Alertas sanitarias de productos médicos subestándares, falsificados y no registrados al inicio de la pandemia de COVID-19 en las Américas / Health alerts for substandard, falsified, and unregistered medical products at the onset of the COVID-19 pandemic in the Americas / Alertas de saúde para produtos médicos abaixo do padrão, falsificados e não registrados no início da pandemia de COVID-19 nas Américas

RESUMEN Objetivo. Identificar y analizar los incidentes de productos médicos subestándares, falsificados, no registrados y robados al inicio de la pandemia de COVID-19. Métodos. Búsqueda detallada en los sitios web de las autoridades reguladoras de las Américas. Identificación de los incidentes de medicamentos y dispositivos médicos (incluidos los de diagnóstico in vitro) subestándares falsificados, no registrados y robados. Se determinaron los tipos de productos, las etapas de la cadena de suministro en las que se detectaron y las medidas tomadas por las autoridades. Resultados. Se identificaron 1 273 incidentes en 15 países (1 087 productos subestándares, 44 falsificados, 123 no registrados y 19 robados). La mayor cantidad de incidentes corresponden a dispositivos médicos, desinfectantes y antisépticos. El punto en la cadena de suministro con mayor frecuencia de informes fue la adquisición a través de internet. Las medidas tomadas por las autoridades reguladoras corresponden en su mayoría a: alerta, prohibición de uso, prohibición de publicidad y fabricación, retiro del mercado y seguimiento de eventos adversos. Conclusiones. Se evidenció un número destacable de incidentes de productos médicos subestándares, falsificados, no registrados y robados al inicio de la pandemia por COVID-19. La escasez de insumos, la flexibilización en los requisitos regulatorios y el aumento de la demanda son factores que pueden favorecer el incremento del número de incidentes. Las autoridades reguladoras nacionales de referencia presentaron mayores frecuencias de detección de incidentes y de aplicación de medidas sanitarias. Se observó que se debe abordar el canal de venta por internet con alguna estrategia reguladora para garantizar la distribución segura de productos médicos.

ABSTRACT Objective. Identify and analyze incidents of substandard, falsified, unregistered, and stolen medical products at the onset of the COVID-19 pandemic. Methods. Detailed search of the websites of regulatory authorities in the Americas. Identification of incidents of substandard, falsified, unregistered, and stolen medicines and medical devices (including in vitro diagnostics). The types of products were determined, as were the stages in the supply chain where they were detected, and the actions taken by authorities. Results. A total of 1 273 incidents were identified in 15 countries (1 087 substandard, 44 falsified, 123 unregistered, and 19 stolen products). The largest number of incidents involved medical devices, disinfectants, and antiseptics. The most frequently reported point in the supply chain was online purchasing. The principal measures taken by the regulatory authorities were: alerts, prohibition of use, prohibition of advertising and manufacture, recall, and monitoring of adverse events. Conclusions. A substantial number of incidents involving substandard, falsified, unregistered, and stolen medical products at the onset of the COVID-19 pandemic were identified. Shortages of supplies, easing of regulatory requirements, and increased demand are factors that may have led to an increase in the number of incidents. The national regulatory authorities of reference reported more frequent detection of incidents and more frequent application of health measures. A regulatory strategy is needed in order to address online sales and ensure the safe distribution of medical products.

RESUMO Objetivo. Identificar e analisar incidentes de produtos médicos abaixo do padrão, falsificados, não registrados e roubados no início da pandemia de COVID-19. Métodos. Foi realizada uma busca detalhada nos sites das autoridades reguladoras das Américas. Foram identificados incidentes envolvendo medicamentos e dispositivos médicos (incluindo para diagnóstico in vitro) abaixo do padrão, falsificados, não registrados e roubados. Foram determinados os tipos de produtos, os estágios da cadeia de abastecimento em que foram detectados e as medidas tomadas pelas autoridades. Resultados. Foram identificados 1 273 incidentes em 15 países (1 087 produtos abaixo do padrão, 44 falsificados, 123 não registrados e 19 roubados). O maior número de incidentes estava relacionado a dispositivos médicos, desinfetantes e antissépticos. O ponto na cadeia de abastecimento com a maior frequência de relatos foi a de aquisição pela internet. As medidas tomadas pelas autoridades reguladoras foram principalmente alertas, proibições de uso, proibições de publicidade e fabricação, recolhimento de produtos do mercado e monitoramento de eventos adversos. Conclusões. Houve um número significativo de incidentes envolvendo produtos médicos abaixo do padrão falsificados, não registrados e roubados no início da pandemia de COVID-19. A escassez de insumos, a flexibilização das exigências regulatórias e o aumento da demanda são fatores que podem levar a um maior número de incidentes. As autoridades reguladoras nacionais de referência informaram um aumento na frequência de detecção de incidentes e implementação de medidas sanitárias. O canal de vendas pela internet precisa ser abordado com alguma estratégia regulatória para garantir a distribuição segura de produtos médicos.

Analysis of status quo and influential factors of substandard feeding in patients with mechanical ventilation in intensive care unit / 中国实用护理杂志

Objective:To analyze the failure rate of enteral nutrition feeding in patients with mechanical ventilation, explore the influencing factors, and find out the existing problems and deficiencies in the process of nutrition support.Methods:Patients who were admitted to the ICU of Zhejiang People′s Hospital from June 2020 to January 2022 for mechanical ventilation and continuous enteral nutrition through the nose were retrospectively collected as the research subjects. The patients were divided into a standard group and a substandard group. Comparing the feeding status of enteral nutrition patients in the two groups on the 7th day, Logistic regression was used to analyze the influencing factors of feeding substandard.Results:A total of 82 patients (57.34%, 82/143) had feeding failure. Logistic regression analysis showed that complications ( OR=34.47, 95% CI 9.49 to 125.21) and infusion speed ( OR=0.21, 95% CI 0.08 to 0.57) were the influencing factors of feeding failure in ICU mechanical ventilation patients ( P<0.05). Conclusions:The feeding failure rate of ICU mechanical ventilation patients is higher than the feeding failure rate, and the slow infusion speed caused by complications and feeding intolerance is the main reason for the failure. It is suggested to set personalized feeding program for patients, optimize feeding measures, and improve the feeding failure rate.

Vigilância e controle de medicamentos abaixo do padrão, falsificados e não registrados: revisão integrativa / Market surveillance and control of substandard, falsified and unregistered medicines: integrative review / Vigilancia y control de medicamentos subestándar, falsificados y no registrados: una revisión integral

RESUMO Objetivo. Identificar as estratégias de atuação dos sistemas regulatórios na vigilância e controle de medicamentos abaixo do padrão, falsificados e não registrados em nível regional-global, especialmente quanto aos processos de recall. Métodos. Foi realizada uma revisão integrativa da literatura nas bases de dados MEDLINE via PubMed, Embase e SciELO. Foram selecionados estudos publicados no período de 2007 a 2019, em inglês, português e espanhol, que abordavam estratégias desenvolvidas pelos sistemas regulatórios dos países, com foco no recall de medicamentos abaixo do padrão, falsificados e não registrados. Resultados. Dos 483 estudos inicialmente identificados, foram incluídas 21 publicações de alcance global, regional ou nacional. As estratégias de prevenção, detecção e resposta, incluindo o recall, foram agrupadas em dois modelos (passivo-reativo e proativo) de atuação dos sistemas regulatórios na vigilância e controle de medicamentos. Esses modelos parecem combinar estratégias passivas e proativas, complementares ou concorrentes, variando conforme o nível de desenvolvimento dos países e a capacidade regulatória. Embora seja considerado a resposta mais eficaz de proteção da população, o recall não foi implementado de forma uniforme no âmbito dos sistemas regulatórios, segundo os estudos. Conclusões. A complexidade e a magnitude do problema dos medicamentos abaixo do padrão, falsificados e não registrados exigem esforços, investimentos e mudanças profundas na abordagem, nos processos e nas capacidades dos sistemas regulatórios, podendo as estratégias de vigilância e controle do mercado convergir para um modelo híbrido, multisetorial, multidisciplinar, global e sistêmico de proteção da saúde humana.

ABSTRACT Objective. To identify the strategies employed by regulatory systems for the market surveillance and control of substandard, falsified, and unregistered medicines at the regional-global levels, especially regarding drug recall procedures. Method. An integrative literature review was performed. Searches were performed in MEDLINE via PubMed, Embase, and SciELO to select articles published from 2007 to 2019 in English, Portuguese, and Spanish, covering national regulatory system initiatives, with a focus on the recall of substandard, falsified, and unregistered medicines. Results. Of 483 articles initially identified, 21 global, regional, or national scope studies were selected. Prevention, detection, and response strategies, including drug recall, were grouped according to two broad market surveillance and control models (passive-reactive and proactive) used by regulatory systems. These models seem to combine passive and proactive, complementary or concurring actions that varied according to country development level and regulatory capacity. Although considered the most effective response for protection of populations, medicine recall was not implemented in a uniform manner in different regulatory systems as indicated by the studies. Conclusions. Addressing the complexity and magnitude of the problem of substandard, falsified, and unregistered medicines will demand effort, investment, and profound changes in the approaches, processes, and capacity of regulatory systems, with market surveillance and control strategies possibly converging toward a hybrid, multisectoral, multidisciplinary, global, and systemic model of human health protection.

RESUMEN Objetivo. Identificar las estrategias de actuación de los sistemas regulatorios en la vigilancia y control de los medicamentos subestándar, falsificados y no registrados a nivel regional-mundial, especialmente en lo que se refiere a los procesos de retirada de medicamentos del mercado (recall). Métodos. Se realizó una revisión bibliográfica integral en las bases de datos de MEDLINE a través de PubMed, Embase y SciELO. Se seleccionaron los estudios publicados entre 2007 y 2019, en inglés, portugués y español, en los que se abordaban las estrategias elaboradas por los sistemas regulatorios de los países, con énfasis en la retirada de los medicamentos subestándar, falsificados y no registrados. Resultados. De los 483 estudios identificados inicialmente, se incluyeron 21 publicaciones de ámbito nacional, regional o mundial. Las estrategias de prevención, detección y respuesta, incluida la retirada de medicamentos, se agruparon en dos modelos de actuación (pasivo-reactivo y proactivo) de los sistemas de regulación en la vigilancia y el control de los medicamentos. Estos modelos parecen combinar estrategias pasivas y proactivas, complementarias o concurrentes, que varían según el nivel de desarrollo de los países y su capacidad de regulación. Aunque la retirada de productos se considera la respuesta más eficaz para proteger a la población, según los estudios esta no se ha aplicado de manera uniforme en los sistemas de regulación. Conclusiones. La complejidad y la magnitud del problema de los medicamentos subestándar, falsificados y no registrados exigen esfuerzos, inversiones y cambios profundos en el enfoque, los procesos y las capacidades de los sistemas de regulación; y las estrategias de vigilancia y control del mercado pueden converger hacia un modelo híbrido, multisectorial, multidisciplinar, mundial y sistémico de protección de la salud humana.

Reports of substandard medicines: a lexicographic analysis of the Brazilian Health Surveillance Report System

Regulatory agencies are responsible for collecting and evaluating spontaneous reports of suspected problems related to medications, including those from substandard medicines (SM). Objectives: The aim was to evaluate the profile of SM reports submitted to the Brazilian Health Surveillance Notification System (Notivisa) and classify these reports objectively by means of lexicographic analysis. Methods: Was extracted all SM reports available in Notivisa during the period 1 January 2007 to 31 December 2017. Descriptive statistics were performed and the reasons for SM reporting were standardized (using OpenRefine and Microsoft Excel). The following analyses were performed using IRAMuTeQ 0.7 alpha2: lexicographic analysis to obtain the frequency of active words; descending hierarchical classification (DHC) to categorize the active words into lexical classes; factorial correspondence analysis (FCA) to obtain graphs of the classes. Approved by the Ethics Committee of the Hospital do Trabalhador/SES/PR CAAE 81873417.3.0000.5225 (protocol number: 2.506.594). Results: A total of 61,775 reports were analyzed, most of them reported by hospitals (46%). The DHC of the reasons for SM produced four classes visualized in the FCA: (i) packaging problems (16%) mainly leakages/opening issues; (ii) inadequate drug identification (22%), such as illegible label information; (iii) stability and contamination issues (11%) such as presence of particles; (iv) damaged tablets/blisters (23%) mainly broken tablets. Most SM (52%) were solutions for parenteral use; sodium chloride (9%), glucose and dipyrone (3%) were the products with most complaints. Conclusions: The reasons for SM reporting can be objectively classified into classes that represent the main problems submitted to Notivisa. This classification could guide the standardization of SM reporting and contribute to improving surveillance reporting systems worldwide.

Poor-quality medicines: a global threat to health / Lao Medical Journal

@#Poor quality medicines have been described as a global pandemic that threatens the lives of millions of people. The problem is much more severe in poor-resource countries where pharmaceutical legislation and regulation are limited. Poor quality medicines are divided into three categories: substandard, degraded and falsified and the countermeasures vary according to each category. The use of poor quality medicine leads from minimal to severe complications (including death) for the individuals but also harms the community. Furthermore, they lead to a loss of confidence of the patients in essential medicines, in manufacturers and in health system and they increase the work burden for health workers, customs and police. To detect them, different techniques have been developed, each with advantages and limits. This article describes these aspects of poor quality medicines and also presents the factors that contribute to the existence and spread of poor quality medicines. A section of the article is devoted to the issue of poor quality medicine in Laos.

Increasing Trends in Unhealthy Practices of Clinical Laboratory Medicine Service in Nepal

The medical laboratories are increasing significantly with striking challenges in ensuring praiseworthy public health service in Nepal. Quality medical laboratory service provision is important in order to enhance diagnostic value and save lives. Poverty, poor infrastructure, unskilled manpower and incompetency are major contributing factors leading to inefficient provision of health services in developing countries. Nepal has been increasing its network of clinical health laboratories in the Government and private sectors that are scattered in various geographical regions. The quality of service remains a growing concern even as medical diagnostic laboratories are undergoing the process of accreditation for quality services in line with WHO standards. But, still the status of clinical laboratory practice regarding quality assurance, skilled manpower, standard labs and cost effective quality service remains challenging due to different loopholes in policy making. The regulatory bodies and legal provisions seem to be in non-functional state. The malpractices in clinical laboratory medicine service are increasing exponentially. Therefore, this review draws attention towards unhealthy practices in clinical laboratory services and critically examines different factors affecting the healthy practice in medical laboratory science.

Evaluation of the Pharmaceutical Quality of Different Brands of Ranitidine Tablets Manufactured in Bangladesh: A Pharmaceutical and Public Health Prospective.

Drug counterfeiting and production of substandard drug is a global problem. Substandard or counterfeit drugs are threat for the effective treatment of diseases and highly worsen the quality of life of patients. This study was aimed to assess the pharmaceutical quality of ranitidine hydrochloride tablets manufactured in Bangladesh. Tablets were collected from different parts of Bangladesh and quality parameters were evaluated according to the United States Pharmacopoeia and the British Pharmacopoeial methods. The potency of tablets was measured spectrophotometrically. Weight variation and disintegration time were performed according to pharmaceutical monographs. Among 43 brands tested, 8 failed to comply with the USP specification (active ingredient: 90±10%) due to containing of less amount of ranitidine of which 6 brands were spurious and 2 were substandard in nature. Two brands did not comply with the specification for weight variation of tablets whereas all brands passed disintegration time test. The findings clearly demonstrate the production of substandard ranitidine tablets in Bangladesh. The drug control authority of Bangladesh should take effective steps to prevent the production of substandard drugs to secure public health.

Pilot Study of Quality of Diclofenac Generic Products Using Validated In-House Method: Indian Drug Regulatory Concern.

Globally, the expanding issues over the extent of substandard or spurious medicines remain a challenge. It is operated largely by encompassing wrong therapeutic doses or adulterated formulations that necessitates routine monitoring to avoid any potential public health adversity. This study was aimed to determine the diclofenac sodium content in generic products available in northern Indian market. Therefore, 32 commercially available generic products of diclofenac sodium tablet were procured from the open market and subjected to assay evaluation using in-house developed and validated high performance liquid chromatography (HPLC) method. Product identification was confirmed by thin layer chromatography (TLC) method; and the quantitative results by validated in-house HPLC method showed 34.37% (11/32) products as out of Indian Pharmacopoeia specification including 15.62% (5/32) substandard products. This makes the health situation miserable for public and their trust. On comparing the assay with price of each tablet, it was noticed that quality of products was irrespective of price. People rely completely on manufacturer quality promises and on regulatory process. However, such substandard products which still exist in the market for use by the patient; unfortunately not identified yet, poses a serious issue and require some interventions to stop them in entering into market. So there is an urgent need to carry out the quality evaluation on regular and large scale by the state and national drug authorities to ensure better quality medicines.

Reason analysis of QC substandard cryoprecipitate prepared from fresh frozen plasma with siphonage method / 中国现代医生

Objective To explore the incidence and the reason of substandard cryoprecipitate prepared from fresh frozen plasma with siphonage method and provide a theoretical basis for preparing high-quality cryoprecipitate for blood collection agencies. Methods Quality control results of cryoprecipitate with siphonage method were dealed by retrospective analysis from January 2011 to January 2014 in our Blood Centre. Substandard reasons were counted, sub-standard rates were calculated, then factors influencing the quality of cryoprecipitate were analyzed from different links. Results Four bags were randomly sampled per month, for 36 consecutive months, and 144 bags were sampled totally. 17 bags of 144 were substandard prouducts, substandard rate was 11.8%. The content of factor Ⅷ of 17 bags were in-adequate. Conclusion The inadequate content of factor Ⅷ is the main reason of the substandard cryoprecipitate pre-pared from fresh frozen plasma with siphonage method, it can be reduced or prevented the emergence of substandard prouducts by controling whole blood, fresh frozen plasma and cryoprecipitate prepared and so on.

Substandard artemisinin-based antimalarial medicines in licensed retail pharmaceutical outlets in Ghana.

Background & objectives: The artemisinin-based antimalarial medicines are first line medicines in the treatment of severe and uncomplicated falciparum malaria. Numerous brands of these medicines manufactured in various countries are available in the Ghanaian market. The study was aimed at evaluating the authenticity and quality of selected brands of artemisinin-based antimalarial medicines marketed in Ghana. Methods: In all, 14 artemisinin-based antimalarial medicines were purchased from pharmacies (P) and licensed chemical shops (LCSs) in the Kumasi metropolis, Ghana. Simple field tests based on colorimetry and thin layer chromatography were employed in determining the authenticity of the samples. Important quality assessment tests, namely uniformity of mass, crushing strength, disintegration time, and the percentage content of active pharmaceutical ingredients (APIs) were determined. Results: All the brands tested contained the stipulated APIs. Artesunate tablet AT2 failed the uniformity of mass test while artesunate tablets AT3 & AT4 as well as amodiaquine tablets AM4 & AM6 failed the crushing strength test. All the six artemether-lumefantrine tablet brands passed the uniformity of mass, crushing strength and disintegration tests. Only artemether-lumefantrine tablet brand AL1 contained the correct amount of the drugs. The other 13 artemisinin products contained either a lower (underdose) or higher (overdose) amount of the specified drug. Artesunate monotherapy tablets were readily available in pharmacies and licensed chemical shops. Interpretation & conclusion: All the artemisinin-based medicines tested (except AL1) were of substandard quality. The results demonstrate the need for continuous monitoring and evaluation of the quality of artemisininbased antimalarials in the Ghanaian market. Also, the practice of artemisinin antimalarial monotherapy is prevalent in Ghana. Determined efforts should, therefore, be made to eradicate the practice to prevent the development of resistance to the artemisinins.

Accelerated stability and antimicrobial sensitivity studies of amoxicillin dry suspensions marketed in Bangladesh.

Since its introduction, amoxicillin dry suspension has been the mainstay for the antibacterial therapy for paediatric patients. But use of substandard preparation of antibiotic is one of the most important causes of microbial resistance. The present study has been carried out to evaluate the quality and stability status of 10 marketed amoxicillin dry suspensions of Bangladesh. All the brands were analyzed for their potency using chemical and microbiological methods described in the United States Pharmacopoeia and British Pharmacopoeia. Potency determination was done at three controlled temperatures - refrigerated, room and elevated (40C) showed that two samples were over potent but one sample was substandard out of the 10 samples. The initial potencies of the two samples were within USP range when freshly reconstituted but after 7 days, at room temperature, potencies deteriorated and came down to 90%. In refrigerated condition, all the samples remained in good condition and at 40C, a considerable loss of potencies in all the samples were observed. Results of microbiological assay also support the results of chemical assay. The study emphasizes the necessity of routine inspection, monitoring and evaluation of quality of formulations containing amoxicillin dry syrup.

Using High Performance Liquid Chromatography to quantitate Artemether and Artesunate anti-malarial tablets in the National Capital District, Papua New Guinea

Malaria is a major public health problem in Papua New Guinea (PNG). The Artemisinin-based combination therapy is widely used as the first-line treatment for malaria in PNG. This study was to assess the quantity of the Artemether and Artesunate ingredients in the antimalarial drugs used for the treatment of malaria in the National Capital District (NCD) PNG. Artemether and Artesunate tablets were purchased from various pharmacies in NCD. Artemether and Artesunate solutions were prepared according to the Standard United States Pharmacopoeial protocol for assay of active ingredients by high performance liquid chromatography (HPLC). The results indicated that the percent Artemether content in the three brands (ART 01, ART 02 and ART 03) of Artemether purchased in the NCD were 93.2%, 87.6% and 89.3% respectively. Four brands (ATS 01/02, ATS 03/04, ATS 05, and ATS 06) of Artesunate were purchased in the NCD. The % Artesunate content in the four brands were 109.0%, 110.0%, 101.2% and 96.2%% respectively. The three Artemether brands (100%) and two (ATS 01/02 and ATS 03/04) of the Artesunate brands (50%) did not satisfy the USP specifications for the amount of active ingredients in the drugs. Our data indicate that poor quality Artemether and Artesunate antimalarial drugs are sold in the National Capital District in PNG. This indicates the urgent need to advocate for more efficient drug monitoring and effective enforcement of regulations that prevents importation of substandard drugs into the NCD.