19 November 2009

Is it possible to resurrect the Russian pharmaceutical industry? Part 2

Bitter pill-2
How does pharmaceutical science, which is still preserved in Russia, live and what hopes does it haveAlexander Emelianenkov, Rossiyskaya Gazeta, 18.11.2009.

"A bitter pill" – under this heading in the "RG" on November 17, an attempt was made to understand: how and why did imported medicines flood Russia and in what condition was the domestic pharmaceutical industry? Today we continue the conversation on a topical topic.

...Academician Seredenin hesitated. The call from Rossiyskaya Gazeta didn't exactly puzzle him, but it clearly didn't inspire him. Well, what is it again to shake the air, if it has already been said so many times, stated on paper, but there are no necessary decisions or are they taken only for visibility?!

– So do you agree with the statement that over the past 17 years, not a single new original pharmaceutical product of Russian production has been brought to the market?

– Do not repeat this nonsense after others, – I heard in response. – And if there is such a question – come and talk.

Who supports whomSergey Borisovich Seredenin has been the head of the V.V. Zakusov Research Institute of Pharmacology and the profile Scientific Council of the Russian Academy of Medical Sciences for many years.

That's why I was so eager to talk to him. To begin with, I was asked to compare the amount of budget funding that the Seredenin Institute has received in recent years with direct budget revenues from the sale of medicines that have been developed here. Such an analysis, conducted by experts of the independent company RMBC only for eight drugs of the Research Institute of Pharmacology (mexidol, phenazepam, afobazole, picamilon, noopept, etacizine, sodium oxybutyrate, etmosine), showed at least three times the excess of income over expenses.

– Unlike officials who persistently try not to notice us, – says Academician Seredenin, – we not only pay off budget expenses for our institute, but also provide replenishment of the budget. After all, in addition to the taxes that pharmaceutical companies pay, these are new jobs associated with the production and promotion of pharmaceuticals to the market. And the overall contribution to the development of medical science is not empty words...

Now the Research Institute of Pharmacology has about two hundred employees, in Soviet times there were 450. Optimal, according to the director, would be three hundred – there is enough work for everyone. But it has become very difficult to retain young people.

– Literally in front of you, – Sergey Borisovich admitted bitterly, – a very capable guy came with a request for dismissal. He grew up with us, we pinned our hopes on him. But what can you do? I can't set him a salary of more than 20 thousand – our owners get 25. And where he is called, they immediately offer forty – with a subsequent increase to sixty and beyond. How he will show himself. Eight of our best students are now working in America – they left back in the 90s, when there was nothing to support their families. And I don't blame them...

How was it possible to preserve the research team and the institute itself against the background of the general collapse of the Russian pharmaceutical industry? My interlocutor is not prone to pretentious speeches and unaddressed reproaches. He only notices in passing: maybe he just turned out to be a little younger than his fellow directors. Hands were not lowered even in the most crisis years. In 1996, colleagues from the USA donated to them a batch of specially grown experimental animals - the price of one rat reached up to one hundred dollars.

– Oil for them and greens, when the institute's budget was cut to the limit, were bought on the market for their own money, – Academician Seredenin lands our conversation again. – We have saved the opportunity to conduct fundamental research and preclinical tests at home. And this is our advantage over some other institutions. We are able not only to formulate a promising idea, but also to bring it to a visible result in pharmacological work. As a rule, up to the stage of clinical trials and beyond. Up to the registration of the finished drug. Therefore, it is at least incorrect to pretend that we do not exist or that we are hopelessly behind.

Vector of changesIn addition to the academic institute on Baltiyskaya Street in Moscow, there is a similar in name and profile of the work of the Research Institute of Pharmacology of the Siberian Branch of the Russian Academy of Medical Sciences in Tomsk.

He is much younger – in the spring, the 25th anniversary was celebrated at a specially timed scientific conference, and he got his bearings in the market element of the last decade even faster than his metropolitan counterpart. In the list of drugs that Tomichi consider "their own", there are also original developments (some of them are heard every day), and three dozen generics reproduced by order of specific pharmaceutical companies. In 2005, the founder of the Tomsk Research Institute of Pharmacology, Academician of the Russian Academy of Medical Sciences Evgeny Goldberg and its current director Alexander Dygai were awarded the prize of the Government of the Russian Federation in the field of science and technology. And last year, 2008, the team of scientists of the Institute was recognized as the leading scientific school in Russia and received a grant from the president of the country.

There are, of course, institutes in the Russian Academy of Sciences that conduct research in order to create new drugs and medicines. Among the most famous is the Institute of Molecular Genetics of the Russian Academy of Sciences. In cooperation with the biofac of Moscow State University, where the profile department was headed by Academician of the Russian Academy of Medical Sciences Igor Petrovich Ashmarin, a nootropic drug was created and brought to the market here, which helps to adapt to stress. And together with the V.V. Zakusov Research Institute of Pharmacology, they patented a new drug with an original spectrum of psychotropic properties. Academician of the Russian Academy of Sciences Nikolay Fedorovich Myasoedov played a key role in the research and development of these drugs, for which he deservedly received the award of the Government of the Russian Federation.

The Institute of Bioorganic Chemistry has its own unconditional achievements. academicians M.M. Shemyakin and Yu.A. Ovchinnikov. And the branch of this institute created in the Pushchinsky Scientific Center of the Russian Academy of Sciences has a modern base for conducting preclinical tests of biomedical drugs both in vitro (that is, in vitro) and in vivo (on living organisms) in accordance with the international standard GLP (good laboratory practice). The production of laboratory animals (mice, rats, hamsters) of the SPF category (free from pathogenic flora) is also organized here.

The institutes of the Russian Academy of Sciences – and the Pushchina branch is no exception – have a much broader and more fundamental approach to research in comparison with research institutes of medical and purely pharmaceutical profiles. In a strategic sense, this is justified, since the vector has changed before our eyes and the very nature of research in this area continues to change.

The general approach, according to Academician Seredenin, has become "more biological". They are, figuratively speaking, from unresolved issues, trying to close the "holes in pharmaceuticals". This is largely due to socio-demographic trends in developed countries, where life expectancy is increasing, and with it the nature and statistics of diseases are changing. A lot of attention, for example, is now focused around Alzheimer's and Parkinson's diseases. A huge flow of research – what provokes, how the disease develops, how to treat it.

Geneticists, biologists, physiologists are looking for a kind of target in the human body, when exposed to which it is possible to "extinguish" (best of all – in the bud) the disease, and ideally – to prevent it. And even at the stage when the disease is started, such a narrowly focused approach allows you to achieve the best results in the fight against the most complex diseases, including various types of oncology and mental disorders.

And here big science quite justifiably comes to the fore. Those laboratories that have been created and are successfully operating at all major pharmaceutical companies, without the support of fundamental science, would have run out of steam a long time ago. In the West, this is well understood. And that's why fundamental science, like the chicken that lays golden eggs, is cherished and cherished here. They are not extolled in words, as we have, but fully subsidized. The US National Institutes of Health (a kind of analogue of our Academy of Medical Sciences) receives $30 billion from the budget.

– These funds, – emphasizes Academician Seredenin, – not only go to research, but also allow scientists, which is important, to protect their ideas, methods, approaches and found substances with patents. And then, already with their own money, commercial structures that have their own interest are connected...

Indeed, companies from the list of "Big Pharma" are able to allocate up to $ 500 million annually for research and development. The mechanisms and channels of such financing may be different, but they are all, as they say, focused on the result. We do not have such a bridge between fundamental science and even the most advanced innovative business. And no, first of all, because the amount of budget funding for science does not allow us to advance the original findings of the same pharmacologists to the stage when innovative business may be interested in them.

In order not to be unfounded and not to give figures from memory, Sergey Borisovich, in my presence, contacted the financial service of the Russian Academy of Medical Sciences and received the most accurate data on what budget our medical science in general and its biomedical department in particular can count on this year.

– Five and one–tenth of a billion rubles – for basic research, of which about 700 million - for nine institutes of medical and biological profile, – having hung up, the academician summed up. – So compare: $ 30 billion in the US and 5 billion rubles in our country.

The resulting gap between science and the Russian pharmaceutical industry is considered possible at this stage to fill up with two billion dollars, and three quarters of these funds are requested from government sources. And venture funds and the industry itself can only get involved "at the stage of commercialization of previously developed intellectual property."

The trouble is also that even this frankly meager – "tears were dripping" – funding is sprayed all over the field – irrigates the general shoots, but does not give chances to start and mature earlier than competitors, promising developments. This, in fact, is what analysts from the Center for High Technologies "HimRar" rely on in the "Strategy for the development of the pharmaceutical industry of the Russian Federation for the period up to 2020". They will not be denied knowledge of the trends and patterns of this specific market. But you can't discount the Russian specifics with a trail of unresolved problems, not to mention the living people who worked here and continue to work here.

One of the reasons for the current gaping gap between Russian fundamental science and modern pharmaceutical production is the industrial research institutes and research centers that were abandoned at the beginning of the 90s, and then mired in commercial leases or dubiously privatized in a dubious way. As a rule, they were taken into their hands without noise and dust, having secured the support and patronage of the right people in a timely manner. But it also happened in another way - the conflict of interests struck such sparks that the scandal flared up in newspapers, on the television screen, and spread to the Internet.

Scythe on a stoneLate in the evening of December 20, 2006, with the participation of fighters of a private security company, a change of leadership was made, and in fact – the seizure, followed by bankruptcy and corporatization of the oldest scientific and pharmaceutical center in our country - VNIHFI–TsHLS, which is some three kilometers from the Kremlin (at the intersection of Zubovskaya, Leo Tolstoy and Rossolimo streets).

And his permanent head for thirty years, academician of the Russian Academy of Sciences, laureate of the State Prize of the Russian Federation Robert Glushkov was removed from office – with the wording "by the decision of the owner", which was then the Moscow property. The federal officials in charge of this FSUE took a tacit and expectant position.

The conflict around this research and production center has become very indicative both for the pharmaceutical industry and for that time, although to this day it is interpreted ambiguously. One thing can be reliably stated: the property complex of the All-Russian Research Chemical and Pharmaceutical Institute, and since the late 90s - the Center for the Chemistry of Medicines (the total area of buildings is 13,145 square meters) was in federal ownership until the end of 2006, and now belongs to JSC VNIHFI-TsHLS. The current structure and further transformation of its share capital remains a mystery behind seven seals.

As "RG" managed to find out, two years before the redistribution of property happened, it was planned to create a Federal innovative chemical and pharmaceutical company on the basis of this center. According to the plan, it was given broader functions than those of a Soviet-style NGO: not only design, development, preclinical testing and production of medicines, but also their distribution, that is, bringing them to the final consumer.

At the first stage, such a company was supposed to unite nine industry research centers and two or three of the largest chemical and pharmaceutical enterprises at that time. Candidates for joining the "powerful research unit" were also named. These are the All-Russian Scientific Center for the Safety of Biologically Active Substances, the State Scientific Center for Antibiotics, the Sintezbelok Research Institute, the Biotechnika Research Institute, the Vitamins Research Institute. However, even then there were concerns that such integration "on the terms of the owner", and they saw, of course, Academician Glushkov, deprived other directors of structural independence and most of the authority.

However, this was not the real reason for the shift. According to Robert Georgievich himself, to him – and more than once! – we drove up with persuasions to give one of the buildings that belonged to the center. He didn't agree. And for more than two years he has not left attempts to prove in court that his dismissal was illegal.

By this time, the patent protection period for the currently most famous drug developed at VNIHFI under the leadership of Academician Glushkov had expired. Channel One is now so busily advertising it, scaring Russians with SARS and flu, which I won't call it. And in the period from 2001 to 2007, when the patent was in effect, the institute received in the form of royalties only from sales of this immunomodulator up to 10-12 million rubles annually, Svetlana Yakovleva, who worked with Glushkov and was fired after the boss, shared with RG.

– What did this amount mean for the team? – Svetlana Viktorovna seemed even surprised by my question. – Yes, this is several times more than what we received on the budget line.

Yakovleva has not been behind the checkpoint where she once worked for a long time. But he knows from former colleagues that in those squares where they were going to place a new production for the production of ointments, now a barber shop – an advertising sign is still striking from afar. According to Glushkov himself, the first and second floors of the main building have been leased, a parking lot has been organized in the courtyard, and the detached building along Rossolimo Street is entirely at the mercy of tenants.

Vigilant secretaries were not allowed to communicate directly with the current CEO of the center, allegedly referring to the fact that "we are now in the process of moving." It was possible to contact by phone only with his deputy for science Viktor Chistyakov. He, quite understandably, did not want to go into explanations about the lease and everything related to corporatization. And with regard to science, he assured that not everything is as sad as they try to imagine from the outside.

– All the former architecture of the center has been preserved, – Viktor Vladimirovich convinced me. – From exploratory research, chemical synthesis to the stage of clinical trials and registration of finished dosage forms.

Not so long ago, according to Chistyakov, Professor Vladimir Granik and his group returned to them. At one time they went to the Institute of Antibiotics, but now "everything has been safely closed there, and now we have a full–fledged department of medicinal chemistry," my interlocutor concluded not without pleasure.

Tobacco – apart?Competition in pharmacology, as in any scientific field with direct access to high-tech production, has always been, is and will always be.

And this is certainly a powerful incentive for development. But healthy competition against the background of stable and sufficient funding for science is one thing, and departmental and professional disunity of scientists in conditions of a total shortage of funds for new developments is quite another.

Comparisons of this kind inevitably arise, one has only to take a closer look at the activities of the two academic communities. The Russian Academy of Medical Sciences has created 57 scientific councils on complex problems of medicine. There are councils on medical instrumentation and biotechnologies, separately – the interdepartmental council on microbiology, as well as its own scientific councils on virology, antibiotics and vaccinology. The 39th in a row is the Council of Pharmacology. It is headed, as already mentioned, by Academician Seredenin. We had a long and frank conversation with him, but Sergey Borisovich, for reasons that are understandable to me, is recovering from some public assessments today.

There was a time, the late 1990s - early 2000s, when, by his own admission, he actively spoke in the media: gave interviews, wrote to newspapers and magazines himself. I was hoping to reach out. Now the illusions are dispelled. A whole bunch of newspaper clippings and photocopies of his boss's publications were brought from his reception room. And to my question, how can I still gather the capabilities of the Russian pharmaceutical and related sciences into a fist, I took a multi-page document in a burgundy binding out of the closet.

– This is the last of five or six copies of the research program that we have prepared following the results of a joint session of the Russian Academy of Sciences and our Medical Academy. If you remember, it was held in December 2003 and was devoted to just these problems.

– You have prepared a joint program – and what?

– We've been working on it for almost two years. And in 2005, when everything was agreed, they handed it over to the President of the Russian Academy of Sciences, Yuri Osipov, for approval. The president of our academy, Mikhail Davydov, approved the program in early 2006. Here's his signature. The decisions of colleagues from the big academy have not been received so far. And in words, they made it clear that there was no money "for pills"...

Indeed, where would they come from? In recognition of Academician Gennady Month, Vice-President of the Russian Academy of Sciences and Director of the Physical Institute. Lebedeva, 37 percent of the total budget of the Academy falls on the Department of Physical Sciences. For eight other departments, including the Department of Biological Sciences – what's left.

And also to the issue of priorities, concentration of attention and funds in the academic environment. 15 scientific and seven interdepartmental scientific councils on various issues have been created and generate activity under the Presidium of the Russian Academy of Sciences. There are 16 more functional councils and commissions and nine independent committees. In addition, the Russian Academy of Sciences "maintains close ties" with 26 scientific societies and seven associations, and there are seven other associations with which the Russian Academy of Sciences simply "interacts". Among this variety there are 78 structures! – and there is no hint of at least some kind of joint platform with the Russian Academy of Medical Sciences to discuss common tasks and coordinate efforts in the pharmaceutical field.

Is the band too narrow, in the understanding of the "big academy", for its strategic outlook? Or should the Presidium of the Russian Academy of Sciences, which includes several academicians of the Russian Academy of Medical Sciences, be considered such a platform? But even there they cannot remember the last time they delved deeply into the problems of the Russian pharmaceutical industry and the sciences that feed it.

And if so, why should we be surprised and indignant that in some of our research institutes, menees and managers pack pills brought from Turkey from bags into pharmacy packages?

Of the first 36 projects that received financial support from Rusnano, only two are related to the development of new medicines and medical diagnostics. One of them involves the N.F. Gamalei Research Institute of Epidemiology and Microbiology of the Russian Academy of Sciences, the other – the Center for Theoretical Problems of Physico-Chemical Pharmacology of the Russian Academy of Sciences. In the first case (the creation of two nanovaccines against human and avian influenza and three new therapeutic biological products), the project budget is 1,547 million rubles, including 1,300 million from Rusnano funds. They intend to place innovative production in the Moscow and Yaroslavl regions. The second project is aimed at creating promising diagnostic tools for blood diseases (clotting disorders), as well as determining the risk of thrombosis and thromboembolism. The total budget is 1079 million rubles.

In vivo (Latin – literally "in (on) the living") – conducting experiments on (or inside) living tissue in a living organism. Animal testing of new drugs and human clinical trials are forms of in vivo research.
In vitro (lat. "in glass") is a technology for performing experiments when experiments are carried out in a test tube or, more generally, outside a living organism – on certain fragments of living or already dead tissue. Modern in vitro techniques in pharmacology provide the necessary reliability of the results and allow saving the lives of millions of experimental animals.
In silico is a relatively new term for computer modeling (simulation) of an experiment, most often biological. The designation has taken root by analogy with the long-known in vivo and in vitro, although it is only close in spelling to the Latin in silicio, which would mean "in silicon".

Portal "Eternal youth" http://vechnayamolodost.ru19.11.2009

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