Collected bit by bit
How the production of antibiotics was revived in Russia
Irina Khaletskaya, RIA Novosti
In Saransk, the Biochemist plant launched the production of full-cycle antibiotics. The first in the line is "Vancomycin". The start of the process was given by the Minister of Health of Russia Veronika Skvortsova, who specially came to Mordovia. The head of the department was handed the first prototype of "Vancomycin".
Four antibiotics
Last year, the Minister of Health has already visited the enterprise: then an agreement was signed on the establishment of a pharmaceutical research, production and engineering center "Antibiotics" on the basis of the plant.
After the official launch, the company will begin industrial production of four types of drugs. "Vancomycin" – first in line. Thanks to the upgraded infrastructure, the center will fully provide them with the Russian market in six months.
Also this year, the plant will begin production of a full cycle of three more drugs – "Telavancin", "Oritovancin" and "Ramoplanin".
How the "Biochemist" works
Biochemist has been developing and manufacturing drugs since the 1950s, providing medicines to the entire USSR, as well as supplying substances for export. In the 1970s, there was no synthesis of new drugs here, which significantly affected the economic stability of the enterprise. However, in the post-perestroika period, the company was on the verge of bankruptcy.
With the advent of a new owner, the situation has radically changed. Biochemist was the first in the country to establish a unique production of antibiotics: from the producer strain to finished medicines.
To achieve such results in just a year, we had to raise everything from scratch, explained to RIA Novosti the chairman of the Board of Directors of Promomed Management Company, Pyotr Bely.
"When we set the task to make antibiotics, we didn't even think that we would have to create everything all over again. We thought that we would find substances, register new antibiotics, and fill the deficit. It turned out that it was impossible to obtain substances for the latest antibiotics: there is no base left in Russia for this. Then we decided to synthesize them ourselves. I had to assemble a team bit by bit, bring specialists, look for bright minds on the basis of "Biochemist". There were no strains, no technologies. Actually, there was no factory as such. No one believed in success, but we accepted the challenge," recalls Bely.
According to him, the old, but workable giant fermenters already available at the plant were taken as a basis. We have installed modern equipment that allows us to produce products that meet the requirements of the State Pharmacopoeia of the Russian Federation, USP, BP and EP. And then the scientists said their word: they have developed a technology that has no analogues in There is no Russia.
The life of a bacterium
The strains of the antibiotic manufacturer live in a special bank where the desired temperature is maintained. White did not reveal the secret of exactly how the samples were found.
So far, four strains have been developed on the basis of Biochemist. "Vancomycin" – the biggest of them. However, in addition to it, there are also supernova antibiotics – "Telavancin", "Oritovancin" and "Ramoplanin".
First, the strains are transferred to the seed laboratory. There the fungi are sown on a solid nutrient medium. This is the first reproduction, resulting in up to a hundred colonies. The procedure takes place in the light of a flame. The temperature is one thousand degrees – absolute sterility. So far, humanity has not invented anything better.
Laboratory technicians use a microscope to look at the grown colonies and select samples that are suitable for further work, that is, they correspond as much as possible in form and content. "There should be no sticks, yeast," explains one of the laboratory assistants.
According to her, the youngest cells are chosen, with outlines similar to the "sun" – the circle from which the rays come. Eventually, the drug will be created from them. The grown crops are transplanted into a liquid medium and sent to a shaker for a week, where they continue to grow. This is the best phase of bacteria's life: they don't have to do anything, just breathe air and multiply – up to a billion. Then they are transferred through the gateway to a large 15-liter fermenter tank. Here, White jokes, the free life of bacteria ends. The reactor operates on the principle of a pressure cooker: it creates unfavorable conditions that force bacteria to work, defend themselves and show certain qualities.
The technology developed at Biochemistry is unique due to the pipes through which oxygen, alkali, acid and nutrient medium enter the tank. Bely says that this is, in fact, the main circulatory system, which allows you to increase the concentration of the necessary substances.
"Few pharmaceutical companies in the world make Vancomycin. There is a good production in South Korea. They have only seven grams of glycopeptide in one liter of culture fluid, from which "Vancomycin" is made. However, at the plant in Saransk, the indicator is 30% higher – about nine to ten grams. This is important in order to compete in the market," he clarifies.
Through the food pipe, the bacteria are sent to a new fermenter. Each stage of the process is scaled 10 times, so this fermenter is already 150 liters in size. Here the bacterium grows for another day and goes to the main "hall" – it matures for one and a half thousand liters in the reactor for 24 hours.
The final stage is another fermenter for as much as 15 thousand liters (the tank occupies two floors).
"These reactors were built in the 1950s and are still in perfect condition. When the building was in disrepair, the fermenters were tested: it turned out that they are ready to work and are no worse than modern analogues. It's just that a mirror surface is created inside, a new snap is put on, a stainless shirt is put on. By the way, the price of the German equivalent is one and a half million euros," says Deputy Executive Director Vasily Kuptsov.
The entire fermentation process is controlled automatically. For two weeks, while the antibiotic is being prepared, you can watch what is happening on the screens. Moreover, if something goes wrong, employees of the enterprise who have access to fermenters will receive a notification on the phone.
When fermentation ends, the direct preparation of antibiotics begins. Bacteria pass through an industrial filter through the pipeline. The separation process is underway: everything that will be a drug is sent to the next stage, and "non-antibiotics" are collected in containers, heated and sterilized.
Next, the future drug goes through three stages of purification – "micro", "ultra" and "nano" – cutting off the remains of bacteria, large cellular structures, protein, lipids, salts, vitamins and amino acids. It turns out a pure concentrated antibiotic. In the final, he is rejected, receives the conclusion of the technical control department in several structures, after which the drug is ready for sale.
These antibiotics treat mainly diseases caused by multi-resistant strains of microorganisms. According to Kuptsov, it may be staphylococcus, some nosocomial infections and other diseases that cannot be treated with antibiotics of past generations. Each of the four new domestic drugs has approximately the same spectrum of action, but different impact strength.
Working personnel
Today there are about 1.3 thousand employees at the plant, most of them are graduates of the biological Faculty of the Moscow State University named after N. P. Ogarev in Saransk. In addition, the Department of Chemistry and Technology of physiologically active substances was opened on the basis of the enterprise.
"Only excellent students work here. We need a high level of education. There are very few qualified personnel in this field now. In fact, real elders, mature-age specialists and young laboratory assistants should work with us. In fact, fragile young girls have to do all the work, because there is simply no middle link. As such, there has been no synthesis of antibiotics in the country since the late 1970s, nothing new has happened. So two generations of specialists disappeared," White complains.
The main feature and competitive advantage is that all strains and technology are completely Russian. The first tests took place in one workshop on old equipment, where interested scientists were able to manually synthesize the first drug.
"Biochemist", experts say, has made a breakthrough in domestic pharmaceuticals. And further development will make it possible to manufacture about 20 antibiotics based on these four.
As the head of Mordovia, Vladimir Volkov, said at the launch ceremony, a total of 400 million rubles will be allocated for production from the federal budget, another 100 from the regional budget.
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