Potential Liability Research Articles

Substitution of a triazole for the central olefin in biologically active stilbenes

The stilbene moiety is commonly found in natural products and these compounds display an extraordinary range of biological activity. Efforts to derive useful drugs from stilbenes must address the potential liabilities of this structure, including a propensity for cis/trans isomerization. To identify olefin replacements that address this limitation while preserving biological activity we have prepared analogues of two bioactive stilbenes, a pawhuskin and a schweinfurthin, where a 1,2,3-triazole ring formally replaces the stilbene double bond. The new schweinfurthin analogue (23) has been tested for anti-proliferative activity against 60 cell lines, and shows a strong correlation of bioactivity when compared to the compound that inspired its synthesis (22).

Strategies to evaluate potential effector function of glycan variants: A case study of ordesekimab (AMG 714 or PRV-015)

The potential for effector functions of therapeutic antibodies, including antibody-dependent cell-mediated cytotoxicity (ADCC), is a biological activity of interest for characterization, regardless of if ADCC is an intended primary pharmacological effect. The composition of the conserved antibody Fc glycan can vary as a function of post-translational processing which may affect the binding affinity to Fc receptors, leading to a change of effector activity. Ordesekimab (AMG 714 or PRV-015), a fully human immunoglobulin G1-kappa anti-interleukin (IL)-15 monoclonal antibody, is in clinical development for celiac disease. The binding of ordesekimab to IL-15 inhibits the interaction of IL-15 with the IL-2Rβ and common γ chain of the IL-15 receptor complex, but not with the IL-15Rα chain. Therefore, the simultaneous binding of ordesekimab to the Fcγ receptor (R) IIIα expressed on natural killer (NK) cells and to the IL-15/IL-15Rα complex on cells such as monocytes may theoretically enable ADCC toward the IL-15Rα-expressing cells. The high mannose (HM) levels on the Fc glycan were found to vary in different lots of ordesekimab resulting from refinements to the manufacturing process, and the impact on ordesekimab-mediated ADCC activity was evaluated in in vivo and in vitro studies. A review of nonclinical and clinical data found no evidence of ordesekimab-induced depletion of monocytes, or cytotoxicity in organs with wide IL-15Rα expression, suggesting a lack of in vivo ADCC activity. In addition, in vitro peripheral blood mononuclear cells-based ADCC assay did not reveal any cytolytic effect of ordesekimab with various levels of HM content when cocultured with recombinant human IL-15. Taken together, these data demonstrate that ADCC is not a potential liability for ordesekimab and does not contribute to the reduction of IL-15-mediated inflammation, the intended pharmacological effect.

Delictual liability for injuries suffered at childcare centres

The Constitutional Court has recently given an important judgment about the delictual liability of the state for injuries sustained by a child at an early childhood development (ECD) centre: BE obo JE v MEC for Social Development, Western Cape. The Court substantially confirmed the Supreme Court of Appeal (SCA) judgment in the same matter. Both judgments built upon the preceding SCA judgment in Government of the Western Cape: Department of Social Development v CB, which, like BE, involved a tragic accident at an ECD centre. With the appearance of these judgments, it is a good time to assess our courts’ willingness to provide delictual remedies for injuries suffered at childcare centres, and to consider the status of South African public authority liability in general. I explain that the omissions liability of public authorities for negligently caused bodily injury has expanded significantly since 2002. The High Court judgments in BE and CB, which imposed liability on the Department of Social Development, were consistent with this. But the appellate judgments may suggest a retreat from our law’s expansionary approach. I discuss the reasons of policy and principle why such a retreat might be welcome, both for organs of state and the legal system as a whole. I also consider the potential delictual liability of the ECD centres themselves, as well as local authorities, for incidents of the kind in BE and CB. Finally, I consider two hypothetical cases that help to illustrate potential future developments for public authority liability in South Africa.

Tunable Cysteine-Targeting Electrophilic Heteroaromatic Warheads Induce Ferroptosis.

Once considered potential liabilities, the modern era witnesses a renaissance of interest in covalent inhibitors in drug discovery. The available toolbox of electrophilic warheads is limited by constraints on tuning reactivity and selectivity. Following our work on a class of ferroptotic agents termed CETZOLEs, we discovered new tunable heterocyclic electrophiles which are capable of inducing ferroptosis. The biological evaluation demonstrated that thiazoles with an alkyne electrophile at the 2-position selectively induce ferroptosis with high potency. Density functional theory calculations and NMR kinetic studies demonstrated the ability of our heterocycles to undergo thiol addition, an apparent prerequisite for cytotoxicity. Chemoproteomic analysis indicated several potential targets, the most prominent among them being GPX4 protein. These results were further validated by western blot analysis and the cellular thermal shift assay. Incorporation of these heterocycles into appropriate pharmacophores generated highly cytotoxic agents such as the analogue BCP-T.A, with low nM IC50 values in ferroptosis-sensitive cell lines.

Robust, Automated Analysis of Electrophysiology in Induced Pluripotent Stem Cell-Derived Micro-Heart Muscle for Drug Toxicity.

Drugs are often removed from clinical trials or market progression owing to their unforeseen effects on cardiac action potential and calcium handling. Induced pluripotent stem cell-derived cardiomyocytes and tissues fabricated from these cells are promising as screening tools for early identification of these potential cardiac liabilities. In this study, we describe an automated, open-source MATLAB-based analysis software for calculating cardiac action potentials and calcium transients from fluorescent reporters. We first identified the most robust manner in which to automatically identify the initiation point for action potentials and calcium transients in a user-independent manner, and used this approach to quantify the duration and morphology of these signals. We then demonstrate the software by assessing changes to action potentials and calcium transients in our micro-heart muscles after exposure to hydroxychloroquine, an antimalarial drug with known cardiac liability. Consistent with clinical observations, our system predicted mild action potential prolongation. However, we also observed marked calcium transient suppression, highlighting the advantage of testing multiple physiologic readouts in cardiomyocytes rather than relying on heterologous overexpression of single channels such as the human ether-a-go-go-related gene channel. This open-source software can serve as a useful, high-throughput tool for analyzing cardiomyocyte physiology from fluorescence imaging.

When Pan-European Insolvency Twilight Lasts for Years: Are Controlling Lenders Liable?

Companies structured for project finance can be prematurely failed by European insolvency laws, where there is a strict obligation to file for insolvency if the required solvency tests have been failed. Using two technically insolvent windfarm projects in Poland and Romania, this article analyzes why each debtor continued to trade in breach of the law and why the lenders permitted such continued trading. Although facing liability, the directors of the debtors could see that through continued trading the debtors would eventually pay off the secured debt, and the project and the profits could be returned to the shareholders. The debtor had this confidence because of the project finance nature of infrastructure where there is good long-term visibility of cashflows. This article critically analyzes the national insolvency laws for infrastructure projects in Poland and Romania and considers whether the lenders in each case, by allowing the debtors to trade, should share some of the potential liability.

Physiologically-Based Pharmacokinetic Models of CYP2D6 Substrate and Inhibitors Nebivolol, Cinacalcet and Mirabegron to Simulate Drug-Drug Interactions.

Index substrates and inhibitors to investigate the role of the polymorphic enzyme, cytochrome P450 (CYP) 2D6, in the metabolism of new compounds have been proposed by regulatory agencies. This work describes the development and verification of physiologically-based pharmacokinetic (PBPK) models for the CYP2D6-sensitive substrate, nebivolol and the index CYP2D6 inhibitors, mirabegron and cinacalcet. PBPK models for nebivolol, mirabegron and cinacalcet were developed using in vitro and clinical data. The performance of the PBPK models was verified by comparing the simulated results against reported human systemic exposure and clinical drug-drug interactions (DDIs) studies. The exposure of nebivolol, cinacalcet and mirabegron predicted by the PBPK models was verified against pharmacokinetic data from 13, 3 and 9 clinical studies, respectively. For nebivolol, the predicted meanmaximum plasmaconcentration (Cmax)and area under the plasmaconcentration-time (AUC) values in CYP2D6 extensive metaboliser subjects were within 0.9- to 1.49-fold of the observed values. In poor metaboliser CYP2D6 subjects, the predicted Cmax and AUC values were within 0.41- to 0.81-fold of observed values. For cinacalcet, the predicted Cmax and AUC values were within 0.97- to 1.32-fold of the observed data. For mirabegron, the predicted AUC values across all the studies investigated were within 0.71- to 1.88-fold of observed values. The PBPK model-predicted DDIs were in good agreement (within 2-fold) with observed DDIs in all verification studies (n = 8) assessed. The overall precision was 1.26 and 1.21 for Cmax and the AUC ratio, respectively. The developed PBPK models can be used to assess the DDI potential liability of new chemical entities that are substrates or inhibitors of CYP2D6.

Prediction of Adverse Drug Reaction Linked to Protein Targets Using Network-Based Information and Machine Learning.

Drug discovery attrition rates, particularly at advanced clinical trial stages, are high because of unexpected adverse drug reactions (ADR) elicited by novel drug candidates. Predicting undesirable ADRs produced by the modulation of certain protein targets would contribute to developing safer drugs, thereby reducing economic losses associated with high attrition rates. As opposed to the more traditional drug-centric approach, we propose a target-centric approach to predict associations between protein targets and ADRs. The implementation of the predictor is based on a machine learning classifier that integrates a set of eight independent network-based features. These include a network diffusion-based score, identification of protein modules based on network clustering algorithms, functional similarity among proteins, network distance to proteins that are part of safety panels used in preclinical drug development, set of network descriptors in the form of degree and betweenness centrality measurements, and conservation. This diverse set of descriptors were used to generate predictors based on different machine learning classifiers ranging from specific models for individual ADR to higher levels of abstraction as per MEDDRA hierarchy such as system organ class. The results obtained from the different machine-learning classifiers, namely, support vector machine, random forest, and neural network were further analyzed as a meta-predictor exploiting three different voting systems, namely, jury vote, consensus vote, and red flag, obtaining different models for each of the ADRs in analysis. The level of accuracy of the predictors justifies the identification of problematic protein targets both at the level of individual ADR as well as a set of related ADRs grouped in common system organ classes. As an example, the prediction of ventricular tachycardia achieved an accuracy and precision of 0.83 and 0.90, respectively, and a Matthew correlation coefficient of 0.70. We believe that this approach is a good complement to the existing methodologies devised to foresee potential liabilities in preclinical drug discovery. The method is available through the DocTOR utility at GitHub (https://github.com/cristian931/DocTOR).

What Augmented Reality Would Face Today? The Legal Challenges to the Protection of Intellectual Property in Virtual Space

AbstractAugmented Reality (AR) refers to a display of a real-world environment whose elements are augmented by one or more layers of text, data, symbols, images, or other graphical display elements. AR technology is always associated with online games. Beyond online gaming, AR has become part of daily life and affects every aspect of how society interacts with technology. In retail and marketing, AR and other virtual technologies play a very important role in saving costs. AR is also used in the education and medical sector, also in preventing crime. AR is even further used for humanitarian activities to reach remote areas affected by natural disasters and save human lives. Considered a new technology, the commercialization of AR may bring incredible business opportunities as well as potential legal risks. In the context of Intellectual Property (IP), AR systems and services can embody a variety of forms of IP. Meanwhile, the operation of AR systems in virtual spaces is creating issues about how to deal with data breaches and privacy. By using doctrinal methods, this paper will explore the legal challenge of AR in the context of IP protection in the virtual space and investigate the potential liability caused by the failure of AR systems from the Indonesian legal perspective.Keywords: Augmented Reality; Intellectual Property; Legal; Virtual Space.

Risk analysis under attack: How risk science can address the legal, social, and reputational liabilities faced by risk analysts.

The role of the risk analyst is critical in understanding and managing uncertainty. However, there is another type of uncertainty that is rarely discussed: The legal, social, and reputational liabilities of the risk analyst. Recent events have shown that professionals participating in risk analysis can be held personally liable. It is timely and important to ask: How can risk science guide risk analysis with consideration of those liabilities, particularly in response to emerging and unprecedented risk. This paper studies this topic by: (1) Categorizing how professionals with risk analysis responsibilities have historically been held liable, and (2) developing a framework to address uncertainty related to those potential liabilities. The result of this framework will enable individual analysts and organizations to investigate and manage the expectations of risk analysts and others as they apply risk principles and methods. This paper will be of interest to risk researchers, risk professionals, and industry professionals who seek maturity within their risk programs.

Sustainable Operation of Unmanned Ships under Current International Maritime Law

The aim of this paper is to evaluate the current international maritime legislative framework and assess its relevance in sustaining the operations of unmanned ships while addressing the issue of liability from system malfunctions. The paper initially explores the legal definition of a ship and evaluates whether the existence of an on-board crew is an integral part of the definition. Subsequently, the analysis continues with assessing the legal implications and challenges for the sustainable operation of unmanned ships, such as the governing flag state legislation that defines liability parameters, taking into consideration the existing levels of vessel automation. The paper concludes with an evaluation of the contractual issues and potential stakeholder liability related to governing a flag state. In addition, the potential transfer of liability from the ship operators to manufacturers as pertains to unmanned ship operation is also addressed. The concluding remarks suggest that unmanned ship operation is sustainable under the current international maritime legislative framework; however, the current legislation should be considered as a baseline from which specific legislation for the operation of unmanned ships can be drawn. The methodology utilised for this paper is based on the legal doctrine.

Abstract 578: A functional approach to identifying and engineering TCRs results in highly-potent and specific TCRs for TCR-T cell therapy

Abstract Peptide-HLA (pHLA)- targeting therapeutics, such as T cell receptor-engineered T cells (TCR-T), have had clinical success in treating solid tumors. However, challenges related to safety exist: major concerns remain surrounding the cross-reactivity of T cell receptors (TCRs) as well as the ability of therapeutics to discriminate between on-target vs off-target pHLAs while maintaining high potency. Therefore, approaches that survey the diversity of the T cell repertoire to discover optimal TCRs, as well as platforms to comprehensively identify potential off-target liabilities, are critical to de-risking and accelerating the development of this promising class of pHLA-targeting therapeutics. We have developed a strategy that (1) queries the TCR repertoire to enrich and identify multiple active, sequence-distinct endogenous TCRs; (2) uses 3T-TRACE, a high-diversity pHLA library, to screen for cross-reactivity; and (3) exploits functional selections to simultaneously optimize for TCR potency and specificity. We applied this approach to identify TCRs of optimal specificity and potency targeting a peptide derived from the cancer-testis antigen NY-ESO-1 (SLLMWITQC) displayed by HLA-A2. We profiled 6 sequence-distinct TCRs using 3T-TRACE and validated potential endogenous off-target cross-reactivities. Many of the identified off-targets exhibited little to no sequence homology to the NY-ESO-1 epitope, highlighting the importance of diverse combinatorial libraries in identifying unexpected cross-reactivities. Leveraging the off-target liabilities identified by 3T-TRACE, we designed a functional library and selection scheme that enabled the identification of TCRs with increased potency and specificity. Optimized TCRs exhibited enhanced killing activity and improved safety against an NY-ESO-1-expressing melanoma cell line compared to benchmark TCRs, indicating that this approach has potential to improve clinical safety and efficacy. Using this multi-faceted and comprehensive approach we rapidly identified highly potent and specific TCRs against NY-ESO-1. Identifying cross-reactivities using 3T-TRACE proved to be critical in selecting TCRs suitable for engineering and functional selections. This approach can be extended to any pHLA target to create safe and effective TCR-Ts for clinical development. Citation Format: John D. Leonard, Alejandro Ramirez, Jason Romero, Jake Kleiner, Joanna Dreux, Bindu Hegde, Bryan Xie, Akshay Sharathchandra, Nathan Katz, Venita I. DeAlmeida, Hans-Peter Gerber, Marvin H. Gee, Leah V. Sibener. A functional approach to identifying and engineering TCRs results in highly-potent and specific TCRs for TCR-T cell therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 578.

Survey of Vitreoretinal Specialists in the United States Regarding Telemedicine During the COVID-19 Pandemic.

Objective: To evaluate the attitudes, beliefs, and practice patterns of vitreoretinal specialists regarding the utilization of telemedicine during the COVID-19 pandemic, and to identify features which may predict future telemedicine use. Methods: An 11-question anonymous survey was completed electronically in July 2020 by vitreoretinal specialists practicing in the United States. Results: The survey response rate was 13.0% (361/2,774). Thirty-five respondents (9.7%) had used telemedicine before March 1, 2020; after March 1, 2020, 170 (47.1%) reported using telemedicine (p < 0.001). Of the 170 respondents who reported telemedicine use, a majority (65.3%;111/170) performed 0-5 patient visits per week. Female retina specialists, younger physicians, and those with prior telemedicine usage were more likely to use telemedicine. Barriers to telemedicine use included concern for misdiagnosis (332/361, 92.0%), inability to obtain optical coherence tomography imaging (330/361, 91.4%), inability to obtain fundus imaging (327/361, 90.6%), lack of access to and/or comfort with the technology (261/361, 72.3%), potential legal liability (229/361, 63.4%), and low reimbursement (227/361, 62.9%). The majority of respondents (225/361; 62.3%) reported that telemedicine without ancillary imaging was not an acceptable way to evaluate patients. However, 59.2% (214/361) would find telemedicine acceptable if remote imaging was available. Conclusions: The pandemic led to a rapid adoption of telemedicine by vitreoretinal specialists. The majority of specialists using telemedicine performed five or fewer visits per week. The availability of remote imaging may increase confidence in clinical outcomes with a subsequent increase in utilization of telemedicine by vitreoretinal specialists.

Utilizing cross-product prior knowledge to rapidly de-risk chemical liabilities in therapeutic antibody candidates

There is considerable pressure in the pharmaceutical industry to advance better molecules faster. One pervasive concern for protein-based therapeutics is the presence of potential chemical liabilities. We have developed a simple methodology for rapidly de-risking specific chemical concerns in antibody-based molecules using prior knowledge of each individual liability at a specific position in the molecule’s sequence. Our methodology hinges on the development of sequence-aligned chemical liability databases of molecules from different stages of commercialization and on sequence-aligned experimental data from prior molecules that have been developed at Amgen. This approach goes beyond the standard practice of simply flagging all instances of each motif that fall in a CDR. Instead, we de-risk motifs that are common at a specific site in commercial mAb-based molecules (and therefore did not previously pose an insurmountable barrier to commercialization) and motifs at specific sites for which we have prior experimental data indicating acceptably low levels of modification. We have used this approach successfully to identify candidates in a discovery phase program with exclusively very low risk potential chemical liabilities. Identifying these candidates in the discovery phase allowed us to bypass protein engineering and accelerate the program’s timeline by 6 months.

Conformational Entropy as a Potential Liability of Computationally Designed Antibodies.

In silico antibody discovery is emerging as a viable alternative to traditional in vivo and in vitro approaches. Many challenges, however, remain open to enabling the properties of designed antibodies to match those produced by the immune system. A major question concerns the structural features of computer-designed complementarity determining regions (CDRs), including the role of conformational entropy in determining the stability and binding affinity of the designed antibodies. To address this problem, we used enhanced-sampling molecular dynamics simulations to compare the free energy landscapes of single-domain antibodies (sdAbs) designed using structure-based (DesAb-HSA-D3) and sequence-based approaches (DesAbO), with that of a nanobody derived from llama immunization (Nb10). Our results indicate that the CDR3 of DesAbO is more conformationally heterogeneous than those of both DesAb-HSA-D3 and Nb10, and the CDR3 of DesAb-HSA-D3 is slightly more dynamic than that of Nb10, which is the original scaffold used for the design of DesAb-HSA-D3. These differences underline the challenges in the rational design of antibodies by revealing the presence of conformational substates likely to have different binding properties and to generate a high entropic cost upon binding.

Rhetorical Ethnography and the Virtue of Vulnerability in Transdisciplinary Research Methods

This paper considers some of the ways ethnography has been adopted in transdisciplinary rhetoric and also considers theoretical questions internal to rhetorical ethnography that can help transdisciplinary scholars navigate limitations and potential liabilities inherent in transdisciplinary work. I seek to more carefully consider transdisciplinary features of rhetoric though ethnographic study which, in its position as studying cultures both familiar and foreign to the researcher, mirror many of the disciplinary relations expressed in Marilyn Stember’s topology of disciplinarity. Noting that transdisciplinary rhetoricians engage with scholarship by experts in other fields, an ethnographic approach to transdisciplinary rhetoric recognizes that disciplinary experts might have expert knowledge that they struggle to communicate to non-experts, and rhetoricians should tread carefully in offering solutions to these communicative difficulties. I suggest rhetorical vulnerability and self-awareness expressed through standpoint as two strategies scholars of transdisciplinary rhetoric can use to adopt stances of transparent subjectivity rather than feigning scientific objectivity.

Provider Perspective on Being Recorded During Emergency Medicine Discharge Conversations.

Objective: Despite the possible benefits of provider-recorded visit summaries for patient use, the utilization of such recordings has yet to be adopted as standard care in most specialities. The objective of this study was to investigate the perspectives of emergency department (ED) providers regarding the utilization of audio or video recordings during ED patient encounters, particularly during discharge conversations.Methods: This study utilized an eight-question survey pooling the opinions of various emergency medicine nurses, advanced practitioners, residents, and physicians within a local Ohio hospital system. Providers from multiple healthcare centers were studied. Study data were collected using an anonymous online survey database. Results: Fifty-seven providers were surveyed. Twenty (35%) agreed that patients had the right to record medical conversations, and 36 (63%) cited potential legal liability as their reason for hesitation. Twenty-five providers (43.9%) answered that no video or audio recordings should be provided at discharge. There was no significant difference in secondary outcomes comparing between demographic categories of age, sex, and practice facility type (p>0.05). Conclusion: Providers who responded to this survey did not feel comfortable being recorded during any portion of their patient encounter, even when providing discharge instructions. Our study showed that there is at least some hesitation on behalf of ED providers based on fear of legal retaliation or violation of HIPPA. However, more research in this area is necessary for recordings to become the standard of care during ED encounters.

Off‐campus injuries and on‐campus third‐party conduct might present potential liability under Title IX

Higher education law has long been concerned with whether colleges and universities should be held liable for student injuries that happen off‐campus. The law has repeatedly examined whether these institutions should be held liable when non‐student guests inflict injuries to students on campus. These questions have often found life in tort/negligence law, where the focus is whether there is a special (legal) relationship between institutions of higher education and their students.

Potential Liability Issues of AI-Based Embedded Software in Maritime Autonomous Surface Ships for Maritime Safety in the Korean Maritime Industry

Maritime Autonomous Surface Ships (MASS), an emerging area of digital advancement in shipping and shipbuilding industries, presents a different legal paradigm from that of existing ships. Existing maritime-related industries, including shipping, shipbuilding, and logistics, based on large hardware called ships, are rapidly changing into highly autonomous software-centered structures. This study is focused on analyzing the legal issues in preparation for MASS’ commercial operations in the future by applying comparative methods centered on the Republic of Korea and the United Kingdom. The study’s results contribute to the criteria for the manufacturing responsibility of autonomous ship-embedded software and a desirable legal policy improvement plan. Various legal issues and macro legal policy directions related to software product liability were identified. The study also presents concrete implementation strategies to achieve an ideological harmony and a balance between equitable damage relief and the advancement of related technologies to ensure maritime safety in the maritime industry. Based on the issues identified and their legal policy alternatives, it is hoped that the institutional ideal of product liability, which promotes technological advancement and protects consumer rights, is realized in the software domain as well.

Current knowledge of legal determinants of postmortal organ donations among lawyers and physicians — a cross-sectional survey and narrative review regarding potential criminal liability in opt-out donation model country

Introduction: Knowledge of the basic legal acts and regulations concerning postmortal organ donation is a crucial issue in ensuring that the will of the potential donors is respected and that physicians are legally protected from potential consequences. This study aimed to assess the awareness and knowledge of physicians and lawyers about the basic legal determinants and criminal responsibility in an opt-out donation model country. Material and methods: Survey-based study involved 100 participants, including physicians (group P; n = 50) and lawyers (group L; n = 50). An original questionnaire consisted of 21 questions about the knowledge of the legal regulations of organ donation in Poland. Additionally, a narrative review of Polish transplantation legal acts was performed to identify potential criminal responsibility related to postmortal transplantation. Results: In the study group all lawyers and 50% of physicians declare that their routine work does not include donors’ death confirmation. 62% of physicians are included directly in donors’ qualification. 92% of lawyers and 90% of physicians suggest that access to knowledge in the subject is not easy. The results of substantive knowledge in the field of transplantation law did not differ statistically between the groups, the median total score in 9 questions test was 5 (3:6) in L and the same in P 5 (2:6). The authors identified four aspects of a physician’s criminal responsibility in the case of postmortal transplantation. Conclusions: This study has revealed that knowledge of the basic legal acts and regulations of postmortal donation, considered to be of paramount importance in ensuring respect for transplant law, needed to be improved. Therefore, further education in these aspects may result in more sufficient protection of physicians from potential legal consequences.