This document provides an overview of the drug development and clinical trial process. It discusses the various phases of drug discovery and development, including pre-clinical research (discovery and pharmacology) and clinical trials (Phase 1-3). Key points covered include the high costs and risks of drug development, clinical trial design and goals for each phase, pharmacokinetics/dynamics studies to understand drug behavior in the body, and factors like safety, efficacy, and regulatory approval. The overall process takes an average of 15 years and $2.6 billion to bring a new drug to market.
ANVISA is the Brazilian Health Surveillance Agency established in 1999 to coordinate the National Sanitary Surveillance System and other health programs. It is responsible for regulating drugs, medical devices, food, cosmetics and other products. ANVISA monitors prices, conducts inspections, and provides technical support. It aims to protect public health through sanitary control of production, marketing and borders. ANVISA is part of the decentralized National System of Sanitary Surveillance and works with various federal, state and municipal agencies.
This project report discusses drug regulatory affairs and its importance. It provides an overview of regulatory departments and professionals, their roles, and necessary qualities. Regulatory authorities from India, the US, European Union, and Japan are examined. The report outlines the drug approval process in each region and highlights literature on regulatory issues faced by pharmaceutical companies. In conclusion, the report emphasizes that regulatory affairs has become essential for pharmaceutical companies due to globalization and the need to navigate varying international regulations and authorities.
Presented By :- Raghav Sharma
Class :- M.Pharm, 1st sem.
Department :- Pharmaceutics
Institute :- Parul Institute of Pharmacy
Content :-
Introduction to Clinical trials
Importance of Clinical Trials
Phase-I of Clinical Trials
Phase-II of Clinical Trials
Phase-III of Clinical Trials
Phase-IV of Clinical Trials
Conclusion
References
The document discusses Investigational New Drug Applications (INDs), which are required for clinical trials of new drugs. It outlines the key components of an IND, including an introductory statement, investigator's brochure, protocols, chemistry/manufacturing information, and previous human experience. It also describes IND amendments, annual reports, and the roles of the sponsor and investigator. The overall purpose of an IND is to provide information to the FDA on a new drug's safety before it can be tested in humans.
The International Council for Harmonisation (ICH) is a joint regulatory-industry initiative to harmonize technical requirements for pharmaceutical product registration. It aims to reduce duplication of testing by achieving greater harmonization in guidelines' interpretation between Europe, Japan, and the United States. ICH addresses safety, quality, efficacy, and other topics through guidelines developed by expert working groups representing regulators and industry. Over two decades, ICH has successfully harmonized guidelines through scientific consensus.
overview of Japan pharmaceutical regulatory authority - PMDANandhanan
PMDA (Pharmaceuticals and Medical Devices Agency) is Japanese regulatory agency, working together with Ministry of Health, Labour and Welfare.
Its obligation is to protect the public health by assuring safety, efficacy and quality of pharmaceuticals and medical devices.
It conduct scientific reviews of marketing authorization application of pharmaceuticals and medical devices, monitoring of their post-marketing safety and also responsible for providing relief compensation for sufferers from adverse drug reaction and infections by pharmaceuticals or biological products.PMDA (Pharmaceuticals and Medical Devices Agency) is Japanese regulatory agency, working together with Ministry of Health, Labour and Welfare.
Its obligation is to protect the public health by assuring safety, efficacy and quality of pharmaceuticals and medical devices.
It conduct scientific reviews of marketing authorization application of pharmaceuticals and medical devices, monitoring of their post-marketing safety and also responsible for providing relief compensation for sufferers from adverse drug reaction and infections by pharmaceuticals or biological products.
ANVISA is the Brazilian Health Surveillance Agency established in 1999 to coordinate the National Sanitary Surveillance System and other health programs. It is responsible for regulating drugs, medical devices, food, cosmetics and other products. ANVISA monitors prices, conducts inspections, and provides technical support. It aims to protect public health through sanitary control of production, marketing and borders. ANVISA is part of the decentralized National System of Sanitary Surveillance and works with various federal, state and municipal agencies.
This project report discusses drug regulatory affairs and its importance. It provides an overview of regulatory departments and professionals, their roles, and necessary qualities. Regulatory authorities from India, the US, European Union, and Japan are examined. The report outlines the drug approval process in each region and highlights literature on regulatory issues faced by pharmaceutical companies. In conclusion, the report emphasizes that regulatory affairs has become essential for pharmaceutical companies due to globalization and the need to navigate varying international regulations and authorities.
Presented By :- Raghav Sharma
Class :- M.Pharm, 1st sem.
Department :- Pharmaceutics
Institute :- Parul Institute of Pharmacy
Content :-
Introduction to Clinical trials
Importance of Clinical Trials
Phase-I of Clinical Trials
Phase-II of Clinical Trials
Phase-III of Clinical Trials
Phase-IV of Clinical Trials
Conclusion
References
The document discusses Investigational New Drug Applications (INDs), which are required for clinical trials of new drugs. It outlines the key components of an IND, including an introductory statement, investigator's brochure, protocols, chemistry/manufacturing information, and previous human experience. It also describes IND amendments, annual reports, and the roles of the sponsor and investigator. The overall purpose of an IND is to provide information to the FDA on a new drug's safety before it can be tested in humans.
The International Council for Harmonisation (ICH) is a joint regulatory-industry initiative to harmonize technical requirements for pharmaceutical product registration. It aims to reduce duplication of testing by achieving greater harmonization in guidelines' interpretation between Europe, Japan, and the United States. ICH addresses safety, quality, efficacy, and other topics through guidelines developed by expert working groups representing regulators and industry. Over two decades, ICH has successfully harmonized guidelines through scientific consensus.
overview of Japan pharmaceutical regulatory authority - PMDANandhanan
PMDA (Pharmaceuticals and Medical Devices Agency) is Japanese regulatory agency, working together with Ministry of Health, Labour and Welfare.
Its obligation is to protect the public health by assuring safety, efficacy and quality of pharmaceuticals and medical devices.
It conduct scientific reviews of marketing authorization application of pharmaceuticals and medical devices, monitoring of their post-marketing safety and also responsible for providing relief compensation for sufferers from adverse drug reaction and infections by pharmaceuticals or biological products.PMDA (Pharmaceuticals and Medical Devices Agency) is Japanese regulatory agency, working together with Ministry of Health, Labour and Welfare.
Its obligation is to protect the public health by assuring safety, efficacy and quality of pharmaceuticals and medical devices.
It conduct scientific reviews of marketing authorization application of pharmaceuticals and medical devices, monitoring of their post-marketing safety and also responsible for providing relief compensation for sufferers from adverse drug reaction and infections by pharmaceuticals or biological products.
The document discusses orphan drugs and the need for orphan drug development. It defines orphan drugs as medicines developed to treat rare diseases affecting fewer than 5 in 10,000 people. It describes orphan drug policies in the US, EU, Japan and Australia which provide incentives like market exclusivity, tax credits and protocol assistance to encourage orphan drug development. It discusses hurdles to access orphan drugs in India like high prices and lack of formal incentives. It summarizes recent orphan drug approvals in the US and top selling orphan drugs worldwide. It highlights the need for policies and initiatives in India to encourage orphan drug development and ensure affordable access.
The document provides information on periodic safety update reports (PSURs), including:
- PSURs are intended to evaluate the risk-benefit balance of a drug based on new or changing information during the post-approval phase.
- The objectives of a PSUR are to examine if new safety information aligns with previous knowledge, summarize relevant new safety data that could impact risk-benefit analysis, and provide an integrated risk-benefit evaluation.
- Guidelines for PSURs are provided in the ICH E2C guideline and EU's GVP Module VII, with the format and content changing to focus more on risk-benefit analyses and summary tables rather than individual case reports.
The document discusses key aspects of clinical trial strategy and design. It covers the different phases of clinical trials (Phase I, II, III) and provides guidance on optimizing trials at each phase. Phase I focuses on safety and dosing, Phase II evaluates efficacy and further safety, and Phase III confirms efficacy in a larger patient population. The document emphasizes establishing a detailed clinical development plan with timelines and costs to help guide development decisions and reduce risks.
To compare filing process of NDA of different countries of India, US and Euro...Aakashdeep Raval
To compare filing process of NDA of different countries of India, US and Europe.
B) Preparation of global list documents of registration of IND and NDA as per USFDA and Europe.
This document provides an overview of regulatory affairs and the new drug development process. It defines regulatory affairs as a profession focused on collecting, analyzing, and communicating risk-benefit information of healthcare products to regulatory agencies. The new drug development process involves discovery, pre-clinical studies, investigational new drug application, clinical trials, new drug application, and post-marketing activities. Key goals of regulatory affairs include protecting human health, ensuring safety and efficacy, and providing accurate product information.
Risk management plan (RMP) requirements: When and why is an RMP requiredTGA Australia
The document discusses Risk Management Plan (RMP) requirements according to Therapeutic Goods Administration (TGA) guidelines. It provides information on when an RMP is required, the RMP format and submission process, and examples of whether an RMP would be needed for different types of applications including extensions of indication, changes in strength or dosage form, and combination products. An RMP is always required for new drugs and higher risk products and may be required on a case by case basis for changes to approved drugs depending on factors like new patient populations or risk of medication errors. Attendees will learn about current RMP guidelines and practice case studies to determine if an RMP would be necessary in given scenarios.
1) The document defines many terms used in pharmacovigilance, including adverse event, adverse reaction, causality assessment, signal, and serious adverse reaction.
2) An adverse event is any untoward medical occurrence during treatment but not necessarily caused by the treatment, while an adverse reaction is characterized by a suspected causal relationship to the treatment.
3) A signal refers to reported information about a potential causal relationship between an adverse event and drug that was previously unknown or incompletely documented.
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
The Federal Food, Drug, and Cosmetic Act (FFDCA) was enacted in 1938 and gave the U.S. Food and Drug Administration (FDA) authority to oversee food, drugs, and cosmetics. It was passed in response to the 1937 Elixir Sulfanilamide tragedy that killed over 100 people. The FFDCA introduced requirements for pre-market approval of new drugs and mandated that labels disclose ingredients and directions for safe use. It has since been amended multiple times to both strengthen and clarify the FDA's regulatory authority.
The Commonwealth of Independent States (CIS) is an intergovernmental organization formed in 1991 by countries of the former Soviet Union. The document discusses pharmaceutical regulations and drug registration procedures in several CIS countries, including Russia, Ukraine, and Kazakhstan. Key aspects summarized include the regulatory authorities responsible for drug approval in each country, the typical registration process and requirements, and post-marketing pharmacovigilance obligations.
Indian Pharmaceutical Export Market - Top Export Destinations for Indian Phar...Irish Pereira
By Mr. Irish Pereira. The report present snapshot of Indian Pharmaceutical industry in both domestic as well as export market. It is collation of facts pertaining to Indian pharma exports and explore key emerging trends pertaining to pharma export market. It describes key players of Indian pharma market and their export orientation as in their target export destinations, their focus therapies etc.
Fact sheet:
1) Indian Pharma Market size 2015
2) Indian pharmaceutical market segments by value
3)Patented (Innovator) Vs Generics Scenario
4)Growth drivers of Indian pharmaceutical industry
5) Indian Pharmaceutical sector – SWOT Analysis
6)PHARMEXCIL – Facilitating agency for Indian Pharma Exports
7) Indian Pharmaceutical Exports (USD bn)
8)Formulations share in Total Pharma Exports (2014-15)
9) Top 25 destination countries of India’s pharmaceutical exports during 2013-14 (INR mn)
10) Major Indian Pharma Companies (By Revenue-USD mn)
11) Pharma players and their export destinations
Sun Pharma,Dr. Reddy’s Lab,
CIPLA, Lupin, Aurobindo, Cadila Healthcare, Torrent Pharma, Wockhardt,
12) Emerging trends in Indian Pharma Market
The Office of Orphan Products Development (OOPD) at the FDA promotes the development of treatments for rare diseases and conditions. There are more than 6,800 known rare diseases affecting an estimated 25-30 million Americans. The Orphan Drug Act of 1983 provides financial incentives like tax credits, user fee waivers, and exclusive marketing rights for 7 years to encourage development of treatments for rare diseases. The OOPD oversees programs that grant orphan drug designation, provide funding for clinical trials and natural history studies, and award priority review vouchers for rare pediatric diseases.
This document provides an overview of regulatory affairs and its importance in the pharmaceutical industry. It discusses how regulatory affairs developed due to governments' desire to control medicine safety and efficacy. The regulatory affairs professional ensures products comply with all regulations. The document outlines some key drug regulation events that prompted stricter laws, such as the 1901 diphtheria antitoxin contamination and the 1960 thalidomide tragedy. It also summarizes the role of regulatory authorities like the FDA and regulatory affairs departments in obtaining marketing authorization and maintaining compliance.
This document discusses pharmacovigilance and the need for monitoring drug safety post approval. It describes how historical drug safety issues like the Elixir Sulfanilamide and Thalidomide tragedies revealed limitations in pre-approval testing and established the need for ongoing pharmacovigilance. The aims, application and reporting processes of pharmacovigilance are outlined along with terminology and examples of regulatory actions taken based on adverse event reporting.
The document describes the five modules of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Common Technical Document (CTD) format for ASEAN countries. Module 1 contains regional administrative information. Module 2 provides an overall summary of Modules 3, 4, and 5, including quality, non-clinical, and clinical overviews. Module 3 includes chemistry, manufacturing, and quality control documents. Module 4 contains non-clinical safety data. Module 5 provides clinical study reports, though generics only need to include bioequivalence studies. The CTD format is required for both new drug and generic applications in ASEAN countries.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive functioning. Exercise causes chemical changes in the brain that may help protect against mental illness and improve symptoms.
Pharmaceutical globalization: Where are drugs invented?thinkBiotech
The document discusses the globalization of drug discovery and development. It examines factors that influence where research and production occurs such as workforce costs, market size, intellectual property laws, and government policies. Countries like the US and Europe have traditionally led in innovation due to strong markets and patent protection, but Asia is increasing its role with lower costs and a growing skilled workforce. Where drugs are invented is shifting over time, with the US share declining and Asia rising in recent decades.
plasma master file in European countries and requirements in letter of intent...Sanjay batra
This document summarizes the key points of a plasma master file (PMF). A PMF contains all required scientific data on the quality and safety of human plasma used to manufacture medicines, medical devices, and investigational products. It was introduced by the European Union in 2003 to simplify regulatory submissions and ensure consistent evaluation of plasma quality across countries. The certification process involves submitting an application to the European Medicines Agency, which appoints coordinators to evaluate the PMF and issue a certificate valid throughout the EU if compliance is demonstrated. Changes to plasma or products listed in the PMF require recertification through this centralized procedure.
This document discusses orphan drugs and rare disease drug development. It outlines the challenges in developing drugs for rare diseases, including small patient populations and lack of knowledge. The role of clinical pharmacology in drug development is described, including use of innovative analyses, trial designs, and knowledge management to help overcome challenges. Clinical pharmacology can point the way by applying lessons from oncology and pediatric drug models to the orphan drug context. Collaboration across different stakeholders is needed to develop safe and effective drugs for rare diseases.
This document summarizes regulatory perspectives on approving drugs for rare diseases from a presentation given by an FDA official. It provides an overview of drug development for rare diseases before and after the 1983 Orphan Drug Act. While the Act increased incentives for rare disease drug development, approval challenges remain due to small patient populations and lack of understanding of rare diseases. The FDA aims to apply flexibility in effectiveness standards and innovative trial designs and analyses. Ongoing collaborations between the FDA, industry, academia, and patient groups are needed to continue advancing treatments for rare diseases.
The document discusses orphan drugs and the need for orphan drug development. It defines orphan drugs as medicines developed to treat rare diseases affecting fewer than 5 in 10,000 people. It describes orphan drug policies in the US, EU, Japan and Australia which provide incentives like market exclusivity, tax credits and protocol assistance to encourage orphan drug development. It discusses hurdles to access orphan drugs in India like high prices and lack of formal incentives. It summarizes recent orphan drug approvals in the US and top selling orphan drugs worldwide. It highlights the need for policies and initiatives in India to encourage orphan drug development and ensure affordable access.
The document provides information on periodic safety update reports (PSURs), including:
- PSURs are intended to evaluate the risk-benefit balance of a drug based on new or changing information during the post-approval phase.
- The objectives of a PSUR are to examine if new safety information aligns with previous knowledge, summarize relevant new safety data that could impact risk-benefit analysis, and provide an integrated risk-benefit evaluation.
- Guidelines for PSURs are provided in the ICH E2C guideline and EU's GVP Module VII, with the format and content changing to focus more on risk-benefit analyses and summary tables rather than individual case reports.
The document discusses key aspects of clinical trial strategy and design. It covers the different phases of clinical trials (Phase I, II, III) and provides guidance on optimizing trials at each phase. Phase I focuses on safety and dosing, Phase II evaluates efficacy and further safety, and Phase III confirms efficacy in a larger patient population. The document emphasizes establishing a detailed clinical development plan with timelines and costs to help guide development decisions and reduce risks.
To compare filing process of NDA of different countries of India, US and Euro...Aakashdeep Raval
To compare filing process of NDA of different countries of India, US and Europe.
B) Preparation of global list documents of registration of IND and NDA as per USFDA and Europe.
This document provides an overview of regulatory affairs and the new drug development process. It defines regulatory affairs as a profession focused on collecting, analyzing, and communicating risk-benefit information of healthcare products to regulatory agencies. The new drug development process involves discovery, pre-clinical studies, investigational new drug application, clinical trials, new drug application, and post-marketing activities. Key goals of regulatory affairs include protecting human health, ensuring safety and efficacy, and providing accurate product information.
Risk management plan (RMP) requirements: When and why is an RMP requiredTGA Australia
The document discusses Risk Management Plan (RMP) requirements according to Therapeutic Goods Administration (TGA) guidelines. It provides information on when an RMP is required, the RMP format and submission process, and examples of whether an RMP would be needed for different types of applications including extensions of indication, changes in strength or dosage form, and combination products. An RMP is always required for new drugs and higher risk products and may be required on a case by case basis for changes to approved drugs depending on factors like new patient populations or risk of medication errors. Attendees will learn about current RMP guidelines and practice case studies to determine if an RMP would be necessary in given scenarios.
1) The document defines many terms used in pharmacovigilance, including adverse event, adverse reaction, causality assessment, signal, and serious adverse reaction.
2) An adverse event is any untoward medical occurrence during treatment but not necessarily caused by the treatment, while an adverse reaction is characterized by a suspected causal relationship to the treatment.
3) A signal refers to reported information about a potential causal relationship between an adverse event and drug that was previously unknown or incompletely documented.
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
The Federal Food, Drug, and Cosmetic Act (FFDCA) was enacted in 1938 and gave the U.S. Food and Drug Administration (FDA) authority to oversee food, drugs, and cosmetics. It was passed in response to the 1937 Elixir Sulfanilamide tragedy that killed over 100 people. The FFDCA introduced requirements for pre-market approval of new drugs and mandated that labels disclose ingredients and directions for safe use. It has since been amended multiple times to both strengthen and clarify the FDA's regulatory authority.
The Commonwealth of Independent States (CIS) is an intergovernmental organization formed in 1991 by countries of the former Soviet Union. The document discusses pharmaceutical regulations and drug registration procedures in several CIS countries, including Russia, Ukraine, and Kazakhstan. Key aspects summarized include the regulatory authorities responsible for drug approval in each country, the typical registration process and requirements, and post-marketing pharmacovigilance obligations.
Indian Pharmaceutical Export Market - Top Export Destinations for Indian Phar...Irish Pereira
By Mr. Irish Pereira. The report present snapshot of Indian Pharmaceutical industry in both domestic as well as export market. It is collation of facts pertaining to Indian pharma exports and explore key emerging trends pertaining to pharma export market. It describes key players of Indian pharma market and their export orientation as in their target export destinations, their focus therapies etc.
Fact sheet:
1) Indian Pharma Market size 2015
2) Indian pharmaceutical market segments by value
3)Patented (Innovator) Vs Generics Scenario
4)Growth drivers of Indian pharmaceutical industry
5) Indian Pharmaceutical sector – SWOT Analysis
6)PHARMEXCIL – Facilitating agency for Indian Pharma Exports
7) Indian Pharmaceutical Exports (USD bn)
8)Formulations share in Total Pharma Exports (2014-15)
9) Top 25 destination countries of India’s pharmaceutical exports during 2013-14 (INR mn)
10) Major Indian Pharma Companies (By Revenue-USD mn)
11) Pharma players and their export destinations
Sun Pharma,Dr. Reddy’s Lab,
CIPLA, Lupin, Aurobindo, Cadila Healthcare, Torrent Pharma, Wockhardt,
12) Emerging trends in Indian Pharma Market
The Office of Orphan Products Development (OOPD) at the FDA promotes the development of treatments for rare diseases and conditions. There are more than 6,800 known rare diseases affecting an estimated 25-30 million Americans. The Orphan Drug Act of 1983 provides financial incentives like tax credits, user fee waivers, and exclusive marketing rights for 7 years to encourage development of treatments for rare diseases. The OOPD oversees programs that grant orphan drug designation, provide funding for clinical trials and natural history studies, and award priority review vouchers for rare pediatric diseases.
This document provides an overview of regulatory affairs and its importance in the pharmaceutical industry. It discusses how regulatory affairs developed due to governments' desire to control medicine safety and efficacy. The regulatory affairs professional ensures products comply with all regulations. The document outlines some key drug regulation events that prompted stricter laws, such as the 1901 diphtheria antitoxin contamination and the 1960 thalidomide tragedy. It also summarizes the role of regulatory authorities like the FDA and regulatory affairs departments in obtaining marketing authorization and maintaining compliance.
This document discusses pharmacovigilance and the need for monitoring drug safety post approval. It describes how historical drug safety issues like the Elixir Sulfanilamide and Thalidomide tragedies revealed limitations in pre-approval testing and established the need for ongoing pharmacovigilance. The aims, application and reporting processes of pharmacovigilance are outlined along with terminology and examples of regulatory actions taken based on adverse event reporting.
The document describes the five modules of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Common Technical Document (CTD) format for ASEAN countries. Module 1 contains regional administrative information. Module 2 provides an overall summary of Modules 3, 4, and 5, including quality, non-clinical, and clinical overviews. Module 3 includes chemistry, manufacturing, and quality control documents. Module 4 contains non-clinical safety data. Module 5 provides clinical study reports, though generics only need to include bioequivalence studies. The CTD format is required for both new drug and generic applications in ASEAN countries.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive functioning. Exercise causes chemical changes in the brain that may help protect against mental illness and improve symptoms.
Pharmaceutical globalization: Where are drugs invented?thinkBiotech
The document discusses the globalization of drug discovery and development. It examines factors that influence where research and production occurs such as workforce costs, market size, intellectual property laws, and government policies. Countries like the US and Europe have traditionally led in innovation due to strong markets and patent protection, but Asia is increasing its role with lower costs and a growing skilled workforce. Where drugs are invented is shifting over time, with the US share declining and Asia rising in recent decades.
plasma master file in European countries and requirements in letter of intent...Sanjay batra
This document summarizes the key points of a plasma master file (PMF). A PMF contains all required scientific data on the quality and safety of human plasma used to manufacture medicines, medical devices, and investigational products. It was introduced by the European Union in 2003 to simplify regulatory submissions and ensure consistent evaluation of plasma quality across countries. The certification process involves submitting an application to the European Medicines Agency, which appoints coordinators to evaluate the PMF and issue a certificate valid throughout the EU if compliance is demonstrated. Changes to plasma or products listed in the PMF require recertification through this centralized procedure.
This document discusses orphan drugs and rare disease drug development. It outlines the challenges in developing drugs for rare diseases, including small patient populations and lack of knowledge. The role of clinical pharmacology in drug development is described, including use of innovative analyses, trial designs, and knowledge management to help overcome challenges. Clinical pharmacology can point the way by applying lessons from oncology and pediatric drug models to the orphan drug context. Collaboration across different stakeholders is needed to develop safe and effective drugs for rare diseases.
This document summarizes regulatory perspectives on approving drugs for rare diseases from a presentation given by an FDA official. It provides an overview of drug development for rare diseases before and after the 1983 Orphan Drug Act. While the Act increased incentives for rare disease drug development, approval challenges remain due to small patient populations and lack of understanding of rare diseases. The FDA aims to apply flexibility in effectiveness standards and innovative trial designs and analyses. Ongoing collaborations between the FDA, industry, academia, and patient groups are needed to continue advancing treatments for rare diseases.
Clinical Pharmacology in Orphan Drug DevelopmentE. Dennis Bashaw
This is the fourth talk that I gave in Asia back in May. It was presented at the Konect (Korea National Enterprise for Clinical Trials) 3rd symposia that was held in Seoul at Seoul National University.
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.
Slides presented by me at the Korean-American Professional Association in Life Sciences (KAPAL) 5th Annual Meeting in Rockville, MD. Slides discuss the recent reorganization of the Center for Drug Evaluation and Research at the FDA
Naila Kanwal's document summarizes the new drug development and approval process. It describes the preclinical research phase involving animal and lab testing to determine safety and effectiveness. It then explains the clinical trial phases involving human subjects to further evaluate these factors. The document outlines the steps of submitting an Investigational New Drug application to the FDA for review and potential approval or requests for additional information before studies can begin. The overall process is designed to demonstrate a new drug is safe and effective for its intended use before being approved and marketed to the public.
Transalational Sciences and Clinical Pharmacology in Orphan Drug DevelopmentE. Dennis Bashaw
This document discusses challenges and solutions for developing orphan drugs and implementing precision medicine programs. It notes that orphan drug development faces resource constraints as trials require more patients than rare diseases have. However, using clinical pharmacology tools allows learning from small populations by incorporating biomarkers, modeling, and innovative designs. The future of drug development lies in going beyond traditional trials to involve patients more and continually learn from individual experiences. Quantitative tools during all stages of development can extract maximum knowledge from minimal data to improve understanding, approval chances, and labeling.
Drug development is a long, expensive, and high-risk process that takes an average of 10-15 years. It involves preclinical research in animals and humans to test safety and efficacy. Clinical trials in humans have 4 phases - Phase I tests safety in small groups, Phase II explores efficacy in small patient groups, Phase III tests in large patient groups to confirm efficacy and safety for approval, and Phase IV occurs after approval to monitor long-term effects. Only about 1 in 10 drugs that enter clinical trials will ultimately receive regulatory approval due to the high costs and failure rates of drug development. Rigorous testing and regulatory review are required to bring a new drug to market globally.
Clinical trials are scientific studies that test new drugs in human subjects. This document discusses the multi-phase clinical trial process, from pre-clinical animal studies through post-approval monitoring. It notes that trials progress from small Phase I safety studies in healthy volunteers to large Phase III efficacy trials in patients. The goal is to demonstrate a drug's benefits outweigh its risks before regulatory approval and marketing.
This document discusses clinical trials and the drug development process. It begins with an overview of the stages of clinical trials from Phase 0 to Phase IV. It then covers topics like trial design, endpoints, biases, sample sizes, regulatory authorities, and cost-effectiveness. The failures and successes of translating pre-clinical findings to human studies are analyzed. Repurposing existing drugs and the challenges academic researchers face are also addressed.
This document provides an overview of the scope of pharmacology. It discusses the history and evolution of pharmacology from materia medica and early pharmacy to its modern academic, industrial and research applications. Key areas of pharmacology discussed include drug development process, clinical pharmacology, special domains like pharmacovigilance, pharmacoeconomics and emerging areas like pharmacogenomics. The document outlines the past, present and future scope of pharmacology and how it aims to advance human health through rational and safe use of medicines.
Discovery of Drug and Introduction to Clinical Trial_Katalyst HLSKatalyst HLS
Introduction to Discovery of Drug and Introduction to Clinical Trials in Pharmaceuticals, Bio-Pharmaceuticals, Medical Devices, Cosmeceuticals and Foods.
Overview regulatory environment in usa,europe,indiashabana parveen
The document summarizes the process for clinical research and drug approval by the FDA. It describes the multi-step process including pre-clinical research in animals, Phase 1-3 clinical trials in humans to test safety and efficacy, and the submission of a New Drug Application. The FDA rigorously reviews data at each stage before approving progression to the next stage to ensure safety. The overall process aims to establish that new drugs are safe and effective for use by the American public.
Introduction
History
How are new drug discovered?
Bioinformatics in drug discovery
Tools for drug discovery
Successful drug
Software for drug discovery
Conclusion
References
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.
Pharmacoepidemiology involves applying epidemiological methods to study drug use and effects in large populations. It is primarily concerned with post-marketing drug safety surveillance but also analyzes patterns of drug use and assesses effectiveness. Pharmacoepidemiological studies use large healthcare databases and are important for identifying adverse drug reactions, determining risk factors, and improving appropriate medication use. Common study designs include cohort studies, case-control studies, and randomized controlled trials. Pharmacoepidemiology plays a key role in drug regulation, marketing, clinical practice, and public health policy.
Drug Discovery path
Pharma R & D –overview
Discovery & Development
Preclinical research
Clinical Trial
NDA and FDA Approval
Post marketing data
References
The document discusses regulations for clinical trials in India. It begins by explaining that an Investigational New Drug Application (IND) provides an exemption that allows investigational drugs to be transported across state lines for clinical trials. It then describes the process of submitting an IND to the FDA, including providing animal studies data, manufacturing information, clinical protocols, and investigator information. It notes that the FDA has 30 days to review submitted INDs. Finally, it summarizes that in India, an application for clinical trials should be submitted to the DCGI along with chemistry, manufacturing, animal study data and other required documents and trial protocols, and trials can only begin after approval from the DCGI and ethics committee.
Mending Clothing to Support Sustainable Fashion_CIMaR 2024.pdfSelcen Ozturkcan
Ozturkcan, S., Berndt, A., & Angelakis, A. (2024). Mending clothing to support sustainable fashion. Presented at the 31st Annual Conference by the Consortium for International Marketing Research (CIMaR), 10-13 Jun 2024, University of Gävle, Sweden.
Microbial interaction
Microorganisms interacts with each other and can be physically associated with another organisms in a variety of ways.
One organism can be located on the surface of another organism as an ectobiont or located within another organism as endobiont.
Microbial interaction may be positive such as mutualism, proto-cooperation, commensalism or may be negative such as parasitism, predation or competition
Types of microbial interaction
Positive interaction: mutualism, proto-cooperation, commensalism
Negative interaction: Ammensalism (antagonism), parasitism, predation, competition
I. Mutualism:
It is defined as the relationship in which each organism in interaction gets benefits from association. It is an obligatory relationship in which mutualist and host are metabolically dependent on each other.
Mutualistic relationship is very specific where one member of association cannot be replaced by another species.
Mutualism require close physical contact between interacting organisms.
Relationship of mutualism allows organisms to exist in habitat that could not occupied by either species alone.
Mutualistic relationship between organisms allows them to act as a single organism.
Examples of mutualism:
i. Lichens:
Lichens are excellent example of mutualism.
They are the association of specific fungi and certain genus of algae. In lichen, fungal partner is called mycobiont and algal partner is called
II. Syntrophism:
It is an association in which the growth of one organism either depends on or improved by the substrate provided by another organism.
In syntrophism both organism in association gets benefits.
Compound A
Utilized by population 1
Compound B
Utilized by population 2
Compound C
utilized by both Population 1+2
Products
In this theoretical example of syntrophism, population 1 is able to utilize and metabolize compound A, forming compound B but cannot metabolize beyond compound B without co-operation of population 2. Population 2is unable to utilize compound A but it can metabolize compound B forming compound C. Then both population 1 and 2 are able to carry out metabolic reaction which leads to formation of end product that neither population could produce alone.
Examples of syntrophism:
i. Methanogenic ecosystem in sludge digester
Methane produced by methanogenic bacteria depends upon interspecies hydrogen transfer by other fermentative bacteria.
Anaerobic fermentative bacteria generate CO2 and H2 utilizing carbohydrates which is then utilized by methanogenic bacteria (Methanobacter) to produce methane.
ii. Lactobacillus arobinosus and Enterococcus faecalis:
In the minimal media, Lactobacillus arobinosus and Enterococcus faecalis are able to grow together but not alone.
The synergistic relationship between E. faecalis and L. arobinosus occurs in which E. faecalis require folic acid
Evidence of Jet Activity from the Secondary Black Hole in the OJ 287 Binary S...Sérgio Sacani
Wereport the study of a huge optical intraday flare on 2021 November 12 at 2 a.m. UT in the blazar OJ287. In the binary black hole model, it is associated with an impact of the secondary black hole on the accretion disk of the primary. Our multifrequency observing campaign was set up to search for such a signature of the impact based on a prediction made 8 yr earlier. The first I-band results of the flare have already been reported by Kishore et al. (2024). Here we combine these data with our monitoring in the R-band. There is a big change in the R–I spectral index by 1.0 ±0.1 between the normal background and the flare, suggesting a new component of radiation. The polarization variation during the rise of the flare suggests the same. The limits on the source size place it most reasonably in the jet of the secondary BH. We then ask why we have not seen this phenomenon before. We show that OJ287 was never before observed with sufficient sensitivity on the night when the flare should have happened according to the binary model. We also study the probability that this flare is just an oversized example of intraday variability using the Krakow data set of intense monitoring between 2015 and 2023. We find that the occurrence of a flare of this size and rapidity is unlikely. In machine-readable Tables 1 and 2, we give the full orbit-linked historical light curve of OJ287 as well as the dense monitoring sample of Krakow.
TOPIC OF DISCUSSION: CENTRIFUGATION SLIDESHARE.pptxshubhijain836
Centrifugation is a powerful technique used in laboratories to separate components of a heterogeneous mixture based on their density. This process utilizes centrifugal force to rapidly spin samples, causing denser particles to migrate outward more quickly than lighter ones. As a result, distinct layers form within the sample tube, allowing for easy isolation and purification of target substances.
JAMES WEBB STUDY THE MASSIVE BLACK HOLE SEEDSSérgio Sacani
The pathway(s) to seeding the massive black holes (MBHs) that exist at the heart of galaxies in the present and distant Universe remains an unsolved problem. Here we categorise, describe and quantitatively discuss the formation pathways of both light and heavy seeds. We emphasise that the most recent computational models suggest that rather than a bimodal-like mass spectrum between light and heavy seeds with light at one end and heavy at the other that instead a continuum exists. Light seeds being more ubiquitous and the heavier seeds becoming less and less abundant due the rarer environmental conditions required for their formation. We therefore examine the different mechanisms that give rise to different seed mass spectrums. We show how and why the mechanisms that produce the heaviest seeds are also among the rarest events in the Universe and are hence extremely unlikely to be the seeds for the vast majority of the MBH population. We quantify, within the limits of the current large uncertainties in the seeding processes, the expected number densities of the seed mass spectrum. We argue that light seeds must be at least 103 to 105 times more numerous than heavy seeds to explain the MBH population as a whole. Based on our current understanding of the seed population this makes heavy seeds (Mseed > 103 M⊙) a significantly more likely pathway given that heavy seeds have an abundance pattern than is close to and likely in excess of 10−4 compared to light seeds. Finally, we examine the current state-of-the-art in numerical calculations and recent observations and plot a path forward for near-future advances in both domains.
Anti-Universe And Emergent Gravity and the Dark UniverseSérgio Sacani
Recent theoretical progress indicates that spacetime and gravity emerge together from the entanglement structure of an underlying microscopic theory. These ideas are best understood in Anti-de Sitter space, where they rely on the area law for entanglement entropy. The extension to de Sitter space requires taking into account the entropy and temperature associated with the cosmological horizon. Using insights from string theory, black hole physics and quantum information theory we argue that the positive dark energy leads to a thermal volume law contribution to the entropy that overtakes the area law precisely at the cosmological horizon. Due to the competition between area and volume law entanglement the microscopic de Sitter states do not thermalise at sub-Hubble scales: they exhibit memory effects in the form of an entropy displacement caused by matter. The emergent laws of gravity contain an additional ‘dark’ gravitational force describing the ‘elastic’ response due to the entropy displacement. We derive an estimate of the strength of this extra force in terms of the baryonic mass, Newton’s constant and the Hubble acceleration scale a0 = cH0, and provide evidence for the fact that this additional ‘dark gravity force’ explains the observed phenomena in galaxies and clusters currently attributed to dark matter.
Anti-Universe And Emergent Gravity and the Dark Universe
Clinical-Trials.pdf
1. A Resource of PWSA | USA | pwsausa.org
A Resource of PWSA | USA | pwsausa.org
DRUG DEVELOPMENT AND
CLINICAL TRIALS 101
March 27, 2021
2. A Resource of PWSA | USA | pwsausa.org
A Resource of PWSA | USA | pwsausa.org
DISCOVERY - PHASE 1
Dean S. Carson, PhD, Saniona, Inc.
3. A Resource of PWSA | USA | pwsausa.org
DRUG DISCOVERY AND DEVELOPMENT
3
Why is it important?
• Rare hormone producing tumor of the
anterior pituitary gland
• Cabergoline, an ergot derivative, is a
potent dopamine D2 receptor agonist
that blocks pituitary production of
prolactin
• Ergot is a fungus that grows on rye and
related plants, and produces alkaloids
that can cause ergotism in humans and
animals that eat the contaminated grain
• Painful seizures, mania, psychosis,
headaches, nausea, vomiting
4. A Resource of PWSA | USA | pwsausa.org
PHARMACOLOGY
• Pharmacology is the science of how
drugs and biologics act on biological
systems and how the system responds to
the drug
• Clinical Pharmacology applies the basic
science and principles of pharmacology to
the practice of medicine
4
Doctors, pharmacists, dentists, veterinarians use the information discovered from pharmacology to
select the best medications to treat patients
Translational pharmacology
Basic science Clinical practice
5. A Resource of PWSA | USA | pwsausa.org
MECHANISM OF ACTION
• Modern drug discovery is a mechanism
driven field
• Nearly all new experimental therapeutics
have a defined mechanism-of-action and
most have companion diagnostics allowing
researchers to track mechanistic
engagement in complex systems like the
human body
• What are the known consequences of that
mechanism in a disease state? ie.
potential efficacy
• What are the known consequences of that
mechanism in healthy systems? ie.
potential toxicity
• What mechanisms do we know can’t be
tolerated in healthy systems? ie. known
toxicity
5
“All things are poison, and nothing is without poison; the dosage alone makes it so a thing is not a
poison.” - Paracelsus
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PHASES OF DRUG DEVELOPMENT
6
7. A Resource of PWSA | USA | pwsausa.org
HIGH-RISK/HIGH-COST BUSINESS
• The process of discovering a new drug and conducting clinical trials to ensure it is safe
and effective is estimated to take 15 years and cost $2.6 billion on average!!!
• During the discovery process it takes 5,000-10,000 compounds to get just 5 that will be
worthy advancing into the clinical development process (human studies)
• For the 5 compounds that make it into clinical trials, the likelihood of receiving FDA
approval is about 12%
DiMasi et al. 2016 Journal of Health Economic, 47;20-33
Number of FDA approved drugs
https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-
products/novel-drug-approvals-2020FDA Drug Approvals
7
2016 2017 2018 2019 2020
22 46 59 48 53
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DRUG DEVELOPMENT IS A TEAM SPORT
8
Shen et al. Clin Transl Sci (2019), 12, 6-19
9. A Resource of PWSA | USA | pwsausa.org
DISCOVERY
9
• Major aspects of early drug discovery
• Discovery biology
• Discovery chemistry
• In vitro pharmacology (test tube, petri dish)
• In silico models, often aided by artificial
intelligence (AI)
• Ex vivo studies in human tissues
• In vivo pharmacology and efficacy assessment
10. A Resource of PWSA | USA | pwsausa.org
PHASE I STUDIES
• Healthy volunteers
• Double-blind, randomized, placebo
controlled
• Investigate safety/tolerability and identify
maximally tolerated dose (MTD)
• Consider possible drug-drug interactions
(DDI)
• Food interactions and absorption
• Specific populations
• Age, gender, pre-existing conditions
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CLINICAL PHARMACOLOGY
Pharmacokinetics (PK)
• Drug disposition or what the body does to a
drug
• This is calculated using mathematical
equations
• Four processes involved (LADME) (actually 5)
• (Liberation)
• Absorption
• Distribution
• Metabolism
• Elimination
Pharmacodynamics (PD)
• Drug actions or what a drug does to the body
• This is assessed using a wide variety of
measurement tools depending on the drugs
mechanism and disease states of interest
• Cardiovascular – heart function
• Endocrinology – hormone measurement
• Psychiatry – emotional and behavioral signs
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12. A Resource of PWSA | USA | pwsausa.org
PHARMACOKINETICS
Parameters of drug bioavailability
• Maximum concentration (Cmax)
• Time to reach maximum concentration (Tmax)
• Area Under the Curve (AUC)
• Absorption rate
• Elimination half-life
• Pharmacogenomics is a relatively new, but
incredibly important aspect of drug
development
• Liver enzymes (Cytochrome P450 enzymes)
can impact on drug metabolism.
• Poor, intermediate, rapid and ultra-rapid
metabolizers
Routes & dosing regimens
• Parenteral (IV, IM, SC)
• Oral (po)
• Intranasal
• Inhalation
• Topical
• Once daily (QD), twice daily (BID), three times
daily (TID), four times daily (QID), as needed
(PRN)
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ADVERSE DRUG REACTIONS
Risk-Benefit Ratio
• Some toxicities can be managed and may be
acceptable while others are not
• Treatment of aggressive cancers vs treatment of
hypertension
• Pharmacogenomics: patients with certain
genetic predisposition
• eg. Patients with the HLA-B*1502 genetic
variant can lead to Stevens-Johnson syndrome
(severe skin disorder) when treated with
carbamazepine
Thalidomide
• Approved in many countries for sedation and
used in pregnant women
• Prenatal drug exposure resulted in devastating
birth defects
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DRUG REPURPOSING
Cost and Time Savings
• Considerably cuts R&D costs
• Reduces the development timeline, as various
existing compounds have already
demonstrated safety in humans, it does not
require Phase 1 clinical trials
• Potential for reuse despite evidence of adverse
effects and failed efficacy in some indications
Thalidomide
• Complication of leprosy (Erythema Nodosum
Leprosum)
• Clinical observation of benefit
• Multiple Myeloma
• Targeted development
• Special Restricted Distribution Program
• Other examples of repurposed drugs:
apomorphine (Parkinson’s disease), sildenafil
(pulmonary hypertension), taxotere (prostate
cancer), lamotrigine (Bipolar Disorder),
hydroxyurea (Sickle Cell Disease), minoxidil
(hair re-growth)
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15. A Resource of PWSA | USA | pwsausa.org
FREE RESOURCES
15
• NIH Understanding Clinical Trials, Vaccine Development:
https://covid19community.nih.gov/resources/understanding-clinical-trials
• Shen et al. Design and Conduct Considerations for First‐in‐Human Trials, Clin Transl Sci (2019),
12, 6-19: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342261/
• FDA Clinical Pharmacology 1: https://www.fda.gov/media/84920/download
• www.clinicaltrials.gov
• NIH Principles of Clinical Pharmacology course: https://ocr.od.nih.gov/courses/principles-clinical-
pharmacology.html
• Provides an in-depth look at drug absorption, distribution, metabolism, and excretion
• Describe the impact of age, pregnancy, and disease on pharmacokinetics
• Describe the basic principles in the assessment of drug effects
• Describe the process of drug discovery and development
• Provide an overview of clinical pharmacotherapy including pharmacogenomics and medication safety
16. A Resource of PWSA | USA | pwsausa.org
A Resource of PWSA | USA | pwsausa.org
PHASE 2 – 3
Jessica Ernest, Levo Therapeutics, Inc.
Kristen Yen, Soleno Therapeutics, Inc.
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WHAT IS A CLINICAL TRIAL?
Research studies that involve volunteers to test specific intervention(s) such
as a drug, device, procedure or changes in participant’s behavior such as
diet
Interventional (studying a potential new treatment)
Observational (gathering data)
Studies can be funded by pharmaceutical companies, academic institutions,
voluntary groups, federal agencies (e.g., NIH) and can be run by Investigators
or Industry
Trials progress through a series of steps, called Phases
If a potential treatment is successful in one phase, it may be able to move to
the next phase of research
Goal is to gather information on safety and efficacy
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PHASES OF CLINICAL RESEARCH
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INVESTIGATIONAL NEW DRUG APPLICATION (IND)
FDA works to protect participants in clinical
trials
Extensive application submitted to the FDA
before beginning research in humans (21
CFR Part 312)
Provides data on the animal studies and any
signals of toxicity (side effects that may
cause great harm)
Details on how the drug is made, what is in
it, and more
Includes the plan for the studies to be
conducted in humans
“Living application”
19
IND
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PHASE 2 BASICS
Several months
WHO
o Group of patients with
the disease or
disorder being studied
o Several hundred
participants in common
disorders
o May enroll 30-80 in
rare disease
HOW MANY
o A few locations
o Hospitals
o Clinics
WHERE
Up to 2 years
2
1
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PHASE 2 GOALS
21
Further assess safety of the drug in a larger group of patients
Gather preliminary information on safety and potential efficacy
for the dose(s) being studied, to know if it is appropriate for a
larger Phase 3 clinical trial
To accurately compare safety and effectiveness while on and
off the drug, includes a comparison group such as placebo (no
drug) or active comparators (already approved drug)
Does it relieve, reverse or stop the progression of the
condition?
Approximately 33% of drugs move to the next phase
22. A Resource of PWSA | USA | pwsausa.org
PHASE 3 BASICS
Several months
WHO
o Group of patients with
the disease or
disorder being studied
o Several hundred to
thousand patients
o May be ~70-150 in rare
diseases
HOW MANY
o Many locations (multi-
center)
o Hospitals / Clinics
o Possibly several
countries
WHERE
Up to 2 years
1 2
1 to 4+ years
3
23. A Resource of PWSA | USA | pwsausa.org
PHASE 3 GOALS
23
Demonstrate whether or not a product offers benefit to a
specific population of people (for example with Prader-Willi
Syndrome)
Known as pivotal studies
Compare product to other treatments (or placebo) to see if it is
more effective, less effective or the same
Provide more safety information in a larger group of patients
Treatment is longer in duration to monitor maintenance of
efficacy and show any longer-term or rare side effects
Approximately 25-30% of drugs move to the next phase
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CLINICAL TRIAL DESIGN TERMS
Randomized
Each study participant is randomly assigned to receive either the study treatment
or the comparator (placebo, or other approved drug)
Placebo or Active controlled
The use of placebo (fake treatment) or another treatment allows the researchers
to accurately measure the effect of the study treatment
Blinded
Single blind – the participant involved in the study do not know which study
treatment they receive
Double blind – the researchers also do not know which treatment is being given
to any participant
Endpoint
Decided before the start of the study
An event or outcome that can be measured to determine whether the intervention
being studied is beneficial
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RARE DISEASE
A condition that affects less than 200,000 people in the United States (as defined by the FDA)
A drug used to treat a rare disease is called an Orphan Drug
Recognizing the difficulty of clinical trials in rare patient populations, the US Congress passed
the Orphan Drug Act to facilitate development of treatments for rare disorders
Most estimates indicate that PWS may affect between 1 in 10,000 to 1 in 30,000 individuals
This would be considered very rare (likely fewer than 30,000 people in the US)
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WHO IS INVOLVED IN THE RESEARCH?
Sponsor
The organization or person who initiates the study and who has authority
to control the study.
Investigator
Every study location (hospital, clinic) is lead by a Principal Investigator (PI),
usually a medical doctor. The PI may have a team of Investigators at the
study location who all aid in regularly monitoring the participant’s health
Clinical Research or Study Coordinator
An individual that handles the day-to-day organization of the clinical trial
at the clinical site (study center).
The Participant!
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27. A Resource of PWSA | USA | pwsausa.org
HOW ARE SITES CHOSEN FOR A CLINICAL TRIAL?
Key criteria for site selection
Patient population
Investigator experience, expertise
and interest
Sufficient experienced staff and
appropriate facilities
Ability to perform study assessments
adequately and safely
Prior FDA (or other regulatory) audit
findings
Rare disease studies are challenging!
Limited patients
Limited Investigators who specialize
in the treatment of the rare disease
Participants may be required to travel
great distances to a recruiting site
27
~2-8+ months to get a clinical site up and
running to enroll a patient in a clinical trial
28. A Resource of PWSA | USA | pwsausa.org
LEGAL FRAMEWORK / BACKGROUND
Federal Food, Drug, and Cosmetic Act (FD&C Act)
Section 505(i) is the statutory authority for FDA’s oversight of clinical investigations to
test safety and effectiveness
Code of Federal Regulations (CFR)
Regulations under Section 505(i) describing FDA’s authority over the conduct of clinical
investigations including Sponsor responsibilities and Clinical Investigator responsibilities
Guidances
FDA Guidance Documents
Advisory only – to assist Sponsor and Clinical Investigators in complying with the
regulations
International Conference on Harmonization (ICH) E6(R2) – Good Clinical Practice (GCP)
International ethical and scientific quality standard for designing, conducting,
recording, and reporting trials that involve human subjects
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CLINICAL TRIAL PROTOCOL
The research plan detailing how a study is conducted
Designed to answer specific research questions and safeguard the health of
the participants. Protocols contain:
the reason the study is being conducted
who may participate in the study and how many will need to
participate
the schedule of tests, procedures and study drug administration
the information that is gathered by the participant
Investigator / study team must follow this document
Prior to the initiation of the study,
the protocol is submitted to the FDA for review (30-day review clock)
the protocol and related study documents are submitted several
groups (e.g., institutional review board, hospital committees, etc.) for
review and approval
29
21 CFR 312; ICH E6(R2)
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WHO CAN PARTICIPATE?
All clinical trials have guidelines about who can participate called eligibility criteria
Inclusion criteria: The factors that allow someone to participate
Exclusion criteria: The factors that disallow someone from participating
Criteria are based on such factors as age, sex, type and stage of disease, previous treatment
history, and other medical conditions which helps
keep the patients safe
researchers achieve accurate and meaningful results
reduce the variation within the study
Participation should ALWAYS be voluntary, and the participant and family will be well
informed by the researchers at the clinical site about the study details and commitment
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WHAT IS REQUIRED OF THE PARTICIPANT OR
FAMILY?
Informed consent
The process of learning the key facts about a clinical trial before deciding
whether or not to participate.
Continues throughout the study
Explanation of benefits and risks to participating
You should fully understand all aspects of a clinical trial before participating
and have all your questions answered
Assures the participant that personal information is seen only by those
authorized to have access
Updated as new safety information comes available (i.e., current study,
other studies with same drug, preclinical research)
31
21 CFR 50; ICH GCP E6(R2)
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HOW ARE PARTICIPANTS PROTECTED
US Food and Drug Administration (FDA)
Responsible for safeguarding public health by assuring that current and new
medical products are safe and effective, and that the evaluation of potential
new therapies is done properly
There are regulations that govern human subject protection and the conduct
of Clinical Trials (Protection of Human Subjects 21 CFR Part 50, Financial
Disclosure by Clinical Investigators 21 CFR Part 54, Institutional Review Boards
21 CFR Part 56, Investigational New Drug Application 21 CFR Part 312)
Institutional Review Boards
Review clinical research to ensure that appropriate steps are taken to protect
the rights and welfare of humans participating as subjects in the research.
Use a group process to review research protocols and related materials (e.g.,
informed consent documents and investigator brochures)
Has the authority to approve, require modifications in (to secure approval),
or disapprove research.
32
21 CFR 56; ICH E6(R2)
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HOW ARE PARTICIPANTS PROTECTED
Data and Safety Monitoring Board (DSMB)
Also referred to as Data Monitoring Committee (DMC) or Data and Safety Monitoring
Committees (DSMCs) or Data and Safety Monitoring Board (DSMB)
May be established by a sponsor
Independent group of experts who assess progress of a trial
Safety data
Efficacy variables
May recommend modification or termination of study
Must have a written charter and minutes
Typically includes scientists and statisticians with appropriate knowledge
Independence is critical to maintain integrity
33
21 CFR 312; ICH E6(R2);
FDA Guidance Document: Establishment and Operation of Clinical Trial Data Monitoring Committees
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RESPONSIBILITIES
Sponsors are responsible for
selecting qualified investigators
providing investigators with the information they need to conduct clinical study properly
ensuring proper monitoring of the investigation(s)
ensuring that the investigation(s) is conducted in accordance with the general
investigational plan and protocols contained in the IND
maintaining an effective IND with respect to the investigations
ensuring that FDA and all participating investigators are promptly informed of significant
new adverse effects or risks with respect to the drug
34
21 CRF Part 312.50; ICH E6(R2)
35. A Resource of PWSA | USA | pwsausa.org
RESPONSIBILITIES (CONT.)
Investigator
• Ensures that an investigation is conducted according to the Investigational Plan (study protocol)
• Protects the rights, safety and welfare of subjects
• Ensures that informed consent is adequately obtained
• Ensures IRB review, approve and reporting requirements are met
• Maintains control of investigational product (study drug)
• Maintains accurate records and retains these records
• Submitting progress reports / final reports to sponsor
• Report any adverse event (side effect) that is alarming (e.g., an unexpected event that is serious
or life-threatening)
• Financial disclosure to sponsor
35
21 CRF Part 312.60; ICH E6(R2)
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RESPONSIBILITIES (CONT.)
Participant (and Caregivers)
Be willing to come to the study visit appointments as scheduled with the study staff
Follow all instructions of the Investigator and the study staff
Report any side effects or any changes in the medicines that you take
Agree to take study medication as instructed by the Investigator
Not participate in any other clinical trials when a research drug and/or a research device
is being given to you
Understand that participation is voluntary, and, at any time, the participant may
withdraw from the study without any penalty or loss of access to treatment or other
benefits to which you are entitled
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WHERE CAN YOU LEARN MORE?
Used to develop today’s presentation and you
can access for more information!
Learn more about clinical trials:
https://www.fda.gov/patients/clinical-trials-
what-patients-need-know/basics-about-
clinical-trials
https://clinicaltrials.gov/ct2/about-
studies/learn
Step 3: Clinical Research. U.S. Food & Drug
Administration website:
https://www.fda.gov/patients/drug-development-
process/step-3-clinical-research
Check what studies are recruiting
www.clinicaltrials.gov
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NDA AND DRUG
APPROVAL PROCESS
27 March 2021
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NEW DRUG APPLICATION (NDA)
• Sponsor’s formal proposal to FDA to approve a product for marketing and sale in
the US
• Provides all the relevant data and information collected during years of research
and development (Investigational New Drug [IND] phase)
• Includes multiple sections:
• Administrative information, including proposed labeling (Module 1)
• Comprehensive summaries for each discipline (Module 2)
• Chemistry, manufacturing, and controls information (Module 3)
• Nonclinical data (Module 4)
• Clinical data, including tabulations of patient data, clinical study reports, patient
narratives (Module 5)
• Submitted electronically in Common Technical Document (CTD) format
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NEW DRUG APPLICATION (NDA) – CTD FORMAT
• Agreement to assemble all the Quality, Safety and Efficacy information in a common format
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NEW DRUG APPLICATION (NDA)
• NDA must provide sufficient data for FDA to determine:
• Safety and efficacy profile
• Assessment provides an acceptable risk-benefit
• Product quality - adequate manufacturing methods and controls to preserve identity,
strength, and purity of the product
• Countless FDA and International Council for Harmonisation (ICH) guidance
documents
• Cover all aspects of clinical development and NDAs
• FDA website provides a wealth of information
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NEW DRUG APPLICATION (NDA)
• Along the way to NDA
• Sponsor conducts milestone meetings with FDA
• Formal meetings conducted with FDA during the IND phase
• Allows for interaction with FDA to discuss development program, address questions, obtain
agreement for specific questions or issues
• Pre-IND, End of Phase 1, End of Phase 2, pre-NDA
• Pre-NDA meeting
• Addresses final questions regarding submission strategy, requirements, completeness of
data, any outstanding issues
• FDA has developed programs to expedite drug development and review
• Fast track
• Breakthrough therapy
• Accelerated approval
• Priority review
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NDA SUBMISSION PROCESS
• Write and compile NDA
• Subject matter experts
• Writers/authors of sections
• Reviewers
• Document publishers
• Technical experts to build the electronic submission
• Project management to track timelines, movement of documents through the
process from draft to finalization
• Regulatory experts oversee all of this and ultimately guide as well as
drive the process
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PRESCRIPTION DRUG USER FEE ACT (PDUFA)
• Prescription Drug User Fee Act (PDUFA)
• Authorizes FDA to collect user fees for applications and approved products
• Fee schedule for 2020-2021:
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PDUFA TIMELINES
• NDA review timelines (PDUFA review performance goals)
• Review and act on 90% of new chemical entity (NCE) applications within 10
months of the 60-day filing date (6 months for priority review)
• Note review timeline is set based on the 60-day filing date
• Essentially means within 12 months of the receipt date (8 months for priority review)
• Review and act on 90% of non-NCE applications within 10 months of receipt
(6 months for priority review)
• Note review timeline is set based on the receipt date
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NDA REVIEW AND APPROVAL PROCESS
• FDA review teams thoroughly examine all the submitted data related to the drug and decide
to approve or to not approve it
• Upon receipt at FDA, initial administrative processing
• Forwarded to the Division responsible for review
• Assigned to a Division Project Manager
• Screened to assess for completeness
• Technical sections distributed to reviewers in the primary technical review disciplines
• Medical/clinical
• Pharmacology/toxicology
• Chemistry/microbiology
• Consultant reviewers (e.g., statistical, safety, device, clinical outcome assessment [COA])
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NDA REVIEW AND APPROVAL PROCESS
• Review process divided into phases
• Filing determination and review planning
• By Day 60 – inform the Sponsor in writing if Priority Review granted or if a Refusal to File
decision is made
• By Day 74 – communicate that the application is filed, PDUFA goal date, and initial filing
review issues/requests for information
• Review
• Communicate additional requests for information
• Submission of major amendment during last 3 months of the review can extend the PDUFA
goal date by 3 months
• Primary review completed by end of month 8 (for standard review; end of month 5 for priority
review)
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NDA REVIEW AND APPROVAL PROCESS
• Review process phases
• Advisory Committee meeting preparation and conduct
• Some applications go to an Advisory Committee Meeting
• NCE
• Novel clinical or surrogate endpoints were used
• Significant issues regarding safety or efficacy
• Significant public health questions
• Communicated early in the first cycle review process
• Provides FDA with independent advice from outside experts
• FDA often follows the advice of an Advisory Committee but is not required to do so
• Open to the public
• Requires extensive preparation and is labor intense for the Sponsor
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NDA REVIEW AND APPROVAL PROCESS
• Review process phases
• Action
• Labeling discussions occur to determine final approved labeling
• Each review discipline writes a review summary
• Eventually posted to FDA website as the Summary Basis of Approval
• Goal is to complete the review and issue official regulatory action by the PDUFA goal date
• Send official regulatory Action Letter by the PDUFA goal date
• Approval Letter
• Complete Response Letter
• Describes the deficiencies identified during review of the application
• Indicates if any amendments submitted late in the review cycle were not reviewed
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NDA REVIEW AND APPROVAL PROCESS
• Review process phases
• Post-action – Complete Response Letter
• Post-action teleconference or meeting to discuss the deficiencies
• Resubmission of the application to resolve the deficiencies
• Class I – FDA goal is to review within 2 months
• Class II – FDA goal is to review within 6 months
• Resubmission must be a complete response to all deficiencies identified
• Class I resubmissions are for very specific situations that require minor updates to
the application (e.g., final labeling, stability data, validation data)
• Most resubmissions are Class II
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PATIENT-FOCUSED DRUG DEVELOPMENT
• Systematic approach to help ensure that patients’ experiences, perspectives, needs, and
priorities are captured and meaningfully incorporated into drug development and evaluation
• Primary goal is to better incorporate the patient’s voice in drug development and evaluation
• Facilitate and advance use of systematic approaches to collecting and utilizing robust and
meaningful patient and caregiver input to more consistently inform drug development and
regulatory decision-making
• Encourage identification and use of approaches and best practices to facilitate patient enrollment
and minimize the burden of patient participation in clinical trials
• Enhance understanding and appropriate use of methods to capture information on patient
preferences and the potential acceptability of tradeoffs between treatment benefit and risk
outcomes
• Identify the information that is most important to patients related to treatment benefits, risks, and
burden, and how to best communicate the information to support their decision making
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PATIENT-FOCUSED DRUG DEVELOPMENT
• Clinical trials traditionally relied on objective measures for primary and secondary endpoints
• FDA guidance issued in 2009 regarding patient-reported outcome measures
• FDA commitment to further development of patient-focused drug development guidance, as
required by Section 3002 of the 21st Century Cures Act (2016) and the 6th authorization of
the Prescription Drug User Fee Act (PDUFA VI) (2017)
• Additional guidance documents issued (2019 and 2020) following two initial workshops
• Two additional workshops held (2018 and 2019) with guidance documents to come
• Division of Clinical Outcome Assessment (DCOA) established at FDA
• Mission: Integrating the patient voice into drug development through COA endpoints that are
meaningful to patients, valid, reliable and responsive to treatment.
• Supports CDER’s mission for patient-focused drug development by providing leadership,
expertise, and advice to promote the use of patient-focused outcome assessment
• Making strides but still work to be done
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FDA MISSION
• FDA is responsible for protecting the public health by assuring the safety, efficacy and security of
human and veterinary drugs, biological products, and medical devices; and by ensuring the safety of
our nation’s food supply, cosmetics, and products that emit radiation.
• FDA is also responsible for advancing the public health by helping to speed innovations that make
medicines more effective, safer, and more affordable and by helping the public get the accurate,
science-based information they need to use medicines and foods to maintain and improve their
health. FDA also has responsibility for regulating the manufacturing, marketing and distribution of
tobacco products to protect the public health and to reduce tobacco use by minors.
• FDA also plays a significant role in the Nation’s counterterrorism capability. FDA fulfills this
responsibility by ensuring the security of the food supply and by fostering development of medical
products to respond to deliberate and naturally emerging public health threats.
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