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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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All sourcesNASA NTRSDOE OSTI
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↗
DOE OSTI2024

ORNL Peer Review Summary and Recommendations for: Advanced Reactor Designs Security Analysis, Risk, and Recommendations: Risks, Consequences, and Possible Design Mitigation Approaches Associated with Select Advanced Reactors Study

The purpose of this document is to provide a summary of the peer review conducted for the "Advanced Reactor Designs Security Analysis, Risk, and Recommendations: Risks, Consequences, and Possible Design Mitigation Approaches Associated with Select Advanced Reactors" study prepared by researchers at Idaho National Laboratory (INL), Argonne National Laboratory (ANL), and Oak Ridge National Laboratory (ORNL). The National Nuclear Security Administration (NNSA) International Nuclear Security (INS) program team requested that ORNL perform a peer review of the study report prior to publication as a final peer check before distributing the report to a broader audience.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
DOE OSTI2024

Recommendations for improving rigor and reproducibility in site specific characterization

Heterogeneous catalysis is driven by the interaction of reactant molecules and the catalyst surface. The locus of this interaction as well as the surrounding ensemble of atoms is referred to as the catalyst active site. Active site characterization attempts to distinguish active catalytic sites from inactive surface sites, to elucidate the structural and chemical nature of active sites, and to quantify active site concentration. Numerous techniques have been demonstrated to provide compositional and structural information about the active sites within a catalyst. However, each technique has its own limitations and experimental pitfalls that can lead to data misinterpretation or irreproducible results. Further, this work aims to provide an overview of the types of data that can be collected, to outline common experimental challenges and how to avoid them, and to assemble relevant references for the most used active site characterization techniques. More broadly, we aim to outline best practices for researchers to collect, interpret, and report active site characterization data in a way that provides the most benefit to the broader catalysis community. Increasing the rigor and reproducibility of active site characterization offers a strategy to better link properties with catalytic performance and to enable the community to develop consensus concerning these relationships.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

PSTN-055: Survey Cadence Optimization Committee's Phase 2 Recommendations

This document describes the recommendations formulated by the Survey Cadence Optimization Committee (SCOC) of Vera C. Rubin Observatory for the observing strategy of the Legacy Survey of Space and Time (LSST). These "Phase 2" recommendations follow the initial "Phase 1" recommendations released in December 2021 as PSTN-053, and convey the current recommendations for the initial implementation of the LSST. These recommendations are based on the SCOC analysis of LSST simulations generated according to PSTN-053 and the feedback received from the scientific community on those simulations. These recommendations should be considered as the current guidance for implementing the LSST observing survey at the start of the survey, a strategy to be reviewed regularly over the survey lifetime, and are accompanied by a simulation, baseline_v3.0, which represents a specific implementation of these recommendations. While these recommendations dramatically narrow the possible LSST observing parameter choices, we emphasize that at this stage they do not yet represent a final or complete set of recommendations for the survey strategy, and several details are still to be refined. Furthermore, the strategy should be considered "living" and subject to evolution throughout the survey. The SCOC continues to engage with the community to finalize its recommendations. At the time of the release of this document, the final phases of construction of Rubin Observatory are ongoing with an expected first light in mid-2024. We expect the SCOC recommendations to be revised as needed, as knowledge of the system as built and the outcome of commissioning and Science Verification mature. This document describes the Phase 2 SCOC recommendations —highlighting elements that can be considered final and elements that remain to be finalized—, the process through which the SCOC has converged on these recommendations, and the working plan for the SCOC starting in January 2023 through the start of the survey to finalize the initial implementation of the Legacy Survey of Space and Time.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2024

Statin Drug‐Drug Interactions: Pharmacokinetic Basis of FDA Labeling Recommendations and Comparison Across Common Tertiary Clinical Resources

Abstract Statins are widely prescribed and highly susceptible to pharmacokinetic (PK)‐based drug–drug interactions (DDIs). To date, there has not been a comprehensive analysis of the basis upon which statin DDI recommendations in US Food and Drug Administration (FDA) prescribing information (PI) are derived. We have conducted such an analysis. We also assessed the degree of concordance of statin DDI recommendations in FDA PI and those provided in common tertiary clinical resources. We catalogued statin DDI information, including PK data and management recommendations, for statin precipitant drugs approved from 2010 to 2021, available from FDA PI and tertiary clinical resource databases. Recommendations were categorized and mapped with associated PK data to assess consistency in the PK basis for labeling recommendations. From the 80 precipitant drugs evaluated, 180 statin DDIs were identified in FDA PI. Dedicated clinical DDI studies were conducted for 54% (n = 97) of these DDIs and 34% (n = 61) of DDI recommendations were extrapolated from clinical data with other statins. Overall, we found that PK‐based statin recommendations were consistent across PI. These findings highlight regulatory precedence for translating information across statins without conducting dedicated clinical DDI studies, which may support future efforts toward streamlining the approach to investigation and labeling of statin DDIs. In addition, with the exception of some notable discrepancies, general concordance was observed between FDA and tertiary resources regarding “Dose Adjustment” and “Avoid Coadministration” recommendations. However, further analyses are warranted across other DDI pairs to determine whether discordance can routinely lead to different clinical recommendations depending on the drug information resource.

Mease, James↗
DOE OSTI2021

Recommended Practices for Managing Induced Seismicity Risk Associated with Geologic Carbon Storage

The geologic storage of carbon dioxide (CO 2 ) is one method to help reduce or eliminate atmospheric CO 2 emissions. The sequestered CO 2 is originally captured from the atmosphere or from a stationary industrial source and subsequently injected into a deep subsurface porous rock formation. To facilitate the successful deployment of field scale carbon storage projects, the U.S. Department of Energy (DOE) is developing tools and protocols for defensible, science-based frameworks to quantify and mitigate risks associated with the long-term storage of CO 2 . This protocol specifically addresses the risk of induced seismicity due to injection in a geologic carbon storage (GCS) site. This integrated and risk-based protocol is a product of the U.S. DOE Fossil Energy’s National Risk Assessment Partnership (NRAP), a multi-year collaborative research effort of Los Alamos National Laboratory (LANL), Lawrence Berkeley National Laboratory (LBNL), Lawrence Livermore National Laboratory (LLNL), National Energy Technology Laboratory (NETL), and Pacific Northwest National Laboratory (PNNL). These recommended practices describe a set of 7 steps to evaluate, manage, communicate, and mitigate the risk of induced seismicity at GCS sites. The base methodology of the recommended practices follows a framework similar to the Protocol for Addressing Induced Seismicity Associated with Enhanced Geothermal Systems (Majer et al., 2012), developed for the Geothermal Technology Office of the U.S. DOE. These recommended practices present a framework to systematically assess the induced seismicity risk and quantify the associated uncertainties. These recommendations are based on current research and are sufficiently general to allow for modification and application to a variety of different types of sites. The substance of the recommended practices contained herein includes both technical and non-technical issues, and covers all operational stages of the GCS project lifecycle. They start at the preliminary risk assessment phase, continue through site assessment and characterization, include best practice communication and seismic monitoring plan methodologies, discuss the evaluation and mitigation of seismic hazard and risk, and closes with an exploration of operational management plans, which conclude when the induced seismicity risk abates back to background level. The focus of these recommendations is on actively managing the risks associated with induced seismicity by developing an actionable risk management plan that starts at the project proposal stage and continues through site closure through an iterative assessment and improvement process. The audience of this document is expected to include all interested stakeholders (e.g., operators, project developers, regulators, and the general public) and is expressly written to be accessible to this broad range of partners. This document is intended to disseminate knowledge gained through recent advances in the science of induced seismicity hazard and risk assessments, to provide updates based on recent experience gained by similar corollary injection-induced seismicity cases, and most importantly to establish a uniform framework to carry out a successful induced seismicity risk management plan for carbon storage projects in the future. These recommendations do not directly address any domestic or international regulations or standards. A complementary NRAP report makes recommendations for the assessment and management of environmental subsurface risks associated with unwanted fluid migration at GCS sites (Thomas et al., 2021) and should be referred to in order to address those additional GCS site risks.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

Recommended Practices for Managing Induced Seismicity Risk Associated with Geologic Carbon Storage

The geologic storage of carbon dioxide (CO 2 ) is one method to help reduce or eliminate atmospheric CO 2 emissions. The sequestered CO 2 is originally captured from the atmosphere or from a stationary industrial source and subsequently injected into a deep subsurface porous rock formation. To facilitate the successful deployment of field scale carbon storage projects, the U.S. Department of Energy (DOE) is developing tools and protocols for defensible, science-based frameworks to quantify and mitigate risks associated with the long-term storage of CO 2 . This protocol specifically addresses the risk of induced seismicity due to injection in a geologic carbon storage (GCS) site. This integrated and risk-based protocol is a product of the U.S. DOE Fossil Energy’s National Risk Assessment Partnership (NRAP), a multi-year collaborative research effort of Los Alamos National Laboratory (LANL), Lawrence Berkeley National Laboratory (LBNL), Lawrence Livermore National Laboratory (LLNL), National Energy Technology Laboratory (NETL), and Pacific Northwest National Laboratory (PNNL). These recommended practices describe a set of 7 steps to evaluate, manage, communicate, and mitigate the risk of induced seismicity at GCS sites. The base methodology of the recommended practices follows a framework similar to the $\textit{Protocol for Addressing Induced Seismicity Associated with Enhanced Geothermal Systems}$ (Majer et al., 2012), developed for the Geothermal Technology Office of the U.S. DOE. These recommended practices present a framework to systematically assess the induced seismicity risk and quantify the associated uncertainties. These recommendations are based on current research and are sufficiently general to allow for modification and application to a variety of different types of sites. The substance of the recommended practices contained herein includes both technical and non-technical issues, and covers all operational stages of the GCS project lifecycle. They start at the preliminary risk assessment phase, continue through site assessment and characterization, include best practice communication and seismic monitoring plan methodologies, discuss the evaluation and mitigation of seismic hazard and risk, and closes with an exploration of operational management plans, which conclude when the induced seismicity risk abates back to background level. The focus of these recommendations is on actively managing the risks associated with induced seismicity by developing an actionable risk management plan that starts at the project proposal stage and continues through site closure through an iterative assessment and improvement process. The audience of this document is expected to include all interested stakeholders (e.g., operators, project developers, regulators, and the general public) and is expressly written to be accessible to this broad range of partners. This document is intended to disseminate knowledge gained through recent advances in the science of induced seismicity hazard and risk assessments, to provide updates based on recent experience gained by similar corollary injection-induced seismicity cases, and most importantly to establish a uniform framework to carry out a successful induced seismicity risk management plan for carbon storage projects in the future. These recommendations do not directly address any domestic or international regulations or standards. A complementary NRAP report makes recommendations for the assessment and management of environmental subsurface risks associated with unwanted fluid migration at GCS sites (Thomas et al., 2021) and should be referred to in order to address those additional GCS site risks

58 GEOSCIENCES↗
NASA NTRS2022

Recommendations on the Use of Commercial-Off-The-Shelf (COTS) Electrical, Electronic, and Electromechanical (EEE) Parts for NASA Missions - Phase II

This assessment had two Phases. Phase I captured NASA Centers’ current practices for commercial-off-the-shelf (COTS) Electrical, Electronic, and Electromechanical (EEE) parts 1 used in spaceflight systems and ground support equipment (available at https://ntrs.nasa.gov/citations/20205011579) [ref. 1]. The Phase II report provides guidance for selecting and using COTS parts in NASA missions. The approaches proposed in this report differ from current agency practices. This top-level executive summary touches on these new approaches for using COTS parts but does not provide the detailed information that is critical in understanding the rationale behind these new approaches. Readers will need to read the entire report to gain full understanding and effectively use the recommendations herein. NASA’s historical approach to selecting and applying parts has been to define certain parts, primarily specific classes of military specification (MIL-SPEC) parts, as “standard”, leaving all others, including COTS parts, as nonstandard. Standard parts typically are used without further testing (“use-as-is”). Nonstandard parts are subjected to initial screening and subsequent lot acceptance testing of representative samples from each procured lot per MIL-SPEC or similar requirements. Decades later, top-tier commercial part manufacturers have evolved significant manufacturing, statistical control, and technological improvements that can now provide parts as reliable or more reliable than MIL-SPEC parts, when used within their datasheet limits. Concurrently, the space science and exploration community’s needs demand technological advances unavailable with MIL-SPEC parts. This ongoing change necessitates using COTS parts for space missions. Properly selected COTS parts in appropriate applications can offer performance and supply availability advantages compared to MIL-SPEC parts. Their utility and demonstrated reliability result from large volumes and automated production and testing processes. However, careful review and a thorough understanding of their specifications (i.e., datasheet limitations) is needed, and verifying that manufacturer specifications and reliability meet space hardware application needs are necessary. This report recommends MIL-SPEC screening and non-radiation-related lot acceptance testing be reduced or eliminated in cases where evidence of sufficient quality and reliability exists for COTS parts. The extent of NASA's insight into COTS manufacturers and the amount and nature of the needed evidence will differ by mission and will likely be driven by a mission's resources and associated risk posture. To facilitate this goal, two new terminologies have been defined and described: “Industry Leading Parts Manufacturer (ILPM)” and “Established COTS parts.” An ILPM is a COTS manufacturer that produces high quality and reliable parts. Some parts produced by ILPMs, defined as Established COTS parts, do not need any additional MIL-SPEC or NASA screening and lot acceptance testing to be used in space applications. This report provides guidance for selecting, procuring, and applying COTS parts and for performing part-, board-, and system-level COTS parts verification. The recommendation to select Established COTS parts from ILPMs will assure those COTS parts will have comparable quality to corresponding MIL-SPEC parts. Selecting, applying, and verifying Established COTS parts from ILPMs requires a holistic team approach, engaging parts engineers, circuit designers, quality, reliability, and systems engineers, procurement specialists, radiation specialists, avionics leads, and program/project managers. A mission-specific approach tailored to a project’s Mission, Environment, Applications and Lifetime (MEAL) [ref. 2] requirements should be developed and approved by program/project managers. Any associated risks should be clearly identified, quantified, mitigated, and/or accepted. Different approaches are recommended according to program/project Risk Classes A, B, C, and D [ref. 3] and human-rated missions [ref. 4]: 1. Recommend Classes A and B and human-rated missions consider a “MIL-SPEC parts- based design” approach. ”MIL-SPEC parts-based design” approach is one in which most parts are MIL-SPEC parts and Established COTS parts from ILPMs are used only when an equivalent MIL-SPEC part does not meet functional or size, weight, and power (SWaP) or performance requirements, or is not available. 2. Recommend Classes D and Sub-D missions consider a “System of COTS” approach. “System of COTS” approach is one which most parts are Established COTS parts from ILPMs. 3. Recommend Class C missions determine which approach is the best for their projects; that is, use either a “MIL-SPEC parts-based design” approach, “System of COTS” approach, or a combined approach utilizing elements of both. This report intends to provide guidance in using COTS parts for NASA missions with risk classifications of A through D and human-rated missions; but it does not address the costs of using COTS parts. Costs of using COTS parts in different NASA mission classes can vary significantly even if the same parts are used in different risk postures, due to differing verification levels needed. The guidance does not distinguish between critical or non-critical systems, and a given project will need to apply the appropriate guidance based on their risk posture. The intended audience of this report are NASA personnel and commercial practitioners who support NASA’s spaceflight missions, including spaceflight program or project managers, parts engineers, parts manufacturers, radiation engineers, avionics engineers, system engineers, circuit design engineers, reliability engineers, safety and mission assurance (SMA) personnel, and parts procurement specialists. The NEPP Program will perform a pathfinder study to explore implementing the guidance in this NESC report. An ILPM verification process is not the same as conventional vendor qualification processes performed according to military standards and specifications. This NESC report intends to provide guidance in utilizing available parts data from ILPM manufacturers for parts assurance assessments needed for NASA missions. The report also captured the current practices from DoD and Federal Aviation Administration (FAA) in Section 10. Note each DoD and FAA report was provided by the corresponding agencies regarding their practices, which are independent from the NESC recommendations in the report.

Commercial-Off-The-Shelf↗
DOE OSTI2024

Exploring the role of judgement and shared situation awareness when working with AI recommender systems

Abstract AI-advised Decision Making is a form of human-autonomy teaming in which an AI recommender system suggests a solution to a human operator, who is responsible for the final decision. This work seeks to examine the importance of judgement and shared situation awareness between humans and automated agents when interacting together in the form of a recommender systems. We propose manipulating both human judgement and shared situation awareness by providing the human decision maker with relevant information that the automated agent (AI), in the form of a recommender system, uses to generate possible courses of action. This paper presents the results of a two-phase between-subjects study in which participants and a recommender system jointly make a high-stakes decision. We varied the amount of relevant information the participant had, the assessment technique of the proposed solution, and the reliability of the recommender system. Findings indicate that this technique of supporting the human’s judgement and establishing a shared situation awareness is effective in (1) boosting the human decision maker’s situation awareness and task performance, (2) calibrating their trust in AI teammates, and (3) reducing overreliance on an AI partner. Additionally, participants were able to pinpoint the limitations and boundaries of the AI partner’s capabilities. They were able to discern situations where the AI’s recommendations could be trusted versus instances when they should not rely on the AI’s advice. This work proposes and validates a way to provide model-agnostic transparency into recommender systems that can support the human decision maker and lead to improved team performance.

Srivastava, Divya↗
DOE OSTI2021

Recommended conventions for reporting results from direct dark matter searches

Abstract The field of dark matter detection is a highly visible and highly competitive one. In this paper, we propose recommendations for presenting dark matter direct detection results particularly suited for weak-scale dark matter searches, although we believe the spirit of the recommendations can apply more broadly to searches for other dark matter candidates, such as very light dark matter or axions. To translate experimental data into a final published result, direct detection collaborations must make a series of choices in their analysis, ranging from how to model astrophysical parameters to how to make statistical inferences based on observed data. While many collaborations follow a standard set of recommendations in some areas, for example the expected flux of dark matter particles (to a large degree based on a paper from Lewin and Smith in 1995), in other areas, particularly in statistical inference, they have taken different approaches, often from result to result by the same collaboration. We set out a number of recommendations on how to apply the now commonly used Profile Likelihood Ratio method to direct detection data. In addition, updated recommendations for the Standard Halo Model astrophysical parameters and relevant neutrino fluxes are provided. The authors of this note include members of the DAMIC, DarkSide, DARWIN, DEAP, LZ, NEWS-G, PandaX, PICO, SBC, SENSEI, SuperCDMS, and XENON collaborations, and these collaborations provided input to the recommendations laid out here. Wide-spread adoption of these recommendations will make it easier to compare and combine future dark matter results.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2022

Reviewing clinical considerations and guideline recommendations of C1 inhibitor prophylaxis for hereditary angioedema

Abstract Background Hereditary angioedema (HAE), a rare disease that is characterized by painful and recurring non‐allergic swelling episodes, is caused by the deficiency or dysfunction of C1 inhibitor (C1INH) protein. A comprehensive HAE management plan may require long‐term prophylaxis (LTP) in addition to on‐demand treatment to help “normalize” patients' lives so that they may fully engage in work, school, family, and leisure activities. Aim The main objective of this narrative review is to provide an overview of updated guideline recommendations specific to LTP of HAE and discuss clinical considerations and pharmacologic management options, with a focus on C1INH. Materials and Methods The authors reviewed relevant HAE literature for current recommendations regarding LTP and the role of C1NH. Results Acute HAE attacks are treated with on‐demand medication; however, there is a consensus that LTP should routinely be considered for risk reduction and prevention of future episodes. The 2017 World Allergy Organization/European Academy of Allergy and Clinical Immunology guidelines recommend that all patients with HAE be evaluated for LTP routinely and the 2020 HAE Association (HAEA) guidelines emphasize that the decision to use LTP should not be based on rigid criteria, but rather should be based on individual patient needs. Both guidelines recommend C1INH as first‐line/preferred therapy for LTP in a range of patient types including adults, children/adolescents, and pregnant/lactating patients. The HAEA also recommends the kallikrein inhibitor, lanadelumab, as a first‐line option for LTP. HAE pathway‐specific agents for LTP have not been associated with notable safety concerns. Discussion Plasma‐derived C1INH has been available for 40+ years in Europe and impacts multiple targets within the HAE pathway. C1INH has been used for on‐demand treatment and LTP. A subcutaneous formulation of plasma‐derived C1INH is approved for LTP and produces functional C1INH activity levels consistently above the threshold needed for protection from HAE attacks. Other pathway‐specific options for LTP include the plasma kallikrein inhibitors, lanadelumab‐flyo and berotralstat, approved for adults and pediatric patients aged ≥12 years. C1INH is approved for adults and pediatric patients aged ≥6 years. Conclusion Assessing the need for LTP is vital in the ongoing dialogue between clinicians and patients, as both disease‐related factors and patient preferences may change over time. Among available options for LTP, plasma‐derived C1INH is the broadly recommended first‐line option for LTP in patients with HAE, including pregnant/lactating women and pediatric patients (≥6 years).

Anderson, John↗
DOE OSTI2020

Energy impact of human health and wellness lighting recommendations for office and classroom applications

The goal of this investigation was to evaluate potential energy impacts of circadian lighting design recommendations gaining attention in a variety of common applications such as offices and classrooms. The renewed focus on health along with advances in SSL technology capabilities has underscored that there is still much to learn regarding the relationship between light and human physiology. The energy implications of designing to address these possible physiological effects are not yet fully understood. Beyond the fact that the basic metric of luminous efficacy (lumens per watt) does not cover these other effects, the emerging science seems to indicate that addressing a holistic view of the human needs in most applications may mean a need for increased light and associated energy use by electric lighting systems. Within the two applications considered, lumen output, spectral characteristics, surface reflectance distribution and desk orientation were varied to explore the magnitude of potential effects. Meeting current IES illuminance recommendations did not satisfy existing EML and CS recommendations for any of the simulations. In some cases, satisfying circadian metric recommendations required average illuminance that was more than double IES recommendations, which may negatively impact lighting quality as well. Using results from 45 unique simulation conditions, it was estimated that lighting energy use may increase between 10% and 100% due to increased luminaire light levels used to meet circadian lighting design recommendations listed in current building standards such as WELL v2 Q2 2019, UL Design Guideline 24480, and CHPS Core Criteria 3.0.

circadian lighting, lighting simulation, solid sta↗
DOE OSTI2023

Global harmonization of immediate‐release solid oral drug product bioequivalence recommendations and the impact on generic drug development

Immediate-release (IR) solid oral drug products constitute a significant portion of approved drug products and products under development. Bioequivalence (BE) assessment for these oral products is important for establishing therapeutic equivalence for generic products to their respective comparator products. In December 2022, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) published the first new draft guideline on BE for IR solid oral dosage forms (M13A). To support the development of ICH M13A, we comprehensively reviewed the landscape of oral IR products approved by the U.S. Food and Drug Administration (FDA) and compared BE recommendations for these products in the current U.S. FDA and European Medicines Agency (EMA) BE guidances. We utilized databases including Drugs@FDA, Orange Book, and product-specific guidances (PSGs) published on the U.S. FDA and EMA websites to collect information. Oral IR products account for 46% of all FDA-approved new drug applications currently listed in Orange Book with 82.5% solids, 0.9% semi-solids, and 16.6% liquids. For all published U.S. FDA PSGs for solid oral IR products, in vivo BE studies with pharmacokinetic (PK) endpoints account for 88% of BE approaches recommended. Of these PK BE studies, 86.5% recommended fasting and fed BE studies, while only 15.9% EMA PSGs recommended both fasting and fed BE studies. This review helps clarify the scope of U.S. solid oral IR products impacted by the new ICH M13A draft guideline and demonstrates how recommendations in draft ICH M13A could significantly harmonize BE recommendations for IR oral products to facilitate global drug development.

60 APPLIED LIFE SCIENCES↗