Abstract: The public mission of Instituto Butantan (Brazil) engages undoubtedly the reduction of infant mortality rate by being responsible for 80% childhood immunization. One main cause of postnatal mortality is associated with respiratory distress syndrome (RDS) caused by pulmonary surfactant deficiency. Synthetic or biologically derived surfactants has been developed to improve lung function and to decrease the mortality associated with RDS. In 1998 Butantan has begun to develop a porcine pulmonary surfactant (Butantan surfactant). Butantan idea was to offer an alternative surfactant replacement therapy mainly for developing countries, focus on low cost but same efficacy and safety. The Butantan preparation was obtained from ground porcine lungs by organic extraction coupled with adsorption on a cellulose derivative. The lungs were kindly donated by a major Brazilian food producer (Sadia). The key advantages of this preparation are to avoid at any volume high-speed centrifugation or extra steps of liquid-gel chromatography. The in vivo evaluation of Butantan surfactant compared to other commercially available surfactants using the preterm rabbit model showed similar pulmonary effects, improving pulmonary functions as assessed by the decrease of the ventilatory pressure and the increase of the dynamic compliance. After having completed all of the pre-clinical test phases, the validation of the medicine was initiated, covering 19 institutions throughout Brazil. The clinical trial (Phases II and III) showed that both the imported and the Butantan surfactant are equally efficient. "The quantity of the product necessary for the survival of the children is also the same" commemorates Prof. Isaias Raw, the coordinator of the project and its main incentive". Currently, investments to make the surfactant plant production as safe as possible to the environment, and also sustainable still concern, since the hot points of the industrial plant besides the surfactant yield, are the completely recovery of the solvents and the cellulose derivative to mitigate costs. The search of promissory therapeutic molecules on porcine pulmonary extract usually rejected during surfactant production is another possibility to aggregate extra biotechnological value to the process. Purification of surfactant proteins and purification of protease inhibitors are examples of this virtuous circle. In a near future to join these proteins to the surfactant preparation will open new frontiers to the surfactant replacement therapy or other not straight related to surfactant. Butantan surfactant is by definition a me-too (drugs that apparently do not offer any distinction from existing therapy) but this experience is also a good example of the Brazilian governmental initiatives to stimulate the research and development of the biopharmaceutical sector in Brazil.
Supported by: Fundacao Butantan, FAPESP, CNPq, MS.

Brief Biography of the Speaker:
Flavia Saldanha Kubrusly has studied Biology and received her master degree from Universidade Estadual de Campinas (UNICAMP) in 1984 and got her PhD from Universidade de Sao Paulo (USP) in 1992. Both universities are located in Sao Paulo, Brazil. Since 1987, she has a permanent R&D position at the Instituto Butantan, Sao Paulo, Brazil. Most of her career is dedicated to vaccine production and control (measles, hepatitis B, rabies). In the last ten years, she is also dedicated to the purification and production of medical drugs derived by direct extraction from native biological source (pulmonary surfactant, aprotinin, vaccine adjuvant) under coordination of Prof. Dr. Isaias Raw, her former post doctoral supervisor (1994) and the Head of the Butantan Foundation. She has authored more than 70 publications (20 original scientific papers, one book chapter, one scientific prize, four patents and more than 50 presentations in conferences). Since 2000, she supervises graduates on the Biotechnology Graduate Interunit Program (USP), concluding at the present, three masters and one PhD.