In extraordinary circumstances, the government adopted a series of emergency measures to ensuring the safety, organization of specialized hospitals, the needs of the health system and citizens in the means of individual protection and medicines. Some of them have been successful, what are the main lessons of the pandemic period and what solutions it is advisable to save for the future? All these questions were answered by the experts, which “RG” gathered at the “round table” on the theme “Regulatory lessons of the pandemic”.
during a pandemic, the government introduced a number of changes in the sphere of circulation of medicines. Which of the anti-crisis regulatory measures have become the most important and has proved its efficiency?
Alexey Alekhin, Director of Department of development of pharmaceutical and medical industry of Ministry of industry and trade of the Russian Federation:
One of the most effective measures taken by the government of the Russian Federation, was the introduction of expedited registration of medicines, medical products and amendments to registration dossier regarding additional manufacturers of the pharmaceutical substance. It was introduced by the resolution No. 441. The government has also enacted a similar decree No. 430, which relates to medical products. In the case of an emergency has simplified measures with respect to the registration of certain categories of medical devices, allowed the import to Russia of these unregistered medical devices to the extent necessary for testing (testing) and state registration without permission of Roszdravnadzor. Also allowed to be sold unregistered in the Russian Federation of medical products single use without permission of Roszdravnadzor, if such products are duly registered in the country of origin. In addition, decree No. 430 was amended regarding clarification of the procedure and terms of submission of documents for obtaining the opinion of Roszdravnadzor. Expanded the list of medical products which already contains 363 position.
with the introduction of the norms of domestic producers in the shortest time recorded and brought to the market a medicinal product intended for use with novel coronavirus infection – favipiravir and levelmap. They are made in Russia full production cycle, which also ensures the reliability and timeliness of provision of medicines. Registered and put into circulation more than 120 test systems for the presence of viral RNA and antibodies to coronavirus infection.
In the period of the pandemic for the first time introduced a mechanism to conduct inspections for compliance with good manufacturing practices for video meeting related to��I. this decision of the government of the Russian Federation from may 29, 789 N changes in the Rules of organization and conduct of inspections of pharmaceutical manufacturers for compliance with GMP regulations. Also revised the procedure for issuing certificates of compliance the drug manufacturer’s specified requirements in terms of renewal of the conclusions of the GMP, which expired in the period from 15 March to 31 December for 12 months from the day following the date of expiry of the validity of such conclusions. In addition, in some cases it is possible to issue a conclusion on GMP inspection of the production site according to the documents, including with use of means of remote communications, including audio or video communications.
No less important is the decision of the government of the Russian Federation of 21 March N 322, amending the rules of granting from the Federal budget of grants of the Federal state Autonomous institution “Russian Foundation for technological development” in order to stimulate activities in the industry. Under these changes, the Foundation established a new program of providing concessional loans “Combating epidemic diseases”. This program was in demand by enterprises of pharmaceutical industry in the framework of the program approved funding for 25 projects amounting to more than 7.2 billion rubles.
Valentina Kosenko, Deputy head of Roszdravnadzor:
the Most important is to RF government resolution No. 441. It was the peculiarities of registration and examination of quality, efficacy and safety of medicines in the context of registration and/or changes in the registration dossier for the medicinal product. In addition, the Ministry of health of the Russian Federation was created the Interdepartmental Commission the decision on the possibility of a temporary treatment series (batch) of the drug for medical use. He touched the drugs intended for use in conditions of threat of occurrence of emergency situations. The regulations were aimed at facilitating procedures for registration and putting into civil circulation of medicinal products, while maintaining a high level of quality assurance, safety and efficiency in the application.
Yury Olefir, Director General of the National center of expertise of medical application products (ncesmp) of the Ministry of health:
For the purposes of examination and registration of medicines the key document was the decree of the government of the Russian Federation No. 441. It entered into force on 14 April and will operate until January 1, 2021. According to paragraph 3 of the resolution, for the period of emergency featuresand examination of quality of medicines and expert examination of correlation between anticipated benefit and possible risk from use of medicinal product for medical use may be established by the working group established at the Ministry of health of the Russian Federation. Group can reduce the amount of such examinations, and to consider the possibility of replacing laboratory examinations research (trials) conducted in accordance with article 52.1 of the Federal law N 61 “On circulation of medicines”. The possibility of granting an incomplete package of documents, allowed relief when the state registration of a medicinal product, which is a combination of previously registered medicinal products.
Also determined that the MoH should carry out the state registration of the medicinal product within a period not exceeding 20 working days of receipt of the application and relevant documents. To conduct examinations and issue the respective opinion from the expert institution has 15 working days. After the Ministry of health of the Russian Federation will be given an assessment within two working days, the Agency must make a decision on registration of the medicinal product or refusal of registration. Such registration certificate is issued with validity before 1 January 2021, but the circulation on the territory of the Russian Federation is permitted until the expiry of their shelf life.
currently, medicinal products registered in accordance with the resolution, are drugs for which there are encouraging preclinical and clinical pool of data, but there remain a number of questions on the evidence of their clinical effect. As a rule, they are approved for use only in hospital environment. With all the warnings and these methods of application of these drugs is relatively safe.
Vladimir Shipkov, Executive Director of the Association of international pharmaceutical manufacturers (AIPM):
– Pandemic COVID-19 demanded extraordinary and extraordinary measures all participants in the sphere of provision of medicines for the optimization of the control measures aimed at ensuring uninterrupted supply of medicines and speedy access to patients in need of drugs and medical devices. Emergency situation as never before, demonstrated the importance of regulation of the industry on the principle of smart and flexible regulatory mechanisms, the need for complex and fast problem solving with a tolerance of drugs on the market, operational restructuring, operational and organizational issues, the mechanisms of “regulatory trust” and recognition of the results of overseas regulatory assessments and decisions, effective use of the resources of regulators and industry.
Olga Pentegova, kneadingTitel, Director-General of the Association of Russian pharmaceutical manufacturers:
In this period were adopted at least three decisions that significantly affected the market. The first is the whitelisting of remote trade. This law for several years was not accepted, he had both supporters and opponents. The decree of the President has accelerated its adoption in an emergency situation of a pandemic. This is a long awaited opportunity for business, but the mechanism of its implementation still need to hone. The law permits distance selling of OTC medicines. Shipping prescription if necessary, may be allowed by the government until the end of the year. We regard this as a kind of pilot project that will allow in the future to finalize it completely in both directions and successfully organize the delivery including prescription products. Very excited farmrynok a government decree that gave the right to purchase and implement personal protective equipment (PPE) from a single company. That our doctors at the first stage in a timely manner will not get them, blame the ones who lobbied for it. Well, that was smart enough a few days its easy to suspend. I believe that it should be cancelled.
the Important role played by the decree No. 441, which allows in an emergency situation in an expedited manner to register, conducting a limited clinical trial (s) of those drugs which can affect the survival of life. It also gave the opportunity to apply for the conduction of a clinical trial and other procedures on the electronic media rather than on paper. These decisions largely had a positive impact on the treatment of patients with coronavirus pneumonia.
Svetlana Zavidova, Executive Director of the Association of clinical research (AOKI):
Among the regulatory developments in the sphere of circulation of medicines, conceived as a response to the challenges of the pandemic, our greatest attention attracted “features of circulation of medicines for medical use”, approved by decree of the government of the Russian Federation No. 441.
In particular, the mechanism of the use of drugs during the emergency situation according to the indications specified in the instructions for medical use. Paragraphs 29-35 of the document allow it, referring to “use of off-label, study of efficiency of application”, “research of efficiency of application”, and even “mainternational research”, despite the fact that the treatment is totally new disease is, by definition, cannot be considered mainternational.
Due to terminological ambiguity resolution on the use of potentially effective of the drug in an emergency situation simultaneously is a simplified procedure of obtaining of evidence for the efficacy of drugs in studies involving humans, the organizers of which is the decision of the government is actually exempt from compliance with international standards for such research.
In particular, the optional becomes an independent assessment of the study Protocol, not spelled out the requirements for obtaining informed consent and methods of control over their observance. Also not mentioned life insurance and health of participants not provided for the qualification of researchers, it does not assume any external (neither state nor public) monitoring the safety of patients – and this is not a complete list. Have AOKI no problem with the use of off-label in acute need within the legally established procedures. But deeply worried about opening a loophole for uncontrolled studies and registration for new indications of drugs to standards of evidence-based medicine. On the basis of the decision can be extended the indications in the instructions for use of the drug, the drug may be included in the official recommendations for treatment. All this creates risks not only for the participants of such experiments, but also for consumers.
Particularly worried that under the guise of regulations in the media have already appeared the bravura statements by the developers about the incredible effectiveness of drugs for the treatment COVID-19 on the basis of data collected with the use have not undergone an independent assessment and not made public procedures. We are aware of several such cases. As example, press release of the Agency from 22 April 2020 with loud claims about the effectiveness of mefloquine. This press release was stated that reliable conclusions about the effectiveness of the drug will be made by the developer until the end of may. But no information the results have not appeared so far. It remains unclear why the participants in the experiment were at risk, if this study leads to the increment of scientific knowledge in the professional community.
Which of the decisions taken should be maintained and extended to routine practice, to improve availability of medicines to patients, including unregistered in the Russian Federation?
Alexey Alyokhin: currently, in connection with the rise in the cost of raw materials and packaging, more acute question is the profitability of production of drugs in the low price segment. Under government decision No. 441, the mechanisms giving an opportunity of re-registration of maximum ex-works prices for the medicinal preparations included into the list of INVLP intended for the prevention, diagnosis and treatment COVID-19, should be finalized and distributed to the entire list. This will prevent the risks of directory of such drugs.
in addition, the mechanisms in the accelerated order to go through clinical testing and the state registration procedure is also well established. Their introduction will further improve access of patients to drugs breakthrough therapy.
the amendments envisaged by the RF government decree No. 789 concerning the inspection of documents in terms of quarantine restrictions, it is possible to use not only during dissemination of coronavirus infection, but other limits in the Ordinance.
Valentina Kosenko: registration Procedure established by the RF government resolution No. 441, valid until 1 January 2021. In our opinion, the order of registration of medicines with subsequent post-marketing surveillance can be extended for a further period in order to provide patients with innovative medicines.
Olga Pentegova: Remote trade in drugs must be improved. But, of course, it will be necessary to analyse the practice and to Refine its mechanism. In addition, resolution No. 441 is valid until the end of the year. In emergencies it is definitely useful, but in normal conditions, probably in full to keep all these measures are not necessary.
Svetlana Zavidova: AOKI hoped that with the end of the pandemic hastily adopted regulatory documents also will lapse or will be edited so that not to create additional threats to the life and health of people. But there is one feature in the work of regulatory bodies is manifested in the spring of this year, which we hope will continue after the victory over the coronavirus. We saw that the staff of the Ministry of health even in the face of serious constraints associated with compliance with social distancing, are able to consider applications for clinical research with incredible speed. Applications for testing of drugs for the treatment of COVID-19 are considered high for the week instead of the usual three months. And this is the practice that, in our opinion, it is necessary to maintain and disseminate to improve the availability of medicines for patients.
Vladimir Shipkov: ARM actively participated in the development of a set of measures of a regulatory nature in the period of the pandemic, offering to use the experience of leading regulatory agencies in the world. Many of these proposals are reflected in the relevant resolutions of the government of the Russian Federation concerning the issues of optimizing clinical trials registeration of medicinal products, to conduct documentary and remote inspection for compliance with GxP, the use of electronic documents and more. It is very important to evaluate this experience and use it to restart the system of pharmaceutical regulation in Russia. This can significantly increase the efficiency of the entire system and provide the market with necessary medicines.
Oksana Monge, Director General of the company “Sanofi” in the Eurasian countries, the Chairman of the Board of Directors of AIPM:
In Russia the absolute priority of all the companies of the pharmaceutical industry was to ensure an uninterrupted supply of drugs. Public authorities, competitors, patient organizations – we all have to work together faster and more efficiently. Reduced the duration and total number of required approvals on many issues, many times accelerated the introduction of new digital tools. If the registration of clinical trials in Russia is standard usually takes about 5 months, in a situation of a pandemic, creativity and openness of the regulator was allowed to do it much faster. However, there are still unresolved problems, particularly in the implementation of the labelling of medicines. Despite the high demand for many drugs during a pandemic, when priorities shifted with adjustment lines for markings on the uninterrupted provision of increased demand and a ban on travel professionals service organization in the Russian Federation, the implementation of marking remained the same from July 1, and the transition period is a very complex procedure. As a result, the risk to continuity of supply of hundreds of drugs and their availability to Russian patients. Already at customs delayed party drugs. We believe it is necessary in the shortest possible time to eliminate the existing regulatory gaps. It is only by maintaining the spirit of cooperation, listening and hearing each other, focusing on patients ‘ needs, together we can build a truly patient centered health care.
Vasily Ignatiev, General Director of group of companies “R-Pharm”, the Vice-Chairman of the Board of Directors of AIPM:
– Pandemic taught us to work in new conditions – this applies to the industry as a whole and to the regulators. In April, there have been several fundamental documents of unprecedented change in the regulatory environment. Many of the innovations, while temporary, it is advisable to keep in the future. Speech, in particular, expedited permits clinical studies, when the problem is socially important, the transition to electronic document when submitting the registration dossier and the dossier for clinical trials, and in the future – on the accelerated Regis��of radio medicines and medical products, the inspection in virtual application and documentary formats. We must try to develop objective criteria by which the application of such measures will be possible in the future. The trend is very positive. One of the main challenges as the pandemic will be to maintain all of the rational decisions taken in this period.
Katerina Pogodin, managing Director at Janssen Russia & CIS, General Director of the company “Johnson&Johnson”, a member of the Board of Directors of AIPM:
– In a short time all stakeholders managed to establish an open and effective dialogue, which provided stability for the medical care not only to patients with COVID-19, but also with other chronic diseases. Need to further develop patient centered practices that would ensure sustainable and continuous care for patients and increase the accessibility of innovative therapy, regardless of external challenges and threats. In particular, it is necessary to continue to establish mechanisms for providing assistance to patients with cancer, including malignant blood diseases, and to develop new approaches to ensure the continuity of treatment of modern medicines in the outpatient sector, and further improving the safety, quality and efficiency of cancer care in the country. We hope that such approaches will be developed and ready to contribute to their implementation.
