The Minipig – A Rising Star for Nonclinical Safety Testing in Support of Development of Paediatric Medicines?

Abstract Background Breakthroughs in animal studies make the topic of human application of ectogenesis for medical and non-medical purposes more relevant than ever before. While current data do not yet demonstrate a reasonable expectation of clinical benefit soon, several groups are investigating the feasibility of artificial uteri for extracorporeal human gestation. Main text This paper offers the first comprehensive and up to date discussion of the most important pros and cons of human ectogenesis in light of clinical application, along with an examination of crucial ethical (and legal) issues that continued research into, and the clinical translation of, ectogenesis gives rise to. The expected benefits include advancing prenatal medicine, improving neonatal intensive care, and providing a novel pathway towards biological parenthood. This comes with important future challenges. Prior to human application, important questions have to be considered concerning translational research, experimental use of human fetuses and appropriate safety testing. Key questions are identified regarding risks to ectogenesis’ subjects, and the physical impact on the pregnant person when transfer from the uterus to the artificial womb is required. Critical issues concerning proportionality have to be considered, also in terms of equity of access, relative to the envisaged application of ectogenesis. The advent of ectogenesis also comes with crucial issues surrounding abortion, extended fetal viability and moral status of the fetus. Conclusions The development of human ectogenesis will have numerous implications for clinical practice. Prior to human testing, close consideration should be given to whether (and how) ectogenesis can be introduced as a continuation of existing neonatal care, with due attention to both safety risks to the fetus and pressures on pregnant persons to undergo experimental and/or invasive procedures. Equally important is the societal debate about the acceptable applications of ectogenesis and how access to these usages should be prioritized. It should be anticipated that clinical availability of ectogenesis, possibly first as a way to save extremely premature fetuses, may spark demand for non-medical purposes, like avoiding physical and social burdens of pregnancy.

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Method for instrumentation of orthotic joints for measurement of internal joint loads

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2017-0008 ◽

2017 ◽

Vol 3 (1) ◽

pp. 35-38

Author(s):

David Hochmann ◽

Lucien Opitz

Keyword(s):

Gait Analysis ◽

Cross Talk ◽

Inertial Sensors ◽

Small Sample Size ◽

Fem Simulation ◽

Small Sample ◽

Safety Testing ◽

Internal Joint ◽

Custom Made ◽

Joint Loads

Abstract:Introduction:The lack of knowledge of mechanical loads in orthotic joints can lead to oversized or breaking components. Previous studies suffer from small sample size and technical limitations. The goal of this study was to develop and validate a method that allows the direct measurement of moments in sagittal, frontal and transverse planes in knee and ankle joints of existing custom made orthoses.Methods:We developed a modular measurement system based on standard joint components, which were instrumented with strain gauges. To ensure sufficient signals and reduce cross talk an iterative approach based on FEM simulation was utilized. The system also contains inertial sensors for mobile gait analysis.Results:Instrumented joints show good results regarding linearity, hysteresis and cross talk. First pilot trials with post-polio and ICP patients demonstrated that joint loads depend on several factors and not solely on body weight. If combined with conventional gait analysis, measurement results can characterize the individual muscle situation of the patient.Conclusion:A novel method for obtaining data on loads in orthotic components was developed and validated. It provides the basis to develop safety testing standards and clinical guidelines, as well as allowing individual optimization of orthotic devices.

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Regulating Innovation in the Early Development of Cell Therapies

Immunotherapy Advances ◽

10.1093/immadv/ltaa011 ◽

2020 ◽

Author(s):

Andrew R Exley ◽

James McBlane

Keyword(s):

Clinical Trials ◽

Nk Cell ◽

Genetic Manipulation ◽

Clinical Trial Data ◽

Cell Receptor ◽

Mitigation Measures ◽

Safety Testing ◽

Cell Therapies ◽

Commercial Use ◽

Allogeneic Cell

Abstract Clinical need for paradigm shifts in efficacy and safety is driving the rapid and wide-ranging innovation in cell therapies for cancer beyond existing regulatory frameworks. Critical issues emerging during clinical trials frequently reflect unresolved elements of the regulation of innovation conundrum from earlier stages of development. We address this challenge using a global regulators’ perspective on the pre-clinical development of cell therapies, as a navigational aid to intended commercial use which maximises the clinical relevance of developmental data. We examine the implications of tumour targeting based on B cell, NK cell, conventional and unconventional T cell receptor domains; multiplex approaches; genetic manipulation strategies; and autologous versus allogeneic cell sources. We propose that detailed characterisation of both the cell source and final product is critical to optimising manufacture of individualised autologous or off the shelf allogeneic cell therapies, enabling product consistency to underpin extrapolation of clinical trial data to the expected commercial use. We highlight preclinical approaches to characterising target antigens including the Human Cell Atlas initiative, multi-dimensional cell culture, and safety testing against activated, proliferating or stressed control cells. Practical solutions are provided for preclinical toxicity studies when cell therapies target uniquely human tumour antigens, including illustrative mitigation measures for potential toxicity likely to support timely approval of first in human clinical trials. We recommend addressing the regulation of innovation conundrum through serial engagement between innovators and regulators early in the development of cell therapies for cancer, accelerating patient access whilst safeguarding against unacceptable toxicities.

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Ethical, Legal and Regulatory Issues of Paediatric Translational Research. Call for an Adequate Model of Governance

European Journal of Health Law ◽

10.1163/15718093-bja10010 ◽

2020 ◽

Vol 27 (3) ◽

pp. 213-231

Author(s):

Annagrazia Altavilla ◽

Viviana Giannuzzi ◽

Mariangela Lupo ◽

Donato Bonifazi ◽

Adriana Ceci

Keyword(s):

Translational Research ◽

Research Infrastructure ◽

Paediatric Research ◽

Adequate Model ◽

Regulatory Issues ◽

Societal Issues ◽

Translational Approach ◽

Legal Frameworks ◽

Ethical Oversight ◽

Paediatric Medicines

Abstract The lack of paediatric medicines, including innovative and advanced ones, is a long-lasting and well-known problem at European and international levels. Despite the existing legal frameworks and incentives, children remain deprived of many kinds of therapy because of challenges faced in appropriately study and tailoring medicinal and other products for them. In this context, the necessity to foster paediatric research addressing unsolved and uncovered issues within a ‘translational approach’ has appeared. This article, after having clarified the concept of translational research in the perspective of the establishment of a European paediatric research infrastructure (RI), will identify and point out ethical, legal and regulatory issues particularly relevant in a children’s rights perspective. It concludes asking for the setting up of an adequate model of governance within a future RI, including adequate and independent ethical oversight and a pluridisciplinary common service dealing with ethical, legal and societal issues relevant for children.

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Optimising the design of preliminary toxicity studies for pharmaceutical safety testing in the dog

Regulatory Toxicology and Pharmacology ◽

10.1016/j.yrtph.2004.10.006 ◽

2005 ◽

Vol 41 (2) ◽

pp. 95-101 ◽

Cited By ~ 18

Author(s):

David Smith ◽

Robert Combes ◽

Olympe Depelchin ◽

Soren Dyring Jacobsen ◽

Ruediger Hack ◽

...

Keyword(s):

Safety Testing ◽

Toxicity Studies

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Research on Mode of after-Sale Reverse Logistics Operation of Auto Maintenance Industry Based on Time Window

Applied Mechanics and Materials ◽

10.4028/www.scientific.net/amm.121-126.4635 ◽

2011 ◽

Vol 121-126 ◽

pp. 4635-4639

Author(s):

Hao Hao ◽

Xing Gen Wu ◽

Hong Yu Li

Keyword(s):

Supply Chain ◽

Reverse Logistics ◽

High Speed ◽

Time Window ◽

Auto Industry ◽

Road Transport ◽

Motor Vehicles ◽

Safety Testing ◽

Internal Operations ◽

Evaluation Mechanism

The author maintains that, with the quick development of domestic auto industry, the auto maintenance industry is progressing with high speed accordingly. The auto maintenance enterprise are inclined to focus on sales and forward supply chain operation, however, lacking of efficient resource and systematic management into reverse logistics operation, as lead to a few potential risks. In order to avoid and control the risks, the auto maintenance companies need to closely cooperate with channel supply chain partners, meanwhile build up the mode of reverse logistics operation with timing efficiency orientation. This mode consists of eight sub-system modules: organization structure, network planning and layout, reverse logistics operation procedure, time window evaluation mechanism, automatic replenishment system, reverse forecasting system, Kan-ban message system as well as disposal & reuse system. Furthermore, the article makes analysis of the internal operations and external relevance of these eight sub-systems. In recent years, with the overall opening up of road transport market and the rapid growth in domestic economy, the total number of China’s motor vehicles is entering a high-speed growth channel, and “the car goes to the country” policy further promotes the auto industry. Under the situation of quick development, the auto maintenance industry is developing by 10% to 15% each year as a young profession. According to the statistics, there are over 380,000 auto maintenance enterprises in our country at the moment, and various types of auto safety testing stations are built around one after another. The intense competition among auto maintenance manufacturing enterprises does not only focus on product quality, but also on the after-market reverse logistics. According to the statics of Gartner, 70 percent of resale is related with sales service, and 60 percent of resale is related with after market. However, except for few leading business enterprises which have realized the direct influence and value contribution of after-service reverse logistics to profit increase and customer loyalty and take action to pioneer the profit territory in the after-sale reverse logistics, the ‘price war’ is still the main competition method which the majority of enterprises adopt in the market.

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