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The EU, the USA, and Japan account for the majority of biological pharmacotherapy use worldwide. Biosimilar regulatory approval pathways were authorised in the EU (2006), in Japan (2009), and in the USA (2015), to facilitate approval of biological drugs that are highly similar to reference products and to encourage market competition. Between 2007 and 2020, 33 biosimilars for oncology were approved by the European Medicines Agency (EMA), 16 by the US Food and Drug Administration (FDA), and ten by the Japan Pharmaceuticals and Medical Devices Agency (PMDA). Some of these approved applications were initially rejected because of manufacturing concerns (four of 36 [11%] with the EMA, seven of 16 [44%] with the FDA, none of ten for the PMDA). Median times from initial regulatory submission before approval of oncology biosimilars were 1·5 years (EMA), 1·3 years (FDA), and 0·9 years (PMDA). Pharmacists can substitute biosimilars for reference biologics in some EU countries, but not in the USA or Japan. US regulation prohibits substitution, unless the biosimilar has been approved as interchangeable, a designation not yet achieved for any biosimilar in the USA. Japan does not permit biosimilar substitution, as prescribers must include the product name on each prescription and that specific product must be given to the patient. Policy Reviews published in 2014 and 2016 in The Lancet Oncology focused on premarket and postmarket policies for oncology biosimilars before most of these drugs received regulatory approval. In this Policy Review from the Southern Network on Adverse Reactions, we identify factors preventing the effective launch of oncology biosimilars. Introduction to the market has been more challenging with therapeutic than for supportive care oncology biosimilars. Addressing region-specific competition barriers and educational needs would improve the regulatory approval process and market launches for these biologics, therefore expanding patient access to these products in the EU, the USA, and Japan.

Erythropoisis stimulating agent (ESA) use was addressed in Food and Drug Administration (FDA) Oncology Drug Advisory Committee (ODAC) meetings between 2004 and 2008. FDA safety-focused regulatory actions occurred in 2007 and 2008. In 2007, black box warnings advised of early death and venous thromboembolism (VTE) risks with ESAs in oncology. In 2010, a Risk Evaluation Strategies (REMS) was initiated, with cancer patient consent that mortality and VTE risks were noted with ESAs. We report warnings and REMS impacts on ESA utilization among Veterans Administration (VA) cancer patients with chemotherapy-induced anemia (CIA). Data were from Veterans Affairs database (2003-2012). Epoetin and darbepoetin use were primary outcomes. Segmented linear regression was used to estimate changes in ESA use levels and trends, clinical appropriateness, and adverse events (VTEs) among chemotherapy-treated cancer patients. To estimate changes in level of drug prescription rate after policy actions, model-specific indicator variables as covariates based on specific actions were included. ESA use fell by 95% and 90% from 2005, for epoetin and darbepoetin, from 22% and 11%, respectively, to 1% and 1%, respectively, among cancer patients with CIA, respectively (p<0.01). Following REMS in 2010, mean hematocrit levels at ESA initiation decreased from 30% to 21% (p<0.01). Black box warnings preceded decreased ESA use among VA cancer patients with CIA. REMS was followed by reduced hematocrit levels at ESA initiation. Our findings contrast with privately- insured and Medicaid insured cancer patient data on chemotherapy-induced anemia where ESA use decreased to 3% to 7% by 2010-2012. By 2012, the era of ESA administration to VA to cancer patients had ended but the warnings remain relevant and significant. In 2019, oncology/hematology national guidelines (ASCO/ASH) recommend that cancer patients with chemotherapy-induced anemia should receive ESAs or red blood cell transfusions after risk-benefit evaluation.

HVAC systems consumes 37 % of the electricity in educational buildings. Energy consumption varies depending on the ventilation strategy. School buildings have a responsibility of ensuring energy performance and maintenance of indoor environmental quality for its occupants. This study assesses the efficiency of the ventilation system in terms of the microbes present in the spaces. Microorganisms and particulate matters were sampled in classrooms, locker rooms, libraries in two high schools and an elementary school. Six bacterial species and seven fungal species were identified. The most abundant microorganisms were Staphylococcus sp., Bacillus sp., and Micrococcus sp. Elementary school, especially kindergarten, showed higher microbial concentration and particulate matter as a result of higher human activity. Microbial concentration was influenced by the types of room in the same building with the same ventilation system. Canonical correspondence plot (CCA) determined that gender and school type have significant effects. The presence of Bacillus sp., Aerococcus sp., Corynebacterium sp., and Penicillium sp. was significantly related to gender, while Staphylococcus sp. and Alternaria sp. were related to type of school. The presence of Aerococcus sp. and Micrococcus sp. depended on the distance from the vent location. Relatively lower number of Aerococcus sp. was detected when the distance between sampling site and vent was less than 2 m. Micrococcus sp. was generally detected when the distance was < 3.5 m. The distance from the door was not significant.

Cross-contamination between occupants in an indoor space may occur due to transfer of infectious aerosols. Computational fluid dynamics (CFD) provides detailed insight into particle transport in indoor spaces. However, such simulations are site-specific. This study couples CFD with statistical moments and establishes a framework that transitions site-specific results to generating guidelines for designing “healthy” indoor spaces. Eighteen cases were simulated, and three parameters were assessed: inlet/outlet location, air changes per hour, and the presence/absence of desks. Aerosol release due to a simulated “sneeze” in a two-dimensional ventilated space was applied as a test case. Mean, standard deviation, and skewness of the velocity profiles and particle locations gave an overall picture of the spread and movement of the air flow in the domain. A parameter or configuration did not dominate the values, confirming the significance of considering the combined influence of multiple parameters for determining localized air-flow characteristics. Particle clustering occurred more when the inlet was positioned above the outlet. The particle dispersion pattern could be classified into two time zones: “near time”, <60 s, and “far time”, >120 s. Based on dosage, the 18 cases were classified into three groups ranging from worst case scenario to best case scenario.

Experiments were conducted in a controlled environment of a scaled test room. Nebulizer operated at 2L/ min for one hour resulted in a spike of particle count for an hour after approximately three hours of release. Particle count highlighted the difference in two regions of the scaled test room where air flow was minimal. Impingers monitored concentration levels around the mannequin, lower region of the scaled room. Sustained increase was noted after three hours of release on the side the mannequin where the nebulizer was operated. Particle numbers returned to background levels after four hours.

This is a literature review for the year 2013 and contains information specifically related to suspended growth processes including activated sludge and sequencing batch reactors. This review is a subsection of the Treatment Systems section of the annual literature review. The review encompasses modeling, nutrient removal, system design and operation, oxygen transfer, and solids separation. A number of topics that have seen an increase in activity compared to recent past reviews. These include energy efficiency, new strains and methods for determining biodegradation kinetic parameters, fate and occurrence of hormones, endocrine disrupters and pharmaceuticals, which are referred to as microconstituents following current WEF terminology. Microconstituents as they relate to suspended growth reactors are covered in this review, while membrane bioreactors are reviewed in another section in this journal. Other subsections from the Treatment Systems section that might also be related to this section include: Wastewater Collection Systems; Biological Fixed Film Systems; and Modeling, Instrumentation, Automation, and Optimization of Wastewater Treatment Facilities. Many of the subsections in the Industrial Wastes, Hazardous Wastes, and Fate and Effects of Pollutants sections could also have some overlap with this section.

The study analyzes data from field exposure measurements in an aircraft cabin to identify at what point of time or at what distance the influence of the 'release' diminishes and if the contaminant transport transitions from being influenced by the source release characteristics to being influenced by ventilation conditions. Temporally distinct transition in the contaminant transport was noted for one source location within 200 and 400s of release. The results showed that passengers seating at a radial distance of 2 m or greater from the source may be exposed to lower levels of concentration for a shorter duration.

This is a literature review for the year 2012 and contains information specifically related to suspended growth processes including activated sludge and sequencing batch reactors. This review is a subsection of the Treatment Systems section of the annual literature review. The review encompasses modeling, nutrient removal, system design and operation, oxygen transfer, and solids separation. A number of topics that have seen an increase in activity compared to recent past reviews. These include nitrous oxide emissions, fate and occurrence of hormones, endocrine disrupters and pharmaceuticals, which are referred to as microconstituents following current WEF terminology. Microconstituents as they relate to suspended growth reactors are covered in this review, while membrane bioreactors are reviewed in another section in this journal. Other subsections from the Treatment Systems section that might also be related to this section include: Wastewater Collection Systems; Biological Fixed Film Systems; and Modeling, Instrumentation, Automation, and Optimization of Wastewater Treatment Facilities. Many of the subsections in the Industrial Wastes, Hazardous Wastes, and Fate and Effects of Pollutants sections could also have some overlap with this section.

A review of the literature published in 2011 on topics related to activated sludge and other aerobic suspended growth processes is presented. The review encompasses modeling, nutrient removal, system design and operation, oxygen transfer and solids separation. Two topics that have seen an increase in activity compared to historical reviews are membrane bioreactors and fate and occurrence of hormones and pharmaceuticals, which are referred to as microconstituents following current WEF terminology. Microconstituents as they relate to suspended growth reactors are covered in this review, while membrane bioreactors are reviewed in another section in this journal. Other subsections from the Treatment Systems section that might also be related to this section include: Wastewater Collection Systems; Biological Fixed Film Systems; and Modeling, Instrumentation, Automation, and Optimization of Wastewater Treatment Facilities. Many of the subsections in the Industrial Wastes, Hazardous Wastes, and Fate and Effects of Pollutants sections could also have some overlap with this section.

Linear, quadratic, and artificial neural network (ANN)-based metamodels were developed for predicting the extent of anthrax spore inactivation by chlorine dioxide in a ventilated three-dimensional space over time from computational fluid dynamics model (CFD) simulation data. Dimensionless groups were developed to define the design space of the problem scenario. The Hammersley sequence sampling (HSS) method was used to determine the sampling points for the numerical experiments within the design space. A CFD model, comprised of multiple submodels, was applied to conduct the numerical experiments. Large eddy simulation (LES) with the Smagorinsky subgridscale model was applied to compute the airflow. Anthrax spores were modeled as a dispersed solid phase using the Lagrangian treatment. The disinfectant transport was calculated by solving a mass transport equation. Kinetic decay constants were included for spontaneous decay of the disinfectant and for the reaction of the disinfectant with the surfaces of the three-dimensional space. To enhance the mixing of the disinfectant with the room air, a momentum source was included in the simulation. An inactivation rate equation accounted for the reaction between the spores and the disinfectant. The ANN-based metamodels were most successful in predicting the number of viable bioaerosols remaining in an arbitrary enclosed space. Sensitivity analysis showed that the mass fraction of the disinfectant, inactivation rate constant, and contact time had the most influence on the inactivation of the spores.