Gabriel BitarArtistic representation of size difference between nanoparticles, in pink, and a strand of hairGabriel Bitar
Nanocapsules are the new technological strategy deployed by the Brazilian pharmaceutical company, Biolab. The São Paulo-based laboratory will introduce its innovation through two new products now under development, namely an anesthetic cream and a topical solution for alopecia, primarily for treating baldness, but also to a lesser degree lack of body hair. The novelty consists of nanocapsules made from a type of biodegradable plastic polymer that slowly releases its active ingredients into the body, making for a longer period of treatment and mitigating any side effects. The two pharmaceuticals, a result of a decade-long partnership between Biolab and the Federal University of Rio Grande do Sul (UFRGS), are currently undergoing clinical trials and are expected to be ready for use by the end of 2013, after obtaining approval from the National Health Monitoring Agency (ANVISA).
According to Marcio Falci, director of research, development and innovation at Biolab, the idea for developing the two new products sprang from the company’s knowledge management area. The division maintains a database that houses all of Biolab’s knowledge, not to mention everything that the entire world is doing and researching in the company’s field of operations. “This enables us to establish trends and study the technological advances that are related to our products and research, according to the company’s strategic interests,” he explains. “We also map the research institutions, universities and researchers, which greatly helps our technological forecasting for future products.”
One such analysis concluded that the market for anesthetics and hair loss remedies had ample room to grow. “In terms of offering safer and more efficient treatments to meet the medical needs that we identified, we saw that we could innovate by applying nanotechnology to the active ingredients of already existing products,” Falci explains. “Nanoencapsulation was chosen because it was already a part of our production toolkit.”
For its new anesthetic, Biolab will use the active ingredients prilocaine and lidocaine; for its baldness treatment, finasteride. All three are well known by the medical community and extensively used in currently available medications. To infuse its new products with nanotechnology, the company turned to its old partnership with UFRGS, which had already yielded positive results in the creation of other nanotechnological products, including cosmetics and sunscreens (see Pesquisa FAPESP nº 167). Two research groups are working together at the university, each led by a pharmacist: Adriana Pohlmann from the Chemistry Institute and Professor Sílvia Guterres from the School of Pharmacy, both at UFRGS.
The university initiated its collaboration with Biolab for nanoencapsulation projects in 2005, in response to a tender issued in 2004 by the National Council for Scientific and Technological Development (CNPq). “We received financial support from the Ministry of Science, Technology and Innovation through CNPq,” Pohlmann says. “The company also contributed an amount, and then we started the project. It was completed in 2007, when we filed for a patent with the Brazilian Industrial Property Institute (INPI).” From that point on, Biolab went on to develop the products by completing human clinical trials and making the necessary plans for large-scale production.
Ana Paula CamposUFRGS developed the technology to nanoencapsulate the active ingredients that Biolab uses in its anesthetic and hair loss products. The nanocapsules are spherical, with an average diameter of 200 nanometers (one nanometer is one millionth of a millimeter). For comparison, a strand of hair is about 50,000 nanometers thick. In the specific case of Biolab’s two pharmaceuticals, the drugs will be applied topically in the form of a suspension, cream, or gel. “Because the nanocapsules are so small, they act only on the particular layer of skin in which the desired therapeutic effect is to be produced, in this case the dermis, without the active ingredients entering the bloodstream and triggering any side effects,” Falci explains. “In contact with the skin, they can rupture or the polymer coating can erode, gradually releasing the active substances on the targeted region of the dermis.”
Nanodrugs like the two developed by Biolab are part of a broader category, a veritable technological revolution called nanotechnology. This is materials engineering at an atomic or molecular scale, and it is starting to have an impact on a wide variety of industry segments, in agriculture and biology, not to mention medicine and pharmacology. Some of these nanoproducts are already available on the market. They include self-cleaning glasses and ceramics, stain-resistant fabrics, pharmaceuticals that sail unscathed through the bloodstream until they reach the diseased organ, and electronic tongues that can distinguish different flavors better than any human. According to Panorama da Nanotecnologia no Mundo e no Brasil (Panorama of Nanotechnology in the World and in Brazil), a study released in 2010 by the Brazilian Agency for Industrial Development (ABDI), nanotechnology was an industry no larger than US$13 billion worldwide in 2004, representing less than 0.1% of all manufactured goods produced that year. Three years later, the market had expanded tenfold, to US$135 billion (including semiconductors and electronic equipment). Forecasts have that figure hitting the US$1 trillion mark by the end of 2013, and US$2.95 trillion by 2015, or more than 15% of all industrialized products manufactured on the planet. At present, the chemical sector makes up the lion’s share of that market with 53%, followed by semiconductors, with 34%.
Approval time
When it comes to healthcare, nanotechnology is used in the manufacture of medical, veterinary, and diagnostic imaging products, but its heaviest user is the cosmetics industry. In that area, Biolab already markets its Photoprot line of sunscreens, also developed in partnership with UFRGS. The company has also launched an oil control skincare line named Skan, which includes a cleansing mousse and a gel-cream for oily skin. For cosmetics, the time span between the start of a product’s development and its arrival on drugstore shelves is shorter because the laws for approving cosmetic products are less stringent than for new pharmaceuticals.
Biolab intends to try to change that situation, making it quicker to get new drugs approved for sale. “We will petition the government to create a priority queue at the ANVISA for pharmaceuticals that contain an innovation,” says Biolab’s scientific director, Dante Alario Junior. “The present administration’s science policy encourages innovation, so we believe that our request is a sensible one. Today, it can take a year and a half to two years for the ANVISA to analyze and approve a new drug. That time frame should be shortened for innovative products. With things the way they are now, there’s a risk that an innovation will be outdated by the time the drug is approved for sale.”
Biolab predicts that its nanoanesthetic can bring in an estimated R$30 million per year. The sales outlook for the baldness remedy is even better: R$95 million. “These products grew less than the pharmaceutical market in general, which expanded 59% in total units sold and 89.65% in gross revenues over the past five years,” Falci says. “By comparison, the market for anesthetics grew 54% in sales over the same period and 77% in gross revenues, and the market for alopecia treatments advanced 48% and 46.7%, respectively.”
The company does not disclose the amount invested in the two new products. “We actually don’t know, as we don’t separate our expenses on a per project basis,” Alario Junior says. “Our investment in research, development and innovation is between 7% and 8% of our annual revenues, which are expected to be R$780 million in 2012.” In order to catch up, the company hired a consultant to analyze its investments in each project and determine how Biolab can make the most of Brazil’s Innovation Law — better known as the “Lei do Bem”, a set of tax incentives for R&D to boost innovation.
Group innovation
Brazilian pharmaceutical companies join forces to create new medications
Léo RamosTwo new companies were created for the main purpose of producing complex biotechnological medicinesLéo Ramos
The Brazilian pharmaceutical industry has entered a new phase. In recent years, the country’s laboratories invested heavily in generic drugs, which helped them drive up revenues and gain a stronger foothold in the market. Now, they want to transform Brazil into an innovation hub, focusing on advanced synthetic drugs, phytotherapeutic products, and — most importantly — biotechnological medicines. The path they have chosen to accomplish that goal is to work together. Hence, in 2012, they created two large corporations, Orygen and Bionovis, with the goal of conducting research and developing new pharmaceuticals. Each company consists of four Brazilian laboratories.
The two companies were created with financing from the Brazilian Bank for Economic and Social Development (BNDES), which began conducting studies and attempting to define paths for the country’s pharmaceutical industry in 2003. In 2004, the bank launched its Development Support Program for the Pharmaceutical Production Chain (Profarma), designed to reduce the trade deficit in Brazil’s pharmaceutical production chain and stimulate local research, development and innovation initiatives. In 2010, the bank set a plan in motion to amalgamate nine different laboratories into one massive company. During the discussion process, the group split in two, giving rise to Orygen and Bionovis.
Bionovis was created first, in March 2012, as a joint venture by Aché, EMS, União Química, and Hypermarcas. With a total capital of R$500 million – each partner contributed 25% – the company will research, develop and market biotechnological medicines. “In 2013, we will build a research and development laboratory and a pharmaceutical production facility,” says the president of the new company, Odnir Finotti. “During this initial stage, we are establishing partnerships with two international companies that will provide us with the technology to produce two monoclonal antibodies, one for immune system diseases and another for cancer.”
Orygen was created in May, also starting out with R$500 million, with Biolab, Cristália, Eurofarma, and Libbs as partners. To run the company, the foursome went to New York to seek out the British scientist Andrew Simpson, former scientific director of the Ludwig Institute, who was not only familiar with working in Brazil, but had also been the general coordinator of the Xylella fastidiosa and cancer genome projects initiated in the late 1990s and funded by FAPESP (see Pesquisa FAPESP 50th anniversary issue). “The new company would like to establish the capacity to produce therapeutic monoclonal antibodies on an industrial scale in Brazil, in order to provide easier access to these products here. It also wants to develop new therapeutic molecules by running an active RD&I center,” Simpson affirms. “The founding of Orygen and Bionovis creates a more complete pharmaceutical industry group, making it possible to produce and market complex medications.”
In the institutional scenario, these eight companies plus Hebron joined forces to create the Grupo FarmaBrasil (GFB) association, whose mission is to strengthen Brazil’s pharmaceutical industry. Collectively, these nine companies account for 36% of the total volume of pharmaceuticals produced in Brazil and 53% of generic medications. They also employ roughly 30,000 people and invest an average of 6% of their revenues in research and development. According to the entity’s chairman, Reginaldo Arcuri, the association was created to pursue a strategic agenda that has been under discussion since 2010. It includes the implementation of an industrial policy for the sector, designed to enhance the innovation capability of Brazilian laboratories and the country’s total pharmaceutical production. “The market share held by domestic companies in the pharmaceutical market went from 4.7% in 1998 to 20.86% in 2011, a growth of more than 400%,” he says. “This means that the domestic industry is able to respond not only to challenges, but also to the opportunities created by Brazil’s public healthcare policies.”
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