Commercial Launch Research Articles

Development of an advanced injection time model for an autoinjector.

BackgroundThis work describes an advanced physics-based mathematical model that accurately predicts autoinjector injection time. Autoinjectors are a well-established technology for parenteral drug delivery and quantifying the probability to achieve a given injection time is critical to the successful development and commercial launch of the autoinjector.MethodEach parameter that can influence injection time was treated as a statistical variable with an appropriate distribution function. Monte Carlo simulation was used to obtain the probability of achieving the required injection time. Sensitivity analyses were performed to identify those parameters most critical in contributing to the overall injection time. To validate the model, a number of experiments were conducted on autoinjectors, with key contributors to injection time measured and characterized.ResultsThe results showed excellent agreement between modeled and measured injection time. The modeling error for all investigated device configurations was smaller than 12% and the error range was less than 6%. The consistent over-estimation of injection time suggests a small bias in the model which could be accounted for by reducing internal friction.ConclusionThis work provides evidence that the selected modeling approach, which aims for a simple yet computationally inexpensive model, is accurate and enables running comprehensive statistical simulations to determine the full range of expected injection times due to component variability.

Waiting to Exhale

Mitral regurgitation (MR) is the most common valvular disease in Western countries, affecting 2 to 4 million people in the United States alone.1 When severe and left untreated, MR leads to adverse ventricular remodeling and, in many patients, impaired survival with a high rate of morbidity because of heart failure. For primary MR, surgery, particularly valve repair, is the standard of care and is recommended for patients with either symptoms or significant left ventricular dysfunction.2 Conversely, guideline-directed medical therapy is emphasized for patients with secondary MR and typically consists of β-receptor blockers, vasodilators, diuretics, and aldosterone antagonists, with or without cardiac resynchronization.3 For secondary MR, such therapy targets ventricular dysfunction as the cause of MR and has established efficacy for improving symptoms and the prognosis of patients with heart failure.3 See Article by Kortlandt et al Transcatheter mitral repair with MitraClip (Abbott Vascular, Menlo Park, CA) first became available for high-risk or inoperable patients in 2008, when it received Conformite Europeene mark for clinical use in those with primary or secondary MR in Europe. Agency approval in the United States (primary only) and parts of Asia (primary or secondary or both) soon followed, with the most recent commercial launch occurring in Japan earlier this year. The broad, multinational adoption of transcatheter repair of MR with MitraClip is notable, particularly given (1) the relatively small size of the reported randomized clinical trials of this therapy, (2) the absence of demonstrated superior efficacy of the therapy in comparison with current standards for MR treatment, and (3) for patients with secondary MR, the considerable controversy regarding the benefits of MR correction by any means, be it surgical or transcatheter. Indeed, practice guidelines have given a class IIb recommendation for transcatheter repair of MR (primary or secondary MR in Europe; …

147P Clinical testing of ctDNA from NSCLC patients using A 17-gene liquid biopsy mutation panel

Background: The Oncotype SEQ® Liquid Select™ assay is a next-generation sequencing gene panel assay performed as a laboratory-developed test in a central CLIA-certified laboratory by Genomic Health, Inc. Oncotype SEQ® detects clinically relevant genomic alterations in 17 genes using ctDNA isolated from blood plasma. Here we summarize genomic findings from patients (pts) tested after commercial launch of Oncotype SEQ® in June 2016. Methods: 126 NSCLC pts from 17 community cancer centers in the US were tested with Oncotype SEQ® in routine clinical care. Proprietary technologies and bioinformatics tools were used to identify actionable genomic variants, which were reported to pts' medical records. Results: Tested NSCLC pts were stages IV (124), III (1) and II (1). Diagnoses were adenocarcinoma (94), squamous cell carcinoma (19), other (11), or unknown primary (2). Mean age (range) was 69 y (44–90 y), 64% were ≥65 y, 16% were >80 y. 56% were female. Results were reported for 112 (89%) pts. 135 gene variants were detected in 72/112 (64%) pts across 12 genes. 66% of identified variants were SNV, 5% indels, 27% CNV, and 2% fusions. 39 pts had 1 variant, 19 had 2, and 14 had ≥3. In nonsquamous NSCLC, 91/117 (78%) reported variants were SNV/indel/fusions and 26/117 (22%) were CNV; in squamous tumors, these were 7/16 (44%) and 9/16 (56%), respectively. Clinically actionable variants specified in FDA drug labels or in NCCN guidelines for NSCLC were reported for 42/112 (38%) pts in EGFR (13 variants), ALK (3), KRAS (21), MET (7), BRAF (2), and ERBB2 (1). These were observed at allele fractions as low as 0.12% for KRAS G12D and ranging from 0.26% to 22% for EGFR E746_A750del (n = 4). Other reported variants were potentially actionable, either specified in FDA labels of drugs approved for other tumor types, associated with active therapeutic clinical trials in NSCLC, or represented possible germline variants warranting genetic counseling. Conclusions: Oncotype SEQ® sensitively identifies gene variants that are important to inform optimal management decisions for pts with advanced-stage NSCLC. A retrospective review of medical records to examine concurrent tissue testing, treatments received, and clinical outcomes is ongoing and will be presented. Legal entity responsible for the study: Genomic Health, Inc. Funding: Genomic Health, Inc. Disclosure: D.A. Eberhard, J. Bennett, D. Davison, C. Hammond, A. Petty, J. Pluenneke, A. Dei Rossi, G. Alexander, D. Paragas, M. Lopatin: Employment and stock ownership: Genomic Health.

115 - Moffitt's ICE-T Fuels CAR-T Infrastructure Execution for Commercial Launch

115 - Moffitt's ICE-T Fuels CAR-T Infrastructure Execution for Commercial Launch

Status of Endovascular Aneurysm Sealing After 5 Years of Commercial Use

Endovascular aneurysm sealing (EVAS) using the Nellix Endovascular Sealing System was introduced commercially in 2013 with the aim of reducing the incidences of reintervention and late complications observed after conventional endovascular aneurysm repair (EVAR). In the 5 years since its commercial launch, the Nellix system has evolved in terms of its structure, instructions for use, and delivery technique. Complications, including migration and proximal endoleak, have been recognized and treatment strategies developed, although durability remains to be demonstrated. Prospective multicenter trials have shown a low incidence of type I endoleak and reintervention at 1-year follow-up, comparable to conventional EVAR with modern devices. Since the aneurysm sac is “actively managed” with EVAS, similar to open surgical repair, type II endoleaks are rare with the Nellix system. Unexpected benefits of active sac management with EVAS include reduced incidences of postimplantation syndrome and cardiac complications, with low all-cause mortality at 1 year. Less neck dilatation compared to EVAR has also been observed. The Nellix device and procedure continue to evolve, and further prospective studies are indicated. This article analyzes the current EVAS evidence to update our knowledge of this technique in the management of abdominal aortic aneurysm.

Regulating for Disruption: A Case Study of the Outer Space Law Reform

Technology is changing the world faster than ever before, and many conventional industries are at risk of being disrupted. If New Zealand wants be successful in a changing environment, it needs to be prepared to facilitate more innovative and technologically intensive industries. This paper considers the law reform process that has sought to develop a framework for a commercial launch industry in New Zealand. By using this process as a case study, some broader insight is provided into how effective New Zealand’s law reform process is at regulating for disruption. This paper begins by telling the story of Rocket Lab and Peter Beck in order to demonstrate why this reform was necessary. It then considers several discrete elements of the law reform process such as: the framing of the outer space reform, the incorporation of bilateral and multilateral treaties, regulation through contract and integration of the outer space reform within New Zealand’s environmental law framework. This paper discusses some of the unique and innovative approaches that characterise this reform. It also criticises a few elements of New Zealand’s law reform process and considers how they can be improved.

Design, testing and operation phase improvement taking advantage of data obtained in test benches.

The commercial launch of a new component for the aviation industry takes several steps before it is certified for flight. In these steps test benches have a mayor roll. For example, different design options can be tested, to select the optimum. The test specimen can be subjected to accelerated life tests and the behaviour can be analysed in extreme conditions.Different sensors and monitoring concepts are used during tests to validate and assess component behaviour. With the information generated the design and optimization of the components can be improved, although traditionally the information generated has not been used for maintenance.In the present paper a concept is provided to exploit data from different sources. This way, to improve tested product data is used in the different phases: design, test and operation phase. To show the framework for its exploitation in the different phases of the product three different test benches will be presented: gear, electro-mechanical actuators and seals test benches.

Integrated Guidance System of a Commercial Launch Vehicle

This paper proposes a concept of integrated on-board navigation systems for commercial launch vehicles in the context of the current task, and provided mathematical models of its elements for different variants of designing structure and composition. Has been set and simulated the technical problem of the conceptual design of an integrated navigation system for the space launch vehicle qualified to insert small artificial Earth satellites into low and medium circular orbits with application of GPS technologies.

Title IV of the U.S. Commercial Space Launch Competitiveness Act of 2015: A Critical Step Forward in Facilitating the Development of a Viable Space Infrastructure

With the passage of the Commercial Space Launch Competitiveness Act of 2015 (CSLCA), the United States became the first country to recognize the right of its citizens to own resources they obtain in space. Also, known as Title IV of CSLCA, the law mandates the President to actively facilitate the commercial exploration of space resources, discourage government barriers to the development of a U.S. space resource industry, and promote the right of U.S. citizens to engage in commercial recovery of space resources. The U.S. Congress drafted Title IV of CSLCA with careful and detailed consideration to ensure compliance with international law and its treaty obligations. The space resource utilization provisions of the CSLCA were vetted by various agencies of the U.S. Administration, including the Department of State, and included the input of space law and policy experts. The result was the abandonment of the initial ASTEROIDS Act and the creation of a new legislation that explicitly comported with Articles II and VI of the Outer Space Treaty of 1967. The passage of Title IV was not only a historic precedent but also one of the most forward-thinking space regulatory regimes, which will spur the development of an international space resource utilization industry. Before the passage of Title IV, the legal status of ownership rights in extracted space resources was unclear, effectively shuttering the ability of the nascent space resource utilization industry to secure critical financing. The passage of Title IV, however, has provided the necessary regulatory security for potential investors to assist in the development of the industry with private financing. More importantly, it has immediately catalyzed the interest of other nations, such as Luxembourg, to determine whether they too should pass similar space resource utilization legislation. As additional nations draft their own versions of Title IV of CSLCA and as technology rapidly advances, an international space resource utilization industry will organically develop.

Fifty years of herbicide research: comparing the discovery of trifluralin and halauxifen-methyl.

Fifty years separate the commercialization of the herbicides trifluralin and halauxifen-methyl. Despite the vast degree of technological change that occurred over that time frame, some aspects of their discovery stories are remarkably similar. For example, both herbicides were prepared very early in the iterative discovery process and both were developed from known lead compound structures by hypothesis-driven research efforts without the use of in vitro assays or computer-aided molecular design. However, there are aspects of the halauxifen-methyl and trifluralin discovery stories that are substantially different. For example, the chemical technology required for the cost-effective production of halauxifen-methyl simply did not exist just two decades prior to its commercial launch. By contrast, the chemical technology required for the cost-effective production of trifluralin was reported in the chemical literature more than two decades prior to its commercial launch. In addition, changes in regulatory environment since the early 1960s ensured that their respective discovery to commercial launch stories would also differ in substantial ways. Ultimately, the time and cost required to develop and register halauxifen-methyl demanded a global initial business case while the lower registration hurdles that trifluralin cleared enabled a narrow initial business case mainly focused on the USA. © 2017 Society of Chemical Industry.

The Potential Speculative Bubble in the U.S. Commercial Space Launch Industry and the Implications to the United States

Abstract The U.S. federal government has acknowledged the importance of having a robust domestic space launch industry since the 1980s for national military, civil, and commercial purposes. Since t...

Tailoring a ConOps for NASA LSP Integrated Operations

AbstractAn integral part of the Systems Engineering process is the creation of a Concept of Operations (ConOps) for a given system, with the ConOps initially established early in the system design process and evolved as the system definition and design matures. As Integration Engineers in NASA's Launch Services Program (LSP) at Kennedy Space Center (KSC), our job is to manage the interface requirements for all the robotic space missions that come to our Program for a Launch Service. LSP procures and manages a launch service from one of our many commercial Launch Vehicle Contractors (LVCs) and these commercial companies are then responsible for developing the Interface Control Document (ICD), the verification of the requirements in that document, and all the services pertaining to integrating the spacecraft and launching it into orbit. However, one of the systems engineering tools that have not been employed within LSP to date is a Concept of Operations. The goal of this paper is to research the format and content that goes into these various aerospace industry ConOps and tailor the format and content into template form, so the template may be used as an engineering tool for spacecraft integration with future LSP procured launch services. This tailoring effort was performed as the author's final Masters Project in the Spring of 2016 for the Stevens Institute of Technology and modified for publication with INCOSE (Owens, 2016).

An industry update: what is the latest news in therapeutic delivery?

This Industry Update covers the period from 1 through 30 April 2017, and is based on information sourced from company press releases, scientific literature, patents and various news websites. Biogen expanded its portfolio of developmental drugs targeting neurological diseases by licensing a drug from Bristol-Myers Squibb which is currently under investigation for the treatment of progressive supranuclear palsy. Takeda announced a deal with NuBiyota focused on developing treatments for gastrointestinal disorders, based on the manipulation of microbes living in the gut. Novartis announced an expansion of its neuroscience collaboration with Amgen as well as licensing of a developmental compound to treat dry eye. EmulateBio announced a collaboration with the US FDA to explore and evaluate its organs-on-chip technology in toxicological testing of food products, but which has wider opportunities in drug development. In the treatment of pulmonary hypertension, Vectura announced the commercial launch of its Fox nebulizer technology to deliver a Bayer drug and Respira announced a deal in which it exclusively licensed an inhaled drug-device product to United Therapeutics. Published research suggested that the benefit of pumps over multiple injections in the treatment of diabetes maybe more due to training than technology, and a group from the University of Pennsylvania showed that electrical stimulation of the brain can improve memory function but only when applied at the right time. Alzheon published work that explains the mechanism behind its developmental Alzheimer's drug.

Tesla SolarCity Ramping Up for Commercial Launch by Mid-Year

Tesla SolarCity Ramping Up for Commercial Launch by Mid-Year

Law of Space Resources and Operations on Celestial Bodies: Implications for Legislation in the United States

ABSTRACTThe U.S. assertion of a right to own resources harvested from space is consistent with the distinction in international law governing analogous res communis areas between resources harvested from a common area and the common area itself. Under the Outer Space Treaty regime, private entities do not have any more right to appropriate celestial bodies than governments do. However, U.S. law does not give private entities such a right. The U.S. Commercial Space Launch Competitiveness Act’s chapter on Space Resource Commercial Exploration and Utilization generally avoids taking a position on exactly how to deal with disputes in the event the activities of entities from the United States and other states interfere with each other. The U.S. law does not assert a right to declare safety zones or otherwise exercise jurisdiction outside space objects, but doing so can, under some circumstances, be consistent with international law. Many of the specifics of what rules will govern the gathering of space resources remain undetermined, yet the act’s basic premise is correct: international law and the treaty obligations of the United States allow for the U.S. government to authorize its citizens to own resources obtained from space.

Regulating Non-Traditional Space Activities in the United States in the Wake of the Commercial Space Launch Competitiveness Act

With the rapid growth of space technology and the development of new ‘non-traditional’ space ventures there is concern that the United States will suffer from a ‘regulatory gap’ when these new space activities outstrip the existing regulatory framework. Such a gap might support a finding that the United States is not in compliance with Article VI of the Outer Space Treaty which requires a state to ‘authorize and continually supervise’ the space activity of its nationals. Congress responded to this concern by enacting the Commercial Space Launch Competitiveness Act in 2015 (CSLCA) which took the first steps to fill the ‘gap’. New bills are now under consideration which will take the next step in this legislative process to fill the ‘gap’ by giving the Federal Aviation Administration (FAA) authority to license non-traditional space missions. In the so-called section 108 Report, the White House recommended an approach based on the FAA’s existing process of payload review. Sen. Jim Bridenstine proposed a similar approach in his American Space Renaissance Act (ASRA). Until the legislative process is complete, however, the FAA is leveraging its existing authority in order to regulate non-traditional activity, as has been seen in the agency’s actions involving Bigelow Aerospace and, more recently, Moon Express.

Filling the Regulatory Void for Launch and Reentry Safety Resulting from the Commercialization of Space Operations

ABSTRACT The commercial use of space is not a new concept. Satellites have provided commercial services since the 1960s. However, the launch and recovery of space vehicles was dominated by State operators or under State Contract until the end of the last century. While commercial launches continue to increase, the international regulatory frameworks related to launch and reentry are fundamentally unchanged and are not structured to support a competitive commercial launch industry. This paper examines the regulatory gaps in the existing frameworks, particularly in the international domain. While there remain unresolved questions with regard to ICAO as it applies to suborbital flight, the ability of ICAO to develop standards and recommended practices for the portion of the operation that takes place in civil airspace is clear. These standards are necessary to ensure the safety of civil airspace for both traditional airspace users and launch operators, and the interaction of spaceports with civil airspace.

Magmaris preliminary recommendation upon commercial launch: a consensus from the expert panel on 14 April 2016.

Bioresorbable scaffolds represent an exciting milestone in the development of coronary stent technology with the potential to substantially improve the management of patients with coronary artery disease. In an attempt to provide first recommendations for the technology, experienced experts involved in the first-in-man studies met in Zurich on the 14 April 2016 in order to reach consensus on a responsible market introduction. This document will be updated regularly as new information from clinical trials becomes available and should be understood as a review of current data, opportunities, expectations, advice, and recommendations for future investigations.

Next Generation Battery Technologies based on Reversible Lithium Metal Electrodes

In the late 1980’s a number of companies were attempting to commercialize rechargeable lithium metal batteries. Unfortunately these batteries were plagued by safety problems associated with the stripping and plating of lithium metal in liquid electrolytes. This was followed in 1991 by the highly successful commercial launch of Li-ion batteries by Sony. Although Li-ion battery technology has seen steady incremental improvements since that time, the market demand for a disruptive battery technology is undeniable. Accordingly, over the past few decades there have been significant investments in R&D targeted at next generation batteries. In this presentation we will address strategies for realizing this goal through introduction of reversible lithium metal electrodes.

Title IV – Space Resource Exploration and Utilization of the US Commercial Space Launch Competitiveness Act: A Legal and Political Assessment

On November 25, 2015, the President of the United States (US) signed into law the US Commercial Space Launch Competitiveness Act. This event received extensive coverage, both in the press and legal literature, mostly due to the content of its Title IV dedicated to Space Resource Exploration and Utilization. Pursuant to Title IV, US citizens shall be entitled under US law to collect, own, transport and sell asteroid and space resources that they have obtained in the course of resource recovery operations. Considering that international space law does not clarify whether space resources can be appropriated and used for commercial purposes, the enactment of the US Commercial Space Launch Competitiveness Act has been deemed by some commentators to amount to a breach of the international obligations of the US. In light of this controversy, the purpose of the present paper is to assess the consistency of the Act with international space law and to discuss the legal and political implications related to its adoption and (future) implementation.