Safety pharmacology studies are conducted to help protect clinical trial participants and patients from potential adverse effects of pharmaceuticals. The objectives are to adopt a rational approach in study design and conduct based on a drug's properties and intended uses. Safety pharmacology focuses on detecting undesirable pharmacodynamic effects of new drugs on physiological functions like the central nervous, cardiovascular and respiratory systems. Studies are generally conducted using relevant animal models or test systems to derive scientifically valid information. Results inform subsequent toxicology, kinetics and clinical studies.
test item characterization of regulatory of toxicological studies SonaliJain736101
This document provides guidance on characterizing test items used in regulatory toxicology studies conducted in compliance with Good Laboratory Practice principles. It discusses the expectations for characterizing test items regarding transportation, receipt, identification, labeling, sampling, handling, storage, and disposal. The level of characterization may vary depending on the test item, study objectives, and development stage. Characterization should confirm the test item's identity and suitability for the study. Living organisms and medical devices may require unique characterization information. The document aims to promote a consistent approach to test item characterization across studies.
Safety pharmacology is a branch of pharmacology with its aim to predict the potential clinical risk profile of new chemical entities (NCEs).
It has the ability to predict the potential off-target drug effects on major organ systems which are associated with exposure in the therapeutic range and above.
As an essential part of the spectrum of drug discovery and development, safety pharmacology studies are generally conducted to determine the relative drug effect on main organs, including respiratory system, central nervous system, and cardiovascular system.Safety pharmacology is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials.
SP studies are described in the international conference on harmonization (ICH) S7A and S7B Guidelines.
This document discusses the requirements for an investigational new drug (IND) application. An IND is required to initiate clinical trials of an unapproved drug and must contain information on animal studies, manufacturing, and clinical trial protocols. The core battery of safety pharmacology studies evaluates effects on major organ systems like the cardiovascular, central nervous, and respiratory systems. These studies are designed to identify potential adverse effects and safety risks before human clinical trials.
This document discusses methods for assessing drug effects on renal and gastrointestinal systems in safety pharmacology studies. For renal function, in vivo mammalian models using rats and dogs are commonly used to assess glomerular function through clearance tests, tubular function through urine analysis, and hemodynamic function through blood flow measurements. In vitro and in silico models are also discussed. For gastrointestinal function, methods described include assessing gastric emptying and intestinal motility using in vitro tissue/organ baths and in vivo animal models, measuring gastric secretion in cell preparations and ligated rats, modeling nausea and emesis in ferrets and dogs, and measuring absorption in Caco-2 cell cultures and perfused intestinal segments of rats.
Herg assay,Structure, Various screening methods and AdvantagesUrvashi Shakarwal
The document discusses hERG assays, which are used to screen for compounds that may block the hERG potassium channel and prolong the heart's QT interval, potentially causing fatal arrhythmias. It describes the structure and function of the hERG channel, then summarizes various screening methods for hERG activity including electrophysiology, flux assays, fluorescence-based assays, and radioligand binding assays. These methods allow high-throughput screening of large numbers of compounds early in drug development to improve cardiovascular safety.
test item characterization of regulatory of toxicological studies SonaliJain736101
This document provides guidance on characterizing test items used in regulatory toxicology studies conducted in compliance with Good Laboratory Practice principles. It discusses the expectations for characterizing test items regarding transportation, receipt, identification, labeling, sampling, handling, storage, and disposal. The level of characterization may vary depending on the test item, study objectives, and development stage. Characterization should confirm the test item's identity and suitability for the study. Living organisms and medical devices may require unique characterization information. The document aims to promote a consistent approach to test item characterization across studies.
Safety pharmacology is a branch of pharmacology with its aim to predict the potential clinical risk profile of new chemical entities (NCEs).
It has the ability to predict the potential off-target drug effects on major organ systems which are associated with exposure in the therapeutic range and above.
As an essential part of the spectrum of drug discovery and development, safety pharmacology studies are generally conducted to determine the relative drug effect on main organs, including respiratory system, central nervous system, and cardiovascular system.Safety pharmacology is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials.
SP studies are described in the international conference on harmonization (ICH) S7A and S7B Guidelines.
This document discusses the requirements for an investigational new drug (IND) application. An IND is required to initiate clinical trials of an unapproved drug and must contain information on animal studies, manufacturing, and clinical trial protocols. The core battery of safety pharmacology studies evaluates effects on major organ systems like the cardiovascular, central nervous, and respiratory systems. These studies are designed to identify potential adverse effects and safety risks before human clinical trials.
This document discusses methods for assessing drug effects on renal and gastrointestinal systems in safety pharmacology studies. For renal function, in vivo mammalian models using rats and dogs are commonly used to assess glomerular function through clearance tests, tubular function through urine analysis, and hemodynamic function through blood flow measurements. In vitro and in silico models are also discussed. For gastrointestinal function, methods described include assessing gastric emptying and intestinal motility using in vitro tissue/organ baths and in vivo animal models, measuring gastric secretion in cell preparations and ligated rats, modeling nausea and emesis in ferrets and dogs, and measuring absorption in Caco-2 cell cultures and perfused intestinal segments of rats.
Herg assay,Structure, Various screening methods and AdvantagesUrvashi Shakarwal
The document discusses hERG assays, which are used to screen for compounds that may block the hERG potassium channel and prolong the heart's QT interval, potentially causing fatal arrhythmias. It describes the structure and function of the hERG channel, then summarizes various screening methods for hERG activity including electrophysiology, flux assays, fluorescence-based assays, and radioligand binding assays. These methods allow high-throughput screening of large numbers of compounds early in drug development to improve cardiovascular safety.
This document discusses safety pharmacology studies, with a focus on respiratory and central nervous system safety pharmacology. It defines safety pharmacology studies as investigating potential undesirable pharmacological effects of substances on physiological functions. For respiratory safety pharmacology, the core battery studies measure respiratory rate, tidal volume, and oxygen saturation. Supplementary studies measure airway resistance and lung compliance. For CNS safety pharmacology, core studies evaluate behavior, locomotor activity, motor coordination, and seizure liability. Safety pharmacology aims to identify risks and inform safe starting doses in clinical trials.
This presentation provides a knowledge about Safety Pharmacology, It's aim & objectives, issues, consideration in selection and design of study and test study, duration of study, various studies involved in safety pharmacology, its guidelines, preclinical safety pharmacology. An assignment for the subject, Clinical Research and Pharmacovigilance, 1st year M.Pharm, 2nd semester.
The document outlines the studies needed for an Investigational New Drug (IND) submission to the FDA. An IND application must contain information on animal pharmacology and toxicology studies, chemistry and manufacturing, and clinical protocols. It provides a flow chart showing the various preclinical studies required, including chemical and physical properties, biological studies, pharmacology, toxicology, and formulation studies. The goal of the preclinical studies is to generate data for the safety assessment of the new drug in humans.
This document provides guidelines for safety pharmacology studies for human pharmaceuticals from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). The guidelines discuss the objectives, scope, general principles, test systems, experimental design, dose levels/concentrations, duration of studies, and studies on metabolites for safety pharmacology evaluations. The goal is to help protect clinical trial participants and patients by identifying potential adverse effects of pharmaceuticals early in development.
The document discusses the Investigational New Drug (IND) application process with the FDA. An IND application allows a company to ship an experimental drug across state lines and begin clinical trials. It must include preclinical data to show the drug is safe for initial human use as well as protocols for proposed studies. The FDA reviews the IND for 30 days before clinical trials may begin to ensure subject safety. The overall goal of an IND is to facilitate testing of new drugs while protecting clinical trial participants.
This document summarizes a seminar on safety pharmacology. It defines safety pharmacology and outlines the core battery of studies, which evaluate effects on the central nervous, cardiovascular and respiratory systems. It describes when safety pharmacology studies are needed at different stages of drug development and under various conditions. Guidelines for conducting the studies from organizations like ICH are also discussed.
The document discusses safety pharmacology studies that are conducted to evaluate potential adverse effects of pharmaceutical substances on vital organ systems. It describes the safety pharmacology core battery that investigates effects on the central nervous, cardiovascular and respiratory systems. Follow up studies provide more in-depth understanding of effects on these systems. Supplemental studies evaluate effects on other organ systems like renal, gastrointestinal and immune systems. A variety of evaluation methods are used like functional observation, electrocardiography, plethysmography and biomarkers. Conditions where safety pharmacology studies may not be needed are also outlined.
alternative methods of animal toxicity.pptxashharnomani
Alternative methods to animal toxicity testing are needed because animal testing can cause suffering. Some alternative methods include computer modeling, cell and tissue cultures, and organ chips. Computer modeling uses computer programs to simulate biological effects and predict toxicity without animal testing. Cell and tissue cultures grow isolated cells and tissues in vitro to study toxicity. Organ chips are microfluidic devices that contain living cells arranged to simulate organ-level functions, allowing tests on human-relevant systems without whole animals. These alternative methods can help reduce and replace animal use in toxicity testing.
Alternative methods to animal toxicity testingSachin Sharma
This document presents information on alternative methods to animal toxicity testing. It discusses the need for alternatives due to the harms animals face in toxicity testing. The 3Rs principles of reduction, refinement and replacement are explained, which aim to minimize animal use and suffering. The validation process for new alternative methods through organizations like ECVAM is covered. Specific alternative methods mentioned include in vitro tests like the Ames test and HET-CAM test, in silico methods, and mathematical models. The HET-CAM test for eye irritation is described in more detail.
Female reproductive toxicity studies acoording to SECHDULE Y AND ICH S5R3SONALPANDE5
This document outlines the design of female reproductive toxicity studies according to ICH S5R3 guidelines. It discusses three segments of studies: Segment I focuses on fertility and general reproductive performance; Segment II examines teratogenicity; and Segment III is a perinatal study looking at prenatal and postnatal effects. For each segment, the document describes the study design, including species used, dosage levels, duration of treatment, and key parameters measured such as litter outcomes, growth, and gross pathology observations of dams and pups. The goal is to comprehensively evaluate potential effects of test substances on female fertility and development.
The basic aspects of drug discovery starts from target discovery and validation further going to lead identification and optimization. In this particular slide discussion is regarding the target discovery and the tools that have been utilized in this process.
This document provides information about reproductive toxicology studies. It discusses that reproductive toxicology refers to alterations that affect the reproductive system in males and females. The document outlines the three segments of reproductive toxicology studies - effects on fertility in males and non-pregnant females, developmental toxicity in pregnant or lactating females, and prenatal and post-natal studies assessing fertility and early embryonic development. It provides examples of study designs and parameters assessed in reproductive toxicology studies, including dosing, observation of parental animals and offspring, and histopathological examination.
The document describes the hERG assay, which is used to test for potential drug-induced prolongation of the QT interval. It discusses the hERG gene and potassium channel, how mutations can cause long QT syndrome. It then summarizes three methods for conducting the hERG assay: electrophysiological assay using whole-cell patch clamping, Fluorometric imaging plate reader-based thallium flux assay, and radioligand binding with 35S-MK-499. Details are provided on cell preparation and protocol for each type of hERG assay.
Drug development is a long, expensive, and high-risk process that takes an average of 10-15 years. It involves preclinical research in animals and humans to test safety and efficacy. Clinical trials in humans have 4 phases - Phase I tests safety in small groups, Phase II explores efficacy in small patient groups, Phase III tests in large patient groups to confirm efficacy and safety for approval, and Phase IV occurs after approval to monitor long-term effects. Only about 1 in 10 drugs that enter clinical trials will ultimately receive regulatory approval due to the high costs and failure rates of drug development. Rigorous testing and regulatory review are required to bring a new drug to market globally.
The document discusses the economics of drug discovery. It notes that drug discovery takes 3-20 years and costs several billion to tens of billions of dollars. The process involves determining the causes of diseases and finding compounds for treatment. Drugs then undergo pre-clinical and clinical trials, with the three phases of clinical trials costing upwards of $100 million alone. A new 2020 study estimated the median cost of getting a new drug to market is $985 million, with the average being $1.3 billion. This is lower than previous estimates of $2.8 billion. The document also outlines the present costs involved in various stages of drug discovery and development.
This document provides guidance on test item characterization as outlined in the OECD Principles of Good Laboratory Practice. It discusses the characterization, transportation, receipt, identification, labeling, sampling, handling, storage, archiving and disposal of test items. The key aspects covered include documenting the transport conditions, assessing integrity upon receipt, verifying identity, maintaining unique identification, ensuring proper storage conditions, characterizing test item identity, purity, stability for each batch, archiving samples, and disposing of items according to regulations. Special considerations are given to certain test item types like early stage items, organisms, medical devices and radio labeled substances.
Toxicokinetic evaluation in preclinical studies.pptxARSHIKHANAM4
1. Toxicokinetics is the study of how toxic substances are affected by the body in terms of absorption, distribution, metabolism, and excretion. It applies pharmacokinetic principles to doses used in toxicology testing.
2. The primary objective of toxicokinetic evaluation in preclinical studies is to describe systemic exposure levels in animals and relate this to toxicity findings to assess clinical safety. Secondary objectives include supporting species and dose selection for toxicity studies.
3. Toxicokinetic data is collected in various required preclinical safety studies, including repeat-dose toxicity studies, reproduction toxicity studies, and genotoxicity studies, to interpret results and demonstrate drug exposure.
This document discusses various methods for pharmacological and toxicological screening of substances. It provides details on:
- Types of toxicity testing including acute, sub-acute, sub-chronic, and chronic toxicity tests.
- Methods for determining lethal dose 50 (LD50) and lethal concentration 50 (LC50) values which represent doses/concentrations that are lethal to 50% of test subjects.
- Specific acute oral toxicity testing methods like Karber's method, Miller-Tainter method, and up-and-down method.
- Testing procedures which involve administering graduated doses of a test substance to rodents and making observations to determine health hazards.
This document describes guidelines for acute inhalation toxicity studies using rats. It discusses two study types: the traditional LC50 protocol and the concentration x time (C x t) protocol. The traditional protocol exposes animals to a single concentration for 4 hours (mice) or 6 hours (rats). The C x t protocol exposes animals to multiple concentrations for varying durations between 5-240 minutes. Both aim to classify chemicals according to their acute inhalation toxicity and provide data for risk assessment. The guidelines cover topics like animal selection, exposure chambers, monitoring exposure conditions, and procedures for each study type.
This document outlines objectives and principles of safety pharmacology studies. It discusses using such studies to protect clinical trial participants from potential adverse drug effects. The document describes the scope of safety pharmacology, considerations for test systems and study design, and examples of core safety pharmacology assessments of the central nervous, cardiovascular and respiratory systems. Evaluation methods are also summarized for each system. The document concludes by listing some references on safety pharmacology guidelines.
This document provides guidelines for safety pharmacology studies for human pharmaceuticals. It defines safety pharmacology as studies investigating potential undesirable pharmacological effects on physiological functions. The guidelines describe a core battery of studies on the central nervous, cardiovascular and respiratory systems to be conducted prior to first human administration. Follow up and supplemental studies may be warranted based on properties, class effects or safety concerns. The timing of studies in relation to clinical development is outlined.
This guideline was developed to help protect clinical trial participants and patients receiving marketed products from potential adverse effects of pharmaceuticals, while avoiding unnecessary use of animals and other resources. This guideline provides a definition, general principles and recommendations for safety pharmacology studies
This document discusses safety pharmacology studies, with a focus on respiratory and central nervous system safety pharmacology. It defines safety pharmacology studies as investigating potential undesirable pharmacological effects of substances on physiological functions. For respiratory safety pharmacology, the core battery studies measure respiratory rate, tidal volume, and oxygen saturation. Supplementary studies measure airway resistance and lung compliance. For CNS safety pharmacology, core studies evaluate behavior, locomotor activity, motor coordination, and seizure liability. Safety pharmacology aims to identify risks and inform safe starting doses in clinical trials.
This presentation provides a knowledge about Safety Pharmacology, It's aim & objectives, issues, consideration in selection and design of study and test study, duration of study, various studies involved in safety pharmacology, its guidelines, preclinical safety pharmacology. An assignment for the subject, Clinical Research and Pharmacovigilance, 1st year M.Pharm, 2nd semester.
The document outlines the studies needed for an Investigational New Drug (IND) submission to the FDA. An IND application must contain information on animal pharmacology and toxicology studies, chemistry and manufacturing, and clinical protocols. It provides a flow chart showing the various preclinical studies required, including chemical and physical properties, biological studies, pharmacology, toxicology, and formulation studies. The goal of the preclinical studies is to generate data for the safety assessment of the new drug in humans.
This document provides guidelines for safety pharmacology studies for human pharmaceuticals from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). The guidelines discuss the objectives, scope, general principles, test systems, experimental design, dose levels/concentrations, duration of studies, and studies on metabolites for safety pharmacology evaluations. The goal is to help protect clinical trial participants and patients by identifying potential adverse effects of pharmaceuticals early in development.
The document discusses the Investigational New Drug (IND) application process with the FDA. An IND application allows a company to ship an experimental drug across state lines and begin clinical trials. It must include preclinical data to show the drug is safe for initial human use as well as protocols for proposed studies. The FDA reviews the IND for 30 days before clinical trials may begin to ensure subject safety. The overall goal of an IND is to facilitate testing of new drugs while protecting clinical trial participants.
This document summarizes a seminar on safety pharmacology. It defines safety pharmacology and outlines the core battery of studies, which evaluate effects on the central nervous, cardiovascular and respiratory systems. It describes when safety pharmacology studies are needed at different stages of drug development and under various conditions. Guidelines for conducting the studies from organizations like ICH are also discussed.
The document discusses safety pharmacology studies that are conducted to evaluate potential adverse effects of pharmaceutical substances on vital organ systems. It describes the safety pharmacology core battery that investigates effects on the central nervous, cardiovascular and respiratory systems. Follow up studies provide more in-depth understanding of effects on these systems. Supplemental studies evaluate effects on other organ systems like renal, gastrointestinal and immune systems. A variety of evaluation methods are used like functional observation, electrocardiography, plethysmography and biomarkers. Conditions where safety pharmacology studies may not be needed are also outlined.
alternative methods of animal toxicity.pptxashharnomani
Alternative methods to animal toxicity testing are needed because animal testing can cause suffering. Some alternative methods include computer modeling, cell and tissue cultures, and organ chips. Computer modeling uses computer programs to simulate biological effects and predict toxicity without animal testing. Cell and tissue cultures grow isolated cells and tissues in vitro to study toxicity. Organ chips are microfluidic devices that contain living cells arranged to simulate organ-level functions, allowing tests on human-relevant systems without whole animals. These alternative methods can help reduce and replace animal use in toxicity testing.
Alternative methods to animal toxicity testingSachin Sharma
This document presents information on alternative methods to animal toxicity testing. It discusses the need for alternatives due to the harms animals face in toxicity testing. The 3Rs principles of reduction, refinement and replacement are explained, which aim to minimize animal use and suffering. The validation process for new alternative methods through organizations like ECVAM is covered. Specific alternative methods mentioned include in vitro tests like the Ames test and HET-CAM test, in silico methods, and mathematical models. The HET-CAM test for eye irritation is described in more detail.
Female reproductive toxicity studies acoording to SECHDULE Y AND ICH S5R3SONALPANDE5
This document outlines the design of female reproductive toxicity studies according to ICH S5R3 guidelines. It discusses three segments of studies: Segment I focuses on fertility and general reproductive performance; Segment II examines teratogenicity; and Segment III is a perinatal study looking at prenatal and postnatal effects. For each segment, the document describes the study design, including species used, dosage levels, duration of treatment, and key parameters measured such as litter outcomes, growth, and gross pathology observations of dams and pups. The goal is to comprehensively evaluate potential effects of test substances on female fertility and development.
The basic aspects of drug discovery starts from target discovery and validation further going to lead identification and optimization. In this particular slide discussion is regarding the target discovery and the tools that have been utilized in this process.
This document provides information about reproductive toxicology studies. It discusses that reproductive toxicology refers to alterations that affect the reproductive system in males and females. The document outlines the three segments of reproductive toxicology studies - effects on fertility in males and non-pregnant females, developmental toxicity in pregnant or lactating females, and prenatal and post-natal studies assessing fertility and early embryonic development. It provides examples of study designs and parameters assessed in reproductive toxicology studies, including dosing, observation of parental animals and offspring, and histopathological examination.
The document describes the hERG assay, which is used to test for potential drug-induced prolongation of the QT interval. It discusses the hERG gene and potassium channel, how mutations can cause long QT syndrome. It then summarizes three methods for conducting the hERG assay: electrophysiological assay using whole-cell patch clamping, Fluorometric imaging plate reader-based thallium flux assay, and radioligand binding with 35S-MK-499. Details are provided on cell preparation and protocol for each type of hERG assay.
Drug development is a long, expensive, and high-risk process that takes an average of 10-15 years. It involves preclinical research in animals and humans to test safety and efficacy. Clinical trials in humans have 4 phases - Phase I tests safety in small groups, Phase II explores efficacy in small patient groups, Phase III tests in large patient groups to confirm efficacy and safety for approval, and Phase IV occurs after approval to monitor long-term effects. Only about 1 in 10 drugs that enter clinical trials will ultimately receive regulatory approval due to the high costs and failure rates of drug development. Rigorous testing and regulatory review are required to bring a new drug to market globally.
The document discusses the economics of drug discovery. It notes that drug discovery takes 3-20 years and costs several billion to tens of billions of dollars. The process involves determining the causes of diseases and finding compounds for treatment. Drugs then undergo pre-clinical and clinical trials, with the three phases of clinical trials costing upwards of $100 million alone. A new 2020 study estimated the median cost of getting a new drug to market is $985 million, with the average being $1.3 billion. This is lower than previous estimates of $2.8 billion. The document also outlines the present costs involved in various stages of drug discovery and development.
This document provides guidance on test item characterization as outlined in the OECD Principles of Good Laboratory Practice. It discusses the characterization, transportation, receipt, identification, labeling, sampling, handling, storage, archiving and disposal of test items. The key aspects covered include documenting the transport conditions, assessing integrity upon receipt, verifying identity, maintaining unique identification, ensuring proper storage conditions, characterizing test item identity, purity, stability for each batch, archiving samples, and disposing of items according to regulations. Special considerations are given to certain test item types like early stage items, organisms, medical devices and radio labeled substances.
Toxicokinetic evaluation in preclinical studies.pptxARSHIKHANAM4
1. Toxicokinetics is the study of how toxic substances are affected by the body in terms of absorption, distribution, metabolism, and excretion. It applies pharmacokinetic principles to doses used in toxicology testing.
2. The primary objective of toxicokinetic evaluation in preclinical studies is to describe systemic exposure levels in animals and relate this to toxicity findings to assess clinical safety. Secondary objectives include supporting species and dose selection for toxicity studies.
3. Toxicokinetic data is collected in various required preclinical safety studies, including repeat-dose toxicity studies, reproduction toxicity studies, and genotoxicity studies, to interpret results and demonstrate drug exposure.
This document discusses various methods for pharmacological and toxicological screening of substances. It provides details on:
- Types of toxicity testing including acute, sub-acute, sub-chronic, and chronic toxicity tests.
- Methods for determining lethal dose 50 (LD50) and lethal concentration 50 (LC50) values which represent doses/concentrations that are lethal to 50% of test subjects.
- Specific acute oral toxicity testing methods like Karber's method, Miller-Tainter method, and up-and-down method.
- Testing procedures which involve administering graduated doses of a test substance to rodents and making observations to determine health hazards.
This document describes guidelines for acute inhalation toxicity studies using rats. It discusses two study types: the traditional LC50 protocol and the concentration x time (C x t) protocol. The traditional protocol exposes animals to a single concentration for 4 hours (mice) or 6 hours (rats). The C x t protocol exposes animals to multiple concentrations for varying durations between 5-240 minutes. Both aim to classify chemicals according to their acute inhalation toxicity and provide data for risk assessment. The guidelines cover topics like animal selection, exposure chambers, monitoring exposure conditions, and procedures for each study type.
This document outlines objectives and principles of safety pharmacology studies. It discusses using such studies to protect clinical trial participants from potential adverse drug effects. The document describes the scope of safety pharmacology, considerations for test systems and study design, and examples of core safety pharmacology assessments of the central nervous, cardiovascular and respiratory systems. Evaluation methods are also summarized for each system. The document concludes by listing some references on safety pharmacology guidelines.
This document provides guidelines for safety pharmacology studies for human pharmaceuticals. It defines safety pharmacology as studies investigating potential undesirable pharmacological effects on physiological functions. The guidelines describe a core battery of studies on the central nervous, cardiovascular and respiratory systems to be conducted prior to first human administration. Follow up and supplemental studies may be warranted based on properties, class effects or safety concerns. The timing of studies in relation to clinical development is outlined.
This guideline was developed to help protect clinical trial participants and patients receiving marketed products from potential adverse effects of pharmaceuticals, while avoiding unnecessary use of animals and other resources. This guideline provides a definition, general principles and recommendations for safety pharmacology studies
This document outlines guidelines for safety pharmacology studies. It defines safety pharmacology as evaluating undesirable pharmacodynamic properties that may impact human safety. The objectives are to identify potential adverse effects and investigate mechanisms. The guidelines provide recommendations on study design, test systems, dose levels, duration and core battery assessments of cardiovascular, respiratory and central nervous systems. Follow-up studies may further explore areas of concern identified. Application of good laboratory practice depends on the study purpose and potential implications for safety. The overall aim is to rationally assess pharmaceuticals and protect clinical trial and marketed product users from adverse effects.
Safety pharmacology studies in drug developmentAnkita
In the given ppt we get idea about safety pharmacology studies. learn why safety pharmacology is important. concept of safety pharmacology, also get the knowledge from where safety pharmacology is originated
safety pharmacology is the branch of pharmacology specializing in detecting and investigating potential undesirable pharmacodynamic effects of a new chemical on physiological functions .
the content of this presentation is as follows
- introduction
- definition
- history
- ICH - guidelines
- refrences
Preclinical trials involve testing new drugs and medical devices on animals before human testing to assess safety and efficacy. They include various studies such as screening tests, isolated organ tests, and toxicity tests on rodents and larger animals. The goals are to determine dosing, identify adverse effects, and collect sufficient safety data to file for approval to begin clinical trials in humans under good laboratory practices. Preclinical studies help establish that initial human trials can reasonably proceed safely.
Safety pharmacology aims to identify adverse effects of drugs prior to clinical trials through guidelines established by the ICH. The antihistamine terfenadine was found to cause a rare but lethal cardiac effect and highlighted the need for improved preclinical safety testing. Safety pharmacology studies objectives are to detect undesirable pharmacodynamic properties and adverse effects observed in toxicology and help inform decisions about beginning human testing. A variety of in vitro and ex vivo methods are recommended including isolated tissue and cell-based assays, and zebrafish and stem cell models to comprehensively evaluate a new drug's safety profile.
This document discusses safety pharmacology considerations for oncology drugs and biologics according to ICH S7A, S9, and S6 guidelines. It states that standalone safety pharmacology studies are generally not needed before clinical trials for cytotoxic cancer drugs or biologics, though studies may help explain unexpected toxicities. Nonclinical evaluations should assess effects on vital organs and include clinical observations and electrocardiograms in toxicology studies. Three case studies examine when additional nonclinical studies may or may not provide useful information based on findings from clinical trials or toxicology.
This document discusses the process of generating safety data during drug development. It describes the three main phases - drug discovery, preclinical, and clinical trial phases. The preclinical phase involves pharmacodynamics, pharmacokinetic, and toxicological studies in animals over 1.5-2 years. These studies evaluate absorption, distribution, metabolism, excretion, toxicity, and help establish a safety profile before human trials. The clinical trial phase involves 4 phases to test safety and efficacy in humans. After approval, phase 4 surveillance continues to monitor performance and adverse effects through periodic safety reports.
This document provides guidelines for safety pharmacology and toxicology studies for pharmaceutical products. It outlines the objectives and types of studies recommended at different stages of clinical development, including safety pharmacology core battery studies, follow-up studies, reproductive and developmental toxicity studies, and human studies. Test systems, dose levels, durations, endpoints, and good laboratory practice standards are discussed for each type of nonclinical study.
The document discusses safety pharmacology screening methods for the central nervous system, cardiovascular system, and respiratory system. It outlines the objectives and categories of safety pharmacology studies, as well as the core battery tests and evaluation methods for each system. These include tests like electrocardiography, plethysmography, and the hERG assay to identify potential adverse effects of new drug candidates prior to clinical trials.
This document outlines the requirements and contents of an Investigator's Brochure (IB), which provides investigators involved in clinical trials with information on the investigational product. The IB includes a summary of relevant nonclinical and clinical data, including pharmacology, toxicology from animal studies, pharmacokinetics in humans, safety and efficacy results from previous clinical trials, and marketing experience with the product. It also provides guidance to investigators on conducting the clinical trial safely and effectively. The goal of the IB is to inform investigators about the rationale for the clinical trial and enable them to independently assess the risk-benefit of the investigational product.
Assignment on Toxicokinetics- Toxicokinetic evaluation in preclinical studies, saturation kinetics Importance and applications of toxicokinetic studies. Alternative methods to animal toxicity testing.
This document provides an overview of the regulatory guidelines for developing and marketing biologics in Europe. It discusses the EU guidelines for non-clinical and clinical studies from trials through approval. For non-clinical studies, the CHMP has adopted ICH S6 and its addendum which provides guidance on species selection, study design, immunogenicity, reproductive/developmental toxicity, and carcinogenicity assessments. Clinical studies must comply with the Clinical Trials Directive and guidelines on GCP, informed consent, data handling and confidentiality. The marketing authorization application process is similar to other products but requires additional information specific to biologics manufacturing.
Pre-clinical drug development involves several key stages: high throughput screening to identify potential drug candidates, toxicology studies in animal models to determine safety, pharmacological profiling to understand mechanisms of action, and calculating initial human doses. The overall goals are to obtain sufficient data on safety, tolerability and efficacy to receive regulatory approval from the FDA to begin clinical trials in humans. Pre-clinical studies provide critical data required for an Investigational New Drug (IND) application to the FDA.
This document provides an overview of an investigator's brochure (IB) for a clinical trial. The IB is intended to inform investigators about the investigational product and provide safety information. It includes a summary of relevant non-clinical and clinical data, including pharmacology, toxicology, pharmacokinetics, safety and efficacy findings from animal and human studies. The IB also describes the formulation, storage and manufacturing of the investigational product as well as guidance for investigators on risks, adverse reactions and precautions for the clinical trial.
S3A: NOTE FOR GUIDANCE ON TOXICOKINETICS: THE ASSESSMENT OF SYSTEMIC EXPOSURE IN TOXICITY STUDIES
S3B: PHARMACOKINETICS: GUIDANCE FOR REPEATED DOSE TISSUE DISTRIBUTION STUDIES
The document summarizes various screening methods used to evaluate immunomodulators. It discusses in vivo methods like acute systemic anaphylaxis in rats and delayed type hypersensitivity reaction in rats. It also discusses in vitro methods like inhibition of histamine release from mast cells and neutrophil locomotion assays. The document provides details of various protocols used for screening immunomodulators.
This document provides an overview of toxicology and its types. It discusses the history and basic definitions of toxicology. It describes the importance of dose and outlines the major purposes and routes of exposure in toxicology. It then summarizes the general types of toxicology, including analytical, applied, clinical, veterinary, forensic, environmental, and industrial toxicology. Finally, it discusses the major areas of specialization in toxicology, including mechanistic, regulatory, and descriptive toxicology.
Proteomics is the study of proteins, including their composition, structure, function and interactions. It can be used to identify protein-protein interactions and complexes. Expression proteomics analyzes protein quantification and how levels are controlled. Proteomics has applications in new drug discovery by identifying proteins involved in diseases and developing drugs that target or inactivate those proteins. Genomics studies genomes and all their genes, DNA, and proteomes. It has applications in medicine, microbiology, forensics, agriculture and more. Metabolomics studies small molecule metabolites within cells and biofluids and their interactions, with applications in pharmacology, toxicology and functional genomics. Nutrigenomics examines how food constituents affect gene expression and identifies
This document provides information about reproductive toxicology testing guidelines. It discusses what reproductive toxicology is, key aspects of OECD Guideline 422 for testing chemicals for reproductive toxicity effects, and describes the various components involved in male and female reproductive toxicity studies. Some of the main points covered include dosing males for 4 weeks prior to mating and continuing through mating, dosing females throughout mating and pregnancy, examining fertility rates, litter parameters, and conducting gross and histopathological examinations of reproductive organs.
This document provides an overview of cell lines and cell culture. It discusses what cell lines are, how they are established from primary cultures, and how they can become cell strains. It also describes culture conditions, types of cell lines (finite vs continuous), nomenclature, selecting appropriate cell lines based on experimental needs, biosafety levels, cell culture hood and incubator setup. The document is intended as an introduction to cell lines and basic cell culture techniques.
Chronopharmacology is the science dealing with the effects of drugs over biological rhythms and periodicities. It aims to optimize drug effects and minimize adverse effects by timing medication intake relative to biological rhythms. Key aspects include chronopharmacokinetics, which studies temporal changes in drug absorption, distribution, metabolism and excretion. Many diseases have circadian rhythms that impact symptoms. Chronotherapy matches treatment timing to the intrinsic timing of illness for improved outcomes. Applications include timing cardiovascular drugs to morning peaks in events, and asthma drugs to nighttime attacks. Cancer therapies also consider circadian rhythms of tumor vs normal cells.
This document provides an introduction to pharmacoeconomics. It defines pharmacoeconomics as a branch of health economics concerned with the costs and benefits of pharmaceutical products and services. The document outlines the need for pharmacoeconomics to optimize resource allocation and make efficient choices when resources are limited. It also describes different types of economic evaluations used in pharmacoeconomics like cost-minimization analysis, cost-effectiveness analysis, cost-benefit analysis, and cost-utility analysis.
Are you looking for a long-lasting solution to your missing tooth?
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Breast cancer: Post menopausal endocrine therapyDr. Sumit KUMAR
Breast cancer in postmenopausal women with hormone receptor-positive (HR+) status is a common and complex condition that necessitates a multifaceted approach to management. HR+ breast cancer means that the cancer cells grow in response to hormones such as estrogen and progesterone. This subtype is prevalent among postmenopausal women and typically exhibits a more indolent course compared to other forms of breast cancer, which allows for a variety of treatment options.
Diagnosis and Staging
The diagnosis of HR+ breast cancer begins with clinical evaluation, imaging, and biopsy. Imaging modalities such as mammography, ultrasound, and MRI help in assessing the extent of the disease. Histopathological examination and immunohistochemical staining of the biopsy sample confirm the diagnosis and hormone receptor status by identifying the presence of estrogen receptors (ER) and progesterone receptors (PR) on the tumor cells.
Staging involves determining the size of the tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastasis (M). The American Joint Committee on Cancer (AJCC) staging system is commonly used. Accurate staging is critical as it guides treatment decisions.
Treatment Options
Endocrine Therapy
Endocrine therapy is the cornerstone of treatment for HR+ breast cancer in postmenopausal women. The primary goal is to reduce the levels of estrogen or block its effects on cancer cells. Commonly used agents include:
Selective Estrogen Receptor Modulators (SERMs): Tamoxifen is a SERM that binds to estrogen receptors, blocking estrogen from stimulating breast cancer cells. It is effective but may have side effects such as increased risk of endometrial cancer and thromboembolic events.
Aromatase Inhibitors (AIs): These drugs, including anastrozole, letrozole, and exemestane, lower estrogen levels by inhibiting the aromatase enzyme, which converts androgens to estrogen in peripheral tissues. AIs are generally preferred in postmenopausal women due to their efficacy and safety profile compared to tamoxifen.
Selective Estrogen Receptor Downregulators (SERDs): Fulvestrant is a SERD that degrades estrogen receptors and is used in cases where resistance to other endocrine therapies develops.
Combination Therapies
Combining endocrine therapy with other treatments enhances efficacy. Examples include:
Endocrine Therapy with CDK4/6 Inhibitors: Palbociclib, ribociclib, and abemaciclib are CDK4/6 inhibitors that, when combined with endocrine therapy, significantly improve progression-free survival in advanced HR+ breast cancer.
Endocrine Therapy with mTOR Inhibitors: Everolimus, an mTOR inhibitor, can be added to endocrine therapy for patients who have developed resistance to aromatase inhibitors.
Chemotherapy
Chemotherapy is generally reserved for patients with high-risk features, such as large tumor size, high-grade histology, or extensive lymph node involvement. Regimens often include anthracyclines and taxanes.
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The benefits of an ePCR solution should extend to the whole EMS organization, not just certain groups of people or certain departments. It should provide more than just a form for entering and a database for storing information. It should also include a workflow of how information is communicated, used and stored across the entire organization.
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Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
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Nano-gold for Cancer Therapy chemistry investigatory projectSIVAVINAYAKPK
chemistry investigatory project
The development of nanogold-based cancer therapy could revolutionize oncology by providing a more targeted, less invasive treatment option. This project contributes to the growing body of research aimed at harnessing nanotechnology for medical applications, paving the way for future clinical trials and potential commercial applications.
Cancer remains one of the leading causes of death worldwide, prompting the need for innovative treatment methods. Nanotechnology offers promising new approaches, including the use of gold nanoparticles (nanogold) for targeted cancer therapy. Nanogold particles possess unique physical and chemical properties that make them suitable for drug delivery, imaging, and photothermal therapy.
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdfrightmanforbloodline
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
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Lecture 6 -- Memory 2015.pptlearning occurs when a stimulus (unconditioned st...AyushGadhvi1
learning occurs when a stimulus (unconditioned stimulus) eliciting a response (unconditioned response) • is paired with another stimulus (conditioned stimulus)
2. Objectives of the Guideline
To help and protect clinical trial participants and patients receiving marketed
products from potential adverse effects of pharmaceuticals, while avoiding
unnecessary use of animals and other resources.
General Principle
To adopt a rational approach when selecting and conducting safety pharmacology
studies.
• Rational Approach in Design and Conduct Based on Pharmaceutical’s Properties
and Uses
• Scientifically Valid Methods
• Use of New Technologies and Methodologies is Encouraged
• Potential to Incorporate SP End points into Toxicology, Kinetics, Clinical studies
etc.
3. DEFINATION
• Safety pharmacology is a branch of pharmacology specializing in
detecting and investigating potential undesirable pharmacodynamic
effects of new chemical entities on physiological functions in relation to
exposure in the therapeutic range and above .
• Pharmacology studies have been performed worldwide for many years
as part the non-clinical evaluation of pharmaceuticals for human use.
4. • Pharmacodynamic studies can be divided into three categories :-
• Primary pharmacodynamics
• Secondary pharmacodynamics
• Studies on the mode of action and/or effects of a substance in relation
to its desired therapeutic target are Primary Pharmacodynamic
Studies.
• Secondary Pharmacodynamic Studies aimed at investigating the
mode of action and/or effects of a substance not related to its desired
therapeutic target
5. HISTORY
• Safety Pharmacology is the discipline that seeks to predict whether a
drug, if administered to human or animal populations, is likely to be
found unsafe, and its main professional mandate is to prevent such an
occurrence. Before 1990, pharmaceutical companies conducted
toxicological testing of lead compounds as part of preclinical drug
discovery programs. Now, it has become clear over several decades
that drugs may progress as far as phase 3 clinical trials (i.e. the
intended patient population) before rare and potentially lethal adverse
effects become apparent. The vigilant post-marketing surveillance
efforts by regulatory authorities necessary to confirm the existence of
a rare adverse event occur after approval for human use
6.
7.
8. TEST SYSTEM
• 1.General Considerations on Test Systems
• Consideration should be given to the selection of relevant animal models or
other test systems so that scientifically valid information can be derived.
• Selection factors can include the pharmacodynamic responsiveness of the
model, pharmacokinetic profile, species, strain, gender and age of the
experimental animals, the susceptibility, sensitivity, and reproducibility of the
test system and available background data on the substance.
• Data from humans (e.g., in vitro metabolism), when available, should also
be considered in the test system selection.
• The time points for the measurements should be based on
pharmacodynamic and pharmacokinetic considerations. Justification should
be provided for the selection of the particular animal model or test system.
9. 2.Use of In Vivo and In Vitro Studies
• Animal models as well as ex vivo and in vitro preparations can be used as test
systems.
• Ex vivo and in vitro systems can include, but are not limited to: isolated organs and
tissues, cell cultures, cellular fragments, subcellular organelles, receptors, ion
channels, transporters and enzymes.
• In vitro systems can be used in supportive studies (e.g., to obtain a profile of the
activity of the substance or to investigate the mechanism of effects observed in vivo).
• In conducting in vivo studies, it is preferable to use unanesthetized animals. Data
from unrestrained animals that may be chronically instrumented for telemetry, other
suitable instrumentation methods for conscious animals, or animals conditioned to
the laboratory environment are preferable to data from restrained or unconditioned
animals. In the use of unanesthetized animals, the avoidance of discomfort or pain is
a foremost consideration.
10. 3. Experimental Design
• 1.Sample Size and Use of Controls :
• The size of the groups should be sufficient to allow meaningful scientific
interpretation of the data generated. Thus, the number of animals or isolated
preparations should be adequate to demonstrate or rule out the presence of
a biologically significant effect of the test substance.
• This should take into consideration the size of the biological effect that is of
concern for humans. Appropriate negative and positive control groups should
be included in the experimental design.
• In well- characterized in vivo test systems, positive controls may not be
necessary. The exclusion of controls from studies should be justified.
11. DURATION OF STUDIES
• Safety pharmacology studies are generally performed by single dose
administration. When pharmacodynamic effects occur only after a
certain duration of treatment, or when results from repeat dose non-
clinical studies or results from use in humans give rise to concerns
about safety pharmacological effects, the duration of the safety
pharmacology studies to address these effects should be rationally
based.
12. 2. Route of Administration
• In general, the expected clinical route of administration should be
used when feasible. Regardless of the route of administration,
exposure to the parent substance and its major metabolites should be
similar to or greater than that achieved in humans when such
information is available.
• Assessment of effects by more than one route may be appropriate if
the test substance is intended for clinical use by more than one route
of administration (e.g. oral and parenteral), or where there are
observed or anticipated significant qualitative and quantitative
differences in systemic or local exposure.
13.
14. • Safety pharmacology is a branch of pharmacology specializing in detecting
and investigating potential undesirable pharmacodynamic effects of new
chemical entities (NCEs) on physiological functions in relation to exposure in
the therapeutic range and above.
Primary organ systems (so-called core battery systems) are:
Central Nervous System
Cardiovascular System
Respiratory System
Secondary organ systems of interest are:
Gastrointestinal System
Renal System
• Safety pharmacology studies are required to be completed prior to human
exposure (i.e., Phase I clinical trials), and regulatory guidance is provided in
ICH S7A and other documents.
15. SAFETY PHARMACOLOGY CORE BATTERY
• The purpose of the safety pharmacology core battery is to investigate
the effects of the test substance on vital functions.
• In this regard, the cardiovascular, respiratory and central nervous
systems are usually considered the vital organ systems that should be
studied in the core battery.
• In some instances, based on scientific rationale, the core battery
should be supplemented or need not be implemented
• The exclusion of certain test(s) or exploration(s) of certain organs,
systems or functions should be scientifically justified.
16. SAFETY PHARMACOLOGY CORE BATTERY
1.Central Nervous System : Effects of the test substance on the central nervous
system should be assessed appropriately. Motor activity, behavioral changes,
coordination, sensory/motor reflex responses and body temperature should be
evaluated. For example, a functional observation battery (FOB) , modified Irwin’s , or
other appropriate test can be used.
2. Cardiovascular System : Effects of the test substance on the cardiovascular
system should be assessed appropriately. Blood pressure, heart rate, and the
electrocardiogram should be evaluated. In vivo, in vitro and/or ex vivo evaluations,
including methods for repolarization and conductance abnormalities, should also be
considered.
3.Respiratory System : Effects of the test substance on the respiratory system
should be assessed appropriately. Respiratory rate and other measures of
respiratory function (e.g., tidal volume or hemoglobin oxygen saturation) should be
evaluated. Clinical observation of animals is generally not adequate to assess
respiratory function, and thus these parameters should be quantified by using
appropriate methodologies.
17.
18. hERG assay (human Ether-a-go-go Related Gene)
• The alpha subunit of a potassium ion channels in the heart that codes for
a protein known as Kv11.1
• ion channel proteins (the 'rapid' delayed rectifier current IKr)) that
conducts potassium (K+) ions out of the muscle cells of the heart
• Inhibition of the hERG current causes QT interval prolongation resulting
in potentially fatal ventricular tachyarrhythmia called Torsade de Pointes.
19. FOLLOW-UP AND SUPPLEMENTAL SAFETY
PHARMACOLOGY STUDIES
• Adverse effects may be suspected based on the pharmacological
properties or chemical class of the test substance. Additionally,
concerns may arise from the safety pharmacology core battery, clinical
trials, pharmacovigilance, experimental in vitro or in vivo studies, or
from literature reports. When such potential adverse effects raise
concern for human safety, these should be explored in follow-up or
supplemental safety pharmacology studies, as appropriate.
• 1. Follow-up Studies For Safety Pharmacology Core Battery:
Follow-up studies are meant to provide a greater depth of
understanding than, or additional knowledge to, that provided by the
core battery on vital functions.
20. In some cases, it may be more appropriate to address these effects
during the conduct of other non-clinical and/or clinical studies.
a. Central Nervous System : Behavioral pharmacology, learning and
memory, ligand-specific binding, neurochemistry, visual, auditory and/or
electrophysiology examinations, etc.
b. Cardiovascular System : Cardiac output, ventricular contractility,
vascular resistance, the effects of endogenous and/or exogenous
substances on the cardiovascular responses, etc.
c. Respiratory System :Airway resistance, compliance, pulmonary
arterial pressure, blood gases, blood pH, etc.
21. 2. Supplemental Safety Pharmacology Studies
Supplemental studies are meant to evaluate potential adverse pharmacodynamic effects on
organ system functions not addressed by the core battery or repeated dose toxicity studies
when there is a cause for concern.
a. Renal/Urinary System : Effects of the test substance on renal parameters should be
assessed. For example, urinary volume, specific gravity, osmolality, pH, fluid/electrolyte
balance, proteins, cytology, and blood chemistry determinations such as blood urea nitrogen,
creatinine and plasma proteins can be used.
b. Autonomic Nervous System : Effects of the test substance on the autonomic nervous
system should be assessed. For example, binding to receptors relevant for the autonomic
nervous system, functional responses to agonists or antagonists in vivo or in vitro, direct
stimulation of autonomic nerves and measurement of cardiovascular responses, baroreflex
testing, and heart rate variability can be used.
c. Gastrointestinal System : Effects of the test substance on the gastrointestinal system
should be assessed. For example, gastric secretion, gastrointestinal injury potential, bile
secretion, transit time in vivo, ileal contraction in vitro, gastric pH measurement and pooling
can be used.
d. Other Organ Systems :Effects of the test substance on organ systems not investigated
elsewhere should be assessed when there is a reason for concern. For example, dependency
potential or skeletal muscle, immune and endocrine functions can be investigated.
22. TIMING OF SAFETY PHARMACOLOGY STUDIES IN
RELATION TO CLINICAL DEVELOPMENT
When planning a safety pharmacology program, should be reviewed to determine whether
or not specific studies are recommended.
1.Studies Prior to First Administration in Humans: The effects of a test substance on
the functions listed in the safety pharmacology core battery should be investigated prior to
first administration in humans. Any follow-up or supplemental studies identified as
appropriate, based on a cause for concern, should also be conducted. Information from
toxicology studies adequately designed and conducted to address safety pharmacology
endpoints can result in reduction or elimination of separate safety pharmacology studies.
2. Studies During Clinical Development : Additional studies may be warranted to clarify
observed or suspected adverse effects in animals and humans during clinical development.
3. Studies Before Approval : Safety pharmacology effects on systems should be
assessed prior to product approval, unless not warranted, in which case this should be
justified. Available information from toxicology studies adequately designed and conducted
to address safety pharmacology endpoints, or information from clinical studies, can support
this assessment and replace safety pharmacology studies.
•
23. Conditions under which Studies are not
Necessary
• Safety pharmacology studies may not be needed for locally applied
agents (e.g., dermal or ocular)
• For biotechnology-derived products that achieve highly specific
receptor targeting, it is often sufficient to evaluate safety pharmacology
endpoints as a part of toxicology and pharmacodynamic studies, and
therefore safety pharmacology studies can be reduced or eliminated
for these products.
24. Importance of Safety Pharmacology
• Determination of dosage regime, subject selection of novel
compounds.
• Helps in risk evaluation and hazard identification.
• Critical step in design of clinical trials