bioBR 2021 - 5th Edition

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Brazilian Delegation

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SUMMARY 12 18 24 30 TECHNOLOGIES Discover some of the most innovative Brazilian health startups

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OPPORTUNITIES Lights among the chaos VACCINES Biotechnology: an essential tool to fight the pandemic INNOVATION Investments in pharmaceutical research and development in Brazil during the COVID-19 crisis INPUTS The impacts of Brazil’s external dependence on pharmaceutical raw materials and products STRATEGIC AREA The Role of Clinical Research in the Economy BIOTECHNOLOGY Health Biotech Innovation in Brazil: the need for stronger support to bring them from bench to market REGULATORY AGENCIES COVID-19 and the Legacy of Transformations in Regulatory Agency Processes INDUSTRY Challenges and Strategies for Improving the Health Industrial Complex in Brazil

BIO Br Project Management by: Reporter: BIOMINAS Brasil / Planning, Control and Operation: Carolina Sellani Art Editor: Daniel Guedes / Contact us at: marketing@abiquifi.org.br / Visit our site: bph.org.br

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Lights

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he pandemic demanded resilience from all of us. This was not different for the stakeholders of the biotech, pharma, and health sectors. Nonetheless, even in this chaotic situation of a health crisis, they were able to innovate and contribute to society.

Fabio Bussinger, as CEO of the Operational Governance Pharma Institute (IFGO), the first Institute created in Brazil exclusively focused on the development of good operational and industrial governance practices for pharmaceutical companies in Brazil, works closely with them and has accompanied firsthand the different challenges it faced in the last year. According to him, the first hardship was that the Asian suppliers, especially from China and India, interrupted exportations. Brazil relies heavily on imports of pharmaceutical raw materials from such countries, so companies significantly felt the impact of this disruption.

When this situation normalized, the problem was the logistics. Companies were selling, but there were no air or naval routes to deliver the products. When they could be dispatched, the problem was the cost.

Freight price increased exponentially and

added to the high dollar exchange rate, the companies’ margin reduced drastically.

But they kept up with the hard work, because they had a commitment to patients and to health professionals that were working night and day to fight the new coronavirus. Together with innovating in their internal processes and activities to deal with the new risk, they reinforced measures that were already internalized in their culture, such as strict hygiene and sanitary protocols and a robust inventory of raw materials.

Fabio says that the pharmaceutical industry productivity reached an all time high. “In our Benchmarking Operational Competitiveness (BCO Farma) platform we have registered a productivity increase of 15%. Until 2020, the highest rate was 8% in one year”. This avoided shortages for not only medicines to fight against COVID-19 but also for all the other conditions.

Opportunities also emerged in research and development (R&D). The number of clinical trials happening in Brazil has risen. With a massive and diverse population, the high dollar exchange rate diminished the cost of conducting these studies in the country. The Government strengthened its support to health inno-

vation, specially focused on COVID-19, and some companies started projects to develop new treatments or new vaccines.

According to Fabio, the national industry has matured a lot in the last years, which allowed them to take advantage of these new opportunities. “We already have patented Brazilian products, and their number is only going to increase in the following years. I am extremely optimistic about the development of the pharma sector in Brazil. We have state of the art production processes and sites, with some production lines being of the best class in the world.”

One of the biggest challenges brought by the pandemic was the supply of active pharmaceutical ingredients (APIs). With the interruption of international trade chains and an overall shortage of raw materials due to the super demand, countries that rely heavily on importation of such inputs came into trouble. That was not only the case of Brazil, but for dominant markets as well, as the biggest producers of pharmaceutical raw materials are China and India, two countries that were heavily affected by COVID-19 and at some point had to focus on their internal markets.

For Rodrigo Souza, Associate Professor at the Federal University of Rio de Janeiro and Co-founder of NovaSynth, it is the lack of technological mastery for API production that puts Brazil in this uncomfortable position. “We know how to formulate the vaccine, but the main ingredient is missing”, he says. For Brazil, developing the pharma-chemical sector and producing these assets locally will bring countless benefits in the short, medium, and long term. Mastering the synthetic route of the main component of a drug guarantees

its regular supply, price stability and, especially, the availability of that drug in the country. In a broader view, mastering synthetic routes and integrating the process means reducing our technological backwardness, developing the national industry, and increasing our innovation capability.

But it is a process that takes time. According to Rodrigo: “This movement to internalize APIs production is not simple and comprises an understanding of the risks and challenges that lie ahead, especially regarding price competition with established markets. That is why it is important to emphasize that national production cannot be made for any compound, it should be focused on those which the added value or sales volume allows to assume some risk. In the countries where this strategy is stronger, the Government has been highly active in encouraging the pharma-chemical sector to invest in it.

Here it cannot be different, we need the participation of the Government to leverage the national pharma-chemical sector and to have more control of our API market chain.”

In this direction, one important government action that occurred during the pandemic was the Brazilian new regulation for active pharmaceutical ingredients (APIs). It has instituted the Active Pharmaceutical Input Dossier (Difa) and the Adequacy of Active Pharmaceutical Input Dossier Letter (Cadifa) for synthetic APIs used in the manufacture of new, innovative, generic, and similar drugs.

This initiative is a convergence to the rules of the International Council on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and has been discussed to-

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gether with relevant stakeholders from the regulated sector since 2018. The new rules were published in April 2020, with a deadline for implementation until March 2021.

They standardize the evaluation criteria for API producers. Before, Brazilian producers had to follow requirements, such as in-site inspections, that were not asked of international providers. The new rules dynamize the active ingredients market and pose an opportunity for Brazilian producers to boost its sales not only to the internal market but also through exports.

For Luciana Carrasco, Consultant in Regulatory Affairs for the Brazilian Industry Association of Active Pharmaceutical Ingredients (Abiquifi), the isonomy brought by the new legislation is a strengthening opportunity for the industry. Especially together with other initiatives, such as the Bill N⁰ 4209 that is being discussed in Congress and aims at giving priority analysis at the Brazilian Health Regulatory Agency (Anvisa) for drugs that use APIs produced locally.

This is only one example of the Government also adapting to the new context. Another initiative was the institution of a Pharma Working Group (in Portuguese, GT-Farma) within the Ministry of Science, Technology, and Innovations (MCTI). The group seeks to encourage actions to foster the pharmaceutical and medicines sector growth, for consolidating national sovereignty in this segment. It is composed also by the Health and Defense Ministries and other governmental entities – the Brazilian Health Regulatory Agency (Anvisa), the Brazilian Innovation Agency (Finep), the National Council of Scientific and Technological Development (CNPq) and the Brazilian Industrial Research and Innovation Company (EMBRAPII). And also industry representatives, from the FarmaBrasil Group, the Brazilian Association of Fine Chemicals, Biotechnology and its Specialties (ABIFINA), the Association of Nation-

FABIO BUSSINGER, AS CEO OF THE OPERATIONAL GOVERNANCE PHARMA INSTITUTE (IFGO)

For Brazil, developing the pharma-chemical sector and producing these assets locally

WILL BRING COUNTLESS BENEFITS IN THE SHORT, MEDIUM, AND LONG TERM

al Pharmaceutical Laboratories (ALANAC) and the Brazilian Industry Association of Active Pharmaceutical Ingredients (Abiquifi).

GT-Farma was created in June 2020 and ended its initial term of operation in early 2021. This open dialogue between different Government instances and the private representatives is highly prolific. Norberto Prestes, Abiquifi’s President says that many actions were discussed together, for example, the improvement of the statistical data about the APIs industry, a measure that improves transparency and dynamizes the sector, as qualified information can be used for strategic thinking by the companies and the Government in planning public policies. The working group developed a plan of action and is becoming a permanent commission within the MCTI. To contribute to this new roadmap for the APIs sector, Abiquifi is planning to do a mapping of technological skills installed in Brazil, both in research institutions and companies. On one hand, Brazil already has strategic elements, such as well established companies, a traditional and strong scientific environment, and its great biodiversity.

On the other hand, the fine chemistry sector has an extremely complex market chain, and as the public policies for strengthening the sector and building national autonomy have been abandoned in the last years, efforts to reintegrate the different players and catch up with the innovation state of the art are necessary. According to Norberto: “With ten years of hard work, making big investments, we can leave from producing only 5% of the APIs locally and reach 20%. In 2019, we imported USD 2 billion in inputs. And we can produce at least USD 500 million of that in the country and with high-added value. But to have such results, there has to be investments in the order of USD 500 million to USD 1 billion, from both public and private funders.”

Also, the GT-Farma has already fos-

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tered connections between its participants. Abiquifi has signed a strategic alliance agreement with EMBRAPII to foster innovation, local production and make the country more technologically independent. Abiquifi helps the companies identify their technological needs and project opportunities and match them with EMBRAPII competences. This codevelopment is good not only for the companies and researchers involved, but also for the country.

To help stakeholders overcome their technological challenges, EMBRAPII has a network of partner research centers in Brazil, called EMBRAPII Units. With over 60 Units distributed around the country and with diverse knowledge expertise, some of them are competent to develop solutions in drugs, biopharmaceuticals and supplies for the pharmaceutical sector.

Strategies like this, based on the interaction of the industry with research centers, are seen as a core activity for the Brazilian innovation system. EMBRAPII shares the investments with the companies, funding a significant part of the projects.

Rodrigo from NovaSynth experiences this interaction directly, as he works both at a university and at a startup. The company does proprietary development and co-development of molecules starting from basic chemistry and assembling advanced materials of ultimate interest to the industries, whether pharmaceutical, veterinary, food or industrial. It already partners with large Brazilian companies that understand that the development of processes within the national territory can assure them a different degree of competitiveness in the near future.

An interesting and advanced project his startup has is the synthesis of cannabidiol (CBD) and its derivatives. The world has been using CBD and its derivatives in numerous applications, ranging from the treatment of severe epilepsy and parkin-

son’s to fibromyalgia. About this project, Rodrigo mentions: “Our process today uses continuous flow technology, being able to miniaturize the reactors involved in the process, which now fit in a space of 2 square meters. We want to revolutionize the way of dealing with chemistry and there is a path.

Today we operate as a technology start-up that aims to develop synthesis technology for the national and global industry. We believe that flow synthesis technology may be a great technological ally on this path.

Also, NovaSynth was born from the symbiosis between academia and business.”

He also says: “Universities and technology centers, in addition to being a source of highly specialized human resources, can offer industry access to cutting-edge equipment, which is fundamental for creating and developing new processes. In addition, the collaboration in R&D projects between companies and universities/research centers can work to expand the research capacity, either for the introduction of new APIs in the company’s portfolio, or for the optimization of existing processes.”

These and other initiatives are featured on this 5th of bioBr magazine. In the next pages, we present an overview of the Brazilian environment and we detail projects and opportunities especially regarding bioproducts, investments in life sciences and APIs production. Enjoy your reading! ●

RODRIGO SOUZA, ASSOCIATE PROFESSOR AT THE FEDERAL UNIVERSITY OF RIO DE JANEIRO AND CO-FOUNDER OF NOVASYNTH LUCIANA CARRASCO, CONSULTANT IN REGULATORY AFFAIRS FOR THE BRAZILIAN INDUSTRY ASSOCIATION OF ACTIVE PHARMACEUTICAL INGREDIENTS (ABIQUIFI)

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Biotechnology: an essential tool to fight the pandemic

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iotechnology is behind the most effective tools to combat COVID-19, with developers and producers overcoming barriers and working intensively in the search for solutions. It is present not only in the virus identification and genetic sequencing, which happened at an unprecedented speed. And in the key technologies used to fight the virus, from diagnostics to treatment, including prevention.

Immunological tests, polymerase chain reaction (PCR), monoclonal antibodies, the several vaccines’ development and production techniques, including the state-of-theart mRNA platform, are only a few examples of them. The numbers are impressive. From April 2020 to March 2021, about 5,000 clinical trials were registered for COVID-19.

Currently, there are almost 300 vaccine candidates under development and about 40% of them in clinical development. Fifteen have already been authorized for use.

The biotech and pharmaceutical industry

were instrumental in developing and shipping vaccines for COVID-19 in record time.

It worked closely with leading research laboratories, hospitals, diagnostic companies, drug manufacturers and companies of all sizes, including startups. This achievement has highlighted the important and transformative power of science to the public and to many decision-makers. But biotech’s role in the pandemic, and the pandemic’s role in shaping the industry, the economy, and innovation, won’t fade away, even as the vaccines are administered across the globe. Progress has been made not only for COVID-19. This renewed effort has also boosted research for other diseases and may also benefit vaccine development for the most neglected diseases.

The regulatory agencies worldwide had to move fast to be able to deal with this new emergency and complex context and timely respond to the demands brought by the pandemic. Gustavo Mendes, General Manager of Medicines and Biological Products at the Brazilian Health Regulatory Agency (Anvisa), recalls: “From the first moment, I remember meeting with other agencies

and saying that we would be pressured to give quick answers while still maintaining high safety and effectiveness criteria.”

For Anvisa, the pandemic required administrative and technical adaptations. On the administrative part, it reorganized processes to give priority to COVID-19 and the technologies to deal with it, as well as actions to keep these products on the market, quickly resolving supply issues, for example. The Agency has created a committee of experts that aims to evaluate the different cases and give timely answers. And on the technical part, it tried to verify how it could optimize the analysis, by identifying which were the critical decision points that could receive more attention to allow a quick response. These adaptations also serve for products not related to COVID-19.

The fact that Anvisa is part of global networks, such as the International Council on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and the Pharmaceutical Inspection Co-operation Scheme (PIC/S), is especially important

to implement such improvements in a faster way. More than the harmonization of procedures and activities, for example reducing duplication of inspections, they promote information and experience sharing, as well as joint learning. This exchange between agencies was crucial to deal with a global scale sanitary crisis.

Gustavo states: “Brazil has sought to position itself as a country in which the possibility of developing new technologies and their manufacturing and R&D are important, and the scenario has stimulated investments, for example, by having several clinical studies approved in Brazil during the pandemic, as well as initiatives for the national development of vaccines in research institutions. This is due to our robust scientific and regulatory environment.”

Brazil has two main examples of institutions working with biotech to fight the new coronavirus: Instituto Butantan and the Oswaldo Cruz Foundation (Fiocruz). Both are public institutions focused on research, development and manufacturing of pharmaceutical products, the first one located in

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São Paulo and the other one in Rio de Janeiro.

Butantan has several technological platforms for vaccine production, such as cell-based and with embryonated eggs that allow the production of all sorts of vaccines, such as inactivated, viral vector, attenuated virus, recombinant protein, among others. This flexibility is necessary due to the multiple technologies that are used for different vaccines. In the very first reports of COVID-19’s community transmission, Butantan started negotiations with several international vaccine developers for partnerships, and a determining factor to choose the partner and its vaccine technology was the compatibility with Butantan’s current know-how and infrastructure. As its expertise and capacity were more consolidated for inactivated vaccine technology, Butantan decided to follow this path, also due to its better logistical viability and greater production capacity. They partnered with Sinovac, a Chinese pharmaceutical company that already had the CoronaVac vaccine in late stages of development, and Butantan is responsible for its production and distribution in Brazil.

However, the Institute is also working on its own vaccine called ButanVac, produced on eggs and with greater immunogenicity, which will be 100% produced in the country and supplied to low- and middle-income countries. Apart from these projects, the Institute is also working on the coordination of a convalescent plasma network, development of a hyperimmune anti-COVID-19 serum, and a network for sequencing and monitoring of new Sars-Cov-2 variants.

It is evident that the moment demands agility, both on Butantan’s side, in the rapid development of a vaccine, and on the side of the public and regulatory sector that needs to understand the scenario and adapt in favor of agility. Butantan was persistent and faced adversity always grounded on science

and valuing its employees. Historically the Institute has developed and delivered products aimed at public health and needed to adapt to the difficulties imposed by the pandemic by intensifying its strategic planning, organizing and coordinating a testing network for COVID-19, participating in the State of São Paulo contingency committee to establish isolation strategies, while looking for funds and developing the vaccine.

Few institutions have developed so many simultaneous projects, and this shows that they have been working on several fronts with a lot of persistence and resilience.

This process has motivated the Institute to create regional competence to manufacture vaccines and biologicals, to oppose the dependence of many countries on few producers of biological medicines, one of the main challenges posed by the pandemic. In addition, the establishment of productive partnerships increased its capability of absorbing and developing new technologies.

In the future, one of the biggest challenges will be epidemiological surveillance for the screening and monitoring of new variants or viruses with pandemic potential, and Butantan will use its newly implemented alert network for this purpose, which will certainly contribute to the creation of new public policies or even of new generations of vaccines based on the virus variants.

The Oswaldo Cruz Foundation (Fiocruz), since the beginning of the pandemic in Brazil, has been part of several national and international fronts searching for vaccines against COVID-19. With a long tradition of more than 70 years in the production of vaccines, the Foundation has endeavored in various efforts, emphasizing the importance of the Unified Health System (SUS) as the basis for the development, production, and national distribution. Fiocruz’s main bet is an agreement with the biopharmaceutical company As-

traZeneca to produce, in Brazil, the vaccine against the new coronavirus developed by the University of Oxford. This agreement also aims to guarantee a national production with total technology transfer.

The Fiocruz factory is already being prepared for the production of Active Pharmaceutical Ingredients (API) in the country.

Fiocruz is also working on developing its own vaccine. At the moment, it is developing seven other vaccine projects, with different partners, national and foreign. The final products from the technology transfer will be available in the second half of 2021. These vaccines initiatives add to several other efforts in improving diagnostics, genomic surveillance, scientific divulgation and providing reliable information for the public as well as several events and seminars discussing the health industrial complex and public health policies.

For Rodrigo Correa, the Foundation’s Vice President of Research and Biological Collections, Fiocruz and Brazil have a great scientific and innovation capacity, at the same level as the world’s state of the art. Fiocruz presence in all national territory and

GUSTAVO MENDES, GENERAL MANAGER OF MEDICINES AND BIOLOGICAL PRODUCTS AT THE BRAZILIAN HEALTH REGULATORY AGENCY (ANVISA) CRISTIANE SANTOS, CORPORATE AFFAIRS AND COMMUNICATION DIRECTOR AT PFIZER BRAZIL

installed capability allowed it to provide solutions not only to other public institutions as well as private ones. For him, one of the biggest legacies of the COVID-19 is that everyone is talking about science and valuing it. Furthermore, we are seeing a greater involvement of the private sector, not only from the life sciences industry but also from several others, including funding, which is one of the main bottlenecks for science in Brazil. “The actors in the Brazilian innovation system currently work in a fragmented way. It is important to join forces in order to better use the country’s scientific capital and increase investments. Also, bridges between different stakeholders improve the overall innovation capacity, and the results that are being seen today are a result of a collaboration that can and should be improved, given that there is sufficient funding to do so.”

In both examples, the institutions have great experience using biotechnology and are world references in their field and were able to timely implement actions with different degrees of complexity, not only expanding activities that already existed, such as

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testing and genomic surveillance, but also engaging in new products development.

Their expertise in biotechnology allowed them to quickly mobilize their international collaboration networks and adapt to the new environment posed by the pandemic, and to deliver solutions for the population in record time.

Pfizer is another example, having developed a vaccine using a mRNA platform that is being distributed worldwide. This successful development was based on a joint effort with the startup BioNTech.

In addition, Cristiane Santos, Corporate Affairs and Communication Director at Pfizer Brazil, reminds us of the broader importance of bioproducts: “Biological medicines have brought about a real revolution in the treatment of cancer, autoimmune diseases and other diseases that have a major impact on the health of the population. This positive impact promises to be even greater in the future! We have 30 years of experience developing such medicines, currently, our pipeline has development programs, in different stages, covering the areas of oncology, rare diseases, pain and inflammation, immunology, ophthalmology, metabolic and cardiovascular diseases.”

And so is Janssen, the pharmaceutical company of Johnson & Johnson. Janssen believes in the power of innovation and science to overcome health challenges, seeking to build a future in which diseases are a part of the past. Janssen COVID-19 vaccine was developed using proprietary and proven technology called AdVac®, used also to develop and manufacture the company’s vaccine against Ebola, which received marketing authorization from the European Commission in July 2020, and to develop vaccine candidates against Zika, respiratory syncytial virus (RSV) and HIV, which are in stages 2 and 3 of clinical development.

In the case of COVID-19, Janssen’s immunizing agent was designed by the com-

RODRIGO CORREA, VICE PRESIDENT OF RESEARCH AND BIOLOGICAL COLLECTIONS AT THE OSWALDO CRUZ FOUNDATION

pany’s team of scientists, who engaged in developing a vaccine against the new coronavirus with important characteristics to fight the pandemic at this moment, such as being a one-dose vaccine and being able to be stored and transported in accordance with the existing cold chain distribution infrastructure and logistics for medicines and vaccines in Brazil. To develop a vaccine against COVID-19 in record time, Janssen has partnered with the US government’s Biomedical Advanced Research and Development Authority (BARDA) and Beth Israel Deaconess Medical Center (BIDMC) from the Harvard Medical School, as well as a global network of partners aiming to expand the production capacity of the vaccine.

The fact that many vaccines against COVID-19 were developed by biotech/ pharmaceutical companies in partnership with universities, research institutions and startups, demonstrate that this diverse and collaborative approach is key to coping not only with this pandemic but also with others that might come, as well with other unmet health and industrial needs. All stakeholders showed resilience and perseverance and have been strengthened by the lessons learned with this pandemic. ●

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Investments

in pharmaceutical research and development in Brazil during the COVID-19 crisis

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he COVID-19 is one of the biggest global crises of the last decades. Innovation, either through the development of new products or the repurposing of existing alternatives, became a central ingredient for overcoming not only the health aspects of the crisis but also the economic ones, caused by social isolation and trade interruption.

However, innovation is a demanding process, especially for new vaccines, drugs, and other life sciences technologies. Accelerating such a process to timely provide effective tools for containing the new coronavirus was a huge challenge, posed to all actors in the health innovation system: industry, academia, and governments. Public and private investors were especially called to action to fuel such a process.

Considering the overall foreign direct investment (FDI) scenario, Brazil is one of the largest FDI recipients and preferred investment destinations in Latin America. Data from the United Nations Conference on Trade and Development - UNCTAD’s World Investment Report 2020, shows that Brazil was the 6th global recipient of FDI inflows in 2019. Inward FDI flows totaled over USD 1 trillion from 2010 to 2019.

According to Maria Luisa Cravo, Investment Manager of the Brazilian Trade and Investment Promotion Agency (Apex-Brasil), institution that supports international investors in analyzing the opportunities to invest in the country, one of the main reasons Brazil continuously receives foreign direct investment and attracts leading and innovative international businesses is the country’s robust investment protection legislation, enforced by an independent judiciary and a stable regulatory environ-

ment, which provides security for investors.

Nonetheless, the COVID-19 has posed challenges on a scale never seen before, and this is true concerning the Brazilian health sector. Production of pharmaceuticals and medical equipment faced limitations in this period, due to supply chain bottlenecks caused by the COVID-19 pandemic containment measures.

Maria Luisa also states that it is important to highlight, however, that COVID-19 has also opened a broad range of new business opportunities: “At Apex-Brasil we have also observed the speeding up of implementation of innovation in the sector and we expect, for example, that telemedicine services in Brazil are set to expand considerably over the forecast period, helping to increase universal healthcare accessibility and raise the quality of medical services. As a result, demand for connected medicinal equipment and pharmaceuticals will grow in Brazil.

At Apex-Brasil, we have observed an in-

Data from the United Nations Conference on Trade and Development UNCTAD’s World Investment Report 2020, shows that Brazil

WAS THE 6th GLOBAL RECIPIENT OF FDI INFLOWS IN 2019

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crease in the number of investors being supported to enter the Brazilian market with new solutions for digital healthcare.”

The government is an important investor in pharmaceutical innovation, due to the high risk and large sums required. Only the State can invest such an elevated amount of resources and to sustain it through the long periods required by the bio and health sectors. This type of “patient capital” is crucial for adequately fostering this long-cycle innovative processes, made of several and complex steps, which discourages investors.

Nonetheless, according to data from the Institute of Socioeconomic Studies (Inesc), in its Thematic Budget for Science, Technology and Innovation in Medicines (OTMED ST&I), there is a clear downward trend in federal public investments in S,T&I since 2014, reaching 2020 with an authorized budget value corresponding to half of that of 2010. Considering specifically the investments made in pharmaceutical innovation, between 2014 and 2018, there is a real 18% drop in resources.

But in 2020 the government stepped up to the challenge posed by COVID-19 and there was a significant increase in spending driven by actions to combat COVID-19.

Since its beginning, the Brazilian Federal Government has invested on several fronts to stimulate research, development and production related to the health sector.

In 2020, the Ministry of Science, Technology and Innovations (MCTI) made available approximately USD 191 million1 in extraordinary credits to support coping actions against COVID-19. Of this amount, approximately USD 76 million was invested in research and development actions and approximately USD 115 million was directed to support companies, via credit offered by the Brazilian Innovation Agency (Finep).

Marcelo Morales, Secretary for Research and Scientific Education of the MCTI states: “We believe it is important and necessary for the Government to continue allocating resources to face this pandemic and to prevent other emerging diseases. Science, technology, and innovation (S,T&I) actions are necessary and urgent for us to move forward in the production of knowledge and in the search for technological alternatives for this problem’s solution.”

Also according to him, Brazil needs to create incentive mechanisms that favor private investment in research, development and innovation (R,D&I). Private investment in this sector is still very timid in

1. The exchange rate considered for all monetary values in this article was: BRL 5,23 = USD 1 (Source: Central Bank of Brazil; Database: May 31, 2021)

MARIA LUISA CRAVO, INVESTMENT MANAGER OF THE BRAZILIAN TRADE AND INVESTMENT PROMOTION AGENCY (APEX-BRASIL)

relation to other countries. That is why it is needed to work on mechanisms that encourage cooperation between academia and industry, so that academia can develop technological solutions, and the industry can transform them into products. Only through innovation can the Brazilian industry be strengthened and become globally competitive; without innovation, the country will remain dependent on external technology and its fine chemical and pharmaceutical companies will not be able to compete with the multinational giants. Brazil has a wide established scientific and technological competence and with incentive mechanisms for this academia-industry interaction, it will make an important leap.

Marcelo continues: “The Government has a fundamental role in this matter. To reduce risks, it can take some actions, such as, for example, to finance the early stages of development of a medicine or a vaccine, until the initial phases of the clinical trial, but it is important that the industries also participate in these steps as partners, even if the risks are assumed by the State. We need to get out of inertia. From the moment the wheel turns, and the industries become stronger, naturally the sector will start to occupy the role of the State and will invest more. This will make it much more robust and the system of S,T&I more irrigated. The pandemic showed us that we are too dependent on imported inputs. It is past time to articulate a joint effort by academia, industry, and the Government to make our country self-sufficient in health inputs. This is being done at the MCTI with actions aimed at technological development of products and inputs at all stages, until market entry.”

For example, the Brazilian Company of Research and Industrial Innovation (EMBRAPII) is a social organization fostered by the Federal Government that, since 2013, supports technological research institutions and fosters Brazilian industry innova-

tion. As soon as the first cases of the pandemic in Brazil were detected, immediate measures were taken to encourage EMBRAPII Units to prospect projects with companies that already were clients and new ones, and to contract industrial R&D projects to immediately tackle the spread and infectiousness of the new coronavirus, as well as projects aimed at the production of equipment and other inputs for patients already hospitalized with the disease. For this, EMBRAPII used its characteristic agility, flexibility, and reduced bureaucracy to finance projects, allowing the productive sector to have access to quickly and robust sources of funding. In some projects, EMBRAPII’s contributions correspond to about 90%.

EMBRAPII has in its essence a multidisciplinary approach, as the Ministry of Science, Technology and Innovation (MCTI) and the Ministry of Education (MEC) equally share the responsibility for EMBRAPII’s funding. Also, its core working model is based on government, industry, and academia interaction, which is an important lesson to be taken into account when dealing with the COVID-19 pandemic.

According to Jorge Guimarães, President and CEO of EMBRAPII: “The pandemic will certainly mark the warning that

MARCELO MORALES, SECRETARY FOR RESEARCH AND SCIENTIFIC EDUCATION OF THE MCTI

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countries must be better prepared in education and S,T&I to face possible new crises. Any resizing of the initiatives related to the financing of R,D&I in the health area should take into account the need to share public and private investments, taking as example the advances achieved in EMBRAPII’s performance model, based in the Government-Company-Academia interaction.”

During one year of the pandemic in Brazil, EMBRAPII financed 63 R,D&I projects, especially supporting the development of medical and hospital equipment, such as respirators, individual protective equipment, the first Brazilian “artificial lung” for extracorporeal oxygenation, protective masks, mechanical supports, sanitizing products, smart beds that monitor various health patients indicators in the emergency room and in the ICUs (intensive care units), among others. In the health sector, the EMBRAPII Units already had a strong presence in the development of medical and hospital equipment with several companies. The total investment in these 63 projects amounts to USD 8 million, of which USD 3 million are resources from EMBRAPII, USD 2 million from companies and the remainder from the counterpart of the EMBRAPII Units.

Helena Faccioli, President and CEO of Farmacore Biotech, agrees with this joint approach. For her, academia and industry need to work together from the beginning of the projects. “What we saw in this pandemic was a union of the largest universities in the world, with local companies.

This meant that the development time was accelerated and that vaccines were made available in less than a year. The academy has the idea, it has the knowledge, the industry has the industrial vision of what is scalable, what can be produced and marketed, and the regulatory experience to facilitate the testing and registration of products. For a product to be developed quickly,

it is extremely important that the industry partners with the academia from the beginning. This union facilitates investment in projects that are technically and commercially viable; thus, time and resources will not be wasted on projects with lower potential, and the risk is reduced.”

Farmacore is developing a COVID-19 vaccine, in partnership with PDS Biotech and the Faculty of Medicine of Ribeirão Preto from the University of São Paulo (FMRP-USP). The vaccine under development is based on nanoparticles and recombinant proteins. It is currently concluding pre-clinical studies and clinical trials are expected to start this year.

However, few companies have followed Farmacore’s steps in investing in state-ofthe-art high-risk projects. Many have focused their efforts on testing drugs against COVID-19, several of which already existed in their R&D portfolio or production lines for other applications. But the investment in innovation or in higher risk projects, such as the development of vaccines, has been much less seen. For Helena, Brazilian industries find it difficult to work with research and development projects, especially in the initial stages, not being keen to invest in new products, and there has been no change in this pattern because of the pandemic.

These examples show Brazil’s huge potential. It is expected that in the following years, with sustainable government funding, increased private investments in innovation and greater internationalization of national companies, either through exports or partnerships with institutions across the globe, that projects and successful cases multiply. BIO digital is a unique opportunity to build strong links between Brazilian and international stakeholders. ●

JORGE GUIMARÃES, PRESIDENT AND CEO OF EMBRAPII

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INPUTS

The impacts

of Brazil’s external dependence on pharmaceutical raw materials and products

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n recent times, the world has never experienced a crisis such as the one provoked

by COVID-19. In this context, a strong feature of the pharmaceutical sector became a great risk: its global interconnection. The demand for some goods exploded, international trade was interrupted and suddenly the sector’s greatest exporters had to focus on their internal markets.

Brazil has suffered greatly from its dependence on international providers of pharmaceutical goods. Even though the country has a robust pharmaceutical industry, with important local producers and also multinational companies, only 5% of the raw material it uses are manufactured locally. The remaining 95% are imported, with around 70% of these originating in China and India.

But this has not always been the case.

Around the 80’s, Brazil produced 50% of these inputs. At the time, there were incentives for companies to produce Active Pharmaceutical Ingredients (APIs) in the country and the sector consumed the internal production. In the late 80’s and through the 90’s, the Federal Government adopted a market opening policy for foreign companies and the local ones were not able to compete due to price

or technology. This had a great impact not only for Brazilian businesses, but also for the Brazilian economy and public health.

Norberto Prestes, President of the Brazilian Industry Association of Active Pharmaceutical Ingredients (Abiquifi), thinks that there was a lack of a strategy to better define what would be the inputs that should keep being produced in Brazil and that are important for public health, for example. He says: “We will have to rethink this process from now on.

The country has both technological and scientific capacity. Perhaps what Brazil lacked was permanence or perennial and continuous measures so that the incentive to the research and development of vaccines, or medicines and supplies, would never have been interrupted.”

Several Government measures are being taken recently in an attempt to reverse this scenario and reduce Brazil’s external dependence on pharmaceutical raw materials.

They involve more structured public policies, which were instituted through norms, such as, for example: the Innovation Law (and its amendments) and Decree N⁰ 9,283/2018 that regulates it; the National Policy for Technological Innovation in Health (PNITS); and the Partnership Program for Productive De-

Even though the country has a robust pharmaceutical industry, with important local producers and also multinational companies,

ONLY 5% OF THE RAW MATERIAL IT USES ARE MANUFACTURED LOCALLY

velopment (PDP), a program based on technology transfer and the use of the Federal Government immense purchase power related to the Unified Health System (SUS), one of the largest full universal and free access national public health system of the world.

Health legislation has also undergone successive improvements to ensure a better regulatory environment, as is the case with the new regulatory framework for APIs (RDC N⁰ 359, 361 and 362, all of 2020) and RDC N⁰ 55/2010 and 31/2014 that establish the criteria for the registration of biological medicines. The Bill N⁰ 4,209/2019, approved in May 2021 by the Federal Senate is another initiative that aims to strengthen the regulatory framework in Brazil in order to stimulate the local production of APIs, since it proposes a priority analysis at the Brazil Health Regulatory Agency (Anvisa) for national inputs and the decoupling of the API registry issuance from the registration of a drug, allowing, for example, the export of APIs. Other initiatives of great scope and relevance are the Pharma Working Group (GT-Farma), created under the Ministry of Science, Technology, and Innovations (MCTI), that discusses and formulates a proposal of a technological development and innovation incentive policy for the pharmaceutical inputs and medicines sector. The Special Subcommittee on Development of the Economic and Industrial Complex in Health, created within the scope of the Congress Social Security and Family Commission, intends to propose some strategies and guidelines to stimulate the national production of pharmaceutical and health products and inputs.

All these initiatives are aimed at strengthening the Industrial Health Complex and, consequently, reducing Brazil’s scientific, technological, and productive dependence.

Mirna Oliveira, currently Parliamentary Assistant to Government Leadership in Congress, with a long experience in this subject, including coordinating and managing activities related to Pharmaceutical Assistance and the Industrial Health Complex inside the Ministry of Health, believes that the biggest challenge is to coordinate all these initiatives in a single direction, converging efforts, interests and resources.

She says “I believe this situation is mainly due to political, economic, regulatory and social factors. High tax rates, political and economic instability in the country, strict health, environmental, labor, and administrative legislation, and a deficient supply of trained human resources are among the main difficulties faced by the sector and which impact its growth. Also, the absence of a state-focused public policy represents one of the greatest obstacles

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NORBERTO PRESTES, PRESIDENT OF THE BRAZILIAN INDUSTRY ASSOCIATION OF ACTIVE PHARMACEUTICAL INGREDIENTS (ABIQUIFI)

INPUTS

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to the expansion of the pharmachemical sector in Brazil. The existence of different initiatives, but without central coordination ends up being a disincentive at certain times. It is necessary to focus on solutions. In other words, we need to have a specific public policy for the sector and the definition of goals, deadlines and those responsible for its execution. We need to know what we want and where we want to be in a few years.”

Biological inputs are a key element in this scenario. National biosimilars are relatively new products in the Brazilian market, and the Partnership Program for Productive Development (PDP) functioned as the main lever for the production of these drugs nationally.

Currently, SUS distributes 7 biosimilar products that are the object of these partnerships.

The PDPs allowed, for example, the structuring of technological platforms for the manufacture of these products in several Brazilian public and private laboratories to meet the demands of SUS, which in turn acts as an accelerator of this process. In addition, the various international partnerships for technology transfer signed for PDP projects, allowed the establishment of new commercial, scientific, and technological partnerships for the manufacturing of other products, including biosimilars, in the national territory.

Thus, the dynamics of incorporating biological products into SUS ends up having a great influence in defining the direction of national production of biosimilars, as it is the largest consumer market in Brazil and has a greater territorial reach. For this reason, investments in the sector are mostly focused on the manufacture of these products. Therefore, the production of national biosimilars represents an important strategy for the strengthening of the Industrial Health Complex towards Brazilian autonomy in inputs.

Recepta Biopharma is a Brazilian company that directly deals with this area and its issues. Dedicated to the research and de-

MIRNA OLIVEIRA, PARLIAMENTARY ASSISTANT TO GOVERNMENT LEADERSHIP IN CONGRESS

velopment of new drugs for the treatment of cancer, Recepta was founded in 2006 as a result of a partnership between Brazilian businessmen with the Ludwig Cancer Research (LCR) Institute, sharing the view that Brazil offers a significant set of competitive advantages for the development of biotechnology focused on human health.

They have projects with two immunotherapeutic monoclonal antibodies in an advanced stage of clinical development.

Immunotherapeutic drugs, as they act on the immune system of patients, represent a new paradigm for the treatment of cancer.

Recepta’s antibodies were discovered and developed through an international partnership and are innovative medicines with proprietary patents. The registry application in the U.S. Food and Drug Administration (FDA) for one of them has just been submitted, with approval expected for the end of 2021. This antibody has proved to be highly effective in the treatment of cervical cancer, an important disease in Brazil. Registration in Anvisa must be obtained shortly after approval by the FDA. By the end of 2021, another application for registration should be submitted to the FDA, combining this

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INPUTS

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antibody with the other immunotherapeutic.

Jose Fernando Perez, Recepta’s CEO, says “We hold the rights to commercialize, develop and produce these antibodies in Brazil through technology transfer. With production in the country, we would be independent of the availability of contract manufacturing organizations (CMOs) in the international market, nor would we be affected by exchange rate instabilities affecting the product’s import cost. With the pandemic, several CMOs that produce APIs and fill the final product, have run out of capacity due to the demand for vaccine production and packaging. Thus, we are extremely interested in finding partner companies with infrastructure to carry out in Brazil both the production of the API and the packaging, so that we can be totally independent of these circumstances that may affect our ability to offer these drugs to Brazilian patients.”

For biosimilars also, the cost of production is remarkably elevated, as it involves high technology, imported inputs and extremely qualified human resources. Import taxes reach 60% and there are no national alternatives to these inputs. If these recurring challenges were not enough, the pandemic had an even greater impact on costs due to international economic effects, dollar uprising, altered logistics chains and scarcity of raw materials, as many are also part of the production process of vaccines against COVID-19.

Nonetheless, Brazilian companies are investing in this market. The pharmaceutical company Libbs inaugurated in 2016 its Biotechnology Unit, a plant dedicated to the manufacture of Active Biotechnological Pharmaceutical Inputs, with a focus on monoclonal antibodies. In addition to the plant, in that same year Libbs concluded the technology transfer of Rituximab (Vivvaxia), a biosimilar monoclonal antibody indicated for the treatment of chronic lymphocytic lymphomas and leukemias, and started the

JOSE FERNANDO PEREZ, RECEPTA’S CEO MARCIA BUENO, LIBBS’ INSTITUTIONAL AFFAIRS DIRECTOR

production of the composition batches for the registration dossier. This technological advance did not come alone, it also mobilized science and brought an alternative to Brazilian patients: in 2017, the company completed the multicenter clinical study, carried out in 25 Brazilian research centers and in 12 more countries, while disseminating the concepts of the biosimilar medicine in medical and academic circles. The approval from Anvisa was obtained and Libbs launched in 2019 the first monoclonal antibody produced in Brazil on an industrial scale.

For Marcia Bueno, Libbs’ Institutional Affairs Director, “It is extremely necessary and urgent for a State policy to stimulate innovation, focusing on the development of technological platforms and the production chain in the pharmaceutical sector. A policy with a long-term vision that brings legal, regulatory and tax security to investors. This will enable a virtuous cycle to happen, benefiting patients, companies, society and the country.”

These movements, initiatives and concrete projects are important not only for the industry’s economic development but also to guarantee the sustainability of SUS, the regular supply of strategic products and their access by the population. ●

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TECHNOLOGIES

Discover some of the most innovative Brazilian health startups – as known as true

“Hidden Champions”!

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razil is among the largest health markets in the world, as reported by InfoMoney (2019), and according to a 2019 study from IBGE (Brazilian Institute of Geography and Statistics), 9.2% of the Gross Domestic Product (GDP) of the country was spent on health in 2017.

Within this sector, innovation and technological development rely on startups that work in the health sector, that has grown exponentially, and which contributes to solving its problems. According to surveys carried out recently by institutions in the innovation ecosystem, Brazil has around 500 startups operating in this segment and, since 2014, these companies have already received USD 430 million in investments over 189 venture capital rounds.

Brazilian health startups are capable of taking advantage of market opportunities,

offering innovative solutions with agility and efficiency in the face of emerging demands, such as the challenges imposed by the new coronavirus. At least a dozen Brazilian startups presented technologies aimed at fighting the pandemic and supporting the population, doctors, hospitals, and the government at this time of health crisis.

When it comes to innovation in the health sector, certain technologies are promising, as they represent benefits both for companies and professionals, as well as for patients and society in general, reducing time and costs, increasing convenience, and offering increasingly effective treatments and diagnosis. Some of these technologies have been boosted by the advent of digital transformation, such as Artificial Intelligence (AI) and Machine Learning (ML), capable of increasing the accuracy, speed, and efficiency of health assistance, diagnostics, and even of clinics and hospi-

Brazil has around 500 startups operating in this segment and, since 2014, these companies have already received

USD 430 MILLION IN INVESTMENTS OVER 189 VENTURE CAPITAL ROUNDS

tal management. The emergence of applications that support and monitor treatments is also noteworthy, offering approaches that are more individualized for each patient. Other highlights, such as Virtual Reality (VR), wearables, and biosensors, show more and more possibilities of application in therapies and the improvement of patient’s life quality.

Concerning approaches based on hard sciences (i.e.: natural or physical sciences, chemistry, biology, physics), it is worth highlighting cell therapies and other immunotherapies which have been revolutionizing the treatment of cancer, one of the diseases with the highest mortality rate. In addition, the use of aptamers also has a high potential for the treatment of pathologies, as well as for molecular diagnosis. Point-of-Care tests (POCT) are also promising and have continuously increased recently, tending to further develop due to the convenience offered to patients. Finally, advances in 3D printing, which have enabled the creation of organs, tissues, prostheses, and tools, represent numerous promises for medicine.

Considering the potential of these trends and the important role of Brazilian startups in the technological development in the health sector and the solution of its problems, Abiquifi (the Brazilian Industry Association of Active Pharmaceutical Ingredient) and Apex-Brasil (the Brazilian Trade and Investment Promotion Agency) mapped Brazilian health startups, with the support of Biominas Brasil, focusing on two priority segments: Therapeutic Solutions for the areas of oncology, digestive and hormonal systems, neurology, respira-

tory or cardiovascular systems; and Health Products focused on patient care, devices, drug-delivery systems, diagnostics, clinical trials, or laboratory equipment and consumables. These segments have good market prospects, relevance to the Brazilian public health system (SUS), and competitive advantages for manufacturing in Brazil, being considered attractive and relevant.

The purpose of this mapping was to identify true “Hidden Champions” in health, that is, startups with relevant, highly innovative, and attractive solutions for the ecosystem. Thus, were only considered in the mapping the startups with a minimal advanced level of technological maturity (Technology Readiness Level - TRL > 4) and with solutions in the priority segments mentioned above. More than 80 projects were enrolled, and based on a careful analysis concerning technological and business aspects, 11 startups were selected, which we present below in alphabetical order.

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TECHNOLOGIES Bioptamers Bioptamers created a platform to develop nanocarriers and improve precision in delivering chemo/radio/immunotherapies for cancer treatment. Based on the type of patients’ disease, the company synthesizes personalized small molecules to guide and release medical interventions directly to their cancer cells, increasing therapeu-

Celluris Celluris is a startup company that aims to develop a Chimeric Antigen Receptor T-Cell (CAR-T) based therapy for the treatment of different hematological and solid tumors.

This technique is based on modifying the patient’s own cells, which start to recognize

epHealth

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tic efficiency and mitigating adverse effects to improve patient outcomes.

Bioptamers has filed provisional patent and PCT application of its technology. Global corporation, being present in Delaware-US, São Paulo-Brazil, and soon operating in London-UK. Backed

by SOSV venture capital firm.

the tumor as a target, fighting it precisely.

First company in Latin America to develop personalized treatment for cancer patients through a proprietary CAR-T immunotherapy that comprises a switch on/off/modulation system.

epHealth helps to make the health model more proactive and people-centered through four strategic pillars: Full Primary Care Solution for Smart Cities, Social Impact with Frontline Health Workers, Scientific development, and a Healthcare App for People with micro financial services for healthcare.

4 million people being monitored by epHealth’s solutions. Free app access in more than 3,900 cities, used by more than 30.000 health professionals; 50 city halls using the complete solution, with more than 20 million follow-ups carried out; 4 scientific studies with regulatory approval, and partnership with a leading research institute.

GlucoGear

preventive actions to avoid adverse effects.

GlucoGear’s solution is developed to facilitate and improve the treatment and life of people with diabetes through Digital Health and AI. It can predict Blood Glucose curves hours ahead and identify risks of hypoglycemia and hyperglycemia. Consequently, it can optimize insulin dosage and recommend

Proprietary algorithm capable of creating a new generation of insulin dosage and development of autonomous systems for manual injections; Experience in partnerships with big players in the sector (such as Fleury and Medtronic).

GnTech GnTech is a laboratory specialized in genetics that aims to make medical treatments more efficient and accessible, through tests using the sequencing of the human genome, with high precision and easy interpretation.

Present in all regions of Brazil; Registered software with high scalability and internationalization power; High-level exams, comparable to those available on the international market.

InsilicAll InsillicAll is an integrated end-to-end platform based on cloud computing for the personalized acceleration of drug discovery, chemical development, and chemical safety assessment campaigns.Through a low impact technology (ESG), the solution guarantees the optimization of time and cost reduction in the process of developing new products.

First Latin American company to offer a platform for drug discovery and regulatory toxicology applying AI and biological automation; Investments already received: Pre-seed investment by BiotechTown in 2019 (USD 28,7K 1) and Seed investment by Alvarez & Marsal in 2020 (USD 95,6K).

Laura

ly identification of clinical deterioration.

Laura offers AI solutions aiming to democratize health through technology and to generate positive social impact in scale, following the patient’s entire journey. The startup’s first product, “Laura Inteligência Clínica” (Laura Clinical Intelligence), is deployed in hospitals for ear-

Laura is present in more than 40 health institutions throughout Brazil, and since 2016 it has analyzed more than 10.7 million services, reduced the hospital mortality rate by 25%, and helped to save around 24,000 lives.

NAIAD NAIAD is a bioinformatics startup that creates novel bioactive molecules targeting G protein-coupled receptors (GPCRs), the superfamily of receptors involved in a wide range of diseases. NAIAD’s mission is to build a robust pipeline of new molecules with high potential to become next-generation medicines through its computational technology and AI.

Fundraising through Angel investment, PIPE-FAPESP, and Seed investment (has already raised more than USD 153K and is in the last stages to raise more than USD 267,7K); It is headquartered in the State of São Paulo and will open a branch in the US this year; Partnerships with companies from Europe, the United States, and Japan.

Nanoceuticals Nanoceuticals develops smart inputs to service life science industries. The startup has seven different nanotechnology platforms that can be adapted to meet customer demands and a biotechnology platform focused on the development of biomimetic

peptides with pharmacological activities.

8 technological platforms (7 nano & 1 biotech); Interaction with 90 clients; Sales of USD 191K in 2020. Produced more than 12 tons of nanomaterials in the last 3 years.

1. The exchange rate considered for all monetary values in this article was: BRL 5,23 = USD 1

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TECHNOLOGIES

PHP Biotech PHP was created to develop an antitumor drug for the treatment of triple-negative breast cancer, from a molecule created by the company’s founding researchers and a group of pharmaceutical industry executives with more than 30 years of experience in the sector.

RT Medical Systems developed a technology to solve the lack of access to information and the complex workflow in the medical sector by integrating radiotherapy services and making the technology more accessible to doctors and their patients.

Software with modern development practices (web-based) - the pioneer in the sector; The technology has already been supported by Brazilian development agencies, as the Florianópolis Municipal Innovation Fund (USD 20,8K) and SEBRAETEC (USD 19K); The software is already being used in large cancer treatment centers.

To boost the development of projects such as these, it is important to generate opportunities for visibility and connections between the different players in the ecosystem. The cooperation between large companies, startups, investors, and public institutions, accelerates the generation of innovative solutions and, therefore, offers a great positive impact on society. Through partnerships, it is possible to combine skills, share resources and risks to explore new opportunities, and offer products with superior and diversified quality.

In a pandemic context, the importance of these connections has become even more evident for the health and innovation sector, reducing time, costs and optimizing results.

As an example, we can mention the collaborations between research institutes and companies, as well as between the pharma-

ceutical industry and startups for the rapid development of vaccines and other products and services in light of the World’s needs.

Globally, health startups move around USD 9 trillion per year and, according to Globo Economia, there is an expectation that Brazil’s investments in 2021 will quadruple in relation to last year, reaching USD 400 million. Considering the population’s life expectancy, Brazilian expenses in health, the development of new technologies, trends, and demands in the health market, some great challenges and opportunities can be explored by startups. New treatments, diagnostics, equipment, digital technologies, and services focused on health and well-being may continue to grow exponentially, with the maintenance of a heated market, strengthened by an increasingly synergistic and connected ecosystem.●

RT Medical Systems

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Development of a new molecule for a type of breast cancer that still has no specific treatment; Founded after 15 years of research; Obtained results proving the molecules’ anti-tumor action; Has as partners Kaivo Biotech and FCJ Venture Builder.

STRATEGIC AREA

The Role of Clinical Research in the Economy ABRACRO (Brazilian Association of Representative Organizations of Clinical Research)

C

linical Research is a strategic area for the autonomy of a country. Within the pharmaceutical research and development process, clinical research is the stage in which the science developed on laboratory benches and validated with in vitro and in vivo models, involving animals, starts to be analyzed in humans to verify their safety and efficacy. Therefore, it is the final link between the development and arrival of pharmaceutical innovations to society.

It is essential for a country to involve its population in clinical studies. Ethnic aspects are preponderant to understand the pharmacokinetics and pharmacodynamics of a drug or vaccine. The approval of health records based only on foreign data, means leaving the local population aside from participating in clinical studies. It is also noteworthy the importance of clinical research in increasing access to health and improving the standard of treatment offered.

From the health professionals’ point of view, the clinical stage provides the opportunity to interact with the new technology and to learn how to use it, leveraging high-quality and innovative scientific production. All in all, ultimately, it strengthens the country through the improvement of its health system.

Other aspects are also highly relevant for encouraging clinical research in a country, of which we highlight the “Economics”. Clinical studies attract investments and encourage the generation of many jobs. However, for this to happen, the country needs to have predictability in ethical, regulatory, and legal assessments, in addition to a well-established network of clinical research centers, trained health professionals and great universities for these professionals to complete their training and specialization.

Furthermore, it is important to have a fully operating chain, involving pharmaceutical companies, clinical operations service providers, specialized customs clearance, and infrastructure for logistics, transportation, and importation, among others.

Market issues are well established in Brazil. Companies have been managing their staff for years according to market movements, and there is a growth potential. The great barriers to clinical research advancement in Brazil are the long deadlines for the ethical-regulatory analysis, the lack of predictability in the processes, and the absence of alignment with international rules.

To overcome these barriers, the Bill of Law 7082/2017, which establishes guidelines for clinical research in human beings and insti-

tutes the National System of Ethics in Clinical Research in Human Beings, is in discussion in the National Congress. The bill of law is in line with the expectations of patients and health professionals working in the sector. When approved, under the proposed terms, the country will be able to enjoy the benefits of occupying a leading position in clinical research. For example, the bill of law has the potential to stimulate Brazilian participation in clinical studies, jumping from 2.1% to 4.8% of the studies conducted in the world. This would increase direct investments by approximately USD 383 million per year, involve more than 48,000 scientific professionals, and, most importantly, increase the number of benefited patients to 55,000. Everybody wins with the approval of such legislation.

Therefore, the convergence of actions between the Regulated Sector, the Legislative Branch and the Executive Branch, materialized in the approval of the Bill of Law 7082/2017, will lead to jobs generation, investments attraction to Brazil, scientific and technological development, and will also put the country in a deserved protagonism position in the global scenario, without prejudice to the participants of clinical studies.

There is no reason to wait. ●

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BIOTECHNOLOGY

Health Biotech Innovation in Brazil: the need for stronger support to bring them from bench to market José Correia, President at Formil Química / Chairman of the Board at Abiquifi

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he entire world is going through a terrible pandemic for which the only rational solution is mass vaccination of the entire world population. No citizen will be out of danger before everyone is immunized and the serious problems of public and private hospital care can be solved and return to normality. With this in mind, scientists from all over the world, grouped in Universities, independent Research Centers and companies, have made an extraordinary effort to seek the solution in biotechnology, achieving great success.

With support from the main Regulatory Agencies in the world and focusing on a quick solution to the problem – the body’s defense against viral infection – the effort was fruitful and several countries are watching the reduction of the effects of COVID-19.

In Brazil, the pandemic has shown that our Universities are able to support the development

of vaccines with sophisticated technologies, but the difficulty lies in the development after the laboratory bench. We have an academic background and equipped public laboratories, but we do not have the absolutely necessary business/ productive chain, which was decisive in other countries that achieved the capacity to mass-produce vaccines through different platforms.

Brazil is one of the greatest vaccine producers for the veterinary sector (the 2nd largest producer), being able to supply our entire market with vertical and sophisticated platforms entirely available in private companies with foreign and national capital. For this reason, we can say that the Country has to work urgently to obtain productive capacity installed in the private sector also for vaccines for human use.

This movement, which is only possible with the support of the State - as occurred in other countries that were successful with the develop-

ment of the COVID-19 vaccine - still needs to be implemented in Brazil with the deep engagement of companies, academia and Government.

Without this engagement, it will not be possible to have great results in an activity that involves significant technological risks and that requires large investments in productive capacity and sanitary regulation.

We have the academic capacity, as well as good research centers that are already operating. However, we lack the institutional engagement of the State and of private companies, so that the products originated in research laboratories can be made available to citizens.

Brazil has the conditions for development, critical mass, health regulation, investment capacity, and several companies with the potential to work in the area of vaccine biotechnology. Nonetheless, we need to gather our internal strengths to obtain concrete results in the production of these immunobiologicals. ●

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REGULATORY AGENCIES

COVID-19 and the Legacy of Transformations in Regulatory Agency Processes Synova Health

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he consequences brought on by the worldwide COVID-19 pandemic have already left and will continue to leave many marks. This scenario has made it possible to review and speed up the processes of regulatory agencies such as the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Brazilian Health Regulatory Agency (Anvisa). We understand that companies involved in clinical research will enter a new phase with the regulatory agencies from now on.

For the first time in Anvisa’s history, here in Brazil, a guide of rules for emergency grants was made. In addition, several Collegiate Board Resolutions (RDC’s) have been approved during the last few months.

To cite an example, we had the approval of RDC N⁰ 475/2021, which establishes the procedures and requirements for submitting a request for temporary authorization for emergency use of drugs and vaccines for COVID-19, on an experimental basis, to address the

public health emergency of the new coronavirus (SARS-CoV-2).

Brazil has the seventh-largest pharmaceutical market in the world, the ninth-largest economy (based on data from the International Monetary Fund - IMF), and the most extensive public health system in the globe. There are more than 212 million inhabitants (according to the Brazilian Institute of Geography and Statistics - IBGE), with a diverse population. This allows its clinical trials companies to have a broad and diverse range of participants for clinical research. In addition, the Country has excellent centers for studies and a qualified workforce.

The pandemic has made it possible to question and search for strategies that will make Brazil even more competitive. Thus, it is essential to have the companies closer to the regulatory agency to discuss robust solutions in shorter and more attractive times.

For successful studies, it is crucial to have partners that can assertively assist you in the interface with the regulatory agency and with keen expertise on the subject and the location where the study will be conducted.

That said, Synova Health can be your ideal partner in future endeavors!

We will guide you through the pharmaceutical and clinical trial landscape in Brazil. We offer endto-end solutions with all the necessary support, or, if you are looking for more specific assistance, we have customized solutions. Our experienced and sharp team can help you with Clinical Monitoring, Regulatory Affairs, Medical Writing, Project Management and Data Analysis. ●

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INDUSTRY

Challenges and Strategies for Improving the Health Industrial Complex in Brazil The Science, Technology, Innovation and Strategic Ingredients Secretariat / Brazilian Ministry of Health (SCTIE/MS)

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he chemical and biotechnology-based industry makes up a production system that stands out in the Health Industrial Complex. Brazil has the peculiarity of having in its national territory private and public companies in the pharmaceutical segment. The Country is the main market in Latin America and, despite producing more than 70% of the medicines consumed internally, it imports between 85% and 90% of the Active Pharmaceutical Ingredients (API), with China and India accounting for 74 % of this total.

The dominance in the supply of API by multinational companies in the Brazilian market, which prioritizes this item over the final product, makes this near-monopoly of the drug manufacturing technology provide greater profits to these companies, as the API represents 70% to 80% of the final drug price.

Given this dependence, its impact on the entire pharmaceutical chain and the medicine supply to

our population, the constant development of tools and actions that guarantee the desired independence by the Country is recognized as a priority. The development of this sector of the Health Industrial Complex could put Brazil in a position to help other countries.

Furthermore, it is necessary to produce ingredients that are strategic or critical for the Country, thus acquiring the productive and technological capacity in order to respond to moments of severe constraint that may pose a risk to the Brazilian population.

Therefore, the challenge is to improve policies, both in the area of innovation, health regulation, and training of human resources. In this regard, the Brazilian Ministry of Health has been working on the review of policies and legal instruments that deal with strategic products in Brazil, which is the recommended path for the issue of producing national APIs, that can be incorporated by Technology Transfers and Technological Orders, planned

to meet the needs of the Brazilian Unified Health System (SUS).

It is understood that the situation of technological and productive dependence tends to worsen with the forecast increase in the consumption of medicines in Brazil in the coming years, thus demanding that public policies be constantly improved concerning the Health Industrial Complex.

Besides, it is indispensable that Brazil innovates more and more through constant investments in R&D and, consequently, in the national production of pharmaceutical ingredients, to obtain a competitive advantage over the other countries.

Thus, considering the advances in the pharmaceutical area, it is essential to continue to strengthen the national pharmochemical industry, through well-articulated public policies and incentives for innovation, enabling the vertical integration of the pharmaceutical production chain and reducing external dependence on active pharmaceutical ingredients. ●

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