Establishment of a Reference Material in Quality Control for Use in Infectivity and Identity Assays of Recombinant COVID-19 Vaccine, in Accordance with International Standards Organization Guidance.

The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), began in 2019. One of the strategies for pandemic control was mass vaccination. In Brazil, the recombinant COVID-19 vaccine (RCV) was produced on a large scale and offered at no charge to the population. The specifications for quality control analyses of RCV included identity and infectivity determination. To validate the results, a reference material (RM) must be analyzed in parallel with the sample vaccine. This research aimed to establish the RM for use in the identity and infectivity assay for RCV. The candidate RM was analyzed using homogeneity and stability studies. The RM was considered homogeneous for identity (cycle threshold (Ct) ≤ 25.19) and infectivity (average x- was 9.25 log10 infectious units/mL). The RM was considered adequately stable for identity during the total period in all studies, being stable at -70, 5, and 22.5 °C for 380, 313, and 14 days, respectively (Ct ≤ 21.81). For infectivity, the RM was stable at -70, 5, and 22.5 °C for 380, 97, and three days, respectively. Since the property identity and infectivity values of the RM were established, the new RM could be used in quality control analysis.

Development of a new reference material for accurate measurements of lithium in Li-clays.

Currently, there are no national and international certified reference materials (CRM) in lithium clays that can make reliable and traceable lithium measurements for the International System of Units (SI). Hence, it is necessary to have references to meet the needs in terms of mining and activities that involve the use of lithium to favor the economy derived from its multiple uses and associated benefits in the exploration, exploitation, and handling of lithium ore. In this study, a candidate for reference material (RM) of Li in clays was developed and certified based on the provisions of ISO 17034:2016 and ISO Guide 35:2017. Different mass sizes of the RM (0.05, 0.1, and 0.25 g) were used to evaluate homogeneity. An isochronous study (short-term stability) was carried out in the assessment of stability, influenced by the effects of transport at different temperatures (20, 40, and 50 °C) for a determined time of 6 weeks, in addition to a classic (long-term) study for 19 weeks. The sample was treated using microwave-assisted acid digestion and Li measurements were performed using the analytical technique of Flame Atomic Absorption Spectrometry (FAAS). The CRM is homogeneous for the sample mass sizes of 0.05 and 0.1 g, and the mass fraction of w(Li) was stable in the RM for temperatures of 20, 40, and 50 °C. The determined period of validity was 3 years.

Developing Amphetamine Certified Reference Materials: From Batch and Continuous-Flow Synthesis to Certification Protocol.

Certified reference materials (CRM) of amphetamine derivatives were produced through a simple, rapid and efficient synthesis in both batch and continuous-flow conditions, accompanied by the development of a comprehensive certification protocol for this class of substances. Our chemistry enabled the synthesis of MDA, MDMA, PMA and PMMA in two steps from safrole and estragole with overall yields of 38-61 % in 48 hours under batch conditions and 61-65 % in 65 minutes under continuous-flow conditions, followed by the development of a certification protocol for these materials through identity checking, homogeneity, stability, and characterization studies. Furthermore, as result of this work, a very pure CRM of MDA.HCl with 99.1±1.4 g/100 g of certified characterization value was produced. Considering the importance of supplying amphetamine calibrants for public security efforts in Forensic Chemistry, the potential therapeutical applications, and responding to the rising demand for the synthesis of CRM, this work presents a pioneering approach for the production of amphetamine and related compounds.

Establishment of certified reference material for the potency assay in yellow fever vaccine quality control, in accordance with International Standards Organization guidance.

The attenuated yellow fever vaccine (YFV) is offered free of charge to the Brazilian population through the National Immunization Program (NIP). One of the specifications for quality control analyses of the vaccine is the potency determination. This test determines the number of plaque forming units (PFU) in Vero cells. In order to validate the results, the reference material (RM) is analysed in parallel with an established reference vaccine. The aim of this study was to establish certified RM for use as an internal control in the potency assay for the production chain of YFV. The candidate RM homogeneity and stability were determined, and characterized by a collaborative study for further certification. The RM was considered sufficiently homogeneous with average 4.68 log10 IU/HD and stable at (-20 ± 10) ºC and (22.5 ± 2.5) ºC for 715 and 183 days, respectively. When reconstituted and stored in aliquots of 0.6 mL, it was stable at (-20 ± 10) ºC for eight days. But it was not stable at (5 ± 3) ºC for three days. In a collaborative study, two independents' laboratories gave an averaged value of 4.56 ± 0.030 log10 IU/HD. After determining the expanded uncertainty of homogeneity, stability, and characterization, the certified RM lot: 195VFA020Z presented a property value of 4.56 ± 0.22 log10 IU/HD. It was concluded that the new certified RM can be used in routine analysis of a YFV producer, since it has its property value established and it is stable. The possibility of using it in aliquots after reconstitution will also allow the RM to have a much longer shelf life.

Homogeneity and stability assessment of a candidate to pumpkin seed flour reference material by means of computer vision based chemometrics assisted approach.

This study proposes a preliminary assessment of the homogeneity and stability through digital image acquisition of a candidate for mechanically processed pumpkin seed meal reference material, exploring the concepts of homogeneity curve and the analysis of texture characteristics by Continuous-Level Moving Block through Robust Principal Component Analysis. This innovative methodology allowed us to examine the percentage of homogeneity in a set of samples, revealing an average of 41% with only one outlier in relation to the entire sample, indicating low homogeneity. In the stability study carried out after storing samples for 12 months at different temperatures, 83% of the samples were considered regular and 17% were outlier, which means that most of them were considered stable. Therefore, this methodology is useful for screening samples for homogeneity, by textural analysis, and detected non-homogeneity can be corrected in advance for quantification by standard protocols.

Feasibility of Reference Material Certification for Speed of Sound and Attenuation Coefficient Based on Standard Tissue-Mimicking Material.

Speed of sound and attenuation are essential for characterizing reference materials such as biological tissue-mimicking materials (TMMs) used in ultrasonic applications. There are many publications on the manufacture of TMMs and the measurement of their properties. However, no studies in the literature have applied the metrological approach of International Organization for Standardization (ISO) Guide 35 to certify biological ultrasound TMMs as candidates for reference materials (RMs). The work described here was aimed at studying the process for manufacturing fat, muscle and aorta artery TMMs, including the study of the homogeneity, stability, trend and characterization of TMMs. The properties of interest were the speed of sound (SoS) and attenuation coefficient (AttC) at 7.5 MHz, with target expanded uncertainty of 40 m/s and 0.3 dB/cm, respectively. The short-term stability study was 2 mo at 4°C and 40°C (simulating possible transportation conditions). The long-term stability study lasted an additional 4 mo with the TMM at 22°C (simulating possible storage conditions). Homogeneity was evaluated before the stability study. Uncertainties associated with homogeneity, stability, characterization and trend were duly calculated. No trend was observed in this study, but the AttC spread widely during the stability test, substantially enlarging the final uncertainty. Therefore, this property could not be used to certify TMM candidates as RMs. However, the SoSs for most TMMs lay within the target uncertainty, disclosing viability to certify TMMs as RMs for this property. Assigned values for SoS were 1560 m/s for aorta TMM with an average expanded uncertainty for certificate validity of 12 mo (Ue;12=20 m/s), 1552 m/s for muscle TMM (Ue;12=20 m/s) and 1494 m/s for fat TMM (Ue;12=11 m/s). Thus, TMMs were proved suitable to be certified as RMs for SoS.

Elaboration of reference material for cadmium and arsenic in hydrobiological products, for the purpose of being used in a laboratory intercomparation program / Elaboración de un material de referencia para cadmio y arsénico en productos hidrobiológicos, para propósito de ser utilizado en un programa de intercomparación de laboratorios

Reference materials (RM) are tools used in the comparability and traceability of measurements. They are widely used by laboratories for method validation and quality control of assay. Chile must evaluate theperformance of laboratories that analyzing metals in fishery products, despite RM have high prices and are scarce. For that reason, a RM in a hydrobiological product was developed. Reference values for arsenic and cadmium elements for a fishmeal were assigned. The measurement methods for characterization of the material were Inductively Coupled Plasma Mass Spectrometry, Atomic Absorption Spectrometry and Neutron Activation Analysis. Reference values with their expanded uncertainty (U) were established for arsenic 2.64 ± 0.42 mg/kg (U; k = 2) and for cadmium 0.86 ± 0.16 mg/kg (U; k = 2). Homogeneity and stability of the RM allowed its use in a proficiency test for eleven food control laboratories. Results for median were 2.114 mg/kg for arsenic, and 0.863 mg/kg for cadmium. The performance values of the participants were evaluated with a z score obtaining 60% satisfaction for arsenic and 73% for cadmium.The material demonstrated to be suitable for use in interlaboratory proficiency assay. (AU)

Materiales de referencia (MR) son herramientas utilizadas en la comparabilidad y trazabilidad entre mediciones. Laboratorios los utilizan ampliamente en validación de métodos y control de calidad. Chile debe evaluar el desempeño de los laboratorios que analizan metales en productos pesqueros, a pesar de los altos precios y escasez del MR. Por esa razón, se desarrolló un MR en producto hidrobiológico. Se asignaron valores de referencia para arsénico y cadmio en harina de pescado. Los métodos de medición para la caracterización del material fueron Espectrometría de Masas de Plasma Acoplado Inductivamente, Espectrometría de Absorción Atómica y Análisis de Activación de Neutrones. Se establecieron valores de referencia con su incertidumbre (U) para arsénico 2.64 ± 0.42 mg/kg (U; k = 2) y para cadmio 0.86 ± 0.16 mg/kg (U; k = 2). La homogeneidad y estabilidad del MR permitieron su uso en una prueba de aptitud para once laboratorios de control de alimentos. Las medianas fueron 2,114 mg/kg para arsénico y 0,863 mg/kg para cadmio. Se evaluaron los rendimientos de los participantes con un estadístico de puntaje z satisfactorio del 60% para el arsénico y 73% para el cadmio. El material demostró ser adecuado para uso en ensayo de aptitud de intercomparación. (AU)

Analytical and Clinical Performance of Amyloid-Beta Peptides Measurements in CSF of ADNIGO/2 Participants by an LC-MS/MS Reference Method.

BACKGROUND: Cerebrospinal fluid (CSF) amyloid-ß1-42 (Aß42) reliably detects brain amyloidosis based on its high concordance with plaque burden at autopsy and with amyloid positron emission tomography (PET) ligand retention observed in several studies. Low CSF Aß42 concentrations in normal aging and dementia are associated with the presence of fibrillary Aß across brain regions detected by amyloid PET imaging. METHODS: An LC-MS/MS reference method for Aß42, modified by adding Aß40 and Aß38 peptides to calibrators, was used to analyze 1445 CSF samples from ADNIGO/2 participants. Seventy runs were completed using 2 different lots of calibrators. For preparation of Aß42 calibrators and controls spiking solution, reference Aß42 standard with certified concentration was obtained from EC-JRC-IRMM (Belgium). Aß40 and Aß38 standards were purchased from rPeptide. Aß42 calibrators' accuracy was established using CSF-based Aß42 Certified Reference Materials (CRM). RESULTS: CRM-adjusted Aß42 calibrator concentrations were calculated using the regression equation Y (CRM-adjusted) = 0.89X (calibrators) + 32.6. Control samples and CSF pools yielded imprecision ranging from 6.5 to 10.2% (Aß42) and 2.2 to 7.0% (Aß40). None of the CSF pools showed statistically significant differences in Aß42 concentrations across 2 different calibrator lots. Comparison of Aß42 with Aß42/Aß40 showed that the ratio improved concordance with concurrent [18F]-florbetapir PET as a measure of fibrillar Aß (n = 766) from 81 to 88%. CONCLUSIONS: Long-term performance assessment substantiates our modified LC-MS/MS reference method for 3 Aß peptides. The improved diagnostic performance of the CSF ratio Aß42/Aß40 suggests that Aß42 and Aß40 should be measured together and supports the need for an Aß40 CRM.

On the equivalence between homogeneously prepared sources and sources prepared by seeding in layers for different geometries, energies and matrix parameters.

Measuring the radioactive content of environmental samples requires the use of appropriate reference materials with the same composition and density as the matrices to be measured. If they are not available, ad hoc artificially spiked reference materials are an alternative. Spiking in layers requires a detailed study of the drop distribution, as energy and decay scheme of the component radionuclides must be taken into account to produce a reference material that represents, in efficiency terms, a real sample. A method based on Monte Carlo simulation has been developed to find the optimal distribution of drops in layers for the combination of two typical soil samples and four radionuclides. Results have been validated by comparison with samples prepared by two techniques: methanol bath and spiking in layers.

Coffea arabica and C. canephora discrimination in roasted and ground coffee from reference material candidates by real-time PCR.

To produce specific desirable coffee blends, Coffea arabica and C. canephora are mixed each other, in some cases to suit consumer preference, but in others to reduce production costs. In this scenario, the aim of this work was to evaluate standard candidate reference materials (RMc) for analysis of different blends of roasted and ground coffee. For this purpose, we analyzed different percentages of C. arabica and C. canephora (100:0; 50:50; 25:75; and 0:100, respectively). These RMc samples were developed in a previous study with green coffee beans submitted to medium roasting. In this work, coffee species differentiation (C. arabica and C. canephora) was analyzed by real-time PCR, using specific primers previously developed, called ARA primers. The RMc material with 100% C. canephora did not present amplification, in contrast with the samples containing C. arabica, which all presented amplification. These results indicate the specificity of ARA primers for C. arabica and that the detection system assay can be used as a promising molecular tool to identify and quantify percentages of C. arabica in different coffee blends.

Evaluation of a fungal collection as certified reference material producer and as a biological resource center

Abstract Considering the absence of standards for culture collections and more specifically for biological resource centers in the world, in addition to the absence of certified biological material in Brazil, this study aimed to evaluate a Fungal Collection from Fiocruz, as a producer of certified reference material and as Biological Resource Center (BRC). For this evaluation, a checklist based on the requirements of ABNT ISO GUIA34:2012 correlated with the ABNT NBR ISO/IEC17025:2005, was designed and applied. Complementing the implementation of the checklist, an internal audit was performed. An evaluation of this Collection as a BRC was also conducted following the requirements of the NIT-DICLA-061, the Brazilian internal standard from Inmetro, based on ABNT NBR ISO/IEC 17025:2005, ABNT ISO GUIA 34:2012 and OECD Best Practice Guidelines for BRCs. This was the first time that the NIT DICLA-061 was applied in a culture collection during an internal audit. The assessments enabled the proposal for the adequacy of this Collection to assure the implementation of the management system for their future accreditation by Inmetro as a certified reference material producer as well as its future accreditation as a Biological Resource Center according to the NIT-DICLA-061.

Evaluation of a fungal collection as certified reference material producer and as a biological resource center

Considering the absence of standards for culture collections and more specifically for biological resource centers in the world, in addition to the absence of certified biological material in Brazil, this study aimed to evaluate a Fungal Collection from Fiocruz, as a producer of certified reference material and as Biological Resource Center (BRC). For this evaluation, a checklist based on the requirements of ABNT ISO GUIA34:2012 correlated with the ABNT NBR ISO/IEC17025:2005, was designed and applied. Complementing the implementation of the checklist, an internal audit was performed. An evaluation of this Collection as a BRC was also conducted following the requirements of the NIT-DICLA-061, the Brazilian internal standard from Inmetro, based on ABNT NBR ISO/IEC 17025:2005, ABNT ISO GUIA 34:2012 and OECD Best Practice Guidelines for BRCs. This was the first time that the NIT DICLA-061 was applied in a culture collection during an internal audit. The assessments enabled the proposal for the adequacy of this Collection to assure the implementation of the management system for their future accreditation by Inmetro as a certified reference material producer as well as its future accreditation as a Biological Resource Center according to the NIT-DICLA-061.(AU)

Evaluation of a fungal collection as certified reference material producer and as a biological resource center.

Considering the absence of standards for culture collections and more specifically for biological resource centers in the world, in addition to the absence of certified biological material in Brazil, this study aimed to evaluate a Fungal Collection from Fiocruz, as a producer of certified reference material and as Biological Resource Center (BRC). For this evaluation, a checklist based on the requirements of ABNT ISO GUIA34:2012 correlated with the ABNT NBR ISO/IEC17025:2005, was designed and applied. Complementing the implementation of the checklist, an internal audit was performed. An evaluation of this Collection as a BRC was also conducted following the requirements of the NIT-DICLA-061, the Brazilian internal standard from Inmetro, based on ABNT NBR ISO/IEC 17025:2005, ABNT ISO GUIA 34:2012 and OECD Best Practice Guidelines for BRCs. This was the first time that the NIT DICLA-061 was applied in a culture collection during an internal audit. The assessments enabled the proposal for the adequacy of this Collection to assure the implementation of the management system for their future accreditation by Inmetro as a certified reference material producer as well as its future accreditation as a Biological Resource Center according to the NIT-DICLA-061.

Estudo colaborativo nacional para o estabelecimento do material de referência de trabalho da vacina contra sarampo, caxumba e rubéola: evolução para a autossuficência na produção nacional da vacina tríplice viral / National collaborative study for establishing the working reference material of the vaccine against measles/mumps and rubella: evolution to the self-sufficiency in the national production of triple viral vaccine

A monografia farmacopeica da vacina tríplice viral (sarampo/caxumba/rubéola) exige a validação de desempenho do ensaio de potência utilizando-se apropriado material de referência (MR). Com o intuito de estabelecer o primeiro MR de trabalho (MRT) nacional para a vacina tríplice viral, foi realizado o estudo colaborativo nacional com a participação de duas únicas instituições que executam o ensaio de potência desta vacina, o Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos, produtor nacional) e o Instituto Nacional de Controle de Qualidade em Saúde.O material candidato (cMRTBio), preparado pelo produtor, foi avaliado pelos laboratórios participantes utilizando-se as respectivas metodologias in-house de determinação de potência. O cMRTBio foi considerado apropriado como MR in-house por estar em concordância com as especificações recomendadas nas normativas de compêndios, a saber: variações intra- (< 5 %), inter-ensaios (< 10 %) e entre laboratórios (< 10 %) abaixo dos limites aceitáveis; e potência estimada (log10 CCID50/DH) em 3,72 para sarampo, 4,80 para caxumba e 3,70 para rubéola. Este trabalho reflete o compromisso do único produtor nacional da vacina tríplice viral com a saúde pública, descrevendo-se a expansão da tecnologia, o cumprimento às diretrizes internacionais, o cuidado com o controle da qualidade e culminância para a autossuficiência nacional na produção de vacinas.

The pharmacopoeia monograph for the measles/mumps and rubella (MMR) triple vaccine demands to perform the validation of the potency assay by using the suitable reference material (MR). Aiming at establishing the firstwork MR (MRT) for the MMR triple vaccine, a national collaborative study was performed with the participation of the two unique national institutions working on the vaccine potency evaluation test, the Imunobiological Technology Institute (Bio-Manguinhos, national manufacturer) and the National Institute for Quality Control in Health. The candidate product (cMRTBio) prepared by the manufacturer was evaluated by the participant laboratories by employing the respective in-house methodologies for determining the potency. The cMRTBio was considered suitable as in-house MR, according to the specifications based on the normative compendia, being the intra-assay (< 5 %), inter-assay(< 10 %) and between laboratories variations (< 10 %) below the acceptable limits, and the estimate potency(log10 CCID50/DH) in 3.72 for measles, 4.80 for mumps and 3.70 for rubella. This study reflects the commitment of the unique national MMR vaccine producer to the public health, describing the expansion of technology,the compliance with international guidelines and the careful quality control, leading to the national self-sufficiency in the vaccine production.

National collaborative study for establishing the working reference material of the vaccine against measles/mumps and rubella: evolution to the self-sufficiency in the national production of triple viral vaccine / Estudo colaborativo nacional para o estabelecimento do material de referência de trabalho da vacina contra sarampo/caxumba e rubéola: evolução para a autossuficência na produção nacional da vacina tríplice viral

The pharmacopoeia monograph for the measles/mumps and rubella (MMR) triple vaccine demands to perform the validation of the potency assay by using the suitable reference material (MR). Aiming at establishing the first work MR (MRT) for the MMR triple vaccine, a national collaborative study was performed with the participation of the two unique national institutions working on the vaccine potency evaluation test, the Imunobiological Technology Institute (Bio-Manguinhos, national manufacturer) and the National Institute for Quality Control in Health. The candidate product (cMRTBio) prepared by the manufacturer was evaluated by the participant laboratories by employing the respective in-house methodologies for determining the potency. The cMRTBio was considered suitable as in-house MR, according to the specifications based on the normative compendia, being the intra-assay ( 5 %), inter-assay( 10 %) and between laboratories variations ( 10 %) below the acceptable limits, and the estimate potency (log10 CCID50/DH) in 3.72 for measles, 4.80 for mumps and 3.70 for rubella. This study reflects the commitment of the unique national MMR vaccine producer to the public health, describing the expansion of technology, the compliance with international guidelines and the careful quality control, leading to the national self-sufficiency in the vaccine production.(AU)

A monografia farmacopeica da vacina tríplice viral (sarampo/caxumba/rubéola) exige a validação de desempenho do ensaio de potência utilizando-se apropriado material de referência (MR). Com o intuito de estabelecer o primeiro MR de trabalho (MRT) nacional para a vacina tríplice viral, foi realizado o estudo colaborativo nacional com a participação de duas únicas instituições que executam o ensaio de potência desta vacina, o Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos, produtor nacional) e o Instituto Nacional de Controle de Qualidade em Saúde. O material candidato (cMRTBio), preparado pelo produtor, foi avaliado pelos laboratórios participantes utilizando-se as respectivas metodologias in-house de determinação de potência. O cMRTBio foi considerado apropriado como MR in-house por estar em concordância com as especificações recomendadas nas normativas de compêndios, a saber: variações intra- ( 5 %), inter-ensaios ( 10 %) e entre laboratórios ( 10 %) abaixo dos limites aceitáveis; e potência estimada (log10 CCID50/DH) em 3,72 para sarampo, 4,80 para caxumba e 3,70 para rubéola. Este trabalho reflete o compromisso do único produtor nacional da vacina tríplice viral com a saúde pública, descrevendo-se a expansão da tecnologia, o cumprimento às diretrizes internacionais, o cuidado com o controle da qualidade e culminância para a autossuficiência nacional na produção de vacinas.(AU)

USGS48 Puerto Rico precipitation - a new isotopic reference material for δ2H and δ18O measurements of water.

A new secondary isotopic reference material has been prepared from Puerto Rico precipitation, which was filtered, homogenised, loaded into glass ampoules, sealed with a torch, autoclaved to eliminate biological activity, and calibrated by dual-inlet isotope-ratio mass spectrometry. This isotopic reference material, designated as USGS48, is intended to be one of two isotopic reference waters for daily normalisation of stable hydrogen (δ(2)H) and stable oxygen (δ(18)O) isotopic analysis of water with a mass spectrometer or a laser absorption spectrometer. The δ(2)H and δ(18)O values of this reference water are-2.0±0.4 and-2.224±0.012 ‰, respectively, relative to Vienna Standard Mean Ocean Water on scales normalised such that the δ(2)H and δ(18)O values of Standard Light Antarctic Precipitation reference water are-428 and-55.5 ‰, respectively. Each uncertainty is an estimated expanded uncertainty (U=2u(c)) about the reference value that provides an interval that has about a 95 % probability of encompassing the true value. This isotopic reference water is available by the case of 144 glass ampoules containing 5 mL of water in each ampoule.

Estudo de homogeneidade dos soros utilizados em controle de qualidade interno de testes imunodiagnósticos de HIV/Aids / AidsHomogeneity study of the internal quality control sera for immunodiagnosis of HIV/AIDS

Introduction: The present study reports the data from the first homogeneity assessment of samples composing the serum panels produced at the Immunology Center of Instituto Adolfo Lutz, São Paulo. These samples have been distributed to the public laboratories and those partaking in the Brazilian Unified Health System, and to the participants in the Internal Quality Control Program for human immunodeficiency virus (HIV) antibody (Ab) testing. Objective: To assess the homogeneity of serum samples in panels from different lots for HIV/acquired immunodeficiency syndrome (AIDS) immunodiagnosis by using the statistical method to ensure quality of the reference material. Method: Sera homogeneity was evaluated by means of enzyme-linked immunoassay/enzyme immunoassay (ELISA/EIA) for detection of HIV Ab, and the one-way analysis of variance was employed for analyzing the data. No statistically significant differences were found among the several serum vials. Conclusion: The sera dispensed in the vials were homogeneous in the respective lots...

Introdução: No presente estudo estão descritos os resultados das primeiras análises feitas sobre a avaliação da homogeneidade das amostras componentes de painéis de soros produzidos no Centro de Imunologia do Instituto Adolfo Lutz e distribuídos aos laboratórios públicos e conveniados ao Sistema Único de Saúde e participantes do Programa de Controle de Qualidade Interno para imunodiagnóstico de vírus da imunodeficiência humana/síndrome da imunodeficiência adquirida (HIV/AIDS). Objetivo: Avaliar a homogeneidade das amostras de soro componentes de painéis de diferentes lotes para imunodiagnóstico de HIV/Aids por meio de método estatístico para garantir a qualidade do material de referência. Material e método: A homogeneidade das amostras de soro foi avaliada por meio de enzyme-linked immunoassay/enzyme immunoassay (ELISA/EIA) para detecção de anticorpos anti-HIV, e os resultados foram submetidos à análise de variância fator único. Não foram encontradas diferenças significativas entre os resultados obtidos para os diversos frascos de soro. Conclusão: As amostras distribuídas nos frascos foram homogêneas entre si nos respectivos lotes...

Necesidades metrológicas en los laboratorios clínicos / Metrological needs in clinical laboratories / Necessidades metrológicas nos laboratórios clínicos

Los resultados generados por los laboratorios clínicos son elementos claves para el diagnóstico y tratamiento de enfermedades, así como para el seguimiento de los pacientes, por lo tanto se requiere un control metrológico sobre el proceso de medición, el cual determinará el grado de comparabilidad y de confianza requerido sobre los resultados obtenidos. Esta revisión aborda el tema de comparabilidad de las mediciones y de cómo ésta se ve influenciada por factores como la conmutabilidad de los materiales de referencia, los métodos de medición, la disponibilidad de materiales y procedimientos de referencia, además de los intervalos de referencia y límites de decisión para un mensurando en particular. Finalmente se exponen cuáles son los mecanismos adoptados que permitirán garantizar la comparabilidad de las mediciones en esta área.

The results produced by clinical laboratories are key elements in the diagnosis and treatment of diseases and to monitor patients, so, it requires a metrological control over the measurement process, which will determine the degree of comparability and trust required on the obtained measurement results. Therefore, in this paper we discuss about the comparability of measurements and how it is influenced by factors such as commutability of reference materials, measurement methods, availability of materials and reference procedures, in addition to reference intervals and decision limits for a particular measurand. Finally it is exposed what are the mechanisms that allow ensure measurements comparability on this area.

Os resultados gerados pelos laboratórios clínicos são elementos chaves para o diagnóstico e tratamento de doenças, assim como para o seguimento dos pacientes, sendo preciso um controle metrológico sobre o processo de medição, que determina o grau de comparabilidade e confiança requerido sobre os resultados obtidos. Neste documento trata-se o tópico de comparabilidade das medições e de como a mesma se encontra influenciada por fatores como a comutatividade dos materiais de referência, os métodos de medição, a disponibilidade de materiais e procedimentos de referência, além dos intervalos de referência e limites de decisão para um mensurando em particular. Finalmente, são expostos quais são os mecanismos adotados que permitirão garantir a comparabilidade das medições nesta área.

Estimación de la incertidumbre para el análisis de potencia de insulina humana isofana ADN recombinante por cromatografía liquida de alta resolución fase reversa según USP34 NF29 2011 / Uncertainty estimation for the USP34 NF29 2011 analysis of potency recombinant DNA isophane human insulin from PR-HPLC

El propósito de una medición es determinar el valor de una magnitud, llamada el mensurando. La imperfección natural de las mediciones, hace imposible conocer con certeza absoluta el valor verdadero de una magnitud, ya que toda medición lleva implícita una incertidumbre, el cual es un parámetro no negativo que caracteriza la dispersión de los valores atribuidos a un mensurando. En la presente investigación se empleo una estrategia diferente al procedimiento “bottom-up” propuesto por la ISO, el cual nos permitió estimar de forma global la incertidumbre, mediante la agrupación de valores determinados durante la verificación del método analítico. El valor obtenido en nuestro estudio fue de 3.46 UI/mL con un 90% de confianza. Observándose como fuente de mayor contribución al cálculo, el efecto de la matriz del medicamento, dependiente del tipo de insulina presente, además de la precisión y trazabilidad del patrón de referencia, los cuales contribuyen en la incertidumbre final de forma similar. En este sentido, nuestros esfuerzos deben dirigirse a la optimización de los procesos de homogeneización, adquisición del patrón de referencia tipo primario, con la finalidad de garantizar a lo largo del tiempo, resultados reproducibles, trazables y confiables.

The purpose of measurement is to determine the value of a quantity, called the measurand. The natural imperfection of determining measurements, makes impossible to know with absolute certainty the true value of a magnitude, since all measurement implies an uncertainty, which is a non-negative parameter that characterize the dispersion of the values attributed to a measurand. In this research, we employed a different strategy to the "bottom-up" procedure, proposed by the ISO, which allowed us to calculate globally the uncertainty, by grouping values, determined during the verification of the analytical method. The obtained value in our study was 3.46 IU/mL with 90% confidence. The matrix effect of the drug, depending on the insulin type present inside, was observed as the bigger contribution source to the calculation, as well as the accuracy and traceability of the reference pattern, which contribute in the final uncertainty similarly. Thus, our efforts should be directed to the optimization of the homogenization processes and the acquisition of the primary type reference pattern, in order to ensure over time, reproducible, traceable and reliable results.

Desenvolvimento de material de referência para microbiologia de alimentos contendo Listeria monocytogenes em matriz queijo / Development of reference material for food microbiology containing Listeria monocytogenes in matrix

A NBR ISO/IEC 17025:2005, uma das normas mais utilizadas em laboratórios de ensaio, descreve como um de seus critérios para a garantia da qualidade dos resultados analíticos a participação periódica dos laboratórios em ensaios de proficiência (EP). Os analitos, utilizados nos EP são materiais de referência (MR) provenientes de um mesmo lote, e devem apresentar características de homogeneidade e estabilidade. O objetivo deste estudo foi produzir um MR qualitativo destinado ao ensaio de pesquisa de Listeria monocytogenes em matriz queijo pela técnica de liofilização. Para a produção do MR, foi utilizado como matriz o queijo Minas frescal (QMF) ultrafiltrado. A matriz foi distribuída em frascos, contaminada com a bactéria alvo e submetida à liofilização, tendo a sacarose como crioprotetor. O MR produzido foi considerado homogêneo e estável na temperatura de ≤-70°C durante todo o período estudado (10 meses). O material apresentou estabilidade a 4, 25, 30 e 35°C por quatro dias e a -20°C por 48 dias, e os resultados estatísticos indicam tendência à estabilidade. Conclui-se que o material apresentou todos os requisitos necessários de um MR de qualidade e poderia ser transportado aos laboratórios participantes de um EP à temperatura máxima de 35°C por até quatro dias, uma vez que os resultados indicaram a manutenção da concentração celular nesse período. Esse foi o primeiro trabalho a descrever uma metodologia de produção de MR contendo L. monocytogenes em matriz queijo.

The standard most used in testing laboratories, ISO/IEC 17025:2005, describes the participation of laboratories in periodic proficiency testing (PT), as a criteria for quality assurance of analytical results. The analyses used in PT are reference materials (MR) from the same lot, and must have characteristics of homogeneity and stability. This study aimed to produce a qualitative RM for detection of Listeria monocytogenes assays in cheese matrix. For the production of RM, Minas Frescal cheese (MFQ) was used as matrix. The matrix was distributed in flasks, contaminated with the target bacteria and submitted to freeze-drying. Sucrose was used as cryoprotector. The RM produced was considered homogeneous and stable at -70°C during the entire period of study (10 months). The material showed stability at 4, 25, 30 and 35°C for 4 days and at -20°C the RM showed stability for 48 days, and the statistical results indicate a tendency to maintain stability. It was concluded that the material showed all the requirements of an RM quality and could be transported to the laboratory participants of a PT at 35°C up to 4 days, since the results indicate the maintenance of cell concentration during this period. This is the first study to describe a methodology for producing MR containing L. monocytogenes in cheese matrix.