Pharmacovigilance capacity strengthening for WHO prequalification: The case of the trivalent influenza vaccine manufactured by Instituto Butantan Marcelo E. Koike a,⇑ , Vera L. Gattás a , Maria Beatriz B. Lucchesi a , Mayra M. Moura de Oliveira a , Tazio Vanni a , Beatriz da C. Thomé a , Olga Menang b , Muriel Socquet b , Alexander R. Precioso a,c a Division of Clinical Trials and Pharmacovigilance, Instituto Butantan, São Paulo, Brazil b Center for Vaccine Innovation and Access, PATH, Geneva, Switzerland c Pediatrics Department of the School of Medicine of University of São Paulo, São Paulo, Brazil article info Article history: Received 18 July 2019 Received in revised form 9 September 2019 Accepted 26 September 2019 Available online xxxx Keywords: Trivalent influenza vaccine WHO prequalification Pharmacovigilance Instituto Butantan abstract Instituto Butantan is a biomedical research center and vaccine manufacturer affiliated with the São Paulo State Secretary of Health in Brazil. In 2013, Instituto Butantan successfully licensed its trivalent influenza vaccine, in order to support the Brazilian National Immunization Program’s influenza vaccination strat- egy, which was introduced in 1999. In order to respond to the increasing influenza vaccine demand worldwide, Instituto Butantan is undergoing prequalification of its trivalent influenza vaccine by the World Health Organization (WHO). A key requirement of the prequalification review was the submission of a pharmacovigilance plan, including an active surveillance evaluation, for the trivalent influenza vac- cine, and proof of a functional pharmacovigilance system at Instituto Butantan. The aim of this paper is to describe the capacity strengthening process of the pharmacovigilance system at Instituto Butantan for the WHO prequalification of the trivalent influenza vaccine. This process was supported by PATH and the U.S. Federal Government Biomedical Advanced Research and Development Authority (BARDA). The key strategic axes for this capacity strengthening process included the improvement of organizational structure, human resources training, internal processes and procedures, appropriate documentation, and acquisition of an E2B compliant pharmacovigilance database. The project led to the establishment of a functional pharmacovigilance system compliant with international regulatory requirements. Ó 2019 Elsevier Ltd. All rights reserved. 1. Introduction Instituto Butantan is a biomedical research center and vaccine manufacturer affiliated with the São Paulo State Secretary of Health in Brazil. Currently, the institute is one of the major public producers of immunobiologicals in Latin America. Partnerships with public and private institutions for the manufacture of vacci- nes has successfully been one of Instituto Butantan’s core endeav- ors to promote innovation and address public health demands regarding immunization in a timely manner. An example of a successful initiative between Instituto Butan- tan and a private vaccine manufacturer was the technology trans- fer program for the trivalent influenza vaccine (inactivated split virion) established with Sanofi Pasteur (previously Pasteur- Mérieux) in 1999. The objectives were to produce 25 million doses of the trivalent influenza vaccine per year and to create a stockpile of H5N1 vaccine for use at the onset of a potential influenza pan- demic [1]. The production capacity established in the technology transfer was based on the demand to promote immunization of the elderly population of Brazil at that time. By 2013, a trivalent influenza vaccine fully manufactured by Instituto Butantan was delivered to the National Immunization Program of Brazilian Min- istry of Health (NIP). Instituto Butantan has since increased its influenza vaccine production capacity due to inclusion of new vac- cination target groups defined by the NIP [2]. By 2017, Butantan delivered more than 45 million doses of trivalent influenza vaccine annually to the NIP. To promptly and effectively respond to threats associated with potential pandemic influenza viruses, a concern that emerged from the advent of the pandemic caused by H1N1 influenza virus in 2009 [3], the World Health Organization (WHO) identified the need for vaccine producers to invest in innovative solutions https://doi.org/10.1016/j.vaccine.2019.09.082 0264-410X/Ó 2019 Elsevier Ltd. All rights reserved. ⇑ Corresponding author at: Instituto Butantan, Division of Clinical Trials and Pharmacovigilance, Avenida Vital Brasil 1500, São Paulo 05503-900, Brazil. E-mail address: marcelo.koike@butantan.gov.br (M.E. Koike). Vaccine xxx (xxxx) xxx Contents lists available at ScienceDirect Vaccine journal homepage: www.elsevier.com/locate/vaccine Please cite this article as: M. E. Koike, V. L. Gattás, M. B. B. Lucchesi et al., Pharmacovigilance capacity strengthening for WHO prequalification: The case of the trivalent influenza vaccine manufactured by Instituto Butantan, Vaccine, https://doi.org/10.1016/j.vaccine.2019.09.082