The FDA New Animal Drug Approval Process
Rebecca A. Krimins in Learning from Disease in Pets, 2020
Additionally, researchers can assist start-up laboratories and pharmaceutical companies with the new animal drug approval process by conducting early discovery and proof-of-concept research in accordance with new animal drug approval standards (e.g., Good Laboratory Practices, GLPs), such that this research can be readily leveraged if approval is sought for a product conceived from that research. Early quality, GLP- or GCP-conforming research can even expedite the approval process by answering essential regulatory questions, especially for animal cell-based products. For example, investigations of the biodistribution and survival of a particular cell type conducted by a researcher under GLP regulations might be used to inform the requirements for target animal safety studies for a product derived from those cells, once the approval process begins.
Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date *
Valerio Voliani in Nanomaterials and Neoplasms, 2021
In this review we provide an up to date snapshot of nanomedicines either currently approved by the US FDA, or in the FDA clinical trials process. We define nanomedicines as therapeutic or imaging agents which comprise a nanoparticle in order to control the biodistribution, enhance the efficacy, or otherwise reduce toxicity of a drug or biologic. We identified 51 FDA-approved nanomedicines that met this definition and 77 products in clinical trials, with ∼40% of trials listed in clinicaltrials.gov started in 2014 or 2015. While FDA approved materials are heavily weighted to polymeric, liposomal, and nanocrystal formulations, there is a trend towards the development of more complex materials comprising micelles, protein-based NPs, and also the emergence of a variety of inorganic and metallic particles in clinical trials. We then provide an overview of the different material categories represented in our search, highlighting nanomedicines that have either been recently approved, or are already in clinical trials. We conclude with some comments on future perspectives for nanomedicines, which we expect to include more actively targeted materials, multi-functional materials (“theranostics”) and more complicated materials that blur the boundaries of traditional material categories. A key challenge for researchers, industry, and regulators is how to classify new materials and what additional testing (e.g., safety and toxicity) is required before products become available.
Dendrimer Nanocomposites for Cancer Therapy
Mansoor M. Amiji in Nanotechnology for Cancer Therapy, 2006
Understanding biodistribution is a key to success for any medication. Biodistribution is determined by the interactions between the properties of the medicine and the living biologic system. Therefore, to ensure that a therapeutic material has only one concerted action at the molecular level, molecules/particles/devices with identical properties are needed. Mixtures of materials will have fractions with different properties, each with an individual biodistribution (of which only an envelope is observed). Different fractions with differing properties of biodistribution can lead to different actions. In simple terms, only identical particles will have a well-defined biodistribution.
Hurdles of environmental risk assessment procedures for advanced therapy medicinal products: comparison between the European Union and the United States
Published in Critical Reviews in Toxicology, 2019
C. Iglesias-Lopez, M. Obach, A. Vallano, A. Agustí, J. Montané
Biodistribution assessments are also another key point for the ERA, as they provide information about the dissemination of the recombinant vector from the site of administration. This fact may influence the routes of shedding of the virus from the recipient, and therefore, the likelihood of transmission to third parties, including vertical transmission. Similarly to shedding assessments, biodistribution is usually part of the pivotal study and there is a minimum panel of tissues to be analyzed, apart from the ones considered necessary depending on the product and route of administration, i.e. blood, injection site(s), gonads, brain, liver, kidneys, lung, heart, and spleen (FDA Center for Biologics Evaluation and Research (CBER) 2018). If vector is detected in gonads, germline transmission studies should be performed (EMEA/273974/20 2006).
Cumulative administrations of gadolinium-based contrast agents: risks of accumulation and toxicity of linear vs macrocyclic agents
Published in Critical Reviews in Toxicology, 2019
Lara Chehabeddine, Tala Al Saleh, Marwa Baalbaki, Eman Saleh, Samia J. Khoury, Salem Hannoun
In vivo analysis of GBCAs still lacks information to fully assess stability. Biodistribution studies should therefore be the ultimate indicators of in vivo stability and toxicity (Tweedle et al. 1995). Although kinetic and thermodynamic studies showed gadoterate meglumine to be more stable than gadoteridol (Port et al. 2008), gadoteridol (a nonionic mGBCA) was speculated to have a lower Gd retention (Tweedle 2007). In contrast, the ionic lGBCA gadopentetate dimeglumine was more stable in vivo than the nonionic linear contrast gadodiamide, as predicted in vitro (Fretellier et al. 2011). Adding Ca2+ as an excipient to gadodiamide however, decreased Gd retention to less than ten times the value measured for gadoteridol and gadoterate meglumine.
Current status and advances in esophageal drug delivery technology: influence of physiological, pathophysiological and pharmaceutical factors
Published in Drug Delivery, 2023
Ai Wei Lim, Nicholas J. Talley, Marjorie M. Walker, Gert Storm, Susan Hua
Detailed safety and toxicology assessment is essential for clinical translation of any novel formulation (Hua et al., 2018). This is particularly important for pharmaceutical dosage forms containing components that have not yet been validated for safety in humans, as is often the case here with those designed for esophagus-related diseases. In addition to in vitro cellular studies, specialized toxicology studies in animal models need to be used to assess short-term and long-term toxicity. Biodistribution evaluation can also predict potential toxicological responses by determining factors such as off-target accumulation in healthy tissues as well as clearance mechanisms. Implementation of real-time imaging techniques (e.g. IVIS, MRI, CT) can allow improved understanding of the degree of interaction of esophageal targeting formulations with target and non-target organs and tissues after in vivo administration in longitudinal studies (Arms et al., 2018).
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