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
The document discusses the drug development process from discovery to approval. It covers key stages including discovery research, preclinical testing, clinical trials, regulatory review and approval, and product launch. Key aspects addressed are screening compounds for drug candidates, assessing safety and efficacy in animal and human studies, developing formulations, and engaging regulatory agencies for approval to market a new drug. The overall goal is to discover, develop and launch new pharmaceutical products that treat diseases and conditions.
Drug discovery By Neelima Sharma WCC chennai,neelima.sharma60@gmail.comNeelima Sharma
The document provides an overview of the drug discovery process, including the need for new drugs, approaches to discovery, and changes over time. It discusses target identification, validation, lead identification, optimization, and preclinical pharmacology/toxicology. The phases of clinical trials are also summarized, including Phase I safety trials in healthy volunteers, Phase II therapeutic exploration trials, and large Phase III randomized controlled trials. The roles of various parties in clinical trials are also outlined.
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]
The document discusses drug discovery and the new drug development process. It describes how drugs are developed to treat diseases, which can be infections, genetic disorders, or results of environmental conditions. The development process is long and complex, involving many scientific and technical experts. The document also provides numerous examples of plant-based drugs and the plants and chemicals they are derived from to treat various medical conditions.
The document discusses drug discovery and development. It begins with definitions of key terms like drug, drug discovery process, and drug development process. It then describes the main stages of new drug development, including drug discovery, preclinical development, and clinical development. Specific examples of discovered drugs are provided, such as artemisinin from Artemisia annua used to treat malaria, and andrographolide from Andrographis paniculata which has anti-inflammatory properties. The biosynthesis process of andrographolide is also summarized. In conclusion, the document provides an overview of the drug discovery and development process from target identification to clinical trials.
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.
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.
The document discusses the importance of biotechnology in drug discovery. It notes that biotechnology has produced over 200 new therapies targeting various diseases. Biotechnology companies are more entrepreneurial and nimble compared to traditional pharmaceutical companies. The document also provides details on the large and growing biotech market in India and worldwide. It describes several applications of biotechnology across various stages of the drug discovery process, including target identification and validation, assay development, high-throughput screening, biomarker analysis, and protein engineering.
The document discusses the drug development process from discovery to approval. It covers key stages including discovery research, preclinical testing, clinical trials, regulatory review and approval, and product launch. Key aspects addressed are screening compounds for drug candidates, assessing safety and efficacy in animal and human studies, developing formulations, and engaging regulatory agencies for approval to market a new drug. The overall goal is to discover, develop and launch new pharmaceutical products that treat diseases and conditions.
Drug discovery By Neelima Sharma WCC chennai,neelima.sharma60@gmail.comNeelima Sharma
The document provides an overview of the drug discovery process, including the need for new drugs, approaches to discovery, and changes over time. It discusses target identification, validation, lead identification, optimization, and preclinical pharmacology/toxicology. The phases of clinical trials are also summarized, including Phase I safety trials in healthy volunteers, Phase II therapeutic exploration trials, and large Phase III randomized controlled trials. The roles of various parties in clinical trials are also outlined.
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]
The document discusses drug discovery and the new drug development process. It describes how drugs are developed to treat diseases, which can be infections, genetic disorders, or results of environmental conditions. The development process is long and complex, involving many scientific and technical experts. The document also provides numerous examples of plant-based drugs and the plants and chemicals they are derived from to treat various medical conditions.
The document discusses drug discovery and development. It begins with definitions of key terms like drug, drug discovery process, and drug development process. It then describes the main stages of new drug development, including drug discovery, preclinical development, and clinical development. Specific examples of discovered drugs are provided, such as artemisinin from Artemisia annua used to treat malaria, and andrographolide from Andrographis paniculata which has anti-inflammatory properties. The biosynthesis process of andrographolide is also summarized. In conclusion, the document provides an overview of the drug discovery and development process from target identification to clinical trials.
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.
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.
The document discusses the importance of biotechnology in drug discovery. It notes that biotechnology has produced over 200 new therapies targeting various diseases. Biotechnology companies are more entrepreneurial and nimble compared to traditional pharmaceutical companies. The document also provides details on the large and growing biotech market in India and worldwide. It describes several applications of biotechnology across various stages of the drug discovery process, including target identification and validation, assay development, high-throughput screening, biomarker analysis, and protein engineering.
Drug discovery and development is a long, expensive, and complex process that takes an average of 10-12 years and $800 million to $1.7 billion. It involves identifying candidate drugs through methods like molecular designing, screening, and serendipity. Only one in 5000 compounds makes it through preclinical and clinical testing to be approved. The process includes target selection and validation, lead discovery and optimization, and drug development to satisfy regulatory requirements before a new drug can be approved and marketed.
This document discusses various aspects of drug discovery and pharmacogenomics. It defines drugs and the drug discovery process, which involves identifying lead compounds and developing drugs. It also describes computer-aided drug design, pharmacogenomics as the study of an individual's genetic makeup and response to drugs, and antisense technology for treating disease. The goal is to develop personalized medicine by optimizing drug therapy based on a patient's genotype.
Topic explained as a M.Sc. Microbiology Student point of you. It contains general Properties of drug, its discovery process and Rational Drug Design Process using Bioinformatic Tools.
The document summarizes the process of drug discovery and development. It involves several long steps: understanding the disease, finding a biological target, discovering a lead compound through screening or nature, conducting preclinical testing on animals, and then clinical trials in three phases with humans to test safety and efficacy before the FDA decides whether to approve the drug. The entire process from discovery to approval takes an average of 10-15 years and costs $1-2 billion. Drugs also have different categories depending on how they are regulated and prescribed.
Drug discovery and Development by vinay guptaDr Vinay Gupta
The document discusses various aspects of drug discovery and development, including:
1) The drug development process involves pre-clinical and clinical trials that are regulated by agencies like DCGI in India and FDA in the US.
2) Pre-clinical trials involve pharmacological, toxicological, and pharmacokinetic testing in animals to establish safety before human trials.
3) Clinical trials have 4 phases - Phase I evaluates safety in healthy volunteers, Phase II explores efficacy in patients, Phase III confirms efficacy and monitors side effects in large patient groups, and Phase IV involves post-marketing surveillance.
The document provides an overview of the drug development pathway and requirements for clinical trials and regulatory approval.
The document provides an overview of the drug development process. It discusses the major stages of clinical trials from Phase I to Phase IV that drugs must go through for testing and approval. The goals are to determine safety, efficacy, appropriate dosing, and identify any adverse effects. Rigorous clinical trials with control groups, randomization, and large sample sizes are necessary to provide substantial evidence for approval. The overall process takes an average of about 100 months from initial synthesis to approval.
Drug discovery challenges and different discovery approachesHitesh Soni
The document discusses several challenges in drug discovery and different discovery approaches. It outlines issues with the traditional high-throughput screening approach such as low success rates. It then describes alternative approaches like considering transient binding drugs that interact weakly with multiple targets, leveraging natural products as drug leads, and exploring a multi-target drug discovery strategy to address complex diseases involving multiple molecular dysfunctions.
Drug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes preclinical research on microorganisms and animals, filing for regulatory status, such as via the United States Food and Drug Administration for an investigational new drug to initiate clinical trials on humans, and may include the step of obtaining regulatory approval with a new drug application to market the drug
Drug development is considered as a series of well defined steps, culminating, if successful, in market authorization, of the drug
The drug development process involves lengthy preclinical and clinical testing that can take over 12 years and cost $350 million. It begins with drug discovery followed by preclinical studies to test the drug's toxicity, pharmacokinetics, and efficacy in animals. If successful, an IND application is submitted to the FDA to begin human clinical trials. Clinical trials involve 4 phases to test the drug's safety and efficacy in humans. If phase 3 is successful, an NDA is submitted for FDA review and potential approval to market the new drug. Post-approval monitoring continues to ensure safety.
The document outlines regulatory guidelines for validating traditional medicines through preclinical and clinical studies. It discusses the types of information required in investigational new drug applications (INDs) for botanical drug products, including descriptions of the botanical ingredients, manufacturing and quality controls, pharmacology, toxicity studies, and previous human experience. The level of information required increases from initial clinical trials to expanded clinical trials and approaches for new drug applications (NDAs). Preclinical studies help identify compounds likely to be safe and effective in humans, while clinical trials progress from small initial safety studies to larger efficacy trials.
Drug development involves preclinical and clinical phases. Preclinical development can take 1-5 years and involves in vitro and in vivo studies to determine pharmacological efficacy, safety, and first human dose. Clinical development has four phases. Phase I studies a drug's safety on 50-100 healthy volunteers. Phase II assesses efficacy on 100-400 patients. Phase III verifies efficacy and safety on 500-2000 patients across sites. Phase IV monitors safety post-marketing through physician reporting. The goal is to determine a drug's pharmacological properties, safety, and efficacy to support regulatory approval and post-market surveillance.
The document discusses the process for approval of a new drug from development through marketing. It takes 10-15 years on average and costs over $2.6 billion to get a new drug approved. Key steps include:
- Preclinical research to identify biological targets and compounds
- FDA approval to begin clinical trials in three phases involving thousands of subjects to test safety, efficacy, and dosing
- New Drug Application submission including all clinical trial data for FDA review and approval
- Post-marketing studies and generic approval after patents expire
Drug development - Background informationXplore Health
This guide provides background information on the drug development process including the different phases and the ethical, legal and social aspects associated.
clinical and preclinical approaches to drug discovery.Here we mainly deals with preclinical approaches, ie. Pharmacological approach and toxicological approach
The document provides an overview of the drug discovery and development process. It discusses the various stages involved, including target selection using genomics, proteomics and bioinformatics; lead discovery through synthesis, isolation and high-throughput screening; medicinal chemistry such as structure-activity relationships studies; in vitro and preclinical in vivo testing in animal models; and clinical trials in humans. The timeline for this process can span over 10-15 years from drug target identification to regulatory approval. Key techniques and approaches at each stage are also summarized.
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.
INTRODUCTION
A PERFECT THERAPEUTIC DRUG
DRUG DISCOVERY- HISTORY
MODERN DRUG DISCOVERY
BIOINFORATICS IN DRUG DISCOVERY
DRUG DISCOVERY BASED ON BIOINFORMATIC TOOLS
BIOINFORMATICS IN COMPUTER-AIDED DRUG DISCOVERY
ECONOMICS OF DRUG DISCOVERY
CONCLUSION
REFERENCES
Drug design and discovery is a complex, time-consuming and expensive process that involves identifying biological targets and developing ligands to interact with them. Computational tools and global gene expression analysis have increased efficiency by aiding in structure-guided drug design and target identification. The traditional methods of drug design involve developing ligands for targets with known structures or developing ligands with predefined properties for unknown targets. The drug development process takes an average of 10-15 years and has a high failure rate, with only a small fraction of potential drugs ultimately being approved after progressing through clinical trials and regulatory review.
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 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.
Drug discovery and development is a long, expensive, and complex process that takes an average of 10-12 years and $800 million to $1.7 billion. It involves identifying candidate drugs through methods like molecular designing, screening, and serendipity. Only one in 5000 compounds makes it through preclinical and clinical testing to be approved. The process includes target selection and validation, lead discovery and optimization, and drug development to satisfy regulatory requirements before a new drug can be approved and marketed.
This document discusses various aspects of drug discovery and pharmacogenomics. It defines drugs and the drug discovery process, which involves identifying lead compounds and developing drugs. It also describes computer-aided drug design, pharmacogenomics as the study of an individual's genetic makeup and response to drugs, and antisense technology for treating disease. The goal is to develop personalized medicine by optimizing drug therapy based on a patient's genotype.
Topic explained as a M.Sc. Microbiology Student point of you. It contains general Properties of drug, its discovery process and Rational Drug Design Process using Bioinformatic Tools.
The document summarizes the process of drug discovery and development. It involves several long steps: understanding the disease, finding a biological target, discovering a lead compound through screening or nature, conducting preclinical testing on animals, and then clinical trials in three phases with humans to test safety and efficacy before the FDA decides whether to approve the drug. The entire process from discovery to approval takes an average of 10-15 years and costs $1-2 billion. Drugs also have different categories depending on how they are regulated and prescribed.
Drug discovery and Development by vinay guptaDr Vinay Gupta
The document discusses various aspects of drug discovery and development, including:
1) The drug development process involves pre-clinical and clinical trials that are regulated by agencies like DCGI in India and FDA in the US.
2) Pre-clinical trials involve pharmacological, toxicological, and pharmacokinetic testing in animals to establish safety before human trials.
3) Clinical trials have 4 phases - Phase I evaluates safety in healthy volunteers, Phase II explores efficacy in patients, Phase III confirms efficacy and monitors side effects in large patient groups, and Phase IV involves post-marketing surveillance.
The document provides an overview of the drug development pathway and requirements for clinical trials and regulatory approval.
The document provides an overview of the drug development process. It discusses the major stages of clinical trials from Phase I to Phase IV that drugs must go through for testing and approval. The goals are to determine safety, efficacy, appropriate dosing, and identify any adverse effects. Rigorous clinical trials with control groups, randomization, and large sample sizes are necessary to provide substantial evidence for approval. The overall process takes an average of about 100 months from initial synthesis to approval.
Drug discovery challenges and different discovery approachesHitesh Soni
The document discusses several challenges in drug discovery and different discovery approaches. It outlines issues with the traditional high-throughput screening approach such as low success rates. It then describes alternative approaches like considering transient binding drugs that interact weakly with multiple targets, leveraging natural products as drug leads, and exploring a multi-target drug discovery strategy to address complex diseases involving multiple molecular dysfunctions.
Drug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes preclinical research on microorganisms and animals, filing for regulatory status, such as via the United States Food and Drug Administration for an investigational new drug to initiate clinical trials on humans, and may include the step of obtaining regulatory approval with a new drug application to market the drug
Drug development is considered as a series of well defined steps, culminating, if successful, in market authorization, of the drug
The drug development process involves lengthy preclinical and clinical testing that can take over 12 years and cost $350 million. It begins with drug discovery followed by preclinical studies to test the drug's toxicity, pharmacokinetics, and efficacy in animals. If successful, an IND application is submitted to the FDA to begin human clinical trials. Clinical trials involve 4 phases to test the drug's safety and efficacy in humans. If phase 3 is successful, an NDA is submitted for FDA review and potential approval to market the new drug. Post-approval monitoring continues to ensure safety.
The document outlines regulatory guidelines for validating traditional medicines through preclinical and clinical studies. It discusses the types of information required in investigational new drug applications (INDs) for botanical drug products, including descriptions of the botanical ingredients, manufacturing and quality controls, pharmacology, toxicity studies, and previous human experience. The level of information required increases from initial clinical trials to expanded clinical trials and approaches for new drug applications (NDAs). Preclinical studies help identify compounds likely to be safe and effective in humans, while clinical trials progress from small initial safety studies to larger efficacy trials.
Drug development involves preclinical and clinical phases. Preclinical development can take 1-5 years and involves in vitro and in vivo studies to determine pharmacological efficacy, safety, and first human dose. Clinical development has four phases. Phase I studies a drug's safety on 50-100 healthy volunteers. Phase II assesses efficacy on 100-400 patients. Phase III verifies efficacy and safety on 500-2000 patients across sites. Phase IV monitors safety post-marketing through physician reporting. The goal is to determine a drug's pharmacological properties, safety, and efficacy to support regulatory approval and post-market surveillance.
The document discusses the process for approval of a new drug from development through marketing. It takes 10-15 years on average and costs over $2.6 billion to get a new drug approved. Key steps include:
- Preclinical research to identify biological targets and compounds
- FDA approval to begin clinical trials in three phases involving thousands of subjects to test safety, efficacy, and dosing
- New Drug Application submission including all clinical trial data for FDA review and approval
- Post-marketing studies and generic approval after patents expire
Drug development - Background informationXplore Health
This guide provides background information on the drug development process including the different phases and the ethical, legal and social aspects associated.
clinical and preclinical approaches to drug discovery.Here we mainly deals with preclinical approaches, ie. Pharmacological approach and toxicological approach
The document provides an overview of the drug discovery and development process. It discusses the various stages involved, including target selection using genomics, proteomics and bioinformatics; lead discovery through synthesis, isolation and high-throughput screening; medicinal chemistry such as structure-activity relationships studies; in vitro and preclinical in vivo testing in animal models; and clinical trials in humans. The timeline for this process can span over 10-15 years from drug target identification to regulatory approval. Key techniques and approaches at each stage are also summarized.
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.
INTRODUCTION
A PERFECT THERAPEUTIC DRUG
DRUG DISCOVERY- HISTORY
MODERN DRUG DISCOVERY
BIOINFORATICS IN DRUG DISCOVERY
DRUG DISCOVERY BASED ON BIOINFORMATIC TOOLS
BIOINFORMATICS IN COMPUTER-AIDED DRUG DISCOVERY
ECONOMICS OF DRUG DISCOVERY
CONCLUSION
REFERENCES
Drug design and discovery is a complex, time-consuming and expensive process that involves identifying biological targets and developing ligands to interact with them. Computational tools and global gene expression analysis have increased efficiency by aiding in structure-guided drug design and target identification. The traditional methods of drug design involve developing ligands for targets with known structures or developing ligands with predefined properties for unknown targets. The drug development process takes an average of 10-15 years and has a high failure rate, with only a small fraction of potential drugs ultimately being approved after progressing through clinical trials and regulatory review.
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 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.
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.
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.
Drug Development Life Cycle - Costs and RevenueRobert Sturm
Presentation explains the Drug Development Process in terms of time/costs from initial research to final manufacturing. It presents strategies for increasing profits/decreasing costs, shows the impact of generics and details how Information Technology fits into this equation. It uses research from DiMasi and Grabowski to identify drug costs and product revenue.
The document discusses the applications of pharmacokinetics in new drug development, dosage form design, and novel drug delivery systems (NDDS). It covers key topics such as:
1) How pharmacokinetic principles can be applied to the design and development of new drugs, controlled release formulations, and the selection of appropriate routes of administration.
2) The important pharmacokinetic parameters used in characterization and the approaches used for dosage regimen design.
3) How pharmacokinetics can aid in formulation development, bioavailability/bioequivalence testing, and the development of various NDDS.
4) Considerations for dosing adjustments based on patient factors like obesity, age, hepatic or renal impairment
Drug discovery process style 5 powerpoint presentation templatesSlideTeam.net
The document describes the key stages in the drug discovery process, including cellular and genetic target identification, compound synthesis and isolation, high-throughput screening, lead optimization, preclinical testing in animal models and in vitro/in vivo studies, and clinical trials in humans. The flow diagram shows the iterative process moving from early research to identify biological targets through compound development and testing, culminating in clinical evaluation and potential approval of new therapeutics.
Drug discovery and development is and always has been the most exciting part of clinical pharmacology. It is my attempt to compile the basic concepts from various books, articles and online journals. Feel free to comment.
Key Concepts of Clinical Research & Clinical Trial SWAROOP KUMAR K
Clinical trials generate safety and efficacy data for health interventions in human beings and are conducted after satisfactory pre-clinical animal testing. There are various types of clinical trials including observational studies, interventional studies, prevention trials, screening trials, diagnostic trials, and treatment trials. Clinical trials progress through phases including pre-clinical, Phase 1, Phase 2, Phase 3, and Phase 4 post-marketing surveillance trials. The goal is to demonstrate a treatment's safety and efficacy compared to current standard of care.
This document discusses the clinical trials process from protocol development through study completion. It covers developing the protocol, regulatory documents, patient recruitment, safety reporting, interim reports, and end of study activities. Key aspects include writing an approvable protocol, establishing an investigator site file, screening and enrolling suitable patients, maintaining safety oversight, and conducting closeout procedures. The goal is to provide guidance on managing all stages of a clinical trial.
Clinical research involves systematic studies in human subjects to improve quality of life. Clinical trials are a form of clinical research that experimentally tests medications, devices, or biologics to evaluate safety and effectiveness. There are different phases of clinical trials, from small early phase safety studies to larger late phase studies to establish efficacy. Clinical trials require many players including regulators, sponsors, investigators, ethics committees, and participants to design, monitor, and conduct the trials according to strict protocols to safely and effectively evaluate potential new treatments.
Introduction to pre clinical screening of drugsKanthlal SK
Various Techniques and Methods for screening of new chemical entities in preclinical aspects (both invitro & invivo) for effective and safe clinical usage.
Clinical trials involve several phases:
- Phase I trials involve small groups of healthy volunteers or patients and aim to determine the safety and tolerability of a new drug.
- Phase II trials involve larger groups of patients and aim to determine efficacy and further evaluate safety. These trials provide preliminary data on effectiveness.
- Phase III trials involve even more patients and aim to confirm effectiveness, monitor side effects, and compare the new treatment to standard treatment. These trials provide the primary data to support effectiveness. Regulatory approval is based on positive Phase III results showing safety and effectiveness.
The document discusses drug design, development, and delivery. It covers rational drug design using molecular properties and receptor modeling. Computer-assisted drug design uses molecular docking and QSAR methods. Neural networks are also used in drug design. Drug discovery involves identifying candidates and screening for efficacy. Drug development evaluates ADME, toxicity, and safety through preclinical and clinical studies. Drug delivery methods aim to effectively administer pharmaceutical compounds and improve drug release profiles.
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
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 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.
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
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.
Preclinical drug discovery and developmentsamthamby79
This document provides an overview of preclinical drug discovery and development processes. It discusses rational drug design, screening approaches, molecular modification of lead compounds, pharmacokinetic and toxicology studies in animal models, and regulatory requirements for data on a drug's primary pharmacology, secondary effects, and interactions prior to clinical trials. The goal of preclinical research is to obtain sufficient safety and efficacy data on new chemical entities to justify testing in humans.
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.
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.
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 discusses the process of preclinical and clinical evaluation of new chemical entities from drug discovery through approval. In preclinical studies, potential new drugs are tested in animals to evaluate safety, toxicity, pharmacokinetics and pharmacodynamics. If results are promising, human clinical trials are conducted in phases to test safety and efficacy. Phase 0 involves microdosing, Phase I tests first use in humans, Phase II evaluates dosing and efficacy, and Phase III extends these tests to more patients in a blinded study. If successful, the drug can receive approval for marketing and ongoing monitoring in Phase IV. Preclinical data helps determine appropriate human dosing before moving to clinical trials.
This document discusses various types of animal toxicity studies conducted prior to clinical use of drugs in humans. It provides objectives and details of reproductive and developmental toxicity studies, local toxicity studies, carcinogenicity studies, and genotoxicity studies. Reproductive toxicity studies examine effects on fertility and development in offspring. Developmental toxicity studies evaluate effects during pregnancy and across lifespan. Local toxicity studies are required when drugs are administered via non-oral routes. Carcinogenicity studies identify substances that may induce or increase tumors.
Toxicity studies in animals are conducted to identify any toxic effects of a substance prior to clinical use in humans. The document outlines various types of toxicity studies including acute, subacute, chronic, and lethality studies. Acute studies involve a single high dose to determine toxic effects over 14 days, while repeated dose studies like subacute and chronic studies administer multiple lower doses over weeks to years to identify target organ toxicity. Lethality studies determine the lethal dose for 50% of animals (LD50). Systemic toxicity parameters evaluated include effects on liver, kidney, heart and other organs. Toxicity studies provide safety information required for approval to conduct human clinical trials.
This document provides an overview of toxicity testing methods for acute, subacute, and chronic toxicity studies. It discusses the importance and history of toxicity testing, as well as standard methods and guidelines established by organizations like OECD and EPA. A variety of in vivo and in vitro toxicity tests are described, including acute, repeated dose, genotoxicity, carcinogenicity, and local toxicity studies. The document also addresses the large number of animals used annually for toxicity testing globally and the regulatory framework for animal testing in India.
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.
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.
GENERAL GUIDELINES FOR TOXICOPATHOLOGY STUDYRahul Kadam
The nonclinical safety study recommendations for the marketing approval
of a pharmaceutical usually include single and repeated dose toxicity
studies, reproduction toxicity studies, genotoxicity studies, local tolerance
studies, and for drugs that have special cause for concern or are intended
for a long duration of use, an assessment of carcinogenic potential. Other
nonclinical studies include pharmacology studies for safety assessment
(safety pharmacology) and pharmacokinetic (absorption, distribution,
metabolism, and excretion (ADME)) studies. These types of studies and
their relation to the conduct of human clinical trials are presented in this
guidance.
The document discusses various approaches to drug discovery, including pharmacological, toxicological, and preclinical trials. It describes the components of pharmacological evaluation including selectivity testing, pharmacological profiling in vitro and in vivo, and safety pharmacology testing of major organ systems like central nervous system, cardiovascular, and respiratory systems. The goal of preclinical trials is to determine if a new drug works and is safe to test in humans using animal models and evaluating its pharmacological effects, toxicity, and safety pharmacologically.
This document provides an overview of experimental toxicology and the use of animal models. It discusses the importance of animal models in toxicity testing and research. It covers key aspects of conducting animal studies including the four R's (replacement, reduction, refinement, and responsibility), selecting appropriate animal models and strains, husbandry and care of animals, dosing techniques, and understanding animal physiology. The origins of predictive animal testing are reviewed through important cases that prompted regulations requiring pre-market safety testing of drugs and chemicals.
introduction to practical pharmacology, various experimental animal uses, CPCSEA guidelines, different phases of clinical trial, pre-clinical trial, important pharmacological definition
Pre-clinical screening involves testing potential new drugs in animal models before human trials to evaluate safety and efficacy. This includes pharmacological screening to determine mechanism of action and dose response, as well as toxicological testing to identify adverse effects and calculate safe starting doses for clinical trials. Studies progress from molecular and cellular assays to whole animal experiments. Acute and repeated dose toxicity tests are followed by sub-chronic and chronic studies to identify long-term effects. These pre-clinical studies aim to generate data required to deem a new compound safe enough for initial human testing.
This presentation was provided by Racquel Jemison, Ph.D., Christina MacLaughlin, Ph.D., and Paulomi Majumder. Ph.D., all of the American Chemical Society, for the second session of NISO's 2024 Training Series "DEIA in the Scholarly Landscape." Session Two: 'Expanding Pathways to Publishing Careers,' was held June 13, 2024.
How to Setup Warehouse & Location in Odoo 17 InventoryCeline George
In this slide, we'll explore how to set up warehouses and locations in Odoo 17 Inventory. This will help us manage our stock effectively, track inventory levels, and streamline warehouse operations.
Temple of Asclepius in Thrace. Excavation resultsKrassimira Luka
The temple and the sanctuary around were dedicated to Asklepios Zmidrenus. This name has been known since 1875 when an inscription dedicated to him was discovered in Rome. The inscription is dated in 227 AD and was left by soldiers originating from the city of Philippopolis (modern Plovdiv).
Beyond Degrees - Empowering the Workforce in the Context of Skills-First.pptxEduSkills OECD
Iván Bornacelly, Policy Analyst at the OECD Centre for Skills, OECD, presents at the webinar 'Tackling job market gaps with a skills-first approach' on 12 June 2024
ISO/IEC 27001, ISO/IEC 42001, and GDPR: Best Practices for Implementation and...PECB
Denis is a dynamic and results-driven Chief Information Officer (CIO) with a distinguished career spanning information systems analysis and technical project management. With a proven track record of spearheading the design and delivery of cutting-edge Information Management solutions, he has consistently elevated business operations, streamlined reporting functions, and maximized process efficiency.
Certified as an ISO/IEC 27001: Information Security Management Systems (ISMS) Lead Implementer, Data Protection Officer, and Cyber Risks Analyst, Denis brings a heightened focus on data security, privacy, and cyber resilience to every endeavor.
His expertise extends across a diverse spectrum of reporting, database, and web development applications, underpinned by an exceptional grasp of data storage and virtualization technologies. His proficiency in application testing, database administration, and data cleansing ensures seamless execution of complex projects.
What sets Denis apart is his comprehensive understanding of Business and Systems Analysis technologies, honed through involvement in all phases of the Software Development Lifecycle (SDLC). From meticulous requirements gathering to precise analysis, innovative design, rigorous development, thorough testing, and successful implementation, he has consistently delivered exceptional results.
Throughout his career, he has taken on multifaceted roles, from leading technical project management teams to owning solutions that drive operational excellence. His conscientious and proactive approach is unwavering, whether he is working independently or collaboratively within a team. His ability to connect with colleagues on a personal level underscores his commitment to fostering a harmonious and productive workplace environment.
Date: May 29, 2024
Tags: Information Security, ISO/IEC 27001, ISO/IEC 42001, Artificial Intelligence, GDPR
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Slideshare: http://www.slideshare.net/PECBCERTIFICATION
This presentation was provided by Rebecca Benner, Ph.D., of the American Society of Anesthesiologists, for the second session of NISO's 2024 Training Series "DEIA in the Scholarly Landscape." Session Two: 'Expanding Pathways to Publishing Careers,' was held June 13, 2024.
This document provides an overview of wound healing, its functions, stages, mechanisms, factors affecting it, and complications.
A wound is a break in the integrity of the skin or tissues, which may be associated with disruption of the structure and function.
Healing is the body’s response to injury in an attempt to restore normal structure and functions.
Healing can occur in two ways: Regeneration and Repair
There are 4 phases of wound healing: hemostasis, inflammation, proliferation, and remodeling. This document also describes the mechanism of wound healing. Factors that affect healing include infection, uncontrolled diabetes, poor nutrition, age, anemia, the presence of foreign bodies, etc.
Complications of wound healing like infection, hyperpigmentation of scar, contractures, and keloid formation.
Gender and Mental Health - Counselling and Family Therapy Applications and In...PsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
A Visual Guide to 1 Samuel | A Tale of Two HeartsSteve Thomason
These slides walk through the story of 1 Samuel. Samuel is the last judge of Israel. The people reject God and want a king. Saul is anointed as the first king, but he is not a good king. David, the shepherd boy is anointed and Saul is envious of him. David shows honor while Saul continues to self destruct.
Chapter wise All Notes of First year Basic Civil Engineering.pptxDenish Jangid
Chapter wise All Notes of First year Basic Civil Engineering
Syllabus
Chapter-1
Introduction to objective, scope and outcome the subject
Chapter 2
Introduction: Scope and Specialization of Civil Engineering, Role of civil Engineer in Society, Impact of infrastructural development on economy of country.
Chapter 3
Surveying: Object Principles & Types of Surveying; Site Plans, Plans & Maps; Scales & Unit of different Measurements.
Linear Measurements: Instruments used. Linear Measurement by Tape, Ranging out Survey Lines and overcoming Obstructions; Measurements on sloping ground; Tape corrections, conventional symbols. Angular Measurements: Instruments used; Introduction to Compass Surveying, Bearings and Longitude & Latitude of a Line, Introduction to total station.
Levelling: Instrument used Object of levelling, Methods of levelling in brief, and Contour maps.
Chapter 4
Buildings: Selection of site for Buildings, Layout of Building Plan, Types of buildings, Plinth area, carpet area, floor space index, Introduction to building byelaws, concept of sun light & ventilation. Components of Buildings & their functions, Basic concept of R.C.C., Introduction to types of foundation
Chapter 5
Transportation: Introduction to Transportation Engineering; Traffic and Road Safety: Types and Characteristics of Various Modes of Transportation; Various Road Traffic Signs, Causes of Accidents and Road Safety Measures.
Chapter 6
Environmental Engineering: Environmental Pollution, Environmental Acts and Regulations, Functional Concepts of Ecology, Basics of Species, Biodiversity, Ecosystem, Hydrological Cycle; Chemical Cycles: Carbon, Nitrogen & Phosphorus; Energy Flow in Ecosystems.
Water Pollution: Water Quality standards, Introduction to Treatment & Disposal of Waste Water. Reuse and Saving of Water, Rain Water Harvesting. Solid Waste Management: Classification of Solid Waste, Collection, Transportation and Disposal of Solid. Recycling of Solid Waste: Energy Recovery, Sanitary Landfill, On-Site Sanitation. Air & Noise Pollution: Primary and Secondary air pollutants, Harmful effects of Air Pollution, Control of Air Pollution. . Noise Pollution Harmful Effects of noise pollution, control of noise pollution, Global warming & Climate Change, Ozone depletion, Greenhouse effect
Text Books:
1. Palancharmy, Basic Civil Engineering, McGraw Hill publishers.
2. Satheesh Gopi, Basic Civil Engineering, Pearson Publishers.
3. Ketki Rangwala Dalal, Essentials of Civil Engineering, Charotar Publishing House.
4. BCP, Surveying volume 1
2. INTRODUCTION
• Average time to develop new drug is 10 -12 years.
• On an average out of 10,000 – 30,000 potential
substances only 1 could make it to the market.
• As per 2006 estimates, the cost of bringing a new
drug could vary from 500 million to 2,000 million
USD.
3.
4. unmet medical need;
new diseases ( AIDS, Alzheimer’s; obesity);
low efficacy (dementia, cancer);
side effects (antidepressants, antipsychotics)
cost of therapy; (Interleukins)
costs to individual/country; (Alzheimer’s; spinal
injury, depression)
sustain industrial activity ( pharmaceutical industry
employs thousands and makes a massive contribution
to overseas earnings); patent expiry
WHY ARE NEW DRUGS NEEDED?
5. • Folk medicine - natural product remedies
• Early 19th century - extraction of compounds from plants
(morphine, cocaine )
History of Drug Discovery….
• James Lind – Citrus fruits – Scurvy – clinical trail
6. 1909 - First rational drug design.
• Goal: safer syphilis treatment than Atoxyl.
• Paul Erhlich and Sacachiro Hata wanted to maximize toxicity
to pathogen and minimize toxicity to human (therapeutic
index).
• They found Salvarsan (which was replaced by penicillin in the
1940’s)
7. • Mid to late 20th century
- understand disease states, biological structures, processes,
drug transport, distribution, metabolism.
Medicinal chemists use this knowledge to modify chemical
structure to influence a drug’s activity, stability, etc.
• procaine = local anaesthetic; Procainamide = antirhythmic
8. Drug development process – 3 main phases
• 1.drug discovery phase
• 2.preclinical phase
• 3.clinical trial phase
9.
10.
11. Drug discovery phase
1. Random screening
2. Serendipity ( By chance )
3. Rational drug designing
4. Designing of a prodrug or an active metabolite as a
drug
12. 1.RANDOM SCREENING
• Blind hitting procedure where new chemical
entities are subjected to pharmacological
screening procedures
• Studies on animal models , isolated tissues etc
• It is time consuming, expensive, inefficient in
providing fruitful results ,burdensome
• Ex:
• Morphine, Atropine , digitalis, Quinidine,
cyclosporine
13. 2.SERENDIPITY (BY CHANCE / HAPPY
OBSERVATION)
• New use from old drug or its side effects
• Lignocaine & Phenytoin
• Methotrexate – psoriasis
• Cyclophosphamide & Azathioprine – Graft rejection
• Penicillin
1928, Fleming studied Staph, but contamination of plates with
airborne mold. Noticed bacteria were lysed in the area of mold.
A mold product inhibited the growth of bacteria: the antibiotic
penicillin
14. 3.RATIONAL DRUG DESIGNING
• A. compound centered approach
: from natural products – Pencillin,paclitaxel,cyclosporine
DA – complex molecules – difficult to synthesized
: from synthetic products – from pharmacological data
Ex: Based on proponolol structure- B blokers
H2 blockers - modifying structure of histamine
• Molecular modification ended up in molecular
manipulation
New drugs are serving as me too drugs , no added
advantage
15. B. Target centered approach
* Biochemical or molecular targets
Ex: ACE blockers or AT II blockers
-Now a days large number of drugs this way
-Promising agents for lead optimisation
16. 4. DESIGNING OF A PRODRUG OR AN
ACTIVE METABOLITE AS A DRUG
• Administered as the precursor of a drug and is converted
into active therapeutic agent Ex; Levodopa
• Paracetamol, an active metabolite of phenacetin
• N-acetyl procainamide, an active metabolite of
procainamide does not cause SLE
18. • After the synthesis or isolation of the compound =
• Purity by physico chemical and analytical studies
Then these are subjected to biological screening
LEAD COMPOUND - which have a potential of becoming
new drug
•compounds can elicit a positive response in a particular
assay, which is called a hit.
• “Lead” is a hit series for which the structure–activity
relationship is shown and activity demonstrated both in
vitro and in vivo
19. Leads are optimised with respect to
Pharmacodynamic properties-efficacy, potency,
selectivity.
Pharmacokinetic properties- metabolic stability and
toxological aspects
Physiochemical properties
Chemical optimisation-ease of chemical synthesis &
derivation
20. PRECLINICAL EVALUATION PHASE ( ANIMAL
STUDIES)
Major areas are:
Pharmacodynamic studies In vivo in animals, In vitro
preparation
Absorption, distribution , elimination studies
(pharmacokinetics)
Acute ,sub acute, chronic toxicity studies (toxicity profile)
Therapeutic index (safety & efficacy evaluation)
21. Pharmacodynamic studies
•Action relavent to proposed therapeutic use are
studied on animals
Ex: Antihypertensive activity – dogs,cats,rats
To find out – B.P
- ECG changes
- inotropic & chrinotropic efforts
- CO & t.p.r
•Once L.C exibits promising results – futhur studies at
cellular level
•Receptor activity in vitro on cultured cells
•Further extended to molecular level to find out
receptor affinity & selectivity by performing in vitro
studies on cell membrane fractions from organs
•Graded response assy or Quantal assay - ED 50 of
the drug
22. Pharmacokinetic profile
New compounds subjected in several species of
animals.
Studies should establish
a) Relative bioavailability of the compound on oral or
parenteral administration
b) Elimination half life for assessment of optimal dosage
interval
23. Acute toxicity
Acute toxicity studies most commonly median lethal
dose
i.e. LD50 is determined.
Drug is given in graded doses to at least 2 animal
species by at least 2 routes.
To minimize biological variation, animal groups should
be similar.
Percentage of animals dying in each group within
specified time (24 hrs) is plotted against the dose.
Other toxic symptoms suffered also recorded.
Toxicity profile
24. Sub acute toxicity
To identify target organs susceptible to drug toxicity.
Laboratory studies like hematology, renal ,hepatic
function test are carried out.
Animals are maintained at max. tolerated dose for 4 wks
– 3 months & killed for HPE.
Chronic toxicity
If drug intended for chronic use in humans.
2 species of animals ,1 rodent and 1 non rodent are
used.
Drug administered for many months (6-24
months),detailed biochemical & histological
measurements are made.
To evaluate cumulative toxicity
To assist carcinogenic potential
Study may run simultaneously with clinical trial.
25. Test for fertility & reproductive performance
Carried out in rats, treated with new drug before & after
mating period.
Effects on early & late stages of embryonic & fetal
development are studied .
Teratogenicity
Carried out in 2 animal species to assess the effects of
drug on organogenesis.
Drugs given after mating
Fetuses are carefully examined for abnormalities.
26. Genotoxicity/ Mutagenicity:
It is invivo – invitro test conducted to detects
compounds which induces genetic damage directly or
indirectly.
The following standard test is generally expected to be
conducted :
1. A test for gene mutation in bacteria – AMES test
2. An invitro test with cytogenetic evaluation of chromosome
damage with mammalian cells
3. In vivo test for chromosomal damage using rodent
Hematopoietic cells.
Parameters:
Frequency of damage cells ,Total number, types and
frequency of metaphase chromosomal aberration
27. CARCINOGENECITY :
• for all drugs that are expected to be clinically used
for six months as well as for drugs used frequently in
an intermittent manner in the treatment of chronic or
recurrent condition
• Animals :
rodent 2 animal species , same dose of chronic study,
for 2 years.
• Parameters :
Autopsy and detailed Histopathology of organ and
tissues
28. LOCAL TOXICITY:
These studies are required when the new drug is proposed
to be used by some special route in human.
Dermal toxicity
Vaginal toxicity
Rectal tolerance test
Ocular toxicity
1. Dermal toxicity:
Animals: rabbit & rat
Parameters: erythema & edema
2. Vaginal toxicity:
Animals: rabit & dog
Parameters: swelling, closure of introitus & histopathology
of vaginal wall.
29. 3. Rectal tolerance test-
Animals: rabbit & dog
Parameters: sign of pain, blood/mucus in faeces,
histopathology of rectal mucosa.
4. Ocular toxicity-
Animals: rabbit
Parameters: Slit Lamp Test & Fluroscent Dye Test
30. 3.Therapeutic index
Relative margin of safety of a drug
TI =LD50/ED50
• Maximum Tolerated Dose
• No Adverse Effect Dose
• Human Equivalent Dose
31. REDUCING ANIMAL
USAGE
• About 2.6m animals/y used in procedures in UK (11.6m in Europe)
• Likely to increase; more research, more targets, genetic capability
• 3Rs -- 3Rs -- 3Rs
• REPLACEMENT: use non-animal tests if possible (cheaper, less
trouble, less variable but not possible for everything at this time)
• REDUCTION: get the statistics right, don’t replicate work
unnecessarily, don’t overbreed
• REFINEMENT: reduce suffering and severity of procedure, pay
attention to housing, stress, husbandry and rich environments,
proper analgesia and pre- and post- operative care
32. CLINICAL TRIAL PHASE(HUMAN PHASE)
• To determine safety & efficacy of a new drug in humans
• Good clinical practices (GCP) by international Conference on
Harmonization (ICH) and declaration of Helsinki.
• It provides details about – designing the trail
- collection of data
- recording of information
- statistical analysis
- documentation & reporting
33. IND APPLICATION
• When the new compound passes the preclinical phase ,
manufacturer may file a Investigational New Drug (IND)
application to authorized drug control body
• In INDIA - drugs controller general,Govt.of india,Delhi
• It contains information about the test drug –
- source,structure,manufacturing data
- preclinical data
- dosage forms,investigational protocol
- details about investigators
- agreement from the sponsers
- certification that Informed Consent will be
obtained from volunteers
34. Eight basic elements of informed consent
purpose of the research
risks or discomforts
any benefits to the subject which may reasonable be expected from
the research
Any alternative procedures or treatment that may be available to the
subject
confidentiality of records identifying the subject will be maintained
any compensation and whether any medical treatments are
available if injury occurs
An explanation of whom to contact for answers to questions about
the research and research subjects’ rights
A statement that participation is voluntary
Informed consent
35. Ethics committee & its
responsibilities
• At the institutional level – independent E.C to ensure
rights & welfare of the participants
• Responsibilities
- review protocol
- safeguard the rights , safety of trail subjects
- periodical review – SOPs
• 7 members – Member secretary
- chair person (outside)
- medical & non medical persons
36. ROLE OF PLACEBO
• Placebo controls – on healthy volunteers – Appetite
stimulant or new vaccine
• No place – Pt suffering from a disease – effective drug
already available
• Ethics – consent is taken
37. PHASES OF CLINICAL TRIALS
• 4 phases
phase I
phase II
phase III
phase IV
38. PHASE 1 CLINICAL TRIALS :
• Begins after 30 days of filing IND.
• Drug given to 20-100 healthy volunteers
• Duration could vary from 1 month to 1 year.
• Following is studied here :
• Drug absorption/Metabolism in human.
• Effect on organs and tissues. -Side affect of different
dosages.
• Thus early evidences on effectiveness are achieved
*NON BLIND OR OPEN LABEL TRAIL
39. Phase I studies are carried out in 2 stages
Single rising dose
Repeat administration
Each volunteer given a single dose of drug/placebo.
Dose-escalating study design.
Initial dose and route of administration decided from existing
pre-clinical data.
8 -12 volunteers .
2-4 volunteers receive placebo and 6-8 volunteers receive drug
under study.
STAGE 1–SINGLE RISING DOSE
40. Started after single dose administration results
assessed.
Drug / placebo given repeatedly for 1 or more weeks
E. g. Antibiotics given for 5-7 days
Anticonvulsants tested for 4 weeks or more
Interval between doses is usually one half life.
Kinetic data obtained from blood and urine sample
collected after 1st
and last dose
STAGE 2 REPEATED ADMINISTRATION
41. PHASE 2 CLINICAL TRIALS :
• Therapeutic exploratory trial
• First time in patients
• Less than 300 patients
• Doses are usually less than the highest doses
used in phase I
*SINGLE BLIND TRAIL
42. 1. Efficacy in patients
2. Safety issues
3. Optimum dose finding
Dose efficacy relationship
Therapeutic dose regimen
Duration of therapy
Frequency of administration
Therapeutic window
OBJECTIVES
43. PHASE II DIVIDED INTO EARLY & LATE
PHASE
• EARLY PHASE II
small number of pts – upto 200
detail therapeutic benefited & ADR
idea to establish dose range
SINGLE BLIND STUDY
• LATE PHASE II
large number of pts – 200-400
DOUBLE BLIND STUDY
third party holds the code identifying studies
44. PHASE 3 CLINICAL TRIALS :
• By several physicians at many centres
• Large scale – 1000 to 5000 plus
• To further establish the safety & efficacy
• Long term side effects in patients
• Duration could vary from 5 years to 6 years.
• DOUBLE BLIND CROSS OVER design
• At end of trail statistical analysis of data is
performed
45. Pts groups Week 1 Week 2 Week 3
I
STANDARD
DRUG
PLACEBO NEW DRUG
II
PLACEBO NEW DRUG STANDARD
DRUG
III
NEW DRUG STANDARD
DUG
PLACEBO
Double-Blind Cross Over design
46. NDA
• NDA Refers to New Drug Application
• Formal proposal for the FDA to approve a new drug for
sale
• Sufficient evidences provided to FDA to establish:
• Drug is safe and effective.
• Benefits outweigh the risks.
• Proposed labeling is appropriate.
47. PHASE IV
• launched to the Market
• Post marketing surveillance – field trails
• No fixed duration
• To discover relatively rare side
effects(congenital effects) or drug interactions
• From hundreds to thousands of people
• Usually takes place after drug is approved to
provide additional information on the drug’s
risks, benefits and optimal use
48. PERIODIC SAFETY UPDATE REPORT
(PSUR)
• Report any new information about the new drug & its
safety
• Every 6 months for 2 yrs & annually next 2 yrs
Where the drug
fails ?
49.
50. EXAMPLE: THALIDOMIDE
Thalidomide was developed by German pharmaceutical company
Grünenthal. It was sold from 1957 to 1961 in almost 50 countries
under at least 40 names. Thalidomide was chiefly sold and
prescribed during the late 1950s and early 1960s to pregnant
women, as an antiemetic to combat morning sickness and as an aid
to help them sleep. Before its release, inadequate tests were
performed to assess the drug's safety, with catastrophic results for
the children of women who had taken thalidomide during their
pregnancies.
52. EXAMPLE: THALIDOMIDE
From 1956 to 1962, approximately 10,000 children were born
with severe malformities, including phocomelia, because their
mothers had taken thalidomide during pregnancy. In 1962, in
reaction to the tragedy, the United States Congress enacted laws
requiring tests for safety during pregnancy before a drug can
receive approval for sale in the U.S.
Phocomelia presents at birth very short or absent long bones
and flipper-like appearance of hands and sometimes feet.
53. Pharmacovigilance
• Pharmakon – a drug , vigilare – to be observant
• Continuous monitoring for unwanted effects & other
safety related aspects of marketed drugs
• Thalidomide, Isotretinoin ,
• Fenfluramine & Phentermine – PHTN & valvular H.D
• Troglitazone – liver toxicity
• WHO – safety monitoring of medical products -
setting a P.V centre in every country
• P.V – Detection,Assessment, Understanding and
Prevention (DAUP) of ADR
54. • INDIA ,National P.V centre – AIIMS, New Delhi by central
drug standard control organization (CDSCO)
• 2 zonal , 8 regional & 28 peripheral P.V centres
• Generated data – global P.V database at WHO-Uppsala
monitoring centre-Sweden
• Reporting ADR includes:
-drug interaction
-death
-life-threatening reaction
-hospitalization
-disability
-congenital abnormality
55. • Pharmaceutical companies are commercial enterprises
• Pharmaceutical companies will, therefore, tend to avoid
products with a small market (i.e. a disease which only
affects a small subset of the population)
• Pharmaceutical companies will also avoid products that
would be consumed by individuals of lower economic status
(i.e. a disease which only affects third world countries)
Choosing a Disease
56. Most research is carried out on
diseases which afflict “first world”
countries: (e.g. cancer,
cardiovascular diseases,
depression, diabetes, flu, migraine,
obesity).
Choosing a Disease
57. The Orphan Drug Act
• The Orphan Drug Act of 1983 was passed to encourage
pharmaceutical companies to develop drugs to treat
diseases which affect fewer than 200,000 people
• Because the cost incurred will not be recovered
• So rare diseases are left untreated – orphan diseases ,
drugs – orphan drugs
• Govt. offered tax relief and exclusive marketing rights
• > 300 drugs
Ex: factor XIII , Erythropoietin , Atravaquone ,
Antithrombin III , Miltefosine , Acetyl cysteine , Relaxin
58. New tools for drug screening
HIGH THROUGHPUT SCREENING
Screening large libraries of 2 lakh compounds
Rate of 1,00,000 compounds/day
In HTS chemicals are tested for their ability to modify a
target
Methods – screening of combinatorial chemistry
,genomics, proteomics & peptide
libraries
59. Drugs are tested for their activity on these molecules using
plates wherein a large number of compounds are
simultaneously tested.
Screening depends on inhibition of enzymic products which
are detected using fluoroscopy or photometry
Instrumentation
24 WELL PLATE.
96 WELL PLATE.
- COMPOUND STORAGE.
- COMBINATORIAL CHEMISTRY.
- SAMPLE COLLECTION.
-SCREENING.
384 WELL PLATES.
-LOW VOLUME
-DNA LIBRARY MANIPULATION.
1536 WELL PLATES.
60. Advantages
Lead compound.
Molecular mechanism.
Minimizing cost and maximizing patent life time.
Highly efficient development.
Disadvantages
Availability Of Instruments.
Trained Personnels.
61. HTS is a remarkable achievement in drug discovery process
to speed up preclinical discovery process. This automation in
the process is supported by the excellent software packages.
.
The goal of the HTS is to accelerate drug discovery by
screening large libraries at a rate that may exceed 50,000
compounds per week.
62. CASSETTE DOSING / N-IN-ONE DOSING
• Elegant, inexpensive , time intensive novel technique –
aim to rapidly assess P.K of large number of compounds
• Several compounds(5-10) to single animal & rapid sample
analysis by liquid chromatography or mass spectography
• Advantages – to reduce no. of animals
- increased quality of kinetics data
- reduce the amount of the drug
- time minimized
• Disadvantages – drug to drug interactions
- false positives
63. Micro dosing / First In Human( FIH) studies /
Phase O
•Study of new drug in microdoses to derive PK information in
human before undertaking phase I studies is called PHASE 0
•“1/100th
or lower of the expected therapeutic dose.”
A dose less than 100ug
•(The test compound has no pharmacologic effect at
microdose concentrations)
64. • Microdosing approach in man could ‘accelerate’ drug
development without compromising clinical safety
• Microdosing helps researchers select better drug candidates
for clinical trials by providing early human PK and
bioavailability data.
• Reduced cost of development
• Reduced development time
Objectives
Primary:
Determine the pharmacokinetics
Determine a non -toxic dose range
Secondary :
Determine the safety of an chemical entity
65. Limitations
? Predictive accuracy of microdosing
PK at microdose vs. therapeutic dose
False positive/ negatives
Compound metabolism and solubility (limited solubility
at higher doses; ? Microdose too small)
Study mainly based on PK parameters - not efficacy and
safety based
66. • 3rd world diseases?
• orphan drugs with few users?
• improve safety and efficacy records
• reduce animal utilisation (cell lines; early
human volunteers, )
• new diseases (AIDS; Alzheimer’s; CJ
disease;human BSE variant; obesity; cancer)
• new biology - (clone human receptors;
disease model by gene changes)
The future ?
67. References :
• Pharmacological basis of Therapeutics – Goodman &
Gilman 12th Edition .
• Principles of pharmacology – HL Sharma & KK sharma 2nd
edition .
• Drug Screening methods – Gupta 2 nd edition
• Experimental Pharmacology – Bikash Medhi
• Text book of pharmacology – K. D. Tripathi.7th Edition.
• Basics & clinical pharmacology – Katzung 11th
edition
• www.history of clinicaltrails.in