The role and practice of pharmacovigilance in Russian healthcare. What is pharmacovigilance, regulatory documents, regulatory measures Pharmacovigilance as a single functional system

It is necessary to send a message to the pharmacovigilance service, if a case occurs during the medical use of GEROPHARM preparations:

• Adverse reactions that may be associated with the use of the drug
• Lack of drug efficacy
• Drug interactions not described in the instructions for medical use of the drug
• Detection of counterfeit products
• Errors in the medical use of the drug
• Overdoses when using the drug
• Drug abuse
• Incorrect use of the drug
• Development of an adverse reaction when using a medical device

You must send a message, even if

• You are not sure if the adverse reaction is related to this drug
• You don't have all the information

2. How to send a message?

• Fill out the sections of this form in as much detail as possible, according to the information you have.
• If you have information about more than one adverse reaction, please use a new form for each.
• Send a message to the GEROPHARM pharmacovigilance service by e-mail, fax or mail.
• You can also submit the completed form through the medical representative of GEROPHARM

3. When to send a message?

• The message must be sent as soon as possible after the information has become known to you.

4. Where and how to send the completed form?

5. Protection of personal data

Patient information is kept strictly confidential. Filling in this form means the consent of the subject of personal data to their processing by the pharmacovigilance service of GEROPHARM. Information about the reporting person will not be publicly released. They can be submitted to the Federal Service for Surveillance in Healthcare, unless otherwise indicated when submitting a report.

A representative of the GEROPHARM pharmacovigilance service can contact the person who sent the message to clarify the information provided in the message.

If you have any questions, please call the GEROPHARM Hotline

It has no side effects, it is worth considering: does it work at all? With such, perhaps, harsh words, I would like to begin the analysis of one of the most important elements of drug safety monitoring.

Director General of the National Scientific Center for Pharmacovigilance told LekOboz about how to act correctly in the pharmacovigilance system Anatoly Krasheninnikov and an independent GCP and GLP auditor Evgeny Rogov.

According to the recommendations of the World Health Organization, 60 reports of adverse reactions per 100 thousand of the population are considered the norm. In Russia, this figure ranges from 14 to 47 messages (depending on the region). Not the last role in this is played by the lack of awareness of both the patients themselves and doctors and pharmacists.

Today in our country much attention is paid to national security issues. Without a doubt, part of its system in any state should be measures aimed at improving the health status of the population, including the development of the healthcare system. And it, in turn, is unthinkable without adequate drug provision. Thus, the state must control.

But what should be drug control?

In the narrowly specific sense of state control, it is a set of measures that give society confidence that a medicinal product:

1. safe, effective (and its safety and efficacy are in accordance with the instructions for medical use);
2. meets all quality standards.

State control carried out at all stages of the "life" of the drug:

• at the stage of its development, in particular, at the stage of research;
• at the stage of state registration of the drug;
• and necessarily after the drug enters circulation (by creating a pharmacovigilance system).

Before a medicinal product passes state registration and enters the market, it is necessary to obtain comprehensive data on its efficiency and safety. On development stage out of 10,000 potentially promising molecules, only 1 drug reaches the market, and most of the "drug candidates" are eliminated precisely on safety issues.

The primary hypothesis of drug safety is confirmed in the course of preclinical studies using at least two types of test systems (laboratory animals). Unfortunately, the current level of development of science does not allow creating new ones without research involving humans, since not a single biological model is able to reproduce the "behavior" of the drug in the human body. Therefore, it is extremely important that the effectiveness and safety of the drug be proven at the stage of clinical trials - it is the data of these studies that form the basis instructions for medical use.

In other words, mistakes at this stage of development from the moment of state registration of the drug and its entry into the market, in legal terms, pose a threat to the life and health of an indefinite circle of people. This fully applies to both safety data and efficacy data. The use of a medicinal product with an efficiency that differs from the declared one (both up and down) jeopardizes the life and health of patients taking it.

In the world there are no drugs that do not have side effects, and these effects should be described in as much detail as possible in the instructions for medical use. Even in the ancient world, healers warned about the harmful effects of chemical substances on the human body. So, in ancient Greece, the word "pharmakon" meant not only medicine, but also poison. Since then, science has stepped far forward, and today the benefits of drugs far outweigh the risks of their use, but nevertheless, such risks remain.

Russia is in the top ten countries with the largest consumption of drugs in absolute terms (if we compare this figure with the number of inhabitants, much of the behavior of the domestic patient will become clear). The share of the pharmaceutical market in our country is about 1% of GDP.

With such a high level of pharmaceutical consumption, especially in an aging population, the issue of monitoring their correct use and safety is more than relevant in the field of public health. Activities aimed at identifying, assessing and understanding the possible negative consequences of the use of drugs, preventing their occurrence and protecting patients- This the basis of the pharmacovigilance system.

Both among patients and among doctors there is a common misconception that those approved for use in practice have been comprehensively studied and all their side effects are reflected in the instructions for medical use. This is only partly true.

In fact, by the time of registration A new drug is being tested in a limited number of patients and in artificially created conditions, when certain criteria for the selection of subjects are used. In this regard, relatively rare side effects may not be detected at this stage.

Statistical laws indicate that in order to guarantee the detection of side effects that occur with a frequency of 1 in 10,000 (and this is considered relatively frequent), a study must be carried out on 30,000 patients. Registration of drugs is often carried out after clinical trials on a much smaller number of patients.

Plus, the use of the drug in real practice differs from the ideal conditions of a clinical trial: patients have concomitant diseases, take other medications, etc. At the same time, a lot of factors (age of patients, drug interactions with each other, as well as with food, etc.) .) can significantly affect the safety profile of the medicinal product.

But that's not all. Traditionally the Russian market has a large share of generics. In Russia, as elsewhere in the world, in order to register a generic drug, the manufacturer must prove to the regulator that the drugs have the same composition and identical pharmacokinetic parameters in the human body. To evaluate these parameters, bioequivalence study in healthy volunteers, the number of which varies depending on the drug and ranges from 18 to several dozen people. It is assumed that drugs with the same composition and bioequivalent to each other will have a similar efficacy and safety profile.

Or another situation: sometimes side effects can appear several years after the registration of the drug. For example, it was only after 35 years of use that amidopyrine was found to cause agranulocytosis.

It is very important to continue the study of medicines even after their registration and appearance on the shelves of pharmacies. In many respects, the adoption of preventive measures to minimize the consequences of an undesirable reaction to the medicine depends on the responsibility of the doctor and pharmacist. Only a professional understands the importance of timely reporting of adverse reactions.

Therefore, in order to improve the safety of drug therapy - and improve the quality of care within the framework of programs for monitoring the effectiveness and safety of drugs - explanatory work should be carried out in healthcare facilities among doctors about the significance of reports of adverse reactions. And also: advising patients in difficult cases, informing regional and federal centers of pharmacovigilance, familiarizing medical personnel with the most important results of domestic and international monitoring of adverse reactions, cases of recall of drugs from the market or restrictions on their use in Russia and other countries.

According to the order of Roszdravnadzor dated February 15, 2017 No. 1071 "On approval of the procedure for the implementation of pharmacovigilance", the work of medical organizations to identify adverse reactions and other information on safety and efficacy when using drugs should be regulated by the internal documents of the organization. In practice, this means that in each health facility a responsible person (usually a clinical pharmacologist) should be appointed to solve these problems. Explanatory work on pharmacovigilance issues is carried out by Roszdravnadzor and its territorial bodies.

The effectiveness of drug safety monitoring directly depends on the activity of pharmaceutical companies, medical professionals and patients. Only together we can make it more efficient and safer.

Can medicine ever do without pharmacovigilance?

Even if all the instructions become completely clear to the patient, the answer is unequivocal: No . However, effective drug safety monitoring is possible under one condition: if there is not opposition, but interaction between the patient, the doctor and the healthcare system ...

We are ready to offer the development of a pharmacovigilance system for the circulation of medicines: the development of a set of necessary documents, a medical assessment of each safety message for the customer's products, filling in the AIS database of Roszdravnadzor, and conducting pharmacoepidemiological studies.

According to the WHO definition, “ Pharmacovigilance are scientific research and activities related to the identification, evaluation, understanding and prevention of side effects or any other problems associated with the drug, they are designed to ensure the safety of patients when using drugs, their ultimate goal is to reduce the morbidity and mortality caused by drugs means.

Currently, pharmacovigilance is a special scientific discipline that has its own goals, objectives, methods. Pharmacovigilance during clinical trials is a necessary measure to prevent adverse reactions during the medical use of the drug. Due to the limited sample of patients / volunteers, violations of the homogeneity of samples for various indicators, the influence of random factors during clinical trials, it is not always possible to identify rare adverse reactions, delayed adverse reactions, clinically significant drug interactions with other drugs. As part of the pharmacovigilance system, these features of the effect of drugs on the body are revealed.

“The study of the safety of a medicinal product continues throughout the entire period of its use in medical practice” Astakhova A.V., Lepakhin V.K. “Medicines. Adverse reactions and safety controls. The introduction of a large number of medicines into medical practice, the irrational use of medicines, medical errors and other factors contribute to the high urgency of the problem of drug safety. In the course of preclinical and clinical studies of drugs, the level of their safety and effectiveness is determined. However, the results of pharmacoepidemiological studies conducted in recent years have shown the need to identify side effects from taking drugs during the entire time of its use in medical practice. The pharmacovigilance system functions to monitor the safety of drugs throughout their entire “life cycle”.

The main indicators identified during the pre-registration stage of a medicinal product as part of pharmacovigilance: An adverse event is any medically unfavorable event detected in a patient or a subject of a clinical trial after the use of a medicinal product, which may not have a causal relationship with its use. Adverse reaction - all negative reactions associated with the use of any dose of a medicinal product. The term “product-related” means that there is at least a minimal possibility of a causal relationship between the drug product and the adverse event, i.e. relationship is not excluded. An unexpected adverse reaction is a reaction whose nature or severity is inconsistent with known product information (eg, an investigator's brochure for an unregistered investigational product).

A serious adverse event or reaction is any adverse medical event that, regardless of the dose of the medicinal product:

• Led to death;
• Is a threat to life;
• Requires hospitalization or its extension;
• Has resulted in permanent or significant disability or disability;
• It is a congenital anomaly or birth defect.

Tasks of the pharmacovigilance system at the post-registration stage:

• Study of the safety of registered medicinal products in the conditions of their mass clinical use;
• Informing about the safety of registered medicines through specialized mass media;
• Identification of adverse drug interactions with chemicals, other drugs and foods;
• Detection of falsified and substandard medicines, etc.;
• Identification of the use of medicines for unexplored and unauthorized indications;
• Identification of irrational use of drugs;
• Identification of medical errors;
• Identification of the effect of drugs on the quality of life.

Adverse reactions include a wide range of clinical manifestations, which makes it difficult to detect, identify, interpret, and, accordingly, timely conduct adequate measures. Systematized collection of information and detailed analysis of adverse reactions carried out as part of pharmacovigilance will help provide doctors and patients with the most complete and objective information about the safety profile of the drug. Pharmacovigilance carried out by our specialists is carried out in close professional contact with the customer's specialists, which allows us to build a labile pharmacovigilance system under changing conditions.

Pharmacovigilance is a special type of state measures that allow assessing the safety and efficacy of drugs used in medical practice. The main recommendations on the organization of pharmacovigilance in a medical institution are given. Checklist and useful information for download

Pharmacovigilance is a special type of state measures that allow assessing the safety and efficacy of drugs used in medical practice.

This type of state control is regulated by the Order of Roszdravnadzor N 1071: on the procedure for the implementation of pharmacovigilance

On April 1, 2019, a new national database of information on side effects of medicines was launched at external.roszdravnadzor.ru. The full transition to it took place on September 1.

The database automatically processes messages sent using the software of Russian medical institutions, as well as:

• the results of international drug safety monitoring conducted by WHO are stored;
• offers users modern methods for analyzing safety data;
• Russian translation of MedDra regulatory information is supported.

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From the article you will learn

Why and by whom pharmacovigilance is carried out

- one of the areas of state activity, the tasks of which are:

1. Continuous monitoring of the safety and efficacy of medications.
2. Identification and prevention of negative reactions when using medications.

Pharmacovigilance of the drug allows you to warn health workers and patients, protect them from the use of low-quality and ineffective drugs in medical practice.

The order of Roszdravnadzor No. 1071 dated February 15, 2017, describes the organization of the pharmacovigilance system in Russia in the use of medicines, which provides the procedure for organizing control measures in this area.

Pharmacovigilance is carried out by Roszdravnadzor of the Russian Federation, it is this agency that implements the main goals of pharmacovigilance and analyzes information received from all subjects of drug circulation (for example, from medical institutions, holders of registration certificates, etc.).

Subjects submit the following information to the agency for further analysis:

• about the presence of adverse reactions with the direct use of medications (including unforeseen and serious ones);
• about the presence of side effects when using medications;
• about cases of individual intolerance to medicines by patients;
• about the ineffectiveness of specific drugs;
• about other circumstances that indicate the presence of a threat to patients when using a particular drug.

Last changes

The requirements for internal quality control have become unified. An algorithm that will help you quickly reorganize work according to new requirements is in the magazine “Deputy Chief Physician”.

Regulations

The pharmacovigilance system in Russia is supported by the following basic regulatory sources:

1. The main law is “On the Circulation of Medicines.
2. The order of pharmacovigilance, approved by the order of Roszdravnadzor No. 1071.
3. Selective control of medicines - order of the Ministry of Health of the Russian Federation No. 5539 of 09/07/2015.
4. European GVP pharmacovigilance standards approved in 2016 by the Council of the Eurasian Economic Commission.
5. Uniform rules and principles for the circulation of medicines in force within the EEC countries.

Pharmacovigilance in the drug circulation system

In the process of circulation of medicines for the implementation of the pharmacovigilance system, the subjects send notifications to Roszdravnadzor in the approved forms.

These include the following forms:

• notification of an adverse reaction or lack of therapeutic effect of a medicinal product;
• reports of a serious unexpected adverse reaction to a medicinal product being studied in a clinical trial.

Any subject who has doubts about the safety of medicines, as well as when adverse reactions and other manifestations are identified, can send an e-mail to Roszdravnadzor or send a message through the unified information system of the department.

Pharmacovigilance in a particular medical institution is organized in order to identify signs of unsafe use of drugs for medical use and is regulated by a set of local acts approved by the head physician.

note

Roszdravnadzor began to more often hold medical organizations liable for violations in the provision of emergency and emergency care. The department's expert explained how to reduce risks and prepare for emergency situations. In the magazine "Deputy chief physician" - ready-made styling and instructions for staff.

In particular, an authorized person for pharmacovigilance is appointed in a medical institution. It is it that sends reports to the department about the unsafety or ineffectiveness of medicines.

When to Report Adverse Drug Reactions to Regulatory Authorities

The table below shows the time frame in which Roszdravnadzor requires medical institutions to report adverse reactions to the agency.

For the purpose of control, medical commissions prescribing subsidized drugs and identifying cases of their individual intolerance must report this to Roszdravnadzor from the moment it is prescribed to the patient. In this case, the drug must be prescribed by trade name.

Thus, an authorized person for pharmacovigilance is responsible for sending notifications to Roszdravnadzor, the requirements for which are not imposed by law.

In the folder of the head

When does a clinic have the right to deviate from the standards? Four cases from practice and counterarguments for inspectors to avoid sanctions from Roszdravnadzor - in the magazine "Deputy Chief Physician".

Notification periods are calculated from the day when the following information about the undesirable effects of taking medicines became known to the person in charge:

• identification of the person or entity that identified the exception or adverse reaction;
• data about the patient or other person who experienced such a reaction/situation;
• identification data on the medicinal product;
• information about the symptoms that appeared after taking the drug.

As part of internal monitoring of drug efficacy and safety, copies of notifications to Roszdravnadzor should be kept in patients' medical records.

In the future, the agency responsible for pharmacovigilance, Roszdravnadzor, publishes on its portal information about what decisions were made regarding the applications received.

It could be one of the following solutions:

1. The drug was withdrawn from circulation for medical use.
2. The instructions for the medication have been amended accordingly.
3. Stopping medication.
4. Resumption of the use of the drug for medical purposes.

Order of the Ministry of Health and Social Development No. 758n dated August 26, 2010, describes in detail the procedure for suspending the action of medications.

Responsibility

Pharmacovigilance of the drug is mandatory for all subjects of drug circulation.

In order to implement the approved requirements for the pharmacovigilance system, the personal responsibility of officials who became aware of the danger of a particular drug, the presence of adverse reactions and other situations, if they did not report this to Roszdravnadzor, was established.

So, for hiding information about the safety of medicines, if this information created a danger to the health and life of patients, nursing staff and doctors are liable under Art. 237 of the Criminal Code of the Russian Federation. At the same time, health workers can pay a large fine (up to 500 thousand rubles) or be sentenced to imprisonment for up to 2 years.

Medical institutions that do not send periodic reports to departments may be held administratively liable under Art. 19.7 of the Code of Administrative Offenses, the fine is up to 5 thousand rubles.

Methods

Pharmacovigilance system around the world uses different methods. The main one is the method of spontaneous messages.

MO level control

Pharmacovigilance is carried out in medical institutions based on the following basic principles:

• functioning of an effective drug safety system in each unit;
• implementation of a quality management system for maintaining medical records, including electronic;
• well-established system of succession of medical care;
• active interaction between doctor and patient;
• control of the use of medicines at all stages - from their storage and prescription to the intake or administration of the drug to the patient.

Read more about how to organize pharmacovigilance in a medical institution in the appendices.

Is a medical organization obliged to monitor letters from Roszdravnadzor

Roszdravnadzor, within the framework of pharmacovigilance, periodically publishes monitoring data in the form of information letters on its website. The legal obligation of medical institutions to study and track them is not established.

This is due to the fact that information letters are not normative acts, which means that they do not contain mandatory rules for medical institutions.

As a rule, in such letters, the agency invites organizations to check the presence of specific drugs in them, which were recognized as unsafe based on the results of monitoring.

However, there is a legal conflict. On the one hand, when a low-quality, unsafe and ineffective medicine is introduced, in accordance with the Federal Law “On the Circulation of Medicines”, its manufacturer is responsible.

On the other hand, in accordance with the Federal Law "On Health Protection", medical institutions are responsible for causing harm to the health and life of patients in the provision of medical care. In addition, medical institutions conduct pharmacovigilance of the drug, are responsible for using only high-quality and officially approved medicines within their walls.

Thus, despite the established responsibility of the manufacturer, medical institutions should exercise reasonable caution and check information about the safety of certain drugs.

All the necessary information is presented on the website of Roszdravnadzor, and, despite the absence of such an obligation, it is advisable to analyze this information for officials who are responsible for pharmacovigilance in a medical institution.