Analysis of non-compliances identified in GMP inspections between 2013 and 2022

Ensuring the quality and safety of medicinal products is of paramount importance to the pharmaceutical industry. Good manufacturing practice (GMP) regulations are part of a pharmaceutical manufacturer’s quality management system and ensure that medicinal products are manufactured, imported and controlled consistently to quality standards appropriate to their intended use. The aim of the present study is to analyze the non-compliant operations identified during GMP inspections carried out by national competent authorities (NCA) in the EU/EEC between 2013 and 2022. A retrospective analysis of non-compliance reports published in the EudraGMDP database between 2013 and 2022 was performed. Overall, 99 reports by 21 national competent authorities were analyzed presenting the results of inspections in 19 countries. A total of 1458 deficiencies were identified, of which 544 (37%) were classified as major and 127 (9%) as critical. The most common non-compliant operations were the manufacturing of active substances (49 deficiencies) and the preparation of non-sterile products (47 deficiencies). In 41 cases, the NCA recommended suspension or voiding of the certificate of suitability (CEP) and in 36 cases revocation of the GMP certificates. The observed deficiencies highlight the importance and need for continuous monitoring and improvement of manufacturers’ production processes and quality management systems

On the age of the hominid fossils at the Sima de los Huesos, Sierra de Atapuerca, Spain: paleomagnetic evidence

We report new paleomagnetic data for the Middle Pleistocene hominid-bearing strata in the Sima de los Huesos, North Spain. Sediments (brown muds with human and bear fossils and the underlying sterile clayey and sandy unit) preserve both normal and reversed magnetic components. The sterile unit has exclusively reversed magnetization, dating back to the Matuyama Chron, and thus is Lower Pleistocene in age. The overlying fossiliferous muds have a dominant normal magnetization that overprints a partially resolved reversed magnetization. These data are compatible with one of the reversal events that occurred during the Brunhes Chron. Combined with the existing U-series dates and evidence from the macro- and microfauna, these paleomagnetic results suggest an age of the hominid fossils between 325 to 205 ka, whereas the underlying sand and silts are older than 780 ka.This research was supported by DGES grants PB96-0815 and PB96-1026-C03, and by the Unidad Asociada CSIC-UCM.Peer reviewe

First examinations with the newly installed posturographic platform at the University medical and dental center, Medical University – Varna, Bulgaria

BackgroundPosture of the human body aims to keep its balance when performing dynamic movements or in the static stance. Posturology is another term for the Global postural recalibration. It is the discipline which studies posture. Postural control is regulated by a complex system, known as the Tonic postural system. Stomatognathic system must not be excluded when discussing posture. Posturology enables clinicians to study the sensory information, entering the body and determine the sensor that work in a suboptimal manner.MethodsA clinical case of a female patient, fully diagnosed, using the newly implemented system, is presented. Apart from it, we have analyzed another fourteen patients. All first filled out specifically designed questionnaires and signed written informed consent forms. Static and dynamic postural, audiological, vestibular, visual and HSAT assessments were performed, along with a dental check-up.ResultsPatient had normal occlusal characteristics – class 1 Angle, but problems with the temporomandibular joint and slight hearing were present. No vestibular, posture (static or dynamic) or visual convergence abnormalities were detected. Refractive abnormalities were present. Apart from that, a group of patients with obstructive sleep apnea is presented. Changes of their posture and balance were studied.ConclusionsAll information gathered by the two integrated static and dynamic analysis systems, along with the postural analyzer, HSAT and dental analysis can be used to define therapeutic interventions and exercise programmes needed

Apology after medical errors: a qualitative vignette study:Medical errors: impact of apology and admission on the resolution and compensation of claims

Studies investigating the impact of apologies and admission of responsibility for medical errors have been primarily observational, making it hard to attach a causal effect to the admission of responsibility and apologies. Second, most research on the settlement of medical malpractice cases were conducted in the US, with its particular litigation laws and culture. In this multi-jurisdictional study, we investigate the impact of apology and admission of responsibility on preferred resolution and compensation of claims. Employing a vignette design, we examine, among a sample of 327 respondents from 10 different countries, whether admission and apology by the doctor impact respondents' preference for resolution through a civil court case, mediation or a disciplinary board, as well as preferred damages for pain and suffering. Admission and apology by the physician in the vignette did not impact respondents' preference for settlement through a civil court case or mediation, nor did it affect the amount respondents found suitable compensation for pains and damages. We perceived the absence of an apology as particularly aggravating. Thematic analysis of open answers reveals that the impact of admission and apology differs for the three resolution modes and is often contextual and conditional. Future (vignette) studies should investigate whether different cases of medical errors yield similar results and whether more knowledgeable or experienced respondents (such as lawyers) would have other preferences and arguments. <br/

Probable mechanism of the operation of the flotation pulp density on the selective flotation of the sulphide minerals

Tyt. z nagłówka.Bibliografia s. 299.Dostępny również w formie drukowanej.STRESZCZENIE: Artykuł ten przedstawia problem badania możliwości, poprzez zmianę zawartości fazy stałej w mętach, poprawy selektywności procesu flotacji podczas flotacji wieloskładnikowych rud. Poszukiwano relacji pomiędzy zmniejszeniem aeracji w warunkach flotacji większej gęstości mętów flotacyjnych, różnicowanie pomiędzy głównymi minerałami siarczkowymi, co do ich hydrofobowości powierzchni oraz procesami przeprowadzanymi w trójfazowej pianie. Wyniki badań wskazują, że zwiększana gęstość nie zawsze prowadzi do obniżenia selektywności procesu. Stwierdzono, że zwiększenie fazy stałej w mętach do pewnej granicy zwiększa selektywność procesu, a może ją pogorszyć powyżej tej granicy. Granica zazwyczaj jest różna dla różnych przypadków technologicznych, ale jest zawsze możliwa do określenia. SŁOWA KLUCZOWE: materiały siarczkowe, flotacja selektywna, gęstość mętów. ABSTRACT: In this report it's looked through the problem about the research of the possibilities, by the change of the solid phase content in the pulp for improvement of the flotation process selectivity during the flotation of the multicomponent ores. It's searched for the relation between the lessened aeration in the conditions of the flotation with higher density of the flotation pulp and the competitive struggle between the main sulphide minerals which differ theirselves of it's hydrophobic mineral surface and of the processes, running in the three-phased froth as well. The results of the research indicate that the increased density doesn't always lead to the decrease of the process of selectivity. It's found that the rising of the solid phase content in the pulp up to a definite limit improves the selectivity of the process, but it can hardly get worse above this limit. The limit is most likely to be different for the different technological cases, but it's obviously to be always available. KEYWORDS: sulphide minerals, selective flotation, pulp density

MINING AND MINERAL PROCESSING 50 years University of Mining and Geology

ABSTRACT The constitution of the three-phase froth is decisive for the selectivity of the running flotation process. The influence of the density of the flotation pulp is investigated as on the process of secondary enrichment of the concentrate also on the selectivity of the process of precipitation of the minerals form the three-phase troth with the drainage waters. This connection of secondary enrichment is investigated as contrary to the hydrophobicity of the minerals and thus with the size of the mineral particles

Assoc. Prof. PhD Nikola Todorov (1955-2018) – A Life Dedicated to Geography

The paper is devoted to Assoc. Prof. PhD Nikola Todorov’s life and professional contributions (1955- 2018) – a prominent Bulgarian geographer, unreservedly dedicated to the science and field researches, who left а rich creative heritage in the field of Physical Geography and Landscape Science. He was the leading author in the development of the second landscape classification system of Bulgaria and in the creation of а landscape map of Bulgaria on a 1:500 000 scale, which is one of his main contributions. An important contribution in his research activity is the developed classification system of anthropogenic changes and landscape disturbances in Bulgaria, which is applicable to the whole country and encompassing the enormous variety of natural-territorial complexes and their changes. He was a scientific mentor for 26 master students and 4 PhD students. Assoc. Prof. Nikola Todorov was a Lecturer who inspired generations of students and many young researchers with his erudition and oratory skills

Analysis of non-compliances identified in GMP inspections between 2013 and 2022

Ensuring the quality and safety of medicinal products is of paramount importance to the pharmaceutical industry. Good manufacturing practice (GMP) regulations are part of a pharmaceutical manufacturer’s quality management system and ensure that medicinal products are manufactured, imported and controlled consistently to quality standards appropriate to their intended use. The aim of the present study is to analyze the non-compliant operations identified during GMP inspections carried out by national competent authorities (NCA) in the EU/EEC between 2013 and 2022. A retrospective analysis of non-compliance reports published in the EudraGMDP database between 2013 and 2022 was performed. Overall, 99 reports by 21 national competent authorities were analyzed presenting the results of inspections in 19 countries. A total of 1458 deficiencies were identified, of which 544 (37%) were classified as major and 127 (9%) as critical. The most common non-compliant operations were the manufacturing of active substances (49 deficiencies) and the preparation of non-sterile products (47 deficiencies). In 41 cases, the NCA recommended suspension or voiding of the certificate of suitability (CEP) and in 36 cases revocation of the GMP certificates. The observed deficiencies highlight the importance and need for continuous monitoring and improvement of manufacturers’ production processes and quality management systems

Economic Burden of Cervical Cancer in Bulgaria

Bulgaria is among the European Union (EU) countries with the highest burden of cervical cancers and life expectancy below the EU average. The majority of cervical cancer cases (more than 95%) are caused by the human papillomavirus (HPV). The aim of this retrospective, cost of illness study is to identify direct healthcare costs of cervical cancer in Bulgaria from the payer perspective and to calculate indirect costs and the associated years of life lost. Costs data were sourced from the National Health Insurance Fund from January 2018 to December 2020. Years of life lost were calculated based on the country and gender-specific life expectancy. Indirect costs due to productivity loss were calculated using the human capital approach. The total treatment costs for 3540 patients with cervical cancer are EUR 5,743,657 (2018), EUR 6,377,508 (2019), and EUR 6,751,182 (2020). The costs associated with drug acquisition and administration accounted for the majority (63%) of total healthcare costs followed by hospital management costs (14%). An estimated total of 20,446 years of life were lost due to cervical cancer for the period 2018&ndash;2020. The costs of productivity losses are estimated at EUR 7,578,014. Our study showed that the economic burden of cervical cancer in Bulgaria is substantial. Focus on cervical cancer prevention via vaccination against the human papillomavirus, timely screening, early diagnosis, and higher vaccine coverage rates could reduce its economic burden in Bulgaria