Medical devices regulatory framework

Charles University in Prague, Faculty of Law Department of Administrative law Candidate: PharmDr. Jan Honegr, Ph.D. Supervisor: JUDr. Ing. Josef Staša, CSc. Title of diploma thesis: Medical devices regulatory framework The subject of this diploma thesis is the regulatory framework for the so-called "general" medical devices with a slight overlap in the field of in-vitro medical devices. The presented work aims to describe the impact of the planned change in the regulatory framework for medical devices on economic operators in the field of production and distribution of medical devices in the Czech Republic. In this work I gradually deal with the historical development of the regulatory framework for goods in the European Communities and subsequently the European Union and the specific regulation of for medical devices. I deal in detail with the multilevel regulatory framework and the relationships between its components. I focus in more detail on the key change in the regulatory framework, which is represented by the hitherto ineffective EU Medical Devices Regulation 2017/745 and government bills to prepare the Czech legal system for the adoption of this directly effective European Union legislation. The main parts of the work are chapters 5 and 6 in which, I deal with the potential impacts of the...Univerzita Karlova v Praze, Fakulta Právnická Katedra: Správního práva Kandidát: PharmDr. Jan Honegr, Ph.D. Školitel: JUDr. Ing. Josef Staša, CSc. Název diplomové práce: Veřejnoprávní úprava požadavků na zdravotnické prostředky Předmětem této diplomové práce je problematika veřejnoprávní regulace tzv. obecných zdravotnických prostředků s mírným přesahem i do oblasti zdravotnických prostředků in-vitro. Předkládaná práce si bere za cíl popsat vliv připravované změny regulačního rámce zdravotnických prostředků na hospodářské subjekty působící oblasti výroby a distribuce zdravotních prostředku v České republice. V práci se postupně zabývám historickým vývojem regulačního rámce pro výrobky na území evropských společenství a následně Evropské unie a specifickou úpravou veřejnoprávních požadavků na zdravotnické prostředky. Podrobně se v práci věnuji zejména mnohoúrovňovosti regulačního rámce a vztahům mezi jeho jednotlivými složkami. Detailněji se zaměřuji zejména na klíčovou změnu regulačního rámce, která je představována zatím neúčinným nařízením o zdravotnických prostředcích (EU) 2017/745 a vládními návrhy zákonů, které mají připravit český právní řád na přijetí tohoto přímo účinného právního předpisu Evropské unie. Stěžejní části práce jsou kapitoly 5. a 6. ve kterých se z pozice adresátů regulačního...Department of Administrative Law and Administrative ScienceKatedra správního práva a správní vědyFaculty of LawPrávnická fakult

Complexity stage model of the medical device development based on economic evaluation-MedDee

The development of a new product is essential for the progress and success of any company. The medical device market is very specific, which is challenging. Therefore, this paper assesses an economic model for medical device evaluation using the economic, health, technology regulatory, and present market knowledge to enable the cost-time conception for any applicant. The purpose of this study is to propose a comprehensive stage model of the medical device development to subsequently describe the financial expenditure of the entire development process. The identification of critical steps was based on the literature review, and analysis, and a comparison of the available medical device development stages and directives. Furthermore, a preliminary assessment of the medical device development steps and procedures on the basis of the interviews was performed. Six interviews were conducted with an average duration of one hour, focusing on areas: relevance and level of detail of the medical device development stages, involvement of economic methods, and applicability of the proposed model. Subsequently, the improvement and modification of the medical device investment process, based on respondents' responses, were conducted. The authors have proposed the complexity model MedDee-Medical Devices Development by Economic Evaluation. This model is comprised of six phases: initiation, concept, design, production, final verification, and market disposition in which the economic methods are incorporated.Web of Science125art. no. 175

Development of Methods for Sensitivity Enhancement in Capillary Zone Electrophoresis of Natural Polyphenolic Compounds with Use of Online Elektromigration Preconcentration Techniques

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Analytical Chemistry Candidate Mgr. Jan Honegr Supervisor Doc. RNDr. Marie Pospíšilová, CSc. Title of Doctoral Thesis Development of methods for sensitivity enhancement in capillary zone electrophoresis of natural polyphenolic compounds with use of online electromigration preconcentration techniques The thesis presented is dealing with the development of capillary zone electrophoresis (CZE) with UV detection for the sensitivity enhancement in the analysis of polyphenolic substances of natural origin. Basic principles of capillary electrophoresis, different online preconcentration techniques (including stacking) and corresponding instrumentation are discussed in the theoretical part. Moreover a survey of properties of polyphenolic compounds and of herbal drugs containing such substances is presented in this section. The experimental part is focused on the development and validation of three new analytical procedures with online electrophoretic preconcentration for the assay of polyphenols in plant extracts. The analytes under study were ferulic, chlorogenic, caffeic, p-coumaric, rosmarinic, carnosolic, cinnamic, protocatechuic, vanillic and syringic acid and a group of flavonoids involving quercitrin, quercetin,..

Rational Design of a New Class of Toll-Like Receptor 4 (TLR4) Tryptamine Related Agonists by Means of the Structure- and Ligand-Based Virtual Screening for Vaccine Adjuvant Discovery

In order to identify novel lead structures for human toll-like receptor 4 (hTLR4) modulation virtual high throughput screening by a peta-flops-scale supercomputer has been performed. Based on the in silico studies, a series of 12 compounds related to tryptamine was rationally designed to retain suitable molecular geometry for interaction with the hTLR4 binding site as well as to satisfy general principles of drug-likeness. The proposed compounds were synthesized, and tested by in vitro and ex vivo experiments, which revealed that several of them are capable to stimulate hTLR4 in vitro up to 25% activity of Monophosphoryl lipid A. The specific affinity of the in vitro most potent substance was confirmed by surface plasmon resonance direct-binding experiments. Moreover, two compounds from the series show also significant ability to elicit production of interleukin 6

Utilisation of electromigration methods in analysis of naturally occuring compounds

UTILISATION OF ELECTROMIGRATION METHODS IN ANALYSIS OF NATURALLY OCCURING COMPOUNDS Jan Honegr ABSTRACT A transient isotachophoresis-capillary zone electrophoresis (tITP-CZE) method has been developed for pre-concentration and determination of nine analytes: caffeic, chlorogenic, o- coumaric, p-coumaric, ferulic and protocatechuic acid, and kaempferol, quercetin and rutin. The effects of several factors such as control of EOF, pH and concentration of the running buffer, addition of organic solvents and their concentrations, addition of cyclodextrins, the duration of injection and the λ max of UV detection were investigated to find the optimum conditions. Under these conditions, the analytes were separated within 15 min. Linearity was evaluated for concentration range 2.5-37.5µg/ml with R = 0.9924-0.9983; the detection limits (S/N 3:1) ranged from 203ng/ml to 5.556µg/ml. The relative standard deviations of the migration times (peak areas) were between 0.79 and 1.01% (1.34 and 2.13%)

Utilisation of electromigration methods in analysis of naturally occuring compounds

UTILISATION OF ELECTROMIGRATION METHODS IN ANALYSIS OF NATURALLY OCCURING COMPOUNDS Jan Honegr ABSTRACT A transient isotachophoresis-capillary zone electrophoresis (tITP-CZE) method has been developed for pre-concentration and determination of nine analytes: caffeic, chlorogenic, o- coumaric, p-coumaric, ferulic and protocatechuic acid, and kaempferol, quercetin and rutin. The effects of several factors such as control of EOF, pH and concentration of the running buffer, addition of organic solvents and their concentrations, addition of cyclodextrins, the duration of injection and the λ max of UV detection were investigated to find the optimum conditions. Under these conditions, the analytes were separated within 15 min. Linearity was evaluated for concentration range 2.5-37.5µg/ml with R = 0.9924-0.9983; the detection limits (S/N 3:1) ranged from 203ng/ml to 5.556µg/ml. The relative standard deviations of the migration times (peak areas) were between 0.79 and 1.01% (1.34 and 2.13%)

Medical devices regulatory framework

Charles University in Prague, Faculty of Law Department of Administrative law Candidate: PharmDr. Jan Honegr, Ph.D. Supervisor: JUDr. Ing. Josef Staša, CSc. Title of diploma thesis: Medical devices regulatory framework The subject of this diploma thesis is the regulatory framework for the so-called "general" medical devices with a slight overlap in the field of in-vitro medical devices. The presented work aims to describe the impact of the planned change in the regulatory framework for medical devices on economic operators in the field of production and distribution of medical devices in the Czech Republic. In this work I gradually deal with the historical development of the regulatory framework for goods in the European Communities and subsequently the European Union and the specific regulation of for medical devices. I deal in detail with the multilevel regulatory framework and the relationships between its components. I focus in more detail on the key change in the regulatory framework, which is represented by the hitherto ineffective EU Medical Devices Regulation 2017/745 and government bills to prepare the Czech legal system for the adoption of this directly effective European Union legislation. The main parts of the work are chapters 5 and 6 in which, I deal with the potential impacts of the..

Gulf war syndrome – a syndrome or not?

After the Gulf war, new diagnostic entity was claimed: the Gulf War Syndrome (GWS). A wide spectrum of exposures is widely discussed in order to explain the reported symptoms. Investigating tentative culprits we did not find clearly conclusive data about the existence of the GWS. The origin of described symptoms can be associated to the use of pesticides and the PB pill. However, the data about the use of both are influenced by a lack of precise records. Although other agents such as nerve agent exposure could not be definitively ruled out, its link to symptoms seems to be improbable.Web of Science341524

Vaccine ingredients: Components that influence vaccine efficacy

Vaccination is defined as the administration of an antigenic material in order to stimulate the immune system, leading to the development of adaptive immunity to a pathogen. Vaccines can prevent or reduce morbidity from a vast number of infections. This manuscript presents an analysis of vaccine types and vaccine substances, concentrating on individual components including the active ingredient, adjuvants, preservatives, stabilizers, inactivators, antibiotics, diluents and other substances. While many papers have been published on individual vaccine components, this review provides detail on a wide range of the most commonly-used vaccine ingredients and components that have been tested in clinical trials.Web of Science17546645

Ligand-based 3D QSAR analysis of reactivation potency of mono- and bis-pyridinium aldoximes toward VX-inhibited rat acetylcholinesterase

PubMed ID: 25588616To predict unknown reactivation potencies of 12 mono- and bis-pyridinium aldoximes for VX-inhibited rat acetylcholinesterase (rAChE), three-dimensional quantitative structure–activity relationship (3D QSAR) analysis has been carried out. Utilizing molecular interaction fields (MIFs) calculated by molecular mechanical (MMFF94) and quantum chemical (B3LYP/6-31G*) methods, two satisfactory ligand-based CoMFA models have been developed: 1. R2 = 0.9989, QLOO2 = 0.9090, QLTO2 = 0.8921, QLMO(20%)2 = 0.8853, Rext2 = 0.9259, SDEPext = 6.8938; 2. R2 = 0.9962, QLOO2 = 0.9368, QLTO2 = 0.9298, QLMO(20%)2 = 0.9248, Rext2 = 0.8905, SDEPext = 6.6756. High statistical significance of the 3D QSAR models has been achieved through the application of several data noise reduction techniques (i.e. smart region definition SRD, fractional factor design FFD, uninformative/iterative variable elimination UVE/IVE) on the original MIFs. Besides the ligand-based CoMFA models, an alignment molecular set constructed by flexible molecular docking has been also studied. The contour maps as well as the predicted reactivation potencies resulting from 3D QSAR analyses help better understand which structural features are associated with increased reactivation potency of studied compounds.Web of Science5612911