A review of the evolution of the transdermal market in the voice of Dr. Francisco Stefano, our director. Challenges of science and passion as protagonists.
Dr. Francisco Stefano is one of the fundamental pieces of Amarin and has been part of the first transdermal developments in Argentina and Latin America. In an exclusive interview he talks to us about the beginnings of transdermal development in the region, the foundation of Amarin and shares his vision about the present and the future of this pharmaceutical form.
An invaluable testimony where, besides sharing his vast experience in the transdermal sector, he opens the doors of his enriching personal story.
We would like to introduce Dr. Francisco Stefano. He graduated as a Physician from the University of Buenos Aires, received a fellowship from Prof. Bernardo Houssay at the Institute of Experimental Biology and completed his training in Pharmacology at the National Institutes of Health (NIH), in Bethesda, Maryland (USA) under the direction of Bernard Brodie.
Upon returning to Argentina, he joined the nascent Instituto de Investigaciones Farmacológicas (ININFA), founded by the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) with the aim of modernizing and promoting the development of pharmacological sciences in Argentina. He directed this Institute from 1975 to 1986.
ININFA played an important role in the modernization of pharmacology in the country. His scientific achievements include the discovery of presynaptic receptors. This research was qualified by the British Pharmacological Journal, one of the most recognized pharmacology publications, as “one of the fifty most important papers they have ever published”.
In 1986 he left basic research to work in industry, joining a national laboratory where he set up an R&D sector initially dedicated to pharmacokinetic studies, which gradually evolved towards the development of formulations that facilitated absorption with low oral bioavailability. These studies were the basis for the development of transdermal products.
He is currently the Director of Amarin. He is also Professor Emeritus at the Department of Pharmacology of the School of Medicine of the University of Buenos Aires and teaches at several private universities. In his career he has published more than 100 scientific papers in international journals and holds several patents in the transdermal area.
Such a prolific career was not by luck. It was the result of tireless work and a series of life lessons such as, for example:
“One has to do scientific work and forget about pride.
That the truth is not always what one believes in,
but the one finds and the result of every
experiment is the only truth that exists”.
Dr. Francisco Stefano
As we told you in the introduction, since the mid-eighties he has been dedicated to the transdermal sector. When we asked him about his beginnings in research in this area, he commented: “In 1986, I was working at the School of Pharmacy and CONICET and I decided to change activities. I went from teaching and basic research to working in the pharmaceutical industry”. Thus, he joined as Director of the Research and Development Department of Laboratorios Beta S.A. where he started working on projects related to the optimization of the absorption of orally administered drugs.
He remembers that, at the end of 1986, the management of Laboratorios Beta invited him to work on a novel system: “While I was doing these studies, a very innovative technique appeared: the administration of drugs with systemic effects through the skin. What we call transdermal systems.”
Up to that time there were only two or three transdermals for motion sickness and menopause, which had been developed by a Uruguayan chemist in California. Dr. Stefano relates how the first transdermal experiments he participated in went: “I put together a small group of collaborators, two of whom came from the research laboratory where I had been developing my activities. So we started to work, in a very precarious way, and to learn what a transdermal system is, something completely new”.
All that effort and the constant desire to generate new products aimed at improving people’s lives did not take long to bear fruit: “We were lucky or had the opportunity and managed to develop the first transdermal that lasted 7 days after its application. It was for the treatment of menopause”.
The product was launched in Argentina and American Home Laboratories bought the license for all Latin America. The expansion process had begun and Dr. Stefano recalls how the production was: “We worked in a small factory in Lanús, where the product was manufactured and began to be exported to all Latin America”.
The excellent performance of the team began to attract attention. So it was that shortly after a Congress in Nice (France), Stefano was interviewed by the owner of a foreign laboratory who was interested in the work being developed by Beta S.A. Referring to this stage, Stefano says: “Then, he began negotiations with Beta and bought the know-how for the manufacture of the transdermal. He made a permanent lease, I think for ten years, of the floor where the people who made transdermals, including me, worked. Then we started working for an English company called Ethical”.
In 2001, with the collapse of the Argentine economy, the English company decided to leave the country. Then, the Doctor together with two other employees of the Argentinean branch, Sergio Lucero and Roberto Gabach, bought the shares of the company and thus Amarin Argentina was born.
It has been 20 years since Amarin was born. When Stefano was asked about the evolution of the company in these decades, he said: “Amarin still has the initial core, as three of the current managers joined Beta in the last century, as we can say. It was an apprenticeship and the pharmaceutical industry has changed a lot over the years”.
And when he talks about learning, the Doctor refers to several aspects: “What the current managers did is to study, to always be aware of and learn where the industry was going. The new regulations. The greater care that exists today compared to twenty years ago in terms of substances that can enter the process by accident. How it is quality-assured work.”
It is important to emphasize that the senior technical staff did not take special courses but were trained through experience inside and outside the laboratory. In this aspect he emphasizes: “Every time we had an interview or when we went abroad to a congress or to discuss a product we listened a lot to the opinions of the partners and the technical-scientific staff of the laboratories. We were sponges.”
“Up to 2015, 70 percent of the company’s work
was focused on developing and selling the idea,
the patent or license of the products it created.”
Dr. Francisco Stefano
Nowadays, not only is it developing, but more and more of these drugs are being manufactured. In this sense, the Doctor adds: “We have a production unit that can be admitted by foreign regulatory authorities. We have never had a problem.
Therefore, when asked about Amarin’s main values, he remarks: “It is a company that is reliable and that always makes every possible effort to obtain a result”.
When asked about how he sees transdermal technology at present, Stefano stresses that it is in a mature stage and is ready for a second phase of growth.
But what are the new technologies that he believes will generate the leap to this second phase? According to his interpretation, this could happen thanks to the development of nanostructures. In this respect, he adds: “Today there are many drugs that have large molecules that, due to their size, have difficulty in crossing the peel-type barriers that are the basis of transdermal administration. (…) Therefore, if one can make these molecules permeate the skin, it is likely that the transdermal systems of the 21st century can be generated”.
We also asked him about two technologies that are becoming more and more widespread, although they are still in the development stage: microneedles and 3D printing.
Regarding microneedles, he considers that “they will work well in some specific cases and they will find a partner, I mean, the drug to micro-cross the skin and make it easier to enter the skin. Again,” he clarifies, “I do not see that there will be 4, 5 or 6 microneedle products”.
On the other hand, he warns that although he has not delved into 3D printing , but anyway he shares his opinion on the subject : “I do not see it for a serial system, due to its low production, and I do not see it for someone to have it at home to make a microneedle every few days”.
This valuable testimony gives us not only an overview of the evolution of the transdermal system, but also helps us to see the importance of the humanization of science in the results. A value that the Doctor has undoubtedly managed to imprint on the spirit of Amarin which, as he says, combines reliability and tireless persistence to achieve the result that our business partners are looking for.
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