Policy and laboratory practice: How quality control procedures for genetic testing perpetuate biological essentialism and discrimination against transgender, gender diverse, and intersex people.

Transgender, gender diverse, and intersex (TGDI) individuals face significant health disparities due to individual and systemic experiences of discrimination, impacting their access to healthcare. While clinical genetic testing has become increasingly accessible to the general population, the field of clinical genetics perpetuates a narrative of biological essentialism, which creates barriers for TGDI patients. Biological essentialism upholds that sex is a binary, fixed, and innate characteristic, a misconception that has been historically weaponized against the TGDI community in both individual experiences of discrimination and anti-trans legislation, among other systemic forms of oppression. Rejecting this discriminatory framework requires careful consideration of, and changes to, long-established practices that often go unquestioned, such as quality control metrics in genetic testing, in order to improve TGDI patients' outcomes and access to genetic services. The sex-check, comparing an individuals reported sex against their sex chromosomes, is an example of how laboratory genetics practices reinforce the narrative that sex is determined purely by chromosomal composition. Additionally, the sex-check "outs" TGDI people in clinical settings, creating a discriminatory and unsafe environment for these patients. Alternative quality control procedures and inclusive practices, such as clearer delineation of sex and gender on test requisition forms, are proposed to improve TGDI patient experiences. Genetic counselors and other clinical providers have a responsibility to address historical discrimination and advocate for changes to laboratory practice, so as to create affirming experiences for TGDI patients.

Online laboratory practices and assessment using training and learning activities as teaching methodologies adapted to remote learning. Student satisfaction and improved academic performance.

This article presents new teaching methodologies implemented in subjects in the Ground Engineering Area. Specifically, it focuses on a series of activities carried out due to the appearance of the COVID-19 pandemic that resulted in restrictions on class attendance. The new teaching methodologies brought about substantial changes in the way students learn and are assessed. For the practice sessions, a series of videos were prepared so students could attend and take part in the laboratory practices remotely. As regards the final theory exam, a comprehensive multiple-choice question bank was made available to students prior to the exam to consolidate the concepts seen in the master classes, which we call training and learning. We evaluated the impact of these new methodologies, implemented during two academic years, through the analysis of voluntary and anonymous student surveys and a series of indicators related to the results of the final exams. After analyzing the impact of the new teaching methodologies, we conclude that students are positive about the video experience for laboratory practices, but only as a complementary activity to in-person laboratory sessions. The students also stated that they would like the multiple-choice question bank to continue to be available in successive academic years. Improvements in the final grades of the theory exams demonstrate the success of this new teaching methodology.

A Comparative Review of ICMR, WHO, and EMA Guidelines for Good Clinical Laboratory Practices.

With the advancement of clinical research and the increased burden on laboratory services, there is an unmet need for guidelines regarding proper laboratory functioning and reliable data generation. Several organizations from all over the world have published guidelines for these clinical and research laboratories. Good Clinical Laboratory Practices (GCLP) are stepwise procedures aimed at strengthening the quality of test results produced by all clinical laboratories engaged in human sample analysis. In this article, we attempt a comparison of the GCLP guidelines recently issued by the Indian Council of Medical Research with the guidelines released by the World Health Organization and the European Medicines Agency. Also, we have included and discussed several suggestions that, if included, will lead to the strengthening of the laboratory practices used for both research and patient care for overall improvement in the Indian healthcare system.

Exploring the gap in the Occupational Safety And Health Administration (OSHA) laboratory standard: a literature review and recommendations to enhance histology laboratory safety practices.

This article discusses current available resources with respect to regulatory agencies including the Occupational Safety and Health Administration (OSHA) for determining the requirements placed upon laboratories for handling of hazardous materials. The focus is specific to the histology laboratory and xylene use, and includes a literature review, admixed with historical reference points. Procedures and tasks in the histology laboratory are highlighted in relation to their connection to the quality of the work environment with an emphasis on air quality. Recommendations are provided for maintaining an appropriate work environment for the prevention of potential adverse health effects. The gap within the OSHA Laboratory Standard, i.e. a lack of explanatory language, leaves much open to interpretation regarding fume hood usage with volatile hazardous chemicals. As a result, both the level of safety training and the awareness of good laboratory practices (GLP) for handling volatile hazardous reagents such as xylene can become compromised.

Opinion on Maintaining In-House GLP Status for Toxicologic Pathology in Pharmaceutical and (Agro)Chemical Development.

Many pharmaceutical companies have recently elected to stop maintaining good laboratory practices (GLP) status of their R&D sites. Similar discussions have also been engaged in the (agro)chemical industry. This opinion paper examines the pros and cons of maintaining facility GLP status for the purposes of performing the pathology interpretation or peer reviews of GLP studies internally. The toxicologic pathologist provides gross and histomorphologic evaluation and interpretation of nonclinical exploratory and regulatory studies during drug and (agro)chemical development. This assessment significantly contributes to human risk assessment by characterizing the toxicological profile and discussing the human relevance of the findings. The toxicologic pathologist is a key contributor to compound development decisions (advancement or termination) and in the development of de-risking strategies for backup compounds, thus playing a critical role in helping to reduce the late attrition of drugs and chemicals. Maintaining GLP compliance is often perceived as a costly and cumbersome process; a common and short-term strategy to reduce the costs is to outsource regulatory toxicity studies. However, there are significant advantages in maintaining the GLP status for toxicologic pathology activities in-house including the sustainable retention of internal pathology expertise that has maintained the necessary training needed to manage GLP studies. [Box: see text].

Non-clinical safety assessment and in vivo biodistribution of CoviFab, an RBD-specific F(ab')2 fragment derived from equine polyclonal antibodies.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has required the urgent development of new therapies, among which passive immunotherapy is contemplated. CoviFab (INM005) is a RBD-specific F(ab')2 fragment derived from equine polyclonal antibodies. We investigate their preclinical security and biodistribution by in vivo and ex vivo NIR imaging after intravenous administration of a dose of 4 mg/kg at time 0 and 48 h. Images were taken at 1, 12, 24, 36, 48, 49, 60, 72, 84, 96, 108, 120, 132 and 144 h after the first intravenous injection. At 96 and 144 h, mice were sacrificed for haematology, serum chemistry, clinical pathology, histopathology and ex vivo imaging. The biodistribution profile was similar in all organs studied, with the highest fluorescence at 1 h after each injection, gradually decreasing after that each one and until the end of the study (144 h). The toxicology study revealed no significant changes in the haematology and serum chemistry parameters. Further, there were no changes in the gross and histological examination of organs. Nonclinical data of the current study confirm that CoviFab is safe, without observable adverse effects in mice. Furthermore, we confirm that bioimaging studies are a useful approach in preclinical trials to determine biodistribution.

Desarrollo y validación de técnicas analíticas para la determinación de biomarcadores sanguíneos en ensayos preclínicos. ¿Por qué y para qué? / Development and validation of analytical techniques for the determination of blood biomarkers in preclinical trials. Why and what for?

Resumen El descubrimiento de un nuevo principio activo farmacéutico implica estudios preclínicos, que tienen como objetivo demostrar que es eficaz y seguro para un posterior ensayo en seres humanos. Esto conduce a la necesidad de desarrollar tecnologías que aprovechen las nuevas herramientas analíticas disponi bles dentro de un contexto donde los resultados de las pruebas realizadas, estén plenamente documentados, bajo sistemas de buenas prácticas de laboratorio auditables. En esta revisión se actualizan y describen algunos de los ensayos realizados en la etapa preclínica del desarrollo de un nuevo fármaco y el estado actual de la tecnología analítica empleada para el dosaje de diferentes biomarcadores sanguíneos de interés. Se analizaron los biomarcadores más relevantes, las normativas de validación de las técnicas analíticas empleadas para su determinación y los problemas que se presentan al tratar de aplicarlas.

Abstract New drug discovery involves preclinical studies to demonstrate its effectivity and safety for further tests in humans. This leads to the need to develop technologies that take advantage of the new analytical tools available within a context where the results of the tests carried out are fully documented, under auditable systems of good laboratory practice. This review updates and describes some of the tests carried out in the preclinical stage of the development of a new drug and the current state of the analytical technology used to measure different blood biomarkers of interest. Biomarker parameters were analyzed at the physiological level, considering both the validation regulations of the analytical techniques used for their determination as the problems that arise when trying to apply them, since many of these biomarkers are endogenous compounds in the used matrices.

Managing COVID-19 Lockdown Impacts: Sustaining GLP Compliance and Man Material Medium (MMM) Strategy for Augmenting Prevention of Workplace Infections.

Good Laboratory Practices (GLP) is a well-established global system that encompass a set of principles or a framework for defining how laboratory studies are planned, performed, monitored, recorded, reported, and stored for future reference. It is important that compliance with the principles of GLP continues to be maintained. Coronavirus disease 2019 (COVID-19) pandemic lockdowns in various countries, including India, have been sudden and over an extended duration. Although every GLP laboratory has Standard Operating Procedure for disaster management, the sudden lockdown due to COVID-19 created specific emergency procedures related to this situation such as travel bans, safe distancing, and work from home notifications. Good Laboratory Practice compliances in the context of animal experimentation during and post lockdown period need effective managerial responses that are not just flexible and innovative but can ensure they are well-calibrated to the challenges of business continuity and maintenance of health directives. On-the-ground realities suggest there may still be practical challenges to compliance, and guidelines may not always be complied with. This article discusses the issues that may be encountered due to COVID-19 that could potentially impact the GLP status of a study and suggests ways to manage them so as to minimize or prevent infection with COVID-19. We propose an MMM (Man, Material, and Medium) strategy to ensure compliance with health directives and guidelines that will help staff to keep themselves and others safe in the workplace while endeavoring to comply with GLP requirements.

[Development and validation of analytical techniques for the determination of blood biomarkers in preclinical trials. Why and what for?] / Desarrollo y validación de técnicas analíticas para la determinación de biomarcadores sanguíneos en ensayos preclínicos. ¿Por qué y para qué?

New drug discovery involves preclinical studies to demonstrate its effectivity and safety for further tests in humans. This leads to the need to develop technologies that take advantage of the new analytical tools available within a context where the results of the tests carried out are fully documented, under auditable systems of good laboratory practice. This review updates and describes some of the tests carried out in the preclinical stage of the development of a new drug and the current state of the analytical technology used to measure different blood biomarkers of interest. Biomarker parameters were analyzed at the physiological level, considering both the validation regulations of the analytical techniques used for their determination as the problems that arise when trying to apply them, since many of these biomarkers are endogenous compounds in the used matrices.

El descubrimiento de un nuevo principio activo farmacéutico implica estudios preclínicos, que tienen como objetivo demostrar que es eficaz y seguro para un posterior ensayo en seres humanos. Esto conduce a la necesidad de desarrollar tecnologías que aprovechen las nuevas herramientas analíticas disponibles dentro de un contexto donde los resultados de las pruebas realizadas, estén plenamente documentados, bajo sistemas de buenas prácticas de laboratorio auditables. En esta revisión se actualizan y describen algunos de los ensayos realizados en la etapa preclínica del desarrollo de un nuevo fármaco y el estado actual de la tecnología analítica empleada para el dosaje de diferentes biomarcadores sanguíneos de interés. Se analizaron los biomarcadores más relevantes, las normativas de validación de las técnicas analíticas empleadas para su determinación y los problemas que se presentan al tratar de aplicarlas.

Mini Review on Laboratory Practices During Covid-19 Pandemic: From Microbiologists Perspective

@#Laboratory practices in a laboratory have changed worldwide due to the emergence of the COVID-19 pandemic. The changes occur concerning specimen collection, handling, transportation, processing, and disposal. Infection control practices are applied in all aspects, starting from specimen collection until the clinician gets the results. A retrospective review of laboratory practices used in a tertiary teaching hospital laboratory from microbiologists’ perspectives was performed, and the practices were compared with previously published articles.

Sistema de Laboratorios Remoto para el estudio de la Microbiología y Parasitología Médica / Remote Laboratory System for the study of Medical Microbiology and Parasitology

Introducción: como parte del proceso de formación de enfermeros, médicos y tecnólogos de la salud son habilitados temas relacionados con la microbiología. Sin embargo, a partir del conjunto de medidas de seguridad y la disponibilidad de recursos físicos, no es posible el estudio de diversos microorganismos. Objetivo: desarrollar un Sistema de Laboratorios Remoto para la práctica de Microbiología y Parasitología Médica. Materiales y métodos: el sistema de Laboratorios Remoto posee un microscopio electrónico controlado mediante una interface de comunicación con un ordenador conectado a la red. Resultados: se obtuvo como resultado un Sistema de Laboratorios Remoto que puede ser accedido mediante Internet o la red institucional. Facilita el estudio y la interpretación de diferentes muestras biológicas. Brinda un conjunto de reportes y estadísticas que permiten realizar análisis históricos de comportamiento. Conclusiones: a partir del desarrollo de las prácticas de laboratorios a distancia, es posible el estudio de diferentes microorganismos sin riesgos biológicos para el estudiante(AU)

Introduction: as part of the training process for nurses, physicians and health technologists, topics related to microbiology are enabled. However, based on the set of security measures and the availability of physical resources, the study of various microorganisms is not possible. Objective: to develop a Remote Laboratory System for the practice of the subject Medical Microbiology and Parasitology. Methods: the Remote Laboratory System has an electronic microscope controlled by a communication interface with a computer connected to the network. Results: a Remote Laboratory System that can be accessed through the Internet or the institutional network. The system facilitates the study and interpretation of different biological samples and also provides a set of reports and statistics that allow for historical behavior analysis. Conclusions: from the development of remote laboratory practices, it is possible to study different microorganisms without biological risks for the student(AU)

Sampling and Quality Assurance and Quality Control: A Guide for Scientists Investigating the Occurrence of Microplastics Across Matrices.

Plastic pollution is a defining environmental contaminant and is considered to be one of the greatest environmental threats of the Anthropocene, with its presence documented across aquatic and terrestrial ecosystems. The majority of this plastic debris falls into the micro (1 µm-5 mm) or nano (1-1000 nm) size range and comes from primary and secondary sources. Its small size makes it cumbersome to isolate and analyze reproducibly, and its ubiquitous distribution creates numerous challenges when controlling for background contamination across matrices (e.g., sediment, tissue, water, air). Although research on microplastics represents a relatively nascent subfield, burgeoning interest in questions surrounding the fate and effects of these debris items creates a pressing need for harmonized sampling protocols and quality control approaches. For results across laboratories to be reproducible and comparable, it is imperative that guidelines based on vetted protocols be readily available to research groups, many of which are either new to plastics research or, as with any new subfield, have arrived at current approaches through a process of trial-and-error rather than in consultation with the greater scientific community. The goals of this manuscript are to (i) outline the steps necessary to conduct general as well as matrix-specific quality assurance and quality control based on sample type and associated constraints, (ii) briefly review current findings across matrices, and (iii) provide guidance for the design of sampling regimes. Specific attention is paid to the source of microplastic pollution as well as the pathway by which contamination occurs, with details provided regarding each step in the process from generating appropriate questions to sampling design and collection.

Recommendations for ecotoxicity testing with stygobiotic species in the framework of groundwater environmental risk assessment.

As a consequence of the growing global dependence on groundwater resources, environmental risk assessments (ERA) for groundwater are increasingly required and, with that, ecotoxicological studies with groundwater fauna (stygofauna). However, the literature on the ecotoxicological studies with stygobiotic species (i.e. species that complete their life cycle exclusively in groundwater) has not expanded significantly since the first paper published in this field. The limitations regarding the use of stygobiotic species for ecotoxicological testing are clear and consistent across the globe; stygobiotic species are often 1) naturally present in low numbers, 2) difficult to collect, and 3) difficult to culture under laboratory conditions. This paper reviews the methods used in ecotoxicological studies performed with stygobiotic species, and provides ten recommendations for Good Laboratory Practice (GLP) for such tests. The recommendations focused on the following 10 points: 1) the taxonomic identification, the life stage/size and gender of the test organisms; 2) collection methodology of the organisms, including collection location, conditions and methods; 3) holding and acclimation conditions in the laboratory; 4) exposure conditions such as test set up and exposure time, number of replicates and densities of organisms in tests and in test vessels; 5) range-finding test set up and schedule; 6) final test design, including details of controls and treatments, and replication options; 7) incubation conditions, specifying temperature, pH and oxygenation levels throughout the test; 8) test duration; 9) observations and endpoints; 10) test validity criteria and compliance. The recommendations were developed for the purpose of supporting future short-term ecotoxicological testing with stygofauna through providing consistency in the protocols. A discussion of the potential implications for groundwater managers and decision-makers committed to ERA for groundwater is included.

Toxicity and pharmacokinetic profile of SGM-101, a fluorescent anti-CEA chimeric antibody for fluorescence imaging of tumors in patients.

The real-time improvement of the intraoperative discrimination between different tissue types (particularly between tumor and adjacent normal tissue) using intraoperative imaging represents a considerable advance for oncology surgeons. However, the development of imaging agents is much slower than that of drug therapies, although surgery represents one of the few curative treatments for many solid tumors. SGM-101 is a recently described, innovative antibody conjugate in which the near-infrared fluorochrome BM-104 is covalently linked to a chimeric monoclonal antibody against carcinoembryonic antigen (CEA). SGM-101 was developed with the goal of providing oncology surgeons with an intraoperative imaging tool that allows the visualization of CEA-overexpressing tumors. This antigen is overexpressed in a wide range of human carcinomas, such as colorectal, gastric, pancreatic, non-small cell lung and breast carcinomas. Here we characterized SGM-101 safety prior to its clinical testing for real-time cancer mapping by oncology surgeons. Safety pharmacology and toxicology studies were performed after intravenous injection of SGM-101 in Wistar rats and in Beagle dogs. SGM-101 metabolism and pharmacokinetics were analyzed in rats and mice. Finally, the potential toxicity of the BM-104 dye and SGM-101 cross-reactivity were assessed in a panel of 42 human tissues. Our pre-clinical toxicology, pharmacology and pharmacokinetic results demonstrated the absence of significant adverse effects of both SGM-101 and BM-104 at doses well above the anticipated maximal human exposure. Taken together, the results of the pharmacology, pharmacokinetic and toxicology studies support the development of SGM-101 as a potentially useful and safe tumor-specific imaging tool that might improve the complete tumor resection rate.

Construction and Validation of Quantification Methods for Determining the Cannabidiol Content in Liquid Pharma-Grade Formulations by Means of Near-Infrared Spectroscopy and Partial Least Squares Regression.

There is an increasing interest in cannabinoids as they are being proved to effectively treat the symptoms of a variety of medical conditions. Commercialization of cannabinoid-based pharmaceutical products is expected to grow in the near future, favored by the recent changes in medical regulations in many developed countries. Hence, robust and reliable analytical methods for determining the content of the active pharmaceutical ingredient will be needed, as this is one of the most relevant parameters for the decision to release the final pharmaceutical product into the market. The aim of this work was to demonstrate that near-infrared (NIR) spectroscopy fulfills the needed requirements for this purpose, as well as to provide a methodology to be applied to other cannabinoid-based products. We present two validated methods for the quantification of different liquid pharma-grade cannabidiol (CBD) formulations based on NIR spectroscopy and partial least squares regression modelling. The methods were constructed and validated with spectra belonging both to production samples and to laboratory samples specifically made for this purpose, and they fulfill European Medicines Agency and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guideline requirements. These methods allow determining the CBD content with results comparable to the usual method of choice while saving reagent- as well as time-related costs.

A Binding Potency Assay for Pritumumab and Ecto-Domain Vimentin.

Pritumumab, a natural human IgG1kappa mAb, was isolated from the regional lymph node of a patient with cervical cancer. This antibody has been reported to bind the cytoskeletal protein vimentin, and to cell surface expressed vimentin referred to as ecto-domain vimentin (EDV). Here, we report details of the development of a potency of binding assay for pritumumab as a prerequisite before pursuing clinical trials. The enzyme linked immunosorbent assay (ELISA) to detect antibody-binding antigen can serve as a potency assay for release of manufactured samples to be used in clinical studies. Several layers of controls for this assay along with suitability testing for reagents and components of the assay must be developed before the assay can be incorporated for stability testing and release of manufatured samples.

Antifungal Susceptibility Testing Practices at Acute Care Hospitals Enrolled in the National Healthcare Safety Network, United States, 2011-2015.

We assessed availability of antifungal susceptibility testing (AFST) at nearly 4000 acute care hospitals enrolled in the National Healthcare Safety Network. In 2015, 95% offered any AFST, 28% offered AFST at their own laboratory or at an affiliated medical center, and 33% offered reflexive AFST. Availability of AFST improved from 2011 to 2015, but substantial gaps exist in the availability of AFST.

Toxicological evaluation of the flavour ingredient N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)-2,6-dimethylisonicotinamide (S2218).

A toxicological evaluation of N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)-2,6-dimethylisonicotinamide (S2218; CAS 1622458-34-7), a flavour with modifying properties, was completed for the purpose of assessing its safety for use in food and beverage applications. S2218 exhibited minimal oxidative metabolism in vitro, and in rat pharmacokinetic studies, the compound was poorly orally bioavailable and rapidly eliminated. S2218 was not found to be mutagenic in an in vitro bacterial reverse mutation assay, and was found to be neither clastogenic nor aneugenic in an in vitro mammalian cell micronucleus assay. In subchronic oral toxicity studies in male and female rats, the NOAEL was 140 mg/kg bw/day (highest dose tested) for S2218 sulfate salt (S8069) when administered as a food ad-mix for 13 consecutive weeks. Furthermore, S2218 sulfate salt demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg bw/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats.

Implementation of Good Laboratory Practices (GLP) in basic scientific research: Translating the concept beyond regulatory compliance.

The principles of Good Laboratory Practices (GLPs) are mainly intended for the laboratories performing studies for regulatory compliances. However, today GLP can be applied to broad disciplines of science to cater to the needs of the experimental objectives, generation of quality data and assay reproducibility. Considering its significance, it can now be applied in academics; industries as well as government set ups throughout the world. GLP is the best way to promote the reliability, reproducibility of the test data and hence facilitates the international acceptability. Now it is high time to translate and implement the concept of GLP beyond regulatory studies. Thus, it can pave the way for better understanding of scientific problems and help to maintain a good human and environmental health. Through this review, we have made an attempt to explore the uses of GLP principles in different fields of science and its acceptability as well as looking for its future perspectives.

Good cell culture practices &in vitro toxicology.

Good Cell Culture Practices (GCCP) is of high relevance to in vitro toxicology. The European Society of Toxicology In Vitro (ESTIV), the Center for Alternatives for Animal Testing (CAAT) and the In Vitro Toxicology Industrial Platform (IVTIP) joined forces to address by means of an ESTIV 2016 pre-congress session the different aspects and applications of GCCP. The covered aspects comprised the current status of the OECD guidance document on Good In Vitro Method Practices, the importance of quality assurance for new technological advances in in vitro toxicology including stem cells, and the optimized implementation of Good Manufacturing Practices and Good Laboratory Practices for regulatory testing purposes. General discussions raised the duality related to the difficulties in implementing GCCP in an academic innovative research framework on one hand, and on the other hand, the need for such GCCP principles in order to ensure reproducibility and robustness of in vitro test methods for toxicity testing. Indeed, if good cell culture principles are critical to take into consideration for all uses of in vitro test methods for toxicity testing, the level of application of such principles may depend on the stage of development of the test method as well as on the applications of the test methods, i.e., academic innovative research vs. regulatory standardized test method.