ALTERNATIVE ANIMAL TOXICITY STUDY .pptx

The document discusses alternatives to animal testing in research. It notes that while animals have traditionally been used for testing, this method is cruel, time-consuming, and not predictive of human outcomes. New alternative methods include in vitro, in silico, in chemico techniques using cells, tissues, organs-on-chips and computer modeling that can replace many animal tests in a more humane, effective and predictive way. Widespread adoption of alternative methods can improve both the ethics and accuracy of medical research.

Presented at INTERPHEX on March 21-23, 2017. Single use process technology is routinely used in the manufacture of pharmaceuticals and biopharmaceuticals. The potential for extractables and leachables from single use systems and their impact on patient safety are an important focus of drug manufacturers and regulators. While current regulatory guidelines and industry standards provide general direction on compound-specific safety assessments, they do not offer a comprehensive approach to safety evaluations of extractables and leachables. Smaller, emerging companies might not even be aware of the extent of the extractables and leachables data expected by regulatory authorities and that the FDA has issued warning letters in cases where the appropriate extractables and leachables studies were missing for a drug product. The author will describe a comprehensive approach to determine the impact single use process technology has on patient safety.

Various Stages of drug development, anaesthesia ,euthanasia, animals used for preclinical analysis, clinical trials, alternative methods for animal testing, blood withdrawal methods, ethical guidelines

ICH's mission to achieve greater harmonization in the interpretation and application of technical guidelines and requirements for product registration thereby reducing duplication of testing and reporting carried out during research and development of new medicines.

This presentation will give you overall idea about the topic.

PRECLINICAL TEST

Description and overview of various tests used to access the biocompatibility of biomaterials with the various body cells or organ/s.

Materi Seminar Sehari Mikrobiologi "Rapid Microbiological Methods" 05 Sept 2013 IPB Convention Center Bogor

In vivo is the Latin word which means with in the living body. When effects of various biological entities are tested on whole, living organism or cells, usually animals including humans and plants. Animal testing and clinical trials are major elements of in-vivo research. In vivo testing is often employed over in vitro because it is better suited for observing the overall effects of an experiment on a living subject in drug discovery. example, verification of efficacy in vivo is crucial, because in vitro assays can sometimes yield misleading results with drug. Harry Smith found that sterile filtrates of serum from animals infected with Bacillus anthracis were lethal for other animals, whereas extracts of culture fluid from the same organism grown in vitro were not. In microbiology Once cells are disrupted and individual parts are tested or analyzed, this is known as in vitro. In vitro studies within the glass, i.e., in a laboratory environment using test tubes, petri dishes, etc. Examples of investigations in vivo include: the pathogenesis of disease. In vitro toxicology:- The bridge exists between new drug discovery and drug development.- Provide information on mechanism of action of a drug Provides an early indication of the potential for some kinds of toxic effects, allowing a decision to terminate or to proceed further. In vitro methods are widely used for:- Screening and ranking chemicals Get a platform for animal studies for physiological actions Studying cell, tissue, or target specific effects Improve subsequent study design Advantages and Disadvantages:- Faster than in vivo studies Less expensive to run Less predictive of toxicity in intact organisms In vitro to in vivo extrapolation (IVIVE) refers to the qualitative or quantitative transposition of experimental results or observations made in vitro to predict phenomena in vivo, biological organisms. The problem of transposing in vitro results is particularly acute in areas such as toxicology where animal experiments are being phased out and are increasingly being replaced by alternative tests. Results obtained from in vitro experiments cannot often be directly applied to predict biological responses of organisms to chemical exposure in vivo. Therefore, it is extremely important to build a consistent and reliable in vitro to in vivo extrapolation method. Two solutions are now commonly accepted: Increasing the complexity of in vitro systems where multiple cells can interact with each other in order recapitulate cell-cell interactions present in tissues (as in "human on chip" systems). Using mathematical modeling to numerically simulate the behavior of a complex system, whereby in vitro data provides the parameter values for developing a model. The two approaches can be applied simultaneously allowing in vitro systems to provide adequate data for the development of mathematical models. To comply with push for the development of alternative testing methods.

Toxicity studies are generally performed to determine drug effects that cannot be evaluated through standard pharmacology profiles or that only occur with repeated administration. Most toxicity tests are performed in two species, such as a rodent and non-rodent, to avoid overlooking unexpected adverse effects before introducing new chemical entities into humans. While animal testing has faced controversy, alternatives using biotechnology tools such as transgenic animal models, cell cultures, and in silico methods are being developed wherever possible to reduce animal use. These alternative techniques include cell line techniques, full thickness skin models, and patch clamp methods to study ion channels at a cellular level.

The resistance of parasites to existing drugs and the availability of better technology platforms has driven the discovery of new drugs. Microfluidic devices have been used to facilitate faster screening of compounds, controlled sampling/sorting of whole animals, and automated behavioral pattern recognition. In most cases, drug effects on small creatures (e.g., Caenorhabditis elegans) are measuredelegant by a single parameter such as worm velocity or stroke frequency. We present a multi-parameter extraction method to characterize modes of paralysis in C. elegans over a longer duration. This was done using a microfluidic device featuring real-time imaging, exposing worms to four anthelmintic drugs at EC75, where 75% of the worm population is affected. We monitored the worms' behavior with metrics such as curls per second, types of paralyzation, mode frequency, and number/duration of active/immobilization periods. Differences were observed in how the worms paralyzed in the various drug environments at equivalent concentrations. This study highlights the importance of assessing drug effects on small animals with multiple parameters, measured at regular intervals over a prolonged period, to accurately detect resistance and adaptability in chemical environments. Roy Lycke, Archana Parashar, and Santosh Pandey, "Microfluidics-enabled method to identify modes of Caenorhabditis elegans paralysis in four anthelmintics", Biomicrofluidics 7, 064103 (2013). https://doi.org/10.1063/1.4829777 https://aip.scitation.org/doi/10.1063/1.4829777

Role of preclinical studies in drug discovery.pptx