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1.
Regul Toxicol Pharmacol ; 150: 105649, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38782234

RESUMO

Permitted Daily Exposure Limits (PDEs) are set for Active Pharmaceutical Ingredients (APIs) to control cross-contamination when manufacturing medicinal products in shared facilities. With the lack of official PDE lists for pharmaceuticals, PDEs have to be set by each company separately. Although general rules and guidelines for the setting of PDEs exist, inter-company variations in the setting of PDEs occur and are considered acceptable within a certain range. To evaluate the robustness of the PDE approach between different pharmaceutical companies, data on PDE setting of five marketed APIs (amlodipine, hydrochlorothiazide, metformin, morphine, and omeprazole) were collected and compared. Findings show that the variability between PDE values is within acceptable ranges (below 10-fold) for all compounds, with the highest difference for morphine due to different Point of Departures (PODs) and Adjustment Factors (AFs). Factors of PDE variability identified and further discussed are: (1) availability of data, (2) selection of POD, (3) assignment of AFs, (4) route-to-route extrapolation, and (5) expert judgement and differences in company policies. We conclude that the investigated PDE methods and calculations are robust and scientifically defensible. Additionally, we provide further recommendations to harmonize PDE calculation approaches across the pharmaceutical industry.


Assuntos
Indústria Farmacêutica , Humanos , Indústria Farmacêutica/normas , Preparações Farmacêuticas/normas , Preparações Farmacêuticas/análise , Medição de Risco , Contaminação de Medicamentos/prevenção & controle , Exposição Ocupacional/normas , Princípios Ativos
2.
Food Chem Toxicol ; 188: 114644, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38615796

RESUMO

Next-Generation Risk Assessment (NGRA) aims to implement New Approach Methodologies (NAMs) into risk assessment and to rely on new in vivo testing in animals only as a last resort. However, various technical and regulatory hurdles impede their regulatory implementation. Assumptions about the public's expectations could act as barriers to the acceptance of NAMs. This study aimed at investigating public views of animal testing and potential alternatives, namely in vitro and in silico testing. An online survey was conducted (N = 965). The results suggest that people make trade-offs, as they experience negative affect regarding in vivo testing, which partly might explain their openness regarding certain alternatives. In vitro tests were attributed the highest ability to determine harmful effects of chemicals for different endpoints, followed by in vivo and in silico tests. Our results further showed that many people accept chemicals to be only tested with alternatives, with highest acceptance for household consumer products, food contact material or building materials and less accepting for medicines and foods. This article addresses potential challenges that might arise from public perceptions and thus, contributes to the bottom-up initiatives to overcome the hurdles to the implementation of NAMs in regulatory risk assessment.


Assuntos
Opinião Pública , Medição de Risco/métodos , Humanos , Animais , Alternativas aos Testes com Animais/métodos , Feminino , Masculino , Adulto , Inquéritos e Questionários , Pessoa de Meia-Idade , Adulto Jovem
3.
J Appl Toxicol ; 42(9): 1443-1457, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35315528

RESUMO

Contract Development and Manufacturing Organizations (CDMOs) that manufacture large, diverse portfolio of chemical and pharmaceutical substances require pragmatic risk-based decisions with respect to the safe carry-over between different chemical entities, as well as for worker protection. Additionally, CDMOs may not have access to primary study data, or data are generally lacking for a specific substance. While pharmaceuticals require the establishment of health-based exposure limits (HBELs) (e.g., occupational exposure limits [OELs] and permitted daily exposure [PDE] limits), the limits for nonhazardous substances could be set in a protective and pragmatic way by using default values, when internally required. Because there is no aligned definition provided by authorities, nor agreed default values for nonhazardous substances, we provide a decision tree in order to help qualified experts (such as qualified toxicologists) to identify the group of nonhazardous substances and to assign default HBEL values for specific routes of exposure. The nonhazardous substances discussed within this publication are part of the following subgroups: (I) inactive pharmaceutical ingredients, (II) pharmaceutical excipients or cosmetic ingredients, (III) substances Generally Recognized as Safe (GRAS), and (IV) food ingredients, additives, and contact materials. The proposed default limit values are 1 mg/m3 for the OEL and 50 mg/day for the PDE oral and intravenous (IV) route.


Assuntos
Exposição Ocupacional , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Preparações Farmacêuticas , Medição de Risco
4.
Lancet Infect Dis ; 22(1): 136-149, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34863336

RESUMO

BACKGROUND: Over the past 20 years, schistosomiasis control has been scaled up. Preventive chemotherapy with praziquantel is the main intervention. We aimed to assess the effect of preventive chemotherapy on schistosomiasis prevalence in sub-Saharan Africa, comparing 2000-10 with 2011-14 and 2015-19. METHODS: In this spatiotemporal modelling study, we analysed survey data from school-aged children (aged 5-14 years) in 44 countries across sub-Saharan Africa. The data were extracted from the Global Neglected Tropical Diseases database and augmented by 2018 and 2019 survey data obtained from disease control programmes. Bayesian geostatistical models were fitted to Schistosoma haematobium and Schistosoma mansoni survey data. The models included data on climatic predictors obtained from satellites and other open-source environmental databases and socioeconomic predictors obtained from various household surveys. Temporal changes in Schistosoma species prevalence were estimated by a categorical variable with values corresponding to the three time periods (2000-10, 2011-14, and 2015-19) during which preventive chemotherapy interventions were scaled up. FINDINGS: We identified 781 references with relevant geolocated schistosomiasis survey data for 2000-19. There were 19 166 unique survey locations for S haematobium and 23 861 for S mansoni, of which 77% (14 757 locations for S haematobium and 18 372 locations for S mansoni) corresponded to 2011-19. Schistosomiasis prevalence among school-aged children in sub-Saharan Africa decreased from 23·0% (95% Bayesian credible interval 22·1-24·1) in 2000-10 to 9·6% (9·1-10·2) in 2015-19, an overall reduction of 58·3%. The reduction of S haematobium was 67·9% (64·6-71·1) and that of S mansoni 53·6% (45·2-58·3) when comparing 2000-10 with 2015-19. INTERPRETATION: Our model-based estimates suggest that schistosomiasis prevalence in sub-Saharan Africa has decreased considerably, most likely explained by the scale-up of preventive chemotherapy. There is a need to consolidate gains in the control of schistosomiasis by means of preventive chemotherapy, coupled with other interventions to interrupt disease transmission. FUNDING: European Research Council and WHO.


Assuntos
Anti-Helmínticos/uso terapêutico , Praziquantel/uso terapêutico , Schistosoma haematobium/efeitos dos fármacos , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose/tratamento farmacológico , Análise Espaço-Temporal , Adolescente , África Subsaariana/epidemiologia , Animais , Quimioprevenção , Criança , Pré-Escolar , Estudos Transversais , Bases de Dados Factuais , Humanos , Praziquantel/administração & dosagem , Prevalência , Esquistossomose/classificação , Esquistossomose/epidemiologia , Instituições Acadêmicas
5.
BMJ Open ; 9(8): e029738, 2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31383708

RESUMO

OBJECTIVE: With the growing prevalence of overweight and obesity, medical students should be prepared to engage in weight management and obesity-related communications in order to prevent patients from having stigmatising experiences. In addition, medical students should have training to reduce anti-fat prejudices. DESIGN: Cross-sectional proof of concept study. SETTING: University Hospital Tuebingen, Germany. PARTICIPANTS: 246 participants (207 second-year medical students, 13 standardised patients (SPs) and 22 teachers) took part in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the assessment of degree of reality of the encounter with the SP wearing an obesity simulation suit (OSS). The secondary outcome was the evaluation of students' awareness and prejudice against patients with obesity in a simulated role play. Additionally, a description of the advantages and disadvantages when using such a teaching tool is delivered. RESULTS: The OSS contributed to a realistic perception of the patient group depicted in a role play according to students, teachers and SPs. OSS body mass index estimation by students, teachers and SPs correctly was over 30 kg/m2-thus in the range of obesity. In a selected subscale of the Anti-Fat Attitudes Test, students showed significantly stronger anti-fat stigmatisation compared with teachers and SPs. CONCLUSIONS: An OSS worn by an SP is a valuable teaching tool to raise awareness about patients with obesity. It gives a realistic picture of the encounter. Stigmatisation was low in general but was especially present in the students. Further research should include intervention studies to address this issue.


Assuntos
Atitude do Pessoal de Saúde , Obesidade , Desempenho de Papéis , Treinamento por Simulação/métodos , Estudantes de Medicina , Adolescente , Adulto , Estudos Transversais , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Preconceito , Estudo de Prova de Conceito , Estereotipagem , Adulto Jovem
6.
Pharm Dev Technol ; 23(3): 261-264, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28535123

RESUMO

Due to newly introduced EU GMP (Good Manufacturing Practice) guideline for Medicinal Products for Human and Veterinary use, product specific permitted daily exposure (PDE) for toxicological evaluation in multi-purpose facilities are required within a documented process for risk assessment. European Medicines Agency (EMA) guidance on setting PDE limits so far focused on systemic administration routes such as intravenous (IV), oral or inhalation. This article provides guidance on setting PDE values for risk management purposes in multi-purpose facilities for active pharmaceutical ingredients (APIs) applied as topical otic drugs to the outer ear canal. The therewith determined PDE otic, is used for the calculation of maximum safe carry-over (MSC) in manufacturing scenarios where a topical otic product is manufactured followed by another topical otic product.


Assuntos
Contaminação de Medicamentos/prevenção & controle , Instalações Industriais e de Manufatura/normas , Preparações Farmacêuticas/normas , Relação Dose-Resposta a Droga , Indústria Farmacêutica/normas , Orelha , Humanos , Medição de Risco
7.
Curr Opin Psychiatry ; 19(4): 361-6, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16721164

RESUMO

PURPOSE OF REVIEW: We provide a summary of issues relevant to healthcare and health delivery in autism and related disorders, with a focus on work published in the past 5 years. RECENT FINDINGS: Autism has a strong genetic basis as evidenced by the high recurrence rate in families and its associations with Fragile X syndrome and tuberous sclerosis. Early diagnosis of autism is important, given the potential for improvement with intervention. Although its associations have been reported with events such as measles-mumps-rubella immunization, large-scale studies have not supported such links. Controlled drug trials have increased in frequency and drug treatment may be helpful in addressing frequently associated behavioural and emotional difficulties. Alternative treatments are frequently preferred by parents. SUMMARY: Knowledge of autism among healthcare professionals has increased but gaps remain. Physicians and other professionals can facilitate the delivery of healthcare services to individuals with autism. Awareness of empirically validated treatments will facilitate work with individuals with autism and related disorders as well as with their families.


Assuntos
Transtorno Autístico/epidemiologia , Serviços de Saúde da Criança/tendências , Austrália/epidemiologia , Criança , Pré-Escolar , Comparação Transcultural , Humanos , Incidência , Inquéritos e Questionários , Estados Unidos/epidemiologia
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