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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Pivotal trial characteristics and types of endpoints used to support Food and Drug Administration rare disease drug approvals between 2013 and 2022

Background/aims Rare disease drug development faces unique challenges, such as genotypic and phenotypic heterogeneity within small patient populations and a lack of established outcome measures for conditions without previously successful drug development programs. These challenges complicate the process of selecting the appropriate trial endpoints and conducting clinical trials in rare diseases. In this descriptive study, we examined novel drug approvals for non-oncologic rare diseases by the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research over the past decade and characterized key regulatory and trial design elements with a focus on the primary efficacy endpoint utilized as the basis of approval. Methods Using the Food and Drug Administration’s Data Analysis Search Host database, we identified novel new drug applications and biologics license applications with orphan drug designation that were approved between 2013 and 2022 for non-oncologic indications. From Food and Drug Administration review documents and other external databases, we examined characteristics of pivotal trials for the included drugs, such as therapeutic area, trial design, and type of primary efficacy endpoints. Differences in trial design elements associated with primary efficacy endpoint type were assessed such as randomization and blinding. Then, we summarized the primary efficacy endpoint types utilized in pivotal trials by therapeutic area, approval pathway, and whether the disease etiology is well defined. Results One hundred and seven drugs that met our inclusion criteria were approved between 2013 and 2022. Assessment of the 107 drug development programs identified 150 pivotal trials that were subsequently analyzed. The pivotal trials were mostly randomized (80%) and blinded (69.3%). Biomarkers (41.1%) and clinical outcomes (42.1%) were commonly utilized as primary efficacy endpoints. Analysis of the use of clinical trial design elements across trials that utilized biomarkers, clinical outcomes, or composite endpoints did not reveal statistically significant differences. The choice of primary efficacy endpoint varied by the drug’s therapeutic area, approval pathway, and whether the indicated disease etiology was well defined. For example, biomarkers were commonly selected as primary efficacy endpoints in hematology drug approvals (70.6%), whereas clinical outcomes were commonly selected in neurology drug approvals (69.6%). Further, if the disease etiology was well defined, biomarkers were more commonly used as primary efficacy endpoints in pivotal trials (44.7%) than if the disease etiology was not well defined (27.3%). Discussion In the past 10 years, numerous novel drugs have been approved to treat non-oncologic rare diseases in various therapeutic areas. To demonstrate their efficacy for regulatory approval, biomarkers and clinical outcomes were commonly utilized as primary efficacy endpoints. Biomarkers were not only frequently used as surrogate efficacy endpoints in accelerated approvals, but also in traditionally approved rare disease drugs. The choice of primary efficacy endpoints varied by therapeutic area, approval pathway, and understanding of disease etiology.

Hong, Kyungwan [Rare Diseases Team, Office of New ↗
NASA NTRS2019

Potential Improvements to the Nuclear Safety and Launch Approval Process for Nuclear Reactors Utilized for Space Power and Propulsion Applications

This study examines potential improvements that could be made to the nuclear safety and launch approval process for fission reactors to reduce the associated uncertainties in cost and schedule while continuing to ensure public safety and environmental protection. It concentrates on the launch approval and mission safety of fission power and propulsion applications of nuclear energy. Improvements to the launch approval process for radioisotope power systems (RPSs) are being considered elsewhere but are acknowledged throughout the report. The study considered technical, process, and organizational improvements to the launch approval processes. The study exclusively evaluated reactors that would not be started up prior to achieving a “sufficiently high orbit,” per United Nations (UN) Resolution 47/68.Potential criticality accidents were considered that could occur during a launch failure or abort or during reentry. Numerous scenarios were examined that might involve one or more Earth flybys as well as potential transportation missions that could intentionally return an active, or previously active fission reactor to Earth orbit. The Study Group was guided in its deliberations according to a number of fundamental principles. These included the paramount importance of adequate and appropriate levels of public safety and environmental protection as well as the importance of the inclusion of independent scientific, engineering, and safety reviews of the applications and proposals as a critical part of the process. Also considered was the need for the development of launch approval processes that might be different, depending upon the source of the application for launch approval, whether it be derived as a governmental launch, a commercial launch, or a hybrid/combination of the two. It is clear that all launches of nuclear reactors into space should have similar safety requirements; however, the safety review effort and the details of the analysis that are required should be commensurate with the potential hazards and the actual risk, which may differ based on the reactor design and its intended purpose. Finally, the study aimed at ensuring that whatever processes and procedures are developed should maximize the sufficiency, simplicity, and transparency of the processes. The Study Group reached five Conclusions and makes thirteen Recommendations. The Conclusions and Recommendations presented here are extensions of those presented previously in other studies. This report attempts to add specificity to the actions that need to be taken in order to move forward with successful space fission reactor programs. Without action to address the perceived and real problems in the launch approval process, designers and mission managers will be reluctant to commit the resources necessary to make space fission reactors a reality.

Camp, Allen↗
DOE OSTI2024

Development and Demonstration of a Risk Assessment Approach for Approval of a Transportation Package of a Transportable Nuclear Power Plant for Domestic Highway Shipment

The U.S. Department of Defense (DoD) Strategic Capabilities Office (SCO) has tasked PNNL to address the regulatory challenges associated with confirming the safe transport of Transportable Nuclear Power Plants (TNPPs) containing irradiated nuclear fuel. A previous report—Proposed Risk-Informed Regulatory Framework for Approval of Microreactor Transportation Packages (PNNL-31867)—determined that the expected radioactive inventory in the irradiated fuel of a TNPP would likely require shipment in an NRC-approved Type B package (or spent nuclear fuel cask) but that a TNPP “package” is unlikely to meet the entire suite of NRC requirements set forth in Part 71 of Title 10 of the Code of Federal Regulations (CFR) for a Type B package. It was therefore concluded that shipment of this initial TNPP transportation package, as well as possibly others, under existing regulations would likely require NRC approval using the 10 CFR 71.12 (“Specific exemptions”) process that relies on risk-informed decision making supported by quantitative risk assessment (i.e., Probabilistic Risk Assessment).

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
DOE OSTI2025

Recommendations to Improve Nuclear Licensing: Update to INL/RPT-23-72206, Recommendations to Improve the Nuclear Regulatory Commission Reactor Licensing and Approval Process

In 2023, various stakeholders had asked for BEA’s thoughts and recommendations to improve the U.S. Nuclear Regulatory Commission’s (NRC) licensing review and approval process. This included an April 14, 2023 request from the House Committee on Energy and Commerce on “information and recommendations to improve the licensing review and approval process, . . . as well as the siting, licensing, construction, and oversight of advanced nuclear reactor technologies.” In response to these requests, BEA prepared and published INL/RPT-23-72206, Recommendations to Improve the Nuclear Regulatory Commission Reactor Licensing and Approval Process (2023 Report). The 2023 Report included 13 recommendations related to streamlining NRC hearings, expediting NRC safety and environmental reviews, otherwise improving NRC licensing, and providing financial benefits to new reactor projects. Many of these earlier recommendations were addressed through various legislative actions or changes made by the NRC. Section 2 of this report addresses the current status of those earlier recommendations. BEA recently received a new request from the House Committee on Energy and Commerce seeking any suggestions for additional areas to examine or potential reforms “that may assist in modernizing the licensing and regulatory process that affects civil nuclear deployment.” Additionally, the new Secretary of Energy has identified initial DOE actions to support unleashing the golden era of American energy dominance, including “Unleash Commercial Nuclear Power in the United States” and “Streamline Permitting and Identify Undue Burdens on American Energy.” Given these developments, BEA has prepared a new set of updated recommendations in this report. The recommendations include updated versions of recommendations from the 2023 Report which have not been fully adopted, as well as entirely new recommendations. This set of recommendations has a slightly broader focus with some recommendations focused on DOE authorizations and some recommendations related to nuclear licensing beyond new reactors. Each recommendation below also identifies whether the recommendation would require legislative action or could be addressed directly by the respective agency.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
NASA NTRS2004

RAT Requisition Approval Team - A L6S Initiative

L6S Project Description - Problem: The current cycle time for generating and approving Requisitions does not meet "Best-In-Class." . Scope: Only looking at the Florida Requisition Approval process for Orbiter (ORBF & ORBG) and Ground (GFAC) stocked items. This includes the time from when a requirement is generated by Logistics Planning and Supportability in Florida until it is approved and received by Procurement. Requisitions generated at other sites or for non stocked items will be out of scope of this Project

Hall, Valerie↗
NASA NTRS2019

Electronic Departure Approval Requests in ATD-2 Daily Operations

The NASA Airspace Technology Demonstration 2 project is investigating Integrated Arrival-Departure-Surface air traffic management through progressive refinement of a surface air traffic management system fielded at Charlotte-Douglas International Airport. Among the areas under study are departure release-time approval request (APREQ) traffic management initiatives. Scheduling departures at downstream points and complying with approved departure release times helps flights fit smoothly into busy traffic streams. This paper presents a review of APREQ operations and compliance data from daily electronic APREQ negotiations over fourteen months beginning in January 2018. It describes APREQ-compliance improvements observed as the electronic negotiation process has matured and discusses contributing factors, including renegotiation of departure release times.

Call for release↗
NASA NTRS2019

Departure Approval Request Compliance Effects on Overhead Stream Insertion

Integrated Arrival-Departure-Surface (IADS) air traffic management relies on information sharing and integration between automation systems for efficiency, predictability, and throughput improvements throughout the National Airspace System (NAS). The NASA Airspace Technology Demonstration 2 (ATD-2) project supports this effort by integrating SWIM (System Wide Information Management) information and evaluating and refining potential TFDM (Terminal Flight Data Manager) functionality in a surface traffic management system fielded at Charlotte-Douglas International Airport (CLT). Among the IADS areas under study during ATD-2 is the use of electronically negotiated departure times for efficiently inserting flights into overhead traffic streams. Stream-insertion accuracy is important for reducing excessive vectoring that negatively impacts the NAS by increasing controller workload along with aircraft fuel burn and emissions. Departure-time approval requests (APREQs) provide center-approved departure times to allow for smooth stream insertion. In this presentation, TBFM (Time-Based Flow Management) and ATD-2 flight summary data are used to empirically show that APREQ compliance leads to improved stream insertion.

Overhead-Stream Insertion↗
NASA NTRS2003

Obtaining NASA Approval for use of Non-Metallic Materials in Manned Space Flight

Material manufacturers and suppliers are often surprised when a material commonly provided to industry is not approved for use on manned spacecraft. Often the reason is a lack of test data in environments that simulate those encountered in space applications, especially oxygen-enriched conditions, which significantly increase both the likelihood of material combustion and the propagation of a fire. This paper introduces the requirements for flight approval of non-metallic materials, focusing on material testing for human-rated space flight programs; it reviews the history of flight materials requirements and provides the rationale for such and introduces specific requirements related to testing and to good material engineering and design practices. After describing the procedure for submitting materials to be tested, the paper outlines options available if a material fails testing. In addition, this treatise introduces the National Aeronautics and Space Administration's (NASA's) Materials and Processes Technical Information System (MAPTIS), a database housing all test data produced in accordance with NASA-STD-6001, Flammability, Odor, Offgassing, and Compatibility Requirements and Test Procedures for Materials in Environments that Support Combustion.

Davis, Samuel E.↗
NASA NTRS2018

Evolution of Electronic Approval Request Procedures at Charlotte Douglas International Airport

At many major U.S. airports, a departure approval request, or 'APREQ,' establishes a later runway departure time for a flight, allowing it to absorb tactical delay on the ground. APREQ times are traditionally coordinated by a process known as 'call-for-release' whereby an airport surface traffic manager calls an airspace traffic manager on the telephone. This research examines new electronic APREQ coordination enabled by the NASA Airspace Technology Demonstration-2 system and compares it to the call-for-release method of coordination. During the initial deployment period, electronic APREQ coordination was used for more than half of eligible flights. A majority of electronic requests were approved in less than one minute on average. Data suggest that both the average tactical delay and compliance with the electronically coordinated departure times did not differ significantly from departure times coordinated using call-for-release.

APREQ↗
NASA NTRS2018

Evolution of Electronic Approval Request Procedures at Charlotte Douglas International Airport

A departure approval request, or APREQ, establishes a later runway departure time for a flight, allowing it to absorb tactical delay on the ground. APREQ times are traditionally coordinated by a process known as "call-for-release" whereby an airport surface traffic manager calls an airspace traffic manager on the telephone. This research examines new electronic APREQ coordination enabled by the NASA Airspace Technology Demonstration-2 system and compares it to the traditional call-for-release method of coordination. During the initial deployment period, electronic APREQ coordination was used for more than half of eligible flights. A majority of electronic requests were approved in less than one minute on average. Both the average tactical delay and compliance with the electronically coordinated departure times did not differ significantly from departure times coordinated using call-for-release.

APREQ↗
NASA NTRS2019

Electronic Departure Approval Requests in ATD-2 Daily Operations

The NASA Air Traffic Management Demonstration 2 project is investigating Integrated Arrival-Departure-Surface (IADS) air traffic management through progressive refinement of a surface air traffic management system fielded at Charlotte-Douglas International Airport. Among the IADS areas under study are departure release-time approval request (APREQ) traffic management initiatives. This paper presents a review of APREQ operations and compliance data from daily electronic APREQ negotiations. It describes APREQ-compliance improvements observed as the ATD-2 electronic negotiation process has matured and discusses contributing factors.

call for release↗
DOE OSTI2024

Impact of structural biology and the protein data bank on us fda new drug approvals of low molecular weight antineoplastic agents 2019–2023

Abstract Open access to three-dimensional atomic-level biostructure information from the Protein Data Bank (PDB) facilitated discovery/development of 100% of the 34 new low molecular weight, protein-targeted, antineoplastic agents approved by the US FDA 2019–2023. Analyses of PDB holdings, the scientific literature, and related documents for each drug-target combination revealed that the impact of structural biologists and public-domain 3D biostructure data was broad and substantial, ranging from understanding target biology (100% of all drug targets), to identifying a given target as likely druggable (100% of all targets), to structure-guided drug discovery (>80% of all new small-molecule drugs, made up of 50% confirmed and >30% probable cases). In addition to aggregate impact assessments, illustrative case studies are presented for six first-in-class small-molecule anti-cancer drugs, including a selective inhibitor of nuclear export targeting Exportin 1 (selinexor, Xpovio), an ATP-competitive CSF-1R receptor tyrosine kinase inhibitor (pexidartinib,Turalia), a non-ATP-competitive inhibitor of the BCR-Abl fusion protein targeting the myristoyl binding pocket within the kinase catalytic domain of Abl (asciminib, Scemblix), a covalently-acting G12C KRAS inhibitor (sotorasib, Lumakras or Lumykras), an EZH2 methyltransferase inhibitor (tazemostat, Tazverik), and an agent targeting the basic-Helix-Loop-Helix transcription factor HIF-2α (belzutifan, Welireg).

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Susceptibility of pESI positive Salmonella to treatment with biocide chemicals approved for use in poultry meat processing as compared to Salmonella without the pESI plasmid

Abstract Salmonella is a common cause of human foodborne illness, which is frequently associated with consumption of contaminated or undercooked poultry meat. Serotype Infantis is among the most common serotypes isolated from poultry meat products globally. Isolates of serotype Infantis carrying the pESI plasmid, the most dominant strain of Infantis, have been shown to exhibit oxidizer tolerance. Therefore, 16 strains of Salmonella with and without pESI carriage were investigated for susceptibility to biocide chemical processing aids approved for use in US poultry meat processing: peracetic acid (PAA), cetylpyridinium chloride (CPC), calcium hypochlorite, and sodium hypochlorite. Strains were exposed for 15 s to simulate spray application and 90 min to simulate application in an immersion chiller. All strains tested were susceptible to all concentrations of PAA, CPC, and sodium hypochlorite when applied for 90 min. When CPC, calcium hypochlorite, and sodium hypochlorite were applied for 15 s to simulate spray time, strains responded similarly to each other. However, strains responded variably to exposure to PAA. The variation was not statistically significant and appears unrelated to pESI carriage. Results highlight the necessity of testing biocide susceptibility in the presence of organic material and in relevant in situ applications.

Biotechnology & Applied Microbiology↗
NASA NTRS1988

STS safety approval process for small self-contained payloads

The safety approval process established by the National Aeronautics and Space Administration for Get Away Special (GAS) payloads is described. Although the designing organization is ultimately responsible for the safe operation of its payload, the Get Away Special team at the Goddard Space Flight Center will act as advisors while iterative safety analyses are performed and the Safety Data Package inputs are submitted. This four phase communications process will ultimately give NASA confidence that the GAS payload is safe, and successful completion of the Phase 3 package and review will clear the way for flight aboard the Space Transportation System orbiter.

Gum, Mary A.↗
NASA NTRS1993

A perspective on the FAA approval process: Integrating rotorcraft displays, controls and workload

The FAA is responsible for making the determination that a helicopter is safe for IFR operations in the National Airspace System (NAS). This involves objective and subjective evaluations of cockpit displays, flying qualities, procedures and human factors as they affect performance and workload. After all of the objective evaluations are completed, and all Federal Regulations have been met, FAA pilots make the final subjective judgement as to suitability for use by civil pilots in the NAS. The paper uses the flying qualities and pilot workload characteristics of a small helicopter to help examine the FAA pilot's involvement in this process. The result highlights the strengths of the process and its importance to the approval of new aircraft and equipments for civil IFR helicopter applications. The paper also identifies opportunities for improvement.

Green, David L.↗
NASA NTRS1997

Application of artificial intelligence (AI) concepts to the development of space flight parts approval model

A cost effective model which uses the artificial intelligence techniques in the selection and approval of parts is presented. The knowledge which is acquired from the specialists for different part types are represented in a knowledge base in the form of rules and objects. The parts information is stored separately in a data base and is isolated from the knowledge base. Validation, verification and performance issues are highlighted.

Krishnan, G. S.↗