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Medication innovation

Brazilian pharmaceutical laboratory Biolab invests in the development of new molecules and medicines

EDUARDO CESAR Equipment used by Biolab scientists to produce new drugsEDUARDO CESAR

One of the 10 largest pharmaceutical companies in Brazil, Biolab this year celebrated its 20th year of operations. The São Paulo–based company’s portfolio is composed of more than 100 products, of which 50% are based on innovative compositions, molecules, or pharmaceutical forms. Two such examples are its Photoprot sunscreen, made with nanocapsules and offering an SPF factor of 100, and its Vonau Flash nausea medicine, a pioneer in the use of immediate oral dissolution technology, taking effect in the body faster. Launched in 2009, Photoprot was created together with scientists from the Federal University of Rio Grande do Sul (UFRGS), while Vonau Flash, which was released on the market in 2005, was developed in partnership with the School of Pharmaceutical Sciences of the University of São Paulo (USP).

“We have always believed that the future of the pharmaceutical industry lies in innovation, not in copying medicines, as is the case with generic drugs. For years, Biolab has been working on the synthesis of molecules capable of leading to new medicines. We are currently testing 60 molecules,” says Biolab science director Dante Alario Junior. To support its innovation program, Biolab invests between 7% and 10% of its revenue into R&D. In 2016, the company’s turnover was R$1.25 billion, and this year it is projecting a growth of 12%. The company is a leading seller of prescription drugs in the cardiology and dermatology market, and plays a major role in the endocrinology, geriatrics, gynecology, orthopedics, pediatrics, and rheumatology sectors.

R&D Centers
São Paulo, Itapecerica da Serra (São Paulo state), and Toronto (Canada)
Nº de pesquisadores
Main Product

The company hopes to launch two more innovative drugs by the end of 2018: antifungal medicine Zilt, the molecule for which was modeled and synthesized in Biolab’s laboratories, and topical nano-anesthetic Nanorap, one of the first of its kind in the world (see Pesquisa FAPESP, issue No. 238). Both are in the final stage of registration with the Brazilian Health Regulatory Agency (ANVISA). Recommended for the treatment of fungal infections, Zilt’s active ingredient is an innovative molecule called dapaconazole. “Zilt is based on a known chemical nucleus called imidazole, which has been modified by our scientists, making it more potent and broadening its action spectrum,” explains Alario. The drug thus acts on a greater number of microorganisms than existing antifungals on the market.

According to physician Gilberto De Nucci, a specialist in pharmacology, professor at USP’s Institute of Biomedical Sciences (ICB), and owner of Galeno Clinical Research, dapaconazole is a me-too drug, a term used by the pharmaceutical industry to describe drugs based on known molecules whose chemical structures have been modified. “Me-too drugs are new chemical entities, truly innovative, but they do not represent a paradigm shift,” says De Nucci, hired by Biolab to conduct preclinical and clinical tests on Zilt.

EDUARDO CESAR Research laboratory with scale model of a molecule developed by the company in the foregroundEDUARDO CESAR

Nanorap is a local anesthetic cream designed for patients undergoing minor skin operations, such as laser treatments and mole removal. It is an incremental innovation, as it results from the modification of two known active ingredients: lidocaine and prilocaine. “The novel aspect of the product is its nano-encapsulation, which ensures better absorption by the skin,” says De Nucci, who was also responsible for the clinical studies of this drug. Nanorap takes effect within 10 minutes, one sixth of the time of conventional non-injectable anesthetics.

Innovation in the pharmaceutical industry can be classified as radical, when it results from a new molecule not yet registered anywhere in the world, or incremental, when it results from improvements to a known molecule. According to chemist Jorge Lima de Magalhães, a researcher at the Technological Innovation Center of the Oswaldo Cruz Foundation’s Institute of Drug Technology (Farmanguinhos) in Rio de Janeiro, medicines like those developed by Biolab are important to Brazil.

“While innovations made by the national pharmaceutical industry in Brazil are usually incremental, they are still important. Some of these new drugs offer improvements that increase patient compliance and make treatment more effective,” says Magalhães. “Making a totally new molecule is something extremely complex, even for the big pharmaceutical multinationals, so imagine how much of a challenge it is for a Brazilian laboratory.”

R&D centers
Over the course of its history, Biolab has filed 263 patent applications with the Brazilian Institute of Industrial Property (INPI)—an average of one patent per month—of which 53 were granted. Pharmaceutical innovations are developed at two research centers. Molecule synthesis is conducted at Sintefina, a Biolab affiliate operating at the Center for Innovation, Entrepreneurship, and Technology (CIETEC), in Cidade Universitária, São Paulo. Sintefina is in the process of being incorporated and will become a Biolab laboratory by the end of the year. The team is composed of six chemists, all with doctorates, and all specialists in molecule synthesis.

One of the molecules tested by Sintefina has shown promise in the treatment of hypertension. “We already have a patent for this molecule. In tests on rodents, it was effective in lowering blood pressure. We are now conducting further tests to find out how long the effects of the drug last on the animal,” says Biolab’s science director. The molecule’s mechanism of action is not yet known. “We plan on agreeing a partnership with a university to study how it works, because this involves basic research.”

EDUARDO CESAR The research team at Sintefina, a Biolab affiliate, is responsible for synthesizing molecules capable of producing new drugsEDUARDO CESAR

In addition to synthesizing molecules, the Sintefina team will soon begin conducting tests to prove their effectiveness. “At the moment, we send our molecules to laboratories in the United States or France to prove their validity. In a few months, we will begin conducting these tests here in Brazil, with the same level of safety, effectiveness, and reliability. We have purchased the equipment and kits needed to conduct the tests, and hired a researcher who is finishing a doctorate to take charge of this area,” says Alario.

The pharmaceutical company has a second R&D center in Itapecerica da Serra, a town 38 kilometers from São Paulo, where roughly 100 researchers work. This center is primarily focused on incremental innovations, such as controlled drug release mechanisms, oral dissolution systems, and new formulations and encapsulations, like nanotechnology. Around 100 new projects are under development in Itapecerica, including the creation of thin films to treat thrush.

BIOLAB The R&D center in Itapecerica da Serra (above) conducts incremental drug researchBIOLAB

To strengthen its R&D structure, Biolab is this month opening a third innovation center, outside Brazil. The new research center will operate in the MArS Discovery District, a pharmaceutical and health research hub in Mississauga, a city near Toronto, Canada’s largest metropolis. At 1,000 square meters, the facility will have a staff of 15 researchers and according to Alario, is part of Biolab’s internationalization strategy. The laboratory cost US$50 million, and its first mission will be to adapt the Zilt and Nanorap documentation to the Canadian, US, and European markets. “We are going to produce dossiers for the regulatory authorities in these countries. If we want to enter developed markets, we have to offer innovative drugs, like Zilt and Nanorap,” says the company’s science director.

The Canadian center will also support the research conducted in Brazil. “Today, when we import reagents to use in new molecule research, we have to wait up to six months for the product to arrive. In Canada, this process takes just a week. This way, part of the development of new molecules or incremental drugs can be carried out there,” explains Alario.

BIOLAB A researcher uses a microscope to analyze a medicine under development at the laboratoryBIOLAB

New factory
The laboratory has three industrial units located in the São Paulo municipalities of Jandira, Taboão da Serra, and Amparo—the latter also produces functional foods and veterinary products. In July this year, Biolab announced the construction of a new plant in Pouso Alegre, Minas Gerais, with an estimated investment of R$450 million. Of this total, about 40% is covered by the company’s own resources, and the rest must be obtained from the Brazilian Development Bank (BNDES) and other sources.

Scheduled to begin operations in 3–4 years, the factory is designed to supply the foreign market as well as Brazil—all its facilities will be constructed according to the requirements of the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The plant will have a manufacturing capacity of 200 million medicine units per year, more than doubling Biolab’s production potential.