Periodic Safety Update Reports Research Articles

Predicting the submission frequency of periodic safety update reports: development and application of the EURD tool.

Periodic Safety Update Reports (PSURs) are a key pharmacovigilance tool for the continuous evaluation of the benefit-risk balance of a medicinal product in the post-authorisation phase. The PSUR submission frequency for authorised active substances and combinations of active substances across the EU is individually determined. The objective of this research was the development and application of the EURD tool, a statistical method based on readily available safety data to predict PSUR frequencies and to ensure a consistent risk-based approach. First, variables considered relevant in determining the PSUR frequency were identified from data sources available at the European Medicines Agency. A subsequent first survey with National Competent Authorities in Europe lead to a prioritisation of identified variables, while a second survey was carried out to propose the PSUR frequencies for a set of substances. Finally, a regression model was built on the information collected, applied to a larger list of substances and its results tested via a third survey with the same experts. The developed EURD tool was applied to the 1,032 EURD list entries with a PSUR assessment deferred to 2025 at the time of the creation of the list in 2012. As the number of procedures would have had a significant impact on the workload for the European Medicines Regulatory Network (EMRN), in a second step the workload impact was estimated after allocating the entries according to their proposed frequency. The analysis suggests that all entries could be reviewed by 2038 by increasing the median workload by 15% (from 868 to 1,000 substances/year). The EURD tool is the first data-driven application for supporting decision making of PSUR frequencies based on relevant active substance safety data. While we illustrated its potential for improving the assignment of PSUR submission frequencies for active substances authorised in the EU, other institutions requiring periodic assessment of safety data and balancing of the resulting workload could benefit from it.

Assessment of pharmacovigilance guidelines in the Southern African Development Community: A document review.

Lack of harmonization in pharmacovigilance (PV) practice in resource-limited states in Africa has led to differentiation and marginalization, thus creating an environment where weak or absent PV systems may benefit from regional guidelines. To compare the PV guidelines of Southern African Development Community (SADC) member states to international guidelines and identify areas for improvement for aligning PV practice within the SADC region. We utilized a 73-item checklist to assess the PV guidelines of the SADC member states. Checklist parameters were rated using binary scoring. Only seven (Botswana, Mauritius, Namibia, South Africa, Tanzania, Zambia, and Zimbabwe) of the 16 SADC member states had guidelines to assess. Of these, only four had supporting legislation. All seven national medicines regulatory authorities (NMRA)'s guidelines required reporting of local serious adverse drug reactions (ADRs). Four NMRAs implemented device vigilance; none specified submission timelines for ADRs associated with substandard or falsified medicines. Only three NMRAs required electronic transmission of individual case safety reports in the E2B format. Five NMRAs mandated safety monitoring during interventional clinical trials. Five NMRAs required aggregate reporting through periodic safety update reports. Only two NMRAs required submission of the development safety update report. Regarding risk management, four NMRAs required notification of actions taken by foreign NMRAs and four NMRAs expected to review Dear Healthcare Professional Letters before distribution by the marketing authorization holder. Areas for improvement of guidelines to establish common process standards and allow for synchronized submissions of comparable data to SADC NMRAs are provided.

PP23 Lost In Translation? The Differences In The Use Of Real-World Evidence Across Key Markets

IntroductionHealth Technology Assessment (HTA) agencies have recognized the importance of real-world evidence (RWE) to inform access decision-making and different HTA agencies establish distinct requirements for their local jurisdictions. The objective of this study is to understand the differences of RWE included in HTA reports and HTA agencies’ perception of RWE.MethodsHTA reports from agencies in France, Germany, Spain, Italy, United Kingdom (UK), Canada, Australia and South Korea from January 2011 to November 2021, including original submissions, resubmissions, extensions of original indications and renewals were analyzed.ResultsAcross the eight countries, RWE has been used in nineteen percent of all HTA reports (N=2,960/15,561), with an exponential increase observed between 2019 and 2021. RWE on clinical effectiveness was mostly used in HTA submissions in the UK (twenty-two percent), with twenty-six percent perceived with full acceptance. In contrast, RWE on safety and epidemiology was reported widely in HTA reports in France and Germany (83% and 87%), respectively. Ninety-three percent of RWE received full acceptance in France, followed by forty-four percent in Germany. A mixed picture of the types of RWE included in HTA reports was observed in the other countries, with high variance of acceptance (between 5 to 37%).ConclusionsFrance, Germany, and the UK are the top three countries with a large proportion of HTA reports where RWE was mentioned. The type of RWE used is related to a large extent to the local evidence requirements. For example, RWE around epidemiology was included widely in Germany due to the needs of providing local data for budget impact analyses required by the Federal Joint Committee (G-BA); RWE on tolerability as reported in periodic safety update reports (PSURs) needs to be included in French HTA submissions. RWE on clinical effectiveness has been evaluated the most by the UK HTA bodies.

34346 Pooled safety analysis of respiratory tract infections, including COVID-19, in psoriasis patients treated with secukinumab

Objective: To assess risk of respiratory tract infections (RTIs) in secukinumab treated psoriasis patients, evaluate potential association of COVID-19 risk factors [age >65, diabetes, obesity (BMI >40), heart and respiratory disease] with RTI incidences and report COVID-19 cases from Periodic Safety Update Report (PSUR: 26-Dec-2019–25-Dec-2020). Methods: Pooled data from clinical trials and postmarketing safety surveillance, including patients who received ≥1 secukinumab dose, were analyzed. RTIs were reported as exposure-adjusted incidence rates (EAIRs) per 100 patient-years. Results: EAIR (95% CI; n) for ‘any RTI’ with secukinumab 150 mg/300 mg/150 mg+300 mg, was 42.1 (39.6–44.8; n = 2117)/47.5 (46.1–48.9; n = 9704)/46.6 (45.3–48.0; n = 11232). EAIR for ‘viral RTI’ at same doses was 7.1 (6.2–8.0)/7.4 (6.9–7.9)/7.3 (6.9–7.7), and for ‘other RTI’ was 34.3 (32.1–36.6)/38.8 (37.5–40.1)/ 37.7 (36.6–38.9). EAIR ratios in obese versus nonobese patients for viral pharyngitis/streptococcal pharyngitis/bacterial sinusitis with secukinumab 150 mg+300 mg were 4.2 (1.2–15.1)/3.4 (1.7–7.0)/6.9 (2.1–22.3), respectively. Strong associations with other COVID-19 risk factors were not observed. Of 952 COVID-19 cases retrieved, outcome was reported in 416 cases: completely recovered (n = 101), recovered with sequelae (n = 7), condition improving (n = 68), unchanged (n = 165), deteriorated (n = 54) and fatal (n = 21). Overall, 221 cases were confounded by risk factors (age >65, comorbidities, or concomitant use of immunosuppressant). Of 21 COVID-19 fatal cases, 14 had risk factors (age >65, comorbidities and smoking) whereas 7 had limited information. Conclusion: RTIs in secukinumab treated psoriasis patients from pooled clinical trials and postmarketing surveillance data were consistent with previous publications. In this analysis, obesity increased the risk for RTIs. COVID-19 cases in the PSUR revealed no new safety signals regarding known risk of ‘infections and infestations.’

Postmarketing pharmacovigilance: Remdesivir and cardiovascular events.

Postmarketing pharmacovigilance: Remdesivir and cardiovascular events.

Spontaneous Reporting Method Used for Safety Evaluation of Nonsteroidal Anti-Inflammatory Drugs and Paracetamol Products, Based on Assessment of Data from Periodic Reports

High rates of adverse drug reactions (ADRs) associated with nonsteroidal anti-inflammatory drugs (NSAIDs), as well as their irrational and uncontrolled use for self-medication require continuous updating of information on safety profiles of these products.The aim of the study was to assess the reporting rate, frequency, and severity of ADRs to NSAIDs and paracetamol products, based on data from periodic safety update reports (PSURs) submitted to the autonomous non-profit organisation “National Pharmacovigilance Research Centre”.Materials and methods: the study covered 104 PSURs for NSAIDs and paracetamol products. Consumption levels were calculated in patient days (PTDs) and patient years (PTYs) for each international nonproprietary name (INN). The authors also analysed clinical manifestations and severity of ADRs.Results: the total number of PTDs and PTYs for all NSAIDs and paracetamol products, including combination medicines, was 1 963 750 485 PTDs or 5 380 138.3 PTYs, respectively. The PSURs reported 459 ADRs, of which 304 (66.2%) were serious ADRs (SADRs). The comparative analysis of ADR frequencies, expressed as the “ADR/PTY” ratio, for individual products, helped to identify INNs with the highest reporting rates.Conclusions: high ADR/PTY and SADR/PTY values indicating better ADR reporting for some INNs, were observed for piroxicam, paracetamol, dexketoprofen, and ketoprofen, while the lowest values were observed for the “acetyl salicylic acid+caffeine+paracetamol” combination, acetylsalicylic acid, and phenylbutazone. Thus, the comparison of ADR/PTY and SADR/PTY ratios can be recommended as an inclusive approach both for analysis of reporting trends for individual products and for comparison of reporting rates of different medicinal products.

EU MDR 2017/745 will reduce the Risk of Medical Devices. Does MDCG got it Right?

Under the new European Union Medical Device Regulation (EU MDR), framed by Medical Device Coordination Group (MDCG), for each device manufacturers must have a documented risk management plan, identify and analyse the known and foreseeable hazards, estimate and evaluate the associated risks and eliminate or control those risks. In contrast with the MDD, the new EU MDR contains an explicit obligation in the new Article 10 (2), that manufacturers establish, document, implement and maintain a system for risk management. The detailed requirements of which are listed in the new Annex I Chapter I.
 Compared to MDD there is more emphasis on Post Market Surveillance (PMS) activities with the inclusion of European Databank or European Database for Medical Devices (EUDAMED) and mandatory submission of Periodic Safety Update Report (PSUR) to all the actors in the possession with the medical devices.
 A poll conducted by Aegis Lifesciences Pvt. Ltd, Ahmedabad, India concludes that the relevant annexures and sections in MDR 2017/745 have more emphasis on PMS, Vigilance, PSUR, EUDAMED, tracking, Implantation card etc. that are directed in regard to the safety of the Medical Device.

14. Postmarketing Safety Experience With MenACWY-TT

BackgroundMenACWY-TT (Nimenrix®), a quadrivalent meningococcal tetanus toxoid conjugate vaccine, was first licensed in 2012 and is available in 82 countries but not in the United States. MenACWY-TT is administered in infants as a 2 + 1 (6 weeks to < 6 months of age) or 1 + 1 (6 to < 12 months of age) schedule with the booster dose at 12 months of age, and from 12 months of age as a single dose. In addition to its widespread use to protect against meningococcal serogroups A, C, W, and Y, MenACWY-TT is a constituent of an investigational pentavalent meningococcal (MenABCWY) vaccine currently undergoing clinical development. MethodsUsing the MenACWY-TT Periodic Safety Update Report (PSUR) with format and content in accordance with Good Pharmacovigilance Practice Module VII and International Council for Harmonisation Guideline E2C, for data up to April 19, 2020, postmarketing safety experience with MenACWY-TT is considered. The PSUR data included herein are spontaneous adverse events (AEs) from the Pfizer safety database. AEs were coded by system organ class (SOC) and preferred term (PT) using MedDRA v.22.1J. ResultsThe cumulative estimated exposure of MenACWY-TT was nearly 26 million doses, with the majority administered in 0- to 16-year-olds and in the Western European Union (Figure 1). Over the reporting period, 13,301 cumulative AEs occurred. The most common SOCs in the reporting period were general disorders and administration site conditions (n=5169; 39%); nervous system disorders (n=1986; 15%); injury, poisoning and procedural complications (n=1266; 10%); and gastrointestinal disorders (n=1031; 8%) (Figure 2). By PT, the most common AEs were pyrexia (n=1613; 12%), headache (n=738; 6%), and vaccination site pain (n=394; 3%) (Figure 3). Of the 3299 serious AEs reported, the most common were pyrexia (n=317; 10%) and headache (n=209; 6%). ConclusionBased on cumulative safety data in conjunction with existing efficacy and effectiveness data, the benefit-risk profile of MenACWY-TT remains favorable and is consistent with the safety profile of MenACWY-TT established in clinical studies. Disclosures Lidia Serra, MS, Pfizer Inc (Employee, Shareholder) Susan Mather, MD, Pfizer Inc (Employee, Shareholder) Cindy Burman, PharmD, Pfizer Inc (Employee, Shareholder) Chris Webber, MD, Pfizer (Employee, Shareholder)

Pharmacovigilance in generic Indian pharmaceutical industries - Need of the moment

Introduction: The pharmacovigilance department is liable for monitoring the safety of medicines during clinical trials and normal clinical use. The necessity of the pharmacovigilance department is an utmost requirement for effective regulations of the drug approval process and conscious pre and post-approval vigilance of the undesired effects, especially in India.&#x0D; Methods: In the light of the regulatory notification GSR 287(E) dated on 8th march 2016 by CDCSO, it has become clear that it is necessary to take measures to set up and improve the operation of the pharmacovigilance of medicinal products for human use in pharmaceutical companies. &#x0D; Results: The regulators have also developed and posted Guidance document for marketing authorization holders (MAH) for Indian marketers and made clear that the MAH should be responsible for continuously monitoring the safety of its medicinal products for human use, for updating the health authorities of any changes related to the drug, and for ensuring that the product information is kept up-to-date. MAH should record all suspected adverse reactions occurring in the country, and which are brought to their attention spontaneously by the patients or their health care, or occurring in the context of the post-authorization study.&#x0D; Conclusions: According to the Regulatory Guidance document, MAH is also responsible for the submission of the information on suspected adverse reactions of a newly approved drug or applicable product, in form of periodic safety update reports (PSURs), to the competent authorities.

Adverse event reporting tools and regulatory measures in India through outcome of Pharmacovigilance Programme of India.

The primary care medical practitioners as well as common public must be made aware of the importance and benefits of reporting adverse drug reactions (ADRs). The reporting of ADRs through periodic safety update reports is a regulatory requirement in many countries including India, however, the importance of ADR reporting through spontaneous reporting system cannot be ignored. After the initiation of Programme for International Drug Monitoring, WHO-Uppsala Monitoring Centre (UMC), Sweden, succeeded in establishing a worldwide pharmacovigilance (PV) network in >150 countries. As a full member of this program, India also has developed a robust PV system through Pharmacovigilance Programme of India (PvPI) involving its various ADR Monitoring Centers and after due quality check of Individual Case Safety Reports (ICSRs), submits this information to UMC through a web-based tool VigiFlow®. This information is then stored into VigiBase® which is the repository of worldwide ICSRs. Based on the drug safety information collected, PvPI issues alerts, recommends label change (if any), and identifies signals thereby supporting National Regulatory Authority. At national level, PvPI has developed several tools for reporting of ADRs by the stakeholders. This article provides an overview of adverse events reporting tools in India vis-a-vis selected countries around the world, based on a comparative literature search. This article also throws light upon the regulatory aspects of PV in India, findings of PvPI and its recommendations to Central Drugs Standard Control Organization, collaboration of PvPI with Public Health Programmes, future prospects of reporting ADRs in India and how it will help enhance the quality of ADR-reporting by citizens of India.

Renal ischemic adverse drug events related to tranexamic acid in women of child-bearing age: an analysis of pharmacovigilance data

PurposeIn response to a large trial, the World Health Organization broadened their recommendation on tranexamic acid to be used for post-partum hemorrhage. A 2013 French periodic safety update report warned of an abnormally high rate of renal cortical necrosis associated with tranexamic acid and other drugs for severe post-partum hemorrhage. We aimed to identify the reporting incidence of adverse thrombo-embolic events among women in child-bearing age who received tranexamic acid, with a focus on renal vascular and ischemic conditions.MethodsWe analyzed individual case safety reports (ICSRs) on renal vascular and ischemic conditions, pulmonary thrombotic and embolic conditions, and peripheral embolism and thrombosis from the database of the World Health Organization – Uppsala Monitoring Centre (WHO-UMC). ICSRs were restricted to reports including tranexamic acid as a suspected drug, sex reported as female, and reported age between 18 and 44 years. Reporting odds ratios (RORs) and 95% confidence intervals (95% CIs) were calculated by comparing ICSRs on tranexamic acid to all other drugs in VigiBase.ResultsWithin 2245 included ICSRs on tranexamic acid, we identified 29 reports of adverse renal vascular and ischemic conditions, 42 reports of pulmonary thrombotic and embolic conditions, and 41 reports of peripheral embolism and thrombosis. RORs were statistically significant by 32.6-fold (32.62, 95% CI: 22.50–47.29), 2.5-fold (2.52, 95% CI: 1.85–3.42), and 2.7-fold (2.67, 95% CI: 1.96–3.64), respectively, when compared to any other drug within VigiBase.ConclusionTranexamic acid might bear an increased risk for renal ischemic adverse drug events in women of child-bearing age.

Pharmacovigilance: procedures for uniform assessment of periodic safety update reports and their implementation in national settings. Focus on analgesics

Pharmacovigilance activities are of vital importance for ensuring effective and safe medicinal products. In order to clarify to which extent marketing authorisation holders (MAHs) meet the requirements of the Law and the Directives related to this activities, we conducted a systematic search among the procedures submitted to the Bulgarian Drug Agency (BDA) related to the implementation of the decisions of the Pharmacovigilance Committee and the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) for a period of 6 years. The results of the study showed significant discrepancies between regulatory requirements and the behavior of the MAH at the national level. This could be a serious problem, as inadequate or late implementations of the PRAC (Pharmacovigilance Risk Assessment Committee)/CMDh/EC recommendations can lead to untimely informing of healthcare professionals and patients about potential safety concerns and risks related to the use of medicinal products.

Commentary - A comprehensive safety understanding of granulocyte-colony stimulating factor biosimilars and Intended Copy Biologics in treating chemotherapy associated febrile neutropenia

Filgrastim, human white cell growth factor, Granulocyte colony-stimulating factor (G-CSF), is a core medicine in the WHO list of Essential Medicines. For this reason, recent reporting of statistically significant safety and efficacy differences between reference and Biosimilar brands of filgrastim by Rastogi and the Indian Pharmacopoeia Commission in Toxicology and Applied Pharmacology in 2020 is of great concern [Shruti Rastogi et al. Towards a comprehensive safety understanding of granulocyte-colony stimulating factor biosimilars in treating chemotherapy associated febrile neutropenia: Trends from decades of data. Toxicology and Applied Pharmacology Volume 395, 15 May 2020, 114,976. https://doi.org/10.1016/j.taap.2020.114976]. This commentary shows that the alarming report is a result of incorrect statistical tests misapplied to inappropriate data sets compounded by a further problem relating to the strict regulatory definition of a Biosimilar Medicine as opposed that of an Intended Copy Biologic. In contrast, the body of evidence from more than seven and a half thousand participants in Confirmatory Clinical Studies and Post Approval Clinical Studies as well as the Periodic Safety Update Reports confirms that European approved filgrastim Biosimilars show no meaningful difference in quality, safety or efficacy compared to the reference brand.

Incidence of Uveitis in Secukinumab-treated Patients With Ankylosing Spondylitis: Pooled Data Analysis From Three Phase 3 Studies.

ObjectiveThe objective of this study was to report the incidence of uveitis in secukinumab‐treated patients with ankylosing spondylitis (AS) in a pooled analysis of three phase 3 trials (MEASURE 1‐3 [ClinicalTrials.gov identifiers NCT01358175, NCT01649375, NCT02008916]).MethodsAnalysis included pooled patient‐level data from all patients (N = 794) who received any dose (one or more) of secukinumab up to the last patient attending the week 156 study visit in MEASURE 1 and up to the week 156 visit in MEASURE 2 and the week 104 visit in MEASURE 3 for each patient. Postmarketing data were from the periodic safety update report. Incidence of uveitis is reported as the exposure‐adjusted incidence rate (EAIR) per 100 patient‐years of secukinumab exposure.ResultsOverall, 135 (17%) patients reported preexisting (but not active or ongoing) uveitis at baseline, and 589 (74.2%) patients were HLA antigen B27 positive. The EAIR for uveitis was 1.4 per 100 patient‐years over the entire treatment period. Among all cases of uveitis (n = 26), 14 (54%) were flares. The exposure‐adjusted reporting rate of uveitis in the postmarketing data (which included patients across the three approved indications of psoriasis, psoriatic arthritis, and AS) was 0.03 per 100 patient‐years based on cumulative secukinumab exposure of 96 054 patient‐years.ConclusionThe incidence rate of uveitis in secukinumab‐treated patients with active AS does not suggest an increased risk with secukinumab treatment.

Impact of increased focus on pharmacovigilance on knowledge and attitude towards adverse drug reaction reporting among medical students in India.

Recent years have seen a surge in pharmacovigilance (PV) related activities in India. In the present study the impact of these initiatives on medical students from across the country was evaluated to identify their effectiveness, lacunae and arrive at remedial measures. A cross-sectional, questionnaire based study was conducted. The survey questionnaire consisted of 28 multiple response items. The areas covered included subject knowledge (theoretical and practical), attitude and awareness towards pharmacovigilance. The survey participants (n = 253) were from 71 medical colleges and 17 states across India. While 60% of the participants were familiar with the term 'Pharmacovigilance', many could not distinguish side effect and adverse drug reaction. The majority was unaware that 'Periodic Safety Update Report' (PSURs) is a mandatory pharmacovigilance activity by the industry. 91% felt reporting is a useful practice and causes for under-reporting are a lack of awareness followed by attitude, misconceptions about what to report, fear of litigation and interestingly the least important is lack of time. However, most were reluctant to have reporting as mandatory tool; they would rather use it voluntary. In spite of collaborative and synchronized efforts by various agencies there is a need to further improve the PV milieu in India by confidence building exercises, imparting training on PV programme, updating of the current knowledge on PV and also sustaining motivation.

Overview of Periodic Safety Update Reports: Where Have We Reached?

Periodic safety update report (PSUR) is now known as the Periodic Benefit-Risk Evaluation Report (PBRER). In July 2012, as per the new European Legislation, 16 Good Pharmacovigilance Practices (GVP) modules came into effect by replacing Vol 9A guidelines. GVP module VII provides the guidance for the preparation, submission and assessment of PSURs. There are twice as many sections to the new PSUR as compared to ICH E2C (R1) document and Volume 9A PSUR guidelines. The new legislation mainly focuses on benefit-risk assessment of medicinal product and promises much more, but after more than 6 years, how much new lesiglation is able to deliver is still unclear. In the literature, various articles have been published regarding the new Legislation module VII but none of them have highlighted the differences between old and new Legislation, How successful are we? What challenges are we facing? The understanding all these points is the need of the hour for Pharmacovigilance audience which will be helpful to implement the Pharmacovigilance (PV) in a more efficient and effective way. Thus, in this article, we have explained the differences between new and old Legislation and when they come into play. Finally, this article provides a brief examination of current challenges and future perspectives of periodic safety update reporting.

Recent changes in the pharmacovigilance system in the Russian Federation and the EAEU

The Eurasian Economic Union (EAEU) is an international organization for regional economic integration, established by the Treaty on the Eurasian Economic Union, which currently includes 5 countries - Russia, Kazakhstan, Belarus, Armenia and Kyrgyzstan. The EAEU ensures the freedom of goods movement, as well as services, capital and labor, conducting a coordinated, agreed/unified economic policy. The current practice of pharmacovigilance in the EAEU is of interest to potential foreign investors and market players. The aim of this study was to analyze the recent changes in pharmacovigilance in the EAEU countries in order to adopt the strategy of the pharmaceutical industry players. Materials and methods . The regulatory base of pharmacovigilance in the EAEU countries and the unified EAEU provisions on adverse reactions (ADR) were analyzed. A critical analysis of the current periodic safety update reports (PSUR) and risk management plans (RMP) was also carried out. Results. The united EAEU drug market is a complex system that incorporates 35 regulations, including the variety of good practice guidelines regarding the circulation of medicinal products (GMP, GCP, GLP, GDP, and GVP). This group of regulations contains basic documents on the inspection of production lines, the assessment of generic equivalence, the development of biological drugs, and the pharmacovigilance (PV). Currently, the ADR reporting in the EAEU countries is at a level lower than that in Russia. The common EAEU database of identified ADRs has been already initiated, but the number of incoming signals is quite small. The most common flaws of the PSUR are the late reports, the incorrect format and contents of those; the inconsistent information about the product, different from that of Roszdravnadzor, the discrepancy between the Patients information leaflet (“Instruction for medical use”) and the Summary of Product Characteristics (SmPC), and the lack of important and relevant scientific and clinical information. In the EAEU, the submission of Risk Management Plan (RMP) as part of the registration dossier is required for any new medication (New Chemical Entity), including a new combination of drugs. The present article also covers other updates in the Pharmacovigilance system, regulated by the Good Pharmacovigilance practice, which entered into effect on 01.01.2017, as well as the updated tasks for harmonization within the EAEU. Conclusions. The medicinal products circulating in the EAEU have to be checked for their efficacy and safety in order to identify possible negative consequences and/or individual patient intolerance. This information will serve to warn the medical staff and patients, veterinary specialists and animal owners about potential hazards of using these products. In the near future, the Eurasian Union plans to launch a “sanitation” campaign in the pharmaceutical market and get rid of low-effective and unsafe drugs. In this respect, the issues of pharmacovigilance become particularly relevant.

Impact of periodic safety update reporting system: A preliminary trial in a tertiary care teaching hospital of southern India

The objective of this study was to assess impact of implemented periodic safety update report (PSUR) system in our hospital via PSUR function assessment questionnaire (PFAQ) vetted by Delphi panel and by comparing frequency and rate of adverse drug reaction (ADR) reporting for three highly prescribed drugs. A PFAQ was validated by Delphi panel, in two successive rounds of revision and used to record responses on Likert scale. Drugs with well-known ADR profiles in published literature were considered reliable markers of the impact of PSUR system implementation. Pre-PSUR retrospective data retrieved from medical records for nine months and compared with the trend of frequency and rate of ADR reporting post-PSUR system implementation. Frequency and rate of ADR reporting for selected drugs rose by 68% post PSUR system implementation. Participation of wards in ADR reporting and reporting of unexpected/unreported ADRs was also seen increased. Numbers of PFAQ responses for each performance indicator corresponding to the respective success factors were seen shifting favorably on the Likert scale in phase 2 study period. This study illustrates how drug safety reporting network can be established by reallocating existing resources, with minimal expenses on training/human resources and to improve poorly designed pharmacovigilance system in India that relies heavily on data from overseas.

Preparation of a periodic safety update report

This article is a continuation of the publication «Standard form of a Periodic safety update report» in the previous issue of the journal. This article recommendations for the preparation of Periodic safety update report (PSUR) to ensure the development of this report document license holders of certificates of registration of drugs for subsequent submission to the section «Periodic report» Federal Database «Automated system of Pharmacovigilance» and subsequent evaluation of the Roszdravnadzor the information of scientific and clinical nature are presented. This practical advices with step by step recommendations for medical authors are presented.

Infanrix hexa and sudden death: a review of the periodic safety update reports submitted to the European Medicines Agency.

There have been a number of spontaneous reports of sudden unexpected death soon after the administration of Infanrix hexa (combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliomyelitis and Haemophilus influenza type B vaccine). The manufacturer, GlaxoSmithKline (GSK), submits confidential periodic safety update reports (PSURs) on Infanrix hexa to the European Medicines Agency (EMA). The latest is the PSUR 19. Each PSUR contains an analysis of observed/expected sudden deaths, which shows that the number of observed deaths soon after immunisation is lower than that expected by chance. This commentary focuses on that aspect of the PSUR which has a bearing on policy decisions. We analysed the data provided in the PSURs. It is apparent that the deaths acknowledged in the PSUR 16 were deleted from the PSUR 19. The number of observed deaths soon after vaccination among children older than one year was significantly higher than that expected by chance once the deleted deaths were restored and included in the analysis. The manufacturer must explain the figures that have been submitted to the regulatory authorities. The procedures undertaken by the EMA to evaluate the manufacturer's claims in the PSUR need to be reviewed. The Drugs Controller General of India nearly automatically accepts drugs and vaccines approved by the EMA. There is a need to reappraise the reliance on due diligence by the EMA.