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Organized by
Promoted by
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Gold partners
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Exhibitors
Brazilian Delegation
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24 BIODIVERSITY as a new perspective for radical innovation
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SUMMARY 16 40 50 58 62 64 66
OPPORTUNITIES and challenges of the Health Industrial Productive Chain in the next 10 years COVID-19 The role of public health institutions in coping with Covid NEW REALITY How Covid 19 impacted scientific expectations and transformed the way we see science in Brazil NEW TRENDS How to overcome the biological manufacturing gap in Brazil THERAPEUTIC ALTERNATIVE Regulation of Cannabis-derived products for medical purposes in Brazil BIOTECHNOLOGY Innovation & partnerships for public health FUTURE Janssen Brazil: A Commitment to the Country for 89 Years
BIO Br Project Management by: Reporter: BIOMINAS Brasil / Planning, Control and Operation: Carolina Sellani, Jéssica Cerqueira and Gabriel Keniti Art Editor: Daniel Guedes / Contact us at: abiquifi@abiquifi.org.br / Visit our site: bph.org.br
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Opportunities and challenges of the Health Industrial Productive Chain in the next 10 years
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he health sector in Brazil has grown in recent years due to its strong scientific base, the development of its industrial complex, and the growing demands of the population. According to a survey carried out by IQVIA, the Brazilian drug market moved around BRL 88.28 billion in 2021 (equivalent to USD 14.92 billion), a growth of 14.21% over the previous year (in BRL). Until this year, there were 349 pharmaceutical companies in the national market. Of these companies, 118 (33.81%) were of international origin, holding 40.73% of the market, and 231 (66.19%) had national capital, holding 59.27%. Currently, Brazil has the first Latin
American market in this segment, ahead of Mexico, Colombia, and Argentina. Globally, it occupies the 8th position in the ranking of the 20 first economies in the world in terms of revenue. By 2023, there are prospects that the country will reach 5th position. Even though the country has a robust pharmaceutical industry, it is currently responsible for producing only 5% of the raw materials needed to manufacture medicines, while the remaining 95% are imported, mainly from China and India. During the Covid-19 pandemic, the impact caused by the dependence on pharmaceutical inputs and products produced by a few international suppliers became evident to society. To solve this problem and ensure the
continuous rise of the sector, it is necessary to understand the current scenario of the health industry in the country and explore the lessons learned in recent years. In that way, it will be possible to devise strategies to overcome the various challenges inherent to the stages of the industrial production chain. Faced with this situation, Norberto Prestes, president of the Brazilian Industry Association of Active Pharmaceutical Ingredient (Abiquifi), highlights: “The main challenge for the Brazilian pharmaceutical industry today is to develop its technological capacity to produce inputs locally and encourage the drug discovery chain. From the promotion of radical innovation, it is possible to increase stages and strengthen the entire production process, adding new clinical trials, basic research, and boosting the emergence of startups in the sector”. Therefore, the technological development of the industry has to be guided by stimulating innovation, promoting a conducive clinical research environment, and adopting public policies to guarantee access to medicines for the entire population. This strategy could position the country as a relevant developer and exporter of products and solutions in the pharmaceutical area. In the regulatory context, the Brazilian Health Regulatory Agency (Anvisa) plays a vital role in ensuring the viability and agility of all processes related to the development of the health production chain in Brazil. Due to the health emergency caused by the new coronavirus, a series of regulations had to be revised and edited so that, after a risk-benefit assessment, it was possible to improve
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the regulatory flexibility in order to encourage national industries to collaborate with the supply of the Brazilian market, through the production of medicines directly or indirectly linked to the fight against Covid-19. Based on this experience, the current director of Anvisa, Meiruze Sousa Freitas, highlights: “Anvisa is working together with the National Congress and the Ministry of Health to strengthen the mechanisms that allow the Agency to act quickly and efficiently. Through the lessons learned from the pandemic, it will be possible to analyze which of the exceptional measures could eventually be incorporated into the Agency’s permanent regulatory framework”. The director also reinforces Anvisa’s commitment to improving the regulatory environment to boost the research and development of medicines in the country and, thus, reduce the national dependence on active pharmaceutical ingredients or drugs considered strategic. It is possible to highlight other initiatives already in force in Brazil that drive the development of the pharmaceutical sector. The Innovation Law (Law No 10.973/2004), for example, establishes measures to encourage innovation through scientific and technological research in the productive environment. These measures are focused on some objectives, such as providing technical training, achieving technological autonomy, and developing the national and regional production system. In addition, it encourages R&D activities in Science and Technology Institutions (ICTs) and companies, including the attraction, constitution, and installation of R&D centers, technology parks, and hubs in the country. Public-private partnerships are also examples of key initiatives for the scientific sustainability of the national health sector. The General-Coordinator for Health, Biotechnology and Agrarian Sciences of the Secretary for Research and Scientific Train-
NORBERTO PRESTES, PRESIDENT OF THE BRAZILIAN INDUSTRY ASSOCIATION OF ACTIVE PHARMACEUTICAL INGREDIENT (ABIQUIFI)
ing of the Ministry of Science, Technology, and Innovations (MCTI), Thiago Moraes, emphasizes the importance of building a joint agenda between government, companies, and academia: “Through investments from the business sector and cooperation between universities and industry, it is possible to boost the development of products, taking advantage of the know-how of Brazilian researchers, and bring to the market new molecules which development has already begun in, but that are awaiting an opportunity to finalize the requirements demanded by Anvisa for use in human beings, a stage of great cost that often ends up not being surpassed”. In the National Congress, the discussion regarding incentives for the industry self-sufficiency in strategic inputs production has been strengthened, making congressmen monitor the matter more closely. Mirna Oliveira, the advisor to the leader of the Government in Congress, Senator Eduardo Gomes, also defends public-private partnerships: “In addition to pro-
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viding agility to meet the demands of the sector, these initiatives are fundamental to relieve the State regarding all this responsibility, especially in a health system like ours, in which health is a constitutional right”. Due to its strong capacity for articulation, Associations play a leading and fundamental role in structuring this type of partnership and other actions to encourage the national pharmaceutical industry. Based on his experience as head of Abiquifi, Norberto explains that, by bringing together representatives from all stages of the production chain, it is possible to discuss the main critical points and opportunities in the sector, disregarding individual strategic factors. Thus, a strategic plan is created to negotiate with funding agencies, the regulatory agency (Anvisa), the Ministry of Health, investment funds, and other players in the sector. Thinking about the post-pandemic scenario, he confirms that some measures are already being taken by the Association to stimulate the national production of Active Pharmaceutical Ingredients (APIs) and expand the development of molecules in Brazil, such as initiatives for research, development, and production of raw materials from Brazilian biodiversity (APIs of vegetable origin). From the same point of view, Moraes (MCTI) also mentions the main measures that are in progress by the government: Investments with non-reimbursable resources in renowned research groups in their areas of activity; investment in specialized infrastructure for biosafety level 3 assays (required for human pathogens); and investment in the structuring of small facilities for the production of clinical batches in Good Manufacturing Practices (GMP). Within the scope of Congress, Mirna reports that more than 50 matters related to this topic are being processed. Among them, she quotes bill 4209/2019, whose objective is to support national pharma chem-
MEIRUZE SOUSA FREITAS, DIRECTOR OF ANVISA
MIRNA OLIVEIRA, THE ADVISOR TO THE LEADER OF THE GOVERNMENT IN CONGRESS, SENATOR EDUARDO GOMES
According to a survey carried out by IQVIA, the Brazilian drug market moved around BRL 88.28 billion in 2021 (EQUIV-
ALENT TO USD 14.92 BILLION)
icals by prioritizing the sanitary registration of inputs produced in the country, in addition to establishing a margin of preference in public purchases of medicines that carry these APIs. She also mentions a bill drafted under the leadership of Senator Eduardo Gomes together with several leaders in the sector and highlights: “the objective is to create a more robust legal structure so that the national industry can develop and, consequently, meet the needs of demands not only of the Unified Health System (SUS) but also of the health private sector”. It is evident that the Covid-19 pandemic has exacerbated the main critical points of the national pharmaceutical production chain. Because of this, a movement was necessary on the part of governmental and regulatory bodies, third sector entities, academia, and private institutions. Brazil has a modern production complex, an embracing health system and a large population with substantial consumption potential, and initiatives to support the industry are essential to guarantee a more favorable scenario for the country in terms of access to APIs and the development and consolidation of a competitive healthcare market. ●
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WORLDWIDE
Biodiversity as a new perspective for radical innovation
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razil is the most biologically diverse country in the world, ranking at the top among the 17 megadiverse countries on Earth. Studies estimate that there are between 10 to 50 million fauna and flora species on the planet, and approximately 20% are present in Brazil. According to data from the Ministry of the Environment of the Federal Government, there are more than 116,000 animal species and more than 46,000 plant species already known in the country. In addition, Brazil has a rich social diversity, represented by more than 200 indigenous peoples and several other communities, which brings together a collection of traditional knowledge associated with species present in the national territory. This immense biological diversity provides a vast genetic heritage for the country and, consequently, carries great potential for obtaining new drugs or bioactive substanc-
es to treat numerous human diseases. Miller Freitas and Cristiano Guimarães, founders of Nintx, a Brazilian startup focused on research and development of new therapies using natural products, complement: “Brazil has an advanced scientific structure and regulatory framework, which coupled with its unparalleled biological diversity, offers a unique opportunity for developing innovative therapies for unmet global medical needs. It could place the country in a position of less dependence and worldwide prominence in the pharmaceutical R&D sector, reversing the logic of importing to exporting innovations’’. Despite all this potential, when analyzing the scenario of the herbal medicine market in Brazil, the number of products developed from plant sources is relatively small compared to the size of the country’s biodiversity. In this context, the Centroflora Group, a national leader in the sustainable production of natural products for the pharmaceutical industry, partnered with researchers
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and relevant institutions in the health and biotechnology sector, such as Fiocruz, Farmanguinhos, Instituto Stela, and Biominas Brasil. Through this partnership, the project InovafitoBrasil Platform was born, an initiative to strengthen the national bioeconomy focusing on health. The platform is motivated to enable the production of new herbal medicines from the approach of the innovation ecosystem players and a complete roadmap guided by the regulatory requirements of each stage of technological development. In 2020, Cristina Dislich Ropke, Director of Innovation at Centroflora Group, and Maria Behrens, Head of the Natural Products Department at Fiocruz, met to discuss a research work focused on the classification of Fiocruz’s phytotherapic development portfolio. From this meeting, they created a multidisciplinary Working Group to structure the roadmap and showcase projects for the InovafitoBrasil platform. On the Centroflora side, the conceptual work was developed in conjunction with Dr. Eduardo Pagani, and it also counted on the participation of Bárbara Sena Barbosa. On behalf of Fiocruz, Sandra Aurora Perez Rodrigues, Cristiane Mota Soares and Paulo Benevides contrib-
uted to the working group. In addition, to implement the platform as a digital tool, the group signed a partnership with Instituto Stela, which became responsible for programming and the technological structure. Peter Andersen, CEO of Centroflora Group, explains: “The role of InovafitoBrasil is to create a library of organized information about Phyto projects around the country, given that, until then, information was extremely fragmented and patents misaligned to market needs and the regulatory framework”. All projects registered on the platform are organized and classified according to their Technological Readiness Level (TRL). This methodology, widely used to measure the stage of technology development, was carefully adapted to the context of herbal medicines to
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MILLER FREITAS AND CRISTIANO GUIMARÃES, FOUNDERS OF NINTX
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meet the objectives of the InovafitoBrasil platform, work carried out through the partnership between Centroflora and Fiocruz. Maria Behrens tells a little about this experience: “There were months of rich interaction of a multidisciplinary team in order to systematize in detail the phytotherapic R&D activities, from the stages of obtaining the vegetable raw material, Active Pharmaceutical Ingredient (API), to the production of the medicine/herbal product, in the questions that determine its quality, efficacy, and safety. The TRL scale applied to the development of herbal medicines aims to facilitate project management as a tool for planning and monitoring activities and steps to be carried out”. In this way, the platform serves an additional function of providing the researcher with instruments regarding the development stages of their product, increasing their productivity potential. From the regulatory point of view, this work will be of great importance and usefulness as it will support those responsible for
the projects to pay attention to the main requirements inherent to the various stages of product development. João Paulo Perfeito, Manager of Herbal and Complementary Medicines at the Brazilian Health Regulatory Agency (Anvisa), states that the process of obtaining a herbal medicine from a medicinal plant is thorough, involving a series of steps, with well-defined specific requirements: “Considering the evidence requirements to prove the quality, safety and efficacy of herbal medicines, it can be said that, in Brazil, these products are subject to extensive regulation, covering assessments and controls from the plant raw material, through the plant derivative and finally the herbal medicine”. For this reason, he argues that based on the shared information and scripts, the InovafitoBrasil Platform could facilitate the path for professionals and institutions involved in R&D, encouraging them to establish strategies to guarantee that the research will meet the regulatory requirements and generate
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MARIA BEHRENS, HEAD OF THE NATURAL PRODUCTS DEPARTMENT AT FIOCRUZ
CRISTINA DISLICH ROPKE, DIRECTOR OF INNOVATION AT CENTROFLORA GROUP
Studies estimate that there are between 10 to 50 million fauna and flora species on the planet, and approximately
20% ARE PRESENT IN BRAZIL
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new phytotherapics for the national market. According to Cristina Ropke, the platform will go beyond organizing projects and providing relevant information with guidelines to instruct the development of herbal medicines. It will also provide a connection environment between researchers and industry, generating impacts for the entire production chain and, for example, contributing to the business model of companies that want to innovate and technology-based startups. For Miller and Cristiano (Nintx), this interaction is very positive and should become more common, with universities PETER ANDERSEN, strengthening the scientific CEO OF pillar and industries, the regCENTROFLORA GROUP ulatory and patent ones. All these advantages offered by the InovafitoBrasil platform facilitate the path to the development of herbal medicine and thus should drive radical innovation in Brazil. As explained by Eduardo Emrich, CEO of Biominas Brasil, an institution dedicated to promoting companies and businesses in the life sciences industry, the platform brings a series of short, medium, and longterm benefits. At first, it will be possible to map the technologies and projects of herbal medicines in the country, their stages of development, and their challenges. Further, collaborations will be facilitated, by bringing research institutions and companies closer together to accelerate the development process. In the long term, all of this can support a chain of development of new products, which will benefit not only the herbal medicine sector but the entire health market in the country. Cristina Ropke also comments on the platform’s potential impact: “We can highlight other opportunities for radical innovation, from research into herbal medicines, which, through cutting-edge technologies in Drug Discovery, can lead to the development of unprecedented synthetic molecules”. As a result of all these positive impacts
that could be generated by the InovafitoBrasil Platform, the expectation is to result in a direct increase in the efficiency and productivity of the pipeline for the development of new herbal medicines in the country; greater ease in interactions between academia and industry; attraction of national and international investments (through the construction of a technological environment of greater stability and trust); and clarity regarding the role of each stakeholder within the phytotherapic development chain, from ideation, research, and to the finished product. For Maria Behrens (Fiocruz), the first step on this path is to raise the standard of processes to ensure
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EDUARDO the achievement of quality, EMRICH, CEO efficacy, and safety criteria, OF BIOMINAS BRASIL and later, through the reduction of errors and failure in projects, to ensure the minimization of investment risks. Confident in the project, Emrich (Biominas) agrees: “The country can effectively take a technological leap, attract resources for investment, and change its level in the world. This is the vision of everyone involved in the platform design”. All of this is only possible from the change in the look at the Brazilian biodiversity, bringing a perspective of source of innovation, which herbal products are seen as a strategy for the country to stand out in the world health market. The InovafitoBrasil Platform effectively allows this potential to become a reality, with safety and respecting communities and the legal framework. ●
DENILSON SELL’S STATEMENT INSTITUTO STELA DIRECTOR AT THE INSTITUTE
All of this is only possible from THE
CHANGE IN THE LOOK AT THE BRAZILIAN BIODIVERSITY, bringing a perspective of source of innovation, which herbal products are seen as a strategy for the country to stand out in the world health market
Instituto Stela, a partner in the creation of the InovafitoBrasil Platform, is a private, non-profit organization that, through its activities, seeks to provide a link between academia and the market to generate high-impact socioeconomic solutions. The Institute is known worldwide for developing the CNPq Lattes Platform, one of the largest databases for recording scientific activity in Brazil. “Following the contemporary vision of digital platforms and platform-based businesses, InovafitoBrasil seeks in its planning to connect with existing initiatives and provide new resources to promote the innovation ecosystem and Brazilian biodiversity. In its first generation, InovafitoBrasil prioritized the provision of resources to academia, researchers and startups, including a roadmap based on stages of maturity for the registration of phytotherapic projects, intending to provide intelligent assistance to the advancement of new projects, in addition to promoting the visibility of projects with potential investors. The platform also offers, in its first version, support to investors and the productive sector in locating new projects for potential investment and in accessing key actors in the ecosystem for the formation of partnerships.” ●
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Aché products have reached new markets through licensing agreements that
CURRENTLY COVER 21 COUNTRIES in Latin America, Africa, Asia and Europe
CARLOS EDUARDO VITOR STATEMENT - ACHÉ SENIOR R&D MANAGER, HEAD OF EARLY-DEVELOPMENT
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Aché is a Brazilian company with 55 years of presence in the pharmaceutical market. Aché products have reached new markets through licensing agreements that currently cover 21 countries in Latin America, Africa, Asia and Europe. Aché collaborated with its experience with InovafitoBrasil. “The InovafitoBrasil platform will be a huge milestone, not only for the pharmaceutical industry but also for researchers who carry out R&D based on Brazilian biodiversity. Through the TRL’s revised methodology, the platform will help researchers understand the phases of research development, guiding them to the next steps and supporting them to make the project more attractive in pitches to industry and investors. Aché looks favorably on the initiative, and therefore, we supported its structuring by bringing the industry’s point of view. The launch of Acheflan (by Aché) in 2006 was a pioneering initiative as it was the first herbal medicine 100% developed in the country. Today, Acheflan is marketed in more than
twenty countries through out-license partnerships. In addition to Acheflan, Aché has other seven projects under development ordering biodiversity assets. The most advanced of these is in Clinical Phase 2, the penultimate one before the global product registration request. In other words, over the last two decades, Aché has built up good expertise in the development of herbal medicines. Therefore, we contributed to the platform based on this industrial development experience, demonstrating the difficulties and the main points of attention on the development stages, in order to facilitate this process for researchers.” ●
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COVID-19
The role of
public health institutions in coping with Covid
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ver two years after the COVID-19 pandemic started in Brazil, the country is experiencing a scenario of stability and control, with the return of face-toface activities and the end of the obligation to wear masks. However, to reach this stage, the participation of several public institutions was imperative, which in turn, even before the first record of the SARS-CoV-2 virus in the country, they were already working to meet the population’s needs. Even without high numbers of infected people in Brazil, in March 2020, the scientific community already pointed to a dire situation. Still, without any standard effective treatment for COVID-19 and vaccines being a distant reality, the first recommendation of the World Health Organization (WHO) as a strategy to control the pan-
demic was mass testing of the population. Given this, the Institute of Technology in Immunobiologicals of the Oswaldo Cruz Foundation (Bio-Manguinhos/Fiocruz), in partnership with the Oswaldo Cruz Institute (IOC/Fiocruz) and the Institute of Molecular Biology of Paraná (IBMP), three Brazilian public health institutions focused on applied research in health, played a central role in the country. Even before SARS-CoV-2 detection in national territory, they had already been working on developing the molecular diagnostic test for the New Coronavirus (nCoV) and in several other initiatives. Maurício Zuma, Director of Bio-Manguinhos, recalls: “The distribution of tests started on March 4, 2020, before the pandemic was declared by WHO, directly to the places indicated by the Ministry of Health, to speed up deliveries. That month, Fiocruz completed the training of the 27 Central Public Health Laboratories (LACENs) in Brazil, and all states were able to carry out testing for
nCoV”. Also, the acquisition of the rapid test started in the same period. This test brings the result in up to 20 minutes for use In Loco with suspected patients. The supply of both testing modalities allowed the Ministry of Health to establish different strategies to contain the virus’s spread. In addition to the molecular diagnostic test, Zuma mentions that the institution also developed the Covid 4 Plex molecular diagnostic kit and the Influenza A, influenza B, and Covid kit. Meanwhile, by appointment of the Ministry of Health, Bio-Manguinhos focused on the prospection and evaluation of numerous vaccines under development. In September 2020, with the signing of the Technology Order agreement with the biopharmaceutical company AstraZeneca to obtain a new vaccine (recombinant technology), then under development by Oxford University. Also, in January 2021, the institution provided the first doses (imported from India) and, starting from March,
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was producing locally. In less than a year, the technology was fully incorporated, and to this day, Brazil is self-sufficient in producing this 100% nationalized vaccine. Another relevant producer of immunobiological in Brazil, the Butantan Institute, played an indispensable role in the direct fight against the virus. In June 2020, an accord was announced between Butantan and Chinese pharmaceutical company Sinovac, aiming to develop a vaccine against the SARS-CoV-2 virus. Clinical studies conducted by the institute were carried out in the country to prove vaccine effectiveness. After the success of the tests and approval by the Brazilian Health Regulatory Agency (Anvisa), on January 17, 2021, vaccination against nCoV was started in Brazil. In addition to the vaccine, the Butantan Institute also carried out other activities to fight the pandemic. Dimas Covas, president of the Butantan Institute, reports: “During the Covid-19 pandemic, Butantan’s involvement was broad and stood out in the Brazilian and international scenario. Not only in the clinical development of CoronaVac, the first vaccine used in Brazil and one of the most used vaccines in the world, but also the institute had other activities in the areas of testing, genotyping, and rapid response to outbreaks in special populations. Butantan took a broad and fundamental action for the state of São Paulo and Brazil in the fight against the harmful effects of the virus and pandemic control”. Another institution that played a central role in the face of the pandemic was Anvisa. Like the other institutions mentioned, the Agency began to prepare to meet the demands resulting from the new disease even before it was declared a pandemic by the WHO (March 2020). In 2021, Anvisa released a report on the actions taken during the Covid-19 pandemic in Brazil till that point. The publication describes the health measures implemented from January 1st, 2020,
MAURÍCIO ZUMA, DIRECTOR OF BIO-MANGUINHOS
to May 15, 2021, totaling 500 days of intense dedication by the Agency. In the highlights of the first measures, we perceive Anvisa’s fundamental role in controlling the entry of nCoV into the country, from the publication of the Technical Note 2/2020, on the adherence of sanitary measures at points of entry, as well as meetings with the air and port sectors on the identification of new cases, prevention and use of personal protective equipment (PPE). With the development of new technologies focused on fighting nCoV, from diagnostic tests to new drugs, and the urgency of evaluating, approving, and regularizing these new technologies, Anvisa had to adapt and be more agile. That is what Gustavo Mendes, General Manager of Medicines and Biological Products at Anvisa, points out: “Some initiatives were taken based on the need to provide quick responses and at the same time maintain the safety, efficacy, and quality criteria for product approval”. According to Gustavo, the collaboration between the different agencies, strengthening the exchange of information and strategies, allowed streamlining processes and avoiding unnecessary efforts in local agencies.
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DIMAS COVAS, PRESIDENT OF THE BUTANTAN INSTITUTE
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In addition, working closely with product and drug developers allowed them to accelerate regulatory approvals. According to Gustavo, changes in Anvisa’s legislation made the approval process more agile. In addition, there was a reduction in administrative requirements that had little impact on the product, along with changes in the way the agency operates, with more frequent meetings to align expectations with developers and engagement of more specialists to analyze the prioritization of products for Covid-19. All these actions brought the results that can be observed now. Over the past two years, society has adapted to the new reality and has learned how to deal with the Covid-19 virus. Wearing masks, especially in closed places, avoiding agglomerations, and washing your hands more often were some of the numerous adaptations that proved to be important in the fight against the pandemic. These adjustments and lessons learned also apply to public health institutions: “There are many lessons learned from the pandemic, but the main thing is that a health emergency like this requires the effort of a large number of people, cooperation and coordination with
various public and private sector bodies. There are no ready-made answers to fight a pandemic. We have to learn every day how to deal with situations and the great challenges that appear. More than two years later, we still have to pay attention to new variants forthcoming, the evolution of vaccines, and the vaccine response toward these variants. The challenges are constant, and we have to be prepared and engaged in this fight”, declares the president of the Butantan Institute. For Gustavo Mendes, the various lessons that Anvisa had during this period contributed to streamlining the workflow: “We were able to rethink the flows that were practiced before the pandemic and the way we saw the risks and benefits of the products changed. That is important because it has changed to become more agile and more focused on what matters: verifying whether the population can use the product or not, without compromising its safety.” Also, the Agency was able to communicate its actions very clearly, and in real-time during the pandemic, which was a relevant gain as it allowed the population to understand the role of a regulatory agency. Another great lesson mentioned by
In June 2020, an accord was announced between Butantan and Chinese pharmaceutical company Sinovac,
AIMING TO DEVELOP A VACCINE AGAINST THE SARSCOV-2 VIRUS
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Gustavo was the collaboration with other agencies, where the regulatory effort is shareable, and it is possible to take advantage of the international experience. “Anvisa was already tracing a path of international convergence, a more aligned posture with international regulatory practices. The pandemic helped position Anvisa as a strategic agency on the global stage. Many of the approvals and disapprovals given to products and medicines in this period turned out to be used by other regulatory agencies that consider Anvisa as references for their actions”, states Gustavo. After the challenges were overcome, and the lessons learned from the pandemic, institutions are now focused on the future. In the regulatory sphere, Anvisa intends to make its role and the role of regulation even more understandable for society altogether, through improved institutional communication and greater transparency. In addition, greater activity in the production chain is necessary, participating from the initial stage of product development, speeding up approval and availability. Bio-Manguinhos and Instituto Butantan, on the other hand, are focused on expanding their projects, whether in obtaining new products for their portfolios or even in new infrastructures. Bio-Manguinhos sustains different actions to combat the pandemic: it submitted to the WHO the request for prequalification of the recombinant vaccine, to make it available to other countries through the United Nations agencies, and bets on new platforms for the production of vaccines (vector viral and RNA), which are rapidly adaptable and allow adaptation to new targets, whether in immunization (vaccines) or therapy (biopharmaceuticals). Furthermore, the search for new products and technology continues, with the expansion of the portfolio of molecular kits. The Butantan Institute, in addition to portfolio expansion, is entering the international market, supplying vac-
GUSTAVO MENDES, GENERAL MANAGER OF MEDICINES AND BIOLOGICAL PRODUCTS AT ANVISA
cines to Latin American countries through the Pan American Health Organization (PAHO), with great possibilities of supplying the flu vaccine to the northern hemisphere. The technical quality available in Brazil is a global benchmark. Proof of this is the participation of the Butantan Institute in the development of CoronaVac, the role played by Bio-Manguinhos in the strategies for the international supply of recombinant and mRNA vaccines (under development), and Anvisa as a member of the Management Committee of the International Council for Harmonization of Technical Requirements for Pharmaceutical Products for Human Use (ICH), an initiative that brings together regulatory authorities and the pharmaceutical industry and is one of the primary bodies of regulatory agencies, responsible for drug approval requirements, not only for these but also for other public institutions spread across the country. It is indisputable that there is still a way to go, and it is necessary to invest in biotechnology and transform it into an asset to the country. However, the articulation of institutions, collaborating for this sector growth to meet the needs of Brazilian society and worldwide. ●
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NEW REALITY
How Covid 19
impacted scientific expectations and transformed the way we see science in Brazil
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he advent of the COVID-19 pandemic caused the world to enter a new modus operandi, where various sectors had to reinvent themselves to face the New Coronavirus (nCoV), which was spreading quickly and advancing across our planet. One of the most impacted sectors was science, which had the task of understanding the virus and seeking solutions to combat it. With the emergence of COVID-19, Brazilian science had to adapt to this new reality, which accentuated and highlighted problems that are gradually being solved, impacting expectations and changing the way Brazilians and the world sees it. The first problem exposed by the health crisis was Brazil’s dependence on the foreign market. The high demand for active pharmaceutical ingredients, materials, and laboratory equipment worldwide generated a short-
age situation in the country, causing many types of research to be interrupted. Helena Faccioli, CEO of Farmacore Biotechnology, a Brazilian technology-based company with experience in immunomodulators and preventive R&D and therapeutic vaccine reports: “There was a lack of many essential actives pharmaceutical ingredients for the pharmaceutical and biotechnological industries. That showed us it is essential to invest in this sector in the country, especially in research and development”. For Helena, a development plan to reduce this dependence is required. Brazil has a great capacity to generate new knowledge and technologies, yet it is necessary to invest in projects from the initial stages. Through coordinated work focused on the market, and following a favorable regulatory strategy, Brazil has a promising future for innovation in the industry. An important movement that was al-
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ready being encouraged in the country and intensified due to the pandemic was the public and private sectors partnership. The development of vaccines is an example of success in this type of cooperation, where Brazilian research conducted clinical trials with enormous competence. Roberto Otto Augusto de Lima, provider of Santa Casa BH, the first health institution installed in the city of Belo Horizonte, recollects: “COVID-19, respecting the number of cases and deaths, demonstrated Brazilian’s potential in conducting clinical research with excellence, with high-performance researchers working with competent and prepared teams. It is important to highlight the universality of the Unified Health System (SUS), which with enormous capillarity and scope, demonstrates a unique potential in the world for the development of research in the health area”. Nonetheless, Helena argues that this interaction is still quite bureaucratic in the country, which generates a very long delay in the development processes. The pharmaceutical industry must seek to strengthen this partnership, offer more attractive mechanisms for science, and above all, invest in partnership with startups and biotechnology companies, which can offer great solutions for the industry. Over the past few years, several startups have emerged with technologies focused on different aspects to assist in the pandemic, such as biotechnology companies focused on diagnosis, prevention, and treatment; health techs enabling telemedicine, medical devices, and digitization of the patient’s journey. Also, startups with technologies to assist the transition to a new reality, like aid in remote work practices and e-commerce. For Helena, startups have a great capacity to generate new solutions, as they focus on the market and the generation of products and not just on knowledge. Industry engagement from the earliest stages of projects can accelerate the technology development process. The need to speed up the evaluation
ROBERTO OTTO AUGUSTO DE LIMA, PROVIDER OF SANTA CASA BH
and regulation of new technologies, which emerged inclined to help fight the virus, meant that the Brazilian Health Regulatory Agency (Anvisa) had to meet the new reality. Anvisa imposed an effective pace of analysis to be able to meet the pandemic demands: “This new way of evaluating, focusing more on risk analysis and on what is critical to be used by people, is a lesson that can be expanded to other products, and not just those focused on the pandemic” declares Gustavo Mendes, General Manager of Medicines and Biological Products at Anvisa. Gustavo points out that Anvisa has sought a more
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agile posture not only for emergencies but also for the approval of products as a whole. All these advances in the regulatory field, added to the use of digital tools, were essential for the research sector. Roberto Otto points out: “We can mainly observe the improvement and processes speed, such as regulatory processes (related to clinical research documentation), contractual processes (with the implementation of electronic signatures), virtual meetings with sponsors, researchers, study teams, and telemedicine with the innovation of patient care processes. Digital tools were essential in this context, as there was a search for digital without compromising good clinical practices and the ethical and scientific rigor of the studies”. These transformations have changed the way Brazilians see science. In a recent international study, the State of Science Index (SOSI) showed that, while Brazilians have 92% confidence in science, the global av-
erage is 89%. The population’s confidence increases their interest and participation in the subject, which is advantageous. Gustavo Mendes sees this participation as fundamental: “What is expected from a regulatory activity and the health sciences are that it becomes beneficial for the population. People need to understand and be able to know what benefits a new technology and what a new product brings to collaborate in health.” The pandemic has highlighted the importance of increasing investments in science and industry, promoting partnerships between the public and private sectors, encouragement of technology-based startups, and increasingly working to eliminate bureaucratic impasses. However, all the lessons learned and advance acquired during these last two years, added to a scenario of population support and international prominence, contribute to the country reaching a benchmark in technological development and innovation. ●
The high demand for active pharmaceutical ingredients, materials, and laboratory equipment worldwide generated a shortage situation in the country, CAUSING 54 bioBr
MANY TYPES OF RESEARCH TO BE INTERRUPTED
HELENA FACCIOLI, CEO OF FARMACORE BIOTECHNOLOGY
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How to overcome
the biological manufacturing gap in Brazil
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uring the past decade, there has been a significant shift in the nature of the products manufactured and sold by the innovative biopharmaceutical (biopharma) industry. Today’s global biopharmaceutical portfolio contains a greater prevalence of large molecule drugs, an increase in the number of personalized or targeted products, and a rise in treatments for many orphan diseases. These trends have increased the number of biopharmaceutical products with extremely limited production runs, highly specific manufacturing requirements, and genotype-specific products(1). The biopharmaceutical industry produces medicines that save, sustain, and improve people’s lives. Biopharmaceuticals are
used to treat and prevent some of the most common and debilitating diseases that affect human health, such as cancer, diabetes, autoimmune disorders, and bacterial and viral infections. It resulted in one of the most important and valuable business sectors in the world. Biopharmaceuticals, unlike other medicines, are manufactured, extracted, or otherwise derived from biological sources and require complex raw materials, equipment, and manufacturing processes, as well as extremely high specialized labor and facilities(2). North America and Europe have the most biological manufacturing capacity. South America represents only 2.19% of the total global biopharmaceutical manufacturing capacity(3). It helps to explain why there are so few biopharmaceutical products launched through extensive Brazil-
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ian research(4). The low manufacturing capacity also implies a high cost of healthcare expenditures by the Brazilian government, which reached 1.3 billion USD in 2015(5). Other reasons for this outlook are the need for pilot-scale facilities and training in the bioprocess industrial environment. Pilot-scale facilities are essential for the risk-reduction process of projects that present challenges not found in laboratory-scale studies. Moreover, the lack of suitable bioprocess infrastructure for training prevents graduates from filling key industrial positions in cell culture and fermentation, downstream processes, analytical development, scale-up, and regulatory affairs(6). Despite the biopharmaceutical scenario appearing to be gloomy and discouraging in Brazil, the reality has been changed. Recently, the Brazilian government updated the Innovation Law, whose goal is to stimulate partnerships between public research institutes and private companies. In 2021, the Brasil-Biotech Initiative was launched with the goal of contributing to the National Policy for Research, Development, and Innovation (R, D&I) in Biotechnology, as well as creating, integrating, and strengthening governmental actions in the field, with a focus on the promotion of science and innovation, as well as economic and social development. Furthermore, one of the most important Brazilian initiatives is the Partnerships for Productive Development (PDP). Its main objective is to promote the development of national biopharmaceutics to reduce the costs of acquiring medicines and health products that are currently imported or that represent a high cost for the Unified Health System (SUS). It is especially important for a country with more than 200 million habi-
tants with a potential market for biosimilars. “The integration of university, industry, and the government is critical for the development of Brazil’s biotechnology sector. Only by combining this triad will we be able to reduce risks and overcome the “valley of death” between academic prototypes and commercial-scale deployment. I think we are heading in the right direction in Brazil”, says Fernando Barbosa, CEO of Biotimize. ●
BIOTIMIZE is an early-stage Biotechnology as a Service company with an innovative business model (BaaS). Led by entrepreneurs with solid experience in innovation, acquired in large companies such as Cristália and B2W Digital, in addition to training in the best research centers in the world (Harvard, UNESP, USP), Biotimize is on its way to being the first biological CDMO in Brazil. With a mission to transform lives through biotechnology, Biotimize enables ideas and treatments to become reality. To learn more about the company, visit www.biotimize.com.br.
(1) https://www2.deloitte.com/content/dam/Deloitte/us/Documents/life-sciences-health-care/us-lshc-advanced-biopharmaceutical-manufacturing-white-paper-051515.pdf / (2) https://niimbl.force.com/s/about-niimbl / (3) Top1000bio.com / (4) https://consultas.anvisa.gov.br/#/ medicamentos / (5) http://repositorio.ipea.gov.br/bitstream/11058/8522/1/TD_2398.pd / (6) DOI: 10.1126/science.abj5040
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Regulation of Cannabis-derived products for medical purposes in Brazil João Paulo Silvério Perfeito Clinical and Industrial Pharmacist; Master’s degree in health sciences. Expert in Health Regulation of General Office of Drugs at the Brazilian Health Regulatory Agency (Anvisa) for 15 years, where currently works as Manager of Herbal and Complementary Medicines
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ecently, Cannabis sativa L. has once again aroused great interest in society. Globally, the therapeutic use of the plant has been rediscovered, and the demand for Cannabis and Cannabis-derived products, to treat or alleviate health conditions not met by the medicines available on the market has challenged health regulatory authorities worldwide. Despite several studies reporting therapeutic benefits using Cannabis-derived products, most of these studies do not yet present conclusive information on efficacy. Thus, there are very few Cannabis-derived products approved worldwide as medicine. In Brazil, there is only one Cannabis-derived product approved as a medicine, Mevatyl® (Sativex), composed of tetrahydrocannabinol and cannabidiol, indicated for the symptomatic treatment of moderate to severe spasticity related to Multiple Sclerosis. Important to emphasize that in Brazil, there is no objection to the
authorization of Cannabis products as medicines once provided that efficacy, safety, and quality are proven. Thus, considering the gap of complete information on efficacy, in many countries, laws that regulate Cannabis and Cannabis-derived products in a specific regulatory category, different from the medicine category, in order to allow controlled and faster access to them have been approved. In Brazil, despite the lack of a specific law on this subject, the Brazilian Health Regulatory Agency
(Anvisa) continues to work, within the limits of its legal and technical prerogative, in order to allow patients without therapeutic alternatives to access these Cannabis products based on medical monitoring and recommendation. Since 2015, with the approval of Resolution RDC nº 17, have been made possible to import, on an exceptional basis, Cannabis products, by individuals for their own use. The Resolution has undergone continuous updates in the last three years in order to simplify the patient’s import authorization process, and today, these rules are established by Resolution RDC nº 660/2022. Anvisa also worked on the construction of a regulatory framework that allowed the regularization of these products in Brazil. In 2019, approved Resolution RDC nº 327, which defined conditions and procedures for the authorization of the manufacture, import, and commercialization of Cannabis-derived products with pharmaceutical quality, as well as established
a control mechanism that enables the monitoring of these products, their manufacture, prescription, distribution, and dispensing. Briefly, there are currently three regulated forms of access to Cannabis-derived products for medical purposes in Brazil: ● as a medicine – licensed according to Resolution RDC nº 26/2014 or RDC nº 24/2011; ● as Cannabis products, imported by individuals for their own use – according to Resolution RDC nº 660/2022; and ● as Cannabis-derived products – authorized according to Resolution RDC nº 327/2019. The Resolution RDC nº 327/2019 is a temporary regulation that aims to frame and regularize the marketing of these products in Brazilian drugstores. The authorized Cannabis-derived product is granted a defined validity period, of 5 years, as an incentive for it to migrate to the med-
icine category, with the conclusion and presentation of the necessary evidence to prove its efficacy and safety. Since it came into force just over two years ago, Resolution RDC nº 327/2019, has already made it possible for Anvisa to approve 18 Cannabis-derived products. There are about 15 other applications under evaluation by the Agency, and demand has been growing. As defined in art. 77 of Resolution RDC nº 327/2019, the guidelines established therein must be reviewed within three years after its publication. Thus, Anvisa has already started the reassessment process, which will lead to the improvement of this regulatory framework. In the second half of 2022, the proposal will undergo public consultation, when all interested parties will be able to participate by submitting contributions to the draft text. This reassessment should consider the progress of research and regulatory maturity on the subject in addition to market experience. ●
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Innovation & partnerships for public health Mauricio Zuma, CEO - Bio-Manguinhos / Oswaldo Cruz Foundation Brazil
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io-Manguinhos is the Fiocruz unit responsible for research, innovation, technological development, and the production of vaccines, diagnostic kits, and biopharmaceuticals aimed at primarily meeting the demands of Brazilian public health. Bio-Manguinhos’ competence goes beyond production. The continuous investment in the innovation chain and technological development is another hallmark of the Institute, as well as the mastery of cutting-edge technologies and advanced production processes. Partnerships with other institutions - public and private - guarantee technology transfer and technological development agreements, contributing to the evolution of the Institute’s projects. Compliance with the GMP requirements, alongside with the quality certification of our laboratories, make the Institute a crucial agent for public health. Not only in Brazil: in the international scenario, we have been exporting our surplus production to more than 70 countries through United Nations agencies. Since 2001, our yellow fever vaccine has been pre-qualified by the WHO (World Health Organization). More than the supply, it was based on a clinical research done by us that the WHO adopted the strate-
gy “Fractional dose yellow fever vaccine as a dose-sparing option for outbreak response” to contain the outbreak in the Democratic Republic of Congo in 2016. The institution has also contributed to the control of meningitis outbreaks, especially in Africa, through the provision of vaccines. Recently, Bio-Manguinhos was nominated as Brazil’s representative at the BRICS Vaccine Research and Development Center, an initiative to strengthen cooperation in the field of vaccines to ensure access to developing countries through equitable distribution as a global public good. It is also part of the Global Community of Technology and Sustainable Innovation, which brings together experts in technological solutions from around the world, focused on the sustainable development goals set out in the UN 2030 Agenda. The Institute is a member of the Developing Countries Vaccine Manufacturers Network (DCVMN), a voluntary public health-driven alliance of vaccine manufacturers from developing countries, firmly engaged in research, development, manufacturing, and supply of high-quality vaccines that are accessible to protect people against known and emerging infectious diseases globally. Also, we were selected by PAHO(A-
frican Health Observatory Platform)/ WHO as a center for the development and production of vaccines with RNA technology in Latin America. The selection occurs because of a call for expressions of interest launched worldwide in April 2021 to increase production, capacity and expand access to vaccines against Covid-19 in the Americas. Our innovative platform, the self-amplifying RNA, can fast become a main goal for worldwide labs. Partnerships are part of our identity: now, our Pilot Plant can be contracted to provide final processing services of vaccines and biopharmaceuticals, in accordance with the requirements of Good Manufacturing Practices and regulatory instructions in force of the National Regulatory Agency (Anvisa), also meeting Good Laboratory Practices and biosafety requirements. The area uses single-use systems and counts with independent industrial pharmaceutical air conditioning and production of purified water and water for injection (WFI), both qualified according to national and international regulations. The facility offers services for the production of small size scale experimental and/or commercial batches, such as: fill and finish, lyophilization and crimping with a fully automated line. ●
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Janssen Brazil: A Commitment to the Country for 89 Years Janssen
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t Janssen, we’re creating a future where disease is a thing of the past. We are the pharmaceutical companies of Johnson & Johnson, working tirelessly to make this future a reality for patients everywhere, fighting sickness with science, improving access with ingenuity and healing hopelessness with heart. We aim to advance innovative solutions for unmet health care needs, being focused on areas in which we believe we can make the biggest difference: Oncology; Immunology; Neuroscience; Infectious Diseases and Vaccines; Pulmonary Hypertension; and Cardiovascular and Metabolism.
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FOCUS ON BRAZILIAN MARKET With the innovation pace being accelerated in recent years, there are already 50 Janssen medicines currently available in Brazil. From 2018 to May 2022, Janssen received 41 new regulatory approvals in the country, with 14 new medicines and 27 line extensions for different disease areas, including treatment-resistant depression, bladder cancer, prostate cancer, multiple myeloma, psoriasis, psoriatic arthritis, and ulcerative colitis, among others.
CLINICAL RESEARCH Currently, Janssen is among the top 3 pharmaceutical companies in clinical trials numbers being conducted in Brazil1. There are 74 ongoing studies. In the last three years, studies involved over 500 institutions and had more than 30,000 volunteers participating. COMMITMENT TO THE LOCAL HEALTHCARE ECOSYSTEM THROUGH INNOVATION In Brazil, we work to ensure broad and timely access to medicines through unique collaborations with governments, healthcare agencies, and o the r s. It be ne fits the country in several ways, including supporting infrastructure modernization, the needed knowledge for key products development, and the highly skilled workers’ training and employment & retention. Some examples of these initiatives include technology transfers through Productive Development Partnerships (PDP) which can create a significant impact on local manufacturing for the Unified Health System (SUS), in addition to the qualification of public and private laboratories in the country. Learn more in Box 1.
BOX 1
Over the last few years, the challenges within the healthcare system have highlighted the need for a favorable innovation environment, which streamlines the development and adoption of healthcare solutions to fulfill unmet patient needs. This innovation fostering has helped to stimulate and encourage new developments in the whole country.
Janssen works with two initiatives based on technology transfers through PDPs, which are conducted along with Bio-Manguinhos/Fiocruz, a national public laboratory, and Bionovis, a private joint-venture of pharmaceutical biotechnology. These alliances encompass manufacturing technology share, including master cells for two innovative biologics being used worldwide to treat patients with immune-mediated diseases in rheumatology, gastroenterology, and dermatology. Through these technology transfers, Brazilian professionals are becoming qualified to work on high-complexity processes, analyses, and quality control initiatives involving biologics manufacturing and supply under the direct supervision of Janssen’s high-skilled specialists. Also, in compliance with all regulations and within estimated timeframes, these successful part-
nerships benefit 88,000² patients with medicines and treatment. In addition to the medicines made available through SUS, these patients have been assisted by Janssen Brazil’s Patient Support Program (PSP), which encompasses initiatives of treatment compliance, safety, minimization of resource use from the Ministry of Health and the avoidance of waste. To keep these achievements moving forward and generating more opportunities, several efforts have been made to establish legal frameworks for PDPs, building assertiveness and legal security for all those involved and thus encouraging the development of innovative projects in the country. Therefore, we conclude that gaining trust for all Brazilian health partners’ ecosystems is positive to the entire country, as it promotes national development, the skill of professionals, and the well-being of thousands of patients.
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At Janssen, our innovation efforts go far beyond internal Research & Development, as we also support an open innovation strategy. In Brazil, through our global innovation framework, we are able to develop several partnerships focused on innovative initiatives. Within our J&J Innovation programs, we provide the ideal environment for emerging companies to catalyze growth and optimize their Research & Development programs, fostering vital industry connections and offering both science- and business-oriented education programs. For instance, at JLABS, our startups incubator, a small company, acquires immediate access to the resources and expertise which are typically available to larger companies as Johnson & Johnson, including entry to our partners in manufacturing, logistics, development, and mentorship. To enable us to partner effectively, we seek to understand the cultural and legal characteristics of each ecosystem where we operate, including its unique strengths and opportunities. In Brazil and Latin America, we have launched five challenges seeking solutions to specific regional needs and recognizing the impact of the work of local scientists. These types of initiatives promote the knowledge, skills, and perspectives exchanges; reduce the time to market of new products; offer the potential to foster the development of transformational innovation for patients and consumers; and ultimate-
ly help build a strong healthcare ecosystem with an increased level of preparation to respond to public health needs and emergencies. The most important outcome of investments made in innovation, science, and technology is the ability to help the people in need of life-changing health care solutions. ●
Within our J&J Innovation programs, we provide the ideal environment for emerging companies to catalyze growth and optimize their Research & Development programs,
FOSTERING VITAL INDUSTRY CONNECTIONS AND OFFERING BOTH SCIENCE- AND BUSINESS-ORIENTED EDUCATION PROGRAMS
(1) TrialTrove, CitelineTM , April/22 / (2) DATASUS. Infliximab Feb/18 - Jan/22: 66.039 patients. Golimumabe from Sep/20 - Jan/22: 21.931 patients.
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