Covance (Germany)

Although scientists are generally motivated to adopt sustainable practices in their research, a lack of education is often limiting. Here, I aim to fill this gap by illustrating how to substantially reduce single-use plastic waste in scientific protocols. This article will outline the translation of the three fundamental principles of reduction, reuse, and miniaturization into experimental practice. The transfection of neurons in sterile conditions will be provided as a concrete example to discuss opportunities for change. Simply by reducing, miniaturizing, and reusing, a decrease in plastic waste of approximately 65% was achieved for exchangeable items. This article demonstrates the feasibility of adopting sustainable practices without compromising workflows or data quality.

DSOs are still facing high volatility regarding their supply task which requires significant adaptations in network structure and operations. In addition to the ongoing integration of DER sites ramp-up in e-mobility and storages lead to multi-sector coupling. These developments induce high uncertainty in the definition of consistent future supply tasks which cannot be addressed by classical grid development and planning. In contrast we present an integrated holistic optimizing approach to these challenges.

The Society of Toxicologic Pathology (STP) explored current institutional practices for selecting between non-blinded versus blinded histopathologic evaluation during Good Laboratory Practice (GLP)-compliant, regulatory-type animal toxicity studies using a multi-question survey and STP-wide discussion (held at the 2019 STP annual meeting). Survey responses were received from 107 individuals representing 83 institutions that collectively employ 589 toxicologic pathologists. Most responses came from industry (N = 46, mainly biopharmaceutical or contract research organizations) and consultants (N = 24). For GLP-compliant animal toxicity studies, histopathologic evaluation usually involves initial (primary) non-blinded analysis, with post hoc informal blinded re-examination at the study pathologist's discretion to confirm subtle findings or establish thresholds. Initial blinded histopathologic evaluation sometimes is chosen by study pathologists to test formal hypotheses and/or by sponsors to address non-pathologist expectations about histopathology data objectivity. Current practice is that a blinded histopathologic evaluation is documented only if formal blinding (ie, using slides with coded labels) is employed, using simple statements without detailed methodology in the study protocol (or an amendment) and/or pathology report. Blinding is not an appropriate strategy for the initial histopathologic evaluation performed during pathology peer reviews of GLP-compliant animal toxicity studies. [Box: see text].

The purpose of this study was to examine the toxicity and side effects of a recombinant adeno-associated virus 8 (AAV8) vector, aimed to treat cyclic nucleotide gated channel alpha 3 (CNGA3)-linked achromatopsia, after a single subretinal administration in cynomolgus macaques. Animals were followed in two studies: a 13-week study with 22 animals and a 28-day study with 12 animals. Both groups were divided into subgroups receiving either vehicle only, a low (1 × 1011 vector genomes (vg)), or a high dose (1 × 1012 vg) of rAAV.hCNGA3. In the 13-week study, an extra group received single high-dose intravitreal injections. Here we present the group results of the histological examinations carried out after necropsy from the 28-day study, the retinal functional (electroretinography) in the 13-week study, and clinical observations from both studies. Treatment-related adverse effects were not found, and parameter changes were mostly related to the surgical procedure. The treatment of achromatopsia with rAAV.hCNGA3 is therefore deemed safe to apply to humans.

SA237 is a humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody in which the constant and variable regions have been engineered for a longer plasma half-life. According to literature, blocking of IL-6 related functions could have an influence on pregnancy sustainment, development of the immune system, and brain growth. SA237 effects on dams, embryo-fetal development, parturition and postnatal development were investigated in an enhanced pre- and postnatal development study, in which SA237 was subcutaneously administered to pregnant cynomolgus monkeys at dose levels of 2 or 50 mg/kg once weekly from gestation day 20 until parturition. Infant development, including immune function and learning ability tests, was comprehensively assessed at multiple examinations until approximately 10 months after birth. SA237 plasma concentrations were almost equivalent between dams and their infants and dropped throughout the postnatal period, pharmacologically relevant exposure was maintained for 147 days after birth at 50 mg/kg. Because the binding of SA237 to IL-6R inhibited IL-6R-mediated clearance of IL-6, serum IL-6 increased in dams and infants. However, there were no SA237-related adverse effects on dams, embryos, fetuses, or infants. SA237 pharmacological effects contributed to the suppression of plasma cell differentiation and antibody production by inhibiting IL-6 signaling, and T cell-dependent antibody reaction was minimally suppressed in infants, but physiological immunoglobulin class switching and general antibody production against a T cell-dependent antigen were maintained. The exposure to SA237 did not adversely affect dams, embryo-fetal development, parturition, and postnatal development, including immune function and neuronal development. Birth Defects Research 109:843-856, 2017. © 2017 Wiley Periodicals, Inc.