This document summarizes a study that evaluated medicines approved for children by the European Medicines Agency (EMEA) from 1995 to 2001. The study found that 35% of approved drugs were authorized for pediatric use on average. Only 11% were approved for children under 2 years old. Medicines for children fell under 9 therapeutic categories, with over half being anti-infectives. Thirty-nine medicines were approved based on clinical trials, while eight were approved without pediatric studies. The study concludes that more efforts are needed to increase pediatric drug development and require manufacturers to study new drugs in children.
Pharmacovigilance aims to detect, assess, monitor, understand, and prevent adverse drug reactions. It has evolved over time in response to drug safety issues. Key events include the Thalidomide disaster in the 1960s which led to clinical trials, and the establishment of reporting systems in the UK, US, and Europe. India launched its national pharmacovigilance program in 2010 to monitor adverse drug reactions, but progress in expanding monitoring centers has been slow. Increased funding and commitment are needed to fully establish nationwide pharmacovigilance in India.
Abacavir is an antiretroviral used in combination with other drugs to treat HIV-1 and HIV-2 infections. It is administered orally in tablet or liquid form, with dosages depending on weight and age. Abacavir can cause hypersensitivity reactions and should not be given to patients with severe liver impairment or a history of intolerance to the drug.
The International Conference on Harmonisation (ICH) is a joint initiative involving regulators from Europe, Japan, and the United States along with research-based pharmaceutical companies to discuss scientific and technical requirements for drug approval. The goal of ICH is to harmonize these requirements to ensure safe and effective drugs are approved efficiently. ICH has created guidelines on topics like good clinical practice, quality assurance, efficacy, and safety that are followed by regulatory agencies worldwide.
Globalization Of Clinical Trials 2010 Josep M. Badenasjosepmariabadenas
Globalization of clinical trials can help bring drugs to market more quickly. While the majority of research and development spending still occurs in developed countries like the US and Western Europe, emerging markets are playing a larger role in global drug development. Countries like India and China provide opportunities for cost-effective clinical trials due to their large patient populations and improving healthcare infrastructures and regulations. However, conducting trials globally also presents challenges around cultural and medical practice differences that need to be addressed.
European medicine agency is one of the finest agency to check the quality, efficacy ,safety of a drug in all European countries . It consists of 27 states of Europe as its member.
1)spontanious reporting schemes for biodrug adverse reactionsNeha Suresh
This document discusses sources of reports on adverse reactions to herbal drugs, herbal products targeted for safety monitoring, and reporting of suspected adverse drug reactions. The main sources of reports are healthcare professionals, consumers, and manufacturers. Herbal products can be categorized based on their regulatory status and marketing status. Only certain professionals can report adverse reactions, and reports should include identification information, herbal product details, adverse reaction data, other medication use, and the reporter's contact information. A single reporting form should be used to submit reports via various methods.
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.
Pharmacovigilance aims to detect, assess, monitor, understand, and prevent adverse drug reactions. It has evolved over time in response to drug safety issues. Key events include the Thalidomide disaster in the 1960s which led to clinical trials, and the establishment of reporting systems in the UK, US, and Europe. India launched its national pharmacovigilance program in 2010 to monitor adverse drug reactions, but progress in expanding monitoring centers has been slow. Increased funding and commitment are needed to fully establish nationwide pharmacovigilance in India.
Abacavir is an antiretroviral used in combination with other drugs to treat HIV-1 and HIV-2 infections. It is administered orally in tablet or liquid form, with dosages depending on weight and age. Abacavir can cause hypersensitivity reactions and should not be given to patients with severe liver impairment or a history of intolerance to the drug.
The International Conference on Harmonisation (ICH) is a joint initiative involving regulators from Europe, Japan, and the United States along with research-based pharmaceutical companies to discuss scientific and technical requirements for drug approval. The goal of ICH is to harmonize these requirements to ensure safe and effective drugs are approved efficiently. ICH has created guidelines on topics like good clinical practice, quality assurance, efficacy, and safety that are followed by regulatory agencies worldwide.
Globalization Of Clinical Trials 2010 Josep M. Badenasjosepmariabadenas
Globalization of clinical trials can help bring drugs to market more quickly. While the majority of research and development spending still occurs in developed countries like the US and Western Europe, emerging markets are playing a larger role in global drug development. Countries like India and China provide opportunities for cost-effective clinical trials due to their large patient populations and improving healthcare infrastructures and regulations. However, conducting trials globally also presents challenges around cultural and medical practice differences that need to be addressed.
European medicine agency is one of the finest agency to check the quality, efficacy ,safety of a drug in all European countries . It consists of 27 states of Europe as its member.
1)spontanious reporting schemes for biodrug adverse reactionsNeha Suresh
This document discusses sources of reports on adverse reactions to herbal drugs, herbal products targeted for safety monitoring, and reporting of suspected adverse drug reactions. The main sources of reports are healthcare professionals, consumers, and manufacturers. Herbal products can be categorized based on their regulatory status and marketing status. Only certain professionals can report adverse reactions, and reports should include identification information, herbal product details, adverse reaction data, other medication use, and the reporter's contact information. A single reporting form should be used to submit reports via various methods.
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.
Essential medicines and counterfeit medicinesAmit Bhondve
The document discusses essential medicines and counterfeit medicines. It defines essential medicines as those that satisfy the priority health needs of a population and are selected based on disease prevalence, efficacy, safety and cost-effectiveness. The WHO publishes a Model List of Essential Medicines every two years to guide countries in developing their own lists. Counterfeit medicines pose serious risks as they may contain incorrect ingredients, too much or too little of the active ingredient, or no active ingredient at all. It is difficult to determine the full extent of counterfeiting due to varying reporting methods across countries and regions. Counterfeiting is most prevalent in areas with weak regulatory and enforcement systems for medicines.
This document provides guidelines for monitoring the safety of herbal medicines. It discusses the importance of including herbal medicines in pharmacovigilance systems to understand adverse effects from combined herbal and conventional medicine use. Sources of safety reports include healthcare professionals, consumers, hospitals, and manufacturers. National regulatory agencies are responsible for communicating safety information through various channels to facilitate safe and effective herbal medicine use.
The International Conference on Harmonization (ICH) is a joint regulatory/industry initiative involving drug regulatory authorities and pharmaceutical industry in the European Union, Japan, and the United States. The goal of ICH is to harmonize technical requirements for pharmaceutical product registration among these three regions to ensure safety and efficacy and allow for more efficient drug development. ICH develops harmonized guidelines covering non-clinical, clinical, and quality topics through expert working groups with representatives from regulatory agencies and industry.
PHARMACOVIGILANCE - A Worldwide masterkey for Drug MonitoringVenugopal N
This document provides a history of pharmacovigilance and discusses key aspects of the field. It begins with important milestones in drug safety regulation dating back to the early 20th century. It then defines pharmacovigilance and describes stakeholders, methods used like individual case safety reporting, and the roles of organizations like the WHO and national regulatory authorities. The document emphasizes the importance of post-market drug safety monitoring to protect public health.
The Pharmacovigilance Program in India (PvPI) was initiated in July 2010 by the Central Drugs Standard Control Organization (CDSCO) in New Delhi to monitor adverse drug reactions. The program aims to ensure the benefits of medicine use outweigh the risks by monitoring adverse reactions. It operates through a network of ADR monitoring centers across India which report adverse reactions using the Vigiflow reporting system. The program is coordinated by the Indian Pharmacopoeia Commission and overseen by steering and advisory committees with technical support from review panels. The program has expanded over the years to include more monitoring centers and now also includes haemovigilance and biovigilance programs.
ASEAN was established in 1967 by 5 countries and has since expanded to include 10 member countries. Singapore regulates pharmaceutical products under the Medicines Act and Health Products Act to ensure safety, quality and efficacy. The regulatory process for medicines involves submitting an application to the Health Sciences Authority, which evaluates the application and issues a regulatory decision of approval, approvable, non-approvable, or rejection.
Pharmacovigilance (PV) is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem. WHO established its Programme for International Drug Monitoring in response to the thalidomide disaster detected in 1961. Together with the WHO Collaborating Centre for International Drug Monitoring, Uppsala, WHO promotes PV at the country level. At the end of 2010, 134 countries were part of the WHO PV Programme. The aims of PV are to enhance patient care and patient safety in relation to the use of medicines; and to support public health programmes by providing reliable, balanced information for the effective assessment of the risk-benefit profile of medicines.
Presentation: Global pharmacovigilance networks - A regulator'sTGA Australia
Global pharmaceutical companies manufacture and distribute a broad portfolio of drug products in multiples regions and countries. The pharmacovigilance system must ensure safety data collection in compliance with local regulations, and consolidate all sources to ensure an ongoing monitoring of potential changes in benefit-risk profiles. It must also guarantee a timely communication to patients, prescribers and regulatory authorities. The complexity resides in the need for a dense network of local safety departments, a strong global organisation processing and analysing cases, and a reporting system ensuring compliance to heterogeneous regulatory requirements. Pfizer has one of the largest pharmacovigilance department among all global companies, and has established patient safety as a core priority. We will describe how pharmacovigilance is organised at Pfizer, global compliance and individual patient safety.
IMPACT OF REGULATIONS ON MEDICAL DEVICES IN CONTEXT OF INNOVATIONSJAYA PRAKASH VELUCHURI
The document discusses the impact of regulations on innovation in the medical devices sector. It provides background on regulations in the United States and European Union, which classify devices based on risk and require clinical trials and quality standards. Regulations influence the entire innovation cycle from design to post-market surveillance. While regulations aim to ensure safety, they can also introduce barriers and uncertainty that slow innovation. Emerging technologies like nanomaterials and 3D bioprinting further complicate classification and evaluation. The document argues for collaboration between developers and regulators to streamline processes while encouraging innovation and access to new treatments.
The document provides an overview of the World Health Organization (WHO) and key regulatory agencies like the Central Drugs Standard Control Organization (CDSCO) of India and the U.S. Food and Drug Administration (FDA). It discusses the roles, structures and functions of WHO in global health governance and national regulatory bodies like CDSCO and FDA in ensuring safety and efficacy of drugs, medical devices and other products. Major sections include organizational structure of WHO, priorities, achievements and challenges. For CDSCO and FDA, it summarizes their roles in approval of new drugs and devices, good manufacturing practices, and enforcement.
The document provides guidelines for the evaluation of similar biotherapeutic products (SBPs). It outlines key principles for licensing SBPs, which include:
1) Development of a SBP involves stepwise comparability exercises starting with quality comparisons to a reference biotherapeutic product (RBP), with demonstration of similarity a prerequisite for reduced non-clinical and clinical data requirements.
2) Licensing of a SBP is based on its demonstrated similarity to a suitable RBP in quality, non-clinical, and clinical parameters.
3) Comparability exercises include integrated quality, non-clinical and clinical studies to provide comparative data between the SBP and RBP. Differences require investigation and may necessitate additional data.
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.
The WHO International Drug Monitoring Program was established in 1963 in response to the thalidomide disaster. It currently has 143 member countries that submit adverse drug reaction reports to the global pharmacovigilance database VigiBase managed by the Uppsala Monitoring Centre (UMC) as a WHO collaborating center. The UMC analyzes VigiBase data to identify new safety signals, conducts research, and provides tools and training to support member countries' pharmacovigilance activities. The overall goals are to identify unknown adverse drug reactions and ensure medicines are used safely worldwide.
Phar 7041 fundamentals of pharmacoepidemiology course outline 2020 21University of Gondar
This document outlines a course on fundamentals of pharmacoepidemiology for postgraduate pharmacy students. The course aims to prepare students to conduct pharmacoepidemiologic research by introducing key concepts and methods. Over the semester, students will learn about study designs, data sources, drug utilization research, pharmacovigilance, and systematic reviews. Assessment methods include assignments, seminar presentations, and a final written exam. Course contents will cover these topics through lectures, discussions, exercises and case studies using recommended textbooks and publications.
- Zehra Ashraf presented on the topic of pharmacovigilance.
- Pharmacovigilance involves assessing, detecting, understanding, and preventing adverse drug reactions. It works through processes like adverse drug reaction reporting and analysis.
- The history of pharmacovigilance began in the early 1900s with laws being passed in response to drug safety issues. Global pharmacovigilance systems have developed and expanded since the mid-1900s.
- Methods of pharmacovigilance include spontaneous reporting of adverse reactions, cohort event monitoring, and periodic safety update reports. Pharmacovigilance is also important during clinical trials and after drug approval.
This document outlines the process for providing scientific advice to medicine developers through the European Medicines Agency (EMA). It describes the following key steps:
1. Medicine developers submit questions to EMA regarding their medicine development plans. Experts from EMA and national regulators form teams to address the questions.
2. The teams provide responses and advice to help developers design studies that will generate robust evidence on a medicine's safety and effectiveness. This advice is non-binding and does not guarantee approval.
3. The advice aims to help developers avoid poorly-designed trials and instead generate strong data to support regulatory approval and access for patients. It can also encourage development of needed new medicines.
The document provides an overview of pharmacovigilance in India, including:
1) The history of adverse drug reactions and establishment of regulatory systems following tragedies like thalidomide.
2) The development of India's national pharmacovigilance program over time, from regional centers established in 1986 to the current Pharmacovigilance Programme of India.
3) The functioning of the National Coordination Centre and monitoring centers like NRSMCH in Kolkata, including their roles in adverse reaction reporting and analysis to improve patient safety.
This document summarizes the progress of globalizing traditional Chinese medicines (TCM). It discusses how several TCM herbal monographs have been adopted by the United States Pharmacopoeia and over 45 by the European Pharmacopoeia. The first TCM product was registered in the Netherlands as a traditional medicine. Currently, nine TCM products are in clinical trials with the US FDA, with one in Phase III trials. However, no TCM products have been approved as drugs by the FDA yet. The document also reviews the registration pathways for herbal medicines in Europe and the classifications of traditional use, well-established use, and full marketing authorization.
The Committee for Advanced Therapies (CAT) is responsible for assessing advanced therapy medicinal products (ATMPs) at the European Medicines Agency. The CAT evaluates gene therapy, cell therapy, and tissue-engineered products. It provides scientific advice, classification, certification, and evaluation of marketing authorization applications for ATMPs. Patients' and healthcare professionals' organizations are represented within the CAT to provide perspectives on regulatory processes and product development for ATMPs.
This document compares the regulatory pathways for approval of advanced therapies in the European Union and United States. It finds that:
- 15 advanced therapies were approved in the EU and 9 in the US, with 7 approved in both regions.
- Over half of approved therapies in each region received orphan drug designation, though the US required less time on average for marketing application assessment.
- While EU and US procedures sometimes differed, most regulatory milestones like orphan designation, expedited review programs, and advisory committee involvement were similar between the two regions.
- Scientific advice from the EMA occurred on average 1.7 times per product, and protocol assistance 3.7 times on average. Most products had their first scientific
The International Classification of Diseases (ICD) is a globally recognized system for classifying and coding diseases, health conditions, and related factors. It is maintained and updated by the World Health Organization (WHO) and serves several critical functions in healthcare and epidemiology. To describe the ICD comprehensively within 3000 characters, we'll cover its history, purpose, structure, and significance.
**History:**
The roots of the ICD can be traced back to the mid-19th century when various countries began documenting statistics on causes of death. The need for a standardized classification system became evident as different nations used their own systems, hindering international comparisons. The ICD was officially established in its modern form in 1948, with subsequent revisions and updates.
**Purpose:**
The primary purposes of the ICD are as follows:
1. **Disease Classification:** The ICD provides a systematic way to categorize diseases and health conditions. Each condition is assigned a unique code, which simplifies data collection and reporting.
2. **Clinical Diagnosis:** Healthcare professionals use the ICD to document and communicate diagnoses. This aids in patient care, medical billing, and insurance claims processing.
3. **Epidemiology:** The ICD is crucial for monitoring and analyzing disease patterns on a global scale. It helps identify emerging health threats, allocate resources, and develop public health policies.
4. **Health Statistics:** Governments and health organizations use the ICD to compile health statistics, such as causes of death and disease prevalence. This information guides healthcare planning and resource allocation.
**Structure:**
The ICD is organized into chapters, sections, and codes. The current version, ICD-10, is divided into 22 chapters, covering a wide range of health-related topics. Here's an overview of some key chapters:
- **Chapter I:** Certain infectious and parasitic diseases
- **Chapter II:** Neoplasms (cancers)
- **Chapter III:** Diseases of the blood and blood-forming organs
- **Chapter IV:** Endocrine, nutritional, and metabolic diseases
- **Chapter V:** Mental and behavioral disorders
- **Chapter VI:** Diseases of the nervous system
- **Chapter VII:** Diseases of the eye and adnexa
- **Chapter VIII:** Diseases of the ear and mastoid process
- **Chapter IX:** Diseases of the circulatory system
- **Chapter X:** Diseases of the respiratory system
- **Chapter XI:** Diseases of the digestive system
- **Chapter XII:** Diseases of the skin and subcutaneous tissue
- **Chapter XIII:** Diseases of the musculoskeletal system and connective tissue
- **Chapter XIV:** Diseases of the genitourinary system
- **Chapter XV:** Pregnancy, childbirth, and the puerperium
- **Chapter XVI:** Certain conditions originating in the perinatal period
- **Chapter XVII:** Congenital malformations, deformations, and chromosomal abnormalities
- **Chapter XVIII:** Symptoms, signs, and abnormal clinical and labor
Essential medicines and counterfeit medicinesAmit Bhondve
The document discusses essential medicines and counterfeit medicines. It defines essential medicines as those that satisfy the priority health needs of a population and are selected based on disease prevalence, efficacy, safety and cost-effectiveness. The WHO publishes a Model List of Essential Medicines every two years to guide countries in developing their own lists. Counterfeit medicines pose serious risks as they may contain incorrect ingredients, too much or too little of the active ingredient, or no active ingredient at all. It is difficult to determine the full extent of counterfeiting due to varying reporting methods across countries and regions. Counterfeiting is most prevalent in areas with weak regulatory and enforcement systems for medicines.
This document provides guidelines for monitoring the safety of herbal medicines. It discusses the importance of including herbal medicines in pharmacovigilance systems to understand adverse effects from combined herbal and conventional medicine use. Sources of safety reports include healthcare professionals, consumers, hospitals, and manufacturers. National regulatory agencies are responsible for communicating safety information through various channels to facilitate safe and effective herbal medicine use.
The International Conference on Harmonization (ICH) is a joint regulatory/industry initiative involving drug regulatory authorities and pharmaceutical industry in the European Union, Japan, and the United States. The goal of ICH is to harmonize technical requirements for pharmaceutical product registration among these three regions to ensure safety and efficacy and allow for more efficient drug development. ICH develops harmonized guidelines covering non-clinical, clinical, and quality topics through expert working groups with representatives from regulatory agencies and industry.
PHARMACOVIGILANCE - A Worldwide masterkey for Drug MonitoringVenugopal N
This document provides a history of pharmacovigilance and discusses key aspects of the field. It begins with important milestones in drug safety regulation dating back to the early 20th century. It then defines pharmacovigilance and describes stakeholders, methods used like individual case safety reporting, and the roles of organizations like the WHO and national regulatory authorities. The document emphasizes the importance of post-market drug safety monitoring to protect public health.
The Pharmacovigilance Program in India (PvPI) was initiated in July 2010 by the Central Drugs Standard Control Organization (CDSCO) in New Delhi to monitor adverse drug reactions. The program aims to ensure the benefits of medicine use outweigh the risks by monitoring adverse reactions. It operates through a network of ADR monitoring centers across India which report adverse reactions using the Vigiflow reporting system. The program is coordinated by the Indian Pharmacopoeia Commission and overseen by steering and advisory committees with technical support from review panels. The program has expanded over the years to include more monitoring centers and now also includes haemovigilance and biovigilance programs.
ASEAN was established in 1967 by 5 countries and has since expanded to include 10 member countries. Singapore regulates pharmaceutical products under the Medicines Act and Health Products Act to ensure safety, quality and efficacy. The regulatory process for medicines involves submitting an application to the Health Sciences Authority, which evaluates the application and issues a regulatory decision of approval, approvable, non-approvable, or rejection.
Pharmacovigilance (PV) is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem. WHO established its Programme for International Drug Monitoring in response to the thalidomide disaster detected in 1961. Together with the WHO Collaborating Centre for International Drug Monitoring, Uppsala, WHO promotes PV at the country level. At the end of 2010, 134 countries were part of the WHO PV Programme. The aims of PV are to enhance patient care and patient safety in relation to the use of medicines; and to support public health programmes by providing reliable, balanced information for the effective assessment of the risk-benefit profile of medicines.
Presentation: Global pharmacovigilance networks - A regulator'sTGA Australia
Global pharmaceutical companies manufacture and distribute a broad portfolio of drug products in multiples regions and countries. The pharmacovigilance system must ensure safety data collection in compliance with local regulations, and consolidate all sources to ensure an ongoing monitoring of potential changes in benefit-risk profiles. It must also guarantee a timely communication to patients, prescribers and regulatory authorities. The complexity resides in the need for a dense network of local safety departments, a strong global organisation processing and analysing cases, and a reporting system ensuring compliance to heterogeneous regulatory requirements. Pfizer has one of the largest pharmacovigilance department among all global companies, and has established patient safety as a core priority. We will describe how pharmacovigilance is organised at Pfizer, global compliance and individual patient safety.
IMPACT OF REGULATIONS ON MEDICAL DEVICES IN CONTEXT OF INNOVATIONSJAYA PRAKASH VELUCHURI
The document discusses the impact of regulations on innovation in the medical devices sector. It provides background on regulations in the United States and European Union, which classify devices based on risk and require clinical trials and quality standards. Regulations influence the entire innovation cycle from design to post-market surveillance. While regulations aim to ensure safety, they can also introduce barriers and uncertainty that slow innovation. Emerging technologies like nanomaterials and 3D bioprinting further complicate classification and evaluation. The document argues for collaboration between developers and regulators to streamline processes while encouraging innovation and access to new treatments.
The document provides an overview of the World Health Organization (WHO) and key regulatory agencies like the Central Drugs Standard Control Organization (CDSCO) of India and the U.S. Food and Drug Administration (FDA). It discusses the roles, structures and functions of WHO in global health governance and national regulatory bodies like CDSCO and FDA in ensuring safety and efficacy of drugs, medical devices and other products. Major sections include organizational structure of WHO, priorities, achievements and challenges. For CDSCO and FDA, it summarizes their roles in approval of new drugs and devices, good manufacturing practices, and enforcement.
The document provides guidelines for the evaluation of similar biotherapeutic products (SBPs). It outlines key principles for licensing SBPs, which include:
1) Development of a SBP involves stepwise comparability exercises starting with quality comparisons to a reference biotherapeutic product (RBP), with demonstration of similarity a prerequisite for reduced non-clinical and clinical data requirements.
2) Licensing of a SBP is based on its demonstrated similarity to a suitable RBP in quality, non-clinical, and clinical parameters.
3) Comparability exercises include integrated quality, non-clinical and clinical studies to provide comparative data between the SBP and RBP. Differences require investigation and may necessitate additional data.
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.
The WHO International Drug Monitoring Program was established in 1963 in response to the thalidomide disaster. It currently has 143 member countries that submit adverse drug reaction reports to the global pharmacovigilance database VigiBase managed by the Uppsala Monitoring Centre (UMC) as a WHO collaborating center. The UMC analyzes VigiBase data to identify new safety signals, conducts research, and provides tools and training to support member countries' pharmacovigilance activities. The overall goals are to identify unknown adverse drug reactions and ensure medicines are used safely worldwide.
Phar 7041 fundamentals of pharmacoepidemiology course outline 2020 21University of Gondar
This document outlines a course on fundamentals of pharmacoepidemiology for postgraduate pharmacy students. The course aims to prepare students to conduct pharmacoepidemiologic research by introducing key concepts and methods. Over the semester, students will learn about study designs, data sources, drug utilization research, pharmacovigilance, and systematic reviews. Assessment methods include assignments, seminar presentations, and a final written exam. Course contents will cover these topics through lectures, discussions, exercises and case studies using recommended textbooks and publications.
- Zehra Ashraf presented on the topic of pharmacovigilance.
- Pharmacovigilance involves assessing, detecting, understanding, and preventing adverse drug reactions. It works through processes like adverse drug reaction reporting and analysis.
- The history of pharmacovigilance began in the early 1900s with laws being passed in response to drug safety issues. Global pharmacovigilance systems have developed and expanded since the mid-1900s.
- Methods of pharmacovigilance include spontaneous reporting of adverse reactions, cohort event monitoring, and periodic safety update reports. Pharmacovigilance is also important during clinical trials and after drug approval.
This document outlines the process for providing scientific advice to medicine developers through the European Medicines Agency (EMA). It describes the following key steps:
1. Medicine developers submit questions to EMA regarding their medicine development plans. Experts from EMA and national regulators form teams to address the questions.
2. The teams provide responses and advice to help developers design studies that will generate robust evidence on a medicine's safety and effectiveness. This advice is non-binding and does not guarantee approval.
3. The advice aims to help developers avoid poorly-designed trials and instead generate strong data to support regulatory approval and access for patients. It can also encourage development of needed new medicines.
The document provides an overview of pharmacovigilance in India, including:
1) The history of adverse drug reactions and establishment of regulatory systems following tragedies like thalidomide.
2) The development of India's national pharmacovigilance program over time, from regional centers established in 1986 to the current Pharmacovigilance Programme of India.
3) The functioning of the National Coordination Centre and monitoring centers like NRSMCH in Kolkata, including their roles in adverse reaction reporting and analysis to improve patient safety.
This document summarizes the progress of globalizing traditional Chinese medicines (TCM). It discusses how several TCM herbal monographs have been adopted by the United States Pharmacopoeia and over 45 by the European Pharmacopoeia. The first TCM product was registered in the Netherlands as a traditional medicine. Currently, nine TCM products are in clinical trials with the US FDA, with one in Phase III trials. However, no TCM products have been approved as drugs by the FDA yet. The document also reviews the registration pathways for herbal medicines in Europe and the classifications of traditional use, well-established use, and full marketing authorization.
The Committee for Advanced Therapies (CAT) is responsible for assessing advanced therapy medicinal products (ATMPs) at the European Medicines Agency. The CAT evaluates gene therapy, cell therapy, and tissue-engineered products. It provides scientific advice, classification, certification, and evaluation of marketing authorization applications for ATMPs. Patients' and healthcare professionals' organizations are represented within the CAT to provide perspectives on regulatory processes and product development for ATMPs.
This document compares the regulatory pathways for approval of advanced therapies in the European Union and United States. It finds that:
- 15 advanced therapies were approved in the EU and 9 in the US, with 7 approved in both regions.
- Over half of approved therapies in each region received orphan drug designation, though the US required less time on average for marketing application assessment.
- While EU and US procedures sometimes differed, most regulatory milestones like orphan designation, expedited review programs, and advisory committee involvement were similar between the two regions.
- Scientific advice from the EMA occurred on average 1.7 times per product, and protocol assistance 3.7 times on average. Most products had their first scientific
The International Classification of Diseases (ICD) is a globally recognized system for classifying and coding diseases, health conditions, and related factors. It is maintained and updated by the World Health Organization (WHO) and serves several critical functions in healthcare and epidemiology. To describe the ICD comprehensively within 3000 characters, we'll cover its history, purpose, structure, and significance.
**History:**
The roots of the ICD can be traced back to the mid-19th century when various countries began documenting statistics on causes of death. The need for a standardized classification system became evident as different nations used their own systems, hindering international comparisons. The ICD was officially established in its modern form in 1948, with subsequent revisions and updates.
**Purpose:**
The primary purposes of the ICD are as follows:
1. **Disease Classification:** The ICD provides a systematic way to categorize diseases and health conditions. Each condition is assigned a unique code, which simplifies data collection and reporting.
2. **Clinical Diagnosis:** Healthcare professionals use the ICD to document and communicate diagnoses. This aids in patient care, medical billing, and insurance claims processing.
3. **Epidemiology:** The ICD is crucial for monitoring and analyzing disease patterns on a global scale. It helps identify emerging health threats, allocate resources, and develop public health policies.
4. **Health Statistics:** Governments and health organizations use the ICD to compile health statistics, such as causes of death and disease prevalence. This information guides healthcare planning and resource allocation.
**Structure:**
The ICD is organized into chapters, sections, and codes. The current version, ICD-10, is divided into 22 chapters, covering a wide range of health-related topics. Here's an overview of some key chapters:
- **Chapter I:** Certain infectious and parasitic diseases
- **Chapter II:** Neoplasms (cancers)
- **Chapter III:** Diseases of the blood and blood-forming organs
- **Chapter IV:** Endocrine, nutritional, and metabolic diseases
- **Chapter V:** Mental and behavioral disorders
- **Chapter VI:** Diseases of the nervous system
- **Chapter VII:** Diseases of the eye and adnexa
- **Chapter VIII:** Diseases of the ear and mastoid process
- **Chapter IX:** Diseases of the circulatory system
- **Chapter X:** Diseases of the respiratory system
- **Chapter XI:** Diseases of the digestive system
- **Chapter XII:** Diseases of the skin and subcutaneous tissue
- **Chapter XIII:** Diseases of the musculoskeletal system and connective tissue
- **Chapter XIV:** Diseases of the genitourinary system
- **Chapter XV:** Pregnancy, childbirth, and the puerperium
- **Chapter XVI:** Certain conditions originating in the perinatal period
- **Chapter XVII:** Congenital malformations, deformations, and chromosomal abnormalities
- **Chapter XVIII:** Symptoms, signs, and abnormal clinical and labor
The International Conference on Harmonization (ICH) brings together regulatory authorities and pharmaceutical industries from Europe, Japan, and the United States to discuss scientific and technical aspects of drug registration. ICH aims to harmonize technical requirements for pharmaceutical registration to ensure safety, quality and efficacy while avoiding redundant testing. ICH has produced numerous guidelines on quality, safety, efficacy and multidisciplinary topics that are implemented by regulatory agencies in ICH regions and used globally to streamline drug development and approval processes.
The document discusses the International Council for Harmonization (ICH). ICH aims to harmonize technical requirements for pharmaceutical product registration among regulators in Europe, Japan, and the United States to reduce duplication of testing and make the development of new medicines more efficient. It outlines the structure of ICH, including its steering committee and expert working groups. ICH guidelines cover quality, safety, efficacy, and multidisciplinary topics. The overall goal is to streamline drug development while maintaining high standards for safety, quality and efficacy.
The document discusses the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. It provides an introduction to ICH, the need for harmonization, the origin and evolution of ICH, its objectives and members. It then describes the process of ICH harmonization and provides examples of ICH guidelines related to quality, safety, efficacy, and multidisciplinary topics. The quality guidelines address stability testing, impurities thresholds, and good manufacturing practices.
This study analyzed drug prescriptions among newborns in Italian neonatal intensive care units (NICUs) to determine the extent of off-label and unlicensed drug use. Data was collected from 36 NICUs on 220 newborns. A total of 720 prescriptions were analyzed, with 73.5% being off-label or unlicensed. Anti-infectives were the most commonly prescribed drugs. The most common reasons for off-label use were age and dosing frequency. Compared to guidelines from the Italian Society of Neonatology, prescriptions most frequently adhered to indications for certain drugs like ampicillin and fluconazole. The results confirm high rates of off-label/
Introduction to Regulatory Affairs - Pauwels Consulting AcademyPauwels Consulting
On Tuesday, June 14, our colleagues Fiorenzo Savoretti, Senior Regulatory and Quality Consultant at Pfizer and Nick Deschacht, Senior RA Consultant at GSK, gave an interesting “Introduction to Regulatory Affairs”.
Fiorenzo and Nick talked about RA and their projects, each from their unique angle. They delivered their presentations for ## attendees at our Brussels office at the Lambroekstraat 5a in Diegem.
The document discusses ICH (International Conference on Harmonization) guidelines. ICH brings together regulatory authorities and pharmaceutical industries from Europe, Japan, and the US to discuss harmonizing technical requirements for drug safety, quality, and efficacy. The guidelines seek to reduce redundant testing, make treatments more affordable and accessible internationally, and reduce divergent regulatory requirements between countries. ICH guidelines are developed through a 5-step process and cover topics such as quality control, nonclinical safety testing, clinical trial standards, and multidisciplinary issues. Adoption of the guidelines helps ensure consistent evaluation of medicines across regions.
ICH GUIDELINES of chemical engineering (2).pdfAjayGhuge9
The document provides an overview of ICH (International Conference on Harmonization) guidelines. ICH is an international non-profit organization that brings together regulatory authorities and pharmaceutical industries from Europe, Japan and the US to discuss scientific and technical aspects of drug registration. The goals of ICH are to reduce duplication of clinical trials, make safe and effective new treatments more affordable/accessible to patients, and harmonize technical requirements for drug approval across countries/regions. ICH has generated numerous guidelines organized under quality, safety, efficacy and multidisciplinary categories that are recognized by many countries as standards for drug development and approval.
The International Council for Harmonisation (ICH) is a joint initiative between regulators and the pharmaceutical industry to harmonize technical requirements for drug registration. The goal is to streamline development, eliminate redundant testing, and make new medicines available more quickly while maintaining standards of safety and efficacy. ICH involves six regulatory and industry parties working to produce unified guidelines for the European Union, Japan, and United States on quality, safety, and efficacy. This helps facilitate mutual acceptance of clinical data between jurisdictions.
To recap the previous month's pharma highlights to Pharma Uptoday members, Monthly magazine Volume 6 has been released with
News Uptoday
New Guidance
New MAPP Release
Audit Findings
483 Observations
- 483 of Impax Laboratories
- 483 of Ipca Labs
- 483 of Bausch & Lomb Inc
- 483 of Alexion
Warning Letters
- Marck Biosciences Ltd.
- The Compounding Shop Inc.
- Zions Rx Formulations Services LLC.
EMA Non-Compliance Reports
- Renown Pharmaceuticals Pvt. Ltd., India
- VETPROM AD, Bulgaria
- SCM PHARMA LIMITED, UK
Guest of the Month
Dr. M Damodharan - Vice President Global Quality & Regulatory
Regulations of the Month
§ 211.180 Subpart J--Records and Reports - General Requirements
§ 211.182 Subpart J--Records and Reports - Equipment cleaning & use log
ICH Guidelines of Quality, Safety, Efficacy and Multidisciplinary guidelines that implemented by International Council for Harmonisation. ich stands for the harmonisation of Technical requirements of Pharmaceuticals for Human use.
JPPT
316 J Pediatr Pharmacol Ther 2015 Vol. 20 No. 4 • www.jppt.org
Clinical Investigation
Unlicensed and Off-Label Drug Use in Children Before and After
Pediatric Governmental Initiatives
Jennifer Corny, PharmD Candidate,1 Denis Lebel, BPharm, MSc,1 Benoit Bailey, MD, MSc,2
and Jean-François Bussières, BPharm, MSc, MBA1,3
1Pharmacy Practice Research Unit, Pharmacy Department, 2Division of Emergency Medicine, Department of
Pediatrics, CHU Sainte-Justine, Montréal, Québec, Canada; 3Faculty of Pharmacy, Université de Montréal, Montréal
OBJECTIVES: Governmental agencies (US Food and Drug Administration and European Medicines Agency)
implemented initiatives to improve pediatric clinical research, starting in 1997 and 2007, respectively. The
aim of this review was to quantify the unlicensed and off-label drug uses in children before and after these
implementations.
METHODS: Literature review of unlicensed and off-label drug uses was performed on PubMed and Google-
Scholar from 1985 to 2014. Relevant titles/abstracts were reviewed, and articles were included if evaluating
unlicensed/off-label drug uses, with a clear description of health care setting and studied population. In-
cluded articles were divided into 3 groups: studies conducted in United States (before/after 2007), in Europe
(before/after 2007), and in other countries.
RESULTS: Of the 48 articles reviewed, 27 were included. Before implementation of pediatric initiatives,
global unlicensed drug use rate in Europe was found to be 0.2% to 36% for inpatients and 0.3% to 16.6%
for outpatients. After implementation, it marginally decreased to 11.4% and 1.26% to 6.7%, respectively.
Concerning off-label drug use rates, it was found to be 18% to 66% for inpatients and 10.5% to 37.5% for
outpatients before the implementation. After implementation, it decreased marginally to 33.2% to 46.5%
and to 3.3% to 13.5%, respectively. In other countries, unlicensed and off-label drug use rates were found to
be, respectively, 8% to 27.3% and 11% to 47%.
CONCLUSIONS: Governmental initiatives to improve clinical research conducted in children seem to have
had a marginal effect to decrease the unlicensed and off-label drug uses prevalence in Europe.
INDEX TERMS: off-label use, pediatrics, review
J Pediatr Pharmacol Ther 2015;20(4):316–328
INTRODUCTION
Before a drug can be approved for sale in a
given market, governmental authorities in each
country have to assess its safety, efficacy, and
quality. At the end of this process, pharmaceuti-
cal companies are granted market authorization,
and the drug gets a license for marketing in the
country (e.g., Notice of Compliance in Canada).
The drug also has a label (i.e. drug monograph),
specifying the details for drug use (e.g., target
population, dose, indication, specific use).
Virtually all drugs that get an approval for use
in adults should also get an approval for use in
children; this is often not the case considering the
paucit.
ICH GUIDELINES Q S E M & REGULATORY REQUIREMENTS OF EU, MHRA, TGA & ROW CO...RushikeshPalkar1
The document discusses the International Conference on Harmonization (ICH), an initiative to harmonize technical requirements for pharmaceutical registration. It describes ICH's mission to reduce redundant testing, outlines its structure and members, and explains the guidelines and regulatory requirements of various countries and regions, including the EU, MHRA, TGA, and rest of world.
The document summarizes regulatory affairs for the MHRA and USFDA. It discusses the history and roles of the MHRA in regulating clinical trials, licensing products, and enforcing regulations in the UK. It then outlines the development process for new drugs from discovery through licensing. Finally, it provides an introduction to the USFDA, covering its definition, history, mission, organization, functions, and products regulated.
The document discusses the International Council for Harmonization (ICH), a joint initiative between regulatory authorities and pharmaceutical industries from Europe, Japan, and the US to harmonize technical requirements for pharmaceutical registration. The goals of ICH are to ensure safety, quality and efficacy of medicines, harmonize technical requirements, and develop drugs in an efficient and cost-effective way. ICH has produced numerous guidelines on quality, safety, efficacy and multidisciplinary topics to harmonize regulatory standards across regions.
This document provides an introduction to pharmacoepidemiology. It defines pharmacoepidemiology as the study of drug use and effects in large populations. It discusses study designs used in pharmacoepidemiology including randomized trials, cohort studies, case-control studies, and case reports. Reasons for performing pharmacoepidemiology studies include fulfilling regulatory and legal obligations, assessing drug safety, and generating or testing hypotheses. Common data sources are spontaneous adverse event reporting, prescription databases, and medical records. Issues like adherence, molecular factors, ethics, and economics are also discussed.
This document provides an introduction to pharmacoepidemiology. It defines pharmacoepidemiology as the study of drug use and effects in large populations. It discusses study designs used in pharmacoepidemiology including randomized trials, cohort studies, case-control studies, and case reports. Reasons for performing pharmacoepidemiology studies include fulfilling regulatory and legal obligations, assessing drug safety, and generating or testing hypotheses. Sources of data include spontaneous adverse event reporting, prescription databases, and electronic health records. The document also briefly discusses molecular pharmacoepidemiology, bioethics, pharmacoeconomics, and measuring quality of life outcomes.
Discovery of Drug and Introduction to Clinical Trial__Katalyst HLSKatalyst HLS
This document provides an overview of the drug discovery and clinical trials process. It discusses the goals of drug discovery which include identifying new chemical entities and developing medicines to address unmet medical needs. The drug discovery process involves target identification, validation, lead generation, and optimization. Pre-clinical testing is then conducted to evaluate safety and effects. If successful, an investigational new drug application is filed with the FDA prior to beginning clinical trials. Clinical trials involve 4 phases to test safety and efficacy in humans. Upon completion, a new drug application can be filed for FDA review and potential approval.
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Etica 04 medicines for children licensed by the european agency
1. SPECIAL ARTICLE
A. Ceci Æ M. Felisi Æ M. Catapano Æ P. Baiardi
L. Cipollina Æ S. Ravera Æ S. Bagnulo Æ S. Reggio
G. Rondini
Medicines for children licensed by the European Agency
for the Evaluation of Medicinal Products
Received: 6 June 2002 / Accepted: 14 August 2002 / Published online: 25 September 2002
Ó Springer-Verlag 2002
Abstract Objective: The aim of this study was to eval-
uate the number and the characteristics of medicines
approved for children in Europe by the European
Agency for the Evaluation of Medicinal Products
(EMEA) and whether the paediatric studies supporting
the authorisation were in accordance with the Note for
Guidance on the Clinical Investigation of Medicinal
Products in children (CPMP/ICH/2711/99). We also
considered any possible difference between the EMEA
and the Food and Drug Administration (FDA) paedi-
atric medicines evaluations.
Methods: We examined the drugs authorised by the
EMEA through the centralised procedure from January
1995 to September 2001 deriving information from the
‘‘European Medicines – Database’’ (EMD) set up in
1998 by the Italian Group for Pharmacoeconomic
Studies (GISF) and sponsored by the Italian Ministry of
Health. The analysis of paediatric data has been man-
aged by experts belonging to the Clinical Pharmacology
Working Group of the Italian Paediatric Society. The
following parameters were assessed: active substance,
year of approval, anatomical therapeutic and chemical
(ATC) code, therapeutic indications, age for which the
drug is authorised, interest to children and paediatric
studies supporting a paediatric authorisation. European
Public Assessment Reports (EPARs) were considered as
reference sources.
Results: The median percentage of drugs authorised for
children from 1995 to 2001 (September) is 35% of the total
of commercially available drugs; only 16 medicines have
been approved for children under 2 years of age (11%),
ten of these being vaccines. Medicines for children shared
out 9 ATC classes, 24 belonging to the J- (anti-infective
agents) -ATC class. Thirty-nine medicines were author-
ised on the basis of at least one clinical trial (27 phase III, 6
phase II, 6 phase I) while eight active substances have been
licensed without any paediatric investigation.
Conclusions: Under the EMEA centralised procedure,
several active substances have been licensed for children.
Consequently serious and life-threatening diseases as
AIDS and diabetes are now treatable, in a legal frame-
work overcoming the orphan status of the past years.
Despite the reported encouraging results, the number of
drugs devoted to children remain low and important
ATC classes, as L-(oncology) or N-(neurology), are still
‘orphans’ of innovative medicines. At the same time few
medicinal products are specifically studied in children.
Consequently, more efforts have to be made to increase
the number of drugs assessed and licensed for the pae-
diatric population, and manufacturers should be
required to supply data on the effects of new drugs in
children when the products are expected to offer a
benefit over existing therapies.
Keywords Children Æ European Community Æ Licensed
medicines Æ Clinical studies
Introduction
For many years, because of the lack of studies specifi-
cally designed to investigate pharmacological and toxi-
cological aspects in paediatric populations, many
approved drugs have been used in children without
proper information on dosage and potential toxicity
[1, 2, 3] or without appropriate dosage forms.
Eur J Clin Pharmacol (2002) 58: 495–500
DOI 10.1007/s00228-002-0511-0
A. Ceci Æ M. Felisi
Department of Pharmacology and Human Physiology,
University of Bari, Bari, Italy
A. Ceci Æ M. Catapano (&) Æ P. Baiardi Æ L. Cipollina
S. Ravera Æ S. Bagnulo
Consortium for Biological and Pharmacological Evaluations,
University of Pavia and the ‘‘S. Maugeri’’ Foundation,
Via Palestro 26, 27100 Pavia, Italy
E-mail: mcatapano@fsm.it
Tel.: +39-0382-25075
Fax: +39-0382-536544
S. Reggio
IRCCS Oasi Maria SS Troina, Italy
G. Rondini
Department of Paediatrics, University of Pavia, Pavia, Italy
2. Consequently, marketed drugs have frequently been
used off-label [4, 5, 6, 7] or unlicensed drugs have been
employed. This attitude seems to lead to an increased
rate of adverse drug reactions and medication errors
[6, 8, 9, 10].
To provide adequate information on paediatric use of
medicinal products, the Food and Drug Administration
(FDA) developed a number of initiatives (1994: Pediat-
ric Labeling Rule [11]; 1997: FDA Modernization Act-
FDAMA, Section 111 [12]; 1998: Mandatory Paediatric
Rule [13]) giving incentives and obligations to the
pharmaceutical industries for conducting paediatric
studies.
The specific issue of paediatric medicines has been
recently considered even by the European Institutions,
defining rules about the principal ethical and method-
ological aspects for clinical trials in children [1997 –
European Agency for the Evaluation of Medicinal
Products (EMEA) Round table of experts [14]; 1999
Note for Guidance on the Clinical Investigation of
Medicinal Products in children (CPMP/ICH/2711/99)
[15]; 2000: Council of the Ministers of Health Resolution
[16]; 2000: Regulation no. 141/2000 [17]; 2001: Directive
EC/2001/20 on the conduct of the clinical experimenta-
tions in humans [18]].
European initiatives, in contrast with those of the
FDA, excluding incentives and obligations, simply
encourage the companies to investigate drugs in children
with the hope that they would result in a change of
attitude by pharmaceutical industries. The aim of the
present study was to evaluate the number and the
characteristics of medicines approved for children in
Europe by the EMEA as well as the number and types of
paediatric studies supporting authorisations.
The medicines approved under the EMEA centralised
procedure represent a homogeneous sample of medicines
useful for this purpose because (a) the centralised pro-
cedure is devoted to innovative drugs for the care of
serious and/or untreatable diseases, (b) the essential
documents used for the marketing authorisation are
currently available and published as European public
assessment reports (EPARs) in the EMEA database and
(c) a single high-level committee is responsible to give
scientific advise for planning clinical studies. In our
analysis we also took into account any possible existing
difference between the EMEA and FDA paediatric
medicines status and evaluations.
Methods
We examined the drugs authorised by the EMEA through the
centralised procedure from 1995 to September 2001, deriving
information from the ‘European Medicines – Database’ set up in
1998 by the Italian Group for Pharmacoeconomic Studies (GISF)
[19] and sponsored by the Ministry of Health with the aim of
collecting information on new and innovative medicinal products
marketed in Europe. EPARs have been considered as reference
sources.
EPAR reflects the scientific conclusion reached by the Com-
mittee for Proprietary Medicinal Products (CPMP) at the end of
the evaluation process for marketing the product. It is made
available by the EMEA for information to the public after deletion
of commercially confidential information. The content of the
EPAR summarises the various reports produced during the cen-
tralised evaluation procedure, resulting from the review of the
documentation submitted by the applicant together with the sci-
entific discussion. It also contains a summary of product charac-
teristics and the information to be included in the patient
information leaflet.
The following parameters were assessed:
• Active substance
• Year of approval
• Anatomical therapeutic and chemical (ATC) code
• Therapeutic indication
• Age/s for which the drug is authorised
• Clinical studies leading to paediatric authorisation
According to CPMP/ICH/2711/99, the ages for which the drug
is intended are defined in completed days, months, or years as
follows:
• New-born infants (0–27 days)
• Infants and toddlers (28 days to 23 months)
• Children (2–11 years)
• Adolescents (12–17 years)
For the purposes of our analysis, we considered four categories
of drugs according to the severity and for interest in treating dis-
eases for children:
• Category 0 = drugs for diseases that do not affect children
• Category 1 = drugs for non-serious diseases that affect both
adults and children or diseases already cured in children
• Category 2 = drugs for serious diseases that affect children and
of significant benefit compared with the existing methods
• Category 3 = drugs for diseases still incurable in children
Category definition was done with the support of the Clinical
Pharmacology Working Group set up by the Italian Society of
Paediatrics. Clinical trials were defined according to the phase of
the study (I, II or III) and to the age of the experimental popula-
tion.
For medicinal products approved by the FDA, we analysed
each product information (PI) document. The PI is the package
labelling reporting the product characteristics. It is written by the
sponsor, approved by the FDA and used during all phases of drug
development; it also contains the design and analysis of clinical
trials that were planned to address and to support the proposed
label. These documents are available on the World Wide Web
(www.rxlist.com, www.micromedex.com). Data management and
analysis were done using the Microsoft Access Office 2000 Software
package.
Results
Since 1995 the EMEA has considered a total of 339
applications for drugs approval, CPMP has provided
217 opinions and 127 active substances, and 14 vaccines
have been granted a community marketing authorisa-
tion. Of these, 47 (33%) are available for use in children,
10 with paediatric dosage forms and 23 with specific
paediatric dosage.
As shown in Table 1:
496
3. i. The percentage of drugs authorised for children per
year varies from 0% to 42%, with a median value of
35%.
ii. Paediatric medicines belong to 9 of 13 ATC classes.
Twenty-four medicines (51%) have been assigned to
J-(anti-infective agents)-ATC code, corresponding to
11 vaccines and 10 antiviral agents for acquired
immunodeficiency syndrome (AIDS) treatment.
Excluding the J-ATC class the percentage of medi-
cines authorised in children falls from 33% to 21%.
iii. Just one medicine refers to category 1 (diseases al-
ready cured), 40 to category 2 (diseases for which no
satisfactory treatment methods exist) and 6 to cate-
gory 3 (diseases still incurable including orphan
diseases).
iv. Sixteen medicines have been approved for children
under 2 years of age (11%), ten of these being vac-
cines. For children under 6 years and 12 years, only
23 (18%) and 33 (26%) medicines, respectively, are
available while the percentage referred to children
over 12 is 25%. For several drugs, the age for which
the medicine is approved does not belong to any of
the age classes listed in the CPMP/ICH/27100/99/EC
document.
In Table 2 the list of Orphan drugs is shown (regis-
tered in Europe) as are drugs for treating rare diseases,
including four drugs belonging to category 2 and eight
drugs to category 3.
Paediatric clinical trials supporting marketing
authorisation were carried out for a total of 36 active
substances including vaccines. All vaccines and 16
active substances had phase-III clinical studies. Six
active substances (sodium phenylbuthirate, etanercept,
telithromicin, temozolomide, insulin aspart, micophen-
olate mofetil) were authorised on the basis of a phase-I
study and six (lopinavir/ritonavir, ritonavir, efavirenz,
nelfinavir mesylate, protein C, stavudine) on the basis of
a phase-II study. Finally, eight medicines (human insu-
lin, ganciclovir, repaglinide, etflornithine, darbepoetin
alfa, factor IX, imiglucerase, lamivudine/zidovudine)
were licensed without any paediatric investigation. The
age of the experimental population was declared in all
but one case, showing that, in 13 cases, it significantly
differed from the age for which the drug has been
licensed. For four active substances (insulin aspart,
stavudine, amprenavir, factor VIII SQ) all groups of age
were included in the clinical studies.
All but four medicines approved by the EMEA for
paediatric use are available in the US market. Moreover
among all the medicines available in both European and
USA markets, four drugs had a negative opinion for
paediatric use by the FDA. On the contrary, three drugs
(abacavir, insulin glargine and desloratadine), approved
in the USA under the FDAMA provisions, were rejected
by the EMEA for the same age group (Table 3).
Discussion
Under the EMEA centralised procedure, 47 medicines
(33%) were licensed for children. This percentage is
significantly higher than that of medicines approved
under the National Procedure and the Mutual Recog-
nition Procedure (MRP) [2, 20]. In fact, in 1996 an Italian
study [2] showed that only 2.1% of 9741 marketed drugs
were labelled for use in paediatric subjects (187 for
children and 18 for infants) . More recently a survey on
drugs approved under the MRP and marketed in
Italy [20] demonstrated that only 19 of 143 (13.2%) were
approved for children during the 1995–2001 period. This
difference was shown to be statistically significant
(P<0.001) [20].
However, our data showed no increasing trend in the
percentage of the EMEA-approved medicines for chil-
dren compared with previously reported data: Impic-
ciatore et al. [20] reported that, of a total of 45
Table 1 Paediatric medicines per year of approval, ATC code,
category of interest in children and medicine availability according
to the groups of age
Paediatric
medicines
and vaccines/
total EMEA
% of
paediatric
medicines on
total EMEA
Year of approval
1995 0/3 0
1996 7/20 35
1997 8/19 42
1998 6/22 27
1999 10/25 40
2000 6/25 24
2001 10/27 37
Total 47/141 33
ATC code
A 7/13 54
B 6/14 43
D 1/2 50
H 1/3 33
J 24/34 71
L 4/25 16
R 2/2 100
S 1/3 33
V 1/16 6
Other 0/29 0
Total 47/141 33
Category of interest in children
0 0/34 0
1 1/11 9
2 40/84 48
3 6/12 50
Total 47/141 33
Groups of age according
to the CPMP/ICH
classification
EMEA-approved
medicines (n)
New-borns (0–27 days) 4
Infants and
toddlers (28 days
to 23 months)
12
Children (2–11 years) 14
Adolescents (12–17 years) 6
Not specified 11
Total 47
497
4. substances licensed by the EMEA until 1998, 34% were
licensed for children [21].
Particularly, the percentage of available medicines
proves to be very low when different groups of age were
considered, falling from 33% to 18% and 11% in chil-
dren under 6 years and 2 years, respectively, while only
four medicines were approved for new-borns. In addi-
tion we noted that, for the majority of medicines, the
ages indicated in the label are not in agreement with the
groups of age listed in the CPMP/ICH/27100/99/EC,
reducing the availability of the drug to a more limited
population.
Several of the new approved medicines are for the
care of serious and life-threatening diseases, such as
AIDS and diabetes, now treatable while in the past were
orphans of specific drugs [21]. A very high percentage of
paediatric drugs was encountered in the J-ATC category
encompassing both the vaccines and drugs for AIDS
treatment. This result could be easily explained because
vaccines represent the only paediatric medicine category
for which the dimension of the market guarantees a
good economic return, while a large amount of incentive
was granted for the development of drugs for AIDS
treatment for research in Europe. This is in contrast with
the absence or the very low percentage of drugs for
treatment of other serious or incurable diseases that
belong to important clinical categories (e.g. central
nervous system and oncology), despite the fact that
many drugs are largely employed in children [22, 23, 24].
The reluctance of pharmaceutical industries to invest
in developing paediatric medicines is furthermore con-
firmed by the absence of paediatric indication in the
group of drugs approved by the EMEA as orphan drugs
(under or before the regulation no. 141/2000 provisions).
Of a total of 11 medicines, 4 are available for children,
while agalsidase (treatment for Fabry disease), levace-
tylmethadol (for opiate addiction), fomivirsen (for local
CMV retinitis in AIDS patients), samarium (for painful
osteoblastic metastases) and tasonermin (for treatment
of soft tissue sarcoma) are not available, notwithstand-
ing the possible paediatric therapeutic interest.
In lack of both interest of industry and public incen-
tives, few clinical paediatric studies have been included in
the documentation for the centralised procedure author-
isation, and medicines for children continue to be gener-
ally understudied. In particular, less than half of the
EMEA-approved paediatric medicines were authorised
after completing phase-III paediatric studies, while 17%
were studied only in adults but authorised in both children
and adults. Moreover, few clinical studies performed in all
groups of age for which the drug was licensed have been
produced. This is of particular concern when the adoles-
cent group is considered, since adolescents are frequently
recruited together with adults while, according to the
CPMP/ICH/2711/99 [15], they are fully entitled to have
access to protocols of study in specific paediatric trials.
In contrast with the European situation described
above, it is pointed out that in USA (September 2001
update), 561 paediatric studies were started up under the
1997 FDA Modernisation Act [12], 20 leading to a
labelling change in dosages or safety announcement. In
addition, 102 studies were completed under the 1998
‘‘Paediatric Rule’’ and more then 32,000 children were
enrolled in studies requested by the FDA or voluntarily
planned by pharmaceutical industries [25].
The European legislative provisions, in contrast with
the 1998 – FDA Paediatric Rule, exclude obligations for
industries to perform paediatric studies for new drugs
that are or could be of interest for children in order to
have a marketing authorisation. The European legisla-
tive provisions also exclude the possibility that the
EMEA could claim for additional studies in case of
Table 2 Orphan drugs (registered in Europe) and drugs for treating rare diseases
Active substance Medicinal product Therapeutic indication Paediatric label-
ling
Cysteamine bitartrate Cystagon* Treatment of proven nephropatic cystinosis 0–12 years
Nonacog alfa BeneFIX* Treatment and prophylaxis of bleeding in patients
with haemophilia B
>6 years
Tasonermin Beromun* Treatment of the irresectable soft tissue sarcoma
of the limbs
None
Imiglucerase Cerezyme* Therapy in patients with a confirmed diagnosis
of type-1 Gaucher disease
Children
Sodium phenylbutyrate Ammonaps* Adjunctive therapy in the chronic management
of urea cycle disorders
0–12 years
Samarium Quadramet* Indicated for the relief of bone pain in patients with
multiplic painful osteoblastic skeletal metastases
None
Fomivirsen Vitravene* Local treatment of cytomegalovirus (CMV) retinitis in
patients with acquired immunodeficiency syndrome (AIDS)
None
Levacetylmethadol Orlaam* Maintenance treatment of opiate addiction in adults
previously treated with methadone
None
Agalsidase Fabrazyme *
Replagal *
Treatment of Fabry disease None
Deferiprone Ferriprox Treatment of iron overload in patients with thalassemia major >6 years
Protein C Ceprotin Treatment of severe congenital protein C deficiency 0–18 years
Temozolomide Temodal Treatment of malignant glioma >3 years
*Orphan or Orphan-like medicinal products registered in Europe
498
5. already marketed drugs that demonstrate to be largely
employed in paediatric populations in accordance with
the demonstrated therapeutic interest. Consequently, the
lack of appropriate clinical studies for paediatric medi-
cines in Europe seems to create a new gap between USA
and Europe, claiming for a new European regulation
that would ensure incentives for research and legal
provisions to require routine studies in paediatric pop-
ulations as part of the marketing authorisation appli-
cation.
Moreover, the different opinions between EMEA
and FDA about the same clinical studies need to be
clarified. This fact could be simply related to the dif-
ferent philosophy of the agencies, but some concern
still exists because the ‘Note for Guidance on the
Clinical Investigation of Medicinal Products in chil-
dren’ (CPMP/ICH/2711/99) [15], which has been set up
to lead a common and scientifically advanced meth-
odology of research, seems to be unsuccessful for this
purpose.
In conclusion, despite the reported encouraging
results, in terms of innovative drugs intended for treat-
ment of serious diseases (AIDS, diabetes), the percentage
of clinical trials supporting marketing authorisation in
children still remains low, and important ATC categories,
such as L-(oncology) or N-(neurology), are still ‘orphans’
of innovative medicines.
To reduce the gap in paediatric medicine availability,
the European Commission–Enterprise Directorate has
recently proposed new regulatory actions [26]. Among
these, the following have to be underlined: incentives for
research, introduction of a period of data protection,
creation of a specific fund that could be used to finance
paediatric research, legal requirements for clinical trials,
central database on off-label uses, establishment of an
EU scientific expert group, follow-up pharmacovigilance
studies for high-risk products and creation of a pan-
European network of clinical excellence for the perfor-
mance of paediatric studies.
These measures seem to entirely fulfil the problems
related to the paediatric medicines in Europe. Therefore,
if these actions were to be promptly adopted, more
effective medicines for children would be possibly as-
sured in the future.
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Table 3 Active substances with
different labelling approved by
the European Agency for the
Evaluation of Medicinal Prod-
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Active substance Labelling
EMEA (EPAR)
FDA (product information
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Indinavir sulphate Indicated for children >4 years Safety and effectiveness in paediatric
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Repaglinide Indicated for children >12 years No paediatric studies submitted
Desloratadinea,b
*
^ Indicated for children >12 years Different dosage for different
age groups
Abacavira
Not recommended in children Indicated for children >3 months
Insulin glarginea
Not recommended in children Safety and effectiveness established
in children <6 years
a
Drugs that have satisfied the
requirements of the FDA’s
implementation of the Paediat-
ric Exclusivity Provision and
already submitted to EMEA
b
In USA loratadine
499
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500