The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Zsombor Zrubka - One of the best experts on this subject based on the ideXlab platform.
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authorized manufacturing changes for therapeutic monoclonal antibodies mabs in european public Assessment Report epar documents
Current Medical Research and Opinion, 2016Co-Authors: Balazs Vezer, Zsuzsanna Buzas, Miklos Sebeszta, Zsombor ZrubkaAbstract:AbstractBackground The quality of biologicals, including biosimilars, is subject to change as a result of manufacturing process modifications following initial authorization. It is important that such product changes have no adverse impact on product efficacy or safety, including immunogenicity.Objectives The aim of this study was to investigate the number and types of manufacturing changes for originator mAbs (the reference for the comparability exercise to confirm biosimilarity) according to European Public Assessment Report (EPAR) documentation and to ascertain the level of risk these changes might impart. The extensive body of evidence contained in the EPAR documents can help support the EMA during the EC marketing authorization approval process for biosimilars, since it provides a broad base of scientific experience.Research designs and methods For EPAR-listed mAbs, details of all changes listed chronologically in the EPAR were evaluated and described. Based on these descriptions the manufacturing ch...
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authorized manufacturing changes for therapeutic monoclonal antibodies mabs in european public Assessment Report epar documents
Current Medical Research and Opinion, 2016Co-Authors: Balazs Vezer, Zsuzsanna Buzas, Miklos Sebeszta, Zsombor ZrubkaAbstract:Background The quality of biologicals, including biosimilars, is subject to change as a result of manufacturing process modifications following initial authorization. It is important that such product changes have no adverse impact on product efficacy or safety, including immunogenicity. Objectives The aim of this study was to investigate the number and types of manufacturing changes for originator mAbs (the reference for the comparability exercise to confirm biosimilarity) according to European Public Assessment Report (EPAR) documentation and to ascertain the level of risk these changes might impart. The extensive body of evidence contained in the EPAR documents can help support the EMA during the EC marketing authorization approval process for biosimilars, since it provides a broad base of scientific experience. Research designs and methods For EPAR-listed mAbs, details of all changes listed chronologically in the EPAR were evaluated and described. Based on these descriptions the manufacturing changes can be categorized by risk status (low, moderate or high). Results Entries for 29 mAbs with publicly available EPAR Reports were reviewed. These contained details of 404 manufacturing changes authorized by the European Medicines Agency (EMA): 22 were categorized as high risk, 286 as moderate risk and 96 as low risk manufacturing changes. A limitation of this analysis is that it only summarizes publicly available data from EPAR documents. Conclusions Manufacturing change data indicate that the EMA has significant experience of process changes for originator mAbs, and the impact they may have on the efficacy and safety of biologicals. This experience will be useful in biosimilar product development to ensure adherence to sound scientific principles. Compared with the established manufacturing process for a reference product, the production of biosimilars will usually be different. Consequently, in addition to a comprehensive comparative functional and physicochemical characterization analysis, clinical data is required to confirm mAb biosimilarity.
Balazs Vezer - One of the best experts on this subject based on the ideXlab platform.
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authorized manufacturing changes for therapeutic monoclonal antibodies mabs in european public Assessment Report epar documents
Current Medical Research and Opinion, 2016Co-Authors: Balazs Vezer, Zsuzsanna Buzas, Miklos Sebeszta, Zsombor ZrubkaAbstract:AbstractBackground The quality of biologicals, including biosimilars, is subject to change as a result of manufacturing process modifications following initial authorization. It is important that such product changes have no adverse impact on product efficacy or safety, including immunogenicity.Objectives The aim of this study was to investigate the number and types of manufacturing changes for originator mAbs (the reference for the comparability exercise to confirm biosimilarity) according to European Public Assessment Report (EPAR) documentation and to ascertain the level of risk these changes might impart. The extensive body of evidence contained in the EPAR documents can help support the EMA during the EC marketing authorization approval process for biosimilars, since it provides a broad base of scientific experience.Research designs and methods For EPAR-listed mAbs, details of all changes listed chronologically in the EPAR were evaluated and described. Based on these descriptions the manufacturing ch...
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authorized manufacturing changes for therapeutic monoclonal antibodies mabs in european public Assessment Report epar documents
Current Medical Research and Opinion, 2016Co-Authors: Balazs Vezer, Zsuzsanna Buzas, Miklos Sebeszta, Zsombor ZrubkaAbstract:Background The quality of biologicals, including biosimilars, is subject to change as a result of manufacturing process modifications following initial authorization. It is important that such product changes have no adverse impact on product efficacy or safety, including immunogenicity. Objectives The aim of this study was to investigate the number and types of manufacturing changes for originator mAbs (the reference for the comparability exercise to confirm biosimilarity) according to European Public Assessment Report (EPAR) documentation and to ascertain the level of risk these changes might impart. The extensive body of evidence contained in the EPAR documents can help support the EMA during the EC marketing authorization approval process for biosimilars, since it provides a broad base of scientific experience. Research designs and methods For EPAR-listed mAbs, details of all changes listed chronologically in the EPAR were evaluated and described. Based on these descriptions the manufacturing changes can be categorized by risk status (low, moderate or high). Results Entries for 29 mAbs with publicly available EPAR Reports were reviewed. These contained details of 404 manufacturing changes authorized by the European Medicines Agency (EMA): 22 were categorized as high risk, 286 as moderate risk and 96 as low risk manufacturing changes. A limitation of this analysis is that it only summarizes publicly available data from EPAR documents. Conclusions Manufacturing change data indicate that the EMA has significant experience of process changes for originator mAbs, and the impact they may have on the efficacy and safety of biologicals. This experience will be useful in biosimilar product development to ensure adherence to sound scientific principles. Compared with the established manufacturing process for a reference product, the production of biosimilars will usually be different. Consequently, in addition to a comprehensive comparative functional and physicochemical characterization analysis, clinical data is required to confirm mAb biosimilarity.
Zsuzsanna Buzas - One of the best experts on this subject based on the ideXlab platform.
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authorized manufacturing changes for therapeutic monoclonal antibodies mabs in european public Assessment Report epar documents
Current Medical Research and Opinion, 2016Co-Authors: Balazs Vezer, Zsuzsanna Buzas, Miklos Sebeszta, Zsombor ZrubkaAbstract:AbstractBackground The quality of biologicals, including biosimilars, is subject to change as a result of manufacturing process modifications following initial authorization. It is important that such product changes have no adverse impact on product efficacy or safety, including immunogenicity.Objectives The aim of this study was to investigate the number and types of manufacturing changes for originator mAbs (the reference for the comparability exercise to confirm biosimilarity) according to European Public Assessment Report (EPAR) documentation and to ascertain the level of risk these changes might impart. The extensive body of evidence contained in the EPAR documents can help support the EMA during the EC marketing authorization approval process for biosimilars, since it provides a broad base of scientific experience.Research designs and methods For EPAR-listed mAbs, details of all changes listed chronologically in the EPAR were evaluated and described. Based on these descriptions the manufacturing ch...
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authorized manufacturing changes for therapeutic monoclonal antibodies mabs in european public Assessment Report epar documents
Current Medical Research and Opinion, 2016Co-Authors: Balazs Vezer, Zsuzsanna Buzas, Miklos Sebeszta, Zsombor ZrubkaAbstract:Background The quality of biologicals, including biosimilars, is subject to change as a result of manufacturing process modifications following initial authorization. It is important that such product changes have no adverse impact on product efficacy or safety, including immunogenicity. Objectives The aim of this study was to investigate the number and types of manufacturing changes for originator mAbs (the reference for the comparability exercise to confirm biosimilarity) according to European Public Assessment Report (EPAR) documentation and to ascertain the level of risk these changes might impart. The extensive body of evidence contained in the EPAR documents can help support the EMA during the EC marketing authorization approval process for biosimilars, since it provides a broad base of scientific experience. Research designs and methods For EPAR-listed mAbs, details of all changes listed chronologically in the EPAR were evaluated and described. Based on these descriptions the manufacturing changes can be categorized by risk status (low, moderate or high). Results Entries for 29 mAbs with publicly available EPAR Reports were reviewed. These contained details of 404 manufacturing changes authorized by the European Medicines Agency (EMA): 22 were categorized as high risk, 286 as moderate risk and 96 as low risk manufacturing changes. A limitation of this analysis is that it only summarizes publicly available data from EPAR documents. Conclusions Manufacturing change data indicate that the EMA has significant experience of process changes for originator mAbs, and the impact they may have on the efficacy and safety of biologicals. This experience will be useful in biosimilar product development to ensure adherence to sound scientific principles. Compared with the established manufacturing process for a reference product, the production of biosimilars will usually be different. Consequently, in addition to a comprehensive comparative functional and physicochemical characterization analysis, clinical data is required to confirm mAb biosimilarity.
Miklos Sebeszta - One of the best experts on this subject based on the ideXlab platform.
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authorized manufacturing changes for therapeutic monoclonal antibodies mabs in european public Assessment Report epar documents
Current Medical Research and Opinion, 2016Co-Authors: Balazs Vezer, Zsuzsanna Buzas, Miklos Sebeszta, Zsombor ZrubkaAbstract:AbstractBackground The quality of biologicals, including biosimilars, is subject to change as a result of manufacturing process modifications following initial authorization. It is important that such product changes have no adverse impact on product efficacy or safety, including immunogenicity.Objectives The aim of this study was to investigate the number and types of manufacturing changes for originator mAbs (the reference for the comparability exercise to confirm biosimilarity) according to European Public Assessment Report (EPAR) documentation and to ascertain the level of risk these changes might impart. The extensive body of evidence contained in the EPAR documents can help support the EMA during the EC marketing authorization approval process for biosimilars, since it provides a broad base of scientific experience.Research designs and methods For EPAR-listed mAbs, details of all changes listed chronologically in the EPAR were evaluated and described. Based on these descriptions the manufacturing ch...
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authorized manufacturing changes for therapeutic monoclonal antibodies mabs in european public Assessment Report epar documents
Current Medical Research and Opinion, 2016Co-Authors: Balazs Vezer, Zsuzsanna Buzas, Miklos Sebeszta, Zsombor ZrubkaAbstract:Background The quality of biologicals, including biosimilars, is subject to change as a result of manufacturing process modifications following initial authorization. It is important that such product changes have no adverse impact on product efficacy or safety, including immunogenicity. Objectives The aim of this study was to investigate the number and types of manufacturing changes for originator mAbs (the reference for the comparability exercise to confirm biosimilarity) according to European Public Assessment Report (EPAR) documentation and to ascertain the level of risk these changes might impart. The extensive body of evidence contained in the EPAR documents can help support the EMA during the EC marketing authorization approval process for biosimilars, since it provides a broad base of scientific experience. Research designs and methods For EPAR-listed mAbs, details of all changes listed chronologically in the EPAR were evaluated and described. Based on these descriptions the manufacturing changes can be categorized by risk status (low, moderate or high). Results Entries for 29 mAbs with publicly available EPAR Reports were reviewed. These contained details of 404 manufacturing changes authorized by the European Medicines Agency (EMA): 22 were categorized as high risk, 286 as moderate risk and 96 as low risk manufacturing changes. A limitation of this analysis is that it only summarizes publicly available data from EPAR documents. Conclusions Manufacturing change data indicate that the EMA has significant experience of process changes for originator mAbs, and the impact they may have on the efficacy and safety of biologicals. This experience will be useful in biosimilar product development to ensure adherence to sound scientific principles. Compared with the established manufacturing process for a reference product, the production of biosimilars will usually be different. Consequently, in addition to a comprehensive comparative functional and physicochemical characterization analysis, clinical data is required to confirm mAb biosimilarity.
M G Schultz - One of the best experts on this subject based on the ideXlab platform.
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tropospheric ozone Assessment Report tropospheric ozone from 1877 to 2016 observed levels trends and uncertainties
Elementa: Science of the Anthropocene, 2019Co-Authors: D W Tarasick, Gerard Ancellet, M G Schultz, O R Cooper, I E Galbally, Thierry Leblanc, Timothy J Wallington, Jerry Ziemke, M Steinbacher, J StaehelinAbstract:From the earliest observations of ozone in the lower atmosphere in the 19th century, both measurement methods and the portion of the globe observed have evolved and changed. These methods have di erent uncertainties and biases, and the data records di er with respect to coverage (space and time), information content, and representativeness. In this study, various ozone measurement methods and ozone datasets are reviewed and selected for inclusion in the historical record of background ozone levels, based on relationship of the measurement technique to the modern UV absorption standard, absence of interfering pollutants, representativeness of the well-mixed boundary layer and expert judgement of their credibility. There are signi cant uncertainties with the 19th and early 20th-century measurements related to interference of other gases. Spectroscopic methods applied before 1960 have likely underestimated ozone by as much as 11% at the surface and by about 24% in the free troposphere, due to the use of di ering ozone absorption coe cients. There is no unambiguous evidence in the measurement record back to 1896 that typical mid-latitude background surface ozone values were below about 20 nmol mol–1, but there is robust evidence for increases in the temperate and polar regions of the northern hemisphere of 30–70%, with large uncertainty, between the period of historic observations, 1896–1975, and the modern period (1990–2014). Independent historical observations from balloons and aircraft indicate similar changes in the free troposphere. Changes in the southern hemisphere are much less. Regional representativeness of the available observations remains a potential source of large errors, which are di cult to quantify. The great majority of validation and intercomparison studies of free tropospheric ozone measurement methods use ECC ozonesondes as reference. Compared to UV-absorption measurements they show a modest (~1–5% ±5%) high bias in the troposphere, but no evidence of a change with time. Umkehr, lidar, and FTIR methods all show modest low biases relative to ECCs, and so, using ECC sondes as a transfer standard, all appear to agree to within one standard deviation with the modern UV-absorption standard. Other sonde types show an increase of 5–20% in sensitivity to tropospheric ozone from 1970–1995. Biases and standard deviations of satellite retrieval comparisons are often 2–3 times larger than those of other free tropospheric measurements. The lack of information on temporal changes of bias for satellite measurements of tropospheric ozone is an area of concern for long-term trend studies.
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tropospheric ozone Assessment Report present day tropospheric ozone distribution and trends relevant to vegetation
Elementa: Science of the Anthropocene, 2018Co-Authors: Gina Mills, M G Schultz, O R Cooper, Hakan Pleijel, Christopher S Malley, Baerbel Sinha, Howard S Neufeld, David Simpson, Katrina Sharps, Zhaozhong FengAbstract:This Tropospheric Ozone Assessment Report (TOAR) on the current state of knowledge of ozone metrics of relevance to vegetation (TOAR-Vegetation) Reports on present-day global distribution of ozone at over 3300 vegetated sites and the long-term trends at nearly 1200 sites. TOAR-Vegetation focusses on three metrics over vegetation-relevant time-periods across major world climatic zones: M12, the mean ozone during 08:00-19:59; AOT40, the accumulation of hourly mean ozone values over 40 ppb during daylight hours, and W126 with stronger weighting to higher hourly mean values, accumulated during 08:00-19:59. Although the density of measurement stations is highly variable across regions, in general, the highest ozone values (mean, 2010-14) are in mid-latitudes of the northern hemisphere, including southern USA, the Mediterranean basin, northern India, north, north-west and east China, the Republic of Korea and Japan. The lowest metric values Reported are in Australia, New Zealand, southern parts of South America and some northern parts of Europe, Canada and the USA. Regional-scale Assessments showed, for example, significantly higher AOT40 and W126 values in East Asia (EAS) than Europe (EUR) in wheat growing areas (p < 0.05), but not in rice growing areas. In NAM, the dominant trend during 1995-2014 was a significant decrease in ozone, whilst in EUR it was no change and in EAS it was a significant increase. TOAR-Vegetation provides recommendations to facilitate a more complete global Assessment of ozone impacts on vegetation in the future, including: an increase in monitoring of ozone and collation of field evidence of the damaging effects on vegetation; an investigation of the effects on peri-urban agriculture and in mountain/upland areas; inclusion of additional pollutant, meteorological and inlet height data in the TOAR dataset; where not already in existence, establishing new region-specific thresholds for vegetation damage and an innovative integration of observations and modelling including stomatal uptake of the pollutant.
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tropospheric ozone Assessment Report global ozone metrics for climate change human health and crop ecosystem research
Elementa: Science of the Anthropocene, 2018Co-Authors: Allen S Lefohn, M G Schultz, Gina Mills, Christopher S Malley, Luther Smith, Benjamin Wells, Milan J Hazucha, Heather Simon, Vaishali Naik, Elena PaolettiAbstract:Assessment of spatial and temporal variation in the impacts of ozone on human health, vegetation, and climate requires appropriate metrics. A key component of the Tropospheric Ozone Assessment Report (TOAR) is the consistent calculation of these metrics at thousands of monitoring sites globally. Investigating temporal trends in these metrics required that the same statistical methods be applied across these ozone monitoring sites. The nonparametric Mann-Kendall test (for significant trends) and the Theil-Sen estimator (for estimating the magnitude of trend) were selected to provide robust methods across all sites. This paper provides the scientific underpinnings necessary to better understand the implications of and rationale for selecting a specific TOAR metric for assessing spatial and temporal variation in ozone for a particular impact. The rationale and underlying research evidence that influence the derivation of specific metrics are given. The form of 25 metrics (4 for model-measurement comparison, 5 for characterization of ozone in the free troposphere, 11 for human health impacts, and 5 for vegetation impacts) are described. Finally, this study categorizes health and vegetation exposure metrics based on the extent to which they are determined only by the highest hourly ozone levels, or by a wider range of values. The magnitude of the metrics is influenced by both the distribution of hourly average ozone concentrations at a site location, and the extent to which a particular metric is determined by relatively low, moderate, and high hourly ozone levels. Hence, for the same ozone time series, changes in the distribution of ozone concentrations can result in different changes in the magnitude and direction of trends for different metrics. Thus, dissimilar conclusions about the effect of changes in the drivers of ozone variability (e.g., precursor emissions) on health and vegetation exposure can result from the selection of different metrics.
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Tropospheric Ozone Assessment Report : Present-day ozone distribution and trends relevant to human health
Elementa: Science of the Anthropocene, 2018Co-Authors: Zoe L Fleming, O R Cooper, Erika Von Schneidemesser, Christopher S Malley, David Simpson, Ruth M Doherty, Joseph P Pinto, Augustin Colette, Xiaobin Xu, M G SchultzAbstract:This study quantifies the present-day global and regional distributions (2010–2014) and trends (2000–2014) for five ozone metrics relevant for short-term and long-term human exposure. These metrics, calculated by the Tropospheric Ozone Assessment Report, are: 4th highest daily maximum 8-hour ozone (4MDA8); number of days with MDA8 > 70 ppb (NDGT70), SOMO35 (annual Sum of Ozone Means Over 35 ppb) and two seasonally averaged metrics (3MMDA1; AVGMDA8). These metrics were explored at ozone monitoring sites worldwide, which were classified as urban or non-urban based on population and nighttime lights data. Present-day distributions of 4MDA8 and NDGT70, determined predominantly by peak values, are similar with highest levels in western North America, southern Europe and East Asia. For the other three metrics, distributions are similar with North–South gradients more prominent across Europe and Japan. Between 2000 and 2014, significant negative trends in 4MDA8 and NDGT70 occur at most US and some European sites. In contrast, significant positive trends are found at many sites in South Korea and Hong Kong, with mixed trends across Japan. The other three metrics have similar, negative trends for many non-urban North American and some European and Japanese sites, and positive trends across much of East Asia. Globally, metrics at many sites exhibit non-significant trends. At 59% of all sites there is a common direction and significance in the trend across all five metrics, whilst 4MDA8 and NDGT70 have a common trend at ~80% of all sites. Sensitivity analysis shows AVGMDA8 trends differ with averaging period (warm season or annual). Trends are unchanged at many sites when a 1995–2014 period is used; although fewer sites exhibit non-significant trends. Over the longer period 1970–2014, most Japanese sites exhibit positive 4MDA8/SOMO35 trends. Insufficient data exist to characterize ozone trends for the rest of Asia and other world regions.
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tropospheric ozone Assessment Report database and metrics data of global surface ozone observations
Elementa: Science of the Anthropocene, 2017Co-Authors: M G Schultz, Sabine Schroder, Olga Lyapina, O R Cooper, I E Galbally, Irina Petropavlovskikh, Erika Von Schneidemesser, Hiroshi Tanimoto, Yasin Elshorbany, Manish NajaAbstract:In support of the first Tropospheric Ozone Assessment Report (TOAR) a relational database of global surface ozone observations has been developed and populated with hourly measurement data and enhanced metadata. A comprehensive suite of ozone data products including standard statistics, health and vegetation impact metrics, and trend information, are made available through a common data portal and a web interface. These data form the basis of the TOAR analyses focusing on human health, vegetation, and climate relevant ozone issues, which are part of this special feature. Cooperation among many data centers and individual researchers worldwide made it possible to build the world's largest collection of in-situ hourly surface ozone data covering the period from 1970 to 2015. By combining the data from almost 10,000 measurement sites around the world with global metadata information, new analyses of surface ozone have become possible, such as the first globally consistent characterisations of measurement sites as either urban or rural/remote. Exploitation of these global metadata allows for new insights into the global distribution, and seasonal and long-term changes of tropospheric ozone and they enable TOAR to perform the first, globally consistent analysis of present-day ozone concentrations and recent ozone changes with relevance to health, agriculture, and climate. Considerable effort was made to harmonize and synthesize data formats and metadata information from various networks and individual data submissions. Extensive quality control was applied to identify questionable and erroneous data, including changes in apparent instrument offsets or calibrations. Such data were excluded from TOAR data products. Limitations of a posteriori data quality assurance are discussed. As a result of the work presented here, global coverage of surface ozone data for scientific analysis has been significantly extended. Yet, large gaps remain in the surface observation network both in terms of regions without monitoring, and in terms of regions that have monitoring programs but no public access to the data archive. Therefore future improvements to the database will require not only improved data harmonization, but also expanded data sharing and increased monitoring in data-sparse regions.
