<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>0034-7418</journal-id>
<journal-title><![CDATA[Revista Colombiana de Ciencias Químico - Farmacéuticas]]></journal-title>
<abbrev-journal-title><![CDATA[Rev. colomb. cienc. quim. farm.]]></abbrev-journal-title>
<issn>0034-7418</issn>
<publisher>
<publisher-name><![CDATA[Departamento de Farmácia, Facultad de Ciencias, Universidade Nacional da Colombia]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0034-74182023000200816</article-id>
<article-id pub-id-type="doi">10.15446/rcciquifa.v52n2.106516</article-id>
<title-group>
<article-title xml:lang="en"><![CDATA[Determination of bacterial endotoxins in normal intravenous human immunoglobulin on the replacement of rabbit pyrogen testing in Brazil]]></article-title>
<article-title xml:lang="es"><![CDATA[Determinación de endotoxinas bacterianas en inmunoglobulina humana intravenosa normal en reemplazo de la prueba de pirógenos de conejo en Brasil]]></article-title>
<article-title xml:lang="pt"><![CDATA[Determinação de endotoxinas bacterianas em imunoglobulina humana intravenosa normal em substituição ao teste de pirogênio em coelhos no Brasil]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Vidal Pereira]]></surname>
<given-names><![CDATA[Alessandra]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Freitas de Farias]]></surname>
<given-names><![CDATA[Hendro]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Faria Fíngula]]></surname>
<given-names><![CDATA[Fernando]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Gomes Albertino]]></surname>
<given-names><![CDATA[Sheila Regina]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Serodio]]></surname>
<given-names><![CDATA[Lilia]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Fundação Oswaldo Cruz  ]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
<country>Brasil</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>08</month>
<year>2023</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>08</month>
<year>2023</year>
</pub-date>
<volume>52</volume>
<numero>2</numero>
<fpage>816</fpage>
<lpage>825</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_arttext&amp;pid=S0034-74182023000200816&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_abstract&amp;pid=S0034-74182023000200816&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_pdf&amp;pid=S0034-74182023000200816&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[SUMMARY  Introduction The normal intravenous human immunoglobulin is a sterile liquid or lyophilized preparation, with immunoglobulins, especially the immunoglobulin G (IgG). The National Institute for Quality Control in Health (NIQCH) performs analysis of biological products before being distributed to the population. The batches are subjected to physicochemical and biosafety assays. The rabbit pyrogen test (RPT) is a biosafety assay performed to check the contamination by agents that cause fever in the patient and, in cases of high concentration, can lead to death.  Aim To compare the results of RPT and bacterial endotoxins assays of ten samples.  Methods In RPT, both the product is injected into the rabbit's marginal ear vein and the individual body temperature variations of the animals are evaluated. The bacterial endotoxin assay uses the kinetic chromogenic method, according to the Brazilian Pharmacopoeia and the international compendiums.  Results The tests of were plotted in a table for comparison. The tests coincided in 9 samples, except for a sample that presented bacterial endotoxin pyrogenicity.  Conclusion Bacterial endotoxin assay must be considered as an alternative method for animal tests.]]></p></abstract>
<abstract abstract-type="short" xml:lang="es"><p><![CDATA[RESUMEN  Introducción la inmunoglobulina humana intravenosa normal es una preparación líquida o liofilizada estéril, con inmunoglobulinas, especialmente la inmunoglobulina G (IgG). El Instituto Nacional de Control de Calidad en Salud (INCQS) realiza análisis de productos biológicos antes de ser distribuidos a la población. Los lotes se someten a ensayos fisicoquímicos y de bioseguridad. La prueba de pirógenos en conejo (RPT) es un ensayo de bioseguridad que se realiza para verificar la contaminación por agentes que causan fiebre en el paciente y, en casos de alta concentración, pueden causar la muerte.  Objetivo comparar los resultados de los ensayos de RPT y endotoxinas bacterianas de diez muestras.  Métodos en RPT, el producto se inyecta en la vena marginal de la oreja del conejo y se evalúan las variaciones de temperatura corporal individual de los animales. El ensayo de endotoxinas bacterianas utiliza el método cromogénico cinético, de acuerdo con la Farmacopea Brasileña y los compendios internacionales.  Resultados las pruebas de se trazaron en una tabla para comparación. Las pruebas coincidieron en 9 muestras, excepto en una muestra que presentó pirogenicidad de endotoxina bacteriana.  Conclusión el ensayo de endotoxinas bacterianas debe considerarse como un método alternativo para las pruebas en animales.]]></p></abstract>
<abstract abstract-type="short" xml:lang="pt"><p><![CDATA[RESUMO  Introdução a imunoglobulina humana intravenosa normal é uma preparação líquida estéril ou liofilizada, com imunoglobulinas, principalmente a imunoglobulina G (IgG). O Instituto Nacional de Controle de Qualidade em Saúde (INCQS) realiza análises de produtos biológicos antes de serem distribuídos à população. Os lotes são submetidos a ensaios físico-químicos e de segurança. O teste de pirogênio em coelhos (RPT) é um ensaio de segurança realizado para verificar a contaminação por agentes que causam febre no paciente e, em casos de alta concentração, podem levar ao óbito.  Objetivo comparar os resultados dos ensaios de RPT e endotoxinas bacterianas de onze amostras.  Métodos no RPT, o produto é injetado na veia marginal da orelha do coelho, e as variações de temperatura corporal individual dos animais são avaliadas. O ensaio de endotoxina bacteriana utiliza o método cromogênico cinético, de acordo com a Farmacopéia Brasileira e os compêndios internacionais.  Resultados os resultados dos ensaios foram plotados em uma tabela para comparação. Os testes coincidiram em 9 amostras, com exceção de 2 amostra que foram discrepantes na comparação entre os dois ensaios.  Conclusão o ensaio de endotoxina bacteriana deve ser considerado como um método alternativo para testes em animais.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[Normal human immunoglobulin]]></kwd>
<kwd lng="en"><![CDATA[pyrogen]]></kwd>
<kwd lng="en"><![CDATA[bacterial endotoxin]]></kwd>
<kwd lng="es"><![CDATA[Inmunoglobulina humana normal]]></kwd>
<kwd lng="es"><![CDATA[pirógeno]]></kwd>
<kwd lng="es"><![CDATA[endotoxina bacteriana]]></kwd>
<kwd lng="pt"><![CDATA[Imunoglobulina humana normal]]></kwd>
<kwd lng="pt"><![CDATA[pirogênio]]></kwd>
<kwd lng="pt"><![CDATA[endotoxina bacteriana]]></kwd>
</kwd-group>
</article-meta>
</front><back>
<ref-list>
<ref id="B1">
<label>[1]</label><nlm-citation citation-type="book">
<collab>ANVISA</collab>
<source><![CDATA[Farmacopéia Brasileira]]></source>
<year>2019</year>
<edition>6ª</edition>
<publisher-loc><![CDATA[Brasil ]]></publisher-loc>
<publisher-name><![CDATA[Resolução de Diretoria Colegiada RDC nº 298]]></publisher-name>
</nlm-citation>
</ref>
<ref id="B2">
<label>[2]</label><nlm-citation citation-type="">
<collab>European Pharmacopoeia</collab>
<source><![CDATA[Human normal immunoglobulin for intravenous administration]]></source>
<year>2022</year>
<volume>10.8</volume>
<page-range>6929-30</page-range></nlm-citation>
</ref>
<ref id="B3">
<label>[3]</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Zervos]]></surname>
<given-names><![CDATA[C.]]></given-names>
</name>
<name>
<surname><![CDATA[Zimmerman]]></surname>
<given-names><![CDATA[T.P.]]></given-names>
</name>
<name>
<surname><![CDATA[Willis]]></surname>
<given-names><![CDATA[T.]]></given-names>
</name>
<name>
<surname><![CDATA[Flexman]]></surname>
<given-names><![CDATA[G.]]></given-names>
</name>
<name>
<surname><![CDATA[Srivastava]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
<name>
<surname><![CDATA[Silverstein]]></surname>
<given-names><![CDATA[R.]]></given-names>
</name>
<name>
<surname><![CDATA[Williams]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
<name>
<surname><![CDATA[Vandeberg]]></surname>
<given-names><![CDATA[P.]]></given-names>
</name>
<name>
<surname><![CDATA[Culp]]></surname>
<given-names><![CDATA[J.L.]]></given-names>
</name>
<name>
<surname><![CDATA[Burns]]></surname>
<given-names><![CDATA[D.]]></given-names>
</name>
<name>
<surname><![CDATA[Barham]]></surname>
<given-names><![CDATA[V.]]></given-names>
</name>
<name>
<surname><![CDATA[Durham]]></surname>
<given-names><![CDATA[A.]]></given-names>
</name>
<name>
<surname><![CDATA[Malinzak]]></surname>
<given-names><![CDATA[D.A.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Immunoglobulin G from single plasma donor in immune globulin intravenous causes false positive pyrogen test]]></article-title>
<source><![CDATA[Biologicals]]></source>
<year>2019</year>
<volume>59</volume>
<page-range>12-9</page-range></nlm-citation>
</ref>
<ref id="B4">
<label>[4]</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[McCullough]]></surname>
<given-names><![CDATA[K.Z.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA["Fit for purpose" endotoxin analytes]]></article-title>
<source><![CDATA[American Pharmaceutical Review]]></source>
<year>2019</year>
</nlm-citation>
</ref>
<ref id="B5">
<label>[5]</label><nlm-citation citation-type="">
<collab>European Medicines Agency</collab>
<source><![CDATA[Guideline on the replacement of rabbit pyrogen testing by an alternative test for plasma derived medicinal products]]></source>
<year>2009</year>
<page-range>1-6</page-range></nlm-citation>
</ref>
<ref id="B6">
<label>[6]</label><nlm-citation citation-type="">
<collab>ANVISA</collab>
<source><![CDATA[Resolução RDC n° 73 de 21/10/2008]]></source>
<year>2008</year>
</nlm-citation>
</ref>
<ref id="B7">
<label>[7]</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Iwanaga]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Biochemical principle of Limulus test for detecting bacterial endotoxins]]></article-title>
<source><![CDATA[Proc. Jpn. Acad. Ser. B, Phys. Biol. Sci.]]></source>
<year>2007</year>
<volume>83</volume>
<numero>4</numero>
<issue>4</issue>
<page-range>110-9</page-range></nlm-citation>
</ref>
<ref id="B8">
<label>[8]</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Halder]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Three Rs potential in the development and quality control of immunobiologicals]]></article-title>
<source><![CDATA[ALTEX]]></source>
<year>2001</year>
<volume>18</volume>
<numero>Suppl 1</numero>
<issue>Suppl 1</issue>
<page-range>13-47</page-range></nlm-citation>
</ref>
<ref id="B9">
<label>[9]</label><nlm-citation citation-type="">
<collab>Food and Drug Administration - FDA</collab>
<source><![CDATA[Guideline on validation of the Limulus Amebocyte Lysate test as an end-product endotoxin test for human and animal parenteral drugs, biological products, and medical devices]]></source>
<year>1987</year>
</nlm-citation>
</ref>
<ref id="B10">
<label>[10]</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Elkhateeb]]></surname>
<given-names><![CDATA[M.A.]]></given-names>
</name>
<name>
<surname><![CDATA[Elkhatib]]></surname>
<given-names><![CDATA[W.]]></given-names>
</name>
<name>
<surname><![CDATA[Aboulwafa]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[An expert review on current approaches for endotoxin detection in various biological products]]></article-title>
<source><![CDATA[Archives of Pharmaceutical Sciences Ain Shams University]]></source>
<year>2019</year>
<volume>3</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>142-53</page-range></nlm-citation>
</ref>
<ref id="B11">
<label>[11]</label><nlm-citation citation-type="">
<collab>World Health Organization</collab>
<source><![CDATA[A WHO guide to good manufacturing practice (GMP) requirements. Part 2: Validation]]></source>
<year>1997</year>
</nlm-citation>
</ref>
<ref id="B12">
<label>[12]</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Castle]]></surname>
<given-names><![CDATA[P.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Alternatives to animal testing: Achievements and recent developments in the European Pharmacopoeia]]></article-title>
<source><![CDATA[Developments in Biological Standardization]]></source>
<year>1996</year>
<volume>86</volume>
<page-range>21-9</page-range></nlm-citation>
</ref>
<ref id="B13">
<label>[13]</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Hartung]]></surname>
<given-names><![CDATA[T.]]></given-names>
</name>
<name>
<surname><![CDATA[Aaberge]]></surname>
<given-names><![CDATA[I.]]></given-names>
</name>
<name>
<surname><![CDATA[Berthold]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
<name>
<surname><![CDATA[Carlin]]></surname>
<given-names><![CDATA[G.]]></given-names>
</name>
<name>
<surname><![CDATA[Charton]]></surname>
<given-names><![CDATA[E.]]></given-names>
</name>
<name>
<surname><![CDATA[Coecke]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
<name>
<surname><![CDATA[Fennrich]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
<name>
<surname><![CDATA[Fischer]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
<name>
<surname><![CDATA[Gommer]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
<name>
<surname><![CDATA[Halder]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
<name>
<surname><![CDATA[Haslov]]></surname>
<given-names><![CDATA[K.]]></given-names>
</name>
<name>
<surname><![CDATA[Jahnke]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
<name>
<surname><![CDATA[Montag-Lessing]]></surname>
<given-names><![CDATA[T.]]></given-names>
</name>
<name>
<surname><![CDATA[Poole]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
<name>
<surname><![CDATA[Schechtman]]></surname>
<given-names><![CDATA[L.]]></given-names>
</name>
<name>
<surname><![CDATA[Wendel]]></surname>
<given-names><![CDATA[A.]]></given-names>
</name>
<name>
<surname><![CDATA[Werner-Felmayer]]></surname>
<given-names><![CDATA[G.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Novel pyrogen tests based on the human fever reaction: The Report and Recommendations of ECVAM Workshop 43. European Centre for the Validation of Alternative Methods]]></article-title>
<source><![CDATA[Alternatives to Laboratory Animals]]></source>
<year>2001</year>
<volume>29</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>99-123</page-range></nlm-citation>
</ref>
<ref id="B14">
<label>[14]</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Charton]]></surname>
<given-names><![CDATA[E.]]></given-names>
</name>
<name>
<surname><![CDATA[Castle]]></surname>
<given-names><![CDATA[P.]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Reduction, replacement and refinement of animal tests in the European Pharmacopoeia: Recent developments for monographs on biological substances and preparations]]></article-title>
<source><![CDATA[PHARMEUROPA]]></source>
<year>2001</year>
<volume>13</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>94-6</page-range></nlm-citation>
</ref>
<ref id="B15">
<label>[15]</label><nlm-citation citation-type="">
<collab>ANVISA</collab>
<source><![CDATA[Resolução RDC nº 658, 30 de março de 2022]]></source>
<year>2022</year>
</nlm-citation>
</ref>
<ref id="B16">
<label>[16]</label><nlm-citation citation-type="">
<collab>CONCEA</collab>
<source><![CDATA[Resolução Normativa no 31, 18 de agosto de 2016]]></source>
<year>2016</year>
</nlm-citation>
</ref>
</ref-list>
</back>
</article>
