Presentations given at the TGA information sessions cover the pharmacovigilance inspection guidelines, preparing for inspections, inspection process, and close out of inspections.
Raj Bhogal, Head of Regulatory Inspections, R&D Quality Takeda on the topic of 'Pharmacovigilance Inspections' at IFAH held at Le Meridien, Dubai on 16th - 18th December, 2019.
Pharmacovigilance "Module I" Pharmacovigilance system & their quality systemMohamed Raouf
This Module contains guidance for the establishment and maintenance of quality assured Pharmacovigilance systems for marketing authorization holders (MAHs) and national medicine authorities (NMAs).
Reference:- Guideline on good pharmacovigilance practices (GVP) version no.3
This document discusses pharmacovigilance risk management audits. It defines an audit and explains why pharmacovigilance system audits are performed. It describes different types of audits, including global pharmacovigilance system audits, company affiliate audits, and marketing partner audits. It also outlines audit scheduling, fundamentals, reporting, corrective actions, follow-up, metrics, and inspection readiness best practices. The overall purpose of pharmacovigilance audits is to ensure compliance and patient safety.
This document provides guidance on conducting pharmacovigilance audits according to international standards. It discusses the legal, technical, and scientific context of pharmacovigilance audits. A risk-based approach to auditing is recommended, focusing on high risk areas like critical processes, quality systems, and areas of noncompliance. Audit findings should be graded based on their criticality and risk level. Corrective actions should address critical and major issues to ensure patient safety and compliance.
The document discusses pharmacovigilance, which involves monitoring the safety of medical products. It outlines various methods for collecting and analyzing adverse event reports, including spontaneous reports from healthcare professionals and patients, literature reviews, and solicited reports from clinical trials. It also discusses prioritizing cases, signal detection methods, and actions that may be taken in response to potential safety issues. The main objectives are to minimize risks for patients and the company while meeting regulatory requirements.
Development safety update report (dsur) pharmacovigilance and safetyAzierta
According to ICH guideline E2F (Step 5) on Development Safety Update Reports (DSURs) already implemented since 2011, companies must submit DSURs on a yearly basis for medicinal products involved in clinical trials. The focus of the DSUR is on data and findings from clinical trials of drugs and biologicals, whether they are authorized or not.
DSURs are internationally-harmonized, safety documents covering the safety summary of medicinal products during their development or clinical trial phase.
They are based heavily on the PSUR format already used for updating the safety record of drugs in their marketing phase.
A DSUR should be prepared after the first authorization of a clinical trial worldwide. A copy of the DSUR should be submitted to each concerned European Member State (MS) if a clinical trial is authorized in this MS for this investigational drug (still using the DIBD). Therefore, the first DSUR can be submitted to a concerned MS earlier than 1 year, but the covered reporting period should not be longer than 1 year.
The DSUR presents an annual review & evaluation of safety information:
• Information reported during the current review period and analysis based on previous knowledge of the products’ safety
• Description of new issues that may impact the overall program or specific clinical trials.
• Summarization of current understanding and management of known and potential safety risks to exposed patients.
• Provide an update on the status of the clinical development program.
In Azierta, scientific and healthcare consulting, we are experts in Pharmacovigilance and we have a team of highly qualified drug safety experts who support our clients to manage pharmacovigilance in an optimal way. Our work covers all areas of pharmacovigilance, both at the level of medicines, as well as medical devices and cosmetic products.
If you are interested in the contents of the good practices of pharmacovigilance (GVPs), as well as in other products related to pharmacovigilance visit our safety reports website for more details and feel free to contact us, we will be pleased to help you.
Raj Bhogal, Head of Regulatory Inspections, R&D Quality Takeda on the topic of 'Pharmacovigilance Inspections' at IFAH held at Le Meridien, Dubai on 16th - 18th December, 2019.
Pharmacovigilance "Module I" Pharmacovigilance system & their quality systemMohamed Raouf
This Module contains guidance for the establishment and maintenance of quality assured Pharmacovigilance systems for marketing authorization holders (MAHs) and national medicine authorities (NMAs).
Reference:- Guideline on good pharmacovigilance practices (GVP) version no.3
This document discusses pharmacovigilance risk management audits. It defines an audit and explains why pharmacovigilance system audits are performed. It describes different types of audits, including global pharmacovigilance system audits, company affiliate audits, and marketing partner audits. It also outlines audit scheduling, fundamentals, reporting, corrective actions, follow-up, metrics, and inspection readiness best practices. The overall purpose of pharmacovigilance audits is to ensure compliance and patient safety.
This document provides guidance on conducting pharmacovigilance audits according to international standards. It discusses the legal, technical, and scientific context of pharmacovigilance audits. A risk-based approach to auditing is recommended, focusing on high risk areas like critical processes, quality systems, and areas of noncompliance. Audit findings should be graded based on their criticality and risk level. Corrective actions should address critical and major issues to ensure patient safety and compliance.
The document discusses pharmacovigilance, which involves monitoring the safety of medical products. It outlines various methods for collecting and analyzing adverse event reports, including spontaneous reports from healthcare professionals and patients, literature reviews, and solicited reports from clinical trials. It also discusses prioritizing cases, signal detection methods, and actions that may be taken in response to potential safety issues. The main objectives are to minimize risks for patients and the company while meeting regulatory requirements.
Development safety update report (dsur) pharmacovigilance and safetyAzierta
According to ICH guideline E2F (Step 5) on Development Safety Update Reports (DSURs) already implemented since 2011, companies must submit DSURs on a yearly basis for medicinal products involved in clinical trials. The focus of the DSUR is on data and findings from clinical trials of drugs and biologicals, whether they are authorized or not.
DSURs are internationally-harmonized, safety documents covering the safety summary of medicinal products during their development or clinical trial phase.
They are based heavily on the PSUR format already used for updating the safety record of drugs in their marketing phase.
A DSUR should be prepared after the first authorization of a clinical trial worldwide. A copy of the DSUR should be submitted to each concerned European Member State (MS) if a clinical trial is authorized in this MS for this investigational drug (still using the DIBD). Therefore, the first DSUR can be submitted to a concerned MS earlier than 1 year, but the covered reporting period should not be longer than 1 year.
The DSUR presents an annual review & evaluation of safety information:
• Information reported during the current review period and analysis based on previous knowledge of the products’ safety
• Description of new issues that may impact the overall program or specific clinical trials.
• Summarization of current understanding and management of known and potential safety risks to exposed patients.
• Provide an update on the status of the clinical development program.
In Azierta, scientific and healthcare consulting, we are experts in Pharmacovigilance and we have a team of highly qualified drug safety experts who support our clients to manage pharmacovigilance in an optimal way. Our work covers all areas of pharmacovigilance, both at the level of medicines, as well as medical devices and cosmetic products.
If you are interested in the contents of the good practices of pharmacovigilance (GVPs), as well as in other products related to pharmacovigilance visit our safety reports website for more details and feel free to contact us, we will be pleased to help you.
An audit is an official inspection done by an independent body to evaluate processes and ensure they comply with regulatory standards. Audits of pharmacovigilance systems are important to ensure patient safety, identify risks for improvement, and maintain compliance. The audit process involves planning, conducting interviews and documentation reviews, reporting findings, developing corrective actions, and following up to ensure issues are addressed. Being prepared for audits at all times is important for pharmacovigilance systems.
The PV audit ensures that a company’s drug safety and pharmacovigilance operations comply with applicable laws, regulations and guidances worldwide, and compare to best practices for organizations of similar size.
Regulatory authorities conduct pharmacovigilance inspections of pharmaceutical companies to ensure adequate PV processes and compliance. Inspections review PV data and processes as part of GMP and GCP audits. Companies should prepare by resolving previous issues, reviewing files for completeness, and identifying contacts. It is best to regularly conduct internal self-inspections and audits. This information is from the book "Pharmacovigilance - An Industry Perspective" which provides an in-depth chapter on pharmacovigilance inspections.
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.
New global regulations have increased requirements for measuring and assessing the benefit-risk profiles of medicines. Quintiles can help companies comply with these changing regulations through safety reporting and benefit-risk assessment services. They have experienced staff across eight global hubs who are trained in pharmacovigilance and regulatory requirements to deliver timely and compliant reports and analyses.
This document summarizes the key aspects of risk management in pharmacovigilance. It discusses how risk management aims to safely use drugs by identifying risks early and minimizing harmful effects. The important steps in risk management include developing a safety specification, pharmacovigilance plan, evaluating the need for risk minimization activities, and creating a risk minimization plan. These steps help identify risks, assess them, and communicate strategies to address safety concerns and optimize the benefit-risk profile of medications.
Safety reports rmp risk management plan pharmacovigilanceAzierta
A Risk management plan is a document based on safety profile of medicines that collects all pharmacovigilance activities and it is used to plan and implement measures in order to minimize risks.
This summary explains how to develop a Risk Management Plan according to European regulatory requirements.
Implementation dates and objectives of RMP module V of Good Pharmacovigilance Practices.
This document provides an overview of pharmacovigilance. It defines key terms like drug, adverse event, and pharmacovigilance. It describes the drug development process including preclinical and clinical trials. It explains the need for pharmacovigilance during clinical trials and after marketing to monitor for adverse events. It discusses how pharmacovigilance benefits public health and drug manufacturers by improving drug safety.
La gestión de riesgos en farmacovigilancia es una actividad global para salvaguardar la salud de los pacientes. Se autoriza un medicamento sobre la base de los resultados de estudios preclínicos y clínicos. Estos estudios generalmente se llevan a cabo en un pequeño número de pacientes en entornos controlados, por ejemplo, edad restringida, comorbilidad, comedicación y excluyendo poblaciones especiales como la población de edad avanzada, niños, mujeres embarazadas y lactantes. En el momento de la autorización, el riesgo-beneficio se considera positivo.
Sin embargo, no todos los riesgos reales o potenciales han sido identificados en el momento de la autorización. La gestión de riesgos es un conjunto de actividades realizadas para la identificación de riesgos, la evaluación de riesgos, la minimización o prevención de riesgos y la comunicación de riesgos. El Plan de gestión de riesgos (RMP) se desarrolla de acuerdo con las regulaciones y pautas aplicables. Sin embargo, en ausencia de pautas para un país, el plan se prepara de acuerdo con la guía ICH E2E sobre planificación de farmacovigilancia.
Presentation: Periodic safety update reportsTGA Australia
The TGA approach to reviewing PSURs (Periodic Safety Update Reports) focuses on evaluating new or emerging safety information to assess the benefit-risk balance of approved medicines. PSUR reviews are prioritized based on risk factors like a product's safety profile and therapeutic importance. If a safety issue is identified that warrants a label change, the PSUR reviewer will recommend an update to the sponsor. Requests may also be made for additional monitoring or analyses in future PSURs. PSUR reviewers collaborate with other TGA departments to enhance post-market vigilance and ensure safety signals are investigated. Sponsors can expect direct communication regarding recommendations from PSUR reviews and are encouraged to submit PSURs using the eCTD format.
This document discusses post marketing surveillance of drugs. It defines post marketing surveillance as monitoring drugs once they reach the market to evaluate their safety and efficacy in wider patient populations than clinical trials. Several methods of post marketing surveillance are described, including spontaneous reporting, cohort studies, and case control studies. The goals of post marketing surveillance include identifying unexpected side effects, assessing drug interactions, and ensuring safe use of medications. It is an important part of pharmacovigilance, the science of monitoring pharmaceutical safety and outcomes.
Introduction to Pharmacovigilance Signal DetectionPerficient
This document provides an introduction to signal detection in pharmacovigilance. It defines key terms like signal and signal detection. It describes qualitative and quantitative signal detection methods including individual case review, data mining algorithms to calculate disproportionality ratios from large safety databases, and visualization tools. Challenges with signal detection include determining what constitutes a "large enough" safety database and assumptions made when using spontaneous reporting data. The document outlines the signal management process from detection to prioritization and evaluation.
Periodic Safety Update Reports (PSURs) are documents submitted by marketing authorization holders to provide an evaluation of a medicine's risk-benefit balance at defined intervals during the post-authorization phase. PSURs must be submitted within 70 or 90 calendar days depending on the interval and contain information on emerging safety issues, benefit-risk analyses, risk management plans, and sources of safety data. The European Medicines Agency publishes the European Union Reference Dates list which mandates the submission timelines and frequencies for PSURs of specific medicines. A single assessment of PSURs is conducted for medicines with the same active substance.
Safety data reconciliation involves comparing safety data between a clinical database and safety database to ensure consistency. Key fields like adverse event term, action taken, causality, and outcome are reconciled. Discrepancies between the databases are identified and queries are issued to sites for resolution. The process aims to clean 100% of agreed upon safety data points and document any acceptable discrepancies.
This document provides an overview of Volume 9A which contains guidelines for pharmacovigilance of medicinal products for human use in the EU. It defines pharmacovigilance and describes the roles and responsibilities of marketing authorization holders, competent authorities, and the EMA. Key aspects covered include pharmacovigilance systems, signal detection, safety reporting, risk management plans, and safety communication.
Pharmacovigilance involves monitoring the safety of drugs at all stages, from development through post-marketing. It aims to detect, understand, and prevent adverse drug reactions through activities like adverse event reporting, drug monitoring, and studying medication errors and drug-related deaths. Pharmacovigilance is important for protecting public health as patterns of drug use change over time with globalization and advances in technology and medicine.
What you need to know about the Pharmacovigilance guidelines for companies marketing drugs in India. A concise overview of the six modules in the Guidance Document and the responsibilities of the Marketing Authorization Holders.
This document discusses signal detection and management in pharmacovigilance. It provides a brief history of pharmacovigilance programs internationally and in India. It defines pharmacovigilance and outlines the objectives, processes, and key steps involved in signal detection, validation, prioritization, assessment, and recommendation for action. These include ongoing monitoring of adverse event reports, signal detection methods, validation criteria, prioritization factors, signal assessment, and potential recommendations that may involve regulatory reporting, labeling changes, or additional studies. The goal is to identify potential safety issues and determine appropriate actions to prevent or minimize patient risk.
MedWatch is the FDA's program for monitoring the safety of medical products. It allows voluntary reporting of adverse events by the public and healthcare professionals. Reports are collected in a database and monitored by FDA professionals. The FDA uses these reports to identify safety issues, communicate new safety information to the public and healthcare providers, and take regulatory actions like requiring label changes or product recalls when needed. The goal is to help protect public health by ensuring the safety of drugs, medical devices and other medical products.
Updates from the Pharmacovigilance and Special Access Branch TGA Australia
Presentation on using new sources of data in Pharmacovigilance, Pharmacovigilance Inspection Program (PVIP) update, International collaboration activities, Adverse Event Management System (AEMS)
Q and A
Presentation: Updates from the Pharmacovigilance and Special Access BranchTGA Australia
This presentation covers using new sources of data in Pharmacovigilance, Pharmacovigilance Inspection Program update, international collaboration activities and Adverse Event Management System.
An audit is an official inspection done by an independent body to evaluate processes and ensure they comply with regulatory standards. Audits of pharmacovigilance systems are important to ensure patient safety, identify risks for improvement, and maintain compliance. The audit process involves planning, conducting interviews and documentation reviews, reporting findings, developing corrective actions, and following up to ensure issues are addressed. Being prepared for audits at all times is important for pharmacovigilance systems.
The PV audit ensures that a company’s drug safety and pharmacovigilance operations comply with applicable laws, regulations and guidances worldwide, and compare to best practices for organizations of similar size.
Regulatory authorities conduct pharmacovigilance inspections of pharmaceutical companies to ensure adequate PV processes and compliance. Inspections review PV data and processes as part of GMP and GCP audits. Companies should prepare by resolving previous issues, reviewing files for completeness, and identifying contacts. It is best to regularly conduct internal self-inspections and audits. This information is from the book "Pharmacovigilance - An Industry Perspective" which provides an in-depth chapter on pharmacovigilance inspections.
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.
New global regulations have increased requirements for measuring and assessing the benefit-risk profiles of medicines. Quintiles can help companies comply with these changing regulations through safety reporting and benefit-risk assessment services. They have experienced staff across eight global hubs who are trained in pharmacovigilance and regulatory requirements to deliver timely and compliant reports and analyses.
This document summarizes the key aspects of risk management in pharmacovigilance. It discusses how risk management aims to safely use drugs by identifying risks early and minimizing harmful effects. The important steps in risk management include developing a safety specification, pharmacovigilance plan, evaluating the need for risk minimization activities, and creating a risk minimization plan. These steps help identify risks, assess them, and communicate strategies to address safety concerns and optimize the benefit-risk profile of medications.
Safety reports rmp risk management plan pharmacovigilanceAzierta
A Risk management plan is a document based on safety profile of medicines that collects all pharmacovigilance activities and it is used to plan and implement measures in order to minimize risks.
This summary explains how to develop a Risk Management Plan according to European regulatory requirements.
Implementation dates and objectives of RMP module V of Good Pharmacovigilance Practices.
This document provides an overview of pharmacovigilance. It defines key terms like drug, adverse event, and pharmacovigilance. It describes the drug development process including preclinical and clinical trials. It explains the need for pharmacovigilance during clinical trials and after marketing to monitor for adverse events. It discusses how pharmacovigilance benefits public health and drug manufacturers by improving drug safety.
La gestión de riesgos en farmacovigilancia es una actividad global para salvaguardar la salud de los pacientes. Se autoriza un medicamento sobre la base de los resultados de estudios preclínicos y clínicos. Estos estudios generalmente se llevan a cabo en un pequeño número de pacientes en entornos controlados, por ejemplo, edad restringida, comorbilidad, comedicación y excluyendo poblaciones especiales como la población de edad avanzada, niños, mujeres embarazadas y lactantes. En el momento de la autorización, el riesgo-beneficio se considera positivo.
Sin embargo, no todos los riesgos reales o potenciales han sido identificados en el momento de la autorización. La gestión de riesgos es un conjunto de actividades realizadas para la identificación de riesgos, la evaluación de riesgos, la minimización o prevención de riesgos y la comunicación de riesgos. El Plan de gestión de riesgos (RMP) se desarrolla de acuerdo con las regulaciones y pautas aplicables. Sin embargo, en ausencia de pautas para un país, el plan se prepara de acuerdo con la guía ICH E2E sobre planificación de farmacovigilancia.
Presentation: Periodic safety update reportsTGA Australia
The TGA approach to reviewing PSURs (Periodic Safety Update Reports) focuses on evaluating new or emerging safety information to assess the benefit-risk balance of approved medicines. PSUR reviews are prioritized based on risk factors like a product's safety profile and therapeutic importance. If a safety issue is identified that warrants a label change, the PSUR reviewer will recommend an update to the sponsor. Requests may also be made for additional monitoring or analyses in future PSURs. PSUR reviewers collaborate with other TGA departments to enhance post-market vigilance and ensure safety signals are investigated. Sponsors can expect direct communication regarding recommendations from PSUR reviews and are encouraged to submit PSURs using the eCTD format.
This document discusses post marketing surveillance of drugs. It defines post marketing surveillance as monitoring drugs once they reach the market to evaluate their safety and efficacy in wider patient populations than clinical trials. Several methods of post marketing surveillance are described, including spontaneous reporting, cohort studies, and case control studies. The goals of post marketing surveillance include identifying unexpected side effects, assessing drug interactions, and ensuring safe use of medications. It is an important part of pharmacovigilance, the science of monitoring pharmaceutical safety and outcomes.
Introduction to Pharmacovigilance Signal DetectionPerficient
This document provides an introduction to signal detection in pharmacovigilance. It defines key terms like signal and signal detection. It describes qualitative and quantitative signal detection methods including individual case review, data mining algorithms to calculate disproportionality ratios from large safety databases, and visualization tools. Challenges with signal detection include determining what constitutes a "large enough" safety database and assumptions made when using spontaneous reporting data. The document outlines the signal management process from detection to prioritization and evaluation.
Periodic Safety Update Reports (PSURs) are documents submitted by marketing authorization holders to provide an evaluation of a medicine's risk-benefit balance at defined intervals during the post-authorization phase. PSURs must be submitted within 70 or 90 calendar days depending on the interval and contain information on emerging safety issues, benefit-risk analyses, risk management plans, and sources of safety data. The European Medicines Agency publishes the European Union Reference Dates list which mandates the submission timelines and frequencies for PSURs of specific medicines. A single assessment of PSURs is conducted for medicines with the same active substance.
Safety data reconciliation involves comparing safety data between a clinical database and safety database to ensure consistency. Key fields like adverse event term, action taken, causality, and outcome are reconciled. Discrepancies between the databases are identified and queries are issued to sites for resolution. The process aims to clean 100% of agreed upon safety data points and document any acceptable discrepancies.
This document provides an overview of Volume 9A which contains guidelines for pharmacovigilance of medicinal products for human use in the EU. It defines pharmacovigilance and describes the roles and responsibilities of marketing authorization holders, competent authorities, and the EMA. Key aspects covered include pharmacovigilance systems, signal detection, safety reporting, risk management plans, and safety communication.
Pharmacovigilance involves monitoring the safety of drugs at all stages, from development through post-marketing. It aims to detect, understand, and prevent adverse drug reactions through activities like adverse event reporting, drug monitoring, and studying medication errors and drug-related deaths. Pharmacovigilance is important for protecting public health as patterns of drug use change over time with globalization and advances in technology and medicine.
What you need to know about the Pharmacovigilance guidelines for companies marketing drugs in India. A concise overview of the six modules in the Guidance Document and the responsibilities of the Marketing Authorization Holders.
This document discusses signal detection and management in pharmacovigilance. It provides a brief history of pharmacovigilance programs internationally and in India. It defines pharmacovigilance and outlines the objectives, processes, and key steps involved in signal detection, validation, prioritization, assessment, and recommendation for action. These include ongoing monitoring of adverse event reports, signal detection methods, validation criteria, prioritization factors, signal assessment, and potential recommendations that may involve regulatory reporting, labeling changes, or additional studies. The goal is to identify potential safety issues and determine appropriate actions to prevent or minimize patient risk.
MedWatch is the FDA's program for monitoring the safety of medical products. It allows voluntary reporting of adverse events by the public and healthcare professionals. Reports are collected in a database and monitored by FDA professionals. The FDA uses these reports to identify safety issues, communicate new safety information to the public and healthcare providers, and take regulatory actions like requiring label changes or product recalls when needed. The goal is to help protect public health by ensuring the safety of drugs, medical devices and other medical products.
Updates from the Pharmacovigilance and Special Access Branch TGA Australia
Presentation on using new sources of data in Pharmacovigilance, Pharmacovigilance Inspection Program (PVIP) update, International collaboration activities, Adverse Event Management System (AEMS)
Q and A
Presentation: Updates from the Pharmacovigilance and Special Access BranchTGA Australia
This presentation covers using new sources of data in Pharmacovigilance, Pharmacovigilance Inspection Program update, international collaboration activities and Adverse Event Management System.
Pharmacovigilance - a regulator's perspectiveTGA Australia
The document discusses pharmacovigilance from the perspective of the Therapeutic Goods Administration (TGA) in Australia. It provides an overview of the TGA's pharmacovigilance activities, including pre-market risk management plans and post-market adverse event reporting and signal detection. It describes how the TGA monitors the safety of medicines throughout their lifecycle to identify new or unknown risks following approval.
This document discusses signal detection and management in pharmacovigilance. It provides a history of pharmacovigilance programs internationally and in India. It defines pharmacovigilance and outlines the objectives, processes, and steps involved in signal detection, validation, prioritization, assessment, and recommendation for action. These include ongoing monitoring of adverse event reports, identifying potential safety signals, validating signals based on factors like strength of association and biological plausibility, prioritizing signals based on impact and evidence, assessing signals, and recommending actions to address validated safety issues.
A pharmacovigilance audit involves several key steps: (1) opening meetings with relevant personnel, (2) document reviews and interviews to evaluate processes for safety data collection, case assessment, and reporting, (3) analyzing data to identify potential safety signals, and (4) closing meetings to discuss preliminary findings. The audit aims to verify that the pharmacovigilance system meets legal requirements for drug safety monitoring and ensure any issues from previous inspections have been addressed. Regular audits are important for regulatory compliance and identifying areas for improvement in pharmacovigilance practices.
Pharmacovigilance-Methods for description..pdfamishapraja123
This document discusses various pharmacovigilance methods used for post-authorization safety studies, including spontaneous reporting, active surveillance, observational studies, clinical trials, and drug utilization studies. It emphasizes that the best method should be selected based on the safety issue being addressed. Regulators may impose additional post-authorization safety studies on marketing authorization holders.
passive_serviallance and responsibilities in pharmacovigilance pptxAyodhya Paradhe
The document discusses the roles and responsibilities in pharmacovigilance and passive surveillance. It defines pharmacovigilance as the monitoring of drugs for safety issues post-marketing. The key roles include investigators who conduct trials, coordinators who manage studies, sponsors who fund studies, monitors who oversee trials, and contract research organizations who assist with management. Passive surveillance involves spontaneous reporting of adverse drug reactions (ADRs) from healthcare professionals and patients, case series which are collections of ADR reports, case reports on individual patients, and stimulated reporting which encourages ADR notification. The goal of pharmacovigilance is to improve drug safety for patients.
Presentation: An Update on post-market regulatory requirementsTGA Australia
Along with implementation of expedited medicine registration pathways TGA has undertaken enhancements to its post-market monitoring of medicines, with a focus on assisting sponsors meet their regulatory requirements. TGA's new Pharmacovigilance Inspection Program (PVIP) involves interviewing sponsors and reviewing documents in order to assess sponsors' level of compliance with pharmacovigilance obligations. Work is also ongoing with sponsors to determine how best to confirm risk management plan (RMP) commitments are being met. This presentation will provide further detail on how TGA is working with and assisting sponsors satisfy their regulatory requirements.
This document discusses pharmacovigilance in clinical trials, which involves monitoring the safety of medicines being tested. It outlines the responsibilities of various stakeholders like sponsors, investigators, and regulators in pharmacovigilance activities like adverse event reporting, risk assessment, and safety monitoring. Key aspects covered are the protocol guidance for safety reporting, use of case report forms and investigator brochures to document adverse drug reactions, and management of safety issues that arise during trials.
Presentation: Spotlight on prescription medicine post-market reformsTGA Australia
An overview of reform initiatives relevant to prescription medicines pharmacovigilance arising from the Review of Medicines and Medical Devices Regulation.
The TGA Pharmacovigilance Inspection Pilot Program: 2015-2016TGA Australia
Firsthand overview of the TGA's Pharmacovigilance Inspection programme from the perspective of both the TGA and companies that have participated in the 'Pilot Inspection Programme'.
Scientific and medical literature is an important source of information for pharmacovigilance and detecting adverse drug reactions. However, marketing authorization holders face challenges in systematically reviewing literature due to a lack of harmonization across regulatory authorities and in developing effective search strategies. Literature screening is important for evaluating drug safety and can impact decisions regarding a drug's risk-benefit analysis. It is important that literature screening is done systematically and documented properly.
ICH pharmacovigilance planning, an efficacy guidelinebibilicavesela
This document provides guidance for developing a pharmacovigilance plan, including a safety specification and action plan. It recommends summarizing important identified risks, potential risks, and missing safety information. The safety specification would then be used to develop a pharmacovigilance plan outlining routine monitoring and specific actions to address safety issues. Milestones should be set to evaluate safety results on a defined schedule. A variety of observational study methods are available to investigate particular safety concerns depending on the product, population, and type of risk being examined.
Patient safety goals effective january 1, 2016Hisham Aldabagh
Includes the patient safety goals which must be achieved during the year 2016, focusing on patient identification, proper patient medication, protection patient against infection, and strict per operative patient safety procedures
Presentation: The Australian Pharmacovigilance Inspection Program (PVIP)TGA Australia
Presentations given at the TGA information sessions cover the pharmacovigilance inspection guidelines, preparing for inspections, inspection process, and close out of inspections.
This document discusses pharmacovigilance, which involves monitoring the safety of medical products. It defines pharmacovigilance and outlines its history, purpose, and key processes. These include collecting adverse event reports, detecting safety signals, evaluating risks, and implementing risk minimization measures. The document also discusses challenges such as distinguishing true safety signals from background noise and standardizing signal evaluations.
This document discusses post-marketing surveillance (PMS), which involves monitoring the safety of pharmaceutical drugs after they have been approved and released on the market. PMS is important because pre-approval clinical trials involve relatively small groups of patients and may miss rare or long-term adverse effects only seen in larger populations. The document outlines various methods for PMS, including spontaneous reporting, cohort studies, and case-control studies. It also discusses the benefits of PMS for improving product quality and safety monitoring, as well as manufacturers' role in establishing PMS procedures and evaluating feedback.
This document discusses post-marketing surveillance (PMS), which involves monitoring the safety of pharmaceutical drugs and medical devices after they have been approved and released on the market. PMS is important because pre-approval clinical trials involve limited numbers of patients and cannot detect all potential adverse effects. The document outlines the history of PMS, sources of PMS information, benefits of PMS systems, methods of surveillance including spontaneous reporting and cohort studies, and how manufacturers can establish PMS procedures and systems to gather feedback on their products.
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1. Permitted indications which provide a list of approved health benefit claims for listed medicines and require sponsors to select from this list, improving transparency.
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3. Overview
• Pharmacovigilance system expectations
• What we inspect
– Management of adverse reaction reports
– Ongoing monitoring of your medicines
– Significant safety issues
– Maintenance of Reference Safety Information
– Periodic Safety Update Reports (PSURs) and Risk Management Plans (RMPs)
– Quality Management Systems
– Contracts and agreements
• How to prepare for an inspection
Pharmacovigilance Inspections: What we inspect 2
4. Pharmacovigilance system expectations
• You should have a robust and effective pharmacovigilance system in place that
allows you to:
– meet all pharmacovigilance recommendations and requirements described in
the Pharmacovigilance responsibilities of medicine sponsors - Australian
recommendations and requirements (Pharmacovigilance Guidelines) and
applicable legislation.
• The TGA expects differing levels of complexity of pharmacovigilance systems
proportionate to a companies product portfolio (i.e. prescription/OTC/comp
meds), sales volume and volume of reports received.
Pharmacovigilance Inspections: What we inspect 3
5. What we inspect
• Inspections assess the appropriateness and compliance of your
pharmacovigilance system to the Australian guidelines and requirements.
• Aspects of the system analysed will vary depending on
– the system in question
– the products available on the ARTG (listed vs registered)
– the medicine’s specific safety requirements (i.e. PSURS and RMPs)
– any specific concerns we might have
Pharmacovigilance Inspections: What we inspect 4
6. What we inspect
• Areas we may inspect include:
– Management of adverse reaction reports
– Ongoing monitoring of your medicines
– Reporting of significant safety issues
– Maintenance of Reference Safety Information
– Periodic Safety Update Reports (PSURs) and Risk Management Plans (RMPs)
– Quality Management Systems
– Computer system validation
– Oversight of the Australian person responsible for PV
– Contracts and Pharmacovigilance agreements
Pharmacovigilance Inspections: What we inspect 5
7. Management of adverse drug reactions (ADRs)
• We will inspect your overall collection and management of adverse drug reactions.
• This will include:
– the collection and collation of reports from all sources and sites
including but not limited to cases reported via medical information enquiries, international
literature, social media and the internet, market research programs, patient support
programs, voluntary patient registries, post-registration studies and partners
– the assessment (validation, seriousness, expectedness and causality), coding and
processing of reports
– follow-up and outcome recording
– reporting within the specified timeframes to the TGA, where required
– record keeping and archiving of adverse drug reaction reports and data
Pharmacovigilance Inspections: What we inspect 6
8. Example findings - ADR management
1. Late ADR reporting
– Serious adverse reaction cases received from a sales representative were identified that were
reported to the TGA 30 days after receipt by the sponsor – this occurred as the ADRs had not
been reported by the representative according to current processes.
– All serious suspected adverse reactions occurring in Australia MUST be reported to the
TGA within 15 days of receipt by the sponsor.
Pharmacovigilance Inspections: What we inspect 7
9. Example findings - ADR management
2. Inappropriate seriousness assessment
• Spontaneous cases were identified in an inspection that were assessed as non-serious and
therefore not reported to the TGA, due to lack of information being reported. Reaction terms
included blindness, anaphylaxis, hepatitis C, renal failure and cancer.
Seriousness assessments should be an independent process to medical evaluation. Where
outcome or treatment information (e.g. hospitalisation) has not been provided, a
conservative approach should be taken and the assessment should be based on the
adverse reaction reported alone. Consequently any medically important reaction should be
considered serious, where further details are unknown, in accordance with the Australian
Pharmacovigilance Guidelines.
Pharmacovigilance Inspections: What we inspect 8
10. Example findings - ADR management
3. Deficiency in identifying ADRs from complaints and enquiries
– ADRs were identified in Product quality complaint cases that had not been collected by the
sponsor and thus not included in the safety database. For example “the tablet was harder to
swallow than normal and made me go all shaky and vomit”.
– It was identified in medical information enquiry cases that reasonable steps had not been taken
to determine if an AE or a special situation event, including off-label use, had occurred. For
example “Can you tell me if low blood pressure is a side effect of medicine X?”, “Is this
medicine safe to use in pregnancy?”, “What is the dose recommended for use in a 3 year old?”
Care should always be taken to determine if an enquiry involves an adverse event or special
situation report for collection and reporting purposes in accordance with best
pharmacovigilance practice. This ensures that all potential safety information is being
collected, reported and evaluated in ongoing analyses of the benefit-risk balance for a
medicine.
9
11. Example findings - ADR management
4. Deficiency in monitoring literature reports
– Several literature reports were identified by the inspector that contained potential ADRs that
had not been collected or collated by the sponsor, either for ADR reporting or ongoing
monitoring purposes.
– The result of weekly searches was not documented nor reproducible and staff completing this
task had not received appropriate training in literature searching strategies
– The search strategy and process used was considered inadequate as it did not contain generic
medicine names and did not encompass relevant journals
You should be undertaking regular—no less than weekly—systematic literature review of
widely used reference databases (such as Medline, Excerpta Medica or Embase) to identify,
report and record adverse reaction reports and significant safety issues. You should use
both trade name and generic names of the medicines in your search strategy.
Your procedures for monitoring literature should sufficiently capture up-to-date and
comprehensive safety information associated with your medicines.
Pharmacovigilance Inspections: What we inspect 10
12. Ongoing monitoring of medicines
• We will assess the ongoing analysis of the risk/benefit profile of your medicine(s) during the
post-authorisation period.
• We will include review of your:
– use of relevant information sources for signal detection
– appropriately applied methodology concerning analysis
– examination of processes, decision-making, communications and actions relating to
signals investigated
– appropriateness of investigations and follow-up actions such as the implementation of
recommendations following data review
– timely identification and provision of complete and accurate data, in particular in response
to specific requests for data from the TGA
Pharmacovigilance Inspections: What we inspect 11
13. Example Findings - Ongoing monitoring
1. Deficiency in database search strategy
– When investigating a signal of “thrombocytopenia” the database search strategy used to
identify relevant cases for analysis did not include all relevant MedDRA terms e.g.
“decreased platelet count”.
– In addition non-valid cases (where a drug-event pair was available) and data from legacy
safety systems were not included in the ongoing monitoring process.
Evaluation of the risks benefits profile of a medicine should be on the basis of full
information i.e. all relevant information should be included in analyses. One medical
concept may be coded in different ways. When analysing signals, it is important to
consider all the MedDRA codes that may relate to the medical concept so that all
relevant cases are reviewed. Erroneous conclusions may be drawn on the basis of an
incomplete dataset.
Pharmacovigilance Inspections: What we inspect 12
14. Example Findings - Ongoing monitoring
2. Deficiency in signal detection
– The sponsor had not implemented a formal and routine procedure for signal detection as they
considered their product well established with a known safety profile.
Ongoing provision to the TGA of any information relevant to an identified change to the
benefits and risks afforded by a medicine is required. Changes in risk-benefit balance may
occur at any point in time in a product lifecycle. New products entering the market may
impact safety of older products (e.g. interactions).
Signal detection should occur on a regular basis for the lifecycle of the medicine in order to
detect any signals that may arise.
Pharmacovigilance Inspections: What we inspect 13
15. Example Findings - Ongoing monitoring
3. Deficiency in signal detection analyses
– A sponsor of medicines with a large market share were undertaking signal detection by
manually reviewing cases. Due to the large number of cases being manually reviewed
potential signals were being missed.
There should be defined criteria and thresholds with which to identify a signal, whether
qualitative or quantitative. These methods should also be relevant and suitable for the
data set they are aimed at, for example, complex disproportionality analyses should
not be applied to limited datasets, and qualitative methods should not be applied to
very large datasets.
Pharmacovigilance Inspections: What we inspect 14
16. Significant Safety Issues
• We will assess the identification and reporting of significant safety issues.
• This will include:
– The examination of processes, decision-making, communications and
actions relating to a specific trigger and/or product safety issue
– The notification to the TGA of significant safety issues that are identified
locally and internationally within the specified timeframes
Pharmacovigilance Inspections: What we inspect 15
17. Example Findings - Significant Safety Issues
1. Non-reporting of significant safety issues
–Two events were identified during the inspection that would be considered significant safety
issues by the inspectors but had not been reported as such by the sponsor. The sponsor
was in the process of updating Australian Reference Safety Information in relation to these
issues but had not yet notified the TGA:
The EMA PRAC had recommended the addition of a contraindication and a precaution
to a sponsors medicine following an increased number of reports of cardiovascular
adverse events in Europe.
The FDA had published a safety alert for an entire class of medicines, mandating a
black box warning to warn of the risk of concomitant use with another commonly used
medicine which may increase the risk of a serious adverse event.
Sponsors MUST report all significant safety issues to the TGA within 72 hours of awareness
Pharmacovigilance Inspections: What we inspect
16
18. Reference Safety Information (RSI)
• We will assess a sponsor’s handling and maintenance of reference safety information,
including company core safety information, minimum product information, labels, PIs and
CMIs.
• We will specifically review:
– how you maintain any reference safety information to ensure product information is up-
to-date and in line with current scientific knowledge
– that required safety updates are promptly identified:
– Signal detection and evaluation outputs.
– Comparison with innovators.
– Competent Authority requests from the TGA and internationally.
– the process and timelines for implementation of new/updated reference safety
information, including internal distribution and external publication
Pharmacovigilance Inspections: What we inspect 17
19. Example Findings - RSI
1. Delays in updating RSI
– Delays in updating Australian Product Information (PI) documents were identified ranging from
8 months to three years after the sponsor had verified individual safety signals. It was
considered that such delays may pose a safety risk to the Australian public.
– In addition, delays in updating product Consumer Medicine Information (CMI) documents,
outside of the required two week timeframe were identified.
TGA expects that a variation to amend the PI will be submitted as soon as possible and
within 6 months from identification of any safety related issue, in order to ensure that the PI
is kept up to date with the current safety information. The 6 month timeline is consistent with
EU expectations and good pharmacovigilance practice.
The CMI document MUST be amended to reflect an amended PI within two weeks of
the date of the changed PI (Conditions of Registration).
Pharmacovigilance Inspections: What we inspect 18
20. Example Findings- RSI
2. Deficiencies in disseminating updated RSI
– It was identified that after approval of the variation by the TGA, the sponsors had not
updated public facing websites with the new PIs, therefore health professionals and
consumers would be accessing outdated PIs and CMIs.
– In addition the new PIs and CMIs had not been internally disseminated and personnel
may therefore be using outdated information to educate or respond to product enquires.
Processes and timeframes need to be in place to implement any of new/updated
reference safety information, including internal distribution and external publication of
these documents and correlating adjustment of minimum product information and
medicines information standard response where relevant.
Pharmacovigilance Inspections: What we inspect 19
21. PSURs/PBRERs and RMPs
• We will assess the preparation of Periodic Safety Update Reports/Periodic Benefit-Risk
Evaluation Reports (PSURs/PBRERs)
– completeness and accuracy of the data included, appropriateness of decisions concerning
data that are not included
– addressing safety topics, providing relevant analyses and actions
– timeliness of submissions
• We will also analyse the implementation, ongoing review and adherence to risk management
plans (RMPs) commitments and other safety commitments (this may include registries, enhanced
surveillance or traceability systems), where relevant
Pharmacovigilance Inspections: What we inspect 20
22. Example Findings - PSURs
1. Review of incomplete case data in PSUR
– The sponsor ran a PSUR ADR case report search in their database which captured all ADRs
received during the period of the report which were considered related to the product by the
reporter. However It was identified during an inspection that a sponsor had migrated
approximately 20000 case reports from Database X to Database Y. Due to an error, the fields
“unlikely” and “not reported” were mapped to the field “No” when the migration occurred and
these cases now appear as unrelated in the new database. Therefore the most recent PSUR
did not contain all cumulative cases previously assigned (in database X) a causality of “not
reported” or “unlikely”.
PSURs MUST be complete and contain accurate data, in order to meet the conditions
of registration
Pharmacovigilance Inspections: What we inspect 21
23. Example Findings - PSURs
2. Missing safety information in PSURs
– The PSUR reviewed for product Y lacked information on pregnancy and off label use.
– In addition the information provided on the signals reviewed and subsequently determined not
be signals was not sufficient to describe their assessment and there was no discussion of
safety findings reported in published literature.
– The PSUR submitted was therefore not considered a comprehensive review of the products
risk safety profile.
PSURs MUST be complete and contain accurate data, in order to meet the conditions
of registration.
Pharmacovigilance Inspections: What we inspect 22
24. Example Findings - RMPs
1. RMP non-compliance
– It was identified during an inspection that the RMP for a sponsor had an additional risk
minimization measure - to provide education material to HCPs and to patients to ensure
awareness of signs and symptoms suggestive for opportunistic infections. The company was
not able to provide evidence that such material was being provided to either HCPs, and there
was no documentation surrounding distribution. The sponsor could not prove they had
complied with their RMP commitment for this measure.
RMP commitments MUST be met as agreed with the TGA on product registration
Pharmacovigilance Inspections: What we inspect 23
25. Quality Management System (QMS)
• We will review:
– whether up-to-date and comprehensive policies and procedures are in place regarding
your role and responsibilities in relation to your pharmacovigilance system
– the accuracy, completeness and maintenance of records
– the quality and adequacy of your staff’s training, qualifications and experience
We will assess the Quality Management System in place to ensure the
suitability and consistency of your pharmacovigilance processes
Pharmacovigilance Inspections: What we inspect 24
26. Quality Management System (QMS)
• We will review (cont’d):
– the coverage of your pharmacovigilance quality system and your adherence to it, including
quality control and quality assurance processes
– the fitness for purpose of computerised systems
– the person responsible for fulfilling your pharmacovigilance obligations in Australia, their
roles and responsibilities (such as access to the quality system, performance metrics and audit
and inspection reports) and their ability to take action to improve compliance
– Record-keeping of safety data
Presentation title 25
27. Example Findings - QMS
1. Deficiency in company Standard Operating Procedures (SOPs)
– Pharmacovigilance SOPs reviewed did not reflect current PV processes and did not contain
timeframes for reporting of ADRs or significant safety issues.
– In addition the collection of special situation reports including exposure during pregnancy and
breastfeeding, lack of efficacy, overdose, abuse, off-label use, misuse, medication error or
occupational exposure were not documented in sponsor procedures. Failures to collect such
reports were identified during the inspection.
SOPs should document PV processes to ensure consistency and compliance with
recommendations and requirements.
Pharmacovigilance Inspections: What we inspect 26
28. Example Findings - QMS
2. Non-compliance in record-keeping requirements
– It was identified that safety information, including historic ADRs associated with a medicine
acquired recently by the sponsor was not available, having not been transferred to the new
sponsor of the medicines appropriately.
A sponsor MUST hold all data pertaining to the safety and pharmacovigilance
activities of the medicine indefinitely for the life of the medicine and for 10 years
(registered) or 5 years (listed) after its removal from the ARTG.
Pharmacovigilance Inspections: What we inspect 27
29. Contracts and Agreements
• We will asses whether contracts and agreements with all relevant third parties (i.e. any
external person or organisation who may market, distribute, manufacture, conduct research
or carry out any pharmacovigilance activities related to your medicine) reflect
pharmacovigilance responsibilities and activities, and are being adhered to.
• Contracts with external parties who may receive safety information for any of a sponsors
medicines should stipulate the pharmacovigilance roles and responsibilities of all parties to
ensure that all safety information is being collected and communicated to the sponsor
effectively.
• Training, if relevant, should also be provide to external parties to ensure they are aware of
their pharmacovigilance obligations
Pharmacovigilance Inspections: What we inspect 28
30. Example findings - Contracts and agreements
1. Lack of safety contracts and agreements
– Examples of external market research providers were identified who where undertaking
research for a sponsor, with no contracts in place specifying their pharmacovigilance
responsibilities and the requirement to collect of safety information including ADRs
– Additionally, no training on PV responsibilities had been given to these providers.
– The sponsor had no assurance that all safety data was being collected and collated and thus
reported in line with regulatory reporting requirements.
Sponsors should have detailed pharmacovigilance agreement in place with third party that
includes explicit roles and procedures such as what safety information is to be collected and
how it is to be exchanged, including timelines, reconciliation and reporting responsibilities.
External companies should be appropriately trained and overseen.
Pharmacovigilance Inspections: What we inspect 29
31. Example findings - Contracts and agreements
2. Deficiency in safety contracts
– Several serious adverse events were identified that had not been reported on review of medical
information enquiries. On further investigation it was noted that the contract with the external
medical information provider was deficient in its detail:
There was no timelines for the exchange of data
There was no provision for the exchange of safety data in special situations (e.g. pregnancy,
misuse, off-label use)
Reconciliation activities are not adequately described and were not being conducted
No training had been provided to the contracted party to ensure they are aware of their PV
obligations
contracts and agreements with all relevant third parties should ensure that all safety
information is being collected and communicated to the sponsor effectively and reflect their
pharmacovigilance responsibilities and activities.
Pharmacovigilance Inspections: What we inspect 30
32. How to prepare for an inspection (a few pointers)
• Ensure you have nominated an Australian contact person for pharmacovigilance to the
TGA
• Ensure an appropriate quality management system is in place as a basis for an effective
PV system - including up-to-date SOPs, training and auditing programs
• Ensure all potential sources are being monitored for ADRs - including but not limited to
marketing programs, medicines information, product quality complaints, literature, company
sponsored internet sites and social media, post market clinical trials etc.
• Ensure you have a robust and secure system to collect, process and analyse medicine
safety data
• Ensure all serious Australian ADRs and significant safety issues are being reported to
the TGA within required timeframes
• Ensure there are procedures in place to receive notification of significant safety issues
from global counterparts
31
33. How to prepare for an inspection (a few
pointers)
• Ensure ongoing monitoring for safety signals is occurring on a regular basis
• Ensure you have safety agreements in place with required partners and contractors
• Ensure PSURs are complete and submitted on time if required
• Ensure any RMP commitments are being met
• Ensure the Australian person responsible for pharmacovigilance has appropriate
oversight of the system
• Ensure CAPA from any previous pharmacovigilance inspection has been completed
• Ensure all safety data is being retained indefinitely for the life of the product and for 10
years (registered) 5 years (listed) after its removal from the ARTG
Pharmacovigilance Inspections: What we inspect 32