Navigating Market Authorization: The Path Holoclar Took to Become the First Stem Cell Product Approved in the European Union

Gene therapy, cell therapy, and tissue engineering have the potential to revolutionize the treatment of disease and injury. Attaining marketing authorization for such advanced therapy medicinal products (ATMPs) requires a rigorous scientific evaluation by the European Medicines Agencyâauthorization is only granted if the product can fulfil stringent requirements for quality, safety, and efficacy. However, many ATMPs are being provided to patients under alternative means, such as âhospital exemptionâ schemes. Holoclar (ex vivo expanded autologous human corneal epithelial cells containing stem cells), a novel treatment for eye burns, is one of the few ATMPs to have been granted marketing authorization and is the first containing stem cells. This review highlights the differences in standards between an authorized and unauthorized medicinal product, and specifically discusses how the manufacture of Holoclar had to be updated to achieve authorization. The result is that patients will have access to a therapy that is manufactured to high commercial standards, and is supported by robust clinical safety and efficacy data. Stem Cells Translational Medicine 2018;7:146â154

Application of statistical methods for the comparison of data distributions

Data analysis is an essential section of all physics experiments; in spite of this only a few analysis standard toolkits are available. Concerning the comparison between distributions, almost all these toolkits are limited to the Chi-squared test. Statistics provides a whole chapter of Goodness-of-Fit tests, from the Chi-squared to tests based on maximum distance (Kolmogorov-Smirnov, Kuiper, Goodman), to tests based on quadratic distance (Fisz-Cramer-von Mises, Anderson-Darling, Tiku). All of these Goodness-of-Fit tests have been collected in a new open-source Statistical Toolkit

A statistical toolkit for data analysis

The present project aims to develop an open-source and object-oriented software Toolkit for statistical data analysis. Its statistical testing component contains a variety of Goodness-of-Fit tests, from Chi-squared to Kolmogorov-Smirnov, to less known, but generally much more powerful tests such as Anderson-Darling, Goodman, Fisz-Cramer-von Mises, Kuiper, Tiku

Data Analysis in HEP: a Statistical Toolkit

The present project in progress aims to develop an object-oriented software toolkit for statistical data analysis

A goodness-of-fit statistical toolkit

Statistical methods play a significant role throughout the life-cycle of physics experiments, being an essential component of physics analysis. The present project in progress aims to develop an object-oriented software Toolkit for statistical data analysis. The Toolkit contains a variety of Goodness-of-Fit (GoF) tests, from Chi-squared to Kolmogorov–Smirnov, to less known, but generally much more powerful tests such as Anderson–Darling, Goodman, Fisz–Cramer–von Mises, Kuiper. Thanks to the component-based design and the usage of the standard abstract interfaces for data analysis, this tool can be used by other data analysis systems or integrated in experimental software frameworks

Un esempio di trasferimento tecnologico dalla fisica delle alte energie alla pratica clinica radioterapica: sviluppo di un toolkit statistico per il confronto di distribuzioni

Lo scopo di questo lavoro è fornire uno strumento di software sofisticato per la validazione statistica delle distribuzioni isodosi calcolate da un toolkit adottato per la simulazione del passaggio delle particelle nella materia (Geant4). Tale validazione si basa sul confronto dei risultati delle simulazioni con set di misure sperimentali, con dati di riferimento disponibili in letteratura o con dati ottenuti da calcoli teorici o da fit

Biological parameters determining the clinical outcome of autologous cultures of limbal stem cells

Aim: Limbal cultures restore the corneal epithelium in patients with ocular burns. We investigated the biological parameters instrumental for their clinical success. Methods: We report a long-term multicenter prospective study on 152 patients carrying corneal destruction due to severe ocular burns, treated with autologous limbal cells cultured on fibrin and clinical-grade 3T3-J2 feeder cells. Clinical results were statistically evaluated both by parametric and nonparametric methods. Results: Clinical outcomes were scored as full success, partial success and failure in 66.05, 19.14 and 14.81% of eyes, respectively. The total number of clonogenic cells, colony size, growth rate and presence of conjunctival cells could not predict clinical results. Instead, the clinical data provided conclusive evidence that graft quality and likelihood of a successful outcome rely on an accurate evaluation of the number of stem cells detected before transplantation as holoclones expressing high levels of the p63 transcription factor. No adverse effects related to the feeder layer have been observed and the regenerated epithelium was completely devoid of any 3T3-J2 contamination. Conclusion: Cultures of limbal stem cells can be safely used to successfully treat massive destruction of the human cornea. We emphasize the importance of a discipline for defining the suitability and the quality of cultured epithelial grafts, which are relevant to the future clinical use of any cultured cell type

Geant4 electromagnetic physics progress

The Geant4 electromagnetic (EM) physics sub-packages are a component of LHC experiment simulations. During long shutdown 2 for LHC, these packages are under intensive development and we report progress of EM physics in Geant4 versions 10.5 and 10.6, which includes faster computation, more accurate EM models, and extensions to the validation suite. New approaches are developed to simulate radiation damage for silicon vertex detectors and for configuration of multiple scattering per detector region. Improvements in user interfaces developed for low-energy and the Geant4-DNA project are used also for LHC simulation optimisation