Technical Document Research Articles

RF15 | PMON304 Utilizing LC-MS/MS for the clinical quantitation of testosterone using dried blood spot and how it compare to serum

Abstract Introduction Hormones are the chemical messengers of your body. Steroid hormones like testosterone are a specific class of hormone that are produced predominantly in the gonads (sex steroids) and less so in the adrenal glands (corticosteroids). When too little or too much of testosterone is produced, adverse symptoms and conditions can occur. In order to restore the vital balance of hormones, detailed and accurate measurement of hormones is needed. Serum currently represents the gold standard when it comes to hormone testing. However, there are other body fluids such as saliva, urine, and capillary blood (finger prick) where the hormone levels correlate well with serum. A significant advantage of these alternative fluids is that they are non-invasive, or semi-invasive, can be collected "on the go" by the patient at home, and don't have the strict requirements for cold-chain shipping. Objectives The primary objective of this work is to show that finger-prick dried blood spot blood is quantitatively equivalent to serum when compared by LC-MS/MS testing in patients only producing endogenous testosterone. We will also show that topically delivered testosterone increases in a dose-dependent fashion, whereas serum levels of testosterone increase very little regardless of topical testosterone dosing. Methods Serum samples were collected by a physician and sent into the lab and analyzed for testosterone on a Siemens Immulite 2000 autoanalyzer. Dried blood spots were collected by the patient and sent into the lab and analyzed on an AB Sciex 5500 triple quadrupole mass spectrometer. Results Patients who don't supplement with topical testosterone show a strong correlation between endogenous venipuncture serum and DBS testosterone levels. In sharp contrast, samples from topical testosterone users show remarkably different results with hormone levels 10-100×higher in the DBS than serum results. Conclusion These results are significant because it gives a glimpse into which forms of testing are most appropriate for different patients based on the mode of steroid hormone delivery. Without using the proper body fluid for testosterone detection, patients potentially could be overdosed if serum results are used to guide therapeutic dosing. Also, venipuncture serum will fail to show "sports-doping" with exogenous testosterone, which easily can be identified with capillary finger stick blood. This is also significant as the World Anti-doping Agency has finally begun accepting these data as fact and have listed dried blood spot as an appropriate form of collection and analysis for drug testing. This can help find athletes using performance enhancers that would normally have skirted by the system (1). WADA. (2021, May 21) WADA Executive Committee approves Technical Document for innovative dried blood spot testing method. https://www.wada-ama.org/en/media/news/wada-executive-committee-approves-technical-document-for-innovative-dried-blood-spot. Presentation: Sunday, June 12, 2022 12:36 p.m. - 12:41 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

CURRENT PHARMACEUTICAL REGULATIONS OF UNITED KINGDOM: POST BREXIT

The Medical and Healthcare Regulatory Agency is a Healthcare agency which was established in the United Kingdom and regulates drugs and medical equipment. The guidelines for marketing drugs and medical equipment are under European Medicines Agency. The United Kingdom officially left the European Union on 31st January 2020. So, the Medical and Healthcare Regulatory Agency was started and the guidelines are given by them. The yellow card scheme was established and it collects the adverse effects data of medicals from the patients directly online on the Medical and Healthcare Regulatory Agency website which helps in drug development and new drug investigation. The licence for drug marketing was done through the Medical and Healthcare Regulatory Agency website. By submitting the documents in electronic Common Technical Document format. It will take around 12-18 months. There are some new marketing authorisation assessment routes Medical and Healthcare Regulatory Agency has published.

Novel and existing flexible survival methods for network meta-analyses.

Aim: Technical Support Document 21 discusses trial-based, flexible relative survival models. The authors generalized flexible relative survival models to the network meta-analysis (NMA) setting while accounting for different treatment-effect specifications. Methods: The authors compared the standard parametric model with mixture, mixture cure and nonmixture cure, piecewise, splines and fractional polynomial models. The optimal treatment-effect parametrization was defined in two steps. First, all models were run with treatment effects on all parameters and subsequently the optimal model was defined by removing uncertain treatment effects, for which the parameter was smaller than its standard deviation. The authors used a network in previously treated advanced non-small-cell lung cancer. Results: Flexiblemodel-based NMAs impact fit and incremental mean survivaland they increase corresponding uncertainty. Treatment-effect specification impacts incremental survival, reduces uncertainty and improves the fit statistic. Conclusion: Extrapolation techniques already available for individual trials can now be used for NMAs to ensure that the most plausible extrapolations are being used for health technology assessment submissions.

Preparation of Module 1 of the Registration Dossier According to the EAEU Procedure

The legislation of the Eurasian Economic Union (EAEU) includes all the necessary requirements and tools to implement a unified approach to preparing Module 1 of the electronic Common Technical Document (eCTD) for the concerned member states (CMSs). However, the approaches to the matter and the recommendations provided to applicants differ across member states. This causes significant ambiguity and imposes an excessive burden on the applicants. Drafting of a guideline on preparation of eCTD Module 1 for the CMSs will allow for tackling this important grey area in the EAEU regulatory framework, as regulatory authorities are lacking consensus on country-specific submissions. Currently, pharmaceutical industry stakeholders consider the Russian experience of implementing the legislation in question the most successful, so it is proposed to convey this experience to the common market of the EAEU.

Perspectives for licensing vaccines in Mexico

Vaccine products represent one of the most successful public health measure to this day. This has been reflected during the current COVID-19 pandemic where more than 4.87 billion people have received at least one vaccine dose. In Latin America, Mexico occupies the second position in terms of the number of vaccinated people with 83.97 million people receiving at least a single dose. As in other countries, regulatory approval in Mexico is one of the key aspects that influences the public access to vaccines. This creates an active interplay between regulatory authorities establishing a regulatory framework to assure the quality, safety and efficacy of the vaccines, and applicants fulfilling this information. Mexico is a member of the International Council for Harmonisation (ICH) and it has adopted the Common Technical Document (CTD) for providing this information. This is particularly useful for vaccines developed abroad where it is expected to speed the evaluation of the new product. The Secretariat of Health of Mexico (SALUD) has published guidelines and laws or regulations related to GMP, labeling, stability, clinical trials, biocomparability and pharmacovigilance for drug products including vaccines which are classified as biological products. SALUD has also established guidelines and international homologating agreements to facilitate the application process for vaccine approval. Nevertheless, technical and scientific information and administrative processes for vaccine approval might be relatively concealed. Therefore, we aim to enable researchers and manufacturers in Mexico and overseas to better understand these requirements. To our knowledge, this is the most up-to-date and comprehensive attempt to present this information, also including information for COVID-19 vaccines. Here we describe the current requirements and processes by COFEPRIS, the national regulatory agency, for vaccine licensing and for emergency use authorization for COVID-19 vaccines in Mexico.

EE111 Adoption of Piecewise Modelling: A Review of Nice Health Technology Appraisals in Oncology

10 years ago, NICE DSU Technical Support Document 14 noted the underutilization of piecewise models as an alternative to fully parametric models for survival extrapolations and recommended their consideration where more flexible survival models are required. This study aimed to review the adoption of the piecewise approach in recent assessments of oncology drugs submitted to the National Institute for Health and Care Excellence (NICE).

MSR66 Implementation of Contrast-Based and Shared Parameter Models in Bugsnet, an R Package for Conducting Bayesian Network Meta-Analysis

BUGSnet is a published, open-source R package to facilitate the execution of network meta-analyses (NMAs) and generation of outputs that satisfy the statistical elements of prominent best-practice NMA guidelines and checklists, including the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, the ISPOR-AMCP-NPC guidelines, and NICE Decision Support Unit (DSU) Technical Support Document (TSD) 2. The first version of BUGSnet lacked support for contrast-based or shared parameter models (i.e.

(Re)Designing Technical Documentation About COVID-19 with and for Indigenous Communities in Gainesville, Florida, Oaxaca de Juárez, Mexico, and Quetzaltenango, Guatemala

<italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><b>Background:</b></i> In this article, we document how our team of translators, interpreters, technical communicators, and health justice workers is collaborating to (re)design COVID-19-related technical documentation for and with Indigenous language speakers in Gainesville, FL, USA; Oaxaca de Juarez, Mexico; and Quetzaltenango, Guatemala. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><b>Literature review:</b></i> Although (mis)representations of Indigenous communities have been an ongoing issue in and beyond technical communication, the COVID-19 pandemic has brought added attention to how government institutions and other agencies fail to consider the cultural values, languages, and communication practices of Indigenous communities when writing, designing, and sharing technical information. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><b>Research questions:</b></i> 1. How can technical communicators work toward social justice in health through collaborative design with Indigenous language speakers? 2. How can technical documentation about COVID-19 be (re)designed alongside members of vulnerable communities to redress oppressive representations while increasing access and usability? <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><b>Methodology:</b></i> Through interviews and other participatory design activities conducted with Indigenous language speakers in the US, Guatemala, and Mexico, we illustrate how Western approaches to creating technical documentation, particularly in health-related contexts such as the COVID-19 pandemic, put communities at risk by failing to localize health messaging for Indigenous audiences. We then document our work intended to collaboratively design and translate COVID-19-related technical information alongside those Indigenous language speakers to benefit Indigenous language speakers in Gainesville and other parts of North Central Florida. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><b>Results:</b></i> Through this discussion, we highlight how technical communicators can collaborate with Indigenous language speakers to create, translate, and share multilingual technical documents that can contribute to social justice efforts by enhancing language access. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><b>Conclusion:</b></i> Through collaborations with Indigenous language speakers, translators, and interpreters, social/health justice projects in technical communication can be combined, localized, and adapted to better serve and represent the diversity of people, languages, and cultures that continue to increase in our world.

Common deficiencies found in generic Finished Pharmaceutical Product (FPP) applications submitted for registration to the South African Health Products Regulatory Authority (SAHPRA)

BackgroundThe aim of the study was to investigate the common deficiencies observed in the Finished Pharmaceutical Product (FPP) section of generic product applications submitted to SAHPRA. The study was conducted retrospectively over a 7-year period (2011–2017) for products that were finalised by the Pharmaceutical and Analytical pre-registration Unit.MethodsThere were 3148 finalised products in 2011–2017, 667 of which were sterile while 2089 were non-sterile. In order to attain a representative sample for the study, statistical sampling was conducted. Sample size was obtained using the statistical tables found in literature and confirmed by a sample size calculation with a 95% confidence level. The selection of the products was according to the therapeutic category using the multi-stage sampling method called stratified-systematic sampling. This resulted in the selection of 325 applications for non-sterile products and 244 applications for sterile products. Subsequently, all the deficiencies were collected and categorised according to Common Technical Document (CTD) subsections of the FPP section (3.2.P).ResultsA total of 3253 deficiencies were collected from 325 non-sterile applications while 2742 deficiencies were collected from 244 sterile applications. The most common deficiencies in the FPP section for non-sterile products were on the following sections: Specifications (15%), Description and Composition (14%), Description of the Manufacturing Process (13%), Stability Data (7.6%) and the Container Closure System (7.3%). The deficiencies applicable to the sterile products were quantified and the subsection, Validation and/or Evaluation (18%) has the most deficiencies. Comparison of the deficiencies with those reported by other agencies such as the USFDA, EMA, TFDA and WHOPQTm are discussed with similarities outlined.ConclusionsThe overall top five most common deficiencies observed by SAHPRA were extensively discussed for the generic products. The findings provide an overview on the submissions and regulatory considerations for generic applications in South Africa, which is useful for FPP manufacturers in the compilation of their dossiers and will assist in accelerating the registration process.

Исследование подсистемы выявления инцидентов интеллектуальной транспортной системы

The main normative and technical documents, methodological manuals on the formation of intelligent transport systems (ITS), as well as trends in the ITS development have been revealed. The structure and functionality of the ITS incident detection subsystem based on the regulatory and technical documentation are substantiated. Target indicators of the effectiveness of the intelligent system of warning drivers of the danger emergence on the roadway are defined. Promising research areas of the ITS incident detection subsystem for adaptation in the Russian Federation are identified.

Risk Assessment of Contaminants in Sewage Sludge Applied on Norwegian Soils

Risk Assessment of Contaminants in Sewage Sludge Applied on Norwegian Soils

You Don’t Need Labeled Data for Open-Book Question Answering

Open-book question answering is a subset of question answering (QA) tasks where the system aims to find answers in a given set of documents (open-book) and common knowledge about a topic. This article proposes a solution for answering natural language questions from a corpus of Amazon Web Services (AWS) technical documents with no domain-specific labeled data (zero-shot). These questions have a yes–no–none answer and a text answer which can be short (a few words) or long (a few sentences). We present a two-step, retriever–extractor architecture in which a retriever finds the right documents and an extractor finds the answers in the retrieved documents. To test our solution, we are introducing a new dataset for open-book QA based on real customer questions on AWS technical documentation. In this paper, we conducted experiments on several information retrieval systems and extractive language models, attempting to find the yes–no–none answers and text answers in the same pass. Our custom-built extractor model is created from a pretrained language model and fine-tuned on the the Stanford Question Answering Dataset—SQuAD and Natural Questions datasets. We were able to achieve 42% F1 and 39% exact match score (EM) end-to-end with no domain-specific training.

ISSUES WITH APPROACHES FOR SIMULATING AGING OF NUCLEAR POWER PLANT CABLE MATERIALS

ABSTRACT Over the past 20 y, the International Electrotechnical Commission and the International Atomic Energy Agency have published several Technical Documents describing recommended methods for carrying out accelerated radiation plus temperature aging of cable materials in nuclear power plants. These methods include the power law method, the time-dependent model, the dose to equivalent damage approach, and the simplified method approach. Because of the expected and observed changes in chemistry that occur as aging conditions transition radiation–temperature space, we highlight issues with the time-dependent and simplified method approaches by showing that they do not simulate the chemistry occurring under ambient conditions. The dose to equivalent damage (DED) approach and a recent modification, the Matched Accelerated Conditions approach, can handle the changes in chemistry for many important cable materials and therefore offer more confident accelerated simulations. Problems with the power law method are then briefly described. Also discussed are the significant issues that occur when trying to simulate the aging of semicrystalline cable materials that show inverse-temperature effects. For these materials, degradation rates under radiation can increase as the aging temperature drops below ∼60 °C, in temperature regions where typical ambient aging conditions occur. A possible approach for dealing with such materials is suggested.

Intercomparison of Gamma Cell 220 Irradiator Facilities and Dr. Mirzan T Razzak Gamma Irradiators Using Harwell Dosimeters

The gamma irradiator is a multi-purpose facility that possibly used to preserve food, sterilize medical equipment, and conduct genetic engineering and polymerization processes, during which the absorbed dose of the product is critical. The standardization of product quality assurance was regulated by the IAEA Technical Document Number 409 considering Dosimetry for Food Irradiation and ISO 14470 and 11137-3 on Food Irradiation, as well as the Guidance on Dosimetric Aspects of Development, Validation, and Routine Control, respectively. The absorbed dose was influenced by the movement of the product to the source, its position, the amount of radioactive activity in the facility, and the dose rate in the irradiation room. The dosimeter performance test and quality assurance of the system were conducted using the Facility Intercomparison Technique which tested the dosimeter (measuring instrument) at 2 different facilities to determine the performance of the measuring instrument.. In this study, 2 irradiation facilities were tested using a Harwell routine dosimeter in the dose range of 1 kGy to 30 kGy and 20 dose points. The results showed that the highest deviation reached 19% and 21% at the Gamma Cell 220 and the Dr. Mirzan T Razzak Gamma irradiator facilities. This elevated the performance of the dosimeters to determine the precision accuracy of the dose-measuring instrument.

Modeling of the stress-deformed state of a capacitive apparatus with geometric deviations when mounting on a foundation

The reliable and trouble-free operation of the capacitive equipment of hazardous production facilities is significantly influenced by the quality of the installation performed before commissioning. So, during the installation of capacitive equipment, various geometric inconsistencies and deviations may occur, which are established by the current regulatory and technical documents for the installation of technological equipment. If unacceptable deviations and inconsistencies established by regulatory and technical documents are found, they must be fully eliminated. However, in certain cases, the regulatory and technical documentation allows operation with various insignificant geometric deviations and inconsistencies that do not go beyond the established limits. This may relate to deviations from the design horizontal position of the apparatus when installed on a foundation. It should be noted that during operation, under the influence of increased pressure, temperature and other loads, an apparatus with deviations of this type can undergo a completely different stress-deformed state compared to an apparatus without geometric deviations, which is not taken into account in expert diagnostics, strength analysis and assessment of residual resource. The solution to this issue can be approached using software systems that allow building 3D models of the objects under consideration with the introduction of all the necessary parameters into these models and getting a real picture of the distribution of zones of increased stress. In this work, the stress-deformed state of the process vessel is simulated due to the impact of working loads and different directions of deviation from the horizontal design position of the body when the apparatus is mounted on the foundation.

Dried blood spots, an emerging tool for doping control

The presentation will afford information on the possibilities for dried blood spot (DBS) samples as a new tool supporting the control of the abuse of prohibited substances in the world of sport. Based on previous developments in other biological fields, recent years have seen increasing studies devoted to the possible application of dried drops of blood collected on different support materials as a promising tool to detect the presence of prohibited substances in the body of potential doping athletes. Among the studied analytes, there are examples of most of the groups of substances in the extensive prohibited list of the World Antidoping Agency (WADA). In general terms, the mere presence of most of those prohibited substances in sports drug testing showed by DBS could be enough to be considered as proof of external application to the body, and therefore susceptible to plausible sanctions. However, in other cases, the decision on potential positivity should be based on quantitative criteria (the so-called threshold substances), which is somehow more challenging for DBS. Pre-analytical aspects such exact volume of blood collected in the spots, hematocrit derived effects or homogeneity of the spots may be relevant. Examples of DBS testing for some of the more representative compounds (e.g. testosterone esters, stimulants, erythropoietin, human growth hormone, GH secretagogues, …) analyzed by chromatographic, mass spectrometric, electrophoretic or immunological methods will be presented. Also, considerations related to: – different potential matrices to collect the blood spots, such as cellulose based materials or polymers supports; – collection from finger prick or upper arm; – comparison of capillary vs. venous blood; – use of either manual or device-based collecting approaches; – insight into the degree of acceptability of those different possibilities by athletes, will be commented. Given the strict requirements for procedures in doping control (e.g. WADA and ISO 17025 accreditations), other aspects such as rigorous sample collection supervision (sample A for initial analysis and sample B for counter analysis), transport, analytical procedures and storage are to be aligned with the strictness for other usual samples such as urine or liquid blood in sport drug testing. To this end, a comprehensive Technical Document is being developed by a Working Group and to be approved by the WADA. In a first step, qualitative applications are included. A second step, addressed to threshold substances requiring quantitative estimations, is to be subsequently developed. DBS appear as an emerging new tool for prohibited drugs testing in sport, initially supporting more traditional procedures in the field such as urine or liquid blood analyses, but also susceptible of further developments by itself alone. Advantages in terms of easiness of collection, greater analyte stability and simple transport and storage, probably will overcome limitations such as the reduced amount of available sample and consequent limit in the number of substances detectable from a single DBS. In any case, its emerging applicability in sports drug testing will need strict technical controls.

RESEARCH OF THE DEPENDENCE OF THE GRAIN SIZE COMPOSITION AND GRADE OF CRUSHABILITY OF RECYCLED CRUSHED STONE ON THE STRENGTH OF THE ORIGINAL RECYCLED CONCRETE

The results of the study of the grain-size composition and the grade of crushability of recycled crushed stone and their dependence on the strength of the original recycled concrete are presented. It is found that recycled crushed stone obtained from the original concrete of classes B10 - B30 does not meet the requirements of GOST 8267-93 for total residues on Ø25, Ø20, Ø5 and Ø2.5 sieves. Regardless of the strength of the original concrete, the main fraction of recycled crushed stone is grains with sizes from 12.5 to 20 mm. The strength (grade in terms of crushability) of the recycled crushed stone increases with an increase in the strength of the original concrete. The study of the main parameters of recycled crushed stone at the current moment has been carried out in an insufficient (for widespread introduction into production) volume and requires further study for the subsequent development of independent regulatory and technical documentation (or additions to the current regulatory and technical documents).

Comparison of generic drug registration strategies between health Canada and Gulf Cooperation Council

Recently, generic drug products have played an increasingly important role in the health care system globally, especially in the developing world, as they provide for an effective and more affordable alternative for healthcare professional. Generic drug products are proven therapeutically equivalent to the corresponding innovator’s product, and hence can be substituted in clinical practice. The Gulf Cooperation Council’s pharmaceutical market is known to be semi-regulated market when compared with Health Canada and the United States of America drug regulatory market. Product regulation in Gulf Cooperation Council and Health Canada are challenging task in comparison to EU and USA. This study aimed to understand the generic drug registration comparison of Health Canada and Gulf Cooperation Council’s. The aim of this study was achieved by review of the Health Canada and Gulf Cooperation council guidelines and publications. Health Canada and Gulf Cooperation council follows Common Technical Document format and also emphasizes on safety, quality and efficacy of the drug. In summary Gulf Cooperation council and Health Canada offers lucrative market for Indian pharmaceutical manufacturer and the process of registration has been simplified by centralized procedure.

Aspects of the industrial manufacture of concentrates for haemodialysis

The import dependence of the pharmaceutical market of Ukraine on concentrates for hemodialysis determines the relevance of their manufacture. Elaboration of the transfer of drug development to industrial manufacture and, accordingly, the development of industrial technology of liquid acid concentrates for hemodialysis involves scaling the process, organization of production control, establishing critical points of the production and determining cleanliness classes for concentrates and risks, including ecological ones.&#x0D; The aim of the work is to develop approaches to the development of technology for industrial manufacture of acid concentrates for hemodialysis, identification of risks in the technological process and quality control, as well as analysis of major ecological risks and development of methods for their reduction.&#x0D; The object of the study was the regulatory and technical documentation regarding the requirements for hemodialysis concentrates, characterization of the hazard profile of acid concentrates as a source of pharmaceutical wastes and generalization of the information about them in the manufacture of acid concentrates. We used the results of our own experimental research on the development of concentrates. The system-survey method of research and content analysis were used in the analysis.&#x0D; On the basis of researches, it was to work up the approaches to the development of technology of industrial manufacture of acid concentrates. Requirements of various normative and technical documents for water for the manufacture were generalized, classes of cleanliness of industrial premises for the preparation of containers, preparation, filtering, and packing of solutions are offered. The scheme of pharmaceutical wastes of acid concentrates, which are formed during pharmaceutical development, industrial manufacture, and medical administration, is presented. The profile of their unsafety is given. Potential and real ecological risks in the manufacture of acid concentrates for hemodialysis and ways to minimize them are presented. The proposed stages of risk management for pharmaceutical waste during the manufacture of acid concentrates of hemodialysis include: determining the hazard profile of acid concentrates for the environment; identification of risks, as well as replenishment of knowledge about the hazard profile; planning and implementation of risk minimization measures as well as evaluation of the effectiveness of these risk reduction measures. Methods for eliminating the safety of pharmaceutical wastes of acid hemodialysis concentrates (dilution with water or electrolysis to obtain by-products) have been developed.

Initial Exploratory Reactor Physics Assessment of Nonconventional Fuel Concepts for Very Compact Small Modular Reactors Using Hydroxides as Coolants and/or Moderators

In this study, lattice physics calculations were carried out to evaluate the reactor physics characteristics of different advanced fuel lattices cooled with 7LiOH/NaOH or FLiBe and moderated externally by graphite and various types of metal hydroxides, such as 7LiOH, 7LiOD, Mg(OD)2, and ZrE(OD)4. The lithium in these compounds is enriched to 99.995 at. % 7Li/Li. Such lattice fuel concepts could be used in compact, thermal-spectrum, high-temperature (700°C) small modular reactors (SMRs). For an SMR with a bare core size of diameter = height = 163.3 cm, there are several lattice design concepts identified that could achieve modest power densities (up to 18 MW/m3) that are higher than those found typically in high-temperature gas cooled reactors (~ 2 to 10 MW/m3) [IAEA Technical Document 1382 (2019); Report PNR-131-20110914, Delft University, Netherlands (2011)], although lower than those found typically in SMRs based on light water reactor technology (for example, the NuScale SMR has a volumetric power density of ~47 MW/m3) [Proc. PBNC 2018, p. 270 (2018)]. In addition, there are lattice designs identified for the fixed core size that could achieve high fuel burnup (up to 126 MWd/kg), long core lifetimes (up to 24 years before refueling), very good fissile utilization (up to 640 MWd/kg-fissile), and very good relative uranium utilization (up to 44% of that achieved with a conventional pressure-tube heavy water reactor using natural uranium fuel). The best lattice concept found to maximize fuel burnup with 7LiOH/NaOH coolant was an 18-cm-pitch lattice with ZrE(OD)4 external moderator (126.5 MWd/kg). The best lattice concept for FLiBe coolant was a 16-cm-pitch lattice with 7LiOH external moderator (125.99 MWd/kg). Although it is recognized that there are numerous and challenging technical issues to be resolved, particularly with corrosion and materials science, the potential use of hydroxides as coolants and/or external moderators could lead to very important performance improvements for very small and compact SMRs.