Regulatory Perspective Research Articles

Sharia crowdfunding in Indonesia: a regulatory environment perspective

Sharia crowdfunding in Indonesia: a regulatory environment perspective

Case Studies on Changes and Proposed Process Development Approaches reflecting applicability of PDA Technical Report No. 89 Strategies for Vaccine Development and Lifecycle Management.

Vaccines are complex and a very diverse group of products with relatively long product lifecycles. The manufacturing programs for these vaccines need to be continually updated to comply with evolving regulatory expectations. Members of the Parenteral Drug Association (PDA) Vaccines Interest Group (VIG) authored and published PDA Technical Report No. 89 Strategies for Vaccine Development and Lifecycle Management (TR 89) which seeks to provide context to vaccine developers and manufacturers regarding key aspects of new or legacy vaccines such as control strategy from process development to vaccine lifecycle management, comparability and lifecycle management including technical, validation, quality and regulatory perspectives. To further explain and illustrate the concepts and topics discussed, seven relevant situations were selected as either case studies associated with changes implemented or proposed process development strategies, which are discussed in this article. The situations described are: working cell bank, modification or update of externally supplied product contact components for vaccine manufacturing, raw material change, new product at an existing site, vaccine development acceleration by leveraging existing platforms, selection and implementation of potency method, and modeling for stability forecast prediction. For each situation, the applicable key concepts from TR#89 are discussed as follows: Control Strategy, Prior Knowledge, Relying on PQS, Classification of Parameters, Validation Approach, Use of a Risk-based Approach, Comparability, Use of ICHQ12 and Additional Regulatory Considerations.

A multichannel graph neural network based on multisimilarity modality hypergraph contrastive learning for predicting unknown types of cancer biomarkers.

Identifying potential cancer biomarkers is a key task in biomedical research, providing a promising avenue for the diagnosis and treatment of human tumors and cancers. In recent years, several machine learning-based RNA-disease association prediction techniques have emerged. However, they primarily focus on modeling relationships of a single type, overlooking the importance of gaining insights into molecular behaviors from a complete regulatory network perspective and discovering biomarkers of unknown types. Furthermore, effectively handling local and global topological structural information of nodes in biological molecular regulatory graphs remains a challenge to improving biomarker prediction performance. To address these limitations, we propose a multichannel graph neural network based on multisimilarity modality hypergraph contrastive learning (MML-MGNN) for predicting unknown types of cancer biomarkers. MML-MGNN leverages multisimilarity modality hypergraph contrastive learning to delve into local associations in the regulatory network, learning diverse insights into the topological structures of multiple types of similarities, and then globally modeling the multisimilarity modalities through a multichannel graph autoencoder. By combining representations obtained from local-level associations and global-level regulatory graphs, MML-MGNN can acquire molecular feature descriptors benefiting from multitype association properties and the complete regulatory network. Experimental results on predicting three different types of cancer biomarkers demonstrate the outstanding performance of MML-MGNN. Furthermore, a case study on gastric cancer underscores the outstanding ability of MML-MGNN to gain deeper insights into molecular mechanisms in regulatory networks and prominent potential in cancer biomarker prediction.

AI-driven corporate governance: a regulatory perspective

ABSTRACT The use of AI-driven or AI-assisted systems in corporate compliance is a novel topic in the business and management literature, only marginally considered by legal academia. While some scholarly pieces have explored the use of artificial intelligence (AI) systems to support compliance in the financial sector (eg, for anti-money laundering purposes), the legal implications of deploying AI systems to fulfil corporate compliance tasks has not yet received the attention it deserves. This article approaches the use of AI in corporate compliance and governance through the eyes of a regulator. Its aim is to present how the use of AI compliance systems within corporations can be leveraged by the entities tasked with ensuring the good governance of firms. Concretely, it explores a not-too-distant future, where some of the regulation of corporations can be driven by a mandate to systematically deploy Automated Compliance Management Systems (ACMS) within corporations as a way to enforce and monitor good governance. The article suggests that several of the limitations that regulators are currently facing to ensure the prevention of fraud, corruption or other forms of corporate non-compliance, could be addressed if regulators offered firms the possibility of being continuously monitored by an automated AI-driven system which systematically tracks the corporation’s data footprint. We then explore what is required for such a regulatory approach to be feasible and effective. In our view, regulators must first establish the standards of reliability for those systems (ie, the legal meaning of ‘red flags’ issued by the system of potential violations) and, second, actively supervise how companies react to the outputs of those systems (ie, what companies do when a red flag is raised by the system). In the final part of the article, we offer a more concrete example to the reader. We suggest it could be possible to test such an approach in Australia through regulatory sandboxes for the mining sector, concretely, to monitor compliance with antibribery obligations overseas.

Hydramethylnon induces mitochondria-mediated apoptosis in BEAS-2B human bronchial epithelial cells

Typically used household chemicals comprise numerous compounds. Determining mixture toxicity, as observed when using household chemicals containing multiple substances, is of considerable importance from a regulatory perspective. Upon examining the toxic effects of household chemical mixtures, we observed that hydramethylnon combined with tetramethrin resulted in synergistic toxicity. To determine the unknown toxicity mechanism of hydramethylnon, which carries the risk of inhalation exposure when using household chemicals, we conducted a further investigation using BEAS-2B cells, a human bronchial epithelial cell line. Hydramethylnon-induced cytotoxicity was determined following 24 and 48 h of exposure using the water-soluble tetrazolium 1 and lactate dehydrogenase assays. To elucidate the toxicity mechanism, we utilized flow cytometry and measured the levels of apoptosis-related proteins and caspase activities. Given that hydramethylnon, as an insecticide, disrupts the mitochondrial electron transfer chain, we analyzed the relevant mechanisms, including mitochondrial superoxide levels as well as the mitochondrial membrane potential (MMP). Hydramethylnon dose-dependently induced BEAS-2B cell apoptosis via the intrinsic pathway. Furthermore, it significantly increased mitochondrial superoxide levels and disrupted the MMP. Pre-treatment with a caspase inhibitor (Z-DEVD-FMK) confirmed that hydramethylnon induced caspase-dependent apoptosis. Apoptosis, a key event in the toxicological process of chemicals, can lead to lung diseases, including fibrosis and cancer. The results of the present study suggest a mechanism of toxicity of hydramethrylnon, an organofluorine biocide whose toxicity has been little studied, to the lung epithelium. Considering the potential risks associated with inhalation exposure, these results highlight the need for careful management and regulation of hydramethylnon.

Aspects of complexity in quality and safety assessment of peptide therapeutics and peptide-related impurities. A regulatory perspective

In recent years, a number of therapeutic peptides have been authorized in the EU market, and several others are in the clinical development phase or under assessment for full dossier or generic applications. Quality and safety guidelines specific to peptides are limited, and some aspects have to be considered. In particular, concerns relate to the analytical investigation for impurities and the toxicological assessment of these substances. The guidelines and the compendial pharmacopoeias provide certain references but that may be questionable if interpreted according to whether therapeutic peptides are considered chemical or biological entities, large or small. The characterization of peptide-related impurities cannot follow the small molecule approach but should consider aspects closely linked to the complex mechanisms of action that these large molecules can exert in the human body. Although direct genotoxic mechanisms cannot be excluded, hazardous interactions on biological systems cannot be ruled out, as in the case of natural peptide toxins and their specific interactions with cellular or membrane targets. From a regulatory perspective, only after specific risk identification and characterization should an equally specific safety threshold in relation to potential toxicity be defined.

Brazilian banks risk-taking and systemic risk

This study analyzes the marginal contribution of Brazilian banks to the systemic risk. The objective is to identify whether banks that share common characteristics similarly contribute to systemic financial shocks. First, the risk assumed by a sample of listed banks is measured from the accounting, market, and regulatory perspectives. Sample banks were segregated using an unsupervised clustering model. The results were compared with the methodology currently used by the Central Bank of Brazil to segment the banking institutions. Finally, we evaluate the banking groups’ marginal contribution to systemic financial risk using ΔCoVaR. These results suggest that institutions that share similar characteristics in relation to their risk profiles behave similarly during times of greater market stress. Notably, size, geographic diversification, and liquidity were common attributes among banks contributing significantly to systemic risk during financial crises. This study advances the field of banking finance by introducing an analytical framework that goes beyond the traditional focus on bank balance sheet size, aligning with international standards for evaluating the systemic importance of financial institutions.

A regulatory focus theory perspective on the dynamics between action and power.

Building on the strong consensus that the experience of power motivates individuals to take action, prior research postulates a positively reinforcing cycle wherein taking action leads to power, which in turn leads to subsequent actions. Applying regulatory focus theory, we differentiate between promotion-oriented and prevention-oriented actions to develop a within-person theory of when and why promotion-oriented and prevention-oriented actions should relate to power, and vice-versa. Across two studies, we find that when employees engaged in promotive voice behaviors, they were more likely to experience a sense of power; this effect was amplified for employees with trait promotion focus. When employees engaged in prohibitive voice behaviors, employees with trait prevention focus were less likely to experience a sense of power. The experience of power subsequently motivated employees to engage in promotive voice behaviors, but not prohibitive voice behaviors. By elucidating the differences between promotion and prevention pathways of action and power, our research challenges the notion that action and power positively reinforce each other. We discuss the theoretical and practical implications of our findings. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Dosage Optimization: A Regulatory Perspective for Developing Oncology Drugs.

Optimized dosages provide a secure foundation for the development of well-tolerated and effective oncology drugs. Project Optimus, an initiative within the Oncology Center of Excellence, strives to reform the dosage optimization and dosage selection paradigm in oncology. This initiative stems from the availability of targeted drugs and from the demand for more tolerable dosages from patients, caregivers, and advocates. Reforming dosage optimization for oncology drugs requires a paradigm shift from the one employed for cytotoxic chemotherapy to one that understands and considers the unique attributes of targeted therapy, immunotherapy, and cellular therapy. Limited characterization of dosage during drug development may result in (1) patients not staying on a therapy long-term due to poor tolerability, (2) failure to establish positive benefit-risk in clinical trials for regulatory approval (3) withdrawal of drugs from the market (4) removal of indications of drugs from the market. Timely access to drugs is important for all patients with cancer, so it is vital to iteratively analyze all nonclinical and clinically relevant data at each stage of development and leverage quantitative approaches, innovative trial designs, and regulatory support to arrive at dosages with favorable benefit-risk. This review highlights the key challenges and opportunities to embracing this new paradigm and realizing the full potential of new oncology therapies.

S18-03 Regulatory perspective for the opportunities afforded by quantitative systems toxicology in chemical safety assessment

S18-03 Regulatory perspective for the opportunities afforded by quantitative systems toxicology in chemical safety assessment

Biofunctionalization of Cellulose Microcarriers Using a Carbohydrate Binding Module Linked with Fibroblast Growth Factor for the Expansion of Human Umbilical Mesenchymal Stromal Cells in Stirred Suspension Bioreactors.

Mesenchymal stromal cells (MSCs) have the potential to be used as autologous or allogenic cell therapy in several diseases due to their beneficial secretome and capacity for immunomodulation and differentiation. However, clinical trials using MSCs require a large number of cells. As an alternative to traditional culture flasks, suspension bioreactors provide a scalable platform to produce clinically relevant quantities of cells. When cultured in bioreactors, anchorage-dependent cells like MSCs require the addition of microcarriers, which provide a surface for cell attachment while in suspension. The best performing microcarriers are typically coated in animal derived proteins, which increases cellular attachment and proliferation but present issues from a regulatory perspective. To overcome this issue, a recombinant fusion protein was generated linking basic fibroblast growth factor (bFGF) to a cellulose-specific carbohydrate binding module (CBM) and used to functionalize the surface of cellulose microcarriers for the expansion of human umbilical MSCs in suspension bioreactors. The fusion protein was shown to support the growth of MSCs when used as a soluble growth factor in the absence of cellulose, readily bound to cellulose microcarriers in a dose-dependent manner, and ultimately improved the expansion of MSCs when grown in bioreactors using cellulose microcarriers. The use of CBM fusion proteins offers a simple method for the surface immobilization of growth factors to animal component-free substrates such as cellulose, which can be used alongside bioreactors to increase growth factor lifespan, decrease culture medium cost, and increase cell production in the manufacturing of therapeutic cells.

Pharmaceutical Product Development: Quality by Design (QbD)

A popular modern strategy in pharmaceutical development is called "quality by design," or QBD, which started with established goals including the product's safety and efficacy. Safety and product efficacy are the primary goals of QBD in pharmaceutical development. With QBD, the design itself is emphasized for excellence. QBD was introduced by the Food and Drug Administration in order to comprehend the production process. An overview of the pharmaceutical quality system, quality risk management, and international council for harmonization (ICH) rules for product development is provided in this article in order to preserve product quality. The scientific foundation of QBD, regulatory industry perspectives, and QBD technologies were briefly discussed. There was a focus on excipients, manufacturing process development, container closure systems, and pharmacological substances. The Q9 guidelines for quality risk management, Q10 guidelines for pharmaceutical quality systems, and Q8 guidelines for pharmaceutical development form its basis. In the research and production of pharmaceuticals, it also provides an application of Quality by Design.

Off the Guardrails: Opportunities and Caveats for Name Image Likeness and the [Student] Athlete Influencer

The landscape of college athletics is undergoing a seismic shift with the advent of Name, Image, and Likeness (“NIL”) opportunities for student-athletes. In Off the Guardrails: Opportunities and Caveats for Name Image Likeness and the [Student] Athlete Influencer, Professor Maureen A. Weston examines the evolving terrain, tracing the journey from the National Collegiate Athletic Association’s (“NCAA’s”) rigid amateurism policies to the current era of NIL legislation and its implications. This Article navigates the complex intersection of athlete empowerment, entrepreneurial ventures, and regulatory challenges, shedding light on the multifaceted opportunities and risks for athletes in the burgeoning NIL market. Delving into the heart of the matter, Weston dissects the dynamics of NIL dealmaking, unveiling the potential windfalls and pitfalls awaiting collegiate student-athletes. From the allure of financial independence to the specter of predatory practices and regulatory ambiguities, the author uncovers the intricate tapestry of concerns surrounding the NIL framework. Drawing on insights from legal, regulatory, and ethical perspectives, Off the Guardrails offers a roadmap for those navigating this uncharted territory, exploring avenues for policy reform, regulatory harmonization, and athlete welfare safeguards in the quest for a balanced and equitable future for student-athlete influencers.

Organizing Supply Chain Modern Slavery Risks: A Regulatory Focus Perspective

Organizing Supply Chain Modern Slavery Risks: A Regulatory Focus Perspective

Managing Your Images Under Workplace Gossip: A Regulatory Focus Perspective

Managing Your Images Under Workplace Gossip: A Regulatory Focus Perspective

Sustainability performance and earnings management: institutional and regulatory perspectives

Sustainability performance and earnings management: institutional and regulatory perspectives

Unveiling barriers to the integration of blockchain‐based circular economy and Industry 5.0 in manufacturing industries: A strategic prioritization approach

AbstractAlthough Industry 4.0 plays the role of a catalyst in the transition from a linear economy to a circular economy (CE), some sustainability goals are neglected by prioritizing machines over humans. Industry 5.0 insists on combining technology with human values to achieve sustainable development goals. Therefore, the integration of CE and Industry 5.0 leads to sustainable synergy in various industries, especially in manufacturing industries. However, their integration is always associated with challenges and barriers. This study identifies a set of these barriers in the electric vehicle battery production industry from the financial, technical, supply chain, cultural, and regulatory and processes perspectives through a deep literature review. The fuzzy weighted influence non‐linear gauge system method is used to analyze the relationship between identified barriers and their prioritization. Finally, we leverage the knowledge of four experts from an electric vehicle battery manufacturing company in Southeast Asia to validate the proposed approach and to rank the barriers. The results demonstrate that immature technology providers are the biggest obstacle in the integration of blockchain‐based CE and Industry 5.0 in the electric vehicle battery manufacturing industry.

Revolutionizing logistics: The impact of autonomous vehicles on supply chain efficiency

This review paper assesses the impact of autonomous vehicles (AVs) on enhancing the efficiency of supply chains, aiming to synthesize existing research and identify future research directions. Through a comprehensive analysis of literature spanning technological, economic, and regulatory perspectives, this paper maps the current landscape of AV integration in logistics. The review finds that AVs offer substantial improvements in supply chain efficiency through continuous operation and reduced human error, leading to decreased costs and improved delivery timelines. It details the potential for up to 30% enhancement in logistical operations with AV adoption. Critical barriers such as technological challenges, regulatory concerns, and cybersecurity risks are also discussed. Conclusively, the paper argues that while AVs present a promising avenue for revolutionizing supply chain management, their widespread adoption depends on overcoming existing barriers. It calls for targeted research into robust AV systems, supportive policy frameworks, and stakeholder engagement strategies to fully realize their benefits.

Carrying the (paper) burden: A portfolio view of systemic risk and optimal bank size

In this paper we propose a two-level portfolio allocation optimization program and use it to explore the banking industry systemic risk management from a regulatory (supervisor) perspective. In our model banks choose their portfolio to maximize their own profits, while the supervisor optimizes the risk and return in the banking system as a whole. This may induce inefficiencies, leading to a banking system that produces excessive risk. We propose three policy scenarios based on current regulation practices and proposals and explore the ability of these regulatory regimes to reduce the systemic risk of the banking industry. We illustrate the use of the model by looking at over 9,000 US banks in the period 1984-2013, covering two major recessions. While all policy scenarios yield a better risk-return trade-off compared with the observed portfolio, the greatest improvements are achieved when the supervisor is able to limit the size of banks.

How to Promote Walking in Women with Fibromyalgia: A Look at Catastrophizing, Goal Conflict, and Avoidance from a Self-Emotional Regulatory Perspective.

The aim of this study was twofold: to explore the concordance between two measures of physical activity (accelerometer and IPAQ) among female fibromyalgia (FM) patients, as well as to examine the impact of psychosocial variables (catastrophism, activity avoidance) on walking among these patients. Helplessness, activity avoidance, and commitment to physical activity were evaluated in 132 FM women. After the first assessment, an accelerometer was placed by a psychologist on each participant for seven consecutive days. Eight days later, accelerometers were collected, and participants were evaluated again using the IPAQ. Two models were tested to analyze mediation and a moderated mediation effect. The mediating role of activity avoidance between helplessness and minutes walked was corroborated regarding the objective measure of walking. The effect of helplessness on minutes walked during a week was mediated by activity avoidance and assessed by accelerometers. Cognitive variables played a contextual role when trying to promote exercise. Activity avoidance must be understood as a key variable in physical activity promotion, specifically in the promotion of walking with the aim to do exercise in individuals with FM.