This document discusses SUPAC (Scale Up and Post Approval Changes) guidelines and post-marketing surveillance. It provides details on SUPAC guidelines for immediate release solid oral dosage forms, including definitions of level 1, 2, and 3 changes for components/composition, site changes, batch size changes, and manufacturing process/equipment changes. It also discusses post-marketing surveillance, including the importance of monitoring drug safety after approval and examples of adverse events discovered only after drugs entered the market like Practolol and Thalidomide.
The document discusses the Investigational Medicinal Product Dossier (IMPD), which contains information about investigational drugs used in clinical trials in the European Union. It provides guidance on the content and legal basis of full and simplified IMPDs. A full IMPD is required for new drugs and includes data on the drug substance, manufacturing, quality controls, preclinical testing, and clinical protocols. A simplified IMPD can be submitted if the drug is already approved or similar information was previously reviewed. The IMPD process aims to standardize information submitted across EU member states for clinical trial authorization.
This document discusses post-approval regulatory affairs for drugs and medical devices. It explains that the FDA may require post-approval studies to ensure continued safety and effectiveness of approved products. Sponsors must comply with post-approval requirements or approval can be withdrawn. Post-approval changes are categorized as major, moderate, or minor depending on their potential effect. Major changes generally require prior approval from the FDA, while moderate changes require notification 30 days before distribution. Minor changes are reported annually. The document provides recommendations for common post-approval changes including components, manufacturing sites, processes, specifications, packaging, and labeling.
The document discusses drug product performance evaluation through in vitro dissolution testing. It provides details on factors that influence drug dissolution like drug substance properties, formulation composition, manufacturing process, and dissolution test conditions. The key goals of in vitro drug product testing are to characterize drug potency and release rate from oral dosage forms, provide information for formulation development, and ensure quality, comparability and stability over time. Common tests include disintegration testing and dissolution testing using apparatus specified in pharmacopeias to simulate gastrointestinal conditions. The results of in vitro testing aid product development and assessment of shelf-life and quality.
The document discusses the process for submitting an Investigational New Drug (IND) application to regulatory agencies like the FDA in the US and DCGI in India to obtain approval to test new drugs in human clinical trials. It explains that an IND application includes preclinical data from animal and lab studies to show safety for testing in humans. It also outlines the types of IND applications and details on protocols, manufacturing, and other information required to be submitted. The application process and timeline for review within 30 days by the FDA is also summarized.
The document discusses the role of Chemistry, Manufacturing, and Controls (CMC) regulatory affairs in managing post-approval changes to drugs. It explains that CMC regulatory affairs professionals work to assure drug quality from clinical trials through marketing by determining the appropriate regulatory submissions for manufacturing changes. They assess proposed changes and provide initial and final responses on whether a prior approval supplement, changes-being-effected supplement, annual report, or no submission is required. This change control process involves interactions with manufacturing and consideration of regulations, guidance, and potential effects on drug quality and equivalence.
The document discusses the requirements and contents of an Investigational Medicinal Product Dossier (IMPD) which provides information on the quality, manufacture, and control of investigational medical products (IMPs) used in clinical trials in the European Union. An IMPD includes summaries of nonclinical and clinical data and is required for authorization to perform clinical trials in EU member states. It must provide an overall risk-benefit assessment of the proposed trial based on nonclinical and clinical analyses. A simplified IMPD may be acceptable in some cases such as if the IMP is already authorized. The IMPD covers quality data, nonclinical pharmacology and toxicology data, previous clinical experience, and an overall risk assessment.
The document discusses the Investigational Medicinal Product Dossier (IMPD), which contains information about investigational drugs used in clinical trials in the European Union. It provides guidance on the content and legal basis of full and simplified IMPDs. A full IMPD is required for new drugs and includes data on the drug substance, manufacturing, quality controls, preclinical testing, and clinical protocols. A simplified IMPD can be submitted if the drug is already approved or similar information was previously reviewed. The IMPD process aims to standardize information submitted across EU member states for clinical trial authorization.
This document discusses post-approval regulatory affairs for drugs and medical devices. It explains that the FDA may require post-approval studies to ensure continued safety and effectiveness of approved products. Sponsors must comply with post-approval requirements or approval can be withdrawn. Post-approval changes are categorized as major, moderate, or minor depending on their potential effect. Major changes generally require prior approval from the FDA, while moderate changes require notification 30 days before distribution. Minor changes are reported annually. The document provides recommendations for common post-approval changes including components, manufacturing sites, processes, specifications, packaging, and labeling.
The document discusses drug product performance evaluation through in vitro dissolution testing. It provides details on factors that influence drug dissolution like drug substance properties, formulation composition, manufacturing process, and dissolution test conditions. The key goals of in vitro drug product testing are to characterize drug potency and release rate from oral dosage forms, provide information for formulation development, and ensure quality, comparability and stability over time. Common tests include disintegration testing and dissolution testing using apparatus specified in pharmacopeias to simulate gastrointestinal conditions. The results of in vitro testing aid product development and assessment of shelf-life and quality.
The document discusses the process for submitting an Investigational New Drug (IND) application to regulatory agencies like the FDA in the US and DCGI in India to obtain approval to test new drugs in human clinical trials. It explains that an IND application includes preclinical data from animal and lab studies to show safety for testing in humans. It also outlines the types of IND applications and details on protocols, manufacturing, and other information required to be submitted. The application process and timeline for review within 30 days by the FDA is also summarized.
The document discusses the role of Chemistry, Manufacturing, and Controls (CMC) regulatory affairs in managing post-approval changes to drugs. It explains that CMC regulatory affairs professionals work to assure drug quality from clinical trials through marketing by determining the appropriate regulatory submissions for manufacturing changes. They assess proposed changes and provide initial and final responses on whether a prior approval supplement, changes-being-effected supplement, annual report, or no submission is required. This change control process involves interactions with manufacturing and consideration of regulations, guidance, and potential effects on drug quality and equivalence.
The document discusses the requirements and contents of an Investigational Medicinal Product Dossier (IMPD) which provides information on the quality, manufacture, and control of investigational medical products (IMPs) used in clinical trials in the European Union. An IMPD includes summaries of nonclinical and clinical data and is required for authorization to perform clinical trials in EU member states. It must provide an overall risk-benefit assessment of the proposed trial based on nonclinical and clinical analyses. A simplified IMPD may be acceptable in some cases such as if the IMP is already authorized. The IMPD covers quality data, nonclinical pharmacology and toxicology data, previous clinical experience, and an overall risk assessment.
The document discusses the abbreviated new drug application (ANDA) regulatory approval process for generic drugs in the United States. It describes the key steps and reviewing bodies involved, including filing review by the Regulatory Support Branch, coordination of reviews by bioequivalence, chemistry, and labeling teams, and final approval. The primary goal of the ANDA process is to determine if the generic drug is bioequivalent to the reference listed drug while ensuring safety and manufacturing quality standards are met.
This document provides guidelines for scale-up and post-approval changes (SUPAC) as outlined by the FDA. It discusses SUPAC documents, levels of changes, and recommendations for changes to components and composition, manufacturing site, batch size, and manufacturing process and equipment. The guidelines provide recommendations for submitting documentation to the FDA for level 1, 2, and 3 changes to ensure quality and performance of drug products after approval. It notes some limitations of the SUPAC guidelines, including that they have not been updated since 1995/1997 and do not cover all potential changes.
Code of federal regulations {cfr} in pharmaceuticalArabinda Changmai
The Code of Federal Regulations (CFR) contains the general and permanent rules published by the executive departments and agencies of the federal government of the United States. Title 21 of the CFR governs food and drugs and is divided into three chapters addressing the Food and Drug Administration, Drug Enforcement Administration, and Office of National Drug Control Policy. Chapter I includes regulations for clinical trials, Good Laboratory Practices, food labeling, and current good manufacturing practices for pharmaceuticals. Title 21 provides the framework for approval of new drugs and biologics in the United States.
NDA and ANDA regulatory approval processNilesh Gawade
This document discusses the regulatory approval processes for new drug applications (NDAs) and abbreviated new drug applications (ANDAs) in the United States. It explains that an NDA contains extensive clinical and non-clinical data submitted by an innovator company to obtain approval for a new drug. An ANDA contains similar data to demonstrate equivalence to an already approved drug for generic versions after patents have expired. The document provides details on the requirements, review processes, and certification pathways for both NDAs and ANDAs.
This presentation includes the detail information about the physics of tablet compression and compaction, Compression, Effect of friction, distribution of forces, compaction profiles,solubility.
The Common Technical Document (CTD) is a standardized format for new drug applications agreed upon by international regulatory agencies. It has 5 modules covering administrative information, summaries, quality, non-clinical studies, and clinical studies. The electronic CTD (eCTD) is the electronic version that regulatory agencies now require. eCTD submissions have granular documents linked by XML and allow for increased transparency, ease of review, and benefits like reduced submission time and costs.
NDA and ANDA regulatory approval processJagrutiKale1
This document provides an overview of New Drug Applications (NDA) and Abbreviated New Drug Applications (ANDA). It discusses the requirements and process for submitting both full NDAs for new drugs and ANDAs for generic drugs. The key aspects covered are the format and content of NDA submissions, the review process by the FDA, and the different types of approval letters. It also explains the goals and requirements of the ANDA pathway for generic drugs established by the Hatch-Waxman Act, including the necessary patent certifications and the review process.
Regulatory requirements for API and BiologicsSimranDhiman12
The document discusses regulatory requirements for active pharmaceutical ingredients (APIs) and biologics. It provides an overview of regulatory guidelines for APIs, including requirements for registration of APIs with agencies like the FDA. It also describes regulatory filings like Drug Master Files (DMFs) that are submitted to provide confidential manufacturing information to support applications. Requirements for biologics are also briefly covered, noting they are complex molecules produced through biotechnology.
Scale up and post approval changes(supac)bdvfgbdhg
The document discusses guidelines for post-approval changes to drug products, including changes to batch size, manufacturing sites and equipment, and composition. It outlines 3 levels of changes - minor, moderate, and major - and provides recommendations for documentation and regulatory filings required for each level of change. Major changes, such as a new manufacturing site or changes in the amount of active ingredients, require more extensive documentation including stability testing and possibly bioequivalence studies.
Validation (intro, scope, merits, ich, who guidelines)PRAJAKTASAWANT33
This document summarizes a presentation on validation given by Prajakta Sawant, a first year M.Pharm student at Alard College of Pharmacy in Pune, India. The presentation covered the need for validation, types of validation including process, cleaning, equipment and analytical method validation. It discussed validation concepts such as the validation master plan, documentation, and ICH and WHO guidelines. The goal of validation is to ensure consistent production of pharmaceuticals meeting quality standards.
The document discusses the regulatory requirements for approval of APIs, biologics, novel drugs, and NDAs. It covers topics such as:
- APIs must be approved through a Drug Master File (DMF) in the US or Active Substance Master File (ASMF) in Europe. A DMF contains confidential manufacturing and quality information for review.
- Biological products like blood components require registration with the FDA and annual listing of manufactured products.
- Approval of novel drugs involves analyzing the medical need and risks/benefits based on clinical trial data, with strategies to manage identified risks.
- The FDA uses various pathways like Fast Track, Breakthrough Therapy, and Accelerated Approval to
The document discusses regulatory requirements for non-clinical drug development, including guidelines from the European Medicines Agency. It describes the types of non-clinical studies done in silico, in vitro, and in vivo to determine efficacy, safety, delivery methods, and manufacturing viability before clinical trials. Key submissions to regulators include the Investigational New Drug Application, New Drug Application, and Abbreviated New Drug Application.
This document discusses various types of documentation required in the pharmaceutical industry, including master formula records (MFR), drug master files (DMF), and generic drug development. It defines MFRs as approved master documents that describe the full manufacturing process for a specific batch size. It provides details on the content required for MFRs based on guidelines from WHO, Health Canada, and the US CFR. It also discusses the purpose and types of DMFs submitted to the FDA, including Type 1 for manufacturing facilities, Type 2 for drug substances/products, and others. Finally, it briefly mentions the Hatch-Waxman Act as it relates to generic drug development.
Documentation in pharaceutical industryJayeshRajput7
documentation in pharmaceutical industry, master formula record (MFR), DMF (drug master file), distribution records, generic drugs product development, hatch waxman act, CFR (code of federal regulation), drug product performance, in vitro ANDA regulatory approval process, NDA approval process, BE and drug product assessment, in-vivo scale up process approval changes, post marketing surveillance, outsourcing BA and BE to CRO (contract research organisation), Regulatory requireents for product approval, API, Biologics, Novel therapies obtaining NDA, ANDA for generic drug ways and means of US registration for foreign drugs.
This document discusses the requirements and contents of an Investigator's Brochure (IB) and Investigational Medicinal Product Dossier (IMPD). The IB is intended to inform investigators about the investigational product and facilitate their understanding of the clinical trial. It includes summaries of nonclinical and clinical data, adverse reactions, and guidance for investigators. The IMPD provides the basis for approval of clinical trials in the EU. It includes quality, nonclinical, clinical, and risk-benefit data for the investigational product as well as other required documents and forms. Both the IB and IMPD aim to ensure the safety of clinical trials and protection of human subjects.
This document summarizes the Hatch-Waxman Act, which established the modern system for regulating generic drugs in the US. The Act aims to make generic drugs more accessible by streamlining the approval process for generics while also providing incentives to brand name drug companies. It allows generics to challenge drug patents and grants exclusivity periods to first generic applicants and brand name drugs for new chemical entities. The Orange Book lists approved drug products and related patent information.
This document discusses mechanically activated drug delivery devices, specifically metered dose inhalers, dry powder inhalers, and nebulizers. Metered dose inhalers precisely deliver medication in aerosol form via inhalation. Dry powder inhalers use breath activation to deliver dry powder medication. Nebulizers convert liquid medication into an inhalable mist using compressed air or ultrasonic power. Each device type has advantages like precision or not requiring compressed gas, but also disadvantages such as potential waste or lower efficiency.
The document discusses scale up and post approval changes (SUPAC) for generic drug applications. It defines SUPAC as changes made to a drug's composition, manufacturing process, equipment, or site after approval. The FDA modernization act of 1997 established four categories for reporting post-approval changes - prior approval, 30-day notice, immediate implementation, and annual report. The FDA has issued SUPAC guidance documents that describe what types of changes require validation studies or prior approval versus those allowable without notice. Post-marketing surveillance is also required to monitor adverse drug events after approval.
This document provides an overview of SUPAC (Scale-Up and Post-Approval Changes), which are FDA-recommended testing and filing actions for changes to manufacturing processes of approved drug products. It discusses the current finalized SUPAC guidelines for immediate-release solid oral dosage forms and nonsterile semisolid dosage forms. The document also proposes additional SUPAC documents for other dosage forms. Changes are categorized into three levels depending on their expected impact, with Level 1 changes having little impact and Level 3 changes requiring bioequivalence testing. The guidelines provide recommendations for chemistry, dissolution, and bioequivalence testing as well as filing documentation required for each level of change.
ATUL CHAUDHARY (STUDENTS)
DEPARTMENT OF PHARMACEUTICS
ISF COLLEGE OF PHARMACY, GHALKALAN, MOGA , PUNJAB
THIS SLIDE IS THE BEST SLIDE FOR PREPARING THE TOPIC SUPAC OF REGULATORY AFFAIRS SUBJECT
SLIDE ARE SPECIALLY DESIGN FOR MASTER STUDENTS AS WELL AS GRADUATION STUDENTS
The document discusses the abbreviated new drug application (ANDA) regulatory approval process for generic drugs in the United States. It describes the key steps and reviewing bodies involved, including filing review by the Regulatory Support Branch, coordination of reviews by bioequivalence, chemistry, and labeling teams, and final approval. The primary goal of the ANDA process is to determine if the generic drug is bioequivalent to the reference listed drug while ensuring safety and manufacturing quality standards are met.
This document provides guidelines for scale-up and post-approval changes (SUPAC) as outlined by the FDA. It discusses SUPAC documents, levels of changes, and recommendations for changes to components and composition, manufacturing site, batch size, and manufacturing process and equipment. The guidelines provide recommendations for submitting documentation to the FDA for level 1, 2, and 3 changes to ensure quality and performance of drug products after approval. It notes some limitations of the SUPAC guidelines, including that they have not been updated since 1995/1997 and do not cover all potential changes.
Code of federal regulations {cfr} in pharmaceuticalArabinda Changmai
The Code of Federal Regulations (CFR) contains the general and permanent rules published by the executive departments and agencies of the federal government of the United States. Title 21 of the CFR governs food and drugs and is divided into three chapters addressing the Food and Drug Administration, Drug Enforcement Administration, and Office of National Drug Control Policy. Chapter I includes regulations for clinical trials, Good Laboratory Practices, food labeling, and current good manufacturing practices for pharmaceuticals. Title 21 provides the framework for approval of new drugs and biologics in the United States.
NDA and ANDA regulatory approval processNilesh Gawade
This document discusses the regulatory approval processes for new drug applications (NDAs) and abbreviated new drug applications (ANDAs) in the United States. It explains that an NDA contains extensive clinical and non-clinical data submitted by an innovator company to obtain approval for a new drug. An ANDA contains similar data to demonstrate equivalence to an already approved drug for generic versions after patents have expired. The document provides details on the requirements, review processes, and certification pathways for both NDAs and ANDAs.
This presentation includes the detail information about the physics of tablet compression and compaction, Compression, Effect of friction, distribution of forces, compaction profiles,solubility.
The Common Technical Document (CTD) is a standardized format for new drug applications agreed upon by international regulatory agencies. It has 5 modules covering administrative information, summaries, quality, non-clinical studies, and clinical studies. The electronic CTD (eCTD) is the electronic version that regulatory agencies now require. eCTD submissions have granular documents linked by XML and allow for increased transparency, ease of review, and benefits like reduced submission time and costs.
NDA and ANDA regulatory approval processJagrutiKale1
This document provides an overview of New Drug Applications (NDA) and Abbreviated New Drug Applications (ANDA). It discusses the requirements and process for submitting both full NDAs for new drugs and ANDAs for generic drugs. The key aspects covered are the format and content of NDA submissions, the review process by the FDA, and the different types of approval letters. It also explains the goals and requirements of the ANDA pathway for generic drugs established by the Hatch-Waxman Act, including the necessary patent certifications and the review process.
Regulatory requirements for API and BiologicsSimranDhiman12
The document discusses regulatory requirements for active pharmaceutical ingredients (APIs) and biologics. It provides an overview of regulatory guidelines for APIs, including requirements for registration of APIs with agencies like the FDA. It also describes regulatory filings like Drug Master Files (DMFs) that are submitted to provide confidential manufacturing information to support applications. Requirements for biologics are also briefly covered, noting they are complex molecules produced through biotechnology.
Scale up and post approval changes(supac)bdvfgbdhg
The document discusses guidelines for post-approval changes to drug products, including changes to batch size, manufacturing sites and equipment, and composition. It outlines 3 levels of changes - minor, moderate, and major - and provides recommendations for documentation and regulatory filings required for each level of change. Major changes, such as a new manufacturing site or changes in the amount of active ingredients, require more extensive documentation including stability testing and possibly bioequivalence studies.
Validation (intro, scope, merits, ich, who guidelines)PRAJAKTASAWANT33
This document summarizes a presentation on validation given by Prajakta Sawant, a first year M.Pharm student at Alard College of Pharmacy in Pune, India. The presentation covered the need for validation, types of validation including process, cleaning, equipment and analytical method validation. It discussed validation concepts such as the validation master plan, documentation, and ICH and WHO guidelines. The goal of validation is to ensure consistent production of pharmaceuticals meeting quality standards.
The document discusses the regulatory requirements for approval of APIs, biologics, novel drugs, and NDAs. It covers topics such as:
- APIs must be approved through a Drug Master File (DMF) in the US or Active Substance Master File (ASMF) in Europe. A DMF contains confidential manufacturing and quality information for review.
- Biological products like blood components require registration with the FDA and annual listing of manufactured products.
- Approval of novel drugs involves analyzing the medical need and risks/benefits based on clinical trial data, with strategies to manage identified risks.
- The FDA uses various pathways like Fast Track, Breakthrough Therapy, and Accelerated Approval to
The document discusses regulatory requirements for non-clinical drug development, including guidelines from the European Medicines Agency. It describes the types of non-clinical studies done in silico, in vitro, and in vivo to determine efficacy, safety, delivery methods, and manufacturing viability before clinical trials. Key submissions to regulators include the Investigational New Drug Application, New Drug Application, and Abbreviated New Drug Application.
This document discusses various types of documentation required in the pharmaceutical industry, including master formula records (MFR), drug master files (DMF), and generic drug development. It defines MFRs as approved master documents that describe the full manufacturing process for a specific batch size. It provides details on the content required for MFRs based on guidelines from WHO, Health Canada, and the US CFR. It also discusses the purpose and types of DMFs submitted to the FDA, including Type 1 for manufacturing facilities, Type 2 for drug substances/products, and others. Finally, it briefly mentions the Hatch-Waxman Act as it relates to generic drug development.
Documentation in pharaceutical industryJayeshRajput7
documentation in pharmaceutical industry, master formula record (MFR), DMF (drug master file), distribution records, generic drugs product development, hatch waxman act, CFR (code of federal regulation), drug product performance, in vitro ANDA regulatory approval process, NDA approval process, BE and drug product assessment, in-vivo scale up process approval changes, post marketing surveillance, outsourcing BA and BE to CRO (contract research organisation), Regulatory requireents for product approval, API, Biologics, Novel therapies obtaining NDA, ANDA for generic drug ways and means of US registration for foreign drugs.
This document discusses the requirements and contents of an Investigator's Brochure (IB) and Investigational Medicinal Product Dossier (IMPD). The IB is intended to inform investigators about the investigational product and facilitate their understanding of the clinical trial. It includes summaries of nonclinical and clinical data, adverse reactions, and guidance for investigators. The IMPD provides the basis for approval of clinical trials in the EU. It includes quality, nonclinical, clinical, and risk-benefit data for the investigational product as well as other required documents and forms. Both the IB and IMPD aim to ensure the safety of clinical trials and protection of human subjects.
This document summarizes the Hatch-Waxman Act, which established the modern system for regulating generic drugs in the US. The Act aims to make generic drugs more accessible by streamlining the approval process for generics while also providing incentives to brand name drug companies. It allows generics to challenge drug patents and grants exclusivity periods to first generic applicants and brand name drugs for new chemical entities. The Orange Book lists approved drug products and related patent information.
This document discusses mechanically activated drug delivery devices, specifically metered dose inhalers, dry powder inhalers, and nebulizers. Metered dose inhalers precisely deliver medication in aerosol form via inhalation. Dry powder inhalers use breath activation to deliver dry powder medication. Nebulizers convert liquid medication into an inhalable mist using compressed air or ultrasonic power. Each device type has advantages like precision or not requiring compressed gas, but also disadvantages such as potential waste or lower efficiency.
The document discusses scale up and post approval changes (SUPAC) for generic drug applications. It defines SUPAC as changes made to a drug's composition, manufacturing process, equipment, or site after approval. The FDA modernization act of 1997 established four categories for reporting post-approval changes - prior approval, 30-day notice, immediate implementation, and annual report. The FDA has issued SUPAC guidance documents that describe what types of changes require validation studies or prior approval versus those allowable without notice. Post-marketing surveillance is also required to monitor adverse drug events after approval.
This document provides an overview of SUPAC (Scale-Up and Post-Approval Changes), which are FDA-recommended testing and filing actions for changes to manufacturing processes of approved drug products. It discusses the current finalized SUPAC guidelines for immediate-release solid oral dosage forms and nonsterile semisolid dosage forms. The document also proposes additional SUPAC documents for other dosage forms. Changes are categorized into three levels depending on their expected impact, with Level 1 changes having little impact and Level 3 changes requiring bioequivalence testing. The guidelines provide recommendations for chemistry, dissolution, and bioequivalence testing as well as filing documentation required for each level of change.
ATUL CHAUDHARY (STUDENTS)
DEPARTMENT OF PHARMACEUTICS
ISF COLLEGE OF PHARMACY, GHALKALAN, MOGA , PUNJAB
THIS SLIDE IS THE BEST SLIDE FOR PREPARING THE TOPIC SUPAC OF REGULATORY AFFAIRS SUBJECT
SLIDE ARE SPECIALLY DESIGN FOR MASTER STUDENTS AS WELL AS GRADUATION STUDENTS
The document discusses SUPAC (Scale-Up and Post-Approval Changes) guidances issued by the FDA for pharmaceutical manufacturing process changes. It provides an overview of existing SUPAC guidances for immediate-release solid oral dosage forms and nonsterile semisolid dosage forms. The document also describes three levels of changes - Level 1, Level 2, and Level 3 - with varying test documentation and filing requirements based on the type and extent of manufacturing changes. Guidance documents for other dosage forms are still under development.
This document discusses post-approval changes to drug products, including changes to batch size, manufacturing sites and equipment, and components/composition. It provides guidance on categorizing the level of changes (Level 1-3) and the associated testing and documentation required for submission to regulatory agencies. Level 1 changes have minimal impact while Level 3 changes are more significant and may require bioequivalence studies. The focus is on allowing certain post-approval changes with limited testing to facilitate drug product improvements and manufacturing changes.
This document outlines the FDA's SUPAC guidance for immediate release solid oral dosage forms. It defines three levels of changes to approved drug products: Level 1 changes require annual reporting, Level 2 prior approval or changes being effected supplements, and Level 3 prior approval supplements. The guidance provides recommendations for chemistry, dissolution, bioequivalence testing and documentation required for component/composition changes at each level. It aims to advise pharmaceutical firms on testing and regulatory filings needed when modifying approved manufacturing processes.
This document provides guidance for changes to modified release oral formulations during the post-approval period. It defines three levels of changes - minor (Level I), moderate (Level II), and major (Level III) - and provides recommendations for chemistry, dissolution, stability, and bioequivalence testing for each level of change. The guidance covers changes to components/composition, manufacturing site, batch size, manufacturing equipment/process, and provides definitions and examples for each type and level of change.
The SUPAC guidelines provide recommendations for post-approval changes to NDAs and ANDAs, including changes to components, manufacturing processes, batch size, and manufacturing sites. The guidelines classify changes as minor (Level 1), moderate (Level 2), or major (Level 3) based on their potential effect on product quality and performance. Level 1 changes require chemistry and dissolution documentation, while Level 2 changes may also require in vivo bioequivalence testing or stability testing. Level 3 changes always require bioequivalence testing and prior approval before implementation. The guidelines aim to streamline regulatory processes for industry while ensuring safety and effectiveness.
This document summarizes guidance on scale up and post-approval changes for pharmaceutical products. It outlines 3 levels for various changes based on their potential impact. Level 1 changes are unlikely to impact quality or performance. Level 2 changes may significantly impact quality or performance. Level 3 changes require full bioequivalence testing. The guidance covers changes to components, manufacturing site, batch size, equipment, and processes. Documentation requirements increase based on the level of change, ranging from chemistry testing to full bioequivalence studies.
This document summarizes guidance on scale up and post-approval changes for pharmaceutical products. It outlines 3 levels for various changes based on their potential impact. Level 1 changes are unlikely to impact quality or performance. Level 2 changes may significantly impact quality or performance. Level 3 changes require full bioequivalence testing. The guidance covers changes to components, manufacturing site, batch size, equipment, and processes. Documentation requirements increase based on the level of change from annual reports to chemistry testing and bioequivalence studies.
The document provides guidance on post-approval changes to immediate release solid oral dosage forms. It defines three levels (I, II, III) of changes based on their potential impact. Level I changes are minor, Level II are moderate, and Level III are major. It provides recommendations for chemistry, manufacturing, dissolution and bioequivalence testing for components/composition, site, batch size and manufacturing changes. Changes are supported by prior approval supplements, changes being effected supplements or annual reports with stability data as appropriate to the level of change.
The document discusses Scale-Up and Post Approval Changes (SUPAC) guidelines established by the FDA. It defines SUPAC as changes made to the manufacturing process, equipment, batch size, or site after a drug has received FDA approval. The guidelines establish three levels of changes with varying documentation and reporting requirements depending on the level of change. Level 1 changes have the least requirements while level 3 changes require extensive testing data and may need pre-approval before implementation.
SUPAC, BACPAC, Post Marketing SurveillanceMANIKANDAN V
This document discusses various guidelines related to product development and technology transfer in the pharmaceutical industry. It covers SUPAC, BACPAC, and post-marketing surveillance. SUPAC provides guidance for scale-up and post-approval changes, categorizing changes into different levels based on their potential impact. BACPAC guidance addresses post-approval changes for bulk active pharmaceutical ingredients. Post-marketing surveillance involves monitoring adverse drug events after approval to ensure ongoing safety and effectiveness.
Introduction to Scale up and post approval changes.
SUPAC Guidelines :
1.In component and composition
2.The site of manufacture
3.The scale up batch of manufacture
4.The manufacturing( equipment and process)
This document discusses granulation processes and quality management in the pharmaceutical industry. It covers topics like cGMP, SUPAC guidelines for post-approval changes, validation of granulation equipment and processes, and questionnaires for auditing granulation. The key points are that granulation is a critical manufacturing step that must be validated; SUPAC provides guidance on composition, batch size, site and equipment changes; and validation involves qualifying equipment and demonstrating consistent product quality through processes.
Chap 1_ SUPAC mpharm quality assurance semester 2christinajohn24
This document discusses the SUPAC (Scale Up and Post Approval Changes) guidance which provides recommendations for sponsors making changes to approved drug applications. It defines three levels of changes - minor, moderate, and major - and recommends tests for each level. Minor changes require limited testing while major changes require more extensive testing such as bioequivalence studies. The guidance provides specific recommendations for changes to components/composition, manufacturing site, batch size (scale up/down), and manufacturing process/equipment. It aims to help sponsors anticipate and evaluate the impact of changes to ensure drug quality is maintained.
(SUPAC- Part 2) (SCALE UP AND POST APPROVAL CHANGES)kavita bahmani
This document provides information on scale-up and post-approval changes for batch size and manufacturing processes. It defines two levels for changes in batch size - level 1 as a scale up of up to 10 times the pilot/bio-batch size, and level 2 as greater than 10 times. For level 1 changes, notification in an annual report is sufficient, while level 2 requires submission of additional stability data. Two levels are also defined for equipment changes - level 1 as alternative equipment of the same design, and level 2 as a different design. Level 1 equipment changes require stability data submission in an annual report, while level 2 requires submission of additional dissolution and stability data in a prior approval supplement.
The document discusses Scale-Up and Post-Approval Changes (SUPAC) guidelines from regulatory agencies like the FDA, MHRA, TGA, and WHO. It outlines the SUPAC classification system which defines three levels of changes - minor, moderate, and major - based on their potential impact. The levels provide recommendations for chemistry, manufacturing, and controls documentation and testing required for approval. The guidelines cover post-approval changes to components, manufacturing site, batch size, equipment, and processes. However, the document notes some limitations of SUPAC like not being recently updated and not directly addressing multiple or modified changes.
This document provides guidelines for post-approval changes to modified release solid oral dosage forms. It outlines 3 levels of changes based on their potential to affect drug release and product performance. Level I changes have minimal effect and only require documentation in annual reports. Level II changes may impact drug release and dissolution testing is required, along with submissions of change supplements. Level III changes are expected to significantly affect drug release and require bioequivalence studies and prior approval supplements.
IN VIVO AND SCALE-UP PROCESS APPROVAL CHANGES.pptxPawanDhamala1
The document discusses in vivo and scale-up process approval changes. It defines in vivo as experiments done on living organisms. SUPAC guidelines provide regulatory guidance for scale-up batches and post-approval changes. Changes are categorized as minor, major, or moderate. Level 1 changes have minimal impact while Level 3 changes likely impact quality. Requirements include chemistry documentation, dissolution testing, and bioequivalence studies depending on the level of change. Site, batch size, equipment, and process changes are also discussed along with associated testing requirements.
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The biomechanics of running involves the study of the mechanical principles underlying running movements. It includes the analysis of the running gait cycle, which consists of the stance phase (foot contact to push-off) and the swing phase (foot lift-off to next contact). Key aspects include kinematics (joint angles and movements, stride length and frequency) and kinetics (forces involved in running, including ground reaction and muscle forces). Understanding these factors helps in improving running performance, optimizing technique, and preventing injuries.
PGx Analysis in VarSeq: A User’s PerspectiveGolden Helix
Since our release of the PGx capabilities in VarSeq, we’ve had a few months to gather some insights from various use cases. Some users approach PGx workflows by means of array genotyping or what seems to be a growing trend of adding the star allele calling to the existing NGS pipeline for whole genome data. Luckily, both approaches are supported with the VarSeq software platform. The genotyping method being used will also dictate what the scope of the tertiary analysis will be. For example, are your PGx reports a standalone pipeline or would your lab’s goal be to handle a dual-purpose workflow and report on PGx + Diagnostic findings.
The purpose of this webcast is to:
Discuss and demonstrate the approaches with array and NGS genotyping methods for star allele calling to prep for downstream analysis.
Following genotyping, explore alternative tertiary workflow concepts in VarSeq to handle PGx reporting.
Moreover, we will include insights users will need to consider when validating their PGx workflow for all possible star alleles and options you have for automating your PGx analysis for large number of samples. Please join us for a session dedicated to the application of star allele genotyping and subsequent PGx workflows in our VarSeq software.
Travel Clinic Cardiff: Health Advice for International TravelersNX Healthcare
Travel Clinic Cardiff offers comprehensive travel health services, including vaccinations, travel advice, and preventive care for international travelers. Our expert team ensures you are well-prepared and protected for your journey, providing personalized consultations tailored to your destination. Conveniently located in Cardiff, we help you travel with confidence and peace of mind. Visit us: www.nxhealthcare.co.uk
The Children are very vulnerable to get affected with respiratory disease.
In our country, the respiratory Disease conditions are consider as major cause for mortality and Morbidity in Child.
The skin is the largest organ and its health plays a vital role among the other sense organs. The skin concerns like acne breakout, psoriasis, or anything similar along the lines, finding a qualified and experienced dermatologist becomes paramount.
Are you looking for a long-lasting solution to your missing tooth?
Dental implants are the most common type of method for replacing the missing tooth. Unlike dentures or bridges, implants are surgically placed in the jawbone. In layman’s terms, a dental implant is similar to the natural root of the tooth. It offers a stable foundation for the artificial tooth giving it the look, feel, and function similar to the natural tooth.
How to Control Your Asthma Tips by gokuldas hospital.Gokuldas Hospital
Respiratory issues like asthma are the most sensitive issue that is affecting millions worldwide. It hampers the daily activities leaving the body tired and breathless.
The key to a good grip on asthma is proper knowledge and management strategies. Understanding the patient-specific symptoms and carving out an effective treatment likewise is the best way to keep asthma under control.
Giloy in Ayurveda - Classical Categorization and SynonymsPlanet Ayurveda
Giloy, also known as Guduchi or Amrita in classical Ayurvedic texts, is a revered herb renowned for its myriad health benefits. It is categorized as a Rasayana, meaning it has rejuvenating properties that enhance vitality and longevity. Giloy is celebrated for its ability to boost the immune system, detoxify the body, and promote overall wellness. Its anti-inflammatory, antipyretic, and antioxidant properties make it a staple in managing conditions like fever, diabetes, and stress. The versatility and efficacy of Giloy in supporting health naturally highlight its importance in Ayurveda. At Planet Ayurveda, we provide a comprehensive range of health services and 100% herbal supplements that harness the power of natural ingredients like Giloy. Our products are globally available and affordable, ensuring that everyone can benefit from the ancient wisdom of Ayurveda. If you or your loved ones are dealing with health issues, contact Planet Ayurveda at 01725214040 to book an online video consultation with our professional doctors. Let us help you achieve optimal health and wellness naturally.
5-hydroxytryptamine or 5-HT or Serotonin is a neurotransmitter that serves a range of roles in the human body. It is sometimes referred to as the happy chemical since it promotes overall well-being and happiness.
It is mostly found in the brain, intestines, and blood platelets.
5-HT is utilised to transport messages between nerve cells, is known to be involved in smooth muscle contraction, and adds to overall well-being and pleasure, among other benefits. 5-HT regulates the body's sleep-wake cycles and internal clock by acting as a precursor to melatonin.
It is hypothesised to regulate hunger, emotions, motor, cognitive, and autonomic processes.
Breast cancer: Post menopausal endocrine therapyDr. Sumit KUMAR
Breast cancer in postmenopausal women with hormone receptor-positive (HR+) status is a common and complex condition that necessitates a multifaceted approach to management. HR+ breast cancer means that the cancer cells grow in response to hormones such as estrogen and progesterone. This subtype is prevalent among postmenopausal women and typically exhibits a more indolent course compared to other forms of breast cancer, which allows for a variety of treatment options.
Diagnosis and Staging
The diagnosis of HR+ breast cancer begins with clinical evaluation, imaging, and biopsy. Imaging modalities such as mammography, ultrasound, and MRI help in assessing the extent of the disease. Histopathological examination and immunohistochemical staining of the biopsy sample confirm the diagnosis and hormone receptor status by identifying the presence of estrogen receptors (ER) and progesterone receptors (PR) on the tumor cells.
Staging involves determining the size of the tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastasis (M). The American Joint Committee on Cancer (AJCC) staging system is commonly used. Accurate staging is critical as it guides treatment decisions.
Treatment Options
Endocrine Therapy
Endocrine therapy is the cornerstone of treatment for HR+ breast cancer in postmenopausal women. The primary goal is to reduce the levels of estrogen or block its effects on cancer cells. Commonly used agents include:
Selective Estrogen Receptor Modulators (SERMs): Tamoxifen is a SERM that binds to estrogen receptors, blocking estrogen from stimulating breast cancer cells. It is effective but may have side effects such as increased risk of endometrial cancer and thromboembolic events.
Aromatase Inhibitors (AIs): These drugs, including anastrozole, letrozole, and exemestane, lower estrogen levels by inhibiting the aromatase enzyme, which converts androgens to estrogen in peripheral tissues. AIs are generally preferred in postmenopausal women due to their efficacy and safety profile compared to tamoxifen.
Selective Estrogen Receptor Downregulators (SERDs): Fulvestrant is a SERD that degrades estrogen receptors and is used in cases where resistance to other endocrine therapies develops.
Combination Therapies
Combining endocrine therapy with other treatments enhances efficacy. Examples include:
Endocrine Therapy with CDK4/6 Inhibitors: Palbociclib, ribociclib, and abemaciclib are CDK4/6 inhibitors that, when combined with endocrine therapy, significantly improve progression-free survival in advanced HR+ breast cancer.
Endocrine Therapy with mTOR Inhibitors: Everolimus, an mTOR inhibitor, can be added to endocrine therapy for patients who have developed resistance to aromatase inhibitors.
Chemotherapy
Chemotherapy is generally reserved for patients with high-risk features, such as large tumor size, high-grade histology, or extensive lymph node involvement. Regimens often include anthracyclines and taxanes.
1. SUPAC AND POST MARKETING
SURVeILLANCE
1
Prepared by:
Mr. Bhavya Jivrajani
M.Pharm 1st sem
(Pharmaceutics)
Guided By:
Dr. Dhaval D. mori
Senior lecturer
BKMGPC
2. CONTENTS
SUPAC
• Introduction
• Purpose of guidelines
• Components and composition
• Site changes
• Changes in batch size
• Manufacturing process/ equipment
Post marketing surveillance
• Introduction
• Safety Monitoring during the Post-Approval Phase of a Drug Product’s Life Cycle
• Types of Post-Marketing Adverse Event Data
• Post-marketing Adverse Event Reporting and MedWatch
• Post-marketing safety reporting requirements
• Serious Adverse Experience
2
4. WHAT IS SUPAC ?
• Scale up post approval changes
• The scale-up process and the changes made after
approval in the composition, manufacturing process,
manufacturing equipment, and change of site have
become known as Scale-Up and Post approval
Changes, or SUPAC.
• SUPAC-IR (immediate release solid oral dosage form)
• SUPAC-MR (modified release solid oral dosage form)
• SUPAC-SS (semi solid dosage form including cream,
ointment, gels, and lotion)
4
5. Purpose of guidelines:-
Provides recommendation to sponsor of NDA,ANDA,
AADA’s who intend, during the post approval period,
to changes:
5
The components or composition
The site of manufacturing
The scale-up/scale-down of manufacturing
The manufacturing process/Equipments
6. The guidance defines:
I. Levels of change;
II. Recommended chemistry manufacturing and control
tests for each level of change;
III. In vitro dissolution tests and/or in vivo bioequivalence
tests for each level of change; and
IV.Documentation that should support the change.
6
7. Level of
changes
• Minor changes
• Moderate changes
• Major changes
filing
• Annual report
• Changes being affected supplement
• Prior approval supplement
tests
• Application/ compendial test
• In-vitro Dissolution/release
• In-vivo Bioequivalence
7
8. 8
DissolutionTesting
Case A: Dissolution of Q = 85% in 15 minutes in 900 milliliters
(mL) of 0.1N hydrochloride (HCl), using the United States
Pharmacopeia (USP) <711>Apparatus 1 at 100 revolutions per
minute (rpm) or Apparatus 2 at 50 rpm.
Case B: Multi-point dissolution profile in the
application/compendial medium at 15, 30, 45, 60, and 120
minutes or until an asymptote is reached for the proposed and
currently accepted formulation.
Case C: Multi-point dissolution profiles performed in water,
0.1N HCl, and USP buffer media at pH 4.5, 6.5, and 7.5 (five
separate profiles) for the proposed and currently accepted
formulations. Adequate sampling should be performed at 15,
30, 45, 60, and 120 minutes until either 90% of drug from the
drug prod is dissolved or an asymptote is reached. A surfactant
may be used with appropriate justification.
10. I. COMPONENTS AND COMPOSITION:-
This section of the guidance focuses on changes
in excipients in the drug product. Changes in the
amount of drug substance are not addressed by
this guidance. Changes in components or
composition that have the effect of adding a new
excipient or deleting an excipient are defined at
Level 3 (defined below), except as described
below.
10
11. 11
Level 1 Level 2 Level 3
Components
and
composition
Test
documents
-CMC
Stability
testing:
-Unlikely to have any
detectable impact on
formulation quality and
performance
-Application/
compendial release
requirements and
stability testing.
-one batch on long-
term stability data
reported in annual
report.
-Significant impact on
formulation quality and
performance.
-vary depending upon three
factor
1.therapeutic range
2.solubility
3.permiability
-1 batch with 3 months
accelerated stability data in
supplement and 1 batch on
long-term stability data
reported in annual report.
-
-Likely to have a
significant impact on
formulation quality and
performance.
-vary depending on the
following three factors:
1.therapeutic range
2.solubility, and
3.Permeability
-1 batch with 3 months
accelerated stability data
reported in supplement; 1
batch on long-term
stability data reported in
annual report.
12. 12
Level 1 Level 2 Level 3
-Dissolution
Documentati
on
-InVivo
Bioequivalen
ce
-Filing
Documentati
on
-None beyond
application/
compendial
requirements.
-None.
-Annual report (all
information including
long-term stability
data).
Case A-high perm., high
solubility.
Case B-low perm., high
solubility.
Case C-high perm., low
solubility.
Case D-low perm., low
solubility.
-None: if the situation does
not meet the description in
Case A, Case B or Case C,
refer to Level 3 changes.
Prior approval supplement
(including accelerated
stability data); annual
report (long-term stability
-Case B
Full bioequivalence study.
Prior approval supplement
(including accelerated
stability data); annual
report (long-term stability
data).
13. II.SITE CHANGES:-
It changes in location of the site of manufacture for both
company-owned and contract manufacturing facilities
and do not include any scale-up changes, changes in
manufacturing (including process and/or equipment), or
changes in components or composition.
13
14. 14
Level 1 Level 2 Level 3
SITE CHANGES
Test
documents
-CMC
Documents
Stability
testing:
site changes within a
single facility where the
same equipment,
standard operating
procedures (SOP's),
environmental
conditions (where no
changes are made to
the manufacturing
batch records)
None beyond
application/compendia
l release requirements.
Site changes within a
contiguous campus, or
between facilities in
adjacent city blocks.
Location of new site and
updated batch records.
None beyond application/
compendial release
requirements. One batch
on long-term stability data
reported in annual report.
Change in manufacturing
site to a different campus.
A different campus is
defined as one that is not
on the same original
contiguous site or where
the facilities are not in
adjacent city blocks.
-Location of new site and
updated batch records.
- One batch with three
months accelerated
stability data reported in
supplement; one batch
on long-term stability
data reported in annual
report.
15. 15
Level 1 Level 2 Level 3
-Dissolution
Documentati
on
-InVivo
Bioequivalen
ce
-Filing
Documentati
on
None beyond
application/compendia
l release requirements.
None
Annual report
None beyond application/
compendial release
requirements.
None
Annual report (long-term
stability test data).
-Case-B.
The dissolution profile of
the drug product at the
current and proposed site
should be similar.
None
Annual report (long-term
stability test data).
16. III. CHANGES IN BATCH SIZE (SCALE-UP/SCALE-
DOWN)
Post approval changes in the size of a batch from the
pivotal/pilot scale bio batch material to larger or smaller
production.
Scale-down below 100,000 dosage units is not covered
by this guidance.
scale-up changes should be properly validated and,
where needed, inspected by appropriate agency
personnel.
16
17. 17
Level 1 Level 2 Level 3
CHANGES IN
BATCH SIZE
(SCALE-
UP/SCALE-
DOWN)
Change in batch size, up to
and including a factor of
10 times the size of the
pilot/bio batch.
1) The equipment used
to produce the test
batch( es) is of the
same design and
operating principles;
2) The batch( es) is (are)
manufactured in full
compliance with
cGMP's
3) Same SOP’s,
controls,
formulation,
manufacturing
procedure followed
Changes in batch size beyond
a factor of ten times the size
of the pilot/bio batch.
-
18. 18
Level 1 Level 2 Level 3
CMC
documents
(stability
testing)
-Dissolution
Documenta
tion
-InVivo
Bioequivale
nce
-Filing
Documenta
tion
One batch on long-term
stability reported in
annual report.
None
None
Annual report (long-
term stability data).
One batch with three
months accelerated
stability data and one
batch on long-term
stability.
-Case : B
None
Changes being effected
supplement; annual report
(long-term stability data).
20. 20
Level 1 Level 2 Level 3
Manufacturing
equipment
Manufacturing
process
1. Change from non-
automated or non-
mechanical equipment to
automated or
mechanical equipment to
move ingredients.
2. Change to alternative
equipment of the same
design and operating
principles of the same or
of a different capacity.
This category includes
process changes
including changes such
as mixing times and
operating speeds within
application/validation
ranges.
Change in equipment to a
different design and different
operating principles.
This category includes process
changes including changes
such as mixing times and
operating speeds outside of
application/validation ranges.
-
This category includes
change in the type of
process used in the
manufacture of the product,
such as a change from wet
granulation to direct
compression of dry powder.
21. 21
Level 1 Level 2 Level 3
CMC
documents
(stability
testing)
-Dissolution
Documenta
tion
-InVivo
Bioequivale
nce
-Filing
Documenta
tion
For
Process
One batch on long-
term stability
reported in annual
report.
-None beyond
application/
compendial release
requirements.
-None
Annual report (long-
term stability data).
As per level 1 of site
change
As per level 3 of the site
change
Case: C
-None
As per level 2 of site
change
As per level 3 of changes
of components and
composition changes.
23. 23
Practolol syndrome:- Practolol, a drug used to treat
cardiovascular disease, was eventually found to cause
skin rashes, eye lesions, hearing impairment, and
sclerosing peritonitis , with deaths occurring in about 2
percent of reported cases.
The drug thalidomide,
taken worldwide, led to
limb deformities
(phocomelia) in the
newborns of those
mothers who took the
drug while pregnant.
HISTORY:
24. • Introduction :-
Safety concerns
Strategies and Actions to Minimize Risk
24
• Preclinical
• Safety and biological activity
Preclinical
• Phase 1
• Safety and dosage
Phase 1
• Phase 2
• Safety and efficacy
Phase 2
• Phase 3
• Safety and efficacy
Phase 3
• Post marketing
• Safety and surveillance
Post marketing
Approval
25. Safety Monitoring during the Post-
Approval Phase of a Drug Product’s Life
Cycle:-
• Less frequent adverse drug experiences (ADEs)
• Patients with higher risk for ADEs
• Chronic and long term use
• Drug-drug interactions
• Drug-food interactions
• Expected ADEs
– Increased severity or frequency
• Misuse or abuse of drug product
• Medication errors
– Product packaging, labelling, other characteristics
25
26. Types of Post-Marketing Adverse Event
Data:-
• Spontaneous/voluntary reporting of cases
• National (FDA MedWatch)
• Local or Regional (Joint Commission Requirement)
• Scientific literature publications
• Post-marketing studies (voluntary or required)
• Observational studies (including automated healthcare
databases)
• Randomized clinical trials
• Active surveillance
• Drug-Induced Liver Injury Network (DILIN) – Sentinel
initiative
26
27. Post-marketing Adverse Event Reporting and
MedWatch:-
• How Post-marketing Reports Get to FDA
voluntary voluntary
regulatory requirement
FDA
5% of all reports 95% of all reports 27
Patients, Caregivers, and Healthcare
Professionals
FDA Med Watch Manufacture
Database
FAERS
28. Post-marketing safety reporting
requirements:-
Under 21 CFR 314.80 post-marketing safety
reports must be submitted to the agency for the
following:
• 15-day Alert reports: Serious and unexpected adverse
experience from all sources (domestic and foreign).
• Periodic Adverse Events Reports: Domestic
spontaneous adverse events that are:
• Serious and expected
• Non-serious and unexpected
• Non-serious and expected
• Quarterly for the first 3 years then annually
28
29. Serious Adverse Experience:-
Results in any of these outcomes:
Death
Life-threatening adverse experience
Inpatient hospitalization – new or prolonged
Persistent/significant disability/incapacity
Congenital birth defect
Other serious: based upon appropriate medical
judgment, they may jeopardize the patient and
require intervention to prevent a serious outcome.
29
30. Spontaneous reports:-
A communication from an individual (e.g.,
health care professional, consumer) to a
company or regulatory authority
Describes a suspected adverse event(s)
Passive and voluntary reports
30
31. Spontaneous Reporting System
Strengths:-
• Relatively affordable system to monitor all drugs
• Can report even if causality is uncertain
• Less restrictive than clinical trials
• Reports can be submitted for any drug, old and new
• Entire US population is “eligible”
• Reports emerge from usual healthcare settings:
i. Patient and prescriber population more heterogeneous
ii. All stages of treated disease
iii. Longer duration of use
iv. Captures “off-label” use, including diagnosis and dose
31
32. Factors Affecting Reporting:-
• Media attention
• Nature of the adverse event
• Type of drug product and indication
• Length of time on market
• Extent and quality of manufacturer’s surveillance
system
• Prescription or over-the counter (OTC) product status
• Reporting regulations
32
33. FDA Adverse Event Reporting System:-
• Fully automated computerized database
• Spontaneous reports
• Contains human drug and therapeutic biologic
reports
• 13 million reports since 1969
• Over 71 new reports in 2018
33
35. Best Applications of FAERS(FDA Adverse
Events Reporting System)
• Events that are linked to specific diagnoses
• Events with a serious outcome that rarely
occur in an untreated population
• Events with a short-to-moderate period
following exposure
• “Safety signal” generation and descriptive
case series
35
36. Components of a Good post-marketing
Report
• Description of adverse event
• Suspected and concomitant product therapy details (e.g.,
dose, dates of therapy)
• Patient characteristics (e.g., age, sex), baseline medical
condition, family history, other risk factors
• Documentation of the diagnosis
• Clinical course and outcomes
• Relevant therapeutic measures and laboratory data
• Dechallenge and rechallenge information
• Reporter contact information
• Any other relevant information
36
37. Evaluation of Case Reports
• Adverse event occurrence in expected time
• Absence of symptoms prior to exposure
• Positive dechallenge or rechallenge
• Consistent with pharmacologic effects
• Consistent with known effects in the class
• Support from pre-clinical studies, clinical trials
• Absence of alternative explanations
37
38. How to Report to MedWatch
38
How to Report:
• Online (www.fda.gov/medwatch)
• Download the form
• Mail
• Fax 1–800–332–0178
• For questions about the form:
1–800–332–1088
39. Development of a Case Series
• Identify a well-documented case (or
cases) in FAERS, published
literature or other source that
supports a safety signal
Step-1
• Formulate a case definition
Step-2
• Search for additional cases using:
• FAERS
• Published literature
• ClinicalTrial Adverse Event Data
• Other databases
Step-3
39
40. Regulatory Actions:-
• Product information changes –Warnings,
Precautions, Adverse Reactions
• Pharmacovigilance activities - enhanced surveillance
(e.g., expedited reporting), registry, epidemiology
studies
• Risk Evaluation and Mitigation Strategy (REMS) –
Communication plan, restricted use
• Drug Safety Communication (DSC)
• Market withdrawal
40
41. Communicating Safety Issues to the
Public and Internationally
• MedWatch Safety Alerts
• Postmarket Drug and Biologic Safety
Evaluations (FDAAA 915)
• Potential Signals of Serious Risks/New Safety
Information Identified from FAERS (FDAAA 921)
• Published literature and scientific meetings
• Video and teleconferences with foreign
regulatory agencies: – EMA: European Medicines
Agency – 4-Way: Canada, Australia, New
Zealand, (Singapore in writing) 41