Medicines in Russian
Junk Medicines
Irina Vlasova, MednovostiWhy are good and high-quality medicines sold in Europe and the USA, but this is not the case in Russia?
This question is especially acute when it is necessary to replace one drug (often original and expensive) with its domestic counterpart. This is a common practice all over the world, but nowhere, except in our country, such a process is not so painful. How do outdated or inactive drugs get into the Russian pharmaceutical market and, accordingly, into pharmacies and clinics?
Where does garbage come fromThere are several reasons for this.
One of them is that some drugs were created a long time ago. "There are quite a lot of old medicines in the pharmaceutical markets of different countries that appeared in the "pre–scientific" time, when there were no reliable methods for evaluating the effectiveness of drugs yet," says Professor Vasily Vlasov, president of the Society of Evidence-Based Medicine Specialists. – In Russia, a vivid example is the tincture of hawthorn. These drugs live and live. If they are harmless, they live as long as they have buyers. When they go bankrupt, they gradually disappear from the market, but there are always buyers for such a "medicine"." There are quite a lot of new drugs on the market that also "don't work". "And there are reasons for this, too," explains Professor Vlasov. – The criteria for evaluating the results of research are inconsistent, and those drugs that should not have been included in the Hamburg account fall into the pharmaceutical market. In Russia, the law implies an assessment of the effectiveness and safety of a drug, but it does not specify what it is. Now we can register a drug that does not have a full proof of efficacy and safety. For example, comparative clinical trials were not conducted, but 100 people were simply treated, and "it became easier for everyone." The drug is allowed." This, in particular, concerns immunomodulators. Studies have shown that such drugs alter immunity indicators. However, this is not enough: in order to be able to speak with confidence about the need for the use of such drugs, they must change the course of the disease. This does not happen, but the drugs are still on the market. Nootropics, which are also common in the post-Soviet space, have been tested in insufficiently good and high-quality clinical trials. And therefore it cannot be said that they have a proven significant effect.
The third reason is elementary corruption. In 2005, the scientific world was very surprised by the recommendations of Russian oncologists on the widespread use of a Chinese emulsion of plant origin, called "Kanglight". An antitumor drug from China was registered in Russia, despite the fact that each study included only a few dozen patients.
However, well-known Russian specialists took part in the tests. The manufacturer also showed a photo of his supposedly modern workshops, and that was all. "This emulsion has not passed the tests even of the first phase in the USA, and the tests in Russia, to put it mildly, are of poor quality," says Professor Vasily Vlasov. – But Lee Dapeng was even accepted as an honorary member of the Russian Academy of Medical Sciences. I am sure that the drug "Kanglight" would never have passed a normal examination." In this situation, the calculation for the terminally ill is justified: in any case, there will be someone willing to pay for an oriental miracle.
The situation of seriously ill patients sometimes provokes the entry into the market of more serious, but still poorly studied drugs. "Patients cannot wait decades for the end of trials, they want a fast availability of the drug on the market. And in all countries, supervisors find themselves in a difficult situation, they have to hurry. As a result, the drug enters the market, but then it turns out to be ineffective, and the side effects are large," explains Professor Vlasov. If, for example, too few patients participated in a clinical trial (CI), the company receives permission to enter the pharmaceutical market with the condition of additional CI, but the condition is then ignored. In January 2014, the Journal of the American Medical Association published the following data: over the past 7 years, in every third case, the drug was allowed to enter the market after one clinical trial. That is, there was nothing to compare these results with. As for Russia, according to experts, CI is not so strictly controlled in our country.
A lot of honor"In my opinion, it is not quite right to raise the issue of the "clogging" of the pharmaceutical market in general," independent expert Nikolay Bespalov believes.
– There are a lot of drugs on any market that, by and large, are not vital or at least have questionable performance indicators. So, among other things, we can talk about the majority of homeopathic medicines that are being used in the world. A significant number of over-the-counter medicines also fall under this definition. If we talk about immunomodulators, nootropics, mild antidepressants or adaptogens, then all these drugs have the right to exist and, moreover, help patients in various situations."
Those medicines that have proven effectiveness may also be useless. The fact is that they are often used for other purposes. This is the sin not only of individual Russian brands, but also quite respectable foreign manufacturers. "Such a problem arises due to the excessive activity of individual companies in the field of promoting their products," says Nikolay Bespalov, "this also applies to prescription drugs. As a result, due to active promotion and positioning, there is a skew. Multivitamins are beginning to be advertised as a drug to improve the structure of hair, as a cure for stress or nervous overstrain, etc."
The deputy chairman of the Formulary Committee of the Russian Academy of Medical Sciences, Professor Pavel Vorobyov, analyzing the Russian List of vital medicines, noted that among these drugs are "activated charcoal, caffeine, piracetam, riboxin (inosine), nicotinamide, riboflavin, which have never been tested, and if there were tests, well-organized studies, then they have shown the ineffectiveness of these drugs." Even according to the calculations of specialists of the Ministry of Health, most of the funds of medical and preventive institutions are spent on medicines with questionable effectiveness.
European protectionIn order for a good medicine to get on the market, and a bad one does not, an effective registration and control system is needed.
Professional and uncorrupted. The entry into the drug market in Russia is characterized in many ways by the lack of clarity of rules and regulations and great opacity. For example, in the UK, the state will purchase drugs only when they are approved by experts. Such an expert body is the National Institute for Health and Care Excellence (NICE). In principle, it works similarly to scientific supervisory agencies: the American Food and Drug Administration (FDA) and the European Medicines Agency (European Medicines Agency, EMEA). An important goal for Western regulators is also to combat patronage in certain countries that do not want to register new drugs that could compete with drugs already produced in these countries.
Both in the European Union and in the United States, expert procedures are open, discussions are public. Drug manufacturers come during preliminary consultations with regulators, when decisions are still being worked out, and after a negative decision is made, they can challenge them in court. "When consultations are held at NICE," says Lisa Osipenko, a senior researcher at the Institute, "independent experts are present at them, there are letters from competitors, representatives of patient organizations are present, and patients themselves, there is a broadcast, all documents are posted on the website. All procedures are absolutely transparent. The Institute's solution is a benchmark of expert solutions. And if the review of the drug is positive, then the state is obliged to finance purchases." The institute conducts only 45 examinations a year, each lasting 4 hours. "First of all, consent for examination is given to those drugs that are especially needed by the state and patients," says Lisa Osipenko, "there are no analogues, the disease is severe or other drugs for the treatment of this pathology are toxic. Sometimes NICE returns to the consideration of the dossier after 3-5 years. Since the examination was postponed in favor of drugs more needed by the healthcare system. Experts are guided not only by the effectiveness of the drug, but also by how much the new drug works better than the existing ones, the economic feasibility in terms of QALY – the cost of 1 year of quality life. According to QALY, the new drug is compared with the existing ones. Will the new one be more expensive or cheaper? A more expensive drug carries a risk to the entire healthcare system. How much more convenient and innovative the drug is. It is desirable that a one-year extension of life or an improvement in its quality does not cost more than 20 thousand pounds, although there are exceptions depending on the pathology." The NICE commission includes leading narrow experts on this disease, and the company invites 8 of its experts to the council – economists, clinicians. The institute gives an answer in 8 weeks. Up to 80% of NICE's decisions are positive, as there is a lot of scrupulous preparatory work on the evidence base, recommendations are issued at consultations even before the dossier is submitted for examination – after the drug has passed the third phase of clinical trials, but before the serial production of the drug begins.
If the company has little evidence of the effectiveness of the drug, the drug will not enter the market in principle. The manufacturer brings the clinical trial plan in advance to the Medicines and Healthcare Products Regulatory Agency (MHRA), which issues licenses to the drugs. The Commission makes a proposal on how to conduct these clinical trials more evidently. It is important that they believe their national regulator in the UK 100%, and if he gave the drug a license, this is a guarantee that the drug is tested and "works". Appeals are sometimes filed against the examinations and the institute, but in recent years NICE has not lost a single case. And how do outdated medicines leave the market? "There is no process of withdrawal of obsolete drugs from the market in the UK – it's just that if the new drug is better, then the old one is sold worse. Government purchases of an outdated drug are also being reduced."
Fights without rulesThe Association of International Pharmaceutical Manufacturers says that the system of registration of drugs in Russia is in crisis.
"All decisions are made behind closed doors, although openness is declared, decisions on specific drugs are delayed indefinitely," says Vladimir Shipkov, executive director of the association. The manufacturers claim that the Russian regulatory system will not be established in any way, responsible services, powers and prices for registration are changing.
For many years, the expertise has been carried out by the Scientific Center for Expertise and State Control of Finished Medicines, which has become the legal successor of several centers and institutes at once: the Russian State Center for Drug Expertise, the State Research Institute for Standardization and Control of Medicines, the Research Institute of Traditional Methods of Treatment and the Scientific and Practical Center for the Control of Side Effects of Medicines. At the same time, the function of the federal body regulating drug circulation has been transferred to the Ministry of Health. And if the institutes used to work under Roszdravnadzor, now they work under the Ministry of Health. Today, the scientific center is responsible for quality control, efficacy and safety of medicines on the market, conducts pharmaceutical, preclinical and clinical examinations of medicines, both domestic and foreign for medical use in Russia. In addition, his duty is to harmonize Russian requirements for medicines with foreign ones. That is, today this center is the main expert who determines which medicines people will buy at the pharmacy, what they will be treated with in hospitals, and what the state will buy for its health programs (taking into account the opinion of the Ministry of Health). The Center also decides where and how drugs with the participation of Russian patients will be tested in clinical trials. The state quality control of medicines is also carried out here, control and analytical laboratories are licensed and manufacturing plants are checked.
It is difficult to assess whether these perturbations have reduced "opacity", bribery and tariffs for speeding up drug registrations. In any case, the Federal Antimonopoly Service (FAS) responds to calls from drug manufacturers to allow the necessary scientific consultations with service specialists before registering the drug with refusals due to fear of past abuses. And manufacturers complain about the unpredictability of requirements and unclear reasons for delays.
The difficulties are also added by the fact that in Russia there are no rules for registering groups of drugs for which special schemes are needed (orphan, children's, first generics, biologics). Senior lawyer of Pepelyaev Group Sergey Klimenko says that amendments to Federal Law No. 61 "On the circulation of Medicines" are being discussed for the seventh time. In accordance with them, the terms of registration of such drugs should be strictly limited (the latest version of the amendments states that they will be 90 days). It is also necessary to determine the rules when the regulator can stop the clinical trial of the drug, now this issue is also not clarified in any way. The procedures for which the drugs are interchangeable are not defined. According to the latest FAS data, some of these amendments have already been agreed with the Ministry of Health, and they may come into force by the beginning of 2015.
Russian testsIn order for the state to register on its territory and allow the turnover of a "good" medicine, the drug is tested after studies on animals and healthy volunteers already in clinical practice.
But there are problems with conducting clinical trials in Russia. Due to the "overregulation" of this area of the market, the number of CI is decreasing annually. The federal Law "On the Circulation of Medicines", which came into force in 2010, not only intimidated, but also greatly complicated the work in this area. It is now extremely difficult for companies to obtain accreditation, to insure participants, and the deadlines for obtaining permits from regulators are also extremely long. Up to 50% of applications are rejected. The public and the media perceive clinical trials of medicines for pediatric practice, that is, with the participation of children, especially painfully. Sensational stories of the past years with unethical practice of CI force the Ministry of Health to blow on the water.
Andrzej Dzerbicki, director of the global Department of Biopharmaceutical and Clinical Research at Polpharma (Poland), says that "in Russia, for reasons of "overregulation" of the CI sphere, new drugs come out on average a year later." Making a decision can take up to 3-4 years, and the Association of International Pharmaceutical Manufacturers laments the impossibility of obtaining exhaustive claims of the regulator to the future drug at one time. According to Vladimir Shipkov, "drug manufacturing companies can bring dossiers on a future drug indefinitely, but eventually get rejected." According to the Synergy Research Group, which monitors this area, 791 clinical trials of medicines from 31 countries are currently being conducted in Russia. But the number of new CI started is decreasing annually. In 2012, there were 322, and in 2013 – only 265. If in 2012 67 thousand Russian patients took part in them, then in 2013 – only 57.6 thousand.
General cleaningIdeally, the drugs should not only be proven effective, safe and economically affordable when admitted to the market – they still need to be produced at the factory in the correct regulatory and sanitary conditions.
For example, the car needs to be thoroughly cleaned of the remnants of the previous drug before laying the substance of the new drug. How real is the danger of poor quality medicines created in Russia? Pharmaceutical factories were mainly built in Soviet times, so the situation is similar in the CIS countries (although, of course, we have advanced factories of foreign manufacturers). You can imagine what is happening in Russia by the state of the factories in Ukraine. Ukraine has introduced strict EU requirements for the production of medicines for 3 years. And the new control system now assumes a regular inspection of industrial sites when licensing production and when issuing a GMP certificate (good manufacturing practice, good manufacturing practice), as well as mandatory follow-up by inspectors at factories.
According to Yuri Podpruzhnikov, professor of the Department of Quality Management at the National Pharmaceutical University, founder of the Ukrainian GMP inspectorate, inspectors who conducted 85 inspections registered 3-4 "critical deficiencies" at the inspected sites of Ukrainian factories, not to mention violations of less significant ones. Only 85% of enterprises met the EU requirements. There were such violations that really threatened the life and health of patients – such shortcomings in which a plant or workshop in the EU or the USA is simply closed. As a result, out of 151 plants (workshops), only 111 received a license, the rest were forced to leave the market for various reasons.
The low quality of many domestic drugs is also affected by raw materials. The main supplies come from Southeast Asia - it's cheaper this way. One can only guess about the quality of these substances: in Asia, the manufacturer does not need to prove the high quality of products, as is done in the USA and the EU, in order to obtain an import license.
The transition of Russian factories to the practice of manufacturing according to GMP requirements adopted in the USA and the EU will eliminate all these risk factors. But the process is delayed for more than 10 years, because it requires serious investments. Although the rules were legally approved in Russia from January 1, 2014, now due to the unavailability of the inspectorate and authorized persons at the plants, they will be introduced from 2014 to 2016. So far, the requirement to provide such a certificate when purchasing medicines does not really work.
But what will happen to the Russian market if you get rid of a huge number of drugs that do not have proven effectiveness or are produced in improper conditions? "Nothing bad will happen," Professor Vasily Vlasov is convinced. – People will just switch to other medications. At first, they may make noise – without valokordin, someone will be unaccustomed, sleep will be disturbed for the elderly, but there will definitely be no catastrophe."
Portal "Eternal youth" http://vechnayamolodost.ru12.03.2014