In late 2016, the Council of the Eurasian Economic Commission adopted the first version of the Rules of Good Pharmacovigilance Practice of the Eurasian Economic Union (EAEU GVP Guideline) based on a similar pharmacovigilance guidance published in the EU in 2014. By Decision No.81 of 19.06.2022, the Council of the Eurasian Economic Commission has amended the EAEU GVP Guideline, and the new version has been effective since 06.12.2022. The amendment has introduced a major revision to the terminology and significant changes to the sections on the risk management system and on organisation of safety information and signal management. The current EAEU GVP Guideline includes new subsections and a reviewed procedure for submitting pharmacovigilance documents to the regulatory authorities.
In this interview, we have discussed the importance of the newly introduced pharmacovigilance changes in EAEU member states for the pharmaceutical industry with Dmitriy A. Rozhdestvensky, Candidate of Medical Sciences, Head of the Section of Coordination of Activities in the Sphere of Circulation of Medicines and Medical Products of the Technical Regulation and Accreditation Department of the Eurasian Economic Commission.

By Decision No. 81 of 19.06.2022, the Council of the Eurasian Economic Commission amended the Guideline on Good Pharmacovigilance Practices of the Eurasian Economic Union (EAEU GVP Guideline), the core regulatory document on pharmacovigilance requirements for the EAEU Member States. The amendment involved all critical pharmacovigilance processes, and its consequences are yet to be assessed.
The aim of the study was to analyse the changes to the EAEU GVP Guideline effective since 06.12.2022.
The author summarised information on the changes made to the EAEU GVP Guideline by Decision No. 81 of the Council of the Eurasian Economic Commission of 19.06.2022 “On Amendments to the Rules of Good Pharmacovigilance Practice of the Eurasian Economic Union”. He described the differences between the old and the new versions of the EAEU GVP Guideline. Having critically reviewed the updated regulatory document, the author commented on its positive and negative aspects. The review created a starting point for further analysis of the changes to the EAEU GVP Guideline. At the time of writing, there were no other published works assessing the significance of most of the changes for the pharmaceutical industry and designated pharmacovigilance organi­sations in the EAEU Member States. The author assessed their significance through the prism of the recent years’ events in Russia and the world, including the COVID-19 pandemic. In connection with the amended guideline coming into force in 2022, the author suggested a transitional standstill period for both the pharmaceutical industry and designated pharmacovigilance organisations. He offered further improvements for the guideline. The article may be of practical interest to pharmacovigilance specialists, heads of pharmaceutical organisations, and employees of regulatory authorities.

The development of international regulatory practices and the accumulation of new experience in pharmacovigi­lance prompted the need to amend the Rules of Good Pharmacovigilance Practice of the Eurasian Economic Union (EAEU GVP Guideline), first adopted in 2016.
The aim of the study was to review, from a regulatory expert’s perspective, the changes to the structure and presentation of the pharmacovigilance system master file (PSMF) introduced with the amendment of the EAEU GVP Guideline effective since December 6, 2022.
The authors compared the requirements for the PSMF outlined in the new edition of the EAEU GVP Guideline adopted by Decision No.81 of the Council of the Eurasian Economic Commission of 19.06.2022 “On Amendments to the Rules of Good Pharmacovigilance Practice of the Eurasian Economic Union” with the requirements described in the previous version of this document.
The structure and content of Module III, Pharmacovigilance System Master File, have been significantly amended in the new version of the EAEU GVP Guideline; this will require marketing authorisation holders (MAHs) to revise the PSMFs describing pharmacovigilance system data. The most significant editorial changes have been made to the paragraphs concerning the PSMF format, the pharmacovigilance quality system, and the presentation of information in the Annexes. The amendment has strengthened the control of records and documentation related to the pharmacovigilance system. Electronic PSMFs are acceptable; electronic book-marking and searchable text make working with the PSMF more convenient for representatives of MAHs and experts of regulatory authorities. Aligning of the PSMF with the requirements of the new edition of the EAEU GVP Guideline will contribute to improving the pharmacovigilance system operation and performance.

The Council of the Eurasian Economic Commission published Decision No. 81 “On Amendments to the Rules of Good Pharmacovigilance Practice of the Eurasian Economic Union” on 19 June 2022 and enacted it on 6 December 2022. A risk management plan (RMP) is a key component of pharmacovigilance system documentation to be submitted in the marketing authorisation dossier for a medicinal product.
The aim of the study was to review the changes to the requirements for the RMP structure, content, and submission from a regulatory expert’s perspective.
Significant changes have been introduced to the requirements set by the regulatory authorities of the Eurasian Economic Union for RMPs for medicinal products. In particular, the requirements for the content of parts and modules of RMPs have been clarified and expanded. Furthermore, the amendments have introduced a new mandatory requirement that the information in parts and modules of the RMP and the dossier for a medicinal product should be consistent. Marketing authorisation holders have been provided with a detailed description of the conditions, procedures, and exceptional situations for submitting RMPs in dossiers. The updated requirements will help marketing authorisation holders improve and streamline their risk management processes.

A periodic benefit–risk evaluation report (PBRER) is a retrospective evaluation document enabling marketing authorisation holders to present the results of a critical analysis of the benefit–risk ratio of a medicinal product. PBRER submission and content requirements changed with the adoption of the second edition of the Guideline on Good Pharmacovigilance Practice of the Eurasian Economic Union (EAEU GVP Guideline) in 2022.
The aim of the study was to analyse the changes to the EAEU GVP Guideline requirements for the submission procedure and the content of PBRERs.
The authors analysed the main changes concerning the procedure for submitting PBRERs on multi-source and well-established medicinal products, herbal and homoeopathic medicines. The authors evaluated the updated requirements for the content of PBRER sections. The analysis identified no significant changes in the aim and concept of PBRERs.
The results of the analysis described in this article will help marketing authorisation holders improve the quality of PBRERs and ensure compliance with the new requirements of the EAEU GVP Guideline.

The Rules of Good Pharmacovigilance Practice of the Eurasian Economic Union (EAEU GVP Guideline) came into force in the EAEU Member States in 2017. Over the next 5 years, marketing authorisation holders and competent authorities managed to build effective pharmacovigilance systems. The current version of the EAEU GVP Guideline was published in May 2022 and enacted on 6 December 2022. Amongst the critical pharmacovigilance processes, a special place is reserved to the process of signal management.
The aim of the study was to analyse the new content of the EAEU GVP Guideline related to signal management.
The authors reviewed the amendments introduced to the module of the EAEU GVP Guideline on signal management. This article is the first scholarly publication in the Russian language on the updated signal management process. The key changes include a detailed consideration of terminology issues, signal validation and prioritisation processes, notifying competent authorities of signal evaluation results, managing emerging safety issues, and functions of new automated systems: an integrated database of adverse drug reactions and a system for tracking safety issues.

In paediatrics, it is a common practice to use pharmaceuticals outside the approved Summary of Product Characteristics (i.e. off-label). According to the literature, up to 45% of inpatient paediatric prescriptions and 10–20% of outpatient ones are for off-label uses. It is essential to analyse such uses, as it helps medical practitioners act reasonably and professionally.
The aim of the study was to explore the possibility of using spontaneous reports to assess the risks of the off-label use of cardiac medicinal products in children in the Irkutsk region.
Materials and methods. The authors analysed 25 reporting forms on adverse drug reactions (ADRs) in paediatric cardiac patients from the database of the Regional Centre for Drug Safety Monitoring of the Irkutsk Region and regional data from the Automated Information System (AIS) of the Federal Service for Surveillance in Healthcare of the Russian Federation (Roszdravnadzor) submitted in 2009–2020. The inclusion criterion for reporting forms was a causal relationship between the off-label use of a medicinal product and the ADR that was scored as “possible” or higher on the Naranjo probability scale.
Results. According to the reporting forms, the off-label use of cardiac medicinal products in children was associated with ADRs, such as angiooedema, cutaneous symptoms, and bronchospasm. The majority of ADRs (84%) were considered severe. The medicinal products were prescribed for heart failure, arterial hypertension, and cardiac arrhythmias. The majority of ADR reports (75%) were submitted by inpatient medical organisations.
Conclusions. The analysis of spontaneous ADR reporting databases is a simple and informative method for studying the safety of medicinal products. It is necessary to raise awareness of ADRs associated with off-label prescribing amongst paediatric cardiologists in order to reduce the incidence of ADRs. The following contributions will improve the quality of medical care: all parties involved with pharmaceuticals should adhere to good pharmacovigilance practices, medical practitioners should be actively involved in treatment safety monitoring, and the professional training curricula of paediatric cardiologists and paediatricians should include specific units on the practical functioning of pharmacovigilance.

Nurse-administered injections come with a special set of risks, including such pharmaceutical factors as preparation of medicinal products in a vial prior to administration, conditions of their further storage, labelling of packages, and the need for personalised dosing of solutions for injection.
The aim of the study was to analyse Russian state standard GOST R 52623.4-2015 and identify factors contributing to the risk of nursing staff’s errors in preparing, storing, and labelling of medicinal products for injection.
Materials and methods. The authors analysed GOST R 52623.4-2015 Technologies for Performing Simple Medical Services of Invasive Interventions and assessed the identified risks by the FMEA method (failure modes and effects analysis).
Results. The authors identified pharmaceutical risks, causes, and sources of hazardous events that occur during administration of parenteral medicinal products. The standard does not instruct readers on the order of mixing medicines in a vial and on choosing solvents for lyophilised powders. There is no labelling procedure for opened vials in the document. It does not stress the inadmissibility of pre-administration storage of a syringe/dropper with a medicinal product. The document lacks information on the need to warm the aqueous solutions that are stored in a refrigerator and/or administered at a temperature of 36–38 °С as per the package leaflet. The standard does not include a procedure for visual estimation of the volume of a solution drawn into a syringe for individual dosing of medicinal products to children. According to the FMEA risk assessment, the highest risks are posed by the order of mixing medicines in a vial and by the storage of syringes/droppers prior to administration to patients.
Conclusions. To improve the safety of injection therapy, it is necessary to supplement the state standard with the identified causes of hazardous events. Nursing staff in medical organisations would benefit from in-house training on prevention of pharmaceutical risks carried out with the help of specialists in pharmaceutics and from wider involvement in discussing pharmacotherapy errors.

Currently, gene therapy medicinal products (GTMPs) are actively developed in many countries, including the Russian Federation. However, the use of GTMPs raises class-specific safety concerns.
The aim of the study was to determine the main requirements for non-clinical safety testing of GTMPs, to identify risks associated with these medicinal products, to establish criteria for expert assessments, and to find optimisation opportunities for GTMP non-clinical safety programmes, using Russian and international experience in the assessment of submissions and the registration of medicinal products of this class.
The Russian Federation, the Eurasian Economic Union, the European Union, and the United States have created regulatory frameworks governing the lifecycle of GTMPs and continue improving these frameworks. The properties of GTMPs may create unique safety issues, such as insertional mutagenesis, unregulated transgene expression, long-term persistence and off-target spread, vertical germline transmission, and environmental risks. To account for these issues, a comprehensive non-clinical safety programme for GTMPs may require additional special studies along with the standard ones. This review focuses on the main approaches to designing non-cellular GTMP safety studies and evaluating the obtained results. The authors identified improvement opportunities for and problematic aspects of study design, as well as conditions for and limitations of non-clinical data extrapolation and clinical safety profile prediction. The continuous improvement and updating of the regulatory frameworks governing non-clinical studies of GTMPs mean that developers of non-clinical safety programmes for GTMPs should use all their experience, as well as relevant national and international guidelines and recommendations.

Contrast-induced nephropathy (CIN) is a serious adverse reaction to contrast agents used in radiography. It is important to study the epidemiology of CIN and the risk factors for developing the complication in order to improve the quality of care that patients receive during coronary interventions.
The aim of the study was to investigate the incidence of CIN after coronary angiography (CAG) with iopromide and analyse the cost-effectiveness of using this contrast agent in a multidisciplinary hospital in Volgograd.
Materials and methods. The first part of the study comprised a medical record review of 147 patients having undergone coronary interventions (CAG and its combinations with balloon angioplasty and stenting) in the cardiology department from September 2020 to October 2021. The review involved identifying CIN cases by serum creatinine changes, assigning CIN risk scores, and assessing the volume of the contrast agent used. The second part of the study included calculating the expenses of the hospital for purchasing the contrast agent, both in total and in average per CAG procedure.
Results. Having analysed serum creatinine changes, the authors identified CIN in 46 (31.3%) of CAG patients. According to Mehran risk scores for developing CIN, the baseline risk was high in 4 (2.7%) patients, moderate in 35 (23.8%) patients, and low in 108 (73.5%) patients. On average, a CAG procedure used 126.19 ± 36.35 mL of the contrast agent. The volume of the contrast agent exceeded 100 mL in 66 (44.9%) patients and the maximum acceptable contrast dose (MACD) in 8 (5.4%) patients. The MACD values were calculated using R.J. Cigarroa’s formula. The average cost of a CAG procedure amounted to 1927.8 rubles.
Conclusions. The authors identified CIN in one third of the CAG patients, and the highest incidence was observed in patients with diabetes mellitus and a high risk according to the Mehran score. The risk of developing CIN increased upon exceeding the maximum acceptable volume of the contrast agent. To reduce the risk of CIN, the authors recommend including MACD calculation using R.J. Cigarroa’s formula and risk assessment using the Mehran score in percutaneous coronary intervention protocols.

Cephalosporins are the empirical antibiotic therapy (ABT) of choice for patients with community-acquired pneumonia (CAP). When treated with antibiotics, elderly patients, especially those with comorbidities, are at higher risk of developing adverse drug reactions (ADRs).
The aim of the study was to analyse data on the safety and efficacy of initial empirical ABT with cephalosporins in elderly patients over 75 years old with CAP admitted to multidisciplinary hospitals in Moscow.
Materials and methods. The retrospective study included 305 medical records of patients with CAP admitted to three multidisciplinary hospitals in Moscow in 2017–2019 and prescribed initial mono- and/or combination ABT including a cephalosporin. Initial ABT was considered effective if the body temperature normalised within 48–72 h from the start of treatment. It was considered safe if there were no ADRs during hospital stay.
Results. Mostly, patients were prescribed ceftriaxone monotherapy or ceftriaxone and azithromycin combination therapy. These ABT regimens were effective in 69.07% and 78.10% of the cases, respectively. Patients with severe CAP needed their initial ABT adjusted significantly more often than those with non-severe CAP. The initial ABT was changed for a number of reasons, including ineffectiveness, ADRs, abscesses formed as a complication of CAP, sputum culture results enabling causal ABT, secondary hospital-acquired infections, and exacerbated chronic infections. All patients had comorbidities, and the most prevalent were arterial hypertension (83.9%), coronary heart disease (45.6%), chronic heart failure (44.9%), cerebrovascular disease (40.9%), atrial fibrillation (26.9%), diabetes mellitus (21.3%), and chronic obstructive pulmonary disease (19.0%). Initial ABT was significantly more often considered ineffective in patients with chronic heart failure and cerebrovascular disease. The most common causative agent of CAP in the study population was Streptococcus pneumoniae (31.9%). In 16% of patients, the authors identified ADRs associated with the antibiotics used as initial therapy. The most common were diarrhoea, anaemia, leucopenia, and hepatopathy. Ceftriaxone was associated with ADRs in 11% of patients.
Conclusions. The study results suggest that initial mono- and/or combination ABT including a cephalosporin is effective and relatively safe; therefore, this treatment option is expedient for elderly patients with CAP. For this population, the safety of ABT may be improved through the wider use of existing markers of ADRs and the identification of new ones.