BIOCOM CRO event May 2013: Being an early stage virtual company is no easy task. Managing resources and timelines while minimizing costs are the new normal for successful virtual companies. This two hour event and panel discussion hosted by Explora Biolabs and MPI Research will explore successful preclinical drug development in a virtual setting. Explora BioLabs will discuss selecting a drug candidate using early biology/efficacy models as well as best practices for screening and partnering with a CRO to streamline your candidate selection in a resource constrained environment. Building on that discussion, MPI Research will describe how to advance a compound from early GLP tox and safety testing into phase 1 while utilizing successful partnerships.
Joining the presenters for a follow-on panel discussion will be:
David Johnson, Director of DMPK, MicroConstants, Inc.
Richard Lin, CEO, Explora Biolabs
Greg Ruppert, Sr. Study Director and Director of Sales, MPI Research
Jennifer Spinella, Vice President, Regulatory Affairs & Quality Assurance, Rare Disease Therapeutics
Visit www.biocom.org or www.biocomcro.org for more information or call 858.455.0300 to learn about BIOCOM's CRO Initiative
A presentation outlining the various processes a chemical compound undergoes (thorough & rigorous screening procedures) before it is finally introduced into the drug market
The document discusses preclinical development and whether changes are needed. It outlines the stages from target discovery to registration, noting the high costs and attrition rates. Exploratory toxicology aims to predict toxicities and select candidates, while regulatory toxicology provides safety margins for starting human trials. A variety of assays are used to evaluate general toxicity, genotoxicity, safety pharmacology and more. Challenges include poor translation between preclinical models and humans. Opportunities exist to improve prediction through new technologies and approaches. Overall, advances have been made but high attrition rates continue to motivate further improvements.
The document summarizes the key events in the discovery and development of penicillin. Alexander Fleming first discovered penicillin in 1928 after noticing bacteria-killing properties of the Penicillium mold in one of his petri dishes. However, he was not able to purify or characterize penicillin at the time. In the 1940s, a team at Oxford led by Howard Florey and Ernst Chain managed to purify and mass produce penicillin, paving the way for clinical trials. The first successful human trials demonstrated penicillin's ability to cure bacterial infections. By the mid-1940s, large-scale production was established. Fleming, Florey and Chain received the 1945 Nobel Prize for their discoveries. Over time, resistance
Drug development process and clinical trial for UGsSameerKhasbage
This document summarizes the process of drug development from discovery through clinical trials and approval. It discusses the main goals and requirements of each phase of clinical trials: Phase I focuses on safety and dosing in healthy volunteers, Phase II evaluates efficacy and side effects in patients, Phase III tests efficacy versus existing treatments in hundreds to thousands of patients, and Phase IV monitors long-term safety and efficacy after approval and marketing. The overall process from discovery to approval takes 10-15 years and costs over $2 billion on average.
This document discusses the process of new drug evaluation, which involves 3 phases - drug discovery, preclinical testing, and clinical trials. In the drug discovery phase, candidate molecules are selected. Preclinical testing involves animal studies to evaluate safety. Clinical trials with human subjects are then conducted in 3 phases to evaluate efficacy, safety, and adverse effects. The clinical trials process is highly regulated to ensure safety and data integrity. If successful, a New Drug Application is filed with regulatory authorities for approval to market the new drug.
Toxicological Approach to Drug DiscoverySuhas Reddy C
This document outlines the toxicological approach to drug development. It discusses the importance of conducting various toxicity studies at different stages of drug development to ensure safety. These include single dose, repeated dose, fertility, reproductive, developmental and genotoxicity studies in animals. It describes the typical safety program involving staged approach and discusses factors to consider in designing toxicity studies. The goal is to obtain sufficient non-clinical safety data to support clinical trials and assess safety for human use.
The pre-clinical trial process involves testing new drugs on animal and cell bioassays before human testing to determine if they are safe and effective. It begins with basic research to identify a drug target related to a disease. Researchers then develop a bioassay and screen drug candidates to find ones that act on the target as intended without toxicity. Effective and toxic doses are established, and approval is sought from the FDA to begin clinical trials on humans by filing an Investigational New Drug application. The goal of pre-clinical trials is to apply findings from basic research on biochemical pathways and identify promising drug candidates ready for initial human testing.
A presentation outlining the various processes a chemical compound undergoes (thorough & rigorous screening procedures) before it is finally introduced into the drug market
The document discusses preclinical development and whether changes are needed. It outlines the stages from target discovery to registration, noting the high costs and attrition rates. Exploratory toxicology aims to predict toxicities and select candidates, while regulatory toxicology provides safety margins for starting human trials. A variety of assays are used to evaluate general toxicity, genotoxicity, safety pharmacology and more. Challenges include poor translation between preclinical models and humans. Opportunities exist to improve prediction through new technologies and approaches. Overall, advances have been made but high attrition rates continue to motivate further improvements.
The document summarizes the key events in the discovery and development of penicillin. Alexander Fleming first discovered penicillin in 1928 after noticing bacteria-killing properties of the Penicillium mold in one of his petri dishes. However, he was not able to purify or characterize penicillin at the time. In the 1940s, a team at Oxford led by Howard Florey and Ernst Chain managed to purify and mass produce penicillin, paving the way for clinical trials. The first successful human trials demonstrated penicillin's ability to cure bacterial infections. By the mid-1940s, large-scale production was established. Fleming, Florey and Chain received the 1945 Nobel Prize for their discoveries. Over time, resistance
Drug development process and clinical trial for UGsSameerKhasbage
This document summarizes the process of drug development from discovery through clinical trials and approval. It discusses the main goals and requirements of each phase of clinical trials: Phase I focuses on safety and dosing in healthy volunteers, Phase II evaluates efficacy and side effects in patients, Phase III tests efficacy versus existing treatments in hundreds to thousands of patients, and Phase IV monitors long-term safety and efficacy after approval and marketing. The overall process from discovery to approval takes 10-15 years and costs over $2 billion on average.
This document discusses the process of new drug evaluation, which involves 3 phases - drug discovery, preclinical testing, and clinical trials. In the drug discovery phase, candidate molecules are selected. Preclinical testing involves animal studies to evaluate safety. Clinical trials with human subjects are then conducted in 3 phases to evaluate efficacy, safety, and adverse effects. The clinical trials process is highly regulated to ensure safety and data integrity. If successful, a New Drug Application is filed with regulatory authorities for approval to market the new drug.
Toxicological Approach to Drug DiscoverySuhas Reddy C
This document outlines the toxicological approach to drug development. It discusses the importance of conducting various toxicity studies at different stages of drug development to ensure safety. These include single dose, repeated dose, fertility, reproductive, developmental and genotoxicity studies in animals. It describes the typical safety program involving staged approach and discusses factors to consider in designing toxicity studies. The goal is to obtain sufficient non-clinical safety data to support clinical trials and assess safety for human use.
The pre-clinical trial process involves testing new drugs on animal and cell bioassays before human testing to determine if they are safe and effective. It begins with basic research to identify a drug target related to a disease. Researchers then develop a bioassay and screen drug candidates to find ones that act on the target as intended without toxicity. Effective and toxic doses are established, and approval is sought from the FDA to begin clinical trials on humans by filing an Investigational New Drug application. The goal of pre-clinical trials is to apply findings from basic research on biochemical pathways and identify promising drug candidates ready for initial human testing.
safety pharmacology is the branch of pharmacology specializing in detecting and investigating potential undesirable pharmacodynamic effects of a new chemical on physiological functions .
the content of this presentation is as follows
- introduction
- definition
- history
- ICH - guidelines
- refrences
Drug discovery clinical evaluation of new drugsKedar Bandekar
The document discusses the process of new drug development from initial idea to market launch. It takes 12-15 years and over $1 billion. The process involves identifying a biological target, screening compounds to find hits, optimizing hits to develop leads, and conducting preclinical and clinical trials. Key steps include target identification and validation, high-throughput screening to find initial hits, hit-to-lead and lead optimization processes to improve properties, and progression through preclinical and clinical phases of drug development. Characteristics of ideal lead compounds include high target affinity and selectivity, efficacy, appropriate physicochemical properties, and favorable ADME profile.
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.
Pre-discovery
Understand the disease
Target Identification
Choose a molecule to target with a drug
Target Validation
Test the target and confirm its role in the disease
Drug Discovery
Find a promising molecule (a “lead compound”)
that could become a drug
Clinical trials play an important role in drug discovery and development. They involve several phases to test drug safety and effectiveness in humans starting with healthy volunteers and progressing to larger studies. Positive results from clinical trials provide evidence for regulatory approval and allow drugs to help patients if their benefits outweigh the risks. The goal is to develop new treatments and demonstrate they are safe and effective for their intended uses.
1. The document outlines various approaches to drug discovery including pharmacological, toxicological, Investigational New Drug (IND) application, drug characterization, and dosage form development.
2. It describes the pharmacological approach which involves identifying molecular targets and establishing modulation for therapeutic intervention through small molecules or antibodies. Preclinical studies and lead optimization are also discussed.
3. The toxicological approach discussed includes performing safety studies in multiple species to determine toxicity profiles and therapeutic indexes to inform initial human clinical trials. Various 'omics' technologies are also described for evaluating toxicity mechanisms.
4. The IND application process and requirements are summarized, including preclinical data, manufacturing information, investigator qualifications, clinical trial protocols, and other commitments necessary for approval
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 10-15 years and costs over $800 million on average to develop a new drug. Only about 1 in 5,000-10,000 compounds tested make it to consumers, and only 3 of 10 drugs that reach the market earn back their R&D costs. The process involves extensive research, pre-clinical testing on animals, and clinical trials on humans in 3 phases before the FDA reviews the new drug application. If approved, large-scale manufacturing must be developed to produce the drug.
This document discusses the process of new drug development. It begins with basic research to understand disease pathways and identify potential drug targets. Promising compounds are identified through screening and optimized in preclinical testing, which evaluates safety and effectiveness in animals. If preclinical results are satisfactory, an Investigational New Drug Application is submitted to regulators to seek approval for clinical trials in humans. The drug development process is long and rigorous, aiming to bring safe and effective medications to market while meeting regulatory guidelines.
This document discusses the requirements for an investigational new drug (IND) application. An IND is required to initiate clinical trials of an unapproved drug and must contain information on animal studies, manufacturing, and clinical trial protocols. The core battery of safety pharmacology studies evaluates effects on major organ systems like the cardiovascular, central nervous, and respiratory systems. These studies are designed to identify potential adverse effects and safety risks before human clinical trials.
The document provides an overview of requirements for an Investigational New Drug (IND) application to the FDA. It discusses key components of the IND including chemistry, manufacturing and controls (CMC), preclinical toxicology studies, and clinical trial protocols. The main points are:
1) An IND application is required to begin clinical testing of new drugs, drugs at new dosages, or drug combinations not previously approved.
2) Key sections of the IND include CMC data on drug manufacturing and quality controls, results of preclinical toxicology studies in animals, and protocols for proposed clinical trials.
3) Preclinical studies aim to identify safe starting doses for clinical trials and target organs of toxicity.
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.
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.
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.
Introduction to the drug discovery processThanh Truong
This document discusses the drug discovery process from target identification through FDA approval. It describes methods used for target identification such as genomics, bioinformatics, and proteomics. The stages of lead identification through high-throughput screening and structure-based drug design are outlined. Key aspects of lead optimization like characterizing potency, efficacy, pharmacokinetics, and toxicity are summarized. Details are provided on preclinical and clinical trial phases from Phase 0 through Phase IV post-marketing surveillance. Factors contributing to the declining drug approval rate like increased safety demands are noted. The high costs and failure rates associated with drug development are highlighted.
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.
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.
Presentation by MicroConstants at BIOCOM CRO event May 2013: Virtual Drug Dev...BIOCOMCRO
May 2013
8-10am
Location: BIOCOM
Speaker(s):
Joining the presenters for a follow-on panel discussion will be: Jennifer Spinella, Vice President, Regulatory Affairs & Quality Assurance at Rare Disease Therapeutics Greg Ruppert, Sr. Study Director and Director of Sales for MPI Research Richard Lin, CEO of Explora Biolabs.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive function. Exercise causes chemical changes in the brain that may help protect against mental illness and improve symptoms.
The document discusses Aptuit, a pharmaceutical services company that conducts drug development on a contract basis. It describes Aptuit's mission to improve the drug development process for both large and small companies. It also introduces Aptuit's INDiGO program which provides expert drug development teams to accelerate programs from the API stage through Phase 2a clinical trials. Outsourcing development to Aptuit can save emerging biopharma companies significant costs compared to developing drugs in-house.
Speaker: Peter Pekos, Dalton Pharma Services. Part of the MaRS Best Practices Series.This session, led by seasoned industry experts, will explore how to effectively set up your pre-clinical POC studies, address pre-clinical safety requirements and issues, and give you an overview of the manufacturing standards required for Phase I studies
More information: http://www.marsdd.com/Events/Event-Calendar/Best-Practices-Series/ind-05132008.html
safety pharmacology is the branch of pharmacology specializing in detecting and investigating potential undesirable pharmacodynamic effects of a new chemical on physiological functions .
the content of this presentation is as follows
- introduction
- definition
- history
- ICH - guidelines
- refrences
Drug discovery clinical evaluation of new drugsKedar Bandekar
The document discusses the process of new drug development from initial idea to market launch. It takes 12-15 years and over $1 billion. The process involves identifying a biological target, screening compounds to find hits, optimizing hits to develop leads, and conducting preclinical and clinical trials. Key steps include target identification and validation, high-throughput screening to find initial hits, hit-to-lead and lead optimization processes to improve properties, and progression through preclinical and clinical phases of drug development. Characteristics of ideal lead compounds include high target affinity and selectivity, efficacy, appropriate physicochemical properties, and favorable ADME profile.
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.
Pre-discovery
Understand the disease
Target Identification
Choose a molecule to target with a drug
Target Validation
Test the target and confirm its role in the disease
Drug Discovery
Find a promising molecule (a “lead compound”)
that could become a drug
Clinical trials play an important role in drug discovery and development. They involve several phases to test drug safety and effectiveness in humans starting with healthy volunteers and progressing to larger studies. Positive results from clinical trials provide evidence for regulatory approval and allow drugs to help patients if their benefits outweigh the risks. The goal is to develop new treatments and demonstrate they are safe and effective for their intended uses.
1. The document outlines various approaches to drug discovery including pharmacological, toxicological, Investigational New Drug (IND) application, drug characterization, and dosage form development.
2. It describes the pharmacological approach which involves identifying molecular targets and establishing modulation for therapeutic intervention through small molecules or antibodies. Preclinical studies and lead optimization are also discussed.
3. The toxicological approach discussed includes performing safety studies in multiple species to determine toxicity profiles and therapeutic indexes to inform initial human clinical trials. Various 'omics' technologies are also described for evaluating toxicity mechanisms.
4. The IND application process and requirements are summarized, including preclinical data, manufacturing information, investigator qualifications, clinical trial protocols, and other commitments necessary for approval
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 10-15 years and costs over $800 million on average to develop a new drug. Only about 1 in 5,000-10,000 compounds tested make it to consumers, and only 3 of 10 drugs that reach the market earn back their R&D costs. The process involves extensive research, pre-clinical testing on animals, and clinical trials on humans in 3 phases before the FDA reviews the new drug application. If approved, large-scale manufacturing must be developed to produce the drug.
This document discusses the process of new drug development. It begins with basic research to understand disease pathways and identify potential drug targets. Promising compounds are identified through screening and optimized in preclinical testing, which evaluates safety and effectiveness in animals. If preclinical results are satisfactory, an Investigational New Drug Application is submitted to regulators to seek approval for clinical trials in humans. The drug development process is long and rigorous, aiming to bring safe and effective medications to market while meeting regulatory guidelines.
This document discusses the requirements for an investigational new drug (IND) application. An IND is required to initiate clinical trials of an unapproved drug and must contain information on animal studies, manufacturing, and clinical trial protocols. The core battery of safety pharmacology studies evaluates effects on major organ systems like the cardiovascular, central nervous, and respiratory systems. These studies are designed to identify potential adverse effects and safety risks before human clinical trials.
The document provides an overview of requirements for an Investigational New Drug (IND) application to the FDA. It discusses key components of the IND including chemistry, manufacturing and controls (CMC), preclinical toxicology studies, and clinical trial protocols. The main points are:
1) An IND application is required to begin clinical testing of new drugs, drugs at new dosages, or drug combinations not previously approved.
2) Key sections of the IND include CMC data on drug manufacturing and quality controls, results of preclinical toxicology studies in animals, and protocols for proposed clinical trials.
3) Preclinical studies aim to identify safe starting doses for clinical trials and target organs of toxicity.
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.
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.
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.
Introduction to the drug discovery processThanh Truong
This document discusses the drug discovery process from target identification through FDA approval. It describes methods used for target identification such as genomics, bioinformatics, and proteomics. The stages of lead identification through high-throughput screening and structure-based drug design are outlined. Key aspects of lead optimization like characterizing potency, efficacy, pharmacokinetics, and toxicity are summarized. Details are provided on preclinical and clinical trial phases from Phase 0 through Phase IV post-marketing surveillance. Factors contributing to the declining drug approval rate like increased safety demands are noted. The high costs and failure rates associated with drug development are highlighted.
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.
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.
Presentation by MicroConstants at BIOCOM CRO event May 2013: Virtual Drug Dev...BIOCOMCRO
May 2013
8-10am
Location: BIOCOM
Speaker(s):
Joining the presenters for a follow-on panel discussion will be: Jennifer Spinella, Vice President, Regulatory Affairs & Quality Assurance at Rare Disease Therapeutics Greg Ruppert, Sr. Study Director and Director of Sales for MPI Research Richard Lin, CEO of Explora Biolabs.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive function. Exercise causes chemical changes in the brain that may help protect against mental illness and improve symptoms.
The document discusses Aptuit, a pharmaceutical services company that conducts drug development on a contract basis. It describes Aptuit's mission to improve the drug development process for both large and small companies. It also introduces Aptuit's INDiGO program which provides expert drug development teams to accelerate programs from the API stage through Phase 2a clinical trials. Outsourcing development to Aptuit can save emerging biopharma companies significant costs compared to developing drugs in-house.
Speaker: Peter Pekos, Dalton Pharma Services. Part of the MaRS Best Practices Series.This session, led by seasoned industry experts, will explore how to effectively set up your pre-clinical POC studies, address pre-clinical safety requirements and issues, and give you an overview of the manufacturing standards required for Phase I studies
More information: http://www.marsdd.com/Events/Event-Calendar/Best-Practices-Series/ind-05132008.html
CFTCC
2015 Learning about the IND/IDE Process and Reimbursements for New Drugs and Devices
Erin O'Reilly, PhD, RAC
Assoc. Director, Regulatory Affairs
Translational Medicine Institute
Introduces the basics of filing an Investigational New Drug (IND) Application with the FDA
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.
This document provides an overview of pharmacology and pharmaceutics. It discusses the definitions and subdivisions of pharmacology, including pharmacokinetics, pharmacodynamics, clinical pharmacology, and toxicology. The history of pharmacology from ancient civilizations through modern developments is summarized. Key figures who advanced the field are mentioned, such as Francois Megendie, who established the foundations of modern pharmacology using animal experiments. The scope of pharmacology is described as providing the rational basis for drug therapeutic use and expanding to incorporate new approaches like computer-assisted design.
How to Become a Thought Leader in Your NicheLeslie Samuel
Are bloggers thought leaders? Here are some tips on how you can become one. Provide great value, put awesome content out there on a regular basis, and help others.
Basics of Drug Discovery and DevelopmentJhony Sheik
The document outlines the process of drug discovery and development from initial screening of chemicals to determine biological activity through clinical trials and regulatory approval. It notes that of 10,000 initially screened chemicals, only 1 may reach the market place due to the high costs, risks and regulatory hurdles. The key stages discussed are preclinical testing in animals, filing an Investigational New Drug application for human trials, conducting clinical trials in four phases, filing a New Drug Application providing trial results for regulatory review and approval, large-scale manufacturing, and filing an Abbreviated New Drug Application for generic approvals relying on previously approved drugs.
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.
This document discusses extrapolating data from in vitro studies to preclinical and human trials. It defines extrapolation as estimating conclusions based on known facts. Two main methods of extrapolation are described: linear scaling and allometric scaling. When estimating a first human dose, the no-observed adverse effect level from animal studies is determined and converted to a human equivalent dose using body surface area. A safety factor is then applied to determine the maximum recommended starting dose. The document also discusses other approaches like using the minimum anticipated biological effect level.
Regulatory requirements for drug approval - industrial pharmacy IIJafarali Masi
Regulatory requirements for drug approval - industrial pharmacy IIDrug Development Teams, Non-Clinical Drug Development, Pharmacology, Drug Metabolism and Toxicology, General considerations of Investigational New Drug (IND) Application, Investigator’s Brochure (IB) and New Drug Application (NDA), Clinical research / BE studies, Clinical Research Protocols, Biostatistics in Pharmaceutical Product Development, Data Presentation for FDA Submissions, Management of Clinical Studies.
The document discusses the complex and unpredictable nature of the FDA drug approval process. While the steps of drug development may seem formulaic, including discovery, preclinical testing, and clinical trials, success is not guaranteed as programs face many risks and intangible factors. Understanding these challenges is important for mitigating risks and strategizing development approaches. The FDA approval process aims to ensure new drugs are safe and effective for patients.
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.
This document discusses regulatory issues related to evaluating biotechnology-derived pharmaceuticals. It defines key terms like biopharmaceuticals, biosimilars, and biogenerics. The EU and US have different regulatory approaches and definitions. In India, products are currently referred to as biogenerics and regulated under Schedule Y, though new guidelines are being developed. The presentation outlines important considerations for preclinical safety testing of biologics, including relevant animal species selection, dose levels, routes of administration, and key study types needed like toxicity, immunogenicity, reproductive, and carcinogenicity assessments.
1) The process of bringing a new medicine from initial discovery to patient use (molecule to medicine) is a long, complex, and expensive process involving target identification, preclinical testing, clinical trials, and regulatory review and approval.
2) Preclinical testing involves evaluating a molecule's pharmacokinetics, pharmacodynamics, safety, and toxicity in cell and animal studies. Positive preclinical results allow filing an Investigational New Drug (IND) application to begin human clinical trials.
3) Clinical trials are conducted in four phases to evaluate a drug's safety, efficacy, side effects, and optimal dosing in humans. The entire development process from discovery to approval takes 8-12 years and costs over $1
This document provides an overview of the regulatory guidelines for developing and marketing biologics in Europe. It discusses the EU guidelines for non-clinical and clinical studies from trials through approval. For non-clinical studies, the CHMP has adopted ICH S6 and its addendum which provides guidance on species selection, study design, immunogenicity, reproductive/developmental toxicity, and carcinogenicity assessments. Clinical studies must comply with the Clinical Trials Directive and guidelines on GCP, informed consent, data handling and confidentiality. The marketing authorization application process is similar to other products but requires additional information specific to biologics manufacturing.
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.
This document provides an introduction to bioequivalence studies, including definitions of key terms, the need for and importance of bioequivalence studies, criteria for establishing a bioequivalence requirement, types of bioequivalence studies, design of bioequivalence studies, evaluation of bioequivalence study results, and clinical significance. It discusses in vivo and in vitro bioequivalence study types and designs, including factors such as single dose, multiple dose, fasting, food effect, and crossover designs. Statistical evaluation methods including ANOVA, confidence intervals, and bioequivalence limits of 80-125% are also summarized.
Pharmacovigilance & Adverse drug reactionRahul Bhati
This document discusses pharmacovigilance and adverse drug reactions (ADRs). It begins by defining pharmacovigilance as the monitoring of drug safety, and describes how the thalidomide disaster in the 1960s prompted significant changes to drug safety systems worldwide. It then discusses various reasons for the need of pharmacovigilance like limited preclinical safety data and changing drug use patterns. The aims and methods of pharmacovigilance including spontaneous reporting, case studies, and periodic safety reports are summarized. It also provides an overview of the Pharmacovigilance Program of India and its goals of monitoring ADRs and ensuring drug benefits outweigh risks. Finally, it defines different types of ADRs and their
Glossary of terms used in pharmacovigilance. FINAL.pdfAlfiaAnsari2
1. The document defines key terms related to pharmacovigilance including adverse drug reactions, adverse drug events, side effects, serious adverse events, and differences between them.
2. An adverse drug reaction is an unwanted reaction that is related to the pharmacological properties of the drug. A side effect is also an unwanted effect but is mild and expected based on the drug's properties.
3. An adverse drug event may or may not be related to the drug and includes any medical occurrence during treatment, while a serious adverse event poses a serious threat to health.
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Presentation by MPI Research: Virtual Drug Development in Southern California
1. How Do I Get Into Phase 1
Trials With My Compound?
Greg Ruppert
Director, North American Sales
May 9, 2013
2. Preface and Disclaimer
This presentation is in regard to nonclinical animal studies provided to
support an investigational new drug (IND) application (21 CFR 312) for
various scenarios and approaches. There are a number of other
aspects to the drug development process that are not covered.
There isn’t a ‘one size fits all’ approach to designing a nonclinical IND
package. Rather, nonclinical studies in support of an IND must be
tailored to the specific investigational agent and the proposed clinical
trials.
3. Preface and Disclaimer
“FDA's guidance documents, including this guidance, do not establish
legally enforceable responsibilities. Instead, guidances describe the
Agency's current thinking on a topic and should be viewed only as
recommendations, unless specific regulatory or statutory
requirements are cited. The use of the word should in Agency
guidances means that something is suggested or recommended,
but not required.”
“Before submitting the application, the applicant should submit a plan to
the appropriate new drug evaluation division identifying the types of
bridging studies that should be conducted. The applicant should
also identify those components of its application for which it expects
to rely on FDA’s finding of safety and effectiveness of a previously
approved drug product. The division will critique the plan and
provide guidance.”
4. What You Need To Do Before You Start
Animal Studies
• Species selection
• Metabolic profiles
• Pharmacology
• Vehicle
• Solution vs. suspension
• Concentration
• Methods
• Formulation
• Bioanalytical
• Immunological for biopharmaceuticals
• Clinical plan
5. How Many Approaches To An IND –
“Standard Approach”
NCE Small Molecule or “Traditional” Approach
• DRF and repeat toxicology in rodents & nonrodent with TK
• Dosing regimen
• Recovery?
• Genotoxicity battery
• Ames
• Mammalian Cell Mutation (Chromosomal Aberration)
• in vivo Micronucleus (optional)
• Safety Pharmacology battery
• CV nonrodent
• in vitro hERG
• CNS rodent
• Respiratory rodent
In general, the differences from this “standard” approach is
presented for the following IND approaches.
6. How Many Approaches To An IND –
Biopharmaceuticals
What is a biopharmaceutical?
• Product derived from characterized cells (bacteria, yeast, insect,
plant, mammalian).
• Includes growth factors, recombinant proteins, antibodies,
endogenous proteins, enzymes etc.
• Does not include antibiotics, heparin, vitamins, vaccines, cellular
and gene therapy etc.
• Oligonucleotides
7. How Many Approaches To An IND –
Biopharmaceuticals
Species selection – Needs to be the most relevant
• Sequence homology
• Cell based assays for binding affinities
• Functional activity - in vivo or in vitro
• If no orthologous target – consider homologous molecules,
transgenic animals or animal models of disease.
Monoclonal antibodies directed against foreign targets
8. How Many Approaches To An IND –
Biopharmaceuticals
How many species?
• If pharmacologically active in two species, then 2 are needed for
initial studies.
• Single species based on well understood pharmacology.
• For novel antibody-drug conjugates (ADC) two species are
recommended
Dose selection
• High dose should be the highest of
• Maximum pharmacological effect.
• Up to 10-fold exposure over expected clinical levels.
.
9. How Many Approaches To An IND –
Biopharmaceuticals
Immunogenicity
• Assessment of anti-drug antibodies (ADAs) not needed if
evidence of sustained pharmacology, no unexpected changes is
PK/TK, no evidence of immune-mediated reactions.
• Take blood samples for analysis of ADAs, analyze if needed.
• If ADAs detected – characterize impact on exposure,
pharmacology, toxicity.
• Neutralizing antibody assays – generally not needed if there is
adequate understanding of PK/PD relationship.
10. How Many Approaches To An IND –
Biopharmaceuticals
Differences in nonclinical approach for IND
• Species selection
• Pharmacology not metabolism
• Number of species
• One or two
• Safety pharmacology
• Separate or incorporated
• Genetic toxicology
• Not needed except for special situations
• Toxicology
• Dose selection
11. How Many Approaches To An IND –
Vaccines
• Single species - generally rabbit
• Single dose toxicity
• Adjuvant toxicity study – if novel adjuvant is used
• Repeat dose toxicity
• Include local tolerance and evaluation of immunogenicity
in repeat-dose study
• Biodistribution and Integration study may be required
• Safety Pharmacology and genotoxicity battery
generally not required
12. How Many Approaches To An IND –
Oncology
Cancer – advanced vs. palliative care
• “The investigation does not … significantly increases the risks (or
decreases the acceptability of the risks) associated with the use
of the drug product.”
• Pharmacology (mechanism of action, resistance, schedule
dependencies, and anti-tumor activity).
• Safety Pharmacology battery generally included in general
toxicology studies.
• Reversibility (in at least one of the repeat-dose studies).
• Genotoxicity battery generally not required.
13. How Many Approaches To An IND –
Animal Rule
• Compounds where conducting a clinical trial in humans
is not feasible – radiation sickness, neurotoxic gas
exposure
• For an IND a standard approach is used along with a
Phase 1 in humans, but the clinical trials for efficacy
are carried out in animals not humans.
14. How Many Approaches To An IND –
Excipients
Excipients- anything other than GRAS requires additional
work
• Studies required will vary from no additional work required
(GRAS) to conducting all studies in the “Traditional” Approach
(Novel).
• Use in previously approved products or GRAS status?
• Indication - lifesaving therapies vs. low morbidity
indications.
• Novel - adequate prior human exposure has not been
documented.
• “The sponsor is encouraged to contact the appropriate review
division to receive specific guidance when necessary.”
15. How Many Approaches To An IND –
Reformulated/Repurposed Drugs
505(b)(2)
• Bridging studies may substitute Safety Pharmacology battery and
General Toxicology studies if they are found to provide an
adequate basis for reliance upon FDA’s finding of safety and
effectiveness.
• Particular toxicities associated with the new route of
administration should be considered/evaluated.
• May require additional nonclinical work based on the
composition of the formulation and known toxicities.
• May be required in two species (ocular, intrathecal, or
epidural) or one species (all other routes).
• Additional nonclinical work may be required depending on
the alternate route being utilized (i.e. hypersensitivity and
phototox for dermal, blood compatibility for IV, etc.).
16. How Many Approaches To An IND –
Biosimilar
• “Generic” form of a biopharmaceutical.
• Not as straightforward as for small molecules where you
synthesize the exact same structure.
• For biopharmaceuticals, the process by which they are
created does not lend itself to duplication – many
processes are proprietary.
• Need to establish the biosimilar is equivalent to the
innovator compound.
17. How Many Approaches To An IND –
Biosimilar
Proving equivalency.
•First step is characterizing the product for structure and activity, typically
done in vitro.
•Guidance documents
• Nothing much from the FDA yet.
• Guidance form Canada, WHO, as well as multiple documents from
EMEA.
•Could involve animal studies prior to IND.
• Typically single species.
• Goal is comparison of biosimilar to innovator – are there any
differences in the tox profile?
18. How Many Approaches To An IND –
Exploratory IND
• Obtain human data on exposure and distribution, no efficacy
or safety.
• Should only be considered when planning limited, early
exploratory IND studies in man.
• Early Phase I studies, limited human exposure, no therapeutic or
diagnostic intent.
• Conducted prior to the “traditional” dose escalation, safety, and
tolerance studies generally conducted in Phase I trials.
• Generally are used to determine if MOA can be achieved in
man, provide PK information in man, select most promising
lead, and/or explore biodistribution characteristics.
19. How Many Approaches To An IND –
Exploratory IND
Reduced scope of the Exploratory IND results in reduced
nonclinical need:
• Expanded acute toxicology studies may suffice if supporting a
microdose study (less than 1/100th
of the dose that produces
pharmacologic effect).
• Single species may be used if supported by in vitro
metabolism and in vivo PD effects.
• Safety Pharmacology and genotoxicity battery generally not
required.
20. How Many Approaches To An IND –
Exploratory IND
• 14-Day Repeat-Dose toxicology studies may suffice if
supporting a study designed to evaluate pharmacologic effect
of up to 14 days.
• Two species with standard designs.
• Dose selection based on anticipated clinical exposures.
• Safety Pharmacology evaluations can be evaluated in the
toxicology studies.
• Genotoxocity limited to Ames assay in specific scenarios*
21. How Many Approaches To An IND –
Imaging Agents
FDA encourages meeting due to uniqueness of each agent
• Biological products should be evaluated similar to
biopharmaceuticals described previously
• Generally single lifetime exposure, or only a few exposures used
to diagnose or monitor diseases or conditions, therefore results in
reduced nonclinical need.
• Need to consider dose (e.g. mass dose), route, frequency of
exposure, and kinetics.
• Studies should be conducted to evaluate effects of a large mass
dose (or maximum feasible dose).
• NOAEL in acute toxicology and safety pharmacology studies
should be at least 100X and NOAEL in repeat-dose toxicology be
at least 25X the maximal mass dose in man.
22. How Many Approaches To An IND –
Botanical Products
• Definition - products that contain vegetable matter as ingredients,
may be a food (including dietary supplement), drug (including
biopharmaceuticals), device, or cosmetic.
• For the guidance, botanical includes plant materials, algae,
macroscopic fungi and combinations thereof – does not include
materials from genetically engineered species, fermentation
products (even if already approved for other uses in US), or highly
purified/chemically modified substances derived from botanical
substances.
• Unique situation in that many of the products in development have
been taken/sold for many years with no nonclinical support.
23. How Many Approaches To An IND –
Botanical Products
Nonclinical approach
• If legally available already and there are no known safety issues
(serious or life threatening), additional toxicology may not be
needed.
• If contains multiple components from different plant, algae, or
fungal species it would be subject to the requirements of a
combination drug product, although this may be changing.
• For compounds marketed outside the US, dependent on route of
administration
• For compounds that have never been marketed such as traditional
herbal medicines – dependent on preparation and dosing
24. How Many Approaches To An IND –
Drug Combinations
Combinations – 3 scenarios
• New + new- Nonclinical combination studies recommended.
• Marketed + new
• If no cause of concern, additional nonclinical studies generally
not required to support POC studies up to 1 month.
• Marketed + marketed
• If clinical experience with co-administration available, additional
nonclinical studies generally not required unless there is a
significant toxicological concern.
• If no clinical experience with co-administration available, but no
cause of concern based on available data, nonclinical studies
generally not required to support short duration clinical trials (up
to 3 months), however are recommended for longer durations.
25. How Many Approaches To An IND –
Drug Combinations
• Nonclinical development programs should be conducted on the
individual entities.
• Duration of combination studies should be equivalent to duration of
clinical trial (not to exceed 90 days) and take into account the
characteristics of the combination.
• Should be limited to single relevant species, unless unexpected toxicity
is identified.
• If complete nonclinical development programs are not available for the
individual entities, a complete program with the combination will suffice
as long as the individual agents are only planned to be used in
combination.
• Combination Safety Pharmacology and genotoxicity battery generally
not recommended.
26. How Many Approaches To An IND –
Juvenile Indications
If starting in humans and expanding into juveniles
• Review of the data from standard toxicology studies to determine if
additional studies are needed
If Juvenile is the target population
• Design of juvenile animal toxicology studies:
• Consider intended use in children, timing of dosing relative
to growth and development phases in intended population,
differences in pharmacological and toxicological profiles
between mature and immature systems.
• Should be designed to evaluate effects on organ systems
that develop postnatally ( nervous, reproductive, pulmonary,
renal, skeletal, and immune) and measurements of growth.
27. How Many Approaches To An IND –
Cellular and Gene Therapies
• Design of nonclinical study package should take into consideration the
population of cells to be administered or the class of vector; the animal
species and physiologic state most relevant for clinical indication and
product class; and the intended doses, route of administration, and
treatment regimens.
• Follow same rules as for biopharmaceuticals.
• Species specificity, permissiveness for infection by viral vectors,
comparative physiology, etc. should be considered in study design.
• Single species (most appropriate, pharmacologically relevant) should be
employed.
• Other “non-standard” endpoints may be required such as cell fate,
functional, product-dependent, or disease-dependent endpoints.
• Generally difference lies in stricter manufacturing regulations and
controls.
28. Which Path Do I Take
Depends on test article type, indication, route, clinical plan
• Review the guidelines (FDA/EMEA/ICH)
• Pre-IND Meeting
• Propose what makes scientific sense, along with the data to
support your approach
• Ask if the Agency agrees with this approach
29. Where Do I Go To Get The Work Done
• What to look for in a CRO
• Inspections – how often, any 483s, if so what were they for (not all 483s
indicate issues)
• Experience – SD and technical
• Capacity – are they overbooked
• Historical data – needed to discern background from test article-related
• Communication – if they are hard to contact during proposal process, will
that carry through to the study
• Reporting history – can they follow through on commitments
• What the CRO needs from you
• Test article
• Understanding of project scope
• Communication
30. Where Do I Go To Get The Work Done
(Continued)
• Common issues that arise
• No material available, insufficient material available
• Protocol approval
• Veterinary intervention
• Communication
• Background information on compound and possible toxicities
31. Summary
How do I get an IND for my compound depends on
• Indication
• Compound class
• Clinical plan
Numerous guidance documents to help
Hire a consultant as needed
Work with your CRO as appropriate
Take advantage of a pre-IND meeting with the Agency
32. Horizontal Bar Chart
Study Traditional Biopharmaceuticals Vaccines Cancer
Single dose/DRF Yes Yes (1 or 2 species) Yes (1 species) Yes
Repeat dose Yes Yes (1 or 2 species) Yes (1 species) Yes
Genotoxicity Yes No No No
Safety Pharmacology Yes Yes – in Tox studies No Yes – in Tox studies
Study Animal Rule Excipients
Reformulated or
Repurposed Biosimilar
Single dose/DRF Yes Yes or No Yes or No Yes (1 species)
Repeat dose Yes Yes or No Yes or No Yes (1 species)
Genotoxicity Yesa
Yes or No Yes or No No
Safety Pharmacology Yesa
Yes or No Yes or No No
a
- dependent on type of test article
33. Horizontal Bar Chart
Study Exploratory Imaging Agents Botanicals Combinations b
Single dose/DRF Yes Yes Yes or No Yes or No
Repeat dose Yes or No Yes Yes or No Yes or No
Genotoxicity No Yes Yes or No No
Safety Pharmacology
Yes – in Tox
studies Yes Yes or No No
Study Juvenile c
Orphan Cellular and Gene Therapeutics
Single dose/DRF Yes or No Yes Yes (1 or 2 species)
Repeat dose Yes or No Yes Yes (1 or 2 species)
Genotoxicity Yes or No Yes No
Safety Pharmacology Yes or No Yes Yes – in Tox studies
b
: May or may not be needed on the combination. “Traditional” studies should be completed on individual entities.
c
: May or may not be needed in the juvenile animal. “Traditional” studies should be completed in the adult animals.
34. The FDA And Their Divisions
Center for Drug Evaluation and Research (CDER)
• Conventional synthetic chemicals
• Antibiotics, natural and recombinant hormones
• Novel drugs such as antisense oligonucleotides and synthetic
peptides (< 40 AA)
35. The FDA And Their Divisions
Center for Biologic Evaluation and Research (CBER)
• Blood and blood products
• Vaccines and allergenics
• Conventional biotechnology-derived products
• Recombinant proteins, monoclonal antibodies, antigenic peptides
• Novel biotechnology-derived products
Center for Devices and Radiological Health (CDRH)
Center for Veterinary Medicine (CVM)
36. Guidelines
• ICH
• Q3A (R2) Impurities in New Drug Substances
• Q3B (R2) Impurities in New Drug Products
• Q3C (R4) Impurities Guidelines for Residual Solvents
• S1A Need for Carcinogenicity Studies for Pharmaceuticals
• S1B Testing for Carcinogenicity of Pharmaceuticals
• S1C (R2) Dose Selection for Carcinogenicity Studies of Pharmaceuticals
• S2 (R1) Guidance on Genotoxicity Testing and Data Interpretation for
Pharmaceuticals Intended for Human Use
• S3A Note for Guidance on Toxicokinetics: The Assessment of Systemic
Exposure in Toxicity Studies
• S3B Pharmacokinetics: Guidance for Repeat Dose Tissue Distribution
Studies
37. Guidelines
• ICH (Continued)
• S4 Duration of Chronic Toxicity Testing in Animals (Rodent and
Nonrodent Toxicity Testing)
• S5 (R2) Detection of Toxicity to Reproduction for medicinal Products &
Toxicity to Male Fertility
• S6 (R1) Preclinical Safety Evaluation of Biotechnology-Derived
Pharmaceuticals
• S7A Safety Pharmacology Studies for Human Pharmaceuticals
• S7B The Non-Clinical Evaluation of the Potential for Delayed
Ventricular Depolarization (QT interval prolongation) by
Human Pharmaceuticals
• S8 Immunotoxicology Studies for Human Pharmaceuticals
• S9 Nonclinical Evaluation of Anticancer Pharmaceuticals
• S10 Photosafety Evaluation
• M3 (R2) Guidance on Nonclinical Safety Studies for the Conduct of
Human Clinical Trials and Marketing Authorization for
Pharmaceuticals
38. Guidelines
• EMEA
• 3BS11A Pharmacokinetics and metabolic studies in the
safety evaluation of new medicinal products in
animals
• CHMP/SWP/302413/08 Need for revision of the guideline single dose
toxicity (3BS1A)
• CHMP/SWP/488313/07 Repeated dose toxicity
• CPMP/SWP/1042/99 Repeated dose toxicity
• CPMP/SWP/5199/02 Limits of genotoxic impurities
• CHMP/QWP/251344/2006
• CHMP/SWP/199726/04 Reflection Paper on the assessment of the
Genotoxic Potential of Antisense
Oligodeoxynucleotides
• EMEA/194898/2006 Carcinogenicity Evaluation of Medicinal Products
for the Treatment of HIV Infection
• CPMP/SWP/2592/02 Rev 1 CHMP SWP Conclusions and recommendations
on the use of genetically modified animal models
for carcinogenicity assessment
39. Guidelines
• EMEA (Continued)
• CPMP/SWP/2877 /00 Carcinogenic potential
• CPMP/SWP/372/01 Points to consider on the Non-clinical
assessment of the carcinogenic potential of
human insulin analogues
• EMEA/CHMP/203927/05 Risk Assessment of Medicinal Products on
Human Reproduction and Lactation: From Data
to Labeling
• CHMP/SWP/169215/05 Need for Non-Clinical Testing in Juvenile
Animals on Human Pharmaceuticals for
Pediatric Indications
• CPMP/SWP/2600/01 Points to consider on the Need for assessment
of reproduction toxicity of human insulin
analogues
• CPMP/SWP/2145/00 Non-clinical local tolerance testing of medicinal
products
• CHMP/SWP/150115/06 Non-clinical guideline on drug-induced
hepatotoxicity
40. Guidelines
• EMEA (Continued)
• CHMP/SWP/94227/04 Non-Clinical Investigation of the Dependence
Potential of Medicinal Products
• CPMP/SWP/398/01 Need for revision of the Note for Guidance on
photosafety testing
• CPMP/SWP/728/95 Replacement of animal studies by in vitro
models
• CHMP/SWP/28367/07 Strategies to identify and mitigate risks for first-
in-human clinical trials with investigational
medicinal products
• CHMP/GTWP/125459/2006 Non-clinical studies required before first clinical
use of gene therapy medicinal products
• EMEA/CHMP/SWP/91850/06 Development of a CHMP Guideline on the Non-
Clinical Requirements to Support Early Phase I
Clinical Trials with Pharmaceutical Compounds
• EMEA/CHMP/94526/05 Annex Guideline on Similar Biological Medicinal
Products containing Biotechnology-Derived
Proteins as Active Substance: Non-Clinical and
Clinical Issues - Guidance on Similar Medicinal
Products containing Recombinant Erythropoietins
41. Guidelines
• EMEA (Continued)
• EMEA/273974/05 Quality, Preclinical and Clinical aspects of Gene
Transfer Medicinal Products - Annex on Non-
Clinical testing for Inadvertent Germline
transmission of Gene Transfer Vectors
• CPMP/SWP/799/95 Non-Clinical Documentation for Mixed Marketing
Authorization Applications
• CHMP/SWP/258498/05 Non-Clinical Development of Fixed
Combinations of Medicinal Products
• CPMP/SWP/1094/04 Evaluation of Control Samples for Non - clinical
Safety Studies: Checking for Contamination with
the Test Substance
• CPMP/SWP/2599/02 Position Paper on the non-clinical safety studies
to support clinical trials with a single micro dose
• CPMP /3097/02* Comparability of medicinal products containing
biotechnology-derived proteins as active
substance -annex on non-clinical and clinical
issues
42. Guidelines
• EMEA (Continued)
• CPMP/SWP/997/96 Pre-clinical evaluation of anti- cancer medicinal
products
• CPMP/SWP/465/95 Pre-clinical pharmacological and toxicological
testing of vaccines
• EMEA/HMPC/107079/07 Assessment of genotoxicity of herbal
substances/preparations
• EMEA/HMPC/32116/05 Non-Clinical Documentation for Herbal Medicinal
Products in Applications for Marketing
Authorization (Bibliographical and Mixed
Applications) and in Applications for Simplified
Registration
43. Guidelines
• CDER
• Animal Models - Essential elements to Address Efficacy under the Animal Rule
• Developing Medical Imaging Drugs and Biological Products - Part 1: Conducting
Safety Assessments
• Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics
in Adult Healthy Volunteers
• Genotoxic and Carcinogenic Impurities in Drug Substances and Products:
Recommended Approaches
• Immunotoxicology Evaluation of Investigational New Drugs
• Nonclinical Evaluation of Late Radiation Toxicity of Therapeutic
Radiopharmaceuticals
• Nonclinical Safety Evaluation of Drug or Biologic Combinations
• Nonclinical Safety Evaluation of Reformulated Drug Products and Products
Intended for Administration by an Alternate Route
• Nonclinical Safety Evaluation of Pediatric Drug Products
44. Guidelines
• CDER (Continued)
• Nonclinical Studies for the Safety Evaluation of Pharmaceutical Excipients
• Photosafety Testing
• Recommended Approaches to Integration of Genetic Toxicology Study Results
• Reference Guide for the Nonclinical Toxicity Studies of Antiviral Drugs Indicated for
the Treatment of N/A Non-Life Threatening Disease Evaluation of Drug Toxicity
Prior to Phase I Clinical Studies
• Safety Testing of Drug Metabolites
• Single Dose Acute Toxicity Testing for Pharmaceuticals
• Statistical Aspects of the Design, Analysis, and Interpretation of Chronic Rodent
Carcinogenicity Studies of Pharmaceuticals
• Content and Format of Investigational New Drug Applications (INDs) for Phase 1
Studies of Drugs
• Exploratory IND Studies
• Codevelopment of Two or More Unmarketed Investigational Drugs for Use in
Combination
• Applications covered by Section 505(b)(2)