scholarly journals Self-contained, low-cost Body-on-a-Chip systems for drug development

2017 ◽  
Vol 242 (17) ◽  
pp. 1701-1713 ◽  
Author(s):  
Ying I Wang ◽  
Carlota Oleaga ◽  
Christopher J Long ◽  
Mandy B Esch ◽  
Christopher W McAleer ◽  
...  
Keyword(s):  
Drug Development ◽  
Development Process ◽  
Mechanical Response ◽  
High Reliability ◽  
Low Cost ◽  
Drug Development Process ◽  
Functional Responses ◽  
Drug Candidates ◽  
Organ Systems ◽  
Microphysiological Systems

Integrated multi-organ microphysiological systems are an evolving tool for preclinical evaluation of the potential toxicity and efficacy of drug candidates. Such systems, also known as Body-on-a-Chip devices, have a great potential to increase the successful conversion of drug candidates entering clinical trials into approved drugs. Systems, to be attractive for commercial adoption, need to be inexpensive, easy to operate, and give reproducible results. Further, the ability to measure functional responses, such as electrical activity, force generation, and barrier integrity of organ surrogates, enhances the ability to monitor response to drugs. The ability to operate a system for significant periods of time (up to 28 d) will provide potential to estimate chronic as well as acute responses of the human body. Here we review progress towards a self-contained low-cost microphysiological system with functional measurements of physiological responses. Impact statement Multi-organ microphysiological systems are promising devices to improve the drug development process. The development of a pumpless system represents the ability to build multi-organ systems that are of low cost, high reliability, and self-contained. These features, coupled with the ability to measure electrical and mechanical response in addition to chemical or metabolic changes, provides an attractive system for incorporation into the drug development process. This will be the most complete review of the pumpless platform with recirculation yet written.

scholarly journals Use of Microdosing and Accelerator Mass Spectrometry To Evaluate the Pharmacokinetic Linearity of a Novel Tricyclic GyrB/ParE Inhibitor in Rats

2014 ◽  
Vol 58 (11) ◽  
pp. 6477-6483 ◽  
Author(s):  
Michael A. Malfatti ◽  
Victoria Lao ◽  
Courtney L. Ramos ◽  
Voon S. Ong ◽  
Kenneth W. Turteltaub
Keyword(s):  
Drug Development ◽  
Development Process ◽  
Dose Range ◽  
Area Under The Curve ◽  
Drug Candidate ◽  
Drug Development Process ◽  
Sprague Dawley ◽  
Drug Candidates ◽  
Biological Fate ◽  
Therapeutic Doses

ABSTRACTDetermining the pharmacokinetics (PKs) of drug candidates is essential for understanding their biological fate. The ability to obtain human PK information early in the drug development process can help determine if future development is warranted. Microdosing was developed to assess human PKs, at ultra-low doses, early in the drug development process. Microdosing has also been used in animals to confirm PK linearity across subpharmacological and pharmacological dose ranges. The current study assessed the PKs of a novel antimicrobial preclinical drug candidate (GP-4) in rats as a step toward human microdosing studies. Dose proportionality was determined at 3 proposed therapeutic doses (3, 10, and 30 mg/kg of body weight), and PK linearity between a microdose and a pharmacological dose was assessed in Sprague-Dawley rats. Plasma PKs over the 3 pharmacological doses were proportional. Over the 10-fold dose range, the maximum concentration in plasma and area under the curve (AUC) increased 9.5- and 15.8-fold, respectively. PKs from rats dosed with a14C-labeled microdose versus a14C-labeled pharmacological dose displayed dose linearity. In the animals receiving a microdose and the therapeutically dosed animals, the AUCs from time zero to infinity were 2.6 ng · h/ml and 1,336 ng · h/ml, respectively, and the terminal half-lives were 5.6 h and 1.4 h, respectively. When the AUC values were normalized to a dose of 1.0 mg/kg, the AUC values were 277.5 ng · h/ml for the microdose and 418.2 ng · h/ml for the pharmacological dose. This 1.5-fold difference in AUC following a 300-fold difference in dose is considered linear across the dose range. On the basis of the results, the PKs from the microdosed animals were considered to be predictive of the PKs from the therapeutically dosed animals.

Intelligent Drug Development

2014 ◽  
Author(s):  
Michael Tansey
Keyword(s):  
Clinical Trials ◽  
Cost Effectiveness ◽  
Drug Development ◽  
Clinical Research ◽  
Development Process ◽  
Drug Development Process ◽  
Individual Trial ◽  
Specific Technology

Clinical research is heavily regulated and involves coordination of numerous pharmaceutical-related disciplines. Each individual trial involves contractual, regulatory, and ethics approval at each site and in each country. Clinical trials have become so complex and government requirements so stringent that researchers often approach trials too cautiously, convinced that the process is bound to be insurmountably complicated and riddled with roadblocks. A step back is needed, an objective examination of the drug development process as a whole, and recommendations made for streamlining the process at all stages. With Intelligent Drug Development, Michael Tansey systematically addresses the key elements that affect the quality, timeliness, and cost-effectiveness of the drug-development process, and identifies steps that can be adjusted and made more efficient. Tansey uses his own experiences conducting clinical trials to create a guide that provides flexible, adaptable ways of implementing the necessary processes of development. Moreover, the processes described in the book are not dependent either on a particular company structure or on any specific technology; thus, Tansey's approach can be implemented at any company, regardless of size. The book includes specific examples that illustrate some of the ways in which the principles can be applied, as well as suggestions for providing a better context in which the changes can be implemented. The protocols for drug development and clinical research have grown increasingly complex in recent years, making Intelligent Drug Development a needed examination of the pharmaceutical process.

Microphysiological systems: What it takes for community adoption

2021 ◽  
pp. 153537022110088
Author(s):  
Passley Hargrove-Grimes ◽  
Lucie A Low ◽  
Danilo A Tagle
Keyword(s):  
Rare Diseases ◽  
Development Process ◽  
Emerging Technology ◽  
National Institutes Of Health ◽  
Drug Development Process ◽  
Microphysiological Systems ◽  
Pediatric Populations ◽  
Neural Disorders ◽  
Future Path

Microphysiological systems (MPS) are promising in vitro tools which could substantially improve the drug development process, particularly for underserved patient populations such as those with rare diseases, neural disorders, and diseases impacting pediatric populations. Currently, one of the major goals of the National Institutes of Health MPS program, led by the National Center for Advancing Translational Sciences (NCATS), is to demonstrate the utility of this emerging technology and help support the path to community adoption. However, community adoption of MPS technology has been hindered by a variety of factors including biological and technological challenges in device creation, issues with validation and standardization of MPS technology, and potential complications related to commercialization. In this brief Minireview, we offer an NCATS perspective on what current barriers exist to MPS adoption and provide an outlook on the future path to adoption of these in vitro tools.

scholarly journals Bayesian meta-analytical methods to incorporate multiple surrogate endpoints in drug development process

2015 ◽  
Vol 35 (7) ◽  
pp. 1063-1089 ◽  
Author(s):  
Sylwia Bujkiewicz ◽  
John R. Thompson ◽  
Richard D. Riley ◽  
Keith R. Abrams
Keyword(s):  
Drug Development ◽  
Analytical Methods ◽  
Development Process ◽  
Surrogate Endpoints ◽  
Drug Development Process

scholarly journals Precision Medicine: From “Omics” to Economics towards Data-Driven Healthcare - Time for European Transformation

2017 ◽  
Vol 2 (Suppl. 1) ◽  
pp. 1-10 ◽  
Author(s):  
Denis Lacombe ◽  
Lifang Liu ◽  
Françoise Meunier ◽  
Vassilis Golfinopoulos
Keyword(s):  
Drug Development ◽  
Development Process ◽  
Precision Oncology ◽  
Drug Development Process ◽  
Cancer Treatments ◽  
True Value ◽  
Efficient Access ◽  
Funding Agencies ◽  
Anti Cancer

There is room for improvement for optimally bringing the latest science to the patient while taking into account patient priorities such as quality of life. Too often, regulatory agencies, governments, and funding agencies do not stimulate the integration of research into care and vice versa. Re-engineering the drug development process is a priority, and healthcare systems are long due for transformation. On one hand, patients need efficient access to treatments, but despite precision oncology approaches, efficiently shared screening platforms for sorting patients based on the biology of their tumour for trial access are lacking and, on the other hand, the true value of cancer care is poorly addressed as central questions such as dose, scheduling, duration, and combination are not or sub-optimally addressed by registration trials. Solid evidence on those parameters could potentially lead to a rational and wiser use of anti-cancer treatments. Together, optimally targeting patient population and robust comparative effectiveness data could lead to more affordable and economically sound approaches. The drug development process and healthcare models need to be interconnected through redesigned systems taking into account the full math from drug development into affordable care.

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