viral vector technology—to enhance the production of COVID-19 vaccines, cancer vaccines, pentavalent vaccines and other vaccines to meet the needs of disease prevention and control. More importantly, the decision clearly states that organizations and manufacturers engaged in vaccine research and development and/or technology transfer for vaccine production are entitled to the same preferential policies as other domestically-produced products. Regarding the development of vaccines against COVID-19 or future pandemics, 100 percent of the budget used for research, clinical trials, trial production, quality control, insurance, and incentives for volunteers is covered by the government. Through this program, the Government also offers incentives to vaccine developers and manufacturers by officially including them among groups that may apply for the benefits stipulated in official letter No. 918/TTg-KGVX of the Prime Minister (dated June 2011) on mechanisms and policies to support investment projects of antibiotic-raw material production, including bank credits from the Vietnam Development Bank, low loan interest rates supported by the State, and granting of tax waivers. Additionally, vaccine projects are also allocated or leased 10 to 15 hectares of land in Hoa Lac Hi-Tech Park to build manufacturing facilities. The Ministry of Science and Technology has been asked to quickly establish a framework to protect key intellectual property in vaccine development, while the Ministry of Finance was tasked with generating a reasonable price when vaccines are available. There are no specific incentives or funds for vaccine R&D conducted by academic institutions, but they can apply to the state budget to conduct vaccine research. Domestic vaccine development was also addressed in the Program for Development of Pharmaceutical Industry and Domestically Produced Medicinal Materials by 2030 and Vision towards 2045, which was approved by the Government, with an Executive Plan for implementing the program signed by MOH. This program highlighted plans to build capacity to improve vaccine 33 quality control and produce pentavalent vaccine in addition to vaccines for outbreaks, including COVID-19 12. During the period 2010-2020, the Government approved the National Program of Vaccine Development for Human Disease Prevention as a part of the Program for National Product Development to 2020, which was implemented under the direction of the Prime Minister in Decision No. 2441/QD-TTg (dated December 2012). This program offered special policies to develop national products, promote the domestic market, and build the export market abroad. The program aimed to be proactive in identifying technology for the creation of vaccine-like strains in order to manufacture vaccines on an industrial scale to serve the NEPI, and to prepare against potential outbreaks. It also aimed to improve the domestic scientific and technological potential for research, production and commercialization of at least 7 important vaccines, including pentavalent, rotavirus, Japanese encephalitis, influenza, typhoid, rabies, and hepatitis A in Vietnam. Five institutions—POLYVAC, VABIOTECH, IVAC, DAVAC, and NICVB—were directly assigned to the program. The program officially started in 2015 with 9 projects covering 11 individual sub-projects. By December 2020, 8 subprojects were completed with 1 licensed product, 1 product pending MOH approval, and owned combining technology of 5-in-1 vaccine (diphtheria, tetanus, whole cell pertussis, hepatitis B, and Hib conjugates). However, targets for vaccine commercialization were not achieved within the short program timetable 13 14 (Table 7). 12 Prime Minister Decision No. 376/QD-TTg, dated 17-3-2021. 13 Ministry of Health. Decision No. 2792/QD-BYT dated 05-06-21. 14 Prime Minister Decision approved strategy for science and technology development, period 2011-2020. 34 Table 7. Subprojects funded under the National Program for the Development of Vaccines for the Prevention of Human Diseases Budget Sub-project Implementer Period (Billion VND) 1. Completion of technological standard operational procedure (SOP) for POLYVAC 28 2018- 2021 manufacturing measles vaccine meeting WHO pre-qualification 2. Evaluation of safety and immunogenicity of inactivated polio vaccine under the Project POLYVAC 7.5 2015-2020 "Research and production of inactivated polio vaccine" 3. Research and manufacture 11 standard NICVB 30.1 2017-2021 vaccine samples used for testing vaccines 4. Completion of the technological SOP for the manufacturing ingredients of Hib conjugate VABIOTECH 22.420 2015-2020 vaccines at industrial scale 5. Completion of the technological manufacturing process for the Japanese VABIOTECH 24.2 2015-2020 encephalitis vaccine in Vero cells 6. Research and development of the manufacturing process for 5-in-1 vaccines (diphtheria, tetanus, whole-cell pertussis, IVAC 14.130 2018-2020 hepatitis B and Hib conjugates) with solution absorption form at the scale of 40,000 doses/lot 7. Research and development of the process for the ingredients of the acellular pertussis IVAC 14.2 2015-2018 vaccine with purified and inactivated forms at the basic standard for mixing 8. Research and development of manufacture DAVAC 9.36 2015-2019 process for typhoid Vi-conjugate vaccine Source: Prime Minister, 2012. Decision approved strategy for science and technology development, period 2011- 2020. Patent Registration and Intellectual Property 35 Patent registration is managed by the Vietnam Intellectual Property Office, which belongs to the Ministry of Science and Technology. As with other products, vaccines are expected to follow national patent registration procedures. The office complies with international treaties related to intellectual property (IP). Vietnam is a member of the WTO and as such, it must adopt IP enforcement measures stipulated by the TRIPS Agreement including civil remedies, customs interceptions of infringements, criminal remedies (at least for willful trade), and administrative remedies for handling administrative offences. An administrative enforcement system is a primary feature of Vietnam's IP protection. Vietnam is a country with a high rate of IP infringement, especially in online cases, while the enforcement of IP right protection is low. In 2019, the government approved a new strategy that prioritized the completion of IP legislation, policies, and laws. Furthermore, Vietnam’s laws and regulations on IP protection are currently being reviewed and expected to be amended in accordance with the EU-Vietnam Free Trade Agreement (EVFTA). The EVFTA has an IP chapter that mandates Vietnam to provide greater IP protection to rights holders. Furthermore, given the increasing number of cyber-infringement cases, Vietnam will shift its focus towards developing its legal framework and practical mechanisms to tackle IP infringement in the contemporary digital environment. With additional, higher requirements for IP standards under the Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP) and EVFTA, the laws are expected to be further amended. SWOT Analysis of Vietnam’s Potential in the Vaccine Value Chain STRENGTHS WEAKNESSES Regulatory Old No update Long system infrastructure technology experience Networking Shortage of Maintaining Sufficient WHO-GMP qualified human GMP supply for qualification resources NEPI WHO pre- qualification Investment Comprehensive Low Pandemics cooperation strategy Investment Government Low vaccine Unclear commitment Competition prices restructure Low Mechanism Motivation Brain drain OPPORTUNITIES THREATS 36 The strengths of the Vietnam vaccine manufacturing and production system include: • Years of experience in vaccine R&D and manufacturing and institutional knowledge of the vaccine industry. Vietnam is one of the few countries in the region that supplies vaccines to support NEPI through domestic vaccine manufacturing. The first vaccine produced in Vietnam was the polio vaccine, which was piloted in 1962 after technology transfer from the Soviet Union. Later, with the support from the WHO and Japan, the polio vaccine was produced and fully supplied to NEPI from 1995 until the eradication of polio in 2000. DPT, BCG, and rabies vaccines began production in 1978 and were fully supplied to NEPI by 1980. • An operational regulatory system that provides direction and guidelines for all activities, from the research and development stage to production and post-marketing surveillance. The country’s vaccine management system and NRA have been recognized by WHO since 2018. • State-owned manufacturers that meet WHO-GMP requirements and are responsible for at least 13 production lines that produce 14 different types of vaccines. All vaccines produced locally have complied with the WHO-cGMP (current GMP). • Local vaccine production that has ensured sufficient vaccine supply for NEPI since the 1980s. WHO ranks Vietnam as one of 25 vaccine producing countries, which together account for over 90 percent of global sales. Vietnam is also the fourth country in Asia to produce Measles-Rubella vaccine, after Japan, India and China. • An NEPI distribution network that is available and functioning at all levels and in all provinces. As described throughout the report, Vietnam’s vaccine system has weaknesses as well, including: • Old and out of date infrastructure and facilities at all state-owned manufacturing facilities, which are the result of chronic insufficient investment. As such, it is difficult for vaccine innovators to implement high-tech research, receive new technology, increase production capacity, and perform quality control for new technology platforms. However, this is not the case in the two private companies, which were recently equipped with modern production lines and research facilities. • The predominance of “traditional” technology platforms within vaccine production system, especially among state-owned companies. Adequate attention has not been paid to technology updates, though the two private vaccine companies are applying new technology in vaccine development of COVID-19 vaccines. • A shortage of qualified human resources to independently develop new vaccines, especially high-tech vaccines. This may be due to several factors, including lack of a long- term strategy for vaccine development or a training and capacity building plan. • High cost of maintaining GMP among local manufacturers, especially considering budget shortages and limited government investment. However, this may not be a problem for the two private companies. 37 • Inability to access the vaccine export market, as no domestic manufacturers have been prequalified by the WHO. Obtaining WHO prequalification for vaccine production is very difficult for state-owned institutions because of poor facilities, funding shortages, incomplete or insufficient dossiers, and other factors. Among private manufactures, obtaining WHO prequalification was mentioned in their future plans; however, as none of their vaccines have yet been licensed, it is not clear if they will be pursuing WHO prequalification. • Lack of quality control capacity for a new technology platforms, due to limited human resources and equipment. However, opportunities exist for Vietnam to increase its vaccine manufacturing capacity, such as: • A history of cooperation between research and manufacturing entities and international organizations around technology transfer for vaccine development. These manufacturers have also received funding from the ODA and preferential loans for infrastructure and facilities in the past. Recently, opportunities for investment cooperation from private enterprises and external organizations have been offered to state-owned local manufacturers while they wait for government approval of proposed restructuring. • Stated government commitment to prioritize vaccine security, as articulated in the decision of the National Priority Science and Technology Program Research and Production of Human Vaccines by 2030, the Program for Development of Pharmaceutical Industry and Domestically Produced Medicinal Materials by 2030 and Vision to 2045 approved by the Government and Executive Plan for implementing this program signed by the MOH. The program focuses on improvement of vaccine quality control, pentavalent vaccine, and vaccines for existing/potential pandemics, i.e. COVID-19. 15, 16 • The potential for pandemics and emerging health crises, which, though tragic, can also trigger action from top-level decision makers to invest in public health preparedness infrastructure. Finally, threats to Vietnam reaching its vaccine security goals include: • The lack of a comprehensive and clear strategy in the short- and long-term for vaccine development. This was the most crucial issue mentioned by all manufacturers. The lack of such a strategy has resulted in unexpected consequences, including improper investment, and uncertain R&D and business planning. • Impractical and/or ineffective policy enforcement, which brings hardship to manufacturers. • Insufficient investment from the government to all state-owned institutions, in addition to limited revenue earned by enterprises due to low vaccine prices as set by the government and the inability to export vaccines. This lack of investment has impeded infrastructure upgrading, access to new technology, and even staff training. 15 Prime Minister, 2019. Approval of intellectual property strategy by 2030. 16Prime Minister, 2021. Decision No. 1657/QD-TTg dated 1-10-21 approved the National Priority Science and Technology Program “Research and Production of Human Vaccines by 2030.” 38 • Competition from imported vaccines, which are preferred by segments of the population. This limits both the domestic and global market for Vietnam-manufactured vaccines. • MOH pricing of NEPI vaccines that has not changed since 2008, despite increases in production costs. None of state-owned enterprises have negotiating power to change the vaccine pricing scheme. The situation results in low revenue/income for manufacturers, which negatively impacts the amount of resources available for R&D, reinvestment in company infrastructure (for example, to maintain GMP status), and even for staff compensation. • Low motivation and a lack of optimism among vaccine R&D and manufacturers due to a number of constraints, including low income, low investment, no infrastructure upgrades, lack of a comprehensive strategy, etc. • Unclear and changing structures of state-owned manufacturers that impede the development of long-term strategic plans. Four state-owned vaccine manufacturers are now para-statal, with the government retaining at least 50 percent ownership. Recently, two of the four manufacturers have been directed towards equitization. However, the companies face issues of property valuation, which are very complicated and will be challenging to solve in forthcoming years. • Brain drain from the public to the private sector or from vaccine R&D to other fields, such as biological, reagents and medicines, due to existing constraints in the vaccine production field. Conclusion Vietnam has a demonstrated capacity to manufacture vaccines for the domestic market and great potential to manufacture new vaccines and vaccines that can be exported to the global market. A priority area for Vietnam manufacturers would be investing in achieving WHO prequalification, an essential standard for global export. From a policy perspective, Vietnam would benefit from formulating a very clear vaccine industry development roadmap with sufficient funding allocation so that manufacturers feel assured that their investments align with national goals. Vietnam has strengths in several key areas that would benefit regional vaccine security efforts. Vietnam’s NEPI has strong program planning and annual forecasting processes that ensure sufficient vaccine is produced by local manufacturers; Vietnam could spearhead regional efforts to tighten the intersection between planning and production. In addition, Vietnam manufacturers have considerable experience cultivating strategic partnerships for technology transfer and successfully integrating new technologies; further, the country was selected to be part of the mRNA technology transfer hub to support global dissemination of mRNA vaccine technology. Vietnam is positioned to take the lead on pursuing technology transfer arrangements that have regional benefit. 39 References GAVI. 2018. Joint Appraisal report 2018. General Statistics Office. 2021. Key results of census survey on population change and family planning by 1 April 2020. General Statistics Office. 2021 (b). Statistical summary book of Vietnam in 2020. General Statistics Office. 2022. Infographic of population, labour and occupations in 2021. Available online at: https://www.gso.gov.vn/du-lieu-va-so-lieu-thong-ke/2022/01/infographic-dan-so-lao-dong-va- viec-lam-nam-2021/ Government Resolution No. 104/NQ-CP dated 15/8/2022 on the roadmap to increase types of vaccines in NEPI period 2021-2030. Ministry of Health. (n.d.) NRA Activities webpage. https://vncdc.gov.vn/hoat-dong-nra-nc5644.html Ministry of Health. 2015. Comprehensive Multi-Year Plan cMYP for Extended Program on Immunization 2016-2020. Ministry of Health. 2019. Health Statistics Yearbook 2018. Ministry of Health, 2020. Decision No. 3659/QĐ-BYT dated 21/8/2020 on research, clinical trials, marketing authorization and use of COVID-19 vaccine. Ministry of Health. Information of National Program of Vaccine Development for Human Disease Prevention 2021. Available online at: https://moh.gov.vn/tin-tuc-chuong-trinh-vac-xin. Ministry of Health. 2021. Project proposal on domestic production of vaccines against COVID-19 in the period to 2025 with a vision toward 2030. Ministry of Health. 2021 (b). Decision No. 2792/QĐ-BYT dated 05/06/2021 appoved Executive Plan for implementing Program for Development of Pharmaceutical Industry and Domestically Produced Medicinal Materials by 2030 and vision to 2045. Ministry of Health. 2022. Available online at: https://moh.gov.vn/tin-lien-quan/- /asset_publisher/vjYyM7O9aWnX/content/5-loai-vaccine-phong-covid-19-uoc-nghien-cuu-san-xuat-tai- viet-nam Ministry of Health, General Department of Preventive Medicine. COVID-19 data in Vietnam 2022. Available online at: https://ncov.vncdc.gov.vn/viet-nam-full.html. NEPI. 2018. Annual report of the National Expanded Immunization Program in 2017. NEPI. 2019. Annual report of the National Expanded Immunization Program in 2018. 40 NEPI. 2019 (b). Proposal to apply GAVI support for Cold Chain Equipment Optimisation Platform support in 2019. NEPI. 2020. Annual report of the National Expanded Immunization Program in 2019. NEPI. 2021. Annual report of the National Expanded Program of Immunization in 2020. NEPI. 2022. Annual report of the National Expanded Immunization Program in 2021. Official G. Resolution No.168/NQ-CP dated 31 Dec 2021 about some mechanism and policy in prevention and control of COVID-19 Prime Minister Decision No. 418/QD-TTg dated 1 April 2012 approving the Strategy for Science and Technology Development for the 2011-2020 period. Prime Minister. 2012. Decision approved strategy for science and technology development period 2011 - 2020. Prime Minister. 2019. Approval of intellectual property srategy by 2030. Prime Minister. 2021. Decision No 376/QĐ-TTg dated 17/3/2021 appoved the Program for Development of Pharmaceutical Industry and Domestically Produced Medicinal Materials by 2030 and vision to 2045. Prime Minister. 2021 (b). Decision No. 1657/QĐ-TTg dated 1/10/2021 approved the National Priority Science and Technology Program "Research and Production of Human Vaccines by 2030." UNICEF. 2020. Rapid Assessment on the Social and Economic Impacts of COVID-19 on Children and Families in Vietnam. UNICEF. 2020 (b). Rapid Assessment on Social Assistance Needs among Children and Families affected by COVID-19. United Nations Development Program. 2020. UN Analysis on Social Impacts of COVID-19 and Strategic Policy Recommendations for Vietnam. United Nations Inter-Agency Group for Child Mortality Estimation. Data retrieved October 17, 2022 from https://data.unicef.org. Indicator: Infant mortality rate – Vietnam. United Nations Population Division. 2022a. World Population Prospects: 2022 Revision. Data retrieved October 17 2022 from https://data.worlsbank.org. Indicator: Population ages 65 and above (% of total population) – Vietnam. ---. 2022b. World Population Prospects: 2022 Revision. Data retrieved October 17 2022 from https://data.worldbank.org. Indicator: Fertility rate, total (births per woman) – Vietnam. ---. 2022c. World Population Prospects: 2022 Revision. Data retrieved October 17 2022 from https://data.worldbank.org. Indicator: Mortality rate, adult, male (per 1,000 male adults) – Vietnam. 41 WHO/UNICEF. 2021. Viet Nam: WHO and UNICEF estimates of immunization coverage: 2020 revision. World Health Organization. 2018. Noncommunicable diseases country profiles 2018. Geneva: World Health Organization. WHO. 2021. ‘Vietnam’s vaccine regulatory system reaches WHO’s second highest level.’ Available online at: https://www.who.int/vietnam/news/detail/12-04-2021-viet-nam-s-vaccine-regulatory-system- reaches-who-s-second-highest-level. WHO. 2021 (b). Global Benchmarking Tool (GBT) for evaluation of national regulatory systems of medical products, revision VI. World Health Organization, 2021. Licence: CC BY-NC-SA 3.0 IGO. WHO. 2022. COVID-19 in Viet Nam Situation Report 86. WHO. (n.d.-a). Health Financing in Vietnam. Available online at https://www.who.int/vietnam/health- topics/health-financing. WHO. (n.d.-b). WHO COVID-19 Dashboard. Accessed 9-12-22 at https://covid19.who.int/region/wpro/country/vn 42 ANNEX 1. LIST OF AGENCIES INTERVIEWED # Agencies 1. Ethical Committee in Biomedical research (NEC) 2. Advisory Council for the issuance of Registration certificates for Drugs and Medicinal ingredients (ACRDM) 3. Advisory Council on use of Vaccine and Bio-medical product (ACVB) 4. Advisory Council for Assessment of Adverse Events Following Immunization (ACAEFI) 5. Center for Research and Production of Vaccines and Biologicals (Polyvac) 6. Vaccine and Biologicals Company (Vabiotech) 7. Institute of Vaccines and Biologicals (IVAC) 8. Dalat Vaccine Company (DAVAC) 9. Nanogen Pharmaceutical Biotechnology JSC (Nanogen) 10. VinBiocare, Vingroup 11. National Institute of Hygiene and Epidemiology (NIHE) National Expanded Program for Immunization (NEPI) 12. Ho Chi Minh Pasteur Institute (HCMIP) 43