Table of Contents FIGURES ................................................................................................................................................ 4 TABLES .................................................................................................................................................. 4 ACKNOWLEDGMENTS ......................................................................................................................... 5 EXECUTIVE SUMMARY ........................................................................................................................ 6 INTRODUCTION ..................................................................................................................................... 8 Value Addition of the Project ............................................................................................................... 8 PHILIPPINES COUNTRY CONTEXT AND NATIONAL IMMUNIZATION PROGRAM ........................ 9 The Impact of COVID-19 on Vaccine Service Delivery .................................................................... 10 The National Immunization Program ................................................................................................ 11 COVID-19 vaccination ....................................................................................................................... 13 Vaccine Delivery ............................................................................................................................... 16 Projected Vaccine Needs .................................................................................................................. 16 VACCINE PROCUREMENT ................................................................................................................. 16 ROBUSTNESS OF REGULATORY SYSTEMS................................................................................... 20 Protocol for Registering New Vaccines ............................................................................................. 20 Applicability of Regional Harmonization Policy for New Vaccine Registration ................................. 21 Gaps to be Addressed in order to Enhance Oversight of Vaccine Manufacture .............................. 21 Robustness of Existing Pharmacovigilance and AEFI Systems ....................................................... 21 RESEARCH AND DEVELOPMENT ..................................................................................................... 22 DOMESTIC MANUFACTURING AND DISTRIBUTION CAPACITY ................................................... 22 Other Potential Candidates in the Private Sector ............................................................................. 22 Binding Constraints Encountered by Manufacturers for Domestic Vaccine Production ................... 23 Incentives for Domestic Manufacture of Vaccines ............................................................................ 23 Regulatory and Procurement Rules that Favor Domestic Manufacturers ........................................ 24 Patents .............................................................................................................................................. 24 Local Companies Currently Engaged in Vaccine Distribution .......................................................... 24 CONCLUSION ...................................................................................................................................... 25 SWOT ANALYSIS ................................................................................................................................ 27 REFERENCES ...................................................................................................................................... 28 ANNEXES ............................................................................................................................................. 30 ANNEX 1. FDA requirements on the Certificate of Product Registration (Food and Drug Administration, 2020) ................................................................................................................................................. 30 ANNEX 2. VIP Roadmap (Department of Science and Technology, 2022) ..................................... 38 ANNEX 3.1. Corporate Recovery and Tax Incentives for Enterprises Act of CREATE (Board of Investments) ...................................................................................................................................... 39 ANNEX 3.2. Title XIII Incentives (Board of Investments) .................................................................. 39 ANNEX 3.3. SIPP – Industry Tiers (Board of Investments) .............................................................. 40 ANNEX 3.4. 2020 Investment Priorities Plan (Board of Investments) .............................................. 40 2 ANNEX 3.5. All Qualified Activities Relating to the Fight against the COVID-19 Pandemic (Board of Investments) ...................................................................................................................................... 41 3 Figures Figure 1. Population distribution by age and gender, Philippines, 2020…………………………………………………………9 Figure 2. Ten leading causes of death, Philippines, 2020………………………………………………………………………………10 Figure 3. Leading causes of morbidity, Philippines, 2021 .................................................................................10 Figure 4. Annual coverage per vaccine, Philippines, 2010-2020 ......................................................................13 Figure 5. COVID-19 vaccine doses delivered and administered, Philippines, 2021-2022 .................................14 Figure 6. Diagrammatic workflow of vaccine procurement .............................................................................18 Tables Table 1. Vaccines in the Philippines National Immunization Program ................................................. 11 Table 2. COVID-19 vaccine coverage by region, Philippines, 2022 ..................................................... 15 Table 3. Philippines Department of Health budget for immunization, 2020-2022 ................................ 17 Table 4. NIP vaccine doses procured, Philippines, 2017-2022 ............................................................ 17 Table 5. COVID-19 vaccine doses by source, Philippines, 2022 ......................................................... 19 Table 6. COVID-19 vaccine doses procured/donated by brand, Philippines, 2022.............................. 19 4 Acknowledgments The Philippines case study was prepared by Partnership and Business Development, Dr. Maria Rosario Capeding under the Zuellig Pharma Corporation) and Ms. leadership of Dr. Ronald Mutasa, Practice Jannette Jakosalem (Marketing Managing Leader of Human Development. The report Director, Zuellig Pharma Corporation). benefited from technical inputs from Dr. Special thanks is given to DOH, FDA, DOST Ramana Gandham (Technical Advisor/former and BOI-DTI for their leadership and Lead Health Specialist), Dr. Andreas Seiter guidance and for allowing the active (Technical Advisor/ Industry Expert), Dr. participation of the above key resource Melissa Guerrero (Health Specialist), Mr. persons towards the successful completion Giles Newmarch (Senior Investment Officer, of this study. IFC), Ms. Ridhi Gupta (Investment Officer, IFC), Ms. Erin Sowers (Consultant), and Ms. The Philippines case study is part of a larger Zinaida Korableva (Operations Analyst). regional study with the following components: global desk review, private The information contained in this report sector landscape analysis, economic draws heavily from interviews and analysis, and country deep-dive case consultations conducted with the following studies. Partnership and collaboration with Philippines’ government officials: the ASEAN Secretariat under the leadership Undersecretary Myrna Cabotaje, MD (Chair, of Dr. Ferdinal Fernando and Ms. Jennifer Field Implementation and Coordination Dela Rosa, the UK Foreign, Commonwealth Team, National Vaccination Operation and Development Office, and the Global Center, DOH), OIC-Director General Oscar Financing Facility for Women, Children and Gutierrez, Jr., DVM (FDA), Director Ma. Adolescents was essential to the successful Soledad Antonio, MD (Bureau of International completion of the study. Logistics support Health Cooperation, DOH), OIC-Director Ma. was provided by Marl Jinno Salandanan Joyce Ducusin, MD (Supply Chain Gooc and Mae Myat Moe. The cover and Management Service, DOH), Kim Patrick report layout were designed by Kayleigh Tejano, MD (NIP Program Manager, DOH), Ghiot. Secretary Carlito Galvez, Jr. (Vaccine Czar and Chief Implementer, NTF COVID-19), Mr. Paul Ernest De Leon, MDM (Chief Science This report benefited from the valuable Research Specialist, DOST), Ms. Melissa comments of peer reviewers Dr. Matthew Bulao (Senior Science Research Specialist, Downham (Director, CEPI), Ms. Zeynep DOST), Ms. Guidditta Gelera (Senior Science Kantur (Global Manager, Health, IFC), Dr. Research Specialist, DOST), Mr. Marfil Lombe Kasonde (Senior Health Specialist) Forteza (Senior Project Manager, DOST), Mr. and Dr. Kayla Laserson (Deputy Director, Bill Manuel Cruz (Chief Investments Specialist, and Melinda Gates Foundation). The overall BOI-DTI), Ms. June Villasanta (Supervising technical guidance provided by Daniel Investments Specialist, BOI-DTI) and Lester Dulitzky (Regional Director for Human Angelo Alfonso (Senior Investments Development), Farid Fezoua (Global Specialist, BOI-DTI). Valuable insights were Director, IFC) and Aparnaa Somanathan also provided by private sector (Practice Manager, Health, Nutrition and representatives: Professor Lulu Bravo (Chair, Population) is gratefully acknowledged. NAEFIC/DOH; Executive Director, Philippine Foundation for Vaccination), Dr. Rommel Crisenio Lobo (Vice Chair NAEFIC/DOH; President, Philippine Society of Allergy, Asthma and Immunology), Atty. Jose Maria Ochave (Senior Vice President for External Affairs and Social Partnership, UNILAB), Mr. Michael Quijano (Vice President and COO, DistriPhil), Mr. Giovanni Alingog (CEO/President, Glovax Biotech Corporation), Mr. Robert Kruit (EVP Strategic 5 The Philippines has a large and youthful population of over 113 million (2021), of whom 30 percent are under One area of the age of 15. The Philippines’ Expanded strength in the Program for Immunization (EPI) has been in place since 1976; it currently includes Philippines is its vaccines against twelve diseases, which considerable are provided free of charge to children at government facilities. The Philippines has domestic expertise a devolved system of health care delivery, with the National Department of Health in vaccine clinical (DOH) responsible for forecasting, trials. procuring and monitoring the supply of vaccines, and Local Government Units (LGUs) ensuring vaccine delivery. Execut The Philippines began vaccinating its The Philippines has struggled to achieve high vaccine coverage rates ive citizens against COVID-19 in early nationally, and regional coverage rates 2021; by July 2022, nearly 64 percent Summ of the population had completed the vary widely. The COVID-19 pandemic further challenged the vaccine delivery ary initial vaccine protocol. Vaccine delivery system, as access to public health care proceeded slowly at first due to gaps in facilities was restricted due to community service delivery at the local level as well quarantines, and consumers avoided non- as inadequate knowledge of handling and emergency medical care. In April 2022, storing vaccines that require an ultra-cold DOH reported that more than half of chain. COVID-19 vaccine procurement vaccine-eligible children born during the was overseen by DOH with support from pandemic had not received any vaccine World Bank and Asian Development Bank dose. The Philippines has one central in negotiating and financing contracts with vaccine storage facility in the National global vaccine manufacturers. Capital Region, though another facility is under development. The Philippines has no domestic vaccine manufacturing capacity and The DOH oversees vaccine imports all needed vaccines, though procurement for vaccines with a local the Government has set a goal of distributor or supplier through a becoming vaccine self-sufficient competitive bidding process. through local production and capacity Procurement planning for EPI vaccines is building. One area of strength in the done on an annual basis based on Philippines is its considerable domestic population trends, though the Philippines expertise in vaccine clinical trials, having has a history of supply limitations and conducted hundreds of trials on vaccine vaccine stockouts. Stakeholders safety and efficacy, including for COVID- interviewed as part of this study 19, with globally-credible pharmaceutical suggested that longer-term (2-3 year) and vaccine manufacturers; this is an forecasting could help to secure area for which the Philippines could play a necessary budgets and ensure an leadership role in regional vaccine adequate, consistent vaccine supply. security efforts. As part of its effort to build 6 a domestic vaccine manufacturing In addition, the Philippines National industry, the Government has committed Regulatory Authority (NRA) has yet to to establishing a Vaccine and Virology reach Maturity Level 3, though the new Institute to further grow vaccine R&D administration has made this a priority. capacity. It has also initiated efforts to Significant investments and capacity create public-private partnerships and building are needed to reach this global liberalize incentives and tax exemptions to benchmark of a safe and effective vaccine encourage investment. regulatory system, especially in light of the Philippines’ interest in pursuing There are pharmaceutical companies in domestic vaccine manufacturing. As an the Philippines with the potential to alternative to prioritizing domestic manufacture vaccines, but key manufacturing, the Philippines could informants interviewed for this study benefit from a regional vaccine security described a number of concerns, ecosystem that would allow it to source including: vaccines from regional manufacturers • Dependency on imported raw while focusing on domestic capacity materials for vaccine production; building in vaccine delivery and • Difficult operating environment, procurement planning to ensure sufficient especially related to high labor costs vaccine supply. With its large population, and concerns about transparency in a market guarantee or long-term business transactions; commitment from the Philippines to • Need for policies that support procure vaccines from a regional source investments, such as long-term could help to encourage investment in advance market vaccine manufacture in the ASEAN commitment/guarantee by the region. Government; • Need to capacitate human resources with required technical skills for vaccine manufacturing; • Importance of building relationships with external partners to support technology transfer. 7 Introduction The COVID-19 pandemic 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 activity has three major components: 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. 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 8 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. Philippines Country Context and National Immunization Program The Philippines is the second-most populated country in the East Asia region behind Indonesia, with a population of over 109 million in 2020 living on more than 7,000 islands (Philippine Statistics Authority, 2022a), though more than half the population live in densely-populated urban centers (PSA, 2022b). The median age of the Philippines has increased over the past decade, from 23.3 years in 2010 to 25.3 years in 2020 (PSA, 2022c). The country’s age distribution creates an expansive population pyramid, with 31 percent of the population under the age of 15 and just 5 percent of the population over age 65, based on 2020 census data (Figure 1) (PSA, 2022c). Before the COVID-19 pandemic, the Philippines was one of Asia’s fastest growing economies, poised to move from lower-middle-income status to upper-middle-income status, but COVID-19 exacted a devastating toll on the Philippines, causing a severe economic contraction through 2020, though economic indicators for 2022 show resumed growth (World Bank, 2022). Figure 1. Population distribution by age and gender, Philippines, 2020 Source: Philippines Statistics Authority, 2022 9 The burden of disease has shifted to one of chronic, non-communicable diseases and diseases related to rapid urbanization and industrialization (Philippines Health Agenda 2016-2022) 1, which accounted for 71 percent of all deaths in 2020 (Figure 2). In 2021, the ten leading causes of morbidity affected over 2.64 million people (Department of Health, 2020c); three of them—animal bites (rabies), pneumonia and tuberculosis—relate to vaccine preventable diseases (Figure 3). Figure 2. Ten leading causes of death, Philippines, 2020 Source: Philippines Statistics Authority, 2020 Figure 3. Leading causes of morbidity, Philippines, 2021 Source: Field Health Services Information System 2021 Annual Report, Philippines DOH The Impact of COVID-19 on Vaccine Service Delivery In the Philippines, local transmission of COVID-19 was declared on March 7, 2020 (Department of Health, 2020b); by the end of June 2022, the Philippines had reported approximately 3.7 million 1 Philippine Health Agenda 2016-2022 https://www.slideshare.net/faboritoz/philippine-health-agenda-2016-2022 10 cases, resulting in over 60,500 deaths (Republic of the Philippines, 2022c). The pandemic severely challenged the delivery of health services as strict community quarantines and travel restrictions were implemented and manpower and resources diverted for COVID-19 response. The disruption of these services varied greatly across the nation, with urbanized cities bearing the brunt of COVID- 19 case management while geographically-isolated areas with minimal healthcare capacity were deprived of emergency care units due to travel and other restrictions (Bayani and Tan, 2021). Healthcare capacity was further challenged as healthcare workers fell ill with COVID-19 (Dy and Rabajante, 2020) and experienced psychological and emotional distress (Biana and Joaquin, 2020) as the pandemic continued to unfold. Immunization services in the Philippines also sustained pandemic-related disruptions: the Department of Health reported in 2022 that more than half of vaccine-eligible children born during the pandemic – 1.4 million children – had not received any vaccine. 2 UNICEF reported that between 2020 and 2021, national coverage rates declined by approximately 15-20 percentage points for nearly every vaccine in the national immunization schedule (WHO and UNICEF, 2022). The DOH, in partnership with WHO and UNICEF, is working to reach this population through targeted vaccine drives and a social media campaign (UNICEF, n.d.). The National Immunization Program In 1992, the Philippine government devolved the delivery of basic health services, including immunizations, from the National Department of Health (DOH) to Local Government Units (LGUs). National DOH maintained responsibility for forecasting, procuring and monitoring the supply of vaccines and other medical supplies used during routine immunization, and ensuring adequate provision of needed resources to local government unit (LGUs). LGUs took responsibility for ensuring the delivery of health services as well as managing the records on vaccines and communicating to the necessary stakeholders (e.g. DPCB-NIP) should there be a need for increased supply. The Expanded Program for Immunization (EPI) was implemented in the Philippines in 1976 by Presidential Decree 996 and aimed to provide basic immunization for children below eight years of age. Six vaccine preventable diseases (VPDs) were initially targeted—tuberculosis, poliomyelitis, diphtheria, tetanus, pertussis, and measles (Department of Health, 2014). By 2016 the program had expanded to include 12 VPDs (Table 1). Table 1. Vaccines in the Philippines National Immunization Program Vaccine Age Recommended No. of Doses in Primary Series BCG Birth 1 Dose Hepatitis B Birth 1 Dose Pentavalent (DTwP-Hep B-Hib) 6, 10, 14 weeks 3 Doses Oral Polio Vaccine (OPV) 6, 10, 14 weeks 3 Doses Inactivated Polio Vaccine (IPV) 14 weeks 1 Dose given with Oral Polio dose 2 DOH Press Release. https://doh.gov.ph/press-release/DOH-WHO-UNICEF-LEAD-REGULAR-ROUTINE-AND-CATCH-UP- IMMUNIZATION-DRIVES 11 Pneumococcal Cojugate Vaccine (PCV) 6, 10, 14 weeks 3 Doses Measles, Mumps, Rubella (MMR) 9 months and 12 months 2 Doses Tetanus-Diphtheria (Td) For children: 2 Doses 5-7 years old (Grade1) 12-15 years old (Grade 7) For childbearing women: 2 doses for first pregnancy 1 dose in each subsequent pregnancy for 5 total doses Measles Rubella (MR) 5-7 years old (Grade 1) 2 Doses 12-15 years old (Grade 7) Human Papillomavirus (HPV) Female 9-10 years old 2 Doses Influenza 60 years old and above 1 Dose Pneumococcal Polysaccharide Vaccine 60 and 65 years old 1 Dose (PPV) Source: National Immunization Program, Manual of Procedures. DOH Booklet 3, Chapter 4, The Vaccines NIP plans to add Rotavirus and Japanese Encephalitis vaccines to the NIP in the coming years, as recommended by the Philippine Pediatric Society (PPS), Pediatric Infectious Diseases Society of the Philippines (PIDSP) and the Philippine Foundation for Vaccination (PFV). Both vaccines are currently administered by private medical practitioners. An estimated 600,000 doses of JE vaccine were administered by private practitioners between 2016 and 2022. 3 Coverage levels for NIP vaccines have fluctuated over time, though recent data shows a generally decreasing trend for a number of vaccines (UNICEF, 2021) (Figure 4). Between 2008 and 2017, the percentage of children who had received all basic vaccinations decreased from 79.5 percent to 69.9 percent, while the percentage of children with no vaccination history rose from 39.3 percent to 43.7 percent (PSA and ICF, 2018). Decreasing coverage in recent years may be due in part to the effect of the Dengvaxia controversy in 2017, which caused significant consequences not only for vaccine confidence but on public trust in local leaders and experts (Mendoza et al., 2021). Other explanations for decreasing coverage include supply-side constraints (i.e. inadequate cold chain equipment to properly store vaccines) as well as demand-side factors, including lack of physical proximity to a health center or inconvenient timing of immunization services (World Bank, 2021). 3 Extrapolated data from Philippine FDA Lot Release Certificate for IMOJEV JE vaccine. Accessed online on 10-31-2022 at: https://verification.fda.gov.ph. 12 Figure 4. Annual coverage per vaccine, Philippines, 2010-2020 Source: UNICEF, 2022 COVID-19 vaccination COVID-19 vaccination levels have steadily increased since the National Vaccination Program began in early 2021, and as of July 2022, nearly 72 million Filipinos are fully vaccinated, representing 64 percent of the total population (Figure 5). However, COVID-19 vaccination coverage varies across regions: the National Capital Region, where the COVID-19 vaccine rollout began, has the highest number of completed vaccinations, while the Bangsamoro Autonomous Region in Muslim Mindanao has the lowest coverage (Table 2); this is consistent with coverage of childhood vaccines in the NIP. There is also a wide disparity between the number of fully vaccinated individuals and the number of individuals with a first booster dose. This is concerning as waning immunity can lead to additional surges in COVID-19 cases. Vaccine hesitancy has proven to be a challenge among some populations, especially the elderly and parents/guardians of vaccine-eligible children. DOH has worked with LGUs to combat vaccine hesitancy by engaging trusted community members and peer- educators to communicate the benefits of vaccination, and rolling out incentive programs to drive vaccine uptake. 13 Figure 5. COVID-19 vaccine doses delivered and administered, Philippines, 2021-2022 250 240 230 220 210 200 190 180 170 160 COVID-19 Doses (Million) 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 - Q1-21 Q2-21 Jul-21 Aug-21 Sep-21 Oct-21 Nov-21 Dec-21 Jan-22 Feb-22 Mar-22 Apr-22 May-22 Jun-22 Delivered Administered Source: Republic of the Philippines, 2022a 14 Table 2. COVID-19 vaccine coverage by region, Philippines, 2022 No. of No. of No. of Percent Individuals with Percent Individuals with Percent Population Target Fully Vaccinated Coverage (%) Region 1st booster Coverage (%) 2nd booster Coverage (%) Estimates 2022 Population as of June 20, (Fully as of June 20, (1st Booster) as of June 20, (2nd Booster) 2022 Vaccinated) 2022 2022 NCR 14,118,673 11,389,534 12,282,151 107.84 4,127,419 36.24 278,364 2.44 1 5,353,139 4,318,377 3,684,460 85.32 839,833 19.45 33,062 0.77 2 3,727,548 3,041,564 2,515,525 82.70 479,174 15.75 14,489 0.48 3 12,706,460 10,215,761 8,400,620 82.23 2,119,961 20.75 99,990 0.98 CAR 1,836,857 1,481,793 1,205,989 81.39 316,883 21.39 11,506 0.78 6 8,033,041 6,480,257 5,111,580 78.88 746,614 11.52 15,500 0.24 CALABARZON 16,654,975 13,435,568 10,338,692 76.95 2,508,784 18.67 121,635 0.91 10 5,128,964 4,137,535 3,083,599 74.53 485,137 11.73 14,083 0.34 11 5,451,448 4,397,685 3,181,741 72.35 494,053 11.23 33,733 0.77 7 8,147,078 6,572,248 4,733,096 72.02 713,644 10.86 17,121 0.26 Caraga 2,810,426 2,267,168 1,631,348 71.96 217,728 9.60 3,721 0.16 9 3,834,801 3,093,538 2,223,849 71.89 342,545 11.07 5,936 0.19 8 4,865,157 3,924,719 2,741,501 69.85 315,914 8.05 9,459 0.24 5 6,248,843 5,040,943 3,424,543 67.93 399,479 7.92 10,200 0.20 MIMAROPA 3,247,680 2,619,903 1,773,686 67.70 221,837 8.47 5,378 0.21 12 5,048,327 4,072,486 2,566,314 63.02 305,630 7.50 6,575 0.16 BARMM 4,358,837 3,516,278 1,169,857 33.27 128,035 3.64 1,457 0.04 TOTAL 111,572,254 90,005,357 70,068,551 77.85 14,762,670 16.40 682,209 0.76 Source: Republic of the Philippines, 2022b 15 Vaccine Delivery The Research Institute for Tropical Medicine (RITM) is the country’s central vaccine storage facility, with capacity to store up to a six month national supply; a new storage facility is currently in development with eight cold rooms and a digitized inventory system. From the central storage facility, vaccines are transported to all regions, provinces, cities and municipalities (LGUs) throughout the country. Once they reach the municipal level, the LGU is responsible for vaccine storage, on-site program implementation and vaccine administration. As a matter of policy, all levels within the national cold chain system should be equipped with functional cold chain equipment necessary at their respective levels, though this is not always the case, especially at the local level. National government funding for the NIP is primarily directed to vaccines, with minimal investment in transport and storage (Department of Health, 2022b). With regards to COVID-19 vaccine distribution, government respondents reported that DOH addressed their logistics needs (storage and distribution) through a third party following a competitive bidding process. The Philippines experienced challenges relating to COVID-19 vaccine delivery, especially early in the pandemic. As DOH has little control over service delivery within LGUs, there were considerable gaps in vaccine delivery at the local level. Additionally, knowledge and capabilities to handle specialized commodities in the field are quite limited. There is also evidence of significant wastage of vaccines due to a number of demand- and supply-side constraints, including: special requirements for storage of vaccines and scheduling of vaccination within a specific timeframe, operation-related issues, and natural disasters that affected vaccine storage and delivery. Similar to other countries, COVID-19 vaccine hesitancy is a considerable problem in the Philippines. Projected Vaccine Needs Currently, procurement planning for NIP vaccines is made on an annual basis with respect to the population trend. Respondents have suggested that transitioning to a 2 to 3 year supply forecast will help to secure necessary budgets for an adequate vaccine supply. In terms of COVID-19 vaccines, the Philippines has sufficient COVID-19 vaccine supply for 2022, according to DOH Bureau of International Health Cooperation (BIHC), while plans for vaccine procurement for 2023 have yet to be finalized as DOH is still looking into the epidemiologic shift and public acceptability of the vaccine. DOH has reported that maintaining a stockpile of the vaccine will be beneficial if or when a spike in cases occurs. Vaccine Procurement The Philippines has no domestic vaccine manufacturing capacity and must procure vaccines to ensure adequate supply. The process of procuring routine vaccines using government funds is overseen by DOH Financial Management and Supply Chain Monitoring Division and goes through DOH’s Procurement Management Service, abiding by the National Procurement Law. For vaccines with a local market, DOH connects directly with these distributors and suppliers through a competitive bidding process. The World Health Organization (WHO) and UNICEF support procurement efforts when local tender/bidding fails or there is no local vaccine supplier. Despite being a DOH priority program, the NIP faces procurement challenges. Vaccine stockouts at the national level are not uncommon and contribute to decreasing vaccine coverage rates. A DOH 16 self-assessment finds a lack of accountability that stems from limited governance and data generation. Limited data may be the result of a paper-based reporting system, incomplete reporting, and high staff turnover at the local level. Ensuring sustained funding has also been a challenge, with fiscal decentralization causing inconsistent funding for human and other resources (Department of Health, 2022b). All routine EPI vaccines are purchased with national government funds. In 2020, PHP 7.3 billion (US$125 million) was allotted for the NIP, accounting for 7.2 percent of the Philippine DOH budget (Department of Health, 2022b). The immunization budget increased in succeeding years to include the procurement of COVID-19 vaccine doses (Table 3) (Department of Health, 2020a, 2021b, 2022b). The observed decreased allocation for 2022 NIP vaccine doses is attributed to the abundance of supplies at the national and regional levels from the previous year, the result of delayed or missed vaccinations during the pandemic (Table 4). Table 3. Philippines Department of Health budget for immunization, 2020-2022 Year 2020 2021 2022 Budget for immunization 7.3 10.0 8.6 (in billions) Source: Department of Health, 2020a, 2021b, 2022b Table 4. NIP vaccine doses procured, Philippines, 2017-2022 Doses Vaccine 2017 2018 2019 2020 2021 2022 BCG 8,735,106 9,006,815 8,119,176 8,119,176 8,000,000 4,000,000 Hepatitis B 3,837,927 3,957,479 3,832,251 3,832,251 3,000,000 500,000 DPT-HEPB- HIB 11,530,340 11,888,995 10,230,162 10,230,162 8,000,000 2,000,000 bOPV 16,821,106 17,349,046 12,468,075 12,468,075 11,000,000 4,500,000 PCV 8,084,011 8,392,205 10,354,573 10,354,573 7,000,000 2,000,000 MMR 13,478,031 13,900,870 8,342,020 8,342,020 8,342,020 4,000,000 IPV 4,361,281 4,497,135 3,832,251 3,832,251 7,000,000 1,200,000 HPV 11,420,648 11,318,806 436,735 - 173,463 1,200,000 TD 7,675,854 7,550,171 7,374,601 7,374,601 7,374,601 2,000,000 FLU 11,325,256 2,000,000 15,011 15,011 5,000,000 5,600,000 PPV23 1,366,559 1,409,066 1,364,022 1,364,022 750,000 1,250,000 Source: Department of Health, 2022a For COVID-19 vaccines, the World Bank and the Asian Development Bank (ADB) played key roles in assisting DOH in obtaining vaccine supplies from the global market (Figure 6). When procuring COVID-19 vaccines using Loan Funds (e.g. funds from World Bank or ADB), the DOH-BIHC provided oversight, with guidance from the DOH Financial Management and Supply Chain Monitoring Division. In these cases, the rules of the international agreement superseded the Philippines’ procurement law requirements, resulting in a faster vaccine procurement process. As of June 2022, the Philippines had procured or received donations of over 245 million doses of COVID-19 vaccines of varying brands (Tables 5 and 6). Sinovac and AstraZeneca vaccines were used in the early stage of the National Vaccination Program, as they were the first to arrive in the 17 country. Then President Rodrigo Duterte issued Executive Order No. 121, which authorized the FDA to issue Emergency-Use Authorization (EUA) for COVID-19 vaccines that were still under development; all such EUA vaccines were used in the primary series—including Sinovac, AstraZeneca, Pfizer, Moderna, Janssen and Sputnik V—and as first heterologous booster dose according to DOH recommendations. The Philippine government began recommending a second booster in May 2022, for which mRNA vaccines were recommended. The availability of particular COVID-19 vaccines was dependent on vaccines distributed at respective vaccination sites. Figure 6. Diagrammatic workflow of vaccine procurement 18 Table 5. COVID-19 vaccine doses by source, Philippines, 2022 Source Doses National Government (procured) 134,087,880 COVAX (donation) 73,916,210 LGU and Private Sector (procured) 24,463,160 Other Countries (donation) 12,615,830 TOTAL 245,083,080 Source: Republic of the Philippines, 2022a Table 6. COVID-19 vaccine doses procured/donated by brand, Philippines, 2022 Source Doses Pfizer 92,428,260 Sinovac 56,105,400 AstraZeneca 38,846,950 Moderna 33,871,820 Johnson & Johnson 12,725,650 Sputnik V 10,000,000 Sinopharm 1,100,000 Sputnik Light 5,000 TOTAL 245,083,080 Source: Republic of the Philippines, 2022a 19 Robustness of Regulatory Systems The Philippine Food and Drug Administration (PFDA) has not yet achieved WHO Global Benchmarking Tool (GBT) Maturity Level (ML) 3, though it continually assesses its strengths and weaknesses against WHO GBT standards. In June 2022, the PFDA was visited by international experts from the WHO Western Pacific Regional Office (WPRO) Focal Point Regulatory System Strengthening Team and WHO Pre-Benchmarking Team. At that time, the PFDA received an overall rating of ML1, though some functions received higher scores than others; specifically, national regulatory system, registration and marketing, and clinical trials oversight were rated ML1; vigilance, licensing establishments, regulatory inspection, and laboratory testing were rated ML2; and the NRA lot release function was rated ML3. The WHO team determined that nine functions have greater than 80 percent implementation, and two have greater than 90 percent. There will be a follow-up assessment in October 2022 followed by a formal assessment scheduled for 2023. Prior to the COVID-19 pandemic, the FDA was limited in its ability to grant EUA for vaccines during health emergencies. As a matter of general policy, the Center for Drug Regulation and Research (CDRR) and an Expert Panel on vaccines conducts reviews and provides recommendations on the issuance of EUA, but quicker action was needed during the pandemic; as described previously, the Office of the President issued Executive Order No. 121, s. 2020 to address this need. In addition, there was a lack of provisions on indemnification of vaccine manufacturers during emergency situations, which led to some delays in COVID-19 vaccine procurement; this was a particular issue for the Pfizer vaccine, as the company required an indemnification clause prior to signing a supply agreement. This prompted the Philippine Government to pass the ‘COVID-19 Vaccination Act,’ which indemnified all vaccine manufacturers and vaccinators. However, as both of these policies relate to COVID-19 specifically and not to health crises generally, the need remains for broader legislation on disaster and emergency response to a pandemic. Protocol for Registering New Vaccines The Philippine FDA is a participating member of the National Medicines Regulatory Authority (NMRA) for the Collaborative Registration Procedure. It implements the guidelines on accelerated registration of WHO-prequalified pharmaceutical drugs and vaccines to ensure a constant supply and facilitate access to safe, effective, and quality drugs and vaccines. New vaccines must be registered and reviewed by the PFDA and are subject to the provisions of Republic Act No. 9711 or the “FDA Act of 2009” (Congress of the Philippines, 2009). The full requirements for the application for registration are included in Annex 1. Marketing approval in the form of a Certificate of Product Registration (CPR) is issued by the PFDA for the sale and distribution of the product in the Philippines; this certifies that the product meets the standards for quality, safety, and efficacy. A Health Technology Assessment Council (HTAC) was recently created as part of the Philippines’ UHC Law to evaluate the clinical and economic benefit of vaccines that will be included in the NIP. The HTAC, which is funded and implemented by DOH, also aims to ensure that proposed vaccines meet standards of equity/fairness, affordability, social acceptability and feasibility of implementation. Manufacturers of COVID-19 vaccines have committed to applying for marketing authorization once efficacy studies have been completed. The regular registration pathways will be enforced for both EUA and non-EUA vaccine applicants. 20 Applicability of Regional Harmonization Policy for New Vaccine Registration Registration of new vaccines in the Philippines follows the ASEAN Common Technical Dossier (ACTD), a guideline agreed upon by ASEAN member states for the preparation of applications for the registration of pharmaceuticals for human use. The Integrated Application Form and Process is used for filing and receiving of registration, licensing and other applications; it is also used by other ASEAN member states. Gaps to be Addressed in order to Enhance Oversight of Vaccine Manufacture The Philippine FDA is not yet a member of the Pharmaceutical Inspection Cooperation Scheme (PICS), though it is working to meet the requirements for inclusion and is planning to apply for PICS membership by second quarter of 2023. Following an assessment visit conducted by PICS members from Thailand, Indonesia, Malaysia, and Singapore, the Philippine FDA was given authority to conduct onsite inspections in 7 PICS non-member countries; it has also issued 175 GMP clearances in PICS member countries. The PFDA is included among ASEAN Listed Inspection Services effective January 2020, which was endorsed by ASEAN member states under the Mutual Recognition Arrangement (MRA). The Philippine FDA is moving forward with its application for ISO-17020. This accreditation process involves an assessment of competency for performing inspections and consistency of inspection activities. However, government respondents have reported that additional support in the form of manpower and training are required if the PFDA is to meet global standards. Robustness of Existing Pharmacovigilance and AEFI Systems The national policy and program on pharmacovigilance has been in existence in the DOH Epidemiology Bureau and PFDA since the 1990s and was formally recognized by the WHO as a National Monitoring Center in 1995. The DOH published a manual of procedures for adverse events following immunization (AEFI) in 2014 in response to increasing public concern for vaccine safety. It provides guidelines on the surveillance and management of AEFI for health professionals nationwide. The DOH has established several committees relevant to AEFI. The National AEFI Committee (NAEFIC) is composed of independent experts and has a goal of strengthening NIP and Vaccine Preventable Diseases (VPD) surveillance in the country; the Philippines has also established Regional AEFI committees. Epidemiology Surveillance Units at the local and regional levels receive reports of AEFIs and transmit them to Regional and National AEFI Committees to study causality; findings are then shared with the DOH Epidemiology Bureau and the PFDA. A separate NAEFIC was created during the COVID-19 pandemic to monitor AEFI cases related to COVID-19 vaccines. Experts from various fields were tasked with reviewing serious AEFI cases and assessing them according to the WHO AEFI causality assessment methodology. To facilitate the reporting of AEFI cases related to COVID-19 vaccines, DOH-FDA introduced the VigiFlow reporting system, which allows vaccination sites in the public and private sector to directly report cases of AEFI by link or QR code. As of July 2022, over 100,000 suspected adverse reactions had been reported (0.07 percent of doses administered) and over 9,200 cases of severe adverse events (less 21 than 1 percent of doses administered). 4 The Philippines government has an indemnification fund for all those who experience AEFIs following vaccination. In the case of AEFIs needing hospitalization, costs for the management of the adverse events are incurred by the National Health Insurance Program (PhilHealth). Research and Development The Inter-Agency Task Force for the Management of Emerging Infectious Diseases (IATF), convened by the Philippine government to respond to affairs concerning emerging infectious diseases in the country, has issued a resolution that COVID-19 vaccine trial applications shall be submitted directly to the Philippine FDA. A Panel of Vaccine Experts under the Department of Science and Technology (DOST) conducts reviews of clinical trial applications and real-world effectiveness data to ensure that the benefits outweigh the known and potential risks of candidate vaccines; the sponsor or Clinical Research Organization (CRO) simultaneously submits the study protocol to the Single Joint Research Ethics Board (SJREB) of DOH and to the individual Ethical Review Board (ERB) of the Institution. The Philippines has conducted numerous clinical trials on safety, immunogenicity and efficacy of vaccines, including those for COVID-19: 5 in 2020-21, 126 clinical trials approved by the PFDA were underway in sites throughout the Philippines, including eight Phase 1 clinical trials, 42 Phase 2, 75 Phase 3, and one Phase 4 trial. The country is recognized globally for its experience conducting clinical trials that meet Good Clinical Practice (GCP) standard. Domestic Manufacturing and Distribution Capacity The Philippines currently lacks domestic vaccine manufacturing capacity, though the government sees this as a goal and recently developed a vaccine manufacturing roadmap to guide its efforts to become vaccine self-sufficient through local production and capacity building (Annex 2). To this end, the country has committed to establishing a Php150 million (US$ 2.6 million) facility for the Vaccine and Virology Institute of the Philippines (VIP); it is envisioned to be the country’s premier research and development institute in the field of virology, where possible vaccine candidates would be explored, developed and taken through clinical trials, though not necessarily manufactured. Public-private partnerships have also been cultivated to build local vaccine manufacturing capacity. A tripartite agreement was signed in May 2022 among Department of Trade and Industry (DTI)- Board of Investments (BOI), National Development Company (NDC) and Glovax Biotech Corp. for the establishment of a Php7.5 billion (US$127 million) vaccine manufacturing facility. According to a key stakeholder, the partnership combines and builds on the technical and logistics capacities of each partner towards the development of a functional manufacturing facility for vaccines, with a focus on those that use protein subunit technology. The proposed facility will have the capacity to manufacture from the formulation stage of production. Other Potential Candidates in the Private Sector 4 According to Philippines FDA Reports of Suspected Adverse Reaction to COVID-19 (March 1 2021 to July 25 2022). 5 According to the Philippine Food and Drug Administration, Clinical Research Section, Product Research and Standards Development Division, Center for Drug Regulation and Research 22 There are pharmaceutical companies in the Philippines that have the potential to become vaccine manufacturers, such as United Laboratories, Inc. (UNILAB). In the early stages of the pandemic, UNILAB was prepared to turn their small volume parenteral (SVP) facility into a fill and finish facility, though this did not occur as the transformation of the facility required too long a timeline. UNILAB has also engaged in talks with partners offering mRNA and protein subunit technology for vaccine development. UNILAB is not a member of the Developing Country Vaccine Manufacturers Network. Binding Constraints Encountered by Manufacturers for Domestic Vaccine Production Key informant interviews revealed that there is interest in fill and finish vaccine production among potential domestic vaccine manufacturers, though there are concerns related to bulk importation of raw materials, which are still purchased outside the region. Furthermore, considering the huge investment required to establish a new vaccine manufacturing facility, there should be strong support by the government, which is currently not evidenced. Nevertheless, a respondent from the private sector expressed concern that the high number of government regulations could limit flexibility and collaborative opportunities with industry partners. Labor costs, political concerns, and bureaucracy related to business transactions suggest there may be a preference for importing vaccines from neighboring countries over domestic vaccine production. According to respondents from the pharmaceutical and vaccine supply industry, with the procurement laws of competitive bidding, vaccine importers could merely lower their prices to compete with locally manufactured vaccines, making investments in local vaccine production less attractive. Thus, the rationale for establishing a local vaccine manufacturing facility must be grounded in the premise of vaccine security instead of cost savings, with relevant long-term advance market commitment by the government. Capacity building is needed to grow the technical capabilities of health human resources. Key informant interviews with potential vaccine manufacturers revealed a preference for scientists with an industrial background or approach, implying that it would be preferable to recruit scientists with hands-on vaccine manufacturing experience over academic researchers. Technology transfer agreements will also be vital for increased capacity. Taiwan is an ideal partner for enhancing vaccine manufacturing capacity in the Philippines, with its strong scientific mission and advanced technology. Taiwan may also be an ideal option to supply the Philippines with vaccines given its small domestic vaccine demand and geographic proximity. Incentives for Domestic Manufacture of Vaccines The ‘Bayanihan To Heal As One Act,’ which declared a national emergency arising from COVID-19, also authorized the government to liberalize incentives and tax exemptions for manufacturing activities related to the pandemic, including for drugs and vaccines. Incentives include: a reduction of the corporate income tax (CIT) rate from 30 to 25 percent (or 20 percent for qualified domestic corporations), a two-year income tax holiday, and enhanced tax deductions. Additional details are included in Annex 3. The DTI-BOI has initiated negotiation efforts with foreign vaccine developers and/or originators that may be interested in partnering with local pharmaceutical companies. The BOI has identified 3- 23 4 local manufacturers that are capable of fill and finish vaccine production, though information about these efforts has not yet been made public. Regulatory and Procurement Rules that Favor Domestic Manufacturers A Joint Memorandum between various government agencies established a Green Lane to expedite the securing of permits, license processes and authorizations needed for the establishment and operations of a local COVID-19 fill and finish manufacturing facility. It also authorized the President to liberalize the granting of incentives for manufacturers. However, at this time there are no import restrictions to limit international competition nor price advantage for local pharmaceutical companies. Patents The Philippines has been a member of the World Trade Organization since 1995 and is compliant with provisions in the Trade-Related Aspects of Intellectual Property Rights (TRIPS). Specific to the Philippines context: • Pursuant to Philippine Technology Transfer Act of 2009, IP ownership is bestowed to the implementing agency with patent protection for 20 years without possibility of renewal (Intellectual Property Office of the Philippines, 2022). • The implementing agency and its concerned research team shall enjoy the economic rights on the IPs they produce. Recommended percent sharing between Research and Development Institutions (RDIs) and research teams on the gross revenue that will be generated from the commercialization of these IPs is 60/40. Local Companies Currently Engaged in Vaccine Distribution Several companies currently operating in the Philippines—namely Zuellig Pharmaceutical, DistriPhil, and Glovax Biotech Corporation—have the capacity to distribute vaccines as last-mile distributors. Zuellig Pharmaceutical is the largest distributor of multinational vaccines in the ASEAN region. The company possesses strong in-house cold chain capacity, with six warehouses (four in Luzon, one in Cebu, and one in Davao) equipped with state-of-the-art cold chain infrastructure. Three of these warehouses (one in Manila plus the two in Cebu and Davao) have the capacity to store the Pfizer COVID-19 vaccine at -70-80°C, while all have the capacity to store the Sinovac COVID-19 vaccine and influenza vaccines at 2-8°C. Zuellig uses a specialized packing cooler system which can maintain temperature for up to 72 hours during vaccine transport. The company delivers directly to immunization sites nationwide, which ensures efficient transportation and minimal handling. DistriPhil is the second-largest vaccine distributor in the Philippines after Zuellig. With the company’s license for importation and exportation of medical supplies, its focus is on ensuring vaccines and other medical services are accessible to the public. The company is able to house vaccines that require a storage temperature of 2-8°C and -20°C with multiple large warehouses (three in Luzon and one in Cebu) across the country. These include vaccines of GSK, Sanofi, Abbott, and Pfizer for NIP vaccines, and AstraZeneca and Moderna for COVID-19 vaccines. The company 24 offers end-to-end service with 21 COVID-19 vaccination sites nationwide as well as reverse logistics, including proper disposal of needles and syringes. Finally, Glovax Biotech Corporation has ten vaccine storage depots (eight in Luzon, one in Cebu, and one in Davao) with a capacity to store vaccines at 2-8°C. Vaccine transportation is done in cold chain boxes with thermal temperature logging, or in refrigerated or ambient temperature vehicles. Glovax distributes NIP vaccines from Pfizer, Merck, GSK, Sanofi, LG Chem, EuBiologics, Biotech, and Serum Institute of India, among other vaccine developers. Local Pharmaceutical Companies in the Vaccine Supply Chain There are a number of companies in the Philippines whose existing portfolios involve key ingredients or elements in the vaccine manufacturing and/or distribution supply chain. Euro-Med Laboratories Philippines, Inc. manufactures and sells various pharmaceutical products in-country and internationally. It distributes venipuncture and IV administration sets, supplies syringes for the NIP, and manufactures and distributes large and small volume parenterals and pharmaceutical products in liquid forms, including solvents for other drugs, sterile solutions for inhalation and irrigation, and specialty fluids such as dialysis solutions, mannitol injection, and plasma volume expander (Dextran 70). Hizon Laboratories, Inc. manufactures drugs and medicines including biological products, sera, and plasma. Drugmaker’s Laboratories, Inc. develops, manufactures, and sells medical devices and pharmaceuticals; it also undertakes clinical trials. Interphil Laboratories, Inc. manufactures, processes, and packages drugs, chemicals, pharmaceuticals, and veterinary products. The BOI has a Cold Chain Roadmap for the food industry, which identifies local manufacturers of special purpose vehicles (SVP) or retrofitted refrigerated trucks. BOI has spoken with these manufacturers to determine if vehicles could be used for the transport of vaccines when needed. Likewise, BOI has met with a local manufacturer of syringes to discuss a possible expansion. BOI aims to complement vaccine manufacturing with supply chain industries. Conclusion Potential domestic vaccine manufacturers would need to make considerable investments to establish vaccine manufacturing facilities and develop the capacity for new vaccine technologies, hence government assurance of support is greatly needed. The Filipino workforce, with expertise in vaccine research and development from both public and private institutions, can be responsive to the needs of the vaccine industry. There are numerous national and multi-country clinical trials being conducted in the country, which are sponsored by globally-credible pharmaceutical and vaccine manufacturers; researchers can readily collaborate with international vaccine research institutions. This experience conducting a large volume of clinical trials with GCP standard is an area of strength for the Philippines and one way that the country could contribute to regional vaccine security efforts. The Philippines’ large population and young median age require a substantial domestic vaccine supply, in particular for NIP vaccines. A commitment to meeting this need through procurement from the local or regional vaccine industry could be an incentive for potential domestic 25 manufacturers, as would a move towards multi-year forecasting of vaccine needs to ensure continued supply. A near-term priority for the Philippines is achieving ML3 status, which the country is already investing in. The Philippines has submitted an application to be accepted into PIC/S and is working to meet PIC/S GMP standard guidelines. It is also preparing for an upcoming WHO GBT audit by working to address challenges identified during a previous audit. Facility and manpower needs have been identified and the PFDA is working to address them through ongoing capacity-building efforts. Achievement of ML3 status would enable the Philippines to better support and participate in regional vaccine efforts. 26 SWOT Analysis Strengths • Strong commitment to the NIP by DOH (allocated budget and inclusion of vaccines of public health importance). • A large birth cohort, which contributes to the vaccine demand. • A workforce with expertise in vaccine R&D from both public and private institutions. • Established regulatory and ethical processes for conduct of clinical trials that meet Good Clinical Practice (GCP) standards. • Strong support by professional medical societies and advocacy groups for vaccination programs. • Established AEFI and pharmacovigilance system in DOH and FDA. • Government incentive programs for potential domestic vaccine manufacturers. Weaknesses • Planning for the NIP budget is done annually, which adversely affects the procurement process. • The Philippine FDA has yet to achieve Maturity level 3 based on the WHO GBT. • There is limited technical expertise on vaccine assessment and GMP-related procedures/processes. Opportunities • Strong political will of the new administration as evidenced in the creation of Vaccine and Virology Institute of the Philippines (VIP). • Recognition of legislative opportunities for passage of laws related to the importance of vaccination in the context of the COVID-19 experience. • Signed tripartite agreement to establish a domestic vaccine manufacturing facility. • Established partnerships with vaccine laboratories and manufacturing companies for hand- on training and biological transfers. • Approved budget for the improvement of FDA vaccine testing laboratory. • Building of a new central vaccine storage facility with greater capacity. • Improved cold chain capacity (storage and delivery) in the context of COVID-19 pandemic response. • Presence of efficient private sector vaccine distributors. Threats • Growing regional competitiveness in vaccine manufacture could challenge potential domestic vaccine manufacturers. • Impact of vaccine hesitancy in the National Vaccination Program. 27 References Bayani, D. B. S., & Tan, S. G. (2021). Health Systems Impact of COVID-19 in the Philippines. In DC (Vol. 416). www.cgdev.orgwww.cgdev.org Biana, H. T., & Joaquin, J. J. B. (2020). COVID-19: The need to heed distress callsof healthcare workers. In Journal of Public Health (pp. 1–2). Elsevier Ltd. https://doi.org/10.1016/S2215-0366(20)30047-X Board of Investments. (2022). Make it happen in the Philippines. Congress of the Philippines. (2009). Republic Act No. 9711: Food and Drug Administration (FDA) Act of 2009. Department of Health. (2020a). Budget Briefer 2021. Department of Health. (2020b). DOH Confirms Local Transmission of COVID-19 in PH; Reports 6th Case. https://doh.gov.ph/doh-press-release/doh-confirms-local-transmission-of-covid-19-in-ph Department of Health. (2020c). The 2019 Philippine Health Statistics. Department of Health. (2021a). Administrative Order No. 2021-0045: Guideline on the Conduct of Catch- Up of Routine Immunization for Children. http://www.doh.gov.ph; Department of Health. (2021b). Budget Briefer 2022. Department of Health. (2021c, March 18). Why does the Philippine Government need to buy different brands of vaccines? https://doh.gov.ph/node/28132 Department of Health. Field Health Services Information System 2021 Annual Report Department of Health. National Immunization Program, Manual of Procedures. Booklet 3, Chapter 4, The Vaccines Department of Health. (2022a). Annual Allocation Of National Immunization Program Vaccines 2017- 2022. Department of Health. (2022b). The Philippine National Immunization Strategic Plan and Direction 2022- 2026 (Draft May 2022). [Manuscript in preparation] Department of Health. (2014). National Immunization Program: Manual of Operations. Department of Science and Technology. (2022). Virology and Vaccine Institute of the Philippines Research & Development Roadmap: Gearing Towards Local Development of Vaccines. Dy, L. F., & Rabajante, J. F. (2020). A COVID-19 infection risk model for frontline health care workers. Network Modeling Analysis in Health Informatics and Bioinformatics, 9(1). https://doi.org/10.1007/s13721-020-00258-3 Intellectual Property Office of the Philippines. (2022). Patent. https://www.ipophil.gov.ph/patent/# Lassi, Z. S., Naseem, R., Salam, R. A., Siddiqui, F., & Das, J. K. (2021). The Impact of the COVID-19 Pandemic on Immunization Campaigns and Programs: A Systematic Review. J. Environ. Res. Public Health, 18. https://doi.org/10.3390/ijerph 28 Mendoza, R. U., Dayrit, M. M., Alfonso, C. R., & Ong, M. M. A. (2021). Public trust and the COVID-19 vaccination campaign: lessons from the Philippines as it emerges from the Dengvaxia controversy. International Journal of Health Planning and Management, 36(6), 2048–2055. https://doi.org/10.1002/hpm.3297 Philippine Statistics Authority. (2022a). Household Population, Number of Households, and Average Household Size of the Philippines (2020 Census of Population and Housing). https://psa.gov.ph/population-and-housing/node/166426 Philippine Statistics Authority. (2022b). Urban Population of the Philippines (2020 Census of Population and Housing). https://psa.gov.ph/population-and-housing/node/167692 Philippine Statistics Authority. (2022c). Age and Sex Distribution in the Philippine Population (2020 Census of Population and Housing). https://psa.gov.ph/content/age-and-sex-distribution-philippine- population-2020-census-population-and-housing Philippine Statistics Authority and ICF. (2018). National Demographic Health Survey 2017. Republic of the Philippines. (2022a). Vaccine Updates as of 21 June 2022. Republic of the Philippines. (2022b). Vaccines Administered per Region (per Individual) as of 20 June 2022. Republic of the Philippines. (2022c, June 30). COVID-19 Dashboard. https://www.covid19.gov.ph/ UNICEF. (2021, July). Immunization coverage estimates data visualization (Philippines). https://data.unicef.org/resources/immunization-coverage-estimates-data-visualization/ UNICEF. (n.d.) Building Confidence in Routine Immunization in the Philippines. Available online at https://www.unicef.org/philippines/building-confidence-routine-immunization-philippines World Bank. (2021). The Transition to Universal Health Coverage in BARMM. https://openknowledge.worldbank.org/handle/10986/35234 World Bank. (2022). Philippines Economic Update June 2022 Edition: Strengthening the Digital Economy to Boost Domestic Recovery. https://documents1.worldbank.org/curated/en/099325006072264961/pdf/P177408091735101c0b 25405cf39f312c86.pdf World Health Organization. (2020). WHO Director-General’s opening remarks at the media briefing on COVID-19 - 11 March 2020. https://www.who.int/director-general/speeches/detail/who-director- general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020 World Health Organization and UNICEF. (2022). Philippines: WHO and UNICEF estimates of immunization coverage: 2021 revision. https://cdn.who.int/media/docs/default-source/country- profiles/immunization/2022-country-profiles/immunization_phl_2022.pdf 29 Annexes Annex 1. FDA requirements on the Certificate of Product Registration (Food and Drug Administration, 2020) Document Where to Secure AO No .47-a, series of 2001 Applicant Company 44 Rules and Applicant Company Regulations on the Registration, including Approval and Conduct of Clinical Trials, and Lot or Batch Release Certification of Vaccines and Biological Products ASEAN Common Technical Dossier Part I: Administrative Data and Product Information Applicant Company Sec. An Introduction Applicant Company Sec. B Overall ASEAN Common Technical Dossier Table of Contents Applicant Company Sec. C Guidance on the Administrative Data and Product Applicant Company Information 1. Integrated Application Form (with proof of payment) 2. Letter of FDA Website Applicant Company/ Authorization (where applicable) Manufacturer 3. Certifications Applicant Company /Manufacturer Applicant Company/ Manufacturer For contract manufacturing: Applicant Company/ Manufacturer a. License of pharmaceutical industries and contract manufacturer b. Contract manufacturing agreement c. GMP certificate of contract manufacturer For manufacturing “under-license” a. License of pharmaceutical industries b. GMP certificate of the manufacturer c. Copy of “under-license” agreement For locally manufactured products: a. License of pharmaceutical industries b. GMP certificate (country specific) For imported products a. License of pharmaceutical industries/importer/wholesaler (country specific) Applicant Company/ Manufacturer 45 b. Certificate of Pharmaceutical Product (CPP) issued by the competent authority in the country of origin according to the current WHO format c. Foreign GMP Clearance 30 Document Where to Secure 4. Site Master File Applicant Company /Manufacturer 5. Labeling Applicant Company/ Manufacturer 6. Representative Sample with corresponding Certificate of Analysis Applicant Company/ Manufacturer (upon request of the evaluator) Applicant Company/ Manufacturer 7. Product Information a. Package Insert b. Summary of Product Characteristics (Product Data Sheet) 8. Risk Management Plan (RMP) 9. Periodic Safety Update Report (PSUR)/Periodic Benefit Risk Evaluation Report 10.List of Countries where the product is already licensed and the date of approval 11. Names of the medical director of the importer/distributor and local manufacturer who will monitor event/s reactions and prepare appropriate report to be submitted to FDA 12.Person/s responsible for production and control of the product (Name/s Position, Department, and sample of signature) 13. Description of the cold-chain procedures employed from the origin to the port of entry and in the Philippines (how and where) Part II: Quality Applicant Company/ Manufacturer Sec. A Table of Contents (For whole Part II: Quality) Sec. B Quality Overall Summary Sec. C Body of Data Drug Substance (S) S 1 General Information S 1.1. Nomenclature S 1.2. Structural Formula S 1.3. General Properties S 2 Manufacture S 2.1. Manufacturer(s) S 2.2. Description of Manufacturing Process and Process Controls S 2.3. Control of Materials S 2.4. Control of Critical Steps and Intermediates S 2.5. Process Validation and/or Evaluation S 2.6. Manufacturing Process Development S 3 Characterization S 3.1. Elucidation of Structure and Characteristics S 3.2. Impurities S 4 Control of Drug Substance S 4.1. Specifications S 4.2. Analytical Procedures S 4.3. Validation of Analytical Procedures S 4.4. Batch Analyses 31 Document Where to Secure S 4.5. Justification of Specifications S 5 Reference Standards or Materials S 6 Container Closure System S 7 Stability Drug Product (P) P 1 Description and Composition P 2 Pharmaceutical Development P 2.1. Information on Development Studies P 2.2. Components of the Drug Product • P 2.2.1. Active Ingredients • P 2.2.2. Excipients P 2.3. Finished Product • P 2.3.1. Formulation Development • P 2.3.2. Overages • P 2.3.3. Physicochemical and Biological Properties P 2.4. Manufacturing Process Development P 2.5. Container Closure System P 2.6. Microbiological Attributes P 2.7. Compatibility P 3 Manufacture P 3.1. Batch Formula P 3.2. Manufacturing Process and Process Control • Information on the number system of the lots or batches • System for the re-processing of the product in the event of rejection of the lot or batch by the manufacturer’s QA/QC P 3.3. Controls of Critical Steps and Intermediates P 3.4. Process Validation and/or Evaluation P 4 Control of Excipients P 4.1. Specifications P 4.2. Analytical Procedures P 4.3. Excipients of Human and Animal Origin P 4.4. Novel Excipients P 5 Control of Finished Product P 5.1. Specifications P 5.2. Analytical Procedures P 5.3. Validation of Analytical Procedures P 5.4. Batch Analyses • Summary Lot Protocol • Lot to Lot Consistency from three (3) consecutive batches P 5.5. Characterization of Impurities P 5.6. Justification of Specifications P 6 Reference Standards or Materials P 7 Container Closure System P 8 Product Stability 32 Document Where to Secure P 9 Head-to-Head Comparability – for biosmilars Part III: Nonclinical Document Applicant Company/Manufacturer Sec. A Table of Contents (For whole Part III: Nonclinical Sec. B Nonclinical Overview Document) 1. General Aspect 2. Content and Structural Format Sec. C Nonclinical Written and Tabulated Summaries 1. Nonclinical Written Summaries 1.1. Introduction 1.2. General Presentation Issues 2.Content of Nonclinical Written and Tabulated Summaries 2.1. Pharmacology 2.1.1. Written Summary 2.1.1.1. Primary Pharmacodynamics 2.1.1.2. Secondary Pharmacodynamics 2.1.1.3. Safety Pharmacology 2.1.1.4. Pharmacodynamic Drug Interactions 2.1.2. Tabulated Summary 2.2. Pharmacokinetics 2.2.1. Written Summary 2.2.1.1. Absorption 2.2.1.2. Distribution 2.2.1.3. Metabolism 2.2.1.4. Excretion 2.2.1.5. Pharmacokinetic Drug Interaction (Nonclinical) 2.2.2. Tabulated Summary 2.3.Toxicology 2.3.1.Written Summary 2.3.1.1.Single-Dose Toxicity 2.3.1.2.Repeat-Dose Toxicity 2.3.1.3.Genotoxicity 2.3.1.4.Carcinogenicity 2.3.1.5.Reproductive and Developmental Toxicity 2.3.1.5.1.Fertility and Early Embryonic Development 2.3.1.5.2.Embryo-Foetal Development 2.3.1.5.3.Prenatal and Postnatal Development 2.3.1.6.Local Tolerance 2.3.1.7.Other Toxicity Studies (if available) 2.3.2. Tabulated Summary 3.Nonclinical Tabulated Summaries Sec. D Nonclinical Study Reports 1. Table of Contents 33 Document Where to Secure 2. Pharmacology 2.1. Written Study Reports 2.1.1. Primary Pharmacodynamics 2.1.2. Secondary Pharmacodynamics 2.1.3. Safety Pharmacology 2.1.4. Pharmacodynamic Drug Interactions 3. Pharmacokinetics 3.1. Written Study Reports 3.1.1. Analytical Methods and Validation Reports 3.1.2. Absorption 3.1.3. Distribution 3.1.4. Metabolism 3.1.5. Excretion 3.1.6. Pharmacokinetic Drug Interaction (Nonclinical) 3.1.7. Other Pharmacokinetic Studies 4. Toxicology 4.1. Written Study Reports 4.1.1. Single-Dose Toxicity 4.1.2. Repeat-Dose Toxicity 4.1.3. Genotoxicity 4.1.3.1. In vitro Reports 4.1.3.2. In vivo Reports 4.1.4. Carcinogenicity 4.1.4.1. Long Term Studies 4.1.4.2. Short- or Medium-Term Studies 4.1.4.3. Other Studies 4.1.5. Reproductive and Developmental Toxicity 4.1.5.1. Fertility and Early Embryonic D 4.1.5.2. Embryo-Foetal Development 4.1.5.3. Prenatal and Postnatal Development 4.1.5.4. Studies in which the Offspring are Dosed and/or further Evaluated 4.1.6. Local Tolerance 4.1.7. Other Toxicity Studies (if available) 4.1.7.1. Antigenicity 4.1.7.2. Immunotoxicity 4.1.7.3. Dependence 4.1.7.4. Metabolites 4.1.7.5. Impurities 4.1.7.6. Other Sec. E List of Key Literature References Applicant Company/Manufacturer (For whole Part IV: Clinical Document) Part IV: Clinical Document Sec. A Table of Contents 34 Document Where to Secure Sec. B Clinical Overview 1. Product Development Rationale 2. Overview of Biopharmaceutics 3. Overview of Clinical Pharmacology 4. Overview of Efficacy 5. Overview of Safety 6. Benefits and Risks Conclusions Sec. C Clinical Summary 1. Summary of Biopharmaceutic Studies and Associated Analytical Methods 1.1. Background and Overview 1.2. Summary of Results of Individual Studies 1.3. Comparison and Analyses of Results across Studies Appendix 1 2. Summary of Clinical Pharmacology Studies 2.1. Background and Overview 2.2. Summary of Results of Individual Studies 2.3. Comparison and Analyses of Results across Studies 2.4. Special Studies Appendix 2 3. Summary of Clinical Efficacy 3.1. Background and Overview of Clinical Efficacy 3.2. Summary of Results of Individual Studies 3.3. Comparison and Analyses of Results across Studies 3.3.1. Study Populations 3.3.2. Comparison of Efficacy Results of all Studies 3.3.3. Comparison of Results in Sub-populations 3.4. Analysis of Clinical Information Relevant to Dosing Recommendations 3.5. Persistence of Efficacy and/or Tolerance Effects Appendix 3 4. Summary of Clinical Safety 4.1. Exposure to the Drug 4.1.1. Overall Safety Evaluation Plan and Narratives of Safety Studies 4.1.2. Overall extent of Exposure 4.1.3. Demographic and Other Characteristics of Study Population 4.2. Adverse Events 4.2.1. Analysis of Adverse Events 4.2.1.1. Common Adverse Events 4.2.1.2. Deaths 4.2.1.3. Other Serious Adverse Events 4.2.1.4. Other Significant Adverse Events 35 Document Where to Secure 4.2.1.5. Analysis of Adverse Events by Organ System or Syndrome 4.2.2. Narratives 4.3. Clinical Laboratory Evaluations 4.4. Vital Signs, Physical Findings, and Other Observations Related to Safety 4.5. Safety in Special Groups and Situations 4.5.1. Patient Groups 4.5.2. Drug Interactions 4.5.3. Use in Pregnancy and Lactation 4.5.4. Overdose 4.5.5. Drug Abuse 4.5.6. Withdrawal and Rebound 4.5.7. Effects on Ability to Drive or Operate Machinery or Impairment of Mental Ability 4.6. Post-Marketing Data Appendix 4 5. Synopses of Individual Studies Sec. D Tabular Listing of All Clinical Studies Sec. E Clinical Study Reports (if applicable) 1. Reports of Biopharmaceutic Studies 1.2 In vitro-In vivo Correlation Study Reports 1.2 Reports of Bioanalytical and Analytical Methods for Human Studies 2. Reports of Studies Pertinent to Pharmacokinetics Using Human Biomaterials 2.1. Plasma Protein Binding Study Reports 2.2. Reports of Hepatic Metabolism and Drug Interaction Studies 2.3. Reports of Studies Using Other Human Biomaterials 3. Reports of Human Pharmacokinetic (PK) Studies 3.1. Healthy Subject PK and Initial Tolerability Study Reports 3.2. Patient PK and Initial Tolerability Study Reports 3.3. Population PK Study Reports 4. Reports of Human Pharmacodynamic (PD) Studies 4.1. Healthy Subject PD and PK/PD Study Reports 4.2. Patient PD and PK/PD Study Reports 5. Reports of Efficacy and Safety Studies 5.1. Study Reports of Controlled Clinical Studies Pertinent to the Claimed Indication 5.2. Study Reports of Uncontrolled Clinical Studies 5.3. Reports of Analyses of Data from more than One Study, Including any Formal Integrated 36 Document Where to Secure Analyses, Meta-Analyses, and Bridging Analyses 5.4. Other Clinical Study Reports 6. Reports of Post-Marketing Experience 7. Case Report Forms and Individual Patient Listing Additional Requirements: 1. For products to be registered using Collaborative Registration Procedure (CRP), Expression of Interest submitted to WHO 2. For MRE/MR to Initial applications, proof of approval/clearance/extension of Post- Marketing Surveillance (PMS) Report and Post Approval Commitments as specified in the provided RMP. 37 Annex 2. VIP Roadmap (Department of Science and Technology, 2022) 38 Annex 3.1. Corporate Recovery and Tax Incentives for Enterprises Act of CREATE (Board of Investments) Annex 3.2. Title XIII Incentives (Board of Investments) 39 Annex 3.3. SIPP – Industry Tiers (Board of Investments) Annex 3.4. 2020 Investment Priorities Plan (Board of Investments) 40 Annex 3.5. All Qualified Activities Relating to the Fight against the COVID-19 Pandemic (Board of Investments) 41