Good Manufacturing Practice for Medicinal Products in Bulgaria: an Analysis of Regulatory Inspection Findings.

BACKGROUND: The manufacture of medicinal products for human use in the European Economic Area is governed by European Directives and Regulations stipulating the relevant principles and guidelines of Good Manufacturing Practice, describing the minimum standard to be fulfilled in the production processes. AIM: To present analysis of the deficiencies reported following Good Manufacturing Practice inspections in Bulgaria in two consecutive years (2016, 2017) and to compare them with results from similar inspections reported by other EU member states. MATERIALS AND METHODS: A retrospective study was carried out by reviewing the complete Good Manufacturing Practice inspection reports of all manufacturers conducted by the Bulgarian Drug Agency in 2016 and 2017, according to relevant requirements and applicable local legislation. The items reviewed were scope of inspection, type of companies, classification of deficiencies ­ 'critical', 'major' and 'other significant deficiencies', their nature and reference to EU Good Manufacturing Practice. RESULTS: The analyzed data included 55 inspections, revealing 460 various deficiencies, of which 2 were critical and 102 ­ major. Twenty inspections were performed in 2016 vs. 35 inspections in 2017. The pattern of deficiencies was similar to the findings of other EU regulatory agencies, showing that equivalent requirements were applied. Our analysis showed that Bulgarian Drug Agency inspectors rarely raised deficiencies related to Computer Systems, Qualification/Validation, Personnel and Qualification of Suppliers unlike other EU regulators agents. CONCLUSIONS: Our analysis of Good Manufacturing Practice inspection findings in 2016 and 2017 showed that the Bulgarian Drug Agency demonstrated its ability to detect non-compliances and take necessary regulatory actions. Quality related issues constitute the main reasons for non-compliances with the requirements.

Written Health Education Materials for Women with Gestational Diabetes Mellitus - Evaluation of Usefulness and Patients' Satisfaction.

BACKGROUND: Written health educational materials are an integral part of the treatment process. Because of the constantly increasing gestational diabetes mellitus (GDM) global rate, pregnant women require accessible, easy-to-understand and evidence-based medical information about this pregnancy complication. AIM: To adapt and elaborate printed educational materials on GDM and to evaluate the usefulness of the produced training materials and pregnant women's satisfaction. MATERIALS AND METHODS: The present study implemented a methodological approach covering three phases: (1) systematic literature review; (2) compilation of printed educational materials for pregnant women with GDM; (3) evaluation of the usefulness and satisfaction with the produced educational materials through a focus group consisting of pregnant women. A seven-item self-administered feedback questionnaire was adopted for evaluation of patient satisfaction after the use of educational materials. RESULTS: An educational manual was developed in compliance with the main requirements for effectiveness of educational materials referring to content, structure, language, layout and illustrations. The usefulness of the educational manual and patient satisfaction were evaluated by a sample group of 20 women with GDM. Approximately 95% agreed or strongly agreed that the information in the educational manual was useful. The patients' assessment of the understanding and readability of the written materials showed a satisfaction rate of 85%. The overall assessment for the educational materials was very high - excellent (65%), very good (30%) and good (5%). CONCLUSION: The provision of educational materials on GDM can enhance pregnant women's health literacy as well as their responsibility, motivation and attitude to their personal health.

Bulgarian Experience with Adverse Drug Reaction Reports from Patients and Consumers - Retrospective Data-base Study.

BACKGROUND: Since 2012, in compliance with the changes in the European legislation, the Bulgarian Drug Agency (BDA) has been receiving adverse drug reaction (ADR) reports directly from patients as well as from healthcare professionals and marketing authorization holders (MAH). Adverse reaction reports from patients and consumers have different characteristics from those sent by healthcare professionals. Moreover, they may require specific algorithm and assessment methods in order to be informative and beneficial to the pharmacovigilance system. AIM: The study aims to analyze the data-base of consumer reports in Bulgaria in order to distinguish and classify the main characteristics of the ADR reports from non-healthcare professionals. MATERIALS AND METHODS: In-depth analysis of the Bulgarian data-base of consumer ADR reports for 2012-2016 was conducted. The criteria include patient demographic characteristics, preferred method of reporting, seriousness and expectedness criteria and most frequently reported pharmacological groups. RESULTS: The data showed the current trends in patient reporting in the country. It also marked new courses for development of the spontaneous reporting system and collection of safety data. The analysis of the data-base showed a rather stable level of patient reporting with a tendency for constant growth every year. Bulgaria follows the world tendencies for high number of reports for insufficiently studied ADRs which meet the seriousness criteria. The review of the most frequently reported ATC codes could lead to the conclusion that the current pharmacovigi-lance methods are not sensitive enough for specific groups of medicines. CONCLUSIONS: The results from the conducted study confirm the importance of patient reporting as a valuable source of information on adverse drug reactions. Moreover, it draws the attention to the lack of more sensitive methods for evaluation of drug safety in specific pharmacological groups. Maintenance of consumer-friendly ADR reporting system and innovative assessment algorithms should be the future directions for development in post-marketing surveillance.

Assessment of the expectancy, seriousness and severity of adverse drug reactions reported for chronic obstructive pulmonary disease therapy.

INTRODUCTION: Adverse drug reactions can cause increased morbidity and mortality, and therefore information needs to be studied systematically. Little is known about the adverse drug reactions for chronic obstructive pulmonary disease therapy. The goal of this study is to assess the expectedness, seriousness and severity of adverse drug reactions during chronic obstructive pulmonary disease therapy based on their reporting in the national pharmacovigilance system. METHODS: This was a prospective, observational, 1-year, real-life study about the pharmacotherapy of a sample of 390 chronic obstructive pulmonary disease patients. Prescribed medicines were systematized and national pharmacovigilance databases were searched for reported adverse drug reactions. The expectedness was evaluated through the review of the summary of product characteristics, the seriousness was evaluated by the clinicians based on the life threatening nature of the adverse drug reactions, and the severity was evaluated through Hartwig's Severity Assessment Scale. Descriptive statistics of the reported adverse drug reactions was performed and the relative risk of developing an adverse drug reaction with all international non-proprietary names included in the analysis was calculated. RESULTS: Results confirm that the chronic obstructive pulmonary disease is a disease with high appearance of adverse drug reactions, and causes many additional costs to the healthcare system. Unexpected and severe adverse drug reactions are frequent. A total of 4.8% of adverse drug reactions were evaluated as life threatening. Majority of adverse drug reactions are classified in Levels 1 (32.6%), 2 (26.4%) and 3 (19%) according to Hartwig's Severity Assessment Scale. Approximately 22% of reported adverse drug reactions affect people's everyday life to a greater extent and require additional therapy which might further increase the risk. The relative risk of developing an adverse drug reaction was highest for novphyllin (relative risk = 0.65), followed by aclidinium bromide (relative risk = 0.09). Both indacaterol and salbutamol are with a relative risk of 0.07. CONCLUSION: In conclusion, the medicines for chronic obstructive pulmonary disease cause many serious adverse drug reactions, most of them were unexpected, lacking in the short product characteristics. Appropriate reporting of adverse drug reactions is necessary to decrease the risk of patients and healthcare system.

ISO 9001 certification for hospitals in Bulgaria: does it help service?

The aim of our study is to review the published literature on establishment and implementation of ISO 9001 QMS in European hospitals, to study the availability of International Organization for Standardization (ISO) quality management systems (QMS) in Bulgarian hospitals and to outline the main advantages of ISO implementation in the hospitals in Bulgaria. The information on availability of ISO QMS in the hospitals in Bulgaria was gathered via Bulgarian certification register, the registries of various quality associations, websites of hospitals and certification companies presented in Bulgaria. A total number of 312 hospitals in Bulgaria were screened for the availability of QMS certified against the ISO 9001 requirements. The experience of European hospitals that implemented QMS is positive and the used approaches to improve the processes and the demonstrated effects from ISO implementation are analysed by the researchers. Unlike other European Union member states, the establishment of quality management systems in Bulgaria is not compulsory. However, our study revealed that 14.42% of the hospitals in Bulgaria have implemented and have certified quality systems against the requirements of ISO 9001. Our study confirmed that a quality management system using the ISO 9001 standard is useful for the hospitals as it can help to increase the operational efficiencies, to reduce errors, improve patient safety and produce a more preventive approach instead of a reactive environment.

Use of complementary and alternative medicine by children in Europe: published data and expert perspectives.

INTRODUCTION: Few data document the use of complementary and alternative medicine (CAM) in Europe, with even fewer investigating use by children. METHODS: A narrative, non-systematic review of CAM use in Europe was performed by combining data from published surveys with expert perspectives. Limitations created by a lack of representative studies, varying definitions of CAM use, and what qualifies as CAM in different countries was partially overcome by integrating local experts to summarise information available only in the national language and provide their perspectives about CAM availability, quality, use and popularity in their countries using a semi-structured questionnaire. Local and international published surveys were summarised, and the prevalence of CAM use was extrapolated. RESULTS: Data from 20 European countries were available, representing 69% of the European population. Some data about CAM use by the general population were available for 90% of the examined countries, whereas peer-reviewed published surveys were available for only 60%. We extrapolated that 56% (range: 10-90%, adjusted for population size) of the European population in general had used CAM at least once in the past year. Surveys in CAM use by children were available for 55% of the investigated countries. The extrapolated prevalence of CAM use by children in Europe was 52% (range: 5-90%, adjusted for population size). Paediatric CAM experts reported an increasing awareness for and use of CAM in healthcare institutions. CONCLUSION: This precursor for further surveys indicates that CAM appears to be popular not only among adults in Europe, but also for children. Development of a pan-European definition of CAM use and CAM therapies are required to achieve surveys comparable between European countries. Additionally, more research investigating the efficacy and potential adverse effects of CAM therapies is needed because of increasing CAM use by children in Europe.

Pharmacy network and access to medicines in selected eastern European countries: comparative analysis.

AIM: To analyze the pharmacy network (structure and resources) in Bulgaria, Croatia, Serbia, and Slovenia and its relation to public expenditures for medicines. METHODS: We performed a cross-sectional study using the officially published data for the period 2003-2008 in four selected countries. Data sources were relevant national institutions. RESULTS: In 2008, Serbia had 27.5, Bulgaria 66.8, Croatia 59.5, and Slovenia 71.2 pharmacists per 100000 inhabitants. There was a significant difference in the number of pharmacists per 100000 inhabitants between all countries except between Bulgaria and Slovenia. The number of inhabitants per one pharmacy was significantly different between all observed countries. The expenditures for medicines per capita in 2008 were between €30.34 in Bulgaria to €137.03 in Slovenia, with a significant difference between all countries except between Bulgaria and Serbia. The number of pharmacists per 100000 inhabitants and expenditures for medicines per capita were positively correlated in all observed countries, except in Bulgaria. CONCLUSION: There were significant difference in the structure and availability of the pharmacy service in all selected countries. Expenditures for medicines were positively correlated with the number of pharmacists in all countries, except in Bulgaria. Our findings could be valuable to national regulatory bodies for the creation of national drug policies.