A review of key issues that can make or break the success of a clinical study conducted outside the United States, with an emphasis on site, GCP issues, challenges that vary nationally, and enforcement concerns.
Regulatory Challenges In Executing Clinical Trials GloballyMichael Swit
This document discusses regulatory challenges for conducting successful global clinical trials. It covers keys to regulatory success such as standards of care, ethical standards, and following essential sponsor procedures. It also provides case studies on key regulatory issues and considerations for specific countries and regions, including Europe, India, China, Indonesia, and more. The document emphasizes the importance of properly designing global clinical trials to account for cultural, infrastructure, and other local factors in different countries and regions. It also focuses on the risks of non-compliance and fraud at clinical sites that can undermine trial integrity.
management of clinical trials: sponser perspective from falgun vyasFalgun Vyas
The document discusses standard operating procedures (SOPs) that are written instructions to standardize clinical trial functions, the importance of protocols that define trial objectives and methodology, selecting qualified clinical investigators and training them on GCP guidelines and the trial protocol, and monitoring investigator sites through periodic monitoring and audits to ensure compliance.
This document discusses Contract Research Organizations (CROs) and their role in supporting pharmaceutical clinical trials. It provides the following key points:
- CROs are service organizations that conduct clinical trials and other drug development work on behalf of pharmaceutical companies. They help companies that lack sufficient resources or expertise to conduct all required trials themselves.
- Selecting the right CRO is important for a successful clinical trial. Sponsors should clearly define study specifications, evaluate a CRO's capabilities and compatibility, and consider cost. Ongoing management of the sponsor-CRO relationship also impacts success.
- Common issues like selecting an inappropriate CRO, unclear study specifications from the sponsor, or poor management can lead
Essential Regulatory Documents in Clinical TrialsTrialJoin
The term ‘’essential documents’’ refers to the documents which, according to the ICH-GCP Guidelines, serve to evaluate the trial conducted, data quality and integrity. These documents are contained in the Trial Master File and are otherwise known as Regulatory Documents. Such documents are usually the important agreements, contracts, delegation logs, training logs, etc.
Maintaining and storing these essential regulatory documents is an important practice in clinical research. The proper filing and organization of these documents can greatly improve a clinical trial management. Usually, Regulatory Documents will be stored in a binder (or binders) that’s provided to the site for that specific study.
Filling out these documents and filing them properly is the site’s and especially the PI’s responsibility. Storing them properly is also the site’s responsibility, not the CRA’s. In any case, after the study is over, the sponsor or the CRO will inform the site if they should keep the originals or make copies of the Regulatory Documents for storage. Similarly, the sponsor or the CRO will also tell the site how long they need the documents to be kept and stored on-site.
Investigation Device Exemptions (IDEs) for Early Feasibility Medical Device C...BostonBiomedical
The document discusses the FDA's Early Feasibility Study (EFS) program, which provides more flexibility for early-stage medical device clinical studies compared to a traditional Investigational Device Exemption. The EFS program allows initial human testing with less preclinical data due to the exploratory nature of early studies. Key aspects of the EFS include enhanced risk mitigation strategies, limited initial enrollment of fewer than 10 subjects, and an iterative process to refine the device design based on clinical findings. The goal of the EFS program is to encourage medical device innovation and clinical testing in the US rather than overseas.
Key stakeholders in clinical research include study sponsors, investigators and site personnel, monitors, institutional review boards (IRBs), study subjects, and regulators. Sponsors are responsible for the design and oversight of studies, including selecting investigators and monitoring sites. Investigators conduct the research and ensure ethical and safe treatment of subjects. IRBs and ethics committees review studies to protect subject safety and rights. Monitors verify compliance and safety on behalf of sponsors. Subjects participate in studies after providing informed consent. Regulators such as the FDA and CDSCO approve studies and ensure compliance.
Pharma-CRO Relationships Managing Risk A Lawyer\'s Viewalbinpaul
The document discusses sponsor-CRO relationships and managing risks when outsourcing clinical trials to contract research organizations (CROs). It defines CROs and site management organizations (SMOs) and their roles. It also discusses selecting CROs, establishing metrics to measure performance, managing personnel changes and communications, and proactively avoiding and resolving disputes. The key aspects are selecting the right CRO based on expertise and compatibility, establishing metrics for accountability and continuous improvement, and clear communications and dispute resolution processes to facilitate the relationship.
This document discusses Contract Research Organizations (CROs) and their role in supporting pharmaceutical clinical trials. It provides the following key points:
- CROs are service organizations that conduct clinical trials and other drug development work on behalf of pharmaceutical companies. This outsourcing has grown as drug development has become more complex.
- When deciding whether and how to use a CRO, companies consider tactical, maximal, or strategic outsourcing based on their internal resources. Selecting the right CRO requires evaluating their capabilities, compatibility with the sponsor's needs, and costs.
- Managing the sponsor-CRO relationship is critical to ensure success. This involves clearly defining roles and responsibilities, establishing performance metrics,
Regulatory Challenges In Executing Clinical Trials GloballyMichael Swit
This document discusses regulatory challenges for conducting successful global clinical trials. It covers keys to regulatory success such as standards of care, ethical standards, and following essential sponsor procedures. It also provides case studies on key regulatory issues and considerations for specific countries and regions, including Europe, India, China, Indonesia, and more. The document emphasizes the importance of properly designing global clinical trials to account for cultural, infrastructure, and other local factors in different countries and regions. It also focuses on the risks of non-compliance and fraud at clinical sites that can undermine trial integrity.
management of clinical trials: sponser perspective from falgun vyasFalgun Vyas
The document discusses standard operating procedures (SOPs) that are written instructions to standardize clinical trial functions, the importance of protocols that define trial objectives and methodology, selecting qualified clinical investigators and training them on GCP guidelines and the trial protocol, and monitoring investigator sites through periodic monitoring and audits to ensure compliance.
This document discusses Contract Research Organizations (CROs) and their role in supporting pharmaceutical clinical trials. It provides the following key points:
- CROs are service organizations that conduct clinical trials and other drug development work on behalf of pharmaceutical companies. They help companies that lack sufficient resources or expertise to conduct all required trials themselves.
- Selecting the right CRO is important for a successful clinical trial. Sponsors should clearly define study specifications, evaluate a CRO's capabilities and compatibility, and consider cost. Ongoing management of the sponsor-CRO relationship also impacts success.
- Common issues like selecting an inappropriate CRO, unclear study specifications from the sponsor, or poor management can lead
Essential Regulatory Documents in Clinical TrialsTrialJoin
The term ‘’essential documents’’ refers to the documents which, according to the ICH-GCP Guidelines, serve to evaluate the trial conducted, data quality and integrity. These documents are contained in the Trial Master File and are otherwise known as Regulatory Documents. Such documents are usually the important agreements, contracts, delegation logs, training logs, etc.
Maintaining and storing these essential regulatory documents is an important practice in clinical research. The proper filing and organization of these documents can greatly improve a clinical trial management. Usually, Regulatory Documents will be stored in a binder (or binders) that’s provided to the site for that specific study.
Filling out these documents and filing them properly is the site’s and especially the PI’s responsibility. Storing them properly is also the site’s responsibility, not the CRA’s. In any case, after the study is over, the sponsor or the CRO will inform the site if they should keep the originals or make copies of the Regulatory Documents for storage. Similarly, the sponsor or the CRO will also tell the site how long they need the documents to be kept and stored on-site.
Investigation Device Exemptions (IDEs) for Early Feasibility Medical Device C...BostonBiomedical
The document discusses the FDA's Early Feasibility Study (EFS) program, which provides more flexibility for early-stage medical device clinical studies compared to a traditional Investigational Device Exemption. The EFS program allows initial human testing with less preclinical data due to the exploratory nature of early studies. Key aspects of the EFS include enhanced risk mitigation strategies, limited initial enrollment of fewer than 10 subjects, and an iterative process to refine the device design based on clinical findings. The goal of the EFS program is to encourage medical device innovation and clinical testing in the US rather than overseas.
Key stakeholders in clinical research include study sponsors, investigators and site personnel, monitors, institutional review boards (IRBs), study subjects, and regulators. Sponsors are responsible for the design and oversight of studies, including selecting investigators and monitoring sites. Investigators conduct the research and ensure ethical and safe treatment of subjects. IRBs and ethics committees review studies to protect subject safety and rights. Monitors verify compliance and safety on behalf of sponsors. Subjects participate in studies after providing informed consent. Regulators such as the FDA and CDSCO approve studies and ensure compliance.
Pharma-CRO Relationships Managing Risk A Lawyer\'s Viewalbinpaul
The document discusses sponsor-CRO relationships and managing risks when outsourcing clinical trials to contract research organizations (CROs). It defines CROs and site management organizations (SMOs) and their roles. It also discusses selecting CROs, establishing metrics to measure performance, managing personnel changes and communications, and proactively avoiding and resolving disputes. The key aspects are selecting the right CRO based on expertise and compatibility, establishing metrics for accountability and continuous improvement, and clear communications and dispute resolution processes to facilitate the relationship.
This document discusses Contract Research Organizations (CROs) and their role in supporting pharmaceutical clinical trials. It provides the following key points:
- CROs are service organizations that conduct clinical trials and other drug development work on behalf of pharmaceutical companies. This outsourcing has grown as drug development has become more complex.
- When deciding whether and how to use a CRO, companies consider tactical, maximal, or strategic outsourcing based on their internal resources. Selecting the right CRO requires evaluating their capabilities, compatibility with the sponsor's needs, and costs.
- Managing the sponsor-CRO relationship is critical to ensure success. This involves clearly defining roles and responsibilities, establishing performance metrics,
A sponsor in literal terms is defined as an individual or a company or an institution that takes the responsibility for the initiation, management and/or financing of a clinical study.
In case an investigator independently initiates and takes full responsibility for a trial, he/she automatically assumes the role of a sponsor.
This document outlines the steps for conducting a clinical trial and conducting a site qualification visit. It discusses preparing essential documents, selecting an investigator and site, conducting the qualification visit to assess the site's capabilities, and reviewing requirements like the protocol, informed consent, reporting procedures, documentation, facilities, staff experience, and regulatory approvals. The qualification visit confirms the site's readiness before initiating a clinical trial.
Clinical Research Associate (CRA) - A Growing Career Path in Biotechnology / ...SOCRA CCRP Certification
SOCRA study guide - ES’ SOCRA CCRP Exam Study Guide – A resource to help those who is preparing for the SOCRA Certified Clinical Research Professional (CCRP) certification.
The document discusses factors to consider when selecting clinical trial sites and investigators. Key criteria for site selection include the experience and qualifications of staff, availability of suitable patients, and ability to perform required assessments. Important considerations for investigator selection are their education, training, experience recruiting patients, and ability to properly conduct the trial within the required timelines. The selection process involves sponsors asking CROs to evaluate potential sites and investigators through feasibility interviews and assessments of qualifications.
This document defines a source document as an original document where clinical trial data is first recorded, such as medical records, laboratory notes, or subjects' diaries. Source documents can be either electronic or paper. Electronic source documents must meet requirements regarding computer system validation, electronic records, electronic signatures, and technical support. Paper source documents are typically handwritten forms or records with the investigator's original signature. The document discusses challenges of source document verification like informed consent processes and adverse event reporting. It provides examples of informed consent procedures for patients who cannot read, are disabled, or lack decision-making capacity.
The clinical research associate (CRA), also known as the monitor, acts as the main line of communication between the sponsor and investigator. The CRA is responsible for evaluating investigators to ensure they are qualified through training and experience and have adequate resources to properly conduct the trial. Additional responsibilities include conducting pre-study visits to assess investigator experience and facilities, site initiation visits to detail study obligations, and routine monitoring visits to ensure subjects' rights and data accuracy and compliance with regulations. The CRA also performs site closeout visits when enrollment and subjects' activities are complete and data are finalized.
Careers In Clinical Research Industry Gp 06 Nov11Gopalkrishna Pai
The document provides an overview of the stages involved in drug development from pre-clinical testing through clinical trials and regulatory approval. It outlines the various tests, studies and requirements at each stage, including in vitro and animal model screening, toxicity studies, pharmaceutical development, clinical trials in four phases, and post-marketing surveillance. It also describes the roles and requirements for different departments involved in clinical research.
The document discusses the roles and responsibilities of investigators in clinical trials. It states that the principal investigator is responsible for leading the clinical trial team at a trial site and ensuring proper conduct of the trial. Key responsibilities include being qualified to conduct the trial, obtaining necessary approvals, following good clinical practice guidelines, properly storing and using investigational products, obtaining informed consent, adhering to the protocol, maintaining accurate records, and communicating with regulatory bodies and the institutional review board. The investigator must ensure patient safety and welfare, medical care for participants, and protection of participant rights and confidentiality.
1) The document discusses the responsibilities of a sponsor in conducting clinical trials, which include implementing quality control systems, securing agreements from parties involved in the trial, and ensuring compliance with regulations.
2) The sponsor is responsible for selecting qualified investigators and facilitating IRB/IEC approval of the trial.
3) Key responsibilities of the sponsor involve proper design of the trial, management of data handling and record keeping, safety monitoring of investigational products, and reporting of adverse events.
Monitoring in clinical trials serves several key purposes: to protect the rights and welfare of human subjects, ensure the accuracy and completeness of trial data, and confirm compliance with regulatory standards and the study protocol. There are various types of monitoring, including central monitoring of data for unusual patterns, risk-based monitoring focusing on higher risk aspects, and on-site monitoring to check participant enrollment and informed consent, study conduct, drug accountability, and accuracy of source data documentation. Routine monitoring visits evaluate study progress, resources, laboratory facilities, investigational products, compliance with the protocol and regulations, case report forms, source data verification, adverse events documentation, and regulatory files.
Feasibility Solutions to Clinical Trial Nightmaresjbarag
Slow patient recruitment and poor retention cause recurrent nightmares and perpetual problems often resulting in missing recruitment milestones. The cost of these delays represents hundreds of thousands of dollars for drug and device developers. By recognizing this issue, early detailed feasibility can provide planning and contingency solutions that are focused on reducing the impact of delayed recruitment. Furthermore understanding what motivates investigators and patients to actively participate in clinical studies and how patient recruitment strategies and materials can support all stakeholders to complete studies on time are critical aspects of clinical study delivery planning.
During this presentation, an experienced Premier Research feasibility and patient recruitment specialist, reviewed feasibility approaches to address protocol evaluation as well as addressed influences on country selection, site distribution and patient recruitment strategies to provide for more effective clinical trial planning and conduct.
For more information, go to http://www.premier-research.com.
The document discusses the roles and responsibilities of investigators in clinical trials. It states that an investigator is responsible for proper conduct of a trial at their site and must be qualified by education and experience. Investigators must obtain approval from an ethics committee for the trial protocol and consent forms. They must ensure accurate reporting of trial data and documentation. Key responsibilities include proper storage and use of investigational products, training staff, protecting subjects, and record keeping.
This document discusses clinical trial fraud, including definitions, common types of fraud, perpetrators, frequency, impacts, red flags, and recommendations. It notes that fraud includes falsification of data through both omission and fabrication. Common perpetrators include study coordinators, nurses, and investigators. Red flags include implausible or perfect data patterns, inconsistent subject documentation, and questionable visit dates. Recommendations include assuming fraud until proven otherwise, cultivating whistleblowers, and emphasizing fraud policies.
Monitoring plan and basic monitoring visits: everything that a cra needs to knowTrialJoin
A monitor in a clinical trial is also called a CRA - clinical research associate. This person is a professional who’s responsible for monitoring the clinical trial and making sure that everything is according to rules, regulations, and good clinical practice.
Whether you already are a CRA or you’re trying to become one, the most important thing you should be aware of is the monitoring plan. You, as a CRA or a future CRA, should know what a monitoring plan is, what it serves for, and what it consists of. The second most important information for you are the monitoring visits. Below, we’ll explain all the components of a monitoring plan, as well as which are the most basic and important monitoring visits.
Monitoring and auditing in clinical trialsJyotsna Kapoor
Monitoring and auditing are important quality control activities in clinical trials. Monitoring ensures accurate and compliant conduct of trials, while auditing independently evaluates trial conduct and compliance. Key aspects include:
Monitoring involves overseeing trial progress to ensure compliance. Monitors verify participant rights and data accuracy. Auditing independently examines trials and documents to determine GCP compliance. Audit findings help ensure future compliance. Together, monitoring and auditing protect participants and validate trial results.
The CRA oversees all stages of clinical trials from site selection to completion. They identify investigators, set up trial sites, train staff, monitor compliance, and verify informed consent and data collection. The CRA ensures protocols are followed, documents are collected, and supplies are accounted for throughout the trial. Effective communication, relationship building, attention to detail, and strong organizational skills are important for this role.
The difference between practice and research 111607Lanka Praneeth
The document discusses the key differences between clinical practice and clinical research. Clinical research must be conducted according to an approved protocol and involves more oversight, documentation and risk to subjects. It outlines sponsor and investigator responsibilities, good clinical practice standards, and FDA expectations for clinical trial design, conduct and oversight. Clinical trials aim to generate generalizable knowledge, while practice focuses on individual patient treatment.
Regulatory Challenges to Successful Global Clinical StudiesMichael Swit
A review of key issues that can make or break the success of a clinical study conducted outside the United States, with an emphasis on site, GCP issues, challenges that vary nationally, and enforcement concerns.
Roadmap to Emerging Regions: Clinical Trials in Developing CountriesMichael Swit
Presentation focusing on how to implement a clinical trial in developing countries, with case studies and an emphasis on studies in India and Indonesia, but also in the EU countries, especially in eastern Europe such as Slovenia.
A sponsor in literal terms is defined as an individual or a company or an institution that takes the responsibility for the initiation, management and/or financing of a clinical study.
In case an investigator independently initiates and takes full responsibility for a trial, he/she automatically assumes the role of a sponsor.
This document outlines the steps for conducting a clinical trial and conducting a site qualification visit. It discusses preparing essential documents, selecting an investigator and site, conducting the qualification visit to assess the site's capabilities, and reviewing requirements like the protocol, informed consent, reporting procedures, documentation, facilities, staff experience, and regulatory approvals. The qualification visit confirms the site's readiness before initiating a clinical trial.
Clinical Research Associate (CRA) - A Growing Career Path in Biotechnology / ...SOCRA CCRP Certification
SOCRA study guide - ES’ SOCRA CCRP Exam Study Guide – A resource to help those who is preparing for the SOCRA Certified Clinical Research Professional (CCRP) certification.
The document discusses factors to consider when selecting clinical trial sites and investigators. Key criteria for site selection include the experience and qualifications of staff, availability of suitable patients, and ability to perform required assessments. Important considerations for investigator selection are their education, training, experience recruiting patients, and ability to properly conduct the trial within the required timelines. The selection process involves sponsors asking CROs to evaluate potential sites and investigators through feasibility interviews and assessments of qualifications.
This document defines a source document as an original document where clinical trial data is first recorded, such as medical records, laboratory notes, or subjects' diaries. Source documents can be either electronic or paper. Electronic source documents must meet requirements regarding computer system validation, electronic records, electronic signatures, and technical support. Paper source documents are typically handwritten forms or records with the investigator's original signature. The document discusses challenges of source document verification like informed consent processes and adverse event reporting. It provides examples of informed consent procedures for patients who cannot read, are disabled, or lack decision-making capacity.
The clinical research associate (CRA), also known as the monitor, acts as the main line of communication between the sponsor and investigator. The CRA is responsible for evaluating investigators to ensure they are qualified through training and experience and have adequate resources to properly conduct the trial. Additional responsibilities include conducting pre-study visits to assess investigator experience and facilities, site initiation visits to detail study obligations, and routine monitoring visits to ensure subjects' rights and data accuracy and compliance with regulations. The CRA also performs site closeout visits when enrollment and subjects' activities are complete and data are finalized.
Careers In Clinical Research Industry Gp 06 Nov11Gopalkrishna Pai
The document provides an overview of the stages involved in drug development from pre-clinical testing through clinical trials and regulatory approval. It outlines the various tests, studies and requirements at each stage, including in vitro and animal model screening, toxicity studies, pharmaceutical development, clinical trials in four phases, and post-marketing surveillance. It also describes the roles and requirements for different departments involved in clinical research.
The document discusses the roles and responsibilities of investigators in clinical trials. It states that the principal investigator is responsible for leading the clinical trial team at a trial site and ensuring proper conduct of the trial. Key responsibilities include being qualified to conduct the trial, obtaining necessary approvals, following good clinical practice guidelines, properly storing and using investigational products, obtaining informed consent, adhering to the protocol, maintaining accurate records, and communicating with regulatory bodies and the institutional review board. The investigator must ensure patient safety and welfare, medical care for participants, and protection of participant rights and confidentiality.
1) The document discusses the responsibilities of a sponsor in conducting clinical trials, which include implementing quality control systems, securing agreements from parties involved in the trial, and ensuring compliance with regulations.
2) The sponsor is responsible for selecting qualified investigators and facilitating IRB/IEC approval of the trial.
3) Key responsibilities of the sponsor involve proper design of the trial, management of data handling and record keeping, safety monitoring of investigational products, and reporting of adverse events.
Monitoring in clinical trials serves several key purposes: to protect the rights and welfare of human subjects, ensure the accuracy and completeness of trial data, and confirm compliance with regulatory standards and the study protocol. There are various types of monitoring, including central monitoring of data for unusual patterns, risk-based monitoring focusing on higher risk aspects, and on-site monitoring to check participant enrollment and informed consent, study conduct, drug accountability, and accuracy of source data documentation. Routine monitoring visits evaluate study progress, resources, laboratory facilities, investigational products, compliance with the protocol and regulations, case report forms, source data verification, adverse events documentation, and regulatory files.
Feasibility Solutions to Clinical Trial Nightmaresjbarag
Slow patient recruitment and poor retention cause recurrent nightmares and perpetual problems often resulting in missing recruitment milestones. The cost of these delays represents hundreds of thousands of dollars for drug and device developers. By recognizing this issue, early detailed feasibility can provide planning and contingency solutions that are focused on reducing the impact of delayed recruitment. Furthermore understanding what motivates investigators and patients to actively participate in clinical studies and how patient recruitment strategies and materials can support all stakeholders to complete studies on time are critical aspects of clinical study delivery planning.
During this presentation, an experienced Premier Research feasibility and patient recruitment specialist, reviewed feasibility approaches to address protocol evaluation as well as addressed influences on country selection, site distribution and patient recruitment strategies to provide for more effective clinical trial planning and conduct.
For more information, go to http://www.premier-research.com.
The document discusses the roles and responsibilities of investigators in clinical trials. It states that an investigator is responsible for proper conduct of a trial at their site and must be qualified by education and experience. Investigators must obtain approval from an ethics committee for the trial protocol and consent forms. They must ensure accurate reporting of trial data and documentation. Key responsibilities include proper storage and use of investigational products, training staff, protecting subjects, and record keeping.
This document discusses clinical trial fraud, including definitions, common types of fraud, perpetrators, frequency, impacts, red flags, and recommendations. It notes that fraud includes falsification of data through both omission and fabrication. Common perpetrators include study coordinators, nurses, and investigators. Red flags include implausible or perfect data patterns, inconsistent subject documentation, and questionable visit dates. Recommendations include assuming fraud until proven otherwise, cultivating whistleblowers, and emphasizing fraud policies.
Monitoring plan and basic monitoring visits: everything that a cra needs to knowTrialJoin
A monitor in a clinical trial is also called a CRA - clinical research associate. This person is a professional who’s responsible for monitoring the clinical trial and making sure that everything is according to rules, regulations, and good clinical practice.
Whether you already are a CRA or you’re trying to become one, the most important thing you should be aware of is the monitoring plan. You, as a CRA or a future CRA, should know what a monitoring plan is, what it serves for, and what it consists of. The second most important information for you are the monitoring visits. Below, we’ll explain all the components of a monitoring plan, as well as which are the most basic and important monitoring visits.
Monitoring and auditing in clinical trialsJyotsna Kapoor
Monitoring and auditing are important quality control activities in clinical trials. Monitoring ensures accurate and compliant conduct of trials, while auditing independently evaluates trial conduct and compliance. Key aspects include:
Monitoring involves overseeing trial progress to ensure compliance. Monitors verify participant rights and data accuracy. Auditing independently examines trials and documents to determine GCP compliance. Audit findings help ensure future compliance. Together, monitoring and auditing protect participants and validate trial results.
The CRA oversees all stages of clinical trials from site selection to completion. They identify investigators, set up trial sites, train staff, monitor compliance, and verify informed consent and data collection. The CRA ensures protocols are followed, documents are collected, and supplies are accounted for throughout the trial. Effective communication, relationship building, attention to detail, and strong organizational skills are important for this role.
The difference between practice and research 111607Lanka Praneeth
The document discusses the key differences between clinical practice and clinical research. Clinical research must be conducted according to an approved protocol and involves more oversight, documentation and risk to subjects. It outlines sponsor and investigator responsibilities, good clinical practice standards, and FDA expectations for clinical trial design, conduct and oversight. Clinical trials aim to generate generalizable knowledge, while practice focuses on individual patient treatment.
Regulatory Challenges to Successful Global Clinical StudiesMichael Swit
A review of key issues that can make or break the success of a clinical study conducted outside the United States, with an emphasis on site, GCP issues, challenges that vary nationally, and enforcement concerns.
Roadmap to Emerging Regions: Clinical Trials in Developing CountriesMichael Swit
Presentation focusing on how to implement a clinical trial in developing countries, with case studies and an emphasis on studies in India and Indonesia, but also in the EU countries, especially in eastern Europe such as Slovenia.
The Small Company Clinical Study SponsorRoles & Duties Vis-à-vis LiabilityMichael Swit
This document summarizes a presentation given by Michael Swit on roles and responsibilities of small company clinical trial sponsors and how to minimize liability when outsourcing clinical trial activities. Key points discussed include clarifying what sponsors are responsible for versus outsourcing partners, ensuring compliance of outsourcing partners, maintaining oversight of critical trial activities in-house, and explaining to funders that quality must be prioritized over cost.
The Small Company Clinical Study Sponsor -- Roles & Duties Vis-à-vis LiabilityMichael Swit
September 24, 2014 presentation to the Outsourcing in Clinical Trials: Southern California Conference, sponsored by Arena Conferences, focusing on:
* Clarifying exactly what you are responsible for and what you made be held accountable for
* Analyzing degrees of liability between bigger and smaller companies
* Ensuring that you are enforcing compliance from your outsourcing partners to avoid repercussions on yourselves
* Determining aspects of your trial management that you should retain in-house as a minimum so as to avoid liability issues
* Explaining to funders why quality and risk-assessments are a necessary expenditure above the cheapest options
This document discusses Contract Research Organizations (CROs) and their role in supporting the pharmaceutical industry. It provides information on:
- What CROs are and the services they offer pharmaceutical companies, such as conducting clinical trials.
- Best practices for pharmaceutical companies when partnering with CROs, including clearly defining study specifications, selecting the right CRO based on capability and cost, and managing the relationship.
- Key aspects of contracts between sponsors and CROs such as defining roles and responsibilities, compliance with regulations, intellectual property, and termination policies.
The document aims to provide guidance to pharmaceutical companies on effectively partnering with CROs for outsourced drug development activities.
A presentation by Niklas Nielsen at the 2017 meeting of the Scandinavian Society of Anaestesiology and Intensive Care Medicine.
All available content from SSAI2017: https://scanfoam.org/ssai2017/
Delivered in collaboration between scanFOAM, SSAI & SFAI.
This document discusses Contract Research Organizations (CROs) and their role in supporting pharmaceutical clinical trials. It provides the following information:
- CROs are service organizations that support the pharmaceutical industry by conducting various research services essential for clinical trials, like trial operations and data management. They help pharmaceutical companies that may lack sufficient staff or time resources.
- Selecting the right CRO is important for a successful clinical trial. Key criteria include the CRO's capabilities, compatibility with the sponsor's needs, and cost. Sponsors should provide accurate specifications and clearly define roles and responsibilities. Ongoing monitoring of performance metrics is also important.
- Clinical trial contracts between sponsors and CROs should address
Successfully Responding to FDA Inspections (483s) & Warning LettersMichael Swit
Presentation reviewing key issues and tactics associated with dealing with a company's reply to an FDA inspection and related warning letters. Includes lessons from actual responses
ANDAs, OTCs, Orphans and Cosmetics – Key IssuesMichael Swit
June 24, 2015 lecture to RAC Test review course sponsored by San Diego Regulatory Affairs Network (SDRAN). Focus:
♦ ANDAs and generic drug regulation
♦ OTC drug regulation
♦ Orphan drug regulation
♦ Cosmetic Regulation
Successfully Responding to FDA Inspections (483s) & Warning LettersMichael Swit
Presentation reviewing key issues and tactics associated with dealing with a company's reply to an FDA inspection and related warning letters. Includes lessons from actual responses.
ANDAs, OTCs, Orphans and Cosmetics – Key IssuesMichael Swit
August 7, 2013 lecture to RAC Test review course sponsored by San Diego Regulatory Affairs Network (SDRAN). Focused on:
♦ ANDAs and generic drug regulation
♦ OTC drug regulation
♦ Orphan drug regulation
♦ cosmetic regulation
Navigating Government Investigations of Health Care FraudPolsinelli PC
This presentation will cover the nuts and bolts of responding to a government subpoena and investigation, from recognizing when and how an investigation starts through to the aftermath of an investigation. We will walk through the steps you can take before your organization receives a subpoena, issues that may arise in responding to a subpoena, when to conduct your own internal investigation, and possible outcomes. Finally, we will review recent developments and trends in the healthcare enforcement landscape.
Our agenda:
-Relevant government agencies
-Steps in responding to a government subpoena
-When to conduct, and how to conduct, an internal investigation
-Recent developments and trends
Global Clinical Trials: Best Practices & Common PitfallsImperial CRS
This document discusses best practices and common pitfalls to avoid when planning and conducting global clinical trials. It identifies key factors to consider such as study feasibility, regulatory requirements, site selection, and patient recruitment. Specific pitfalls addressed include unrealistic protocol design, poor planning, incomplete feasibility data, lack of customized recruitment strategies, and inadequate consideration of local regulatory, cultural and logistical factors. The importance of leveraging local expertise and collecting metrics to guide a data-driven approach is emphasized. A case study example illustrates how challenges can reshape a study's scope and timeline.
Clinical Trial Registries & Databases: An UpdateMichael Swit
This document summarizes an educational conference presentation about clinical trial registries and databases. It defines key terms like clinical trial registries and results databases. It outlines the evolution of demands for more transparency including laws passed in 2000 requiring registration of certain trials. Major registries discussed include ClinicalTrials.gov, the WHO's ICTRP platform, and PhRMA's ClinicalStudyResults.org. Challenges of registries discussed include protecting competitive information and determining what data to publish. Future developments could include laws requiring disclosure of results.
This document discusses managing relationships between sponsors and investigators in clinical trials. It outlines the objectives and responsibilities of both parties. The sponsor's objectives include continued study of the test article, meeting enrollment objectives, and obtaining valid data. The investigator's objectives include access to new therapies, prestige from publications, and supplemental income. The sponsor is responsible for developing the protocol, selecting qualified investigators, providing required documents, monitoring investigations, reviewing data, and notifying regulators of issues. The investigator is responsible for complying with all requirements, conducting the study properly, maintaining records, and reporting required information. The document notes potential issues like noncompliance, FDA enforcement actions, and congressional investigations. It provides recommendations to increase compliant collaboration like detailed agreements, training,
Regulatory & Quality Considerations in Virtual Drug DevelopmentMichael Swit
Presentation to Strategies for Success in Virtual Drug Development Conference on April 15, 2013, in San Diego, focusing on:
• General Considerations
• Why Quality & Regulatory Matter
• What Problems to Look For
• How to Find Problems
• Special Considerations
GMP Review -- Legal Letter from America Column -- How Data Integrity Issues S...Michael Swit
Article appearing in the October 2018 issue of GMP Review by Michael A. Swit explores how data integrity issues sunk a $4.3 billion acquisition of Akorn by Fresenius. Article stresses lessons not just for quality professionals, but also their top management.
FDA Regulation of Promotion & Advertising -- Part 8: Handling Promotional Com...Michael Swit
Presentation to the Compliance Online 2-day course on Ensuring Compliance with FDA Requirements for the Promotion & Advertising of Drugs and Medical Devices,November 2, 2018, Boston.
FDA Regulation of Promotion & Advertising -- Part 7: FTC RegulationMichael Swit
Presentation to the Compliance Online 2-day course on Ensuring Compliance with FDA Requirements for the Promotion & Advertising of Drugs and Medical Devices,
FDA Regulation of Promotion & Advertising -- Part 6: First Amendment, Off-Lab...Michael Swit
Presentation to the Compliance Online 2-day course on Ensuring Compliance with FDA Requirements for the Promotion & Advertising of Drugs and Medical Devices, November 2, 2018, Boston.
FDA Regulation of Promotion & Advertising -- Part 5: Social Media & InternetMichael Swit
Presentation to the Compliance Online 2-day course on Ensuring Compliance with FDA Requirements for the Promotion & Advertising of Drugs and Medical Devices, November 1-2, 2018, Boston
FDA Regulation of Promotion & Advertising -- Part 4: FDA Enforcement – Action...Michael Swit
Presentation to the Compliance Online 2-day course on Ensuring Compliance with FDA Requirements for the Promotion & Advertising of Drugs and Medical Devices, November 1-2, 2018, Boston.
FDA Regulation of Promotion & Advertising -- Part 3: Disseminating Scientific...Michael Swit
Presentation to the Compliance Online 2-day course on Ensuring Compliance with FDA Requirements for the Promotion & Advertising of Drugs and Medical Devices, November 1-2, 2018, Boston
FDA Regulation of Promotion & Advertising --Part 2: Direct-to-Consumer AdsMichael Swit
Presentation to the Compliance Online 2-day course on Ensuring Compliance with FDA Requirements for the Promotion & Advertising of Drugs and Medical Devices,November 1-2, 2018, Boston
FDA Regulation of Promotion & Advertising -- Part 1: The BasicsMichael Swit
Presentation to the Compliance Online 2-day course on Ensuring Compliance with FDA Requirements for the Promotion & Advertising of Drugs and Medical Devices, November 1-2, 2018, Boston.
Ensuring FDA Regulatory Success for Biomedical Companies -- Key Lessons for S...Michael Swit
Supporting Materials for Michael Swit's Panel remarks at the Workshop Co-sponsored by the Orange County Regulatory Affairs (OCRA) Discussion Group and the Small Business Development Center (SBDC) @ UCI Applied Innovation
Regulatory, Quality & Clinical Due Diligence: The Oft Overlooked Keys to Suc...Michael Swit
June 23, 2010 webinar sponsored by The Weinberg Group, with an emphasis on key issues to explore during due diligence in acquiring FDA-regulated products or companies.
Quality Considerations in Due Diligence for Pharmaceutical TransactionsMichael Swit
The document discusses quality considerations in due diligence for pharmaceutical transactions. It outlines general considerations for due diligence structure and challenges. It emphasizes that quality matters because drugs made in non-compliant facilities can be considered adulterated by the FDA and result in criminal and civil penalties. The document provides examples of problems to look for, including manufacturing, pharmacovigilance, compliance history, FDA inspection history, and audits. It discusses techniques for probing issues, including reviewing FDA correspondence and litigation. Special considerations are outlined for different drug development stages. Helpful charts on diligence issues by stage and analyzing identified issues are presented.
Presentation on Critical Legal Issues Facing GMP ComplianceMichael Swit
August 27, 2018 Presentation to the 23rd Annual GMP by the Sea Conference in Cambridge, Maryland, focusing on the potential legal consequences faced by companies that violate FDA's requirements on Good Manufacturing Practices (GMPs) for drugs and biologics
Overview of FDA Drug Manufacturing RequirementsMichael Swit
Presentation on FDA Regulation of Drug Manufacturing to the Introduction to Drug Law Course sponsored by the Food & Drug Law Institute (FDLI) on July 25, 2018 in San Francisco.
Combination Products, Orphan Drugs, and OTC DrugsMichael Swit
Presentation to the San Diego Regulatory Affairs Network (SDRAN) Regulatory Affairs Certification (RAC) Exam review course on FDA regulation of combination products, orphan drugs, and OTC drugs.
Latest Developments in and the Future of the Regulatory Landscape for Approv...Michael Swit
Presentation on "Latest Developments in and the Future of the
Regulatory Landscape for Approving Treatments
for Orphan and Rare Diseases," given at the Orphan Drugs & Rare Diseases -- 2018 Americas West Coast Conference.
June 25, 2018. San Diego, CA.
Lifting the Corporate Veil. Power Point Presentationseri bangash
"Lifting the Corporate Veil" is a legal concept that refers to the judicial act of disregarding the separate legal personality of a corporation or limited liability company (LLC). Normally, a corporation is considered a legal entity separate from its shareholders or members, meaning that the personal assets of shareholders or members are protected from the liabilities of the corporation. However, there are certain situations where courts may decide to "pierce" or "lift" the corporate veil, holding shareholders or members personally liable for the debts or actions of the corporation.
Here are some common scenarios in which courts might lift the corporate veil:
Fraud or Illegality: If shareholders or members use the corporate structure to perpetrate fraud, evade legal obligations, or engage in illegal activities, courts may disregard the corporate entity and hold those individuals personally liable.
Undercapitalization: If a corporation is formed with insufficient capital to conduct its intended business and meet its foreseeable liabilities, and this lack of capitalization results in harm to creditors or other parties, courts may lift the corporate veil to hold shareholders or members liable.
Failure to Observe Corporate Formalities: Corporations and LLCs are required to observe certain formalities, such as holding regular meetings, maintaining separate financial records, and avoiding commingling of personal and corporate assets. If these formalities are not observed and the corporate structure is used as a mere façade, courts may disregard the corporate entity.
Alter Ego: If there is such a unity of interest and ownership between the corporation and its shareholders or members that the separate personalities of the corporation and the individuals no longer exist, courts may treat the corporation as the alter ego of its owners and hold them personally liable.
Group Enterprises: In some cases, where multiple corporations are closely related or form part of a single economic unit, courts may pierce the corporate veil to achieve equity, particularly if one corporation's actions harm creditors or other stakeholders and the corporate structure is being used to shield culpable parties from liability.
Guide on the use of Artificial Intelligence-based tools by lawyers and law fi...Massimo Talia
This guide aims to provide information on how lawyers will be able to use the opportunities provided by AI tools and how such tools could help the business processes of small firms. Its objective is to provide lawyers with some background to understand what they can and cannot realistically expect from these products. This guide aims to give a reference point for small law practices in the EU
against which they can evaluate those classes of AI applications that are probably the most relevant for them.
Synopsis On Annual General Meeting/Extra Ordinary General Meeting With Ordinary And Special Businesses And Ordinary And Special Resolutions with Companies (Postal Ballot) Regulations, 2018
What are the common challenges faced by women lawyers working in the legal pr...lawyersonia
The legal profession, which has historically been male-dominated, has experienced a significant increase in the number of women entering the field over the past few decades. Despite this progress, women lawyers continue to encounter various challenges as they strive for top positions.
Defending Weapons Offence Charges: Role of Mississauga Criminal Defence LawyersHarpreetSaini48
Discover how Mississauga criminal defence lawyers defend clients facing weapon offence charges with expert legal guidance and courtroom representation.
To know more visit: https://www.saini-law.com/
Matthew Professional CV experienced Government LiaisonMattGardner52
As an experienced Government Liaison, I have demonstrated expertise in Corporate Governance. My skill set includes senior-level management in Contract Management, Legal Support, and Diplomatic Relations. I have also gained proficiency as a Corporate Liaison, utilizing my strong background in accounting, finance, and legal, with a Bachelor's degree (B.A.) from California State University. My Administrative Skills further strengthen my ability to contribute to the growth and success of any organization.
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Standard Disclaimers
• The views here are mine and do not necessarily
reflect those of my law firm or any of our clients.
• These slides support an oral briefing and should not,
alone, be relied upon to support any conclusion of
fact or law.
• This presentation is for general educational
purposes and is not intended to be legal advice or to
create an attorney-client relationship with any
person.
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• Keys to Regulatory Success in Global Clinical Trials
• Case Studies on Key Issues –Selected Country
Examples
• Focus on Enforcement – What Can Go Wrong
• Final Thoughts -- Lessons Learned
What We Will Cover
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Why Go Global?
• Higher number of patients, especially naive patients
• Large patient populations with diseases of both
developed and developing countries (e.g., HIV/AIDS)
• Multi-ethnic/multiracial populations
• Wide spectrum of diseases
– Especially important for rare diseases
• Potential new markets (e.g., China)
• Competent/motivated PIs
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• Standards of care -- differ around the world. In
doing a clinical trial OUS, seek to ensure trials are (can
be) done the same in each jurisdiction – but, “the
universal protocol” is extremely elusive
– Can add to cost
– Example – device study – labs for three days after implant
U.S. – to be done in hospital
OUS – standard of care is discharge after 1 day; labs not
done
• Ethical standards -- particularly as to informed
consent are different – know this issue
General Considerations
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• Hire the right CRO -- if you lack a “presence” in the
country, right CRO is crucial to getting good data
• Follow-up -- in developing countries, can be
difficult. Subjects need access to the treatment facility
-- you may need to ensure they get there
• Equipment – if specific piece of lab or other
equipment needed, make sure they have it
• GCP Compliance – Audit before contract to ensure
trained per FDA/ICH standards
• IRBs/Ethical Committees – can be much more
bureaucratic – and slower
General Considerations …
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• Time Zone Differences – if U.S. based, need to be
able to juggle these (e.g., 10 pm call from San Diego to
Tel Aviv – 8 am next day)
– Make sure they are working (e.g., Sunday may not be the
sabbath where they are)
• Language – translations – validate; don’t rely on a
non-professional translator
• Drug import challenges – plan in advance
– EU – QP (“Qualified Person”) release required
• Record retention – some countries require that all
docs be kept “in country” (e.g., Australia)
General Considerations …
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• Multiple contracts may be needed
– Hospital, investigators, pharmacy, laboratory
• Some countries require submissions be made by a
someone who lives in that country – e.g., Italy
• Regulations – may not be available in English – e.g.,
Italy
• Summer holidays – July or August – country may be
shut down; know what their practice is and plan
• Applicability of patient populations – need to
assess this carefully due to genetic differences; will it
fly with FDA?
General Considerations …
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Sponsors – Key Required Procedures
• How they will deal with any reports of PI or CRO
non-compliance.
• U.S. sponsors – be very careful about payments to
doctors and others – in some cases, they are
government employees and the payment could trigger
Foreign Corrupt Practices Act concerns
e.g., Eastern Europe – may ask for payments to
referring doctors
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Sponsors – Key Required Procedures …
• Ensure that local requirements are heeded
– Be aware of trend in some countries for continued duty to
provide drug after study end
• Adverse events – OUS or ex-EU adverse events still have
to be reported back to FDA or EU competent authorities
• Make sure sites know documentation requirements
Keeping source data (e.g., blood pressure printouts from automatic
machine tossed out after being transcribed)
“Cleaning up records” – Japanese site did not like messy records
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• Sponsors – make sure contracts with clinical
investigators and CROs have adequate provision
covering GCP compliance.
– Require an immediate escalation of compliance concerns to the
sponsor.
– CRO agreements must have a detailed transfer of obligations
form.
– Make sure CRO is not also a SMO – site management
organization – not unusual overseas and can create conflicts
– Be careful with excessive payments – even if legal and not
subject to disclosure under 21 CFR 54, might “taint” data
– Audit your sites per U.S. GCP standards
Clinical Trial Agreement -- Keys
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• Scientific Advice --
– Difficult to balance going to Europe before hearing back
from FDA on EOP2 meeting and Phase 3 protocol
agreement (especially if using a SPA).
Timing – Scientific Advice is on a more rigid schedule –
predict in advance if possible
EMA – may be a little off-put if you are late, however
Europe
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• Insurance issues -- allow extra time for coverage and
review (especially in Germany)
– Example: Phase 3 study required an extra 6-8 months to
get coverage before would be considered by Ethics
Committee. Result -- sponsor could not use Germany in
first global study; only able to include in a parallel second
study.
Europe
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• Phase 1 studies
– Ethics Committee and regulatory agency have suspicion that
we (U.S.) are going to India to test because it is less likely to
have problems if the drug "poisons" the patients. Do not want
the Indian people to be guinea pigs.
SOLUTION: convinced them that safety data about the
product was sufficient by taking extra steps to document in the
cover letter both the safety measures included in the study
protocol and outline the key points from the investigator
brochure rather than simply providing the investigator brochure.
• Fraud is rampant (former FDA General Counsel) –
although government is taking efforts to reform
India
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• Center for Drug Evaluation (CDE) Evaluation
meeting:
– Monthly meetings, over 3-4 days, held in Chinese (translators
may or may not be acceptable). Need to bring subject matter
expert (CMC, Tox, etc.).
– CDE issues final evaluation ~ 2 months after the meeting.
– Much of the information that we are used to submitting for a
NDA is required as part of the CTA in China.
– A strong, local regulatory person may get the questions before
the meeting and feed them back to the sponsor.
– Local QC testing of test article for biologicals required.
Average > 5 months to complete testing.
Fear here – IP pirating
China
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• Challenges:
– CTA approval time ~ 15 months.
– Lack of flexibility
– Requires information about previous studies
– Two different regulatory bodies:
Center for Drug Evaluation (CDE) reviews the trial scientifically
while the CFDA approves the trial.
Sometimes, CDE reviews and OKs and then CFDA rejects the
trial.
– Fraud is rampant (per former FDA GC)
China …
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• Advantages/Logistics:
– Large Country
– Government and investigators receptive to industry knowledge
– GCP implemented into national laws and guidelines governing
clinical trials
– National Agency for Drug and Food Control is competent authority
for clinical trial authorization
• Disadvantages:
– Very few trials being conducted, but numbers are growing.
– ECs to be established at institutional, regional/provincial, and
national levels according to need
– Lack of population-based registries
Example: Hospital based-cancer registries in 13 cities
A Deeper Look -- Indonesia
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• Challenge: Designing a clinical trial to account for the
specifics of the region
– Cultural issues
– Inclusion/Exclusion Criteria
– Trial Length and approval timings
– Infrastructure issues
– Investigator and Staff Training
• An approach:
– Trial designed to account:
Differences in medical practice (disease diagnosis, investigator-patient
relationship)
Translation of study/regulatory documents
Validation of measurement scales (patient questionnaire)
– Understood need to apply “partnership approach” to build
supportive relationships
Indonesia
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• Challenge: Identifying and vetting the appropriate
CRO partner
– No local CROs
– Only a handful of Regional CROs working in Indonesia
• The approach:
– Decided on one regional CRO
– Worked on setting clear expectations on how the study should
be conducted
Task distribution (assigning of responsibility)
Which SOPs were going to be used
– Increased communication
– Thorough training of CRO staff and co-monitoring visits
Indonesia
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• Challenge: Investigators and Staff experience
– Lack of clinical trial experience
– Gaps between concept and reality in the field
• The approach:
– Incorporation of GCP, ethical practices, clinical management
training into Investigator Meetings, CRA/interviewer training,
monitor training
Special emphasis on informed consent process
The training methods paralleled the expected performance of the study
team
– Site-based CRAs conducting source data verifications during patient
recruitment process
– Increased site monitoring
Indonesia
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• Challenge: Local infrastructure and sites constraints
– Lack computerized central patient database systems
– Lack of secure storage space
– Difficult internet and phone access
– Understaffing
• The approach:
– Site auditing prior to contract signature
– Financial investments made into resources and personnel
– Regular monitoring
Indonesia
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• Challenge: Cultural Complexities
– Hierarchical social structure impacts recruitment
Investigator
Site
Patient
• Our approach:
– Build trust and cultivate relationships
Principal Investigator
Key Opinion leaders
– Involve hospital administration in site selection and start up
activities
– Train and inform on “foreign” practices and international
expectations
Indonesia
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Clinical Sites –
Inspections by The Numbers
(closed since 1977; as of 2009 and / = 10/1/2008 to 9/30/2013)
U.S. – 7,920/1,082
Canada – 159/31
UK – 98/25
Germany – 67/51
France – 53/28
Russia – 50/53
Italy – 38/18
Poland – 38/48
Sweden – 38/4
South Africa – 30/16
Belgium – 28/4
Netherlands – 27/8
Argentina – 25/16
Brazil – 20/18
Mexico – 18/5
Spain – 18/13
Australia – 9/5
India – 8/33
China – 7/16
Japan – 3/7
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FDA -- Enforcing GCP Compliance Overseas
• Very limited foreign examples – only a few
warning letters aimed at foreign clinical
investigators.
• But, if done under a U.S. IND, must meet all
clinical study requirements
– IND rules – Part 312
– Informed Consent – Part 50
– Financial Disclosure – Part 54
– EC/IRB – Part 56
– AE reporting
• Thus, U.S. enforcement activity provides clear
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Moscow City Hospital WL -- 2006
• You failed to maintain adequate and accurate case
histories that record all observations and data pertinent to
the investigation [21 CFR 312.62(b)] .
– For Subject #_, the baseline ECG recording obtained on June 21, 2004,
and the, Visit 4 ECG recording obtained on August 3, 2004, were
identical except for the information hand-written on each ECG,
including subject number and date of tracing.
– For Subject #_, the baseline ECG recording obtained on June 21, 2004,
and the Visit 4 ECG recording obtained on Aug 2, 2004, were identical
except for the information hand-written on each ECG, including subject
number and date of tracing.
– Source records for Subjects #_ and #_, document that the same
individual performed the baseline physical examinations on the same day
(June 21, 2004) and at the same time (0900).
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Moscow City Hospital WL – 2006 …
• You failed to maintain adequate records of the
disposition of the drug including dates, quantity
and use by subjects [21 CPR 312.62(a)] .
– Dispensing records show 5 mg. given out to Subject X, but
2.5 mg. tabs returned by same Subject
• Length of inspection – 3 days
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Children’s Hospital of E. Ontario WL -- 2003
• You failed to protect the rights, safety, and welfare
of subjects under your care and failed to ensure
that the investigation was conducted according to
the investigational plan. [21 CFR 5 312.60]
– overdoses of the study drug interleukin-2 (IL-2) that were
22 to 25 times higher than the dose specified in the protocol
One death
– Cause – incorrect dosing form used that did not jibe with
the protocol
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Children’s Hospital of E. Ontario WL …
• You failed to ensure that the investigation was conducted
according to the investigational plan. [21 CFR 312.60].
– Subject hospitalized for three days, but not so documented.
– Records did not say at all how long she was in hospital
– CRFs submitted 4 months late; required under protocol to be filed in
one week
– No record of storage in refrigerated conditions as required by protocol
• Length of inspection – 5 days per WL
• Average length of U.S. inspections leading to WL’s –
sampling of 10 from last two years, showed average
number of days (measured start to finish) was 28 days
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• Bioequivalence study in Argentina – pivotal to
application
• FDA audited site -- retained samples of drug were
thrown out
• FDA -- not clear which patients got Study drug vs.
brand
• FDA – Complete Response Letter -- we can’t verify
what drugs the patients got, thus the study results are
not acceptable
• Company – the test drug was very different looking than
the comparator (but do the CRFs, etc., reflect that)?
Adventrx
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• Advance preparation and strategy development
• Thorough knowledge of local processes and operations
• Design trial with an implementable protocol
• Upfront dialogue and partnership-oriented approaches
• Identify a CRO that is suitable for you
• Know your limitations and how much you are willing to concede to
your vendors
• Audit CRO, site and monitors
• GCP training before start of the study
• Close monitoring during the study
• What is your plan B? Have one!
Lessons Learned
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• International Compilation of Human Research Protections
(OHRP) [new version coming soon]
http://www.hhs.gov/ohrp/international/intlcompilation/hspcom
pilation-v20101130.pdf
• European Forum for Good Clinical Practice (EFGCP) – state
by state info available
– http://www.efgcp.be/efgcpreports.asp?l1=5&l2=1
• Legislations, Regulations and Guidelines – from
GCPHelpDesk – country by country links
http://www.gcphelpdesk.com/index.php/gcp-guidelines
• Reviewing Clinical Trials: A Guide for the Ethics
Committee; Editors: Johan PE Karlberg and Marjorie A Speers
http://www.pfizer.com/files/research/research_clinical_trials/et
hics_committee_guide.pdf
Some Resources
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Acknowledgements
• My thanks to these clinical research, legal and
regulatory professionals who contributed key points
included in this presentation:
– Damien Bove, Bove Consulting
– Robert Church, Hogan Lovells
– Susanna Corritori, Corritori Consulting
– Stephanie Finnegan, bioRASI
– Laurie Halloran, Halloran Consulting
– Donald Harkness, Edwards Lifesciences
– Kristine Rapp, Hospira
– Jerry Stein, Halloran Consulting
– Laurie Taddonio, Taddonio Consulting
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Questions?
• Call, e-mail or fax:
Michael A. Swit, Esq.
Special Counsel, FDA Practice
Duane Morris LLP
San Diego, California
direct: 619-744-2215
fax: 619-923-2648
maswit@duanemorris.com
• Follow me on:
– LinkedIn: http://www.linkedin.com/in/michaelswit
– Twitter: https://twitter.com/FDACounsel
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About Your Speaker
Michael A. Swit, Esq., is a Special Counsel in the San Diego office of the international law firm,
Duane Morris, LLP, where he focuses his practice on solving FDA legal challenges faced by
highly-regulated pharmaceutical and medical device companies. Before joining Duane Morris in
March 2012, Swit served for seven years as a vice president at The Weinberg Group Inc., a
preeminent scientific and regulatory consulting firm in the Life Sciences. His expertise includes
product development, compliance and enforcement, recalls and crisis management, submissions
and related traditional FDA regulatory activities, labeling and advertising, and clinical research
efforts for all types of life sciences companies, with a particular emphasis on drugs, biologics and
therapeutic biotech products. Mr. Swit has been addressing vital FDA legal and regulatory issues
since 1984, both in private practice with McKenna & Cuneo and Heller Ehrman, and as vice
president, general counsel and secretary of Par Pharmaceutical, a top public generic and specialty
drug firm. He also was, from 1994 to 1998, CEO of FDANews.com, a premier publisher of
regulatory newsletters and other specialty information products for FDA-regulated firms. He has
taught and written on many topics relating to FDA regulation and associated commercial
activities and is a past member of the Food & Drug Law Journal Editorial Board. He earned his
A.B., magna cum laude, with high honors in history, at Bowdoin College, and his law degree at
Emory University.
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