Case Study: The Policy for the Introduction of New Vaccines in Brazil

Case Study: The Policy for the Introduction of New Vaccines in Brazil CARLA MAGDA ALLAN SANTOS DOMINGUES, ANTÔNIA MARIA TEIXEIRA, AND SANDRA MARIA DEOTTI CARVALHO

2 Case Study: The Policy for the Introduction of New Vaccines in Brazil Case Study: The Policy for the Introduction of New Vaccines in Brazil Carla Magda Allan Santos Domingues National Immunization Program Ministry of Health, Brazil Antônia Maria Teixeira National Immunization Program Ministry of Health, Brazil Sandra Maria Deotti Carvalho National Immunization Program Ministry of Health, Brazil Introduction The National Immunization Program (NIP) of the Ministry of Health (MoH) of Brazil was created in 1973, and the first national immunization schedule was published in 1977 with four mandatory vaccines in the first year of life (tuberculosis, poliomyelitis, measles, and DTPw [diphtheria, tetanus and pertussis]). 1 During this time, vaccine production in the country was going slowly. The private sector considered that the national vaccine market was limited in contrast to other areas within the pharmaceutical sector, given its low profitability as compared to other profitable lines of business within the sector. This was a discouragement for the entry of private vaccine manufacturers to the national vaccine market. 2 Despite the institutional effort to maintain the flow of supplies offered by the PNI, a significant crisis erupted in connection with the shortage of immunobiologicals as a result of the closure of Sintex of Brazil that was a privately-owned foreign-capital company that addressed the demand for products such as sera and the DTP vaccine. So, in 1985, the need for such products demanded the creation of the National Program for Self- Sufficiency in Immunobiologics (PASNI). VACCINOLOGY IN LATIN AMERICA With PASNI, the MoH sought to establish coordinated actions by stimulating investments and improving the quality of the production between the national vaccine manufacturers: Instituto Butantan (São Paulo), Instituto de Tecnologia em Imunobiológicos Bio-Manguinhos/Fiocruz and Instituto Vital Brazil (Rio de Janeiro), Instituto de Tecnologia do Paraná (TECPAR) (Paraná), and Fundação Ezequiel Dias (Minas Gerais). PASNI led to the expanding production of sera and vaccines in the Brazilian market aiming to meet the NIP s 1 demands and allowing for an increased supply of vaccines for other population segments other than just infants under one year of age. 3

Domingues, Teixeira, and Carvalho 3 Current Situation Presently, Brazil is one of the countries that offers the highest number of vaccines distributed free of charge as part of a defined schedule covering all age groups. The immunization schedule for children includes 14 vaccines, for adolescents and adults it includes five vaccines, and for older adults it includes four vaccines (Table 1). Table 1. National Immunization Schedule, 2018 CHILDREN 1. BCG 2. Hepatitis B vaccine 3. Pentavalent vaccine (DTP/Hib/Hep B) 4. IPV (Inactivated poliovirus vaccine) 5. OPV (Oral poliovirus vaccine) 6. RV (Human-attenuated oral rotavirus vaccine) 7. PCV-10 (10-valent pneumocccal vaccine) 8. Yellow Fever vaccine 9. MMR (Measles, Mumps & Rubella vaccine) 10. DTP (Diphtheria, Tetanus & Pertussis vaccine) 11. MenC (Meningococcal C conjugate vaccine) 12. Influenza vaccine 13. MMRV (Measles, Mumps, Rubella & Varicella vaccine) 14. Hepatitis A vaccine ADOLESCENTS AND ADULTS 1. Hepatitis B vaccine 2. Td (Tetanus, Diphtheria) 3. Yellow Fever vaccine 4. MMR (Measles, Mumps & Rubella) 5. Tdap (pregnant women) 6. Influenza vaccine 7. HPV (Human papillomavirus vaccine) 8. MenC (Meningococcal C conjugate vaccine) OLDER ADULTS 1. Influenza vaccine 2. PCV-23 (23-valent pnemococcal polysaccharide vaccine) 3. Td (Tetanus, Diphtheria) 4. Yellow Fever vaccine 5. Hepatitis B vaccine Personalized immunization schedules are available for the indigenous populations and for groups under special conditions such as immunodeficiencies at the Reference Centers for Special Immunobiologicals (CRIE). In total, NIP purchases 45 types of immunobiologicals (including vaccines, sera and immunoglobulins) and every year an estimated 300 million doses are distributed. As the immunization schedule expansion request is increasing every day, the MoH has adopted new criteria for the introduction of new vaccines. This policy implementation has guaranteed an efficient and quick expansion still in observance of the regulations for immunization actions throughout the country. So, the introduction of new vaccines relies on an epidemiological criterion which considers the population needs to reduce morbidity and mortality rates for a specific disease. In addition, other aspects are considered as the vaccine itself (immunobiological factors) as well as the operational, socioeconomic, technological, financing and legal factors. 4

4 Introduction Sustainability of National Production The MoH sustainability policy is based on the strengthening of the national health industrial park, where the main strategic supplies must be produced by the public laboratories. This action guarantees the self-sufficiency of national production, avoids product shortages and any restrictions due to market forces besides the maintenance of high vaccination coverages in all Brazilian municipalities. Two main mechanisms were adopted to foster national production: the incentivization of development of national products and the identification of partnership (private manufacturers) with the purpose of technology transfer to the Brazilian s public manufacturers. These actions have enabled the national production of all the main strategic supplies. In this context, the introduction of new vaccines favors and implements the policy of supporting financial investments in the public vaccine manufacturers, strengthens the national market, decreases import costs and benefits the national trade balance in Brazil. This complex process involves several social actors from various other sectors besides the MoH. This policy has guaranteed the provision of vital strategic inputs and so the NIP has efficiency contributed to the control, elimination and eradication of vaccine-preventable diseases. In the event that acquiring immunobiologicals from the national producers is not possible, the acquisition of these inputs is sought by the Revolving Fund for Strategic Public Health Supplies that was created in 2000 by the Pan American Health Organization (PAHO) as a request of the Member States. This initiative was intended to facilitate the purchasing and access of medicines and strategic supplies and by facilitating low cost procurement on behalf of the Member States. The chance of acquiring immunobiologicals through the Revolving Fund has made it possible to guarantee the NIP s supply of the needed inputs, especially for those inputs in which there are no established technology transfer partnerships or in situations where national production does not meet the country demand. 5 New vaccines introduction demands additional resources which requires a budget proposal and the approval by the National Congress. The States and municipalities also need to allocate resources to guarantee the payment of human resources, the logistics of storage and distribution of the immunobiologicals and the acquisition of needles and syringes supplies. Once this additional budget has been approved, there is an annually guaranteed allocation of funds (Law 12.919 of 12/24/2013) as a mandatory action, which does not allow contingency of this action. Furthermore, the inclusion of a new vaccine in the National Immunization Schedule requires consideration of the cold chain networks capacity at all the three government levels (national, state and municipal). For this, a structured cold chain network is essential from the manufacturer to the vaccination room, with responsibilities defined by the receipt, storage and distribution of the immunobiologicals. The MoH maintains the National Center for Storage and Distribution of Inputs CENADI, responsible to receive all the national and international products purchased by NIP and to distribute them to the States and the Federal District where they are stored in central cold chains for redistribution to regional and/or municipal centers, and from there to the vaccination rooms. VACCINOLOGY IN LATIN AMERICA The MoH has been putting in its investment plan the restructuring of this network as a priority action. However, it is an extremely expensive and complex process that demands effort and financial resources. Between 2006 and 2015, an additional eight new vaccines were introduced in the National Immunization Schedule and even some conjugated vaccines already included in the schedule. Such vaccine additions have reduced the total number of vaccines in the national schedule without impacting the number of diseases

Domingues, Teixeira, and Carvalho 5 targeted for prevention, such as the pentavalent vaccine (diphtheria, tetanus, pertussis, Haemophilus influenzae type b and hepatitis B vaccine). During the same period the following vaccines were introduced into the National Immunization Schedule for children: oral rotavirus vaccine (2006) 6 ; 10-valent pneumococcal vaccine (2010); meningococcal serogroup C conjugate vaccine (2010) 7 ; DTP/Hib/HB vaccine (2012); inactivated polio vaccine (2012) as part of the sequential schedule with the oral polio vaccine (OPV) 8 ; tetravalent measles-mumps-rubella-varicella (MMRV) vaccine (2013); and the hepatitis A vaccine (2014). In 2014, the quadrivalent human papillomavirus vaccine (HPV4) was added for adolescent girls aged 11 13 years and the diphtheria-tetanus-acellular pertussis (dtpa) vaccine for pregnant women. 9 Despite the progress in the implementation of those new vaccines, NIP faces the challenge of achieving and maintaining high vaccination coverages for all the vaccines included in the vaccination schedule. Vaccination coverage plays an important role in changing the morbidity and mortality profile of the country, allowing for the control and above all, the elimination of the transmission of diseases, such as the elimination of the transmission of autochthonous measles virus. Conclusions Vaccination strategies either in routine schedules or campaigns have increased the offer of vaccines and have reached the target populations established in the National Immunization Schedules. In Brazil, the proven impact of the vaccination program, such as the eradication of poliomyelitis, the elimination of rubella and congenital rubella syndrome, and the contribution to the drastic reduction of vaccinepreventable diseases has prioritized vaccination goals amongst public health policies. Consequently, ongoing epidemiological studies become necessary to measure the impact of new vaccines on the disease burden. Proper documentation for each disease and new vaccine introduced in the schedule is critically important. The guarantee of the maintenance of the national health industrial park has been essential for the success achieved, as an important health benefit to the population, as well as to the country s economic sector, since the continuity of the national production guarantees the sustainability of the supply of the 36,000 vaccine rooms in the country, reducing the acquisition costs of acquiring immunobiologicals and strengthening the national productive sector. However, given the complexities surrounding the introduction of new vaccines into the national immunization schedule, not only vaccine impact on disease morbidity and mortality should be taken into consideration, but also the cost-effectiveness of the vaccine (i.e., whether it produces benefits for health and reduces the diseaserelated costs of treatment, hospitalization, and work/school days lost by the patient and/or their relatives, plus their survival) as well as all the operational aspects that ensure sustainability and quality of the product to be offered in the country s service network. Policies for introducing vaccines need to be standardized to guarantee efficiency, allow new vaccines to be incorporated into the National Immunization Schedule and to become available to other population groups in the light of scientific evidence.

6 Introduction References 1. Ministry of Health. Health Surveillance Secretariat. Department of Epidemiological Surveillance. General Coordinating Office of the National Vaccination Program. 40 anos do PNI. Brasília (DF), 2013. 2. Risi Jr JB. A produção de vacinas é estratégica para o Brasil. Hist Ciênc Saúde Manguinhos [serial online] 2003 [cited jan 15, 2013]; 10 (suppl. 2): 771-83. Available from: http://www.scielo.br/pdf/hcsm/v10s2/a15v10s2.pdf. 3. Gadelha C, Azevedo N. Inovação em vacinas no Brasil: experiência recente e constrangimentos estruturais. Hist Ciênc Saúde - Manguinhos [online publication] 2003 [cited December 12th, 2012]; 10 (suppl. 2): 697-724. Available from: http://www.scielo.br/pdf/hcsm/ v10s2/a12v10s2.pdf 4. Programa nacional de imunização: a política de introdução de novas vacinas Carla Magda Allan Santos Domingues, Jeanine Rocha Woycicki, Kellen Santos Rezende, Cláudio Maierovitch Pessanha Henriques. http://periodicos.unb.br/index.php/rgs/article/view/22110 5. Horst MMLL, Soler O. Fundo estratégico da Organização Pan-Americana da Saúde: mecanismo facilitador para melhorar o acesso aos medicamentos. Pan Am J Public Health. 2010;27(1):43 8 6. Brazil. Ministry of Health. Cabinet of the Ministry. Regulation no. 1607 implementing vaccination schedules for children, adolescents, adults and older adults throughout the national territory. Brasília, DF. 2006 7. Brazil. Ministry of Health. Cabinet of the Ministry. Regulation no. 3.318, dated October 28th, 2010 implementing vaccination schedules for children, adolescents, adults and older adults throughout the national territory. Brasília, DF. 2010 8. Brazil. Ministry of Health. Cabinet of the Ministry. Regulation no.1.498, dated July 19th, 2013 redefining the National Vaccination Schedule, or the National Vaccination Schedule for the Indigenous Peoples and the National Vaccination Campaigns, within the realm of the National Vaccination Program (PNI), throughout the national territory. Brasília, DF. 2013. 9. Ministry of Health. Health Surveillance Secretariat. Epidemiological Bulletin. Volume 46 - no. 30. 2015. Programa Nacional de Imunizações: aspectos históricos dos calendários de vacinação e avanços dos indicadores de coberturas vacinais, no período de 1980 a 2013. VACCINOLOGY IN LATIN AMERICA