{"id":12743,"date":"2022-10-11T17:29:57","date_gmt":"2022-10-11T17:29:57","guid":{"rendered":"https:\/\/insilicall.com\/?p=12743"},"modified":"2023-02-16T19:41:20","modified_gmt":"2023-02-16T19:41:20","slug":"atualizacoes-do-questionario-da-ema-sobre-contaminacao-por-nitrosaminas","status":"publish","type":"post","link":"https:\/\/insilicall.com\/atualizacoes-do-questionario-da-ema-sobre-contaminacao-por-nitrosaminas\/","title":{"rendered":"Atualiza\u00e7\u00f5es do question\u00e1rio da EMA sobre contamina\u00e7\u00e3o por nitrosaminas"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-post\" data-elementor-id=\"12743\" class=\"elementor elementor-12743\" data-elementor-post-type=\"post\">\n\t\t\t\t\t\t<section data-particle_enable=\"false\" data-particle-mobile-disabled=\"false\" class=\"elementor-section elementor-top-section elementor-element elementor-element-283171b elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"283171b\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-e8be842\" data-id=\"e8be842\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-1817251 elementor-widget elementor-widget-heading\" data-id=\"1817251\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.23.0 - 05-08-2024 *\/\n.elementor-heading-title{padding:0;margin:0;line-height:1}.elementor-widget-heading .elementor-heading-title[class*=elementor-size-]>a{color:inherit;font-size:inherit;line-height:inherit}.elementor-widget-heading .elementor-heading-title.elementor-size-small{font-size:15px}.elementor-widget-heading .elementor-heading-title.elementor-size-medium{font-size:19px}.elementor-widget-heading .elementor-heading-title.elementor-size-large{font-size:29px}.elementor-widget-heading .elementor-heading-title.elementor-size-xl{font-size:39px}.elementor-widget-heading .elementor-heading-title.elementor-size-xxl{font-size:59px}<\/style><h2 class=\"elementor-heading-title elementor-size-default\">Atualiza\u00e7\u00f5es do question\u00e1rio da EMA \nsobre contamina\u00e7\u00e3o por nitrosaminas<\/h2>\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section data-particle_enable=\"false\" data-particle-mobile-disabled=\"false\" class=\"elementor-section elementor-top-section elementor-element elementor-element-166d4bd elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"166d4bd\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-1905467\" data-id=\"1905467\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<section data-particle_enable=\"false\" data-particle-mobile-disabled=\"false\" class=\"elementor-section elementor-inner-section elementor-element elementor-element-52adac7 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"52adac7\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-inner-column elementor-element elementor-element-fdc99cd\" data-id=\"fdc99cd\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-0aa53b9 elementor-widget elementor-widget-text-editor\" data-id=\"0aa53b9\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.23.0 - 05-08-2024 *\/\n.elementor-widget-text-editor.elementor-drop-cap-view-stacked .elementor-drop-cap{background-color:#69727d;color:#fff}.elementor-widget-text-editor.elementor-drop-cap-view-framed .elementor-drop-cap{color:#69727d;border:3px solid;background-color:transparent}.elementor-widget-text-editor:not(.elementor-drop-cap-view-default) .elementor-drop-cap{margin-top:8px}.elementor-widget-text-editor:not(.elementor-drop-cap-view-default) .elementor-drop-cap-letter{width:1em;height:1em}.elementor-widget-text-editor .elementor-drop-cap{float:left;text-align:center;line-height:1;font-size:50px}.elementor-widget-text-editor .elementor-drop-cap-letter{display:inline-block}<\/style>\t\t\t\t<p><span style=\"font-weight: 400\">A <\/span><span style=\"color: #003366\"><a style=\"color: #003366\" href=\"https:\/\/www.ema.europa.eu\/en\" target=\"_blank\" rel=\"noopener\"><b>European Medicines Agency (EMA)<\/b><\/a><\/span><span style=\"font-weight: 400\">, ag\u00eancia respons\u00e1vel pela avalia\u00e7\u00e3o cient\u00edfica, supervis\u00e3o e monitoriza\u00e7\u00e3o da seguran\u00e7a dos medicamentos na Uni\u00e3o Europeia, publicou um <\/span><span style=\"color: #003366\"><strong><a style=\"color: #003366\" href=\"https:\/\/www.ema.europa.eu\/en\/documents\/referral\/nitrosamines-emea-h-a53-1490-questions-answers-marketing-authorisation-holders\/applicants-chmp-opinion-article-53-regulation-ec-no-726\/2004-referral-nitrosamine-impurities-human-medicinal-products_en.pdf\" target=\"_blank\" rel=\"noopener\">question\u00e1rio de avalia\u00e7\u00e3o de contamina\u00e7\u00e3o <\/a><\/strong><a style=\"color: #003366\" href=\"https:\/\/www.ema.europa.eu\/en\/documents\/referral\/nitrosamines-emea-h-a53-1490-questions-answers-marketing-authorisation-holders\/applicants-chmp-opinion-article-53-regulation-ec-no-726\/2004-referral-nitrosamine-impurities-human-medicinal-products_en.pdf\" target=\"_blank\" rel=\"noopener\"><strong>por nitrosaminas<\/strong><\/a><\/span><span style=\"font-weight: 400\">\u00a0em fevereiro do ano vigente. <\/span><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-2d6fdee elementor-widget elementor-widget-text-editor\" data-id=\"2d6fdee\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><span style=\"font-weight: 400\">Esse documento fornece informa\u00e7\u00f5es sobre quais s\u00e3o os fatores de risco conhecidos para a contamina\u00e7\u00e3o e\/ou forma\u00e7\u00e3o de nitrosaminas, al\u00e9m de orienta\u00e7\u00f5es sobre quais medicamentos para uso humano devem ser avaliados para a presen\u00e7a de nitrosaminas, como realizar e o que priorizar na avalia\u00e7\u00e3o e como proceder caso haja atualiza\u00e7\u00f5es.<\/span><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-2003711 elementor-widget elementor-widget-text-editor\" data-id=\"2003711\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><span style=\"font-weight: 400\">O documento passou por algumas revis\u00f5es e a \u00faltima (Rev. 11) foi divulgada em 29 de julho de 2022. A seguir, um resumo das respectivas adi\u00e7\u00f5es nos textos de resposta \u00e0s perguntas individuais:<\/span><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-1dfc4af elementor-widget elementor-widget-text-editor\" data-id=\"1dfc4af\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><b>(Rev. 8) 4. Quais s\u00e3o os fatores de risco atualmente identificados para a presen\u00e7a de nitrosaminas?<\/b><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-9ba55b3 elementor-widget elementor-widget-text-editor\" data-id=\"9ba55b3\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><span style=\"font-weight: 400\">Os fatores de risco para a forma\u00e7\u00e3o da impurezas foram divididos em tr\u00eas categorias:<\/span><\/p>\n<p><span style=\"font-weight: 400\">A) <strong>Fatores de risco na fabrica\u00e7\u00e3o da IFAs:<\/strong> rea\u00e7\u00f5es qu\u00edmicas que levam \u00e0 forma\u00e7\u00e3o de nitritos como fonte <br>de impurezas de nitrosaminas;<\/span><\/p>\n<p><span style=\"font-weight: 400\">B) <strong>Fatores de risco na fabrica\u00e7\u00e3o do produto acabado:<\/strong> outras causas qu\u00edmicas de forma\u00e7\u00e3o de nitrito;<\/span><\/p>\n<p><span style=\"font-weight: 400\">C) <strong>Fatores de risco em rela\u00e7\u00e3o aos aspectos de Boas Pr\u00e1ticas de Fabrica\u00e7\u00e3o:<\/strong> literatura t\u00e9cnica sobre a qu\u00edmica da forma\u00e7\u00e3o de nitrosaminas. Saiba mais sobre a qu\u00edmica das nitrosaminas neste <\/span><a href=\"https:\/\/insilicall.com\/a-quimica-das-nitrosaminas\/\"><span style=\"font-weight: 400\"><strong>artigo<\/strong><\/span><\/a><span style=\"font-weight: 400\">.<\/span><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-3b63e36 elementor-widget elementor-widget-text-editor\" data-id=\"3b63e36\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><b>(Rev. 10) 5. O que fazer se, ap\u00f3s o envio das respostas da Etapa 1 e\/ou da Etapa 2, forem identificadas novas informa\u00e7\u00f5es (por exemplo, relacionadas a novos fatores de risco potenciais ou causas ra\u00edzes)? <\/b><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-bbe4d0d elementor-widget elementor-widget-text-editor\" data-id=\"bbe4d0d\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><span style=\"font-weight: 400\">Na atualiza\u00e7\u00e3o da resposta, as expectativas sobre os titulares de <strong>Autoriza\u00e7\u00e3o de Introdu\u00e7\u00e3o no Mercado (AIM)<\/strong> s\u00e3o especificadas da seguinte forma:<\/span><\/p>\n<p><span style=\"font-weight: 400\">1) A avalia\u00e7\u00e3o de risco deve ser reexaminada \u00e0 medida que novas informa\u00e7\u00f5es sobre potenciais fontes de contamina\u00e7\u00e3o por nitrosaminas estiverem dispon\u00edveis;<\/span><\/p>\n<p><span style=\"font-weight: 400\">2) As perguntas 4 (fatores de risco) e 10 (limites) do documento de perguntas e respostas devem ser revisadas rotineiramente para atualiza\u00e7\u00f5es.<\/span><\/p><p><span style=\"letter-spacing: -0.2px\">Aten\u00e7\u00e3o especial deve ser dada \u00e0s fontes de nitrosaminas de IFAs. A presen\u00e7a simult\u00e2nea de tra\u00e7os de aminas e nitritos durante a formula\u00e7\u00e3o do produto final ou no armazenamento \u00e9 considerada alto risco.&nbsp;<\/span><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-24302f1 elementor-widget-divider--view-line_icon elementor-view-default elementor-widget-divider--element-align-center elementor-widget elementor-widget-divider\" data-id=\"24302f1\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"divider.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.23.0 - 05-08-2024 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100%;-webkit-mask-repeat:var(--divider-pattern-repeat);mask-repeat:var(--divider-pattern-repeat);background-color:var(--divider-color);-webkit-mask-image:var(--divider-pattern-url);mask-image:var(--divider-pattern-url)}.elementor-widget-divider--no-spacing{--divider-pattern-size:auto}.elementor-widget-divider--bg-round{--divider-pattern-repeat:round}.rtl .elementor-widget-divider .elementor-divider__text{direction:rtl}.e-con-inner>.elementor-widget-divider,.e-con>.elementor-widget-divider{width:var(--container-widget-width,100%);--flex-grow:var(--container-widget-flex-grow)}<\/style>\t\t<div class=\"elementor-divider\">\n\t\t\t<span class=\"elementor-divider-separator\">\n\t\t\t\t\t\t\t<div class=\"elementor-icon elementor-divider__element\">\n\t\t\t\t\t<svg aria-hidden=\"true\" class=\"e-font-icon-svg e-fas-search\" viewBox=\"0 0 512 512\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\"><path d=\"M505 442.7L405.3 343c-4.5-4.5-10.6-7-17-7H372c27.6-35.3 44-79.7 44-128C416 93.1 322.9 0 208 0S0 93.1 0 208s93.1 208 208 208c48.3 0 92.7-16.4 128-44v16.3c0 6.4 2.5 12.5 7 17l99.7 99.7c9.4 9.4 24.6 9.4 33.9 0l28.3-28.3c9.4-9.4 9.4-24.6.1-34zM208 336c-70.7 0-128-57.2-128-128 0-70.7 57.2-128 128-128 70.7 0 128 57.2 128 128 0 70.7-57.2 128-128 128z\"><\/path><\/svg><\/div>\n\t\t\t\t\t\t<\/span>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-956a5c0 elementor-widget elementor-widget-text-editor\" data-id=\"956a5c0\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><strong><em>10. Que limites se aplicam \u00e0s nitrosaminas em medicamentos?<\/em><\/strong><\/p><p><em>\u201cO guia ICH M7 define N-nitrosaminas como subst\u00e2ncias de \u201ccoorte de preocupa\u00e7\u00e3o\u201d, para as quais os limites em medicamentos referem-se \u00e0 chamada ingest\u00e3o aceit\u00e1vel espec\u00edfica da subst\u00e2ncia (IA) [&#8230;], que est\u00e1 associado a um risco insignificante (risco te\u00f3rico de c\u00e2ncer excessivo de <br \/>&lt;1 em 100.000 ao longo da vida de exposi\u00e7\u00e3o).\u00a0<\/em><\/p><p><em>O c\u00e1lculo de IA pressup\u00f5e uma administra\u00e7\u00e3o ao longo da vida de exposi\u00e7\u00e3o da dose m\u00e1xima di\u00e1ria do medicamento e \u00e9 baseado na abordagem descrita na diretriz ICH M7, bem como nos princ\u00edpios descrito em rela\u00e7\u00e3o \u00e0 avalia\u00e7\u00e3o toxicol\u00f3gica no relat\u00f3rio de avalia\u00e7\u00e3o do <br \/>Artigo 5(3) do\u00a0<a href=\"https:\/\/www.ema.europa.eu\/en\/committees\/committee-medicinal-products-human-use-chmp\" target=\"_blank\" rel=\"noopener\"><b>CHMP<\/b><\/a>.\u201d<\/em><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-a0f73b0 elementor-widget-divider--view-line elementor-widget elementor-widget-divider\" data-id=\"a0f73b0\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"divider.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<div class=\"elementor-divider\">\n\t\t\t<span class=\"elementor-divider-separator\">\n\t\t\t\t\t\t<\/span>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-0811fac elementor-widget elementor-widget-text-editor\" data-id=\"0811fac\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><b>(Rev. 8) 8. Como os testes confirmat\u00f3rios devem ser conduzidos pelos titulares de AIM e fabricantes?<\/b><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-189cd1c elementor-widget elementor-widget-text-editor\" data-id=\"189cd1c\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><span style=\"font-weight: 400\">A resposta para esta pergunta especifica o caso em que a causa da contamina\u00e7\u00e3o por nitrosaminas est\u00e1 apenas na fase de fabrica\u00e7\u00e3o do IFA. Se isso for comprovado, os testes confirmat\u00f3rios podem ser limitados apenas ao IFA ou intermedi\u00e1rios e n\u00e3o precisam ser estendidos ao produto acabado.<\/span><\/p><p><span style=\"font-weight: 400\">Os pr\u00e9-requisitos para isso s\u00e3o:<\/span><\/p><ul><li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Nenhum risco adicional \u00e9 identificado na avalia\u00e7\u00e3o de risco do produto acabado;<\/span><\/li><li style=\"font-weight: 400\"><span style=\"font-weight: 400\">O teste de um produto intermedi\u00e1rio n\u00e3o revela nenhum risco adicional para as etapas de fabrica\u00e7\u00e3o subsequentes do IFA;<\/span><\/li><li style=\"font-weight: 400\"><span style=\"font-weight: 400\">A justificativa para a estrat\u00e9gia em que apenas os intermedi\u00e1rios e o IFA devem ser testados \u00e9 cientificamente v\u00e1lida.<\/span><\/li><\/ul><p><span style=\"font-weight: 400\">A responsabilidade pela estrat\u00e9gia do teste de confirma\u00e7\u00e3o \u00e9 do titular de AIM. A estrat\u00e9gia de ensaio deve ser justificada pela avalia\u00e7\u00e3o de risco do produto acabado e documentada no sistema de qualidade farmac\u00eautica do titular de AIM.<\/span><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-0cd4e14 elementor-widget elementor-widget-text-editor\" data-id=\"0cd4e14\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><b>(Rev. 9, Rev. 10) 10. Que limites se aplicam \u00e0s nitrosaminas em medicamentos?<\/b><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-0318dd6 elementor-widget elementor-widget-text-editor\" data-id=\"0318dd6\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><span style=\"font-weight: 400\">Foram adicionadas sete nitrosaminas junto com os seus limites correspondentes na tabela da impureza. \u00c9 explicitamente declarado que as autoridades n\u00e3o aceitem um teste de AMES (m\u00e9todo para detec\u00e7\u00e3o de agentes qu\u00edmicos mutag\u00eanicos) negativo como a \u00fanica evid\u00eancia da aus\u00eancia de propriedades mutag\u00eanicas <br \/>em uma nitrosamina.\u00a0<\/span><\/p><p><span style=\"font-weight: 400\">O fato de que algumas nitrosaminas exibem mutagenicidade <\/span><i><span style=\"font-weight: 400\">in vivo, <\/span><\/i><span style=\"font-weight: 400\">apesar dos resultados negativos do teste de AMES, coloca a signific\u00e2ncia deste teste em perspectiva e testes adicionais s\u00e3o necess\u00e1rios para classificar um composto de nitrosamina como uma impureza Classe 5 (n\u00e3o mutag\u00eanica) &#8211;\u00a0<\/span><span style=\"color: #003366\"><a style=\"color: #003366\" href=\"https:\/\/database.ich.org\/sites\/default\/files\/M7_R1_Guideline.pdf\" target=\"_blank\" rel=\"noopener\"><b>ICH M7<\/b><\/a><\/span><span style=\"font-weight: 400\">.<\/span><\/p><p><span style=\"font-weight: 400\">Na \u00faltima atualiza\u00e7\u00e3o da resposta, o <\/span><i><span style=\"font-weight: 400\">N-nitroso dabigatrano <\/span><\/i><span style=\"font-weight: 400\">e o valor limite associado foram adicionados \u00e0 tabela, na qual foi adicionada uma coluna de &#8220;Fonte&#8221;, onde as subst\u00e2ncias ativas s\u00e3o indicadas em cada caso como uma fonte potencial das nitrosaminas correspondentes. Al\u00e9m disso, \u00e9 explicado mais detalhadamente como o valor limite deve ser determinado se a subst\u00e2ncia ativa estiver presente no produto na forma de sal <br \/>ou outras formas.<\/span><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-f729868 elementor-widget elementor-widget-spacer\" data-id=\"f729868\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"spacer.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.23.0 - 05-08-2024 *\/\n.elementor-column .elementor-spacer-inner{height:var(--spacer-size)}.e-con{--container-widget-width:100%}.e-con-inner>.elementor-widget-spacer,.e-con>.elementor-widget-spacer{width:var(--container-widget-width,var(--spacer-size));--align-self:var(--container-widget-align-self,initial);--flex-shrink:0}.e-con-inner>.elementor-widget-spacer>.elementor-widget-container,.e-con>.elementor-widget-spacer>.elementor-widget-container{height:100%;width:100%}.e-con-inner>.elementor-widget-spacer>.elementor-widget-container>.elementor-spacer,.e-con>.elementor-widget-spacer>.elementor-widget-container>.elementor-spacer{height:100%}.e-con-inner>.elementor-widget-spacer>.elementor-widget-container>.elementor-spacer>.elementor-spacer-inner,.e-con>.elementor-widget-spacer>.elementor-widget-container>.elementor-spacer>.elementor-spacer-inner{height:var(--container-widget-height,var(--spacer-size))}.e-con-inner>.elementor-widget-spacer.elementor-widget-empty,.e-con>.elementor-widget-spacer.elementor-widget-empty{position:relative;min-height:22px;min-width:22px}.e-con-inner>.elementor-widget-spacer.elementor-widget-empty .elementor-widget-empty-icon,.e-con>.elementor-widget-spacer.elementor-widget-empty .elementor-widget-empty-icon{position:absolute;top:0;bottom:0;left:0;right:0;margin:auto;padding:0;width:22px;height:22px}<\/style>\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-0c12f27 elementor-widget elementor-widget-image\" data-id=\"0c12f27\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.23.0 - 05-08-2024 *\/\n.elementor-widget-image{text-align:center}.elementor-widget-image a{display:inline-block}.elementor-widget-image a img[src$=\".svg\"]{width:48px}.elementor-widget-image img{vertical-align:middle;display:inline-block}<\/style>\t\t\t\t\t\t\t<figure class=\"wp-caption\">\n\t\t\t\t\t\t\t\t\t\t<img fetchpriority=\"high\" decoding=\"async\" width=\"400\" height=\"190\" src=\"https:\/\/insilicall.com\/wp-content\/uploads\/2022\/10\/unnamed-2.png\" class=\"attachment-large size-large wp-image-12783\" alt=\"Atualiza\u00e7\u00f5es\" srcset=\"https:\/\/insilicall.com\/wp-content\/uploads\/2022\/10\/unnamed-2.png 400w, https:\/\/insilicall.com\/wp-content\/uploads\/2022\/10\/unnamed-2-300x143.png 300w\" sizes=\"(max-width: 400px) 100vw, 400px\" \/>\t\t\t\t\t\t\t\t\t\t\t<figcaption class=\"widget-image-caption wp-caption-text\">N-nitroso dabigatrano <\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-325c3a5 elementor-widget elementor-widget-text-editor\" data-id=\"325c3a5\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><b>(Rev. 10) 14. Qual \u00e9 a abordagem para pedidos de AIM novos e em andamento?<\/b><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-f7443d1 elementor-widget elementor-widget-text-editor\" data-id=\"f7443d1\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><span style=\"font-weight: 400\">Os requerentes devem projetar seus processos de fabrica\u00e7\u00e3o e controles para prevenir ou, se poss\u00edvel, mitigar a presen\u00e7a de N-nitrosaminas em seus IFAs e produtos acabados.<\/span><\/p><p><span style=\"font-weight: 400\">A presen\u00e7a nitrosaminas deve ser avaliada como parte da Autoriza\u00e7\u00e3o de Introdu\u00e7\u00e3o no Mercado da seguinte forma:<\/span><\/p><ul><li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Na fase de submiss\u00e3o;<\/span><\/li><li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Durante o procedimento de avalia\u00e7\u00e3o da AIM.<\/span><\/li><\/ul><p><span style=\"font-weight: 400\">O modelo completo dessa avalia\u00e7\u00e3o pode ser encontrado no site do <\/span><span style=\"color: #003366\"><strong><a style=\"color: #003366\" href=\"https:\/\/www.hma.eu\/human-medicines\/cmdh.html\" target=\"_blank\" rel=\"noopener\">CMDh<\/a><\/strong><\/span><span style=\"font-weight: 400\">.<\/span><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-ffe9224 elementor-widget elementor-widget-text-editor\" data-id=\"ffe9224\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><b>(Rev.8) 15. Quando um teste para nitrosaminas deve ser inclu\u00eddo no dossi\u00ea de AIM?<\/b><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-b32077b elementor-widget elementor-widget-text-editor\" data-id=\"b32077b\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><b>1) Teste padr\u00e3o do produto acabado para nitrosaminas<\/b><\/p><p><span style=\"font-weight: 400\">S\u00e3o necess\u00e1rios quando a causa da contamina\u00e7\u00e3o por nitrosaminas n\u00e3o \u00e9 evidente ou\u00a0 quando pode ser demonstrado que a contamina\u00e7\u00e3o surgiu durante o processo de fabrica\u00e7\u00e3o do produto acabado ou durante seu armazenamento (a refer\u00eancia ao armazenamento foi adicionada recentemente ao texto).<\/span><b><\/b><\/p><p><b>2) Sele\u00e7\u00e3o do ponto de controle no produto acabado, IFA ou est\u00e1gio intermedi\u00e1rio\u00a0<\/b><\/p><p><span style=\"font-weight: 400\">O requisito de um limite a ser definido na especifica\u00e7\u00e3o do produto acabado, mesmo que o ponto de controle n\u00e3o esteja no est\u00e1gio do produto acabado, foi eliminado.\u00a0<\/span><\/p><p><span style=\"font-weight: 400\">A inclus\u00e3o do teste de nitrosaminas na especifica\u00e7\u00e3o do produto acabado \u00e9 dispens\u00e1vel se o n\u00edvel da impureza estiver abaixo de 10% da ingest\u00e3o aceit\u00e1vel (IA) relacionada \u00e0 subst\u00e2ncia ativa ou produto acabado (a refer\u00eancia \u00e0 IA do IFA \u00e9 nova).<\/span><\/p><p><span style=\"font-weight: 400\">Um teste reduzido para nitrosaminas (<\/span><i><span style=\"font-weight: 400\">skip-testing<\/span><\/i><span style=\"font-weight: 400\">), de acordo com a defini\u00e7\u00e3o <\/span><span style=\"color: #003366\"><a style=\"color: #003366\" href=\"https:\/\/database.ich.org\/sites\/default\/files\/Q6A%20Guideline.pdf\" target=\"_blank\" rel=\"noopener\"><b>ICH Q6A<\/b><\/a><\/span><span style=\"font-weight: 400\">, \u00e9 aceito se o conte\u00fado de uma \u00fanica nitrosamina estiver abaixo de 30% da ingest\u00e3o aceit\u00e1vel relacionada \u00e0 subst\u00e2ncia ativa ou ao produto acabado.<\/span><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-9485a1f elementor-widget elementor-widget-text-editor\" data-id=\"9485a1f\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><b>(Rev. 9) 20. Quais s\u00e3o as medidas regulat\u00f3rias tomadas pelas autoridades ap\u00f3s a identifica\u00e7\u00e3o de uma N-nitrosamina que excede a IA?<\/b><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-573f353 elementor-widget elementor-widget-text-editor\" data-id=\"573f353\" data-element_type=\"widget\" data-settings=\"{&quot;ultimate_floating_fx_translate_y&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><span style=\"font-weight: 400\">Esta quest\u00e3o e os esclarecimentos correspondentes foram inclu\u00eddos recentemente no documento. Ele descreve as medidas regulat\u00f3rias tomadas pelas autoridades para os chamados casos do \u201ccen\u00e1rio A\u201d<\/span><\/p><p><span style=\"font-weight: 400\">Um \u201ccen\u00e1rio A\u201d acontece quando uma ou mais nitrosaminas detectadas em um produto acabado est\u00e3o acima do limite de IA ou quando a soma de todas as nitrosaminas detectadas excede o risco de 1 em 100.000 ao longo da vida.<\/span><\/p><p><span style=\"font-weight: 400\">Para este cen\u00e1rio, uma autoridade pr\u00e9 determinada assume a lideran\u00e7a na an\u00e1lise das informa\u00e7\u00f5es dispon\u00edveis e fornece uma avalia\u00e7\u00e3o preliminar do caso. A criticidade do medicamento \u00e9 avaliada de acordo com os requisitos do documento EMA \u201c<\/span><span style=\"color: #003366\"><a style=\"color: #003366\" href=\"https:\/\/www.ema.europa.eu\/en\/documents\/other\/criteria-classification-critical-medicinal-products_en.pdf\" target=\"_blank\" rel=\"noopener\"><b>Crit\u00e9rios para classifica\u00e7\u00e3o de medicamentos cr\u00edticos para uso humano e veterin\u00e1rio<\/b><\/a><\/span><span style=\"font-weight: 400\">\u201d.\u00a0<\/span><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"<p>Atualiza\u00e7\u00f5es do question\u00e1rio da EMA sobre contamina\u00e7\u00e3o por nitrosaminas A European Medicines Agency (EMA), ag\u00eancia respons\u00e1vel pela avalia\u00e7\u00e3o cient\u00edfica, supervis\u00e3o [&hellip;]<\/p>\n","protected":false},"author":8,"featured_media":12790,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"rank_math_lock_modified_date":false,"footnotes":""},"categories":[110,142,79],"tags":[172,141,230,111,112,229,123],"class_list":["post-12743","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-atualidades","category-ciencia","category-noticias","tag-atualizacoes","tag-contaminacao","tag-ema","tag-n-nitrosaminas","tag-nitrosaminas","tag-revisao","tag-toxicologia-regulatoria","no-social-count","single-post-item mb40"],"_links":{"self":[{"href":"https:\/\/insilicall.com\/wp-json\/wp\/v2\/posts\/12743"}],"collection":[{"href":"https:\/\/insilicall.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/insilicall.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/insilicall.com\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/insilicall.com\/wp-json\/wp\/v2\/comments?post=12743"}],"version-history":[{"count":59,"href":"https:\/\/insilicall.com\/wp-json\/wp\/v2\/posts\/12743\/revisions"}],"predecessor-version":[{"id":15227,"href":"https:\/\/insilicall.com\/wp-json\/wp\/v2\/posts\/12743\/revisions\/15227"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/insilicall.com\/wp-json\/wp\/v2\/media\/12790"}],"wp:attachment":[{"href":"https:\/\/insilicall.com\/wp-json\/wp\/v2\/media?parent=12743"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/insilicall.com\/wp-json\/wp\/v2\/categories?post=12743"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/insilicall.com\/wp-json\/wp\/v2\/tags?post=12743"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}