New drug development is a long and expensive process that can take over 10 years and cost $500-1000 million. It involves drug discovery, preclinical testing in animals, and clinical trials in humans divided into phases. Preclinical testing assesses safety, efficacy, and side effects in animal models and isolated tissues over 2-4 years. If results are promising, clinical trials in human volunteers and patients are initiated to further evaluate safety and efficacy over 3-10 years before regulatory approval and marketing. The overall process aims to discover and optimize drug candidates, evaluate safety and efficacy, and gain regulatory approval for marketing new pharmaceutical treatments.
Clinical trials are research studies performed in humans to test new drugs or treatments. They follow a multi-phase process to test safety and efficacy. The document defines clinical trials and describes their purpose to discover or verify clinical and pharmacological effects of investigational products. It also outlines the different types of clinical trials including treatment, prevention, and screening trials. The phases of clinical trials are explained including phases I-III. Key documents for clinical trials are also listed such as the investigator's brochure, clinical study protocol, case report forms, informed consent forms, and clinical study reports.
This document outlines the rules and regulations for conducting clinical trials and importing or manufacturing new drugs in India. It discusses the various forms and permissions required, including Form 44 for new drug approval and Form 12 for importing study drugs. It also describes the responsibilities of sponsors, investigators, and ethics committees. The document explains the different phases of clinical trials from human pharmacology to post-marketing surveillance. It lists the data that must be submitted with applications and included in clinical study reports.
The document discusses the roles and responsibilities of key members of a clinical research team. It describes the investigator as the leader responsible for ensuring ethical and protocol-compliant conduct of the study. The clinical research coordinator supports the investigator and manages daily trial activities including participant communication and data collection. The sponsor initiates and finances the study, while maintaining responsibility for quality and integrity. A contract research organization may take on some sponsor responsibilities by agreement.
The drug development process involves several phases of clinical trials overseen by regulatory agencies. Drugs must first show safety in pre-clinical animal and lab testing before entering human trials. Clinical trials involve 3 phases - Phase I tests safety in small groups, Phase II assesses efficacy and optimal dosing in larger groups of patients, and Phase III confirms efficacy in even larger groups. If results are positive, the drug company submits a New Drug Application to the regulatory agency which can take 2-3 years to review before approving the drug for the market. Post-market studies in Phase IV further monitor long-term safety and efficacy. The entire process from discovery to market approval takes an average of 10-15 years and over $1 billion
This document provides an overview of acute toxicity studies and OECD test guidelines for assessing acute oral toxicity. It discusses the principles and procedures for acute oral toxicity fixed dose tests per OECD Guideline 420. Key points include:
- Guideline 420 is an alternative to the conventional acute toxicity test that uses fewer animals and causes less suffering
- It involves dosing groups of animals with fixed doses (e.g. 5, 50, 300, 2000 mg/kg) and observing any signs of toxicity or mortality
- A sighting study is conducted to determine the starting dose for the main study
- Multiple animals are tested at each dose level in the main study with observation periods to monitor for any toxic effects
Clinical trials are research studies performed in humans to test new drugs or treatments. They follow a multi-phase process to test safety and efficacy. The document defines clinical trials and describes their purpose to discover or verify clinical and pharmacological effects of investigational products. It also outlines the different types of clinical trials including treatment, prevention, and screening trials. The phases of clinical trials are explained including phases I-III. Key documents for clinical trials are also listed such as the investigator's brochure, clinical study protocol, case report forms, informed consent forms, and clinical study reports.
This document outlines the rules and regulations for conducting clinical trials and importing or manufacturing new drugs in India. It discusses the various forms and permissions required, including Form 44 for new drug approval and Form 12 for importing study drugs. It also describes the responsibilities of sponsors, investigators, and ethics committees. The document explains the different phases of clinical trials from human pharmacology to post-marketing surveillance. It lists the data that must be submitted with applications and included in clinical study reports.
The document discusses the roles and responsibilities of key members of a clinical research team. It describes the investigator as the leader responsible for ensuring ethical and protocol-compliant conduct of the study. The clinical research coordinator supports the investigator and manages daily trial activities including participant communication and data collection. The sponsor initiates and finances the study, while maintaining responsibility for quality and integrity. A contract research organization may take on some sponsor responsibilities by agreement.
The drug development process involves several phases of clinical trials overseen by regulatory agencies. Drugs must first show safety in pre-clinical animal and lab testing before entering human trials. Clinical trials involve 3 phases - Phase I tests safety in small groups, Phase II assesses efficacy and optimal dosing in larger groups of patients, and Phase III confirms efficacy in even larger groups. If results are positive, the drug company submits a New Drug Application to the regulatory agency which can take 2-3 years to review before approving the drug for the market. Post-market studies in Phase IV further monitor long-term safety and efficacy. The entire process from discovery to market approval takes an average of 10-15 years and over $1 billion
This document provides an overview of acute toxicity studies and OECD test guidelines for assessing acute oral toxicity. It discusses the principles and procedures for acute oral toxicity fixed dose tests per OECD Guideline 420. Key points include:
- Guideline 420 is an alternative to the conventional acute toxicity test that uses fewer animals and causes less suffering
- It involves dosing groups of animals with fixed doses (e.g. 5, 50, 300, 2000 mg/kg) and observing any signs of toxicity or mortality
- A sighting study is conducted to determine the starting dose for the main study
- Multiple animals are tested at each dose level in the main study with observation periods to monitor for any toxic effects
Toxicokinetic evaluation in preclinical studies by Shivam Diwaker Shivam Diwaker
Toxicokinetics evaluation in preclinical studies was presented. The presentation covered absorption, distribution, biotransformation and excretion of chemicals. Key points included how toxicokinetics quantifies exposure through measures like volume of distribution and clearance. The importance of evaluating metabolites and the factors influencing distribution and metabolism were discussed. Toxicokinetic studies are conducted at various stages of preclinical and clinical development to interpret toxicity results and support human trials. Alternative approaches to decrease animal usage in toxicokinetics were also presented.
This document discusses microdosing studies, which involve administering very small, sub-therapeutic doses of drug candidates to humans early in clinical trials. The goals are to obtain human pharmacokinetic and metabolic data prior to traditional Phase 1 trials in order to select promising candidates and eliminate unsuccessful ones earlier. Microdosing studies have advantages like accelerating development timelines and reducing costs by focusing resources on candidates more likely to succeed in later trials. The document covers the concept, goals, procedures, uses, advantages, and regulatory guidelines of microdosing studies.
Assignment on Toxicokinetics- Toxicokinetic evaluation in preclinical studies, saturation kinetics Importance and applications of toxicokinetic studies. Alternative methods to animal toxicity testing.
Guidelines for Preparation of Documents, Clinical Study Report Clinical Trial...Dinesh Gangoda
Contents
Guidelines for Preparation of Documentation
Clinical Study Reports
Clinical Trial Monitoring
Safety Monitoring in clinical trials
Introduction
Proper documentation is critical to the success of a clinical study.
Every aspect of the study must be documented in order to obtain useful data and demonstrate compliance with Good Clinical Practice (GCP) guidelines and with all applicable regulations.
Investigator’s Brochure (IB)
List of Abbreviations
Contents & Summary
Introduction provides the chemical name (and generic and trade names, if approved) of the investigational product.
Physical, chemical and pharmaceutical properties and formulation of the medicinal product. Non-clinical studies & Clinical Studies and their results.
The Investigator's Brochure should be reviewed at least annually and revised as necessary in compliance with a standard procedures established by drug development company.
The document summarizes Schedule Y, which outlines the requirements and guidelines for conducting clinical trials and importing or manufacturing new drugs in India. It discusses the regulatory bodies involved, including the Central Drugs Standard Control Organization and various guidelines and regulations. It provides an overview of the application process for clinical trials and requirements for trials, including ethics committee approval and informed consent. It also summarizes recent updates to clinical trials regulations in India.
The document outlines the regulatory requirements and guidelines in India for permission to import, manufacture, and conduct clinical trials of new drugs. It discusses the relevant sections of Schedule Y and the Drugs and Cosmetics Rules, 1945. Key points include the application process for import/manufacture using Form 44, responsibilities of sponsors and investigators, ethics committee oversight, and guidelines for the different phases of clinical trials from Phase I to Phase IV. It also addresses requirements for special populations like pediatrics, geriatrics, and pregnant/nursing women. Post-marketing surveillance and periodic safety update reporting are mandated.
Toxicokinetics describes how the body handles toxicants over time through absorption, distribution, metabolism and excretion (ADME). It is important in drug development to generate kinetic data for toxicity assessment, check safety ratios, and set safe dose levels in clinical trials. Toxicokinetic evaluation helps reduce animal testing, understand inter-individual differences in responses, and has applications in screening anticancer drugs, cell-based assays, and other areas of research.
ROLES AND RESPONSIBLITIES OF CLINICAL TRIAL PERSONNEL-INVESTIGATOR.pptxE Poovarasan
This document outlines the roles and responsibilities of key personnel in clinical trials, including the investigator, study coordinator, and other members of the research team. It describes that the investigator is responsible for conducting the trial according to the protocol and protecting participants. The study coordinator works under the investigator and is responsible for coordinating study visits, obtaining consent, and ensuring compliance. Other duties of the research team include reporting adverse events, maintaining proper records, and following Good Clinical Practice standards.
Roles and Responsibilities in Clinical Trials of Investigator, Study Coordinator, Sponsor, Monitor, a Contract research organization.
The clinical trial, definition, description, Different types of clinical trials, phases of clinical trial.
The clinical trial study team.
Requirements of the clinical trial study team.
Clinical research team role.
GCP- Good clinical practices.
The document provides an overview of good clinical practices (GCP) and the historical standards that contributed to its development. It discusses key milestones like the Nuremberg Code, Declaration of Helsinki, and Belmont Report that established ethical and quality standards for clinical research involving human subjects. The document also outlines the four phases of clinical trials and principles of GCP like prior approval, informed consent, and quality assurance. It notes that GCP provides an international quality standard to ensure the rights, safety, and well-being of clinical trial participants.
This document outlines the phases of clinical drug trials. It discusses the objectives and methods of each phase. Phase I trials test drug safety in healthy volunteers. Phase II trials test efficacy and side effects in patients to determine dosage. Phase III trials test efficacy and safety in large randomized controlled trials. Phase IV trials monitor drug use after marketing to detect rare or long-term effects. Each phase uses different doses, patients, investigators, and sample sizes to progressively evaluate a drug's safety and effectiveness in humans. The overall goal is to translate preclinical animal findings into cautious human testing.
Post-marketing surveillance (PMS) monitors drug and medical device safety after market release using approaches like spontaneous reporting databases, prescription monitoring, and health records. PMS identifies potential safety issues through data review and helps detect rare or long-term adverse effects not seen in pre-market clinical trials which have limited patient populations and durations. PMS provides additional safety and efficacy information on marketed products and allows monitoring of special patient groups. Common PMS methods include spontaneous reporting, observational studies, randomized trials, and active surveillance networks.
The document provides an overview of ICH-GCP (Good Clinical Practice) guidelines, which are international ethical and scientific quality standards for designing, conducting, recording, and reporting trials that involve the participation of human subjects. The summary discusses the key sections and principles of ICH-GCP, which aim to protect trial subjects and ensure valid clinical trial data. It outlines the historical background and development of GCP standards from the Nuremberg Code to the ICH-GCP guidelines of 1996. The document reviews responsibilities of ethics committees, sponsors, investigators, clinical trial protocols, and informed consent processes.
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.
This document outlines the requirements for toxicological studies as specified in Schedule Y of the Drugs and Cosmetics Act of India. It discusses the various medical organizations involved in clinical research regulation and drug development in India. It then describes the key aspects of Schedule Y, including the appendices that cover requirements for non-clinical animal toxicity studies. The appendices specify the types of studies needed, such as single dose toxicity studies, repeated dose toxicity studies, reproductive toxicity studies, and carcinogenicity studies, along with the testing parameters and number of animals required for each.
Clinical trials involve several phases to test a drug's safety and efficacy. Phase I trials test safety in healthy volunteers. Phase II trials test dosage and side effects in patients. Phase III trials test efficacy in large patient groups. Legal and procedural aspects require ethics committee approval, informed consent, and regulatory oversight. Clinical trials involve clinical investigators, institutions to host the trial, sponsors to fund the trial, and regulatory authorities to provide legal approval. The clinical trial protocol, informed consent process, and role of ethics committees are important to protect patient rights and welfare in clinical research.
This document discusses toxicokinetics, which refers to applying pharmacokinetic principles to understand toxicity and adverse effects of drugs and chemicals. It covers several key concepts:
1. Toxicokinetic studies examine systemic exposure after dosing at toxic levels, helping assess safety, while pharmacokinetic studies use lower doses.
2. Models describe the time course of a chemical in the body, including one-compartment open models and multi-compartment models accounting for tissue distribution.
3. Key parameters include volume of distribution, clearance, half-life and how they relate through equations. Non-linear toxicokinetics can occur at high doses due to enzyme saturation.
Clinical trials are conducted to test new drugs, treatments or medical devices in humans to assess their safety and efficacy. There are four main phases of clinical trials:
Phase I trials involve small groups of people to determine basic safety and dosing requirements. Phase II trials expand the testing to more people to determine efficacy and further evaluate safety. Phase III trials involve large groups of people to confirm effectiveness, monitor side effects, compare to commonly used treatments and collect information to allow safe use of the intervention. Phase IV trials occur after the intervention has been marketed to gather information on effects in various populations and any long-term side effects.
Clinical trials involve testing investigational drugs or treatments on human subjects to determine safety and efficacy. They progress through several phases, beginning with small pre-clinical trials on animals. Phase 1 trials involve 20-50 healthy volunteers to assess pharmacokinetics and safety. Phase 2 trials enroll 50-300 patient volunteers to further evaluate safety and dosage. Phase 3 trials are large randomized controlled trials of 250-1000+ subjects comparing the investigational treatment to standard treatment or placebo. If Phase 3 is successful, the results are submitted to regulatory agencies for approval to market the new drug. Post-marketing Phase 4 trials monitor long-term safety and efficacy.
New drug development is a highly complex, costly, and time-consuming process that can take over 10 years. It involves synthesis of new chemical entities, preclinical studies in animals and cells to evaluate safety and efficacy, followed by clinical trials in humans in 4 phases to further assess safety and efficacy. If clinical trials are successful, regulatory approval must be obtained before the drug can be marketed. The overall goal is to bring new treatments to patients while ensuring safety and effectiveness through a rigorous scientific process.
Drug development involves rigorous pre-clinical and clinical testing to prove a drug is safe and effective. Pre-clinical testing involves laboratory and animal studies. Clinical trials in humans have four phases, with each subsequent phase involving more subjects to further evaluate safety, efficacy, and optimal dosage. After Phase III trials demonstrate a drug's benefits outweigh its risks, a New Drug Application is submitted to regulators for review. If approved, Phase IV trials continue monitoring the drug's long-term safety profile after market approval. The entire process from discovery to market approval takes an average of 8-12 years and costs $800-900 million.
Toxicokinetic evaluation in preclinical studies by Shivam Diwaker Shivam Diwaker
Toxicokinetics evaluation in preclinical studies was presented. The presentation covered absorption, distribution, biotransformation and excretion of chemicals. Key points included how toxicokinetics quantifies exposure through measures like volume of distribution and clearance. The importance of evaluating metabolites and the factors influencing distribution and metabolism were discussed. Toxicokinetic studies are conducted at various stages of preclinical and clinical development to interpret toxicity results and support human trials. Alternative approaches to decrease animal usage in toxicokinetics were also presented.
This document discusses microdosing studies, which involve administering very small, sub-therapeutic doses of drug candidates to humans early in clinical trials. The goals are to obtain human pharmacokinetic and metabolic data prior to traditional Phase 1 trials in order to select promising candidates and eliminate unsuccessful ones earlier. Microdosing studies have advantages like accelerating development timelines and reducing costs by focusing resources on candidates more likely to succeed in later trials. The document covers the concept, goals, procedures, uses, advantages, and regulatory guidelines of microdosing studies.
Assignment on Toxicokinetics- Toxicokinetic evaluation in preclinical studies, saturation kinetics Importance and applications of toxicokinetic studies. Alternative methods to animal toxicity testing.
Guidelines for Preparation of Documents, Clinical Study Report Clinical Trial...Dinesh Gangoda
Contents
Guidelines for Preparation of Documentation
Clinical Study Reports
Clinical Trial Monitoring
Safety Monitoring in clinical trials
Introduction
Proper documentation is critical to the success of a clinical study.
Every aspect of the study must be documented in order to obtain useful data and demonstrate compliance with Good Clinical Practice (GCP) guidelines and with all applicable regulations.
Investigator’s Brochure (IB)
List of Abbreviations
Contents & Summary
Introduction provides the chemical name (and generic and trade names, if approved) of the investigational product.
Physical, chemical and pharmaceutical properties and formulation of the medicinal product. Non-clinical studies & Clinical Studies and their results.
The Investigator's Brochure should be reviewed at least annually and revised as necessary in compliance with a standard procedures established by drug development company.
The document summarizes Schedule Y, which outlines the requirements and guidelines for conducting clinical trials and importing or manufacturing new drugs in India. It discusses the regulatory bodies involved, including the Central Drugs Standard Control Organization and various guidelines and regulations. It provides an overview of the application process for clinical trials and requirements for trials, including ethics committee approval and informed consent. It also summarizes recent updates to clinical trials regulations in India.
The document outlines the regulatory requirements and guidelines in India for permission to import, manufacture, and conduct clinical trials of new drugs. It discusses the relevant sections of Schedule Y and the Drugs and Cosmetics Rules, 1945. Key points include the application process for import/manufacture using Form 44, responsibilities of sponsors and investigators, ethics committee oversight, and guidelines for the different phases of clinical trials from Phase I to Phase IV. It also addresses requirements for special populations like pediatrics, geriatrics, and pregnant/nursing women. Post-marketing surveillance and periodic safety update reporting are mandated.
Toxicokinetics describes how the body handles toxicants over time through absorption, distribution, metabolism and excretion (ADME). It is important in drug development to generate kinetic data for toxicity assessment, check safety ratios, and set safe dose levels in clinical trials. Toxicokinetic evaluation helps reduce animal testing, understand inter-individual differences in responses, and has applications in screening anticancer drugs, cell-based assays, and other areas of research.
ROLES AND RESPONSIBLITIES OF CLINICAL TRIAL PERSONNEL-INVESTIGATOR.pptxE Poovarasan
This document outlines the roles and responsibilities of key personnel in clinical trials, including the investigator, study coordinator, and other members of the research team. It describes that the investigator is responsible for conducting the trial according to the protocol and protecting participants. The study coordinator works under the investigator and is responsible for coordinating study visits, obtaining consent, and ensuring compliance. Other duties of the research team include reporting adverse events, maintaining proper records, and following Good Clinical Practice standards.
Roles and Responsibilities in Clinical Trials of Investigator, Study Coordinator, Sponsor, Monitor, a Contract research organization.
The clinical trial, definition, description, Different types of clinical trials, phases of clinical trial.
The clinical trial study team.
Requirements of the clinical trial study team.
Clinical research team role.
GCP- Good clinical practices.
The document provides an overview of good clinical practices (GCP) and the historical standards that contributed to its development. It discusses key milestones like the Nuremberg Code, Declaration of Helsinki, and Belmont Report that established ethical and quality standards for clinical research involving human subjects. The document also outlines the four phases of clinical trials and principles of GCP like prior approval, informed consent, and quality assurance. It notes that GCP provides an international quality standard to ensure the rights, safety, and well-being of clinical trial participants.
This document outlines the phases of clinical drug trials. It discusses the objectives and methods of each phase. Phase I trials test drug safety in healthy volunteers. Phase II trials test efficacy and side effects in patients to determine dosage. Phase III trials test efficacy and safety in large randomized controlled trials. Phase IV trials monitor drug use after marketing to detect rare or long-term effects. Each phase uses different doses, patients, investigators, and sample sizes to progressively evaluate a drug's safety and effectiveness in humans. The overall goal is to translate preclinical animal findings into cautious human testing.
Post-marketing surveillance (PMS) monitors drug and medical device safety after market release using approaches like spontaneous reporting databases, prescription monitoring, and health records. PMS identifies potential safety issues through data review and helps detect rare or long-term adverse effects not seen in pre-market clinical trials which have limited patient populations and durations. PMS provides additional safety and efficacy information on marketed products and allows monitoring of special patient groups. Common PMS methods include spontaneous reporting, observational studies, randomized trials, and active surveillance networks.
The document provides an overview of ICH-GCP (Good Clinical Practice) guidelines, which are international ethical and scientific quality standards for designing, conducting, recording, and reporting trials that involve the participation of human subjects. The summary discusses the key sections and principles of ICH-GCP, which aim to protect trial subjects and ensure valid clinical trial data. It outlines the historical background and development of GCP standards from the Nuremberg Code to the ICH-GCP guidelines of 1996. The document reviews responsibilities of ethics committees, sponsors, investigators, clinical trial protocols, and informed consent processes.
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.
This document outlines the requirements for toxicological studies as specified in Schedule Y of the Drugs and Cosmetics Act of India. It discusses the various medical organizations involved in clinical research regulation and drug development in India. It then describes the key aspects of Schedule Y, including the appendices that cover requirements for non-clinical animal toxicity studies. The appendices specify the types of studies needed, such as single dose toxicity studies, repeated dose toxicity studies, reproductive toxicity studies, and carcinogenicity studies, along with the testing parameters and number of animals required for each.
Clinical trials involve several phases to test a drug's safety and efficacy. Phase I trials test safety in healthy volunteers. Phase II trials test dosage and side effects in patients. Phase III trials test efficacy in large patient groups. Legal and procedural aspects require ethics committee approval, informed consent, and regulatory oversight. Clinical trials involve clinical investigators, institutions to host the trial, sponsors to fund the trial, and regulatory authorities to provide legal approval. The clinical trial protocol, informed consent process, and role of ethics committees are important to protect patient rights and welfare in clinical research.
This document discusses toxicokinetics, which refers to applying pharmacokinetic principles to understand toxicity and adverse effects of drugs and chemicals. It covers several key concepts:
1. Toxicokinetic studies examine systemic exposure after dosing at toxic levels, helping assess safety, while pharmacokinetic studies use lower doses.
2. Models describe the time course of a chemical in the body, including one-compartment open models and multi-compartment models accounting for tissue distribution.
3. Key parameters include volume of distribution, clearance, half-life and how they relate through equations. Non-linear toxicokinetics can occur at high doses due to enzyme saturation.
Clinical trials are conducted to test new drugs, treatments or medical devices in humans to assess their safety and efficacy. There are four main phases of clinical trials:
Phase I trials involve small groups of people to determine basic safety and dosing requirements. Phase II trials expand the testing to more people to determine efficacy and further evaluate safety. Phase III trials involve large groups of people to confirm effectiveness, monitor side effects, compare to commonly used treatments and collect information to allow safe use of the intervention. Phase IV trials occur after the intervention has been marketed to gather information on effects in various populations and any long-term side effects.
Clinical trials involve testing investigational drugs or treatments on human subjects to determine safety and efficacy. They progress through several phases, beginning with small pre-clinical trials on animals. Phase 1 trials involve 20-50 healthy volunteers to assess pharmacokinetics and safety. Phase 2 trials enroll 50-300 patient volunteers to further evaluate safety and dosage. Phase 3 trials are large randomized controlled trials of 250-1000+ subjects comparing the investigational treatment to standard treatment or placebo. If Phase 3 is successful, the results are submitted to regulatory agencies for approval to market the new drug. Post-marketing Phase 4 trials monitor long-term safety and efficacy.
New drug development is a highly complex, costly, and time-consuming process that can take over 10 years. It involves synthesis of new chemical entities, preclinical studies in animals and cells to evaluate safety and efficacy, followed by clinical trials in humans in 4 phases to further assess safety and efficacy. If clinical trials are successful, regulatory approval must be obtained before the drug can be marketed. The overall goal is to bring new treatments to patients while ensuring safety and effectiveness through a rigorous scientific process.
Drug development involves rigorous pre-clinical and clinical testing to prove a drug is safe and effective. Pre-clinical testing involves laboratory and animal studies. Clinical trials in humans have four phases, with each subsequent phase involving more subjects to further evaluate safety, efficacy, and optimal dosage. After Phase III trials demonstrate a drug's benefits outweigh its risks, a New Drug Application is submitted to regulators for review. If approved, Phase IV trials continue monitoring the drug's long-term safety profile after market approval. The entire process from discovery to market approval takes an average of 8-12 years and costs $800-900 million.
The document discusses the process of drug discovery, including target selection, lead discovery, medicinal chemistry, in vitro and in vivo studies, and clinical trials. Target selection involves identifying cellular or genetic targets involved in disease through techniques like genomics, proteomics, and bioinformatics. Lead discovery focuses on identifying small molecule modulators of protein function through methods like synthesis, combinatorial chemistry, assay development, and high-throughput screening. Medicinal chemistry then works to optimize these leads. [/SUMMARY]
Assessment of natural compound influence on periodontal clinicalFeng-wei Yeh
This document outlines the goals of a research collaboration between several international partners to study the effects of a natural compound on periodontal health and levels of matrix metalloproteinases (MMPs). The first goal is to establish the collaboration between the University of Carderal Herrera-CEU, Taiwan Sugar Research Institute, Development Center for Biotechnology, ELITE Dentofacial Esthetic Clinic, and Ventac Partners. The second goal is to develop proposals outlining each partner's roles in clinical trials, animal testing, funding, and clinical work in Asia and Europe. The third goal is to formalize the collaboration through contracts covering rights, responsibilities, data sharing, and business benefits. The fourth goal is to begin the research
Cosmeceuticals are ingredients with medicinal properties that provide topical benefits and protect against skin damage. They were coined in 1980 but have no legal definition. They are not considered drugs by the FDA and have less rigorous testing than drugs. Common cosmeceutical ingredients include antioxidants, peptides, retinoids, and exfoliants which treat signs of aging. Cosmeceuticals are generally safer than drugs for long-term use and promote skin health and beauty through natural ingredients.
Drug development involves basic research to identify drug targets and applied research to develop treatments. Preclinical trials test drug safety and efficacy in animals prior to human trials. They involve pharmacokinetic, pharmacodynamic and toxicology studies in two animal species. This provides data on effective and toxic doses, screens the drug's activity, and identifies formulation. Preclinical trials help determine if a drug warrants further development or should be terminated. They aim to predict potential human adverse effects and provide guidance for initial human clinical trials. However, extrapolating animal data to humans has limitations due to interspecies differences.
The drug development process takes an average of 10-12 years and costs $500 million to $2 billion. Only one in 10,000 to 30,000 potential drug candidates makes it to market. The process involves drug discovery, preclinical testing in animals, and clinical trials in three phases with humans. Phase I tests safety in small groups, Phase II explores efficacy in larger groups, and Phase III tests effectiveness in large patient populations. If successful, the drug sponsor submits a New Drug Application to the FDA for review and potential approval. Post-marketing studies monitor long-term safety and efficacy. Thalidomide caused birth defects when tested inadequately in the late 1950s, highlighting the importance of rigorous preclinical and
Overview of the Patient-Centered Outcomes Research Institute (PCORI), how PCORI views Patient-Centered Outcomes Research and how this is related to PCORI’s major funding mechanisms.
STARBRANDS // BUILT TO SHINE: Krótka analiza rynku nutrikosmetyków / nutricos...SOFAMI.PL
Krótka analiza rynku nutrikosmetyków i obecnych tam marek i komunikacji marek. Our quick view on the nutricosmetics market, key players, brands, brand communication..
Suraj bhong` presentation on drug design satara, contact- 9096288631suraj bhong
This document outlines the process of drug development from discovery through FDA approval. It discusses key stages including drug design, preclinical testing, clinical trials, and FDA review. The goals at each stage are to demonstrate that new drugs are safe, effective, and high quality. The drug development process aims to identify disease targets, design drugs to act on those targets, and test drugs through a multi-year process to prove their safety and efficacy before approval and marketing. Regulatory review by agencies like the FDA helps to ensure that distributed drugs meet prescribed quality standards.
This document outlines the history of drug development and approval processes in the United States from 1820 to 1997. It describes key milestones and legislation that established regulations for new drug applications (NDAs). NDAs were first required in 1938 to show drug safety, and in 1962 were amended to require proof of efficacy. The FDA now reviews NDAs to ensure the benefits of new drugs outweigh the risks based on clinical trial data.
This document outlines the new drug development process (NDDP), including drug discovery through screening, preclinical and clinical evaluation, regulatory approval from bodies like the FDA, and ethical guidelines. It describes the stages of clinical trials from Phase I through III that assess safety, efficacy and side effects in increasing numbers of participants. The goal of the NDDP is to develop new drugs to meet unmet medical needs and obtain regulatory approval to market the drug. Ethical standards like informed consent and minimizing risk to participants are required.
The document discusses alternative techniques to animal testing in drug and chemical research. It defines alternatives as methods that replace, reduce, or refine animal use. Several specific alternative techniques are described, including full thickness skin models, in silico computer modeling, cell line techniques, and patch clamp electrophysiology. The techniques aim to provide comparable data to animal tests while avoiding or minimizing animal use.
Phase 1 clinical trials are the first studies conducted in humans of a new drug or treatment. They aim to determine the drug's safety and tolerability, identify the maximum tolerated dose, and understand the drug's pharmacokinetics. Phase 1 trials typically involve small groups of healthy volunteers or patients and start with low doses that are gradually increased. The results of phase 1 trials provide information needed to design subsequent phase 2 and 3 trials to further evaluate efficacy.
Applications of bio-pharmaceutics in new drug deliveryAkshata shettar
Biopharmaceutics plays an integral role in new drug development from discovery through post-approval stages. The development process takes 10-15 years and costs $800 million to $1 billion, involving testing 5000-10000 molecules to find 1 approved drug. Biopharmaceutics evaluates drug properties like absorption, distribution, metabolism, and excretion during discovery and preclinical testing in animals. If successful, drugs then undergo three phases of clinical trials in humans to test for safety, efficacy, and dosage before potential approval and post-marketing surveillance. Biopharmaceutics aims to develop drug formulations and delivery systems that allow for optimal dosing intervals based on a drug's pharmacokinetic profile.
FDA Guidelines for Drug Development & Approvalrahimbrave
The document discusses the drug development and approval process in the United States. It describes the roles and responsibilities of the Food and Drug Administration (FDA) in regulating drugs, medical devices, and other products. It then outlines the various phases of clinical trials (Phases I-IV) that drugs must go through to test for safety and efficacy before FDA approval. It also discusses the processes for approving generic drugs, biological products, and modifications to approved drugs.
The document discusses various aspects of the drug development process including selection of therapeutic targets, approaches to drug discovery, stages of clinical development, and major challenges. Therapeutic needs are determined based on existing therapies, commercial potential, and individualized treatment. Drug discovery approaches include traditional empirical and molecular methods. Clinical development involves phases to test safety, efficacy, and dosing. Major challenges include high costs, regulatory standards, and individualizing treatment.
Bioassay (commonly used shorthand for biological assay), or biological standardization is a type of scientific experiment. A bioassay involves the use of a live animal (in vivo) or tissue (in vitro) to determine the biological activity of a substance, such as a hormone or drug. Bioassays are typically conducted to measure the effects of a substance on a living organism and are essential in the development of new drugs and in monitoring environmental pollutants. Both are procedures by which the potency or the nature of a substance is estimated by studying its effects on living matter. A bioassay can also be used to determine the concentration of a particular constitution of a mixture.
Alternatives to animal screening methods p'screening. mohammadhusainVasaya Mohammadhusain
1) The document presents information on alternatives to animal testing for toxicity screening such as biotechnology methods like cell cultures and transgenic animal models.
2) In vitro methods like cell lines and tissue cultures can be used to test substances and reduce animal numbers. Full thickness skin models and in silico modeling are also described.
3) Techniques like the patch clamp method allow studying ion channels in isolated cells like kidney cells to understand transport processes without whole animal experiments.
The document discusses the process of new drug development, which involves drug discovery through approaches like exploring natural sources, rational design, and combinatorial chemistry. Drugs then undergo preclinical testing in animals to evaluate safety and efficacy. If promising, drugs enter clinical trials in four phases with humans to further assess safety, efficacy, dosing, and side effects. Successful drugs are approved by regulatory agencies and undergo post-marketing surveillance to monitor long-term effects. The overall process from discovery to marketing can take over 10 years and cost over $500 million.
The document discusses the process of drug discovery and development. It has 5 main stages: drug discovery, pre-clinical testing, clinical trials (phases I-III), regulatory approval, and post-marketing surveillance. Drug discovery involves screening compounds for pharmacological activity through random testing, serendipitous findings, or rational drug design. Pre-clinical testing involves extensive animal studies to evaluate safety, efficacy, and adverse effects. Clinical trials in humans have 3 phases to further assess these factors before regulatory approval and marketing of the drug. Post-approval monitoring continues to study long-term safety and efficacy.
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.
DRUG DISCOVERY & DEVELOPMENT PROCESS, it's a detail description about how drug is made available in market it's development and discovery of drug The Hole Study is given in This Topic.
New Drug Develoment, Pre-Clinical Trial and Clinical Trial.pptxdrarunsingh4
The document discusses the process of new drug development from preclinical trials to clinical trials. It begins with an overview of approaches to drug discovery such as exploring natural sources, chemical synthesis, and biotechnology. It then describes the major steps in preclinical studies which include screening tests, studies on isolated organs and disease models, and tests to determine toxicity, pharmacokinetics, and safety. The goal of preclinical studies is to evaluate drug candidates and reject unfavorable compounds to progress only the most promising candidates to clinical trials in humans.
Preclinical studies, clinical trails and pharmacovigilancekamrudeen samani
The document discusses the various phases of drug development including preclinical, clinical, and post-marketing phases. The preclinical phase involves animal studies to evaluate toxicity, pharmacokinetics, and pharmacodynamics. If promising, the drug enters clinical trials with Phase I studying safety in healthy volunteers, Phase II studying efficacy in patients, and Phase III large scale studies to further confirm safety and efficacy. After approval, Phase IV involves post-marketing surveillance. Pharmacovigilance aims to improve patient safety by monitoring drugs for adverse effects after market entry.
The document summarizes the new drug development process, which takes 10 years and costs $500-1000 million on average. It involves preclinical studies in animals to test safety and efficacy, followed by clinical trials in humans in four phases to further assess safety and efficacy. If successful in clinical trials, the drug receives marketing approval from regulatory authorities. Post-marketing surveillance continues to monitor long-term safety and effectiveness. The goal is to develop new drugs that are clinically safe and effective as well as economically viable.
n drug development, preclinical development, also named preclinical studies and nonclinical studies, is a stage of research that begins before clinical trials can begin, and during which important feasibility, iterative testing and drug safety data are collected, typically in laboratory animals.
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.
The document provides information on various stages of drug discovery. It discusses (1) the introduction to drug discovery and the stages involved, including concept development, pre-clinical and clinical trials; (2) various approaches to lead discovery, such as random screening, targeted screening, drug metabolism studies, and rational drug design; (3) examples of drugs discovered without an initial lead like penicillin and Librium; and (4) target identification and validation which are important for rational drug design. The document presents an overview of the key concepts and processes in drug discovery.
New Drug Discovery And Development (part-2)swatisejwani
The document discusses the steps involved in preclinical trials for new drug development. Preclinical trials involve laboratory and animal testing to evaluate safety and efficacy before human testing. Key steps include: identifying a drug target and developing a bioassay; screening the drug in the bioassay; establishing effective and toxic doses; filing for Investigational New Drug approval with the FDA; and conducting various studies like toxicity, pharmacokinetic, and animal model testing under Good Laboratory Practice standards. The goal of preclinical trials is to obtain sufficient safety and efficacy data to justify moving a drug into clinical trials with human subjects.
The document provides an overview of the drug development process, including its history and modern approaches. It discusses the stages of drug development from discovery through regulatory approval. Key points include: the process involves rigorous testing from cell and animal studies to identify a safe and effective drug; the history of drug discovery dates back to early civilizations but modern drug development began with discoveries like penicillin; modern approaches involve high-throughput screening of large libraries and studies at the genomic and proteomic level to accelerate the discovery process.
A review on stages of drug development and alternative methods for animal stu...Frinto Francis
Various Stages of drug development, anaesthesia ,euthanasia, animals used for preclinical analysis, clinical trials, alternative methods for animal testing, blood withdrawal methods, ethical guidelines
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.
This document provides an overview of the drug development process, which includes early drug discovery through preclinical research on animals, clinical trials with human subjects in four phases, regulatory review and approval, and post-marketing safety surveillance. The process aims to determine if a new drug is safe, effective for its intended use, and has the proper dosage before it can reach patients, and typically takes over a decade. Key steps include identifying drug targets, developing and screening candidate compounds, optimizing leads, conducting preclinical and clinical trials to test safety and efficacy, obtaining regulatory approval, and ongoing monitoring after approval.
This document outlines the stages of drug development, beginning with drug discovery and ending with regulatory approval. It discusses the history of drug development from ancient times to modern pharmaceutical industry. The key stages are described as pre-clinical development involving non-human testing, clinical development involving human trials to test safety and efficacy, and regulatory approval. Drug discovery involves target identification, validation, lead discovery through screening, and lead optimization to improve desired properties. Recent advances like genomics, high-throughput screening, and bioinformatics have accelerated the drug development process.
This document outlines the stages of drug development, beginning with drug discovery and ending with regulatory approval. It discusses the history of drug development from ancient times to modern pharmaceutical industry. The key stages are described as pre-clinical development involving non-human testing, clinical development involving human trials to test safety and efficacy, and regulatory approval. Drug discovery involves target identification, validation, lead discovery through screening, and lead optimization to improve desired properties. Recent advances like genomics, high-throughput screening, and bioinformatics have accelerated the drug development process.
The document provides an overview of the new drug development process, outlining the key steps from discovery and preclinical testing to clinical trials and regulatory approval. It begins with identifying a target and potential drug candidates, then progresses through preclinical screening and safety testing, IND submission, and formal clinical trials in three phases with increasing numbers of participants. The goal is to demonstrate a drug's safety, efficacy, and appropriate dosage before seeking final regulatory review and approval to market the new drug. The entire process from discovery to approval typically takes 10-12 years and costs over $250 million.
Experimental Techniques For Evaluation Of New Drugs.pptKarabiAdak
Experimental techniques are used to evaluate new drugs for toxicity, efficacy, and safety prior to human clinical trials. This includes acute and chronic toxicity studies in two animal species to identify target organ toxicity and establish a maximum tolerated dose. Genotoxicity and carcinogenicity studies are also conducted to assess genetic damage and cancer risk. Alternative methods seek to reduce animal testing through computer models, cell cultures, and organ-specific assays.
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Tags: Information Security, ISO/IEC 27001, ISO/IEC 42001, Artificial Intelligence, GDPR
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This presentation includes basic of PCOS their pathology and treatment and also Ayurveda correlation of PCOS and Ayurvedic line of treatment mentioned in classics.
This presentation was provided by Steph Pollock of The American Psychological Association’s Journals Program, and Damita Snow, of The American Society of Civil Engineers (ASCE), for the initial session of NISO's 2024 Training Series "DEIA in the Scholarly Landscape." Session One: 'Setting Expectations: a DEIA Primer,' was held June 6, 2024.
How to Add Chatter in the odoo 17 ERP ModuleCeline George
In Odoo, the chatter is like a chat tool that helps you work together on records. You can leave notes and track things, making it easier to talk with your team and partners. Inside chatter, all communication history, activity, and changes will be displayed.
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Exploiting Artificial Intelligence for Empowering Researchers and Faculty, In...Dr. Vinod Kumar Kanvaria
Exploiting Artificial Intelligence for Empowering Researchers and Faculty,
International FDP on Fundamentals of Research in Social Sciences
at Integral University, Lucknow, 06.06.2024
By Dr. Vinod Kumar Kanvaria
The simplified electron and muon model, Oscillating Spacetime: The Foundation...RitikBhardwaj56
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New drug development
1. NEW DRUG
DEVELOPMENT
PRESENTED BY-
DR. RAJESH. A.
KAMTANE,
2nd YEAR PG
DEPARTMENT OF
PHARMACOLOGY,
2. From the synthesis /identification of the molecule to its
marketing, a new drug takes at least 10 years and costs
500-1000 million US$.
New drug development is done as per the guidelines
laid down by Schedule Y of Drugs and Cosmetics Act
(10th amendment)2001, which were amended later in
2005.
3. STAGES IN NEW DRUG DEVELOPMENT
1.Synthesis / isolation of compound : (1-2 years)
2. Preclinical studies : (2-4 years)
3. Scrutiny and grant of permission for clinical trials : (3-6 months)
4. Pharmaceutical formulation, standardization of chemical /
biological / immuno-assay of the compound : (0.5-1 year)
5. Clinical studies : phase 1, 2, 3 and long term animal toxicity
testing : (3-10 years)
6. Review and grant of marketing permission : (0.5-2 years)
7. Post marketing surveillance : (phase 4 studies)
4. Does it
work in
double
Is it safe? Does it work? blind
trials?
5. Drug development process can be divided into 3 main
phases-
1. Drug discovery phase- during which candidate
molecules are chosen on the basis of their
pharmacological properties.
2. Preclinical phase- during which wide range of animal
studies are performed.
3. Clinical trial phase- during which the lead compound
is evaluated for safety and efficacy in human
volunteers and patients.
6. Drug Discovery Phase
Most new drugs are discovered and identified through
one of the following approaches-
1.Random Screening-
It is a sort of blind hitting procedure where new
chemical entities (natural or synthetic) are subjected to
series of pharmacological screening procedures to
explore different types of biological activity.
Such tests include studies on animal behaviour, animal
models of the human diseases and on isolated tissues.
7. Although these approaches are time consuming,
expensive and inefficient in providing fruitful results,
sometimes these are valuable, since many drugs like
morphine, atropine, digitalis, quinidine were
discovered in this way.
Cyclosporine, an immunosuppressant drug was also
discovered during routine screening of fungal products.
10. 2. Serendipity (happy observation, by chance)
•Sometimes a new use is discovered for an old drug or
its side effect finds a new therapeutic application.
Examples-
1. Penicillin was discovered in this way, which started
the beginning of antibiotic therapy.
2. Lignocaine (local anaesthetic) and phenytoin
(antiepileptic) were later used as antiarrhythmics .
3. Methotrexate, an anticancer drug, is also used for
psoriasis.
4. Cyclophosphamide and azathioprine (both
cytotoxic drugs) are also used to prevent tissue
rejection in kidney transplant.
11. 3. Rational drug designing-
•Two basic strategies are used in rational drug
designing---compound-centered approach and target-
centered approach.
•Promising agents, through compound-centered
approach, could be obtained from natural products.
E.g. penicillin from penicillium notatum, paclitaxel
(anticancer drug) derived from Pacific yew tree,
cyclosporine (immunosuppressive drug) obtained from
fungus.
12. •The main disadvantage in obtaining lead products from
natural source is that these are often complex molecules
which are difficult to be synthesized. It is ultimately
difficult to synthesize their modified analogues also.
Hence lead optimization becomes difficult.
•Compound centered drug designing can be followed
for synthetic products also.
•Drugs can be developed from pharmacological data
obtained from structure activity relationship of an
established drug.
E.g.--- many beta blocking drugs available today are
based on propranolol structure,
--- many ‘triptans’ are based on structure of
sumatriptan.
13. Target-centered approach---
•Biochemical or molecular targets are used to search for
promising compounds.
•Example—it was known that inhibition of angiotensin-
converting enzyme (ACE) blocks conversion of
angiotensin 1 to angiotensin 2 and hence lowers the
blood pressure. Hence it made sense to look for ACE
inhibitors (ramipril, lisinopril, etc) or for angiotensin 2
receptor antagonists (losartan, candesartan, telmisartan)
as useful antihypertensives.
•With this approach, there is high possibility of
getting useful promising agents for lead
optimisation.
14. 4. Designing of a prodrug or an active
metabolite as a drug-
•Prodrug- e.g. levodopa used in treatment of
parkinsonism.
•Active metabolite-
e.g---Paracetamol, an active metabolite of phenacetin,
was introduced as a safe analgesic this way.
---Similarly, active metabolite of procainamide, N-
acetyl procainamide, is an effective antiarrhythmic
drug which does not cause lupus-like syndrome
that occurs with procainamide.
15. •After the synthesis or isolation of compound, their purity
is ascertained by physico-chemical and analytical
studies.
•Next comes the stage of LEAD OPTIMISATION where
the aim is to identify one or two drug candidates suitable
for further investigation.
16. •Three to five years may be spent to come to this stage.
•The promising LEAD COMPOUND is then subjected to
preclinical evaluation.
•The clinical trials follow only when the results of
preclinical evaluations are encouraging.
19. PRECLINICAL EVALUATION PHASE
(ANIMAL STUDIES)
•After synthesizing / identifying a prospective compound,
it is tested on animals to expose the whole
pharmacological profile.
•Experiments are generally performed on a rodent (rat,
rabbit, mouse, guinea pig, hamster) and then on a
larger animal (cat, donkey, monkey).
•As the evaluation progresses, unfavorable compounds
get rejected at each step, so that only a few out of
thousands reach the stage when administration to
humans is considered.
20. Objectives of animal studies are to evaluate---
1.Activity
2.Toxicity
3.Selectivity and Specificity
4.Mechanism of action
5.Drug metabolism
21. •The following types of studies are performed---
1.Pharmacodynamic Studies---
•Here actions relevant to the proposed therapeutic use
(and other effects) are studied on animals.
•For e.g., antihypertensive activity of the lead compound
on dogs, cats or rats to find out blood pressure changes
and other cardiac effects like ECG changes, etc.
22. 2. Tests on isolated organs, bacterial cultures,etc---
performed to detect specific activity, such as
antihistaminic, antisecretory, antibacterial, etc.
3. Tests on animal models of human diseases---such
as spontaneously (genetically) hypertensive rats,
alloxan induced diabetes in rat or dog, etc.
4. General observational test---The drug is injected in
tripling doses to small groups of mice which are
observed for overt effects. Preliminary clues are drawn
from the profile of effects observed.
23. 5. Confirmatory tests and analogous activities---
Compounds found active are taken up for detailed
study. Other related activities. e.g antipyretic and anti-
inflammatory activity in an analgesic are tested.
6. Mechanism of action---attempts are made to find out
the mechanism of action,
e.g. whether an antihypertensive is an alpha blocker or
beta blocker, etc.
24. 7. Systemic pharmacology---irrespective of the primary
action of drug, its effects on major organ systems such
as CNS, CVS, RS, GIT are worked out.
8. Quantitative tests---the dose-response relationship,
maximal effect and comparative efficacy with existing
drug is ascertained.
25. 9. Toxicological studies---
•Aim – to determine safety of the compound in at least 2
animal species, mostly mouse/rat and dog by oral and
parenteral route.
•Types of toxicity studies are-
(1) Acute toxicity-
Aim is to find out the acute
dose that is lethal to 50% of
the animals (LD 50).
Organ toxicity is examined by
histopathology on all animals.
26. 2. Subacute toxicity-
Aim is to identify the target organs susceptible to drug
toxicity.
The animals are maintained at the maximum tolerated
doses for a period of 1-3 months so as to allow
development of pathological changes.
Finally, animals are killed and subjected to
histopathological examination.
27. 3. Chronic toxicity-
Such studies are important if the drug is intended for
chronic use in human beings.
The duration of study may range from one to two
years.
These studies may also run simultaneously with
clinical trials, to cut short the time factor.
28. 10. Pharmacokinetic studies-
Done after toxicological studies.
Information is obtained for its pharmacokinetic
parameters (ADME, Vd, BA, t1/2)
11. Special long term toxicity-these tests are generally
performed only on drugs which cross phase 1 clinical
trials.
12. Reproduction and teratogenecity-effects on
spermatogenesis, ovulation, fertility and developing
foetus are studied.
29. 13. Mutagenecity-ability of the drug to induce genetic
damage is assessed in bacteria (Ames test), mammalian
cell cultures and in intact rodents.
14. Carcinogenecity-drug is given for long term, even
the whole life of the animal and they are watched for
development of tumours.
Standardizied procedures under ‘Good Laboratory
Practices’ (GLP) are laid down for conduct of animal
experiments, especially toxicity studies.
30. Assessment of Safety Index-
Therapeutic index
Maximum Tolerated Dose (MTD),
No Observable Adverse Effects Level (NOAEL),
No Observable Effects Level (NOEL) and
Human Equivalent Dose (HED) are determined in
species similar to humans (like monkeys), finally to
calculate First in Human Dose (FIH) which will be latter
used in phase 1 clinical trials.
FIH is 1/5 or 1/10th of HED.
32. Ethics Committees
• The ethics committee reviews a protocol before the
study is allowed to start. Their job is to ensure that
the risks of being in the study are not greater than
the potential benefit.
33. IRB( Institutional Review Board)
IEC (Independent Ethical
Committee)
• To ensure the rights and welfare of the participants.
• FDA regulations mandates to review the clinical trial
protocols for ethical and legal issues.
34. IRB
The investigator must furnish the IRB with the
following documents for review and approval:
• Trial Protocol
• Written Informed Consent Forms
• Written Information for Subjects (Advertisements)
• Information about compensation to patients
• Investigator Brochure
• Available (or additional) Safety Information
• Investigator’s CV
• All amendments to study protocol
34
35. IRB
The IRB’s possible responses:
• approval or favorable opinion
• modifications required for approval
• disapproval or negative opinion
• withdrawal or suspension of an earlier approval
No subjects should be enrolled until the IRB has issued
an approval (21 CFR 56.109)
35
36. Informed Consent
• Eight basic elements of informed consent (21 CFR
50.25)
1. Trial involves research, purpose of the research
2. A description of any reasonably foreseeable risks or
discomforts
3. A description of any benefits to the subject which may
reasonable be expected from the research
4. A disclosure of appropriate alternative procedures or
treatment that may be available to the subject
37. Informed Consent
5. A statement describing the extent to which
confidentiality of records identifying the subject will be
maintained.
6. An explanation as to whether any compensation and
whether any medical treatments are available if injury
occurs.
7. An explanation of whom to contact for answers to
questions about the research and research subjects’
rights .
8. A statement that participation is voluntary
37
38. Informed Consent
• Participation in clinical trials is always voluntary.
No, thank you, I’d Yes, I would
rather not participate. like to
participate.
Clinical Trials & Research 38
39. Informed Consent
• Purpose • Risks
• Medicine to be • Potential benefits
studied
• Alternatives to
• Procedures and participation
schedule
• Confidentiality
Clinical Trials & Research 39
40. What is a Clinical Trial?
Identify a health question.
Develop a plan.
Enroll volunteers and follow the plan.
Study the information collected.
Share the results with others.
Improve treatment.
Clinical Trials & Research 40
41.
42. Objectives of a clinical trial are to establish---
1.Safety
2.Efficacy
3.Therapeutic conformation in a large population.
4.Drug metabolism in humans.
5.Unpredicted adverse reactions and new
therapeutic applications during wide use in the
community.
43. CLINICAL TRIALS-
•When a compound deserving trial in man is identified
by animal studies, the regulatory authorities are
approached who on satisfaction issue an
‘investigational new drug’ (IND) license.
•The drug is formulated into a
suitable dosage form and clinical
trials are conducted in a phased
manner.
44. •Standards for design, ethics, conduct, monitoring,
auditing, recording and analyzing data and reporting of
clinical trials have been laid down in the form of ‘Good
Clinical Practice’ (GCP) guidelines by an International
Conference on Harmonization (ICH) and Declaration of
Helsinki.
NAZI HUMAN EXPERIMENTS
45. Declaration of Helsinki-1964
1.The clinical trial must minimize the risk for
participants.
2.Provision for care of the patients.
3.Terminate the trial when the risk becomes
incompatible with the goals of the trial.
4.Adverse events to be reported immediately to
an ethical committee
46. Phases of Clinical Trials
Phase I:
Safety
(15–30 people)
A A A
A
A A
A
A Phase II:
Safety and Effectiveness
(Fewer than 100 people)
A A
A
A Phase III:
Effectiveness compared to standard of care; Safety
(More than 100 to a few thousand) A A A
A A
A
A
A A A A
A
A A A
A A A A A A A
A A
Clinical Trials & Research 46
47. Phase 0 Clinical trials
Known as
Human Micro dosing.
To confirm whether
the drug behaves in
human subject as was
expected from pre clinical
studies.
48. Phase 0 Clinical trials
Single sub therapeutic doses of the study drug is
given to a small number of subjects ( 10 to 15 ).
Purpose is to gather preliminary data on best PK
and PD parameters in humans to take forward for
further development.
It gives no data on Safety or Efficacy.
49. The clinical studies are conventionally divided into 4
phases-
Phase 1: Human pharmacology and Safety.
The objectives of this phase are---
1. To check for safety and tolerability .
2. To determine the pharmacokinetics of the drug in
humans.
50. 3.To determine a safe clinical dosage range in humans.
The common rule is to begin with 1/5th or 1/10th of
the maximum tolerated dose (mg/kg) in animals
and calculating it for an average human body weight
of 70 kg. The drug is then given in small increments till
the therapeutically effective dose is attained by clinical
observation.
51. Phase 1 trial is carried out by qualified clinical
pharmacologists/ trained physicians in a setting where
all emergency/ resuscitative facilities are available.
52. Subjects (mostly healthy volunteers, sometimes
patients) are exposed to the drug one by one (total
20-40 subjects) , starting with lowest estimated dose
and increasing stepwise to achieve the effective dose.
No blinding is done: the study is open label. i.e.
both, the investigator and the subjects know what is
being given.
53. Phase 2: Therapeutic exploration and dose ranging-
•In this phase, the drug is studied for the first time in
patients with target disease, to determine its
efficacy.
•The main purpose is to decide an end point.
e.g.
•pain relief is the end point for testing an analgesic.
•reduction in tumour size for anticancer drugs.
54. •The study is generally carried out at 2-4 centers.
•Phase 2 can be single or double blind study.
55. •Such studies are mainly conducted in two ways-
a. Parallel design---
One group receives the new drug under trial while
other group receives control (established drug) or
placebo.
Then results in one group are compared with those in
other group.
56. b. Crossover design---
Here the new drug is alternated with control
(established drug or placebo) in the same patient.
In this method, patient acts as his own control.
This reduces the chances of erroneous results due to
individual variation amongst the patients.
57. Phase 3: Therapeutic Conformation/ Comparison-
•Generally these are randomized, double blind
comparative, controlled clinical trials.
•Conducted on a larger patient population (500-3000) by
several physicians at many centers.
•Here new drug is compared with previously established
drug or placebo, under standardized conditions.
58. •Safety, tolerability, and possible drug interactions are
assessed on a wider scale.
•Indications are finalized and guidelines for
therapeutic use are formulated.
•A ‘new drug application’ (NDA) is submitted to the
licensing authority, who if convinced gives marketing
permission, with ‘New Drug Status’
60. Phase 4
Drug is placed in the market and patients are
monitored for side effects.
61. Phase 4: Postmarketing surveillance-
•In phase 4, data on safety, efficacy and tolerability is
collected from practicing physicians.
•Uncommon/ idiosyncratic adverse effects and
unsuspected drug interactions are detected at this stage.
•Additional indications may emerge from surveillance
data.
•The phase 4 has no fixed duration as it is the
surveillance phase.
62. •During the ‘New Drug Status’, the manufacturer is
expected to report any new information about the drug
concerning its safety.
•Such Periodic Safety Update Report (PSUR) is to be
submitted every six months for first 2 years and then
annually for the next 2 years.
•The drug may remain in ‘New Drug Status’ for several
years until the Drug Control authorities are confident
about its release to unrestricted marketing.
63. •Further therapeutic trials involving special groups like
children, elderly, pregnant, lactating women, patients
with renal/ hepatic diseases, etc (which are generally
excluded during clinical trials) may be undertaken at this
stage.