Positive List Research Articles

Domestication of the Dromedary Revisited and Its Consequences for Legislation as to Keeping Livestock or Pet Animals.

Being in an advanced stage of domestication is a newly proposed requirement to decide which animals can be safely kept by humans. Dutch legislators were the first to apply it and other European countries may be tempted to adopt a similar approach. Unexpectedly, the Dutch assessors considered the dromedary (Camelus dromedarius) as being insufficiently domesticated and this species will therefore no longer be able to be kept as a production animal from 2024 onwards. In a recent publication on this topic, we showed that the domestication of the dromedary is actually very advanced. In this paper, we apply the same criteria that were used by the Dutch assessors to determine the degree of domestication, taking into account the most recent scientific developments in this area, even though it should be noted that these criteria have neither been peer-reviewed, nor published in an international scientific journal. For the sake of comparison, and in order to validate the procedure, we also applied these criteria to the house cat. The results confirm that the dromedary is highly domesticated, but also that the house cat (Felis silvestris catus) is at most semi-domesticated. Obviously, we agree with the decision of the Dutch legislators to place the house cat on the positive list, but our analysis demonstrates that this was decided on false grounds. Our analysis makes it clear that the requirement of being in an advanced stage of domestication is not suitable. Instead of maintaining this requirement, we recommend implementing evidence-based, peer-reviewed methods to decide which animals can be kept by humans, and to include species specific-guidelines in the legislation on how this can be achieved safely.

Elevated nuclear PIGL disrupts the cMyc/BRD4 axis and improves PD-1 blockade therapy by dampening tumor immune evasion.

To improve the efficacy of lenvatinib in combination withprogrammed death-1 (PD-1) blockade therapy for hepatocellular carcinoma (HCC), we screened the suppressive metabolic enzymes that sensitize HCC to lenvatinib and PD-1 blockade, thus impeding HCC progression. After analysis of the CRISPR‒Cas9 screen, phosphatidylinositol-glycan biosynthesis class L (PIGL) ranked first in the positive selection list. PIGL depletion had no effect on tumor cell growth in vitro but reprogrammed the tumor microenvironment (TME) in vivo to support tumor cell survival. Specifically, nuclear PIGL disrupted the interaction between cMyc/BRD4 on the distant promoter of target genes and thus decreased the expression of CCL2 and CCL20, which are involved in shaping the immunosuppressive TME by recruiting macrophages and regulatory T cells. PIGL phosphorylation at Y81 by FGFR2 abolished the interaction of PIGL with importin α/β1, thus retaining PIGL in the cytosol and facilitating tumor evasion by releasing CCL2 and CCL20. Clinically, elevated nuclear PIGL predicts a better prognosis for HCC patients and presents a positive correlation with CD8 + T-cell enrichment in tumors. Clinically, our findings highlight that the nuclear PIGL intensity or the change in PIGL-Y81 phosphorylation should be used as a biomarker to guide lenvatinib with PD-1 blockade therapy.

HTA7 The Price of Innovation – Oncology Treatments Expenditures: Case from Bulgaria

Beginning in late 2015, health technology assessment (HTA) has taken the lead as the essential tool for governing how new pharmaceuticals are introduced and used in Bulgaria. Since 2017, the National Health Insurance Fund (NHIF) has reimbursed for all oncology medications included on the positive drug list (PDL) following a positive HTA recommendation. The purpose of this study is to describe the evolution of total annual cancer treatments expenditures from 2017 to 2021 following the introduction of HTA as a tool for healthcare decision-making.

Eleven-Year Trends in Lipid-Modifying Medicines Utilisation and Expenditure in a Low-Income Country: A Study from the Republic of Srpska, Bosnia and Herzegovina.

In last two decades, there have been substantial changes in the pattern of lipid-modifying medicines utilisation following the new treatment guidelines based on clinical trials. The main purpose of this study was to analyse the overall utilisation and expenditure of lipid-modifying medicines in the Republic of Srpska, Bosnia and Herzegovina during an 11-year follow-up period and to express its share in relation to the total cardiovascular medicines (C group) utilisation. In this retrospective, observational study, medicines utilisation data were analysed between 2010 and 2020 period using the ATC/DDD methodology and expressed as the number of DDD/1000 inhabitants/day (DDD/TID). The medicines expenditure analysis was used to estimate the annual expenditure of medicines in Euro based on DDD. During the analysed period, the use of lipid-modifying medicines increased almost 3-times (12.82 DDD/TID in 2010 vs 34.32 DDD/TID in 2020), with a rise in expenditure from 1.24 million Euro to 2.15 million Euro in the same period. This was mainly driven by an increased use of statins with 163.07%, and among these, rosuvastatin increased more than 1500-fold, and atorvastatin with 106.95% increase. With the appearance of generics, simvastatin showed a constant decline, while the other lipid-modifying medicines in relation to the total utilisation had a neglecting increase. The use of lipid-modifying medicines in the Republic of Srpska has constantly increased and strongly corresponded to the adopted treatment guidelines and the positive medicines list of health insurance fund. The results and trends are comparable with other countries, but still the utilisation of lipid-lowering medicines represents the smallest share of total medicines use for the treatment of cardiovascular diseases, compared to high-income countries.

Moderating Impact of Dispositional Mindfulness in the Relationship Between Future Expectancies and Psychological Well-Being.

Mindfulness has been studied under cultivated or dispositional divisions where the latter has strong implications for psychological well-being in meditators and non-meditators alike. In addition, future expectations, or prospections, regarding the occurrence of important events in a person's future have recently been hypothesized to be the main cause behind symptoms of major depression. There is, however, a lack of empirical research looking at possible links between dispositional mindfulness, as understood in its facet structure, and future expectations as understood via perceived risk of occurrence and vividness of mental imagery when prompted to imagine a given list of positive and negative prospective event item lists. Therefore, this research aimed at examining how dispositional mindfulness may be related to probabilistic risk assessments of positive and negative future events (Stage I); and how mental imagery vividness may be moderated by mindfulness facets (Stage II). Both stages included healthy participants and incorporated the PROCESS macro for moderated regression analysis done with the SPSS software. Stage I included 204 voluntary college students, and Stage II was conducted online with a public sample of 110 adults. Although no interaction effect was found in Stage I, nonreactivity to inner experience facet of dispositional mindfulness moderated the relationship between negative imagery vividness and psychological distress in Stage II (F(1,103) = 4.00, R2 change=.018, p <.05). This is a novel finding that could inform a future line of research looking into the relationship between prospection and mindfulness, holding a potential for informing research on mindfulness-based interventions.

Uptake of Fungicide Fluopyram from Soil by Scallions during Greenhouse Cultivation.

Unintentional pesticide contamination in rotational crops, often caused by soil contamination from pesticide use in the preceding crops, is a major concern in a positive list system. The residue and dissipation pattern of fluopyram in soil and scallions were investigated to evaluate the uptake of fluopyram from the soil by scallions. In addition, the management concentration in soil (MCsoil) was calculated based on bioconcentration factors (BCFs) and the maximum residue limit (0.2 mg/kg) in leaf-and-stem vegetables. In a field experiment, plots in two different trials, A and B, were treated with 0.06 g fluopyram/m2 and maintained for 30 days according to OECD guidelines. Scallion seedlings were cultivated for 48 days. Soil samples were taken at three different time points: DAP (Days after planting) 0, 34, and 48. Scallion samples were collected at five different time points: DAP 20, 27, 34, 41, and 48. The initial amounts of fluopyram in soil at DAP 0 were 0.94 ± 0.03 and 0.96 ± 0.04 mg/kg in trials A and B, respectively. The half-life of fluopyram in the soil was 87-231 days. Fluopyram uptake by the roots increased over time, but fluopyram residue in the scallions decreased due to the dilution effect caused by an increase in plant weight. The residues in the scallions at DAP 48 were 0.22 ± 0.01 and 0.15 ± 0.01 mg/kg in trials A and B, respectively. The BCFs of scallions for fluopyram were 0.21-0.24 (trial A) and 0.14-0.18 (trial B). The MCsoil was proposed as 0.8 mg/kg, and may be utilized as a safe management guideline for precautionary practices to cultivate safe rotational crops.

An Industry Survey on Unmet Needs in South Korea's New Drug Listing System.

Since introducing the positive listing system in 2007, the South Korean government has undergone multiple changes in its drug listing system. As there is a lack of studies that evaluate the system from an industry perspective, this paper examined South Korea's new drug listing system from the suppliers' perspective. We surveyed members of the three main pharmaceutical industry associations online. The survey (a 5-point Likert scale) covered their satisfactory levels, demands, and updates on the current new drug listing system, especially pharmacoeconomic evaluation, pharmacoeconomic evaluation exemption, and risk-sharing agreement. A total of 56 respondents participated in the survey. The self-reported satisfaction level for value recognition of new drugs was 1.6 (± 0.7) points (5 points = very satisfied). The most highly demanded reforms for PE, RSA, and PEE were incremental cost-effectiveness ratio threshold (92.9%), reimbursement scope expansion (91.1%), and eligible disease (83.9%). Lastly, they also claimed that the indication-based pricing system must be introduced (83.9%). Pricing and reimbursement policies need to improve in such a way that would enable better access to new drugs while still facilitating their development. Given the nature of the current system, some innovative rare disease treatments and anticancer drugs remain unreimbursed, resulting in low satisfaction levels across the pharmaceutical industry. Hence, pathways to speed up the reimbursement assessment process and expand the range of reimbursable diseases are required. Pharmaceutical companies are also important stakeholders, like in the case of clinicians and patients, and their opinions should also be considered in the process of pricing and reimbursement policy reforms.

Sprouting Inhibition after CIPC Spraying on Early and Mid-season Potato Varieties during Storage in Semi-underground Warehouse at Room Temperature in Summer

This study was carried out to determine the sprouting period of early and mid-season varieties, which includes ‘Atlantic’, ‘Chubaek’, and ‘Superior’, during the summer storage period in a semi-underground warehouse without cooling system. And also it was investigated the effect of chlorpropham [Propan-2-yl N-(3-chlorophenyl)carbamate, CIPC] treatment on the sprouting inhibition for the varieties. This study was conducted to figure out a sprout inhibitory effect when CIPC was applied to 1kg of the potato tubers at concentrations of 10 mg and 20 mg which are lower than the treatment concentrations of ca 30 mg prescribed by the positive list system (PLS). The internal temperature of the warehouse used in this experiment was lowered by 5°C or more than the outside temperature. The difference between the lowest and highest temperature during the experiment throughout the day was 5°C. It showed the effect of reducing to 1/2 of the difference in outdoor temperature. As for the sprouting of potatoes, the extremely early variety ‘Chubaek’ sprouts appeared at the 6th week of storage of control and it was the fastest sprouting potato among the control groups of the varieties. Sprouting began to appear in the Superior at the 6th week of storage, while the ‘Atlantic’ sprouted at the 8th week of storage. The appearance of sprouts was suppressed in all treatment groups of ‘Atlantic’ and ‘Superior’ varieties in CIPC treatments. Sprouts were observed in all treatment groups of ‘Chubaek’ after the 7th week, but the elongations of the sprouts in tubers were completely inhibited until the 8th week of storage. ‘Atlantic’ and ‘Superior’ seemed to have a sprouting inhibitory effect even with a low CIPC concentration of 10 mg·kg-1, with the exception of extremely early variety ‘Chubaek’ that breaks out of the dormancy quickly. Although weight loss occurred continuously during storage, it was minor loss of 0.7-1.6%. There was no consistent trend for changes of the loss in the varieties and CIPC treatments. Most common pathological disorder was the dry rot during the experiment, but only few were affected. The use of the tubers treated at 18°C and 90% RH for 10 days and the rack of refrigeration system which lead to lack of convection seemed to have suppressed the spread of pathogens.

A comparative survey of veterinarians, equine owners, and equine keepers regarding the knowledge and implementation of legal requirements in Germany for the use and documentation of veterinary medicines in equines intended for slaughter.

In Europe, equines destined for human consumption (hereafter called slaughter equines) are subject to the same restrictions of usage of veterinary drugs as other food-producing animals, with amendments regulated in the so-called 'positive list', Regulation (EC) No. 1950/2006. Due to the complex legal requirements for drug administration in slaughter equines, it might be that specific knowledge regarding the legislation of slaughter equines may be insufficient among veterinarians, equine owners, and equine keepers. To study this assumption, three target group-specific surveys were conducted in 2021. Answers from 153 equine treating veterinarians, 170 equine owners, and 70 equine keepers were included in the analysis. In total 68.4% (91/133) of the participating veterinarians, the regulations of the 'positive list', Regulation (EC) No. 1950/2006, were 'rather complicated' to 'complicated'. Among the participating veterinarians, 38.4% (58/151) did not or could not answer correctly how to proceed if a slaughter equine is scheduled to receive phenylbutazone, usage of which is prohibited in all livestock by Regulation (EU) No. 37/2010. Simultaneously, 56.2% (86/153) of the participating veterinarians named phenylbutazone as the, or one of the, most often used non-steroidal anti-inflammatory drugs. Altogether, 41.2% (70/170) of participating equine owners and 42.9% (30/70) of equine keepers did not know under which circumstances an equine can legally be slaughtered for human consumption. In total, 34.3% (24/70) of the equine keepers classified their knowledge of national regulations for animal keepers regarding the documentation of drug usage in equines as 'poor' to 'nonexistent'. This lack of knowledge in all three surveyed groups, combined with the complex legal regulations regarding the usage and documentation of drugs in slaughter equines, could result in missing and false documentation, treatment of slaughter equines with prohibited substances and therefore pose a risk factor for drug residues in equine meat.

Time From Marketing Authorization to Reimbursement of Medicines in Greece After the Introduction of the Health Technology Assessment Process From July 2018 to April 2022

ObjectivesThis study aimed to quantify the median time from marketing authorization (MA) to the inclusion of medicines in the reimbursement list after the introduction of the health technology assessment process in Greece. MethodsFrom July 2018 to April 2022, the Ministerial Decisions (MDs) and reimbursement lists, posted on the website of the Ministry of Health, were reviewed. The following information was collected for the medicines: the date that MDs and positive reimbursement lists were issued, the MA date, the date of the official price publication, and the type of the health technology assessment application. The time from MA to listing was calculated as the difference between the MA date and the date that the relevant reimbursement list was issued. ResultsDuring the study period, 93 MDs were issued, from which 79 (85%) were positive and 14 (15%) were negative. Focusing on medicines included in the positive list for the first time, the median time from MA to listing for the new molecules was found to be 34.8 (interquartile range 25.7-41.3) months. This time was statistically significantly shortened for fixed dose combinations (20.9 [15.3-45.4] months, P = .008), and biosimilars (23 [16.6-28.2] months, P = .001). For generics was 17.6 (interquartile range 10-30) months, statistically significantly lower than that of new molecules (P < .001). ConclusionsThe time from MA to the inclusion of medicines in the reimbursement list in Greece is significantly long, especially for innovative medicines. Thus, policy makers should consider this point to optimize and improve patients’ subsidized access.

Study on Machinability of Lead-Free α + β Brass 62.5Cu–1Si–Zn Alloy

Free-cutting brass contains 3% lead to obtain excellent machinability, but because lead is harmful to the human body, lead regulations are being tightened in Europe, starting with the 2010 and 2014 lead control laws for drinking water-related equipment in the United States, and including RoHS regulations, ELV regulations, and the 4MS Positive List. Being affected by these increasingly strict lead regulations in Europe and the United States, demand for brass with significantly reduced lead content is on the rise.

Radiological Protection in Industries Involving NORM: A (Graded) Methodological Approach to Characterize the Exposure Situations

The interest in radiation protection in industrial sectors involving Naturally Occurring Radioactive Materials (NORM) is increasingly growing. This is due also to the recent implementation of the European Council Directive 59/2013/Euratom which in Italy and in the other European Union Member States extends the field of application to industrial sectors never involved before. This paper reports main results of a research project on radiation protection in industries involving NORM carried out in Italy aimed to provide useful tools for stakeholders to comply new legal obligations. The project activities were mainly focused on different aspects relevant to the NORM involving industries, accounting for the positive list reported in the Italian law. Firstly, the inventory of the industries currently operating in Italy in order to identify the industrial sectors with an important radiological impact on population and workers was updated. Based on this information, a general methodology was elaborated taking into account a graded approach. The first phase consists in the identification and characterization of the most critical exposure scenarios and of the radiological content of NORMs involved in the different phases of the industrial processes. In the second phase calculation methods were developed for dose estimation for workers and members of public. These tools require the use of existing and well tested calculation codes, and the development of a dedicated user-friendly software.

Treatment patterns, adherence to international guidelines, and financial mechanisms of the market access of advanced breast cancer therapy in Bulgaria.

Breast cancer is the most common type of cancer affecting women in Europe. Advanced breast cancer (ABC) poses a significant therapeutic challenge, and therefore, timely access to treatment is crucial. The aim of the present study was to evaluate the treatment patterns and patients' access to new therapies for ABC in Bulgaria. We conducted a retrospective study in the period 2008-2021. Based on the European Medicines Agency (EMA) database, we analyzed a number of medicinal products with marketing authorization for ABC in the last 13 years. Time to market access was evaluated as the degree of availability, which is measured by the number of medicines that are available to patients (availability index, AI), and the average time elapsed between obtaining a marketing authorization and time to inclusion in the Positive Drug List. Data were analyzed through descriptive statistics via Microsoft Excel version 10. The average time to access was 564 days for targeted therapy. The availability and compliance index for chemotherapy and hormonal therapy in advanced breast cancer was 1, while the average AI for targeted therapy was 0.67. Patient access to targeted oncology therapy of ABC is above average for Europe and takes 1-2 years. Faster access is more evident for biosimilars. National regulatory requirements for pricing and reimbursement have a major impact on market access.

Control of public expenditure on drug products in Bulgaria – Policies and outcomes

Aim: The aim of this study was to assess the economic performance of the application of the policy for negotiating discounts on drug products and agreements on the controlled access of patients in Bulgaria. Methods: The methodology involves comparison of the amounts of public spending on medicines in two periods – during the course of the analyzed drug policies (January 2007 – June 2009), and the period in which negotiations on the price of medicines and programs for the controlled access of the patients was discontinued (July 2009 – December 2012). Results: In Bulgaria, the government did not apply methods for controlling publicexpenditure on medicines bargaining price concessions from manufacturers andimplementing agreements on controlled access of patients after June 2009. This led to an annual increase in the expenditures on drug products for home treatment (on average, 17% for the period 2009-2012). Conclusion: This trend in Bulgaria will continue in the future since expenditure control only through price control by means of a reference system and the positive list of medicines is ineffective. There is a need for implementation of combined drug policies in Bulgaria in the form of negotiations on rebates with manufacturers and agreements on controlled access of patients and reference pricing.

Research and Practice on online evaluation model of teachers’ ethics and style in Higher Vocational Colleges in the New Era--Take e-commerce major as an example

The construction of online evaluation processing model of teachers’ ethics and style in higher vocational colleges must go deep into the front line of teaching and be scientifically formulated according to the cognitive status of teachers and students and the internal requirements of school development. Based on the questionnaire survey on the problems related to the construction of online evaluation model of teachers’ ethics and style for teachers and students majoring in e-commerce, this paper finds and analyzes the difficulties and puzzles existing in the current school teachers’ ethics and style evaluation model from the first-hand data, and constructs a model composed of positive list and negative list by determining the index content, negative list, parameter score, computer system support, etc Online evaluation and processing model system of teachers’ ethics and style, which is convenient for assessment, evaluation, publicity and education. Among them, the positive list is composed of patriotism and law-abiding, love and dedication, care for students, teaching and educating people, being a teacher, rigorous scholarship and serving the society. The negative list provides the “bottom line” for teachers from the aspects of ideology, politics, discipline, work and life style.

Patient Perspective on Adherence to Reflux Lifestyle Modifications: A Qualitative Study.

Acid reflux disease is a common condition with recurrent symptoms affecting the quality of life of many Americans. Lifestyle/dietary modification is critical for management of acid reflux disease. Adherence to these recommendations is variable. The purpose of this study was to better understand the experience of patients with reflux disease (GERD/LPR) and explore factors that impact the integration of lifestyle modifications into their daily lives. Patient with diagnoses of GERD and/or LPR were recruited from an outpatient laryngology clinic and completed the Reflux Symptom Index (RSI) and a semi-structured interview. Interviews were transcribed and underwent thematic analysis. Twenty-three patients-mean age and RSI of 61 and 16.1 respectively-were recruited. Four main themes emerged: (1) Care team interaction-focus and quality of physician counseling, useful educational handouts, dietician/nutritionist counseling; (2) Motivation to change-impact on symptom severity, avoiding undesired interventions, and poor health outcomes; (3) Implementing lifestyle changes; and (4) Impact of disease on patient. No patient had seen a dietician. Patients who experienced dietary counseling for other conditions felt reflux-specific counseling with a dietician would be beneficial. While patients found educational material on diet to be helpful, lists of foods to avoid were discouraging; providing a positive list of preferred foods may be more helpful. Lifestyle modification counseling should incorporate multiple aspects of the patient experience. Patients desire information regarding medication side effects. Educational handouts should include prioritized list of recommended dietary restrictions and acceptable/alternative food options. Referral for dedicated dietician counseling can also be considered to increase understanding of the importance of, and adherence to, lifestyle modification.

Monitoring of Positive List System on Residual Pesticides Analysis of Agricultural Products in Southwest of Korea

Pesticide residues must be managed for food safety and regulations are being strengthened worldwide. In Korea, the Positive List System (PLS) was introduced to prevent the misuse and manage unregistered pesticides. The PLS is a system that applies 0.01 mg/kg to crops for which maximum residue limits is not set. A more stringent regulatory system could lead to an increase in agricultural products that exceed standards. Therefore it is necessary to confirm the change in the determination rate of agricultural products exceeding the previous pesticide residue standards. In terms of climate change, temperature increase and changes in precipitation patterns are the main pest and pathogen infection determinants. Complex interactions and climate variability will lead to more frequent spraying of pesticides and eventually affect consumer exposure at the end of the food chain. Therefore, we confirmed the relationship between temperature and precipitation, which are climate factors and pesticide residues. Agricultural products (n=5,560) distributed at wholesale market (SeoBu, GakHwa) in the southwest Korea were collected and 311 kind of residual pesticides were analyzed using GC-MS/MS and LC-MS/MS. This study could serve as basic data for pesticide residue prevention, management, control and monitoring in countries seeking to tighten pesticide standards.

STUDY OF CHANGES IN APPENDIX 3 OF THE POSITIVE DRUG LIST IN BULGARIA

The public nature of health care obliges the state to conduct a consistent policy that aims to ensure the protection of human health with optimal use of public funds. Achieving better management in the health care system is in the interest of individuals and society as a whole. And decisions in health care, as in any other area of human activity, must be economically rational, since all economic goods, including those related to health care, are limited in nature.The medicinal products included in Appendix 3 of the Positive Drug List have a reimbursement level of 100% and are negotiated and paid for from the budget of the Ministry of Health. These are medicinal products intended for the treatment of AIDS, infectious diseases, diseases outside the scope of the Health Insurance Act, paid according to a certain order of the Health Act, as well as vaccines for mandatory immunizations and re-immunizations, vaccines for special indications and in emergencies circumstances, specific sera, immunoglobulins.The purpose of the present study is to perform a comparative analysis of the changes in the reference values of the medicinal products included in Appendix 3 of the Positive Drug List.Methodology: The following research methods were used - documentary method, economic analysis, comparative analysis, statistical methods - analysis of the dynamics of phenomena and tabular analysis to visualize the obtained results.Results and analysis: From the research done, it is clear that for the period 2016-2019 only a decrease was observed, while for 2020 there was also an increase in the reference values of some medicinal products included in Appendix 3 of the Positive Drug List, the reasons for this being exclusion of a medicinal product from the list, increase in the price of a medicinal product and new grouping of medicinal products by therapeutic indication.Conclusion: Medicines are of fundamental importance in maintaining life, improving its quality and alleviating suffering. This determines the need to ensure equal access to medicinal products for citizens, according to their needs and regardless of their financial capabilities.

Risk assessment of food contact materials.

In the EU, any material or article intended to come into contact with food, which is placed on the market, has to comply with the requirements of the Regulation (EC) No 1935/2004 - the so called 'framework regulation' for food contact materials (FCM). FCM covers a wide range of materials, including plastics, paper, metal and glass, which contain chemicals that might migrate into food. These chemicals must not migrate into the foodstuff in quantities that could endanger human health, bring about an unacceptable change in the composition of the food, or bring about a deterioration in the organoleptic characteristics thereof. Despite of this general regulation, the safety of new and specific materials that are not covered must be assessed case-by-case. In addition, national authorities can set their own regulations, and in this context, the BfR sets recommendations, which are not legal norms, but represent a standard for the production of materials not subjected to any specific legislation and are well accepted by other European Commission member states according to the mutual recognition principle. The BfR Unit 74 is responsible not only to deal with chemical risk assessment of FCM but also to evaluate application dossiers to include new substances in the positive list of FCM chemicals. In the proposed EU-FORA programme, the fellow had the opportunity to gain experience in the evaluation of toxicological data from applicant dossiers and in the methodologies of migration tests performed in the laboratories. Moreover, the fellow also made a bibliographic review on scientific literature on the migration studies from starch-based materials.

Budget cap and pay-back model to control spending on medicines: A case study of Bulgaria.

Central and Eastern European countries (CEEC) have among the highest rates of increase in healthcare expenditure. External reference pricing, generics and biologics price capping, regressive scale for price setting, health technology assessment (HTA), and positive drug lists for reimbursed medicines are among the variety of implemented cost-containment measures aimed at reducing and controlling the rising cost for pharmaceuticals. The aim of our study was to analyze the influence of a recently introduced measure in Bulgaria-budget capping in terms of overall budget expenditure. A secondary goal was to analyze current and extrapolate future trends in the healthcare and pharmaceutical budget based on data from 2016 to 2021. The study is a retrospective, observational and prognostic, macroeconomic analysis of the National Health Insurance Fund's (NHIF) budget before (2016-2018) and after (2019-2021) the introduction of the new budget cap model. Subgroups analysis for each of the three new budget groups of medicines (group A: medicines for outpatient treatment, prescribed after approval by a committee of 3 specialists; group B: all other medicines out of group A; and group C: oncology and life-saving medicines out of group A) was also performed, and the data were extrapolated for the next 3 years. The Kruskal-Wallis test was applied to establish statistically significant differences between the groups. During 2016-2021, healthcare services and pharmaceutical spending increased permanently, observing a growth of 82 and 80%, respectively. The overall healthcare budget increased from European €1.8 billion to 3.3 billion. The subgroup analysis showed a similar trend for all three groups, with similar growth between them. The highest spending was observed in group C, which outpaced the others mainly due to the particular antineoplastic (chemotherapy) medicines included in it. The rising overall healthcare cost in Bulgaria (from European €1.8 billion to 3.3 billion) reveals that implementation of a mechanism for budget predictability and sustainability is needed. The introduced budget cap is a relatively effective measure, but the high level of overspending and pay-back amount (from European €34 billion to 59 billion during 2019-2021) reveals that the market environmental risk factors are not well foreseen and practically implemented.