Compliance and Regulatory Programs

King, William; Paramastri, Yasmina; GuillÁ©n, Javier

doi:10.1201/9781315152189-7

Cited by 3 publications

(7 citation statements)

References 43 publications

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“…Drawing upon our previously published work, wherein dose–response curves for ApAP and its novel analogs were established across various dosages—10, 32, 100, and 320 mg/kg 28 , we selected median doses of 32 and 100 mg/kg for the current study. Our experimental design adhered to the principles of the 3Rs—Replacement, Reduction, and Refinement—as outlined by Russel and Burch, aiming to minimize 'unnecessary duplication' and reduce the number of animals needed for robust, replicable data of 3Rs 76 – 80 . Additionally, we determined ED 50 values on equimolar (µmol/kg) basis for both ApAP and SRP-001 across all in vivo antinociception assays (Fig.…”

Section: Methodsmentioning

confidence: 99%

Transcriptomic signature, bioactivity and safety of a non-hepatotoxic analgesic generating AM404 in the midbrain PAG region

Bazan,

Bhattacharjee,

Reid

et al. 2024

Sci Rep

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Safe and effective pain management is a critical healthcare and societal need. The potential for acute liver injury from paracetamol (ApAP) overdose; nephrotoxicity and gastrointestinal damage from chronic non-steroidal anti-inflammatory drug (NSAID) use; and opioids’ addiction are unresolved challenges. We developed SRP-001, a non-opioid and non-hepatotoxic small molecule that, unlike ApAP, does not produce the hepatotoxic metabolite N-acetyl-p-benzoquinone-imine (NAPQI) and preserves hepatic tight junction integrity at high doses. CD-1 mice exposed to SRP-001 showed no mortality, unlike a 70% mortality observed with increasing equimolar doses of ApAP within 72 h. SRP-001 and ApAP have comparable antinociceptive effects, including the complete Freund’s adjuvant-induced inflammatory von Frey model. Both induce analgesia via N-arachidonoylphenolamine (AM404) formation in the midbrain periaqueductal grey (PAG) nociception region, with SRP-001 generating higher amounts of AM404 than ApAP. Single-cell transcriptomics of PAG uncovered that SRP-001 and ApAP also share modulation of pain-related gene expression and cell signaling pathways/networks, including endocannabinoid signaling, genes pertaining to mechanical nociception, and fatty acid amide hydrolase (FAAH). Both regulate the expression of key genes encoding FAAH, 2-arachidonoylglycerol (2-AG), cannabinoid receptor 1 (CNR1), CNR2, transient receptor potential vanilloid type 4 (TRPV4), and voltage-gated Ca2+ channel. Phase 1 trial (NCT05484414) (02/08/2022) demonstrates SRP-001’s safety, tolerability, and favorable pharmacokinetics, including a half-life from 4.9 to 9.8 h. Given its non-hepatotoxicity and clinically validated analgesic mechanisms, SRP-001 offers a promising alternative to ApAP, NSAIDs, and opioids for safer pain treatment.

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Section: Methodsmentioning

confidence: 99%

Transcriptomic signature, bioactivity and safety of a non-hepatotoxic analgesic generating AM404 in the midbrain PAG region

Bazan,

Bhattacharjee,

Reid

et al. 2024

Sci Rep

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“…Although alternatives such as in vitro models, computer simulations, and tissue engineering show potential for decreasing the usage of animals, concerns persist over their accuracy, dependability, and capacity to be applied to human biology (4,18,23). Controversies can emerge over the ethical ramifications of employing alternative techniques and the degree to which they may substitute established animal models (50). Regulatory oversight and enforcement involve the task of ensuring that ethical norms and rules for the use of animals in research are followed.…”

Section: Challenges and Ongoing Debates Regarding Animal Consent And ...mentioning

confidence: 99%

“…Discussions on the ethical treatment of animals in research frequently mirror wider societal values, cultural views, and ethical frameworks. It is crucial to involve the public in conversations on animal welfare, ethical issues, and the use of animals in research in order to foster openness, accountability, and responsible research methodologies (50). To summarize, the issues and current discussions around animal consent and welfare in research settings underscore the many ethical, scientific, and societal factors involved in utilizing animals for research purposes.…”

Section: Challenges and Ongoing Debates Regarding Animal Consent And ...mentioning

confidence: 99%

“…Effective oversight and compliance systems are essential for guaranteeing the ethical conduct of animal research. These systems are specifically created to protect the well-being of animals, ensure the honesty and accuracy of scientific work, and maintain high ethical standards in research environments (50). Effective monitoring and compliance in animal research are influenced by several crucial components.…”

Section: Oversight and Compliance Of The Animal Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Ethical Principles and Rules in Experimental Animal Studies: A Comprehensive Review

Kocaman Kalkan,

Kekeçoğlu

2024

Düzce Tıp Fakültesi Dergisi

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When doing scientific research including animal experiments, it is crucial to prioritize ethical issues due to the many moral, legal, and scientific aspects involved. This study provides an in-depth analysis of the core ethical concepts and regulations that govern experimental investigations using animals. The 3R principle (replacement, reduction, refinement), which prioritizes the ethical treatment of animals especially in scientific research, is emphasized. Tracing the historical development of ethical rules sheds light on the important events that shaped the creation of important principles. The review examines the complex relationship between scientific investigation and ethical concerns, focusing on the idea of informed consent in relation to animal care. Also, this explores the ethical dilemmas that arise from experimental techniques and sheds light on how researchers ensure the well-being of the animals involved. The crucial importance of an ethical committee is emphasized in guaranteeing strict ethical standards. The examination of ethical concerns related to certain animal models, and analysis of differing perspectives among the scientific community is done. At the same time, it examines the latest developments in experimental animal research, providing insight into the future of ethical issues in this ever-evolving area. To summarize, this review not only synthesizes the main discoveries and ethical concerns in experimental animal studies but also highlights potential future paths. It supports the idea of continuing to balance scientific progress in the field of experimental animal studies with ethical obligations by suggesting additional areas of research and ethical review.

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“…In addition, regulatory feedback and queries associated with supportive care administration are widely undisclosed and may lead to withholding of supportive care measures that can impact the quality of data that are generated. 9 The current survey helps to bridge the two by defining and providing strategies for administering supportive care in toxicity studies.…”

Section: Introductionmentioning

confidence: 99%

Supportive care for animals on toxicology studies: An industrial best practices survey conducted by the IQ 3Rs TPS CRO Outreach Working Group

Salian-Mehta

Wilson

Burr

et al. 2021

Toxicology Research and Application

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Contract Research Organizations (CROs) conducting toxicology studies on behalf of biopharmaceutical sponsors and others routinely provide supportive care for animals to minimize pain and distress on studies. A large number of guidance documents govern the care of experimental animals, however there is currently no uniform approach on the communication between sponsor and their CRO partners in providing a standard definition of and strategies for administering supportive care in toxicity studies. This survey was conducted by the CRO Outreach Working Group (WG), a part of the 3Rs Translational and Predictive Sciences (TPS) Leadership Group of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium), to better understand the provision of supportive care on nonclinical studies. The survey aimed to define supportive care strategies, identify alternatives to supportive care, and understand regulatory feedback and implications about supportive care decisions. The survey was distributed to members of the 3Rs Leadership Group of the IQ Consortium and several CRO partners, representing 35 organizations as potential respondents. The results of the survey from 13 respondents provided positive feedback that helped in highlighting the existing best practices for supportive care. Areas of enhancements identified included greater consistency in the inclusion of sponsor veterinarians on project teams for externalized studies, the timing of initiation of supportive care, and increased sharing of regulatory outcomes. Suggested best practices include creating a plan of action for veterinary care prior to study start, and enhancing information sharing regarding expected toxicities from previous study findings. Improved communication regarding supportive care will pave the way for enhanced 3Rs initiatives, refining the existing animal care paradigm and helping to ensure the most ethical toxicology study designs.

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Compliance and Regulatory Programs

Cited by 3 publications

References 43 publications

Transcriptomic signature, bioactivity and safety of a non-hepatotoxic analgesic generating AM404 in the midbrain PAG region

Transcriptomic signature, bioactivity and safety of a non-hepatotoxic analgesic generating AM404 in the midbrain PAG region

Ethical Principles and Rules in Experimental Animal Studies: A Comprehensive Review

Supportive care for animals on toxicology studies: An industrial best practices survey conducted by the IQ 3Rs TPS CRO Outreach Working Group

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