ABSTRACT
Since the Coronavirus Disease 2019 (COVID-19) outbreak, unconventional cell line development (CLD) strategies have been taken to enable development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies at expedited speed. We previously reported a novel chemistry, manufacturing, and control (CMC) workflow and demonstrated a much-shortened timeline of 3-6 months from DNA to investigational new drug (IND) application. Hereafter, we have incorporated this CMC strategy for many SARS-CoV-2-neutralizing antibody programs at WuXi Biologics. In this paper, we summarize the accelerated development of a total of seven antibody programs, some of which have received emergency use authorization approval in less than 2 years. Stable pools generated under good manufacturing practice (GMP) conditions consistently exhibited similar productivity and product quality at different scales and batches, enabling rapid initiation of phase I clinical trials. Clones with comparable product quality as parental pools were subsequently screened and selected for late-stage development and manufacturing. Moreover, a preliminary stability study plan was devised to greatly reduce the time required for final clone determination and next-generation sequencing-based viral testing was implemented to support rapid conditional release of the master cell bank for GMP production. The successful execution of these COVID-19 programs relies on our robust, fit for purpose, and continuously improving CLD platform. The speed achieved for pandemic-related biologics development may innovate typical biologics development timelines and become a new standard in the industry.
ABSTRACT
Atmospheric pollution studies have linked diminished human activity during the COVID-19 pandemic to improve air quality. This study was conducted during January to March (2019-2021) in 332 cities in China to examine the association between population migration and air quality, and examined the role of three city attributes (pollution level, city scale, and lockdown status) in this effect. This study assessed six air pollutants, namely CO, NO2, O3, PM10, PM2.5, and SO2, and measured meteorological data, with-in city migration (WCM) index, and inter-city migration (ICM) index. A linear mixed-effects model with an autoregressive distributed lag model was fitted to estimate the effect of the percent change in migration on air pollution, adjusting for potential confounding factors. In summary, lower migration was associated with decreased air pollution (other than O3). Pollution change in susceptibility is more likely to occur in NO2 decrease and O3 increase, but unsusceptibility is more likely to occur in CO and SO2, to city attributes from low migration. Cities that are less air polluted and population-dense may benefit more from decreasing PM10 and PM2.5. The associations between population migration and air pollution were stronger in cities with stringent traffic restrictions than in cities with no lockdowns. Based on city attributes, an insignificant difference was observed between the effects of ICM and WCM on air pollution. Findings from this study may gain knowledge about the potential interaction between migration and city attributes, which may help decision-makers adopt air-quality policies with city-specific targets and paths to pursue similar air quality improvements for public health but at a much lower economic cost than lockdowns.
ABSTRACT
Previous Studies, such as the evaluation of the supply of and demand for regional medical resources and carrying capacity assessments, require further development. This paper aims to evaluate the carrying capacity and spatial distribution of medical resources in Shenzhen from the perspective of supply and demand, and to conduct a time-series variation of the coupling coordination degree from 1986 to 2019. The two-step floating catchment area method was employed to quantify the carrying capacity and coupling coordination degree method and spatial autocorrelation analysis were applied to analyze spatial distribution between supply and demand. The results were as follows. (1) The carrying capacity index in more than 50% of the districts was classified as low-grade. The percentage of regions with good grades was 8.27%. The regions with a high carrying capacity were distributed in the central and southeastern areas. (2) The coupling coordination continued to rise, increasing from 0.03397 in 1986 to 0.33627 in 2019. (3) The level of supply and demand for medical resources in Shenzhen increased from 1986 to 2019, and the highest degree of compatibility between the supply and the population size was largely concentrated in the western and eastern regions. This research can provide a theoretical reference for Shenzhen to rationally plan medical resources and improve the carrying capacity of medical resources.
Subject(s)
Health Services Accessibility , Catchment Area, Health , China , Humans , Spatial AnalysisABSTRACT
During the COVID-19 lockdown in Wuhan, transportation, industrial production and other human activities declined significantly, as did the NO2 concentration. In order to assess the relative contributions of different factors to reductions in air pollutants, we implemented sensitivity experiments by Random Forest (RF) models, with the comparison of the contributions of meteorological conditions, human mobility, and emissions from industry and households between different periods. In addition, we conducted scenario analyses to suggest an appropriate limit for control of human mobility. Different mechanisms for air pollutants were shown in the pre-pandemic, pre-lockdown, lockdown, and post-pandemic periods. Wind speed and the Within-city Migration index, representing intra-city mobility intensity, were excluded from stepwise multiple linear models in the pre-lockdown and lockdown periods. The results of sensitivity experiments show that, in the COVID-19 lockdown period, 73.3% of the reduction can be attributed to decreased human mobility. In the post-pandemic period, meteorological conditions control about 42.2% of the decrease, and emissions from industry and households control 40.0%, while human mobility only contributes 17.8%. The results of the scenario analysis suggest that the priority of restriction should be given to human mobility within the city than other kinds of human mobility. The reduction in the NO2 concentration tends to be smaller when human mobility within the city decreases by more than 70%. A limit of less than 40% on the control of the human mobility can achieve a better effect, especially in cities with severe traffic pollution.