This document summarizes a presentation on responding to FDA inspections and warning letters. It discusses Commissioner Hamburg's 2009 speech that revived FDA's compliance culture and enforcement efforts. It outlines FDA's expectations for timely responses to Form 483 observations and warning letters. It provides tips for how companies can prepare for and handle inspections, including designating personnel roles and training employees. It also offers guidance on writing effective responses to Form 483s and warning letters that address each violation, present corrective actions, and minimize future regulatory risks.
A guide for how to survive a FDA Warning letter. So you got at FDA 483 and now you have a FDA Warning Letter, learn how to survive the storm. For more information go to http://compliance-insight.com/fda-483-warning-letters/
This presentation is aimed at providing information on automation in the GLP practices in the pharmaceutical industry.
-Standard Operating Procedures.
-Documentation in GALP.
-Logs and Related Forms.
Responding Effectively to FDA 483 Observations & Warning LettersMaetrics
You receive a Warning Letter-- you have 15 days to submit a response. If FDA finds your response inadequate, you may receive a Consent Decree, which will cost millions to remediate. You need a process in place to react to a Warning Letter before it is delivered. These experts will discuss planning, procedures, training and ways to keep from getting a warning letter in the first place.
Documentation in Pharmaceutical Industry.pptxAartiVats5
This document discusses various types of documentation required in the pharmaceutical industry, including exploratory product development briefs (EPDBs), product development plans (PDPs), and product development reports (PDRs). It also discusses drug master files (DMFs). The EPDB describes the drug substance and product. The PDP provides guidance for product development stages. The PDR provides a comprehensive understanding of the product and manufacturing process. Finally, the DMF contains confidential information used to support regulatory requirements for quality, safety and efficacy.
This document provides guidance on preparing for an FDA pre-approval inspection. It discusses what to expect during an inspection, including that inspectors will review documentation for compliance with quality standards. It stresses the importance of managing the inspection through preparation, including conducting internal audits and training personnel. It also recommends designating an inspection team to guide the process and handle document requests. The overall goal is to demonstrate control over quality issues to avoid delays in approval.
GAMP 5 provides a framework for validating computerized systems used in regulated industries. It recommends a life cycle approach involving quality risk management throughout planning, development, validation and operation. Key activities for regulated companies include governance, identifying systems' impact, and ensuring compliance. Suppliers play an important role by providing documentation, testing systems, and supporting changes and maintenance. The level of validation should be based on a system's risk, complexity and novelty.
How to succeed when you get a FDA 483 form letter. What to do and how to handle your FDA 483. For more information go to http://compliance-insight.com/fda-483-warning-letters/fda-483-observations/
A guide for how to survive a FDA Warning letter. So you got at FDA 483 and now you have a FDA Warning Letter, learn how to survive the storm. For more information go to http://compliance-insight.com/fda-483-warning-letters/
This presentation is aimed at providing information on automation in the GLP practices in the pharmaceutical industry.
-Standard Operating Procedures.
-Documentation in GALP.
-Logs and Related Forms.
Responding Effectively to FDA 483 Observations & Warning LettersMaetrics
You receive a Warning Letter-- you have 15 days to submit a response. If FDA finds your response inadequate, you may receive a Consent Decree, which will cost millions to remediate. You need a process in place to react to a Warning Letter before it is delivered. These experts will discuss planning, procedures, training and ways to keep from getting a warning letter in the first place.
Documentation in Pharmaceutical Industry.pptxAartiVats5
This document discusses various types of documentation required in the pharmaceutical industry, including exploratory product development briefs (EPDBs), product development plans (PDPs), and product development reports (PDRs). It also discusses drug master files (DMFs). The EPDB describes the drug substance and product. The PDP provides guidance for product development stages. The PDR provides a comprehensive understanding of the product and manufacturing process. Finally, the DMF contains confidential information used to support regulatory requirements for quality, safety and efficacy.
This document provides guidance on preparing for an FDA pre-approval inspection. It discusses what to expect during an inspection, including that inspectors will review documentation for compliance with quality standards. It stresses the importance of managing the inspection through preparation, including conducting internal audits and training personnel. It also recommends designating an inspection team to guide the process and handle document requests. The overall goal is to demonstrate control over quality issues to avoid delays in approval.
GAMP 5 provides a framework for validating computerized systems used in regulated industries. It recommends a life cycle approach involving quality risk management throughout planning, development, validation and operation. Key activities for regulated companies include governance, identifying systems' impact, and ensuring compliance. Suppliers play an important role by providing documentation, testing systems, and supporting changes and maintenance. The level of validation should be based on a system's risk, complexity and novelty.
How to succeed when you get a FDA 483 form letter. What to do and how to handle your FDA 483. For more information go to http://compliance-insight.com/fda-483-warning-letters/fda-483-observations/
The document defines FDA warning letters and describes the process of FDA inspections that can lead to warning letters. It explains that warning letters notify companies of violations found during inspections and investigations. Companies must promptly correct issues and FDA will check that corrections are adequate. The document also describes different types of warning letters for various regulated industries and how to browse existing warning letters on the FDA website.
This document summarizes the objectives and classification system of the Global Harmonization Task Force (GHTF) for in vitro diagnostic (IVD) medical devices. The GHTF was founded in 1993 to harmonize medical device regulations globally. It aims to facilitate trade while preserving public health. IVD medical devices are classified into 4 risk-based classes (A to D) based on 16 general rules related to device invasiveness, energy use, and disease detection. Class A devices pose the lowest risk while Class D the highest. The classification system aims to ensure regulatory oversight is proportionate to device risk.
The document discusses GMP compliance audits. It defines GMP audits as a process to verify that manufacturers follow good manufacturing practices regulations. There are two types of audits - onsite audits, which involve visiting the production site, and desktop audits, which review documentation without a site visit. Audits check various aspects of production including personnel, facilities, equipment, processes, warehousing and more. They help identify issues, ensure proper controls, and improve compliance.
The document discusses the inspection of drug distribution channels. It covers the qualifications and attributes of drug inspectors, which include good knowledge of pharmacy laws and regulations, as well as integrity and communication skills. It also describes the organizational aspects of inspectors and different methods of inspection, such as comprehensive, concise, follow-up, and investigative inspections. The objectives of inspecting establishments are to ensure protection of patients, high ethical standards, and compliance with regulations. Special categories of drugs may require a modified inspection procedure.
Change control is a formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might effect a validated status. The intent is to determine the need for the action that would ensure that the system is maintained in a validated state.
The document summarizes changes to ISO 14155:2020 for clinical investigations involving medical devices. It notes that the standard now explicitly includes post-market investigations and software devices. Key changes include expanded risk-based monitoring allowing on-site or centralized approaches, new event escalation procedures, and emphasis on risk management throughout the clinical trial process. While GCP principles are becoming more aligned between ISO 14155 and ICH-GCP, some differences remain in adverse event reporting and how product risks and training are addressed.
Abriviated new drug application 505(j) fillingshahnawazQuadir
An abbreviated new drug application (ANDA) allows generic drug manufacturers to file for FDA approval of a generic drug. The ANDA relies on the safety and efficacy data of an approved innovator drug and must demonstrate bioequivalence through bioavailability/bioequivalence studies. There are different types of ANDA applications including Paragraph I, II, III, and IV, with Paragraph IV applications being used when a generic applicant is attempting to enter the market before patent expiration by claiming the patents are invalid or would not be infringed by the generic product. The ANDA review process involves a 30 month stay if the innovator sues for patent infringement within 45 days, during which time the first approved generic receives 180 days of market
The document discusses guidelines for Active Substance Master Files (ASMF) and European Drug Master Files (EDMF) in the European Union. Some key points:
- An ASMF/EDMF contains quality and quality control information for an active pharmaceutical ingredient. It has two parts - an applicant part given to marketing authorization applicants, and a restricted part for regulatory authorities.
- The ASMF procedure can be used for new active substances, existing substances not in pharmacopeias, and pharmacopeial substances. It cannot be used for biological substances.
- Marketing authorization applicants must include specified information from the ASMF in their application dossier and have access to the current active substance manufacturer. ASMF
This document provides guidelines on good distribution practices for biological products in India. It outlines general principles for maintaining quality throughout the distribution chain from manufacturer to patient. Key points include:
- Establishing an organizational structure and quality system for all entities involved in storage and distribution. This includes training personnel, implementing standard operating procedures, and conducting self-inspections.
- Ensuring suitable premises, equipment, vehicles and environmental conditions for storage and transportation in compliance with product and regulatory requirements. Critical factors like temperature, humidity and cleanliness must be controlled.
- Maintaining appropriate documentation systems to allow for traceability of products and support recalls or returns if needed. Deviations from storage/transport conditions should be investigated and corrective actions
Lean what 21 CFR Parts 210 and 211 are and how you an implement these regulations in your organization. For more information and tips on compliance go to http://compliance-insight.com/fda-gcp-and-gmp-training/21-cfr-210-211/
This document discusses various post-approval requirements and processes for pharmaceutical drugs, including prior approval supplements, changes being effected in 30 days supplements, annual reports, labeling changes, recalls, FDA inspections, and ISO 31000 risk management standards. It provides details on submission requirements and timelines for different types of post-approval changes, as well as FDA enforcement actions like warning letters, seizures, and injunctions.
Presentation at ACI Conference on FDA Enforcement, covered:
Warning Letters, FDA Case Referral Process/Role of DOJ and U.S. Attorney, Coordination with States, Collateral Consequences of FDA Enforcement Actions
This presentation is about the validation of software. It focus on the validation of software used in pharmacy. It contains definition of validation, computer system and validation of computer system. It explains the models which are used for software validation and on example i.e. HPLC software validation.
plasma master file is a EU requirement for the apploval of the biologics or the biosimilars to the EU in a eCTD format or Nees as per the requirement type and should contain the above given details
The document summarizes the Code of Federal Regulations Title 21 Part 822, which provides procedures and requirements for post-market surveillance of medical devices. It outlines the subparts which address general provisions, notification, post-market surveillance plans, FDA review and action, responsibilities of manufacturers, waivers and exemptions, and records and reports. The purpose is to implement post-market surveillance authority to maximize collection of useful safety data on medical devices after market release. Manufacturers must submit surveillance plans for FDA approval and are responsible for conducting approved plans to monitor devices and report data and issues.
This document discusses clinical trial safety and pharmacovigilance responsibilities in Europe. It outlines legislation and definitions for adverse events, serious adverse reactions, and unexpected serious adverse reactions. It describes investigator responsibilities to notify sponsors of suspected unexpected serious adverse reactions within 24 hours. It also outlines sponsor responsibilities to report fatal or life-threatening unexpected serious adverse reactions to competent authorities and ethics committees within 7 days. Finally, it discusses periodic safety reporting requirements including annual safety reports and periodic safety update reports required for marketed products.
Raj Bhogal, Head of Regulatory Inspections, R&D Quality Takeda on the topic of 'Pharmacovigilance Inspections' at IFAH held at Le Meridien, Dubai on 16th - 18th December, 2019.
The document provides guidance on the Plasma Master File (PMF) certification process and evaluation of transmissible spongiform encephalopathy (TSE) and bovine spongiform encephalopathy (BSE) risk. It outlines the PMF submission and evaluation procedure, including the use of an electronic common technical document format. It also describes TSE and BSE as rare brain diseases caused by prion proteins, and the regulatory compliance and risk assessment measures taken to prevent transmission through pharmaceutical and biological products derived from animal sources.
The document discusses New Drug Applications (NDAs) submitted to the FDA for approval of new drug products. It describes how NDAs contain data from animal and human clinical trials demonstrating a drug's safety and effectiveness. There are different types of NDAs depending on if a drug is novel or similar to existing drugs. The FDA reviews NDAs to determine if manufacturing is adequate and if a drug's benefits outweigh its risks based on the application contents and recommendations are made for approval or further work required. Approved drugs require ongoing safety monitoring and reporting to the FDA.
The European Commission Health and Consumers Directorate – General has published a draft “GUIDELINES ON THE PRINCIPLES OF GOOD DISTRIBUTION PRACTICES FOR ACTIVE SUBSTANCES FOR MEDICINAL PRODUCTS FOR HUMAN USE”.
The guideline addresses Quality systems, Personnel, Documentation, Order, Procedures, Records, Premises and Equipment, Receipts, Storage , Deliveries to Customers, Transfer of Information and Returns.
Following presentation is prepared by “ Drug Regulations” a non profit organization which provides free online resource to the Pharmaceutical Professional.
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
FDA Enforcement: The Cop is Back – How Enhanced Enforcement Can Impact You a...Michael Swit
December 15, 2010 webinar sponsored by The Weinberg Group on increased FDA enforcement activity under the Obama administration, with a focus on:
Enforcement Trends Prior to Obama Administration
Commissioner Hamburg Revives FDA’s Compliance Culture –The August 6, 2009 Speech and its Impact
Key FDA Enforcement Actions
How to Prepare for Increased Enforcement
How to Respond if Targeted
Consequences of Non-Compliance
FDA’s Record under Enhanced Compliance
The document defines FDA warning letters and describes the process of FDA inspections that can lead to warning letters. It explains that warning letters notify companies of violations found during inspections and investigations. Companies must promptly correct issues and FDA will check that corrections are adequate. The document also describes different types of warning letters for various regulated industries and how to browse existing warning letters on the FDA website.
This document summarizes the objectives and classification system of the Global Harmonization Task Force (GHTF) for in vitro diagnostic (IVD) medical devices. The GHTF was founded in 1993 to harmonize medical device regulations globally. It aims to facilitate trade while preserving public health. IVD medical devices are classified into 4 risk-based classes (A to D) based on 16 general rules related to device invasiveness, energy use, and disease detection. Class A devices pose the lowest risk while Class D the highest. The classification system aims to ensure regulatory oversight is proportionate to device risk.
The document discusses GMP compliance audits. It defines GMP audits as a process to verify that manufacturers follow good manufacturing practices regulations. There are two types of audits - onsite audits, which involve visiting the production site, and desktop audits, which review documentation without a site visit. Audits check various aspects of production including personnel, facilities, equipment, processes, warehousing and more. They help identify issues, ensure proper controls, and improve compliance.
The document discusses the inspection of drug distribution channels. It covers the qualifications and attributes of drug inspectors, which include good knowledge of pharmacy laws and regulations, as well as integrity and communication skills. It also describes the organizational aspects of inspectors and different methods of inspection, such as comprehensive, concise, follow-up, and investigative inspections. The objectives of inspecting establishments are to ensure protection of patients, high ethical standards, and compliance with regulations. Special categories of drugs may require a modified inspection procedure.
Change control is a formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might effect a validated status. The intent is to determine the need for the action that would ensure that the system is maintained in a validated state.
The document summarizes changes to ISO 14155:2020 for clinical investigations involving medical devices. It notes that the standard now explicitly includes post-market investigations and software devices. Key changes include expanded risk-based monitoring allowing on-site or centralized approaches, new event escalation procedures, and emphasis on risk management throughout the clinical trial process. While GCP principles are becoming more aligned between ISO 14155 and ICH-GCP, some differences remain in adverse event reporting and how product risks and training are addressed.
Abriviated new drug application 505(j) fillingshahnawazQuadir
An abbreviated new drug application (ANDA) allows generic drug manufacturers to file for FDA approval of a generic drug. The ANDA relies on the safety and efficacy data of an approved innovator drug and must demonstrate bioequivalence through bioavailability/bioequivalence studies. There are different types of ANDA applications including Paragraph I, II, III, and IV, with Paragraph IV applications being used when a generic applicant is attempting to enter the market before patent expiration by claiming the patents are invalid or would not be infringed by the generic product. The ANDA review process involves a 30 month stay if the innovator sues for patent infringement within 45 days, during which time the first approved generic receives 180 days of market
The document discusses guidelines for Active Substance Master Files (ASMF) and European Drug Master Files (EDMF) in the European Union. Some key points:
- An ASMF/EDMF contains quality and quality control information for an active pharmaceutical ingredient. It has two parts - an applicant part given to marketing authorization applicants, and a restricted part for regulatory authorities.
- The ASMF procedure can be used for new active substances, existing substances not in pharmacopeias, and pharmacopeial substances. It cannot be used for biological substances.
- Marketing authorization applicants must include specified information from the ASMF in their application dossier and have access to the current active substance manufacturer. ASMF
This document provides guidelines on good distribution practices for biological products in India. It outlines general principles for maintaining quality throughout the distribution chain from manufacturer to patient. Key points include:
- Establishing an organizational structure and quality system for all entities involved in storage and distribution. This includes training personnel, implementing standard operating procedures, and conducting self-inspections.
- Ensuring suitable premises, equipment, vehicles and environmental conditions for storage and transportation in compliance with product and regulatory requirements. Critical factors like temperature, humidity and cleanliness must be controlled.
- Maintaining appropriate documentation systems to allow for traceability of products and support recalls or returns if needed. Deviations from storage/transport conditions should be investigated and corrective actions
Lean what 21 CFR Parts 210 and 211 are and how you an implement these regulations in your organization. For more information and tips on compliance go to http://compliance-insight.com/fda-gcp-and-gmp-training/21-cfr-210-211/
This document discusses various post-approval requirements and processes for pharmaceutical drugs, including prior approval supplements, changes being effected in 30 days supplements, annual reports, labeling changes, recalls, FDA inspections, and ISO 31000 risk management standards. It provides details on submission requirements and timelines for different types of post-approval changes, as well as FDA enforcement actions like warning letters, seizures, and injunctions.
Presentation at ACI Conference on FDA Enforcement, covered:
Warning Letters, FDA Case Referral Process/Role of DOJ and U.S. Attorney, Coordination with States, Collateral Consequences of FDA Enforcement Actions
This presentation is about the validation of software. It focus on the validation of software used in pharmacy. It contains definition of validation, computer system and validation of computer system. It explains the models which are used for software validation and on example i.e. HPLC software validation.
plasma master file is a EU requirement for the apploval of the biologics or the biosimilars to the EU in a eCTD format or Nees as per the requirement type and should contain the above given details
The document summarizes the Code of Federal Regulations Title 21 Part 822, which provides procedures and requirements for post-market surveillance of medical devices. It outlines the subparts which address general provisions, notification, post-market surveillance plans, FDA review and action, responsibilities of manufacturers, waivers and exemptions, and records and reports. The purpose is to implement post-market surveillance authority to maximize collection of useful safety data on medical devices after market release. Manufacturers must submit surveillance plans for FDA approval and are responsible for conducting approved plans to monitor devices and report data and issues.
This document discusses clinical trial safety and pharmacovigilance responsibilities in Europe. It outlines legislation and definitions for adverse events, serious adverse reactions, and unexpected serious adverse reactions. It describes investigator responsibilities to notify sponsors of suspected unexpected serious adverse reactions within 24 hours. It also outlines sponsor responsibilities to report fatal or life-threatening unexpected serious adverse reactions to competent authorities and ethics committees within 7 days. Finally, it discusses periodic safety reporting requirements including annual safety reports and periodic safety update reports required for marketed products.
Raj Bhogal, Head of Regulatory Inspections, R&D Quality Takeda on the topic of 'Pharmacovigilance Inspections' at IFAH held at Le Meridien, Dubai on 16th - 18th December, 2019.
The document provides guidance on the Plasma Master File (PMF) certification process and evaluation of transmissible spongiform encephalopathy (TSE) and bovine spongiform encephalopathy (BSE) risk. It outlines the PMF submission and evaluation procedure, including the use of an electronic common technical document format. It also describes TSE and BSE as rare brain diseases caused by prion proteins, and the regulatory compliance and risk assessment measures taken to prevent transmission through pharmaceutical and biological products derived from animal sources.
The document discusses New Drug Applications (NDAs) submitted to the FDA for approval of new drug products. It describes how NDAs contain data from animal and human clinical trials demonstrating a drug's safety and effectiveness. There are different types of NDAs depending on if a drug is novel or similar to existing drugs. The FDA reviews NDAs to determine if manufacturing is adequate and if a drug's benefits outweigh its risks based on the application contents and recommendations are made for approval or further work required. Approved drugs require ongoing safety monitoring and reporting to the FDA.
The European Commission Health and Consumers Directorate – General has published a draft “GUIDELINES ON THE PRINCIPLES OF GOOD DISTRIBUTION PRACTICES FOR ACTIVE SUBSTANCES FOR MEDICINAL PRODUCTS FOR HUMAN USE”.
The guideline addresses Quality systems, Personnel, Documentation, Order, Procedures, Records, Premises and Equipment, Receipts, Storage , Deliveries to Customers, Transfer of Information and Returns.
Following presentation is prepared by “ Drug Regulations” a non profit organization which provides free online resource to the Pharmaceutical Professional.
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
FDA Enforcement: The Cop is Back – How Enhanced Enforcement Can Impact You a...Michael Swit
December 15, 2010 webinar sponsored by The Weinberg Group on increased FDA enforcement activity under the Obama administration, with a focus on:
Enforcement Trends Prior to Obama Administration
Commissioner Hamburg Revives FDA’s Compliance Culture –The August 6, 2009 Speech and its Impact
Key FDA Enforcement Actions
How to Prepare for Increased Enforcement
How to Respond if Targeted
Consequences of Non-Compliance
FDA’s Record under Enhanced Compliance
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
FDA’s New Strategy on Enforcement: The Growing Perils of Inadequate ComplianceMichael Swit
September 9, 2009 webinar sponsored by The Weinberg Group, with a focus on FDA's renewed commitment to enforcement announced by FDA Commissioner Hamburg on August 6, 2009, with a focus on:
Enforcement Trends Prior to Obama Administration
Commissioner Hamburg Revives FDA’s Compliance
Culture – The August 6, 2009 Speech and its Impact
How to Prepare for Increased Enforcement
How to Respond if Targeted
Consequences of Non-Compliance
FDA Enforcement -- the Perils of Inadequate ComplianceMichael Swit
This document summarizes a presentation about increased FDA enforcement of compliance. It discusses trends in FDA inspections, warning letters, seizures, and injunctions prior to 2009. It outlines a 2009 speech by FDA Commissioner Hamburg that revived the agency's compliance culture and established new enforcement mandates, including imposing deadlines for inspection responses, prioritizing follow-up on warnings, and taking rapid action when public health is at risk. The presentation advises preparing for enforcement by establishing a culture of compliance, building robust quality systems, and responding promptly and completely if targeted. It notes the serious consequences of non-compliance for companies and individuals.
June 24, 2015 Presentation to the Regulatory Affairs Certification (RAC) Test Review Course sponsored by the San Diego Regulatory Affairs Network, with a focus on regulation of ANDAs, OTC drugs, and Orphan Drugs, covering these issues relating to generic drugs:
♦ Basics
♦ User Fees
♦ Power
♦ Addressing Abuses – by Rule & Statute
♦ Biosimilars – Basics of New Law
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
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.
FDA Enforcement -- the Perils of Inadequate ComplianceMichael Swit
Presentation on December 3, 2009 to Southern California Biomedical Council Regulatory Workshop, Irvine, CA, with a focus on:
Enforcement Trends Prior to Obama Administration
Commissioner Hamburg Revives FDA’s Compliance
Culture – The August 6, 2009 Speech and its Impact
How to Prepare for Increased Enforcement
How to Respond if Targeted
Consequences of Non-Compliance
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.
FDA Regulatory Considerations for Life Sciences CompaniesMichael Swit
April 2008 presentation to Swedish-American Chamber of Commerce Entrepreneurial Days on FDA issues for product development, including focus on:
Planning, approval process, barriers to entry
FDA Warning Letters: Key Legal and Tactical Issues in Dealing with FDA's "Sh...Michael Swit
April 30, 2014 webinar sponsored by Duane Morris, with a focus on:
• Why FDA Issues Warning Letters – and How the
Agency Expects Management to Act When You Get
One
• How to Respond to A Warning Letter
• Inspection Responses That Failed to Hold Off FDA
From Issuing a Warning Letter (quick review)
• FDA Powers Beyond the Warning Letter – What the
Agency Can Do to You if It Does Not Like Your Reply
• The Evidentiary Status of a Warning Letter in Other
Litigation – J&J v. State of Arkansas
GCP Enforcement Trends Lessons Learned from FDA Inspections of Sponsors, Site...Michael Swit
July 21, 2015 Webinar sponsored by FDANews.com, with a focus on:
* How to avoid enforcement by complying
* FDA statistics on enforcement actions in the clinical research arena
* Key observations by sponsor, IRB, and investigator
A FDA Crisis History -- The Generic Drug ScandalMichael Swit
Webinar given to the Regulatory Affairs Professionals Society (RAPS) Rising Leaders Program using a case study of the generic drug scandal as a basis to understanding how to react to a scandal, SEC disclosure duties, collateral consequences of a crisis, and lessons learned.
FDA Enforcement – Trends, Powers and Penalties Or “Why Crime Does Not Pay”Michael Swit
June 12, 2009 presentation to the Southern California Biomedical Council on FDA enforcement, with a focus on:
FDA Regulatory/Enforcement Authority --
Understanding
FDA Enforcement Trends
Drugs
Devices
Clinical Trials
Collateral Consequences of FDA Violations
FDA Inspections: Handling the Consequences -- or Understanding How Ugly It C...Michael Swit
Presentation to the MAGI Clinical Research Conference – 2018 East, given on May 22, 2018 in Arlington, Virginia, and focusing on the collateral consequences of negative FDA inspections in the clinical research arena
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.
Regulatory Considerations in Product DevelopmentMichael Swit
Presentation to the LARTA (www.larta.org) NIH-CAP Workshop in November 2011 on how to develop FDA-regulated products, with a focus on planning, working with FDA,
Similar to Successfully Responding to FDA Inspections (483s) & Warning Letters (20)
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.
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.
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.
June 14, 2018 presentation to the San Diego Regulatory Affairs Network (SDRAN) Regulatory Affairs Certification (RAC) Review Course on the basics of FDA regulation of generic drugs and biosimilars.
Recent FDA Developments in Digital Health & Clinical Decision Support SoftwareMichael Swit
June 7, 2018 presentation at the 4th Annual Medical Device Summit, sponsored by ComplianceOnline, in San Francisco, focusing on the impact of the 21st Century Cures Act and other developments on how FDA regulates software in the medical device arena, including mobile medical applications.
What’s In a Name? FDA and Non-Proprietary Names for Biologics/BiosimilarsMichael Swit
April 20, 2018 Presentation to the 11th Biosimilars & Follow-On Biologics 2018 Americas conference on FDA's Policy on Non-proprietary names for Biosimilars
Sangyun Lee, 'Why Korea's Merger Control Occasionally Fails: A Public Choice ...Sangyun Lee
Presentation slides for a session held on June 4, 2024, at Kyoto University. This presentation is based on the presenter’s recent paper, coauthored with Hwang Lee, Professor, Korea University, with the same title, published in the Journal of Business Administration & Law, Volume 34, No. 2 (April 2024). The paper, written in Korean, is available at <https://shorturl.at/GCWcI>.
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Successfully Responding to FDA Inspections (483s) & Warning Letters
1. Solving FDA Legal Challenges for the Life of a Life Sciences Company -1- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Successfully Responding to FDA
Inspections (483s) & Warning Letters
A Compliance2go Webinar
November 10, 2015
Michael A. Swit, Esq.
2. Solving FDA Legal Challenges for the Life of a Life Sciences Company -2- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Standard Disclaimers
➢ Views expressed here are solely mine and do not
reflect those of my law firm or any of its clients.
➢ This presentation supports an oral briefing and
should not be relied upon solely on its own to
support any conclusion of law or fact.
➢ These slides are intended to provide general
educational information and are not intended to
convey legal advice.
3. Solving FDA Legal Challenges for the Life of a Life Sciences Company -3- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
What I Will Cover
➢ FDA’s Expectations on Replying to Inspections &
Warning Letters – the August 2009 Hamburg Speech
➢ How to Handle The Actual Inspection
➢ How to Respond to 483s & Warning Letters
➢ Lessons from Actual Responses
4. Solving FDA Legal Challenges for the Life of a Life Sciences Company -4- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
How to Avoid Adverse Inspections & Warning
Letters
… in a Single Slide
5. Solving FDA Legal Challenges for the Life of a Life Sciences Company -5- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
The Answer Is Simple – Comply!
➢ But, how? –
➢ Please Teach Vigorous Risk Avoidance
Comprehensively & Corporately
– Thus, to ensure you comply, you must have:
• P = Procedures
• T = Training
• V = Validation
• R = Records
• A = Audits
• C = Communications – open channels
• C = Compliance Culture from the Top
6. Solving FDA Legal Challenges for the Life of a Life Sciences Company -6- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
FDA’s Enforcement Culture under and after
Commissioner Hamburg
6
7. Solving FDA Legal Challenges for the Life of a Life Sciences Company -7- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Commissioner Hamburg Revives FDA’s
Compliance Culture –
The August 6, 2009 Speech
and its Impact
7
8. Solving FDA Legal Challenges for the Life of a Life Sciences Company -8- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Hamburg: Why We Need Effective FDA
Enforcement
• Conceded FDA enforcement efforts have been
deficient
• Five key benefits of effective enforcement:
– Protect public health by promptly intercepting unsafe or
fraudulent products – prevents additional harm
– Deter others who might violate law
– Informs public of potential harm
– Creates level playing field for industry
– Instill public confidence in FDA
8
9. Solving FDA Legal Challenges for the Life of a Life Sciences Company -9- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Hamburg: Four Essential Elements for
Effective FDA Enforcement
➢ Vigilance – both FDA and Industry
– FDA – Regular inspections and follow-ups
– Companies
• Must work quickly and thoroughly to correct problems
• Must understand
– if you cross the line, “you will be caught”
– If you fail to act, FDA will
➢ Strategic enforcement –
– Greater focus on significant risks and violations
– More meaningful penalties to “send a strong message to
discourage future offenses”
10. Solving FDA Legal Challenges for the Life of a Life Sciences Company -10- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Four Essential Elements for
Effective Enforcement …
➢ Quick action – FDA must respond rapidly,
especially to:
– Egregious violations
– Violations that threaten the public health
➢ Visible efforts – FDA must show all stakeholders it
is on the job
– Will publicize enforcement actions widely – including
rationales for action
– Goal:
• Increase confidence in FDA
• Deter non-compliance
11. Solving FDA Legal Challenges for the Life of a Life Sciences Company -11- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Six FDA Enforcement Mandates …
➢ Impose clear post-inspection deadlines
– Generally –15 business days to respond to 483
– After that, agency can issue warning letter or take other
enforcement action
➢ Speed the warning letter process – by limiting review
by FDA Office of Chief Counsel to warning letters
that present significant legal issues
12. Solving FDA Legal Challenges for the Life of a Life Sciences Company -12- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Six FDA Enforcement Mandates …
➢ Work more closely with FDA’s regulatory partners
– Example: in some cases, such as food safety, state, local, and
international officials can act more quickly than FDA
– When public health is at risk, the agency will coordinate with its
regulatory partners to take rapid action
➢ Prioritize follow-up on all warning letters and other
enforcement actions
– FDA will work quickly to assess the corrective action taken by
industry after a warning letter, a major product recall, or other
enforcement action
– Via new inspection or other form of investigation
12
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LAW OFFICES OF MICHAEL A. SWIT
Six Enforcement Mandates …
➢ FDA will be prepared to take immediate action to
respond to public health risks
– Actions may occur before a formal warning letter is issued – at
any time
– Days of multiple responses to inspections – over
➢ Develop and implement a formal warning letter
“close-out” process
– If FDA determines a firm fully corrected violations in a warning
letter, agency will issue an official “close-out” notice and post on
FDA Web site
– Seen as an “important motivator” for corrective action
13
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LAW OFFICES OF MICHAEL A. SWIT
Enhanced Enforcement In Action –
Timely 483 Responses Policy
➢ Aug. 11 Federal Register notice – Post-inspection 483
responses timing policy published – 15 business days
➢ Timely Responses
– FDA will conduct “detailed review” in deciding any
enforcement action
– If FDA issues a warning letter, letter will address sufficiency of
response
14
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LAW OFFICES OF MICHAEL A. SWIT
Enhanced Enforcement In Action –
Timely 483 Responses Policy …
➢ Late responses
– Response will not be considered by FDA in deciding to take
enforcement action such as a warning letter
– If warning letter issues after a late 483 response, FDA will
consider the 483 response in assessing firm’s later reply to
warning letter
➢ Purpose of Warning Letter:
– “ensure … seriousness and scope of the violations are
understood by top management … and that the appropriate
resources are allocated to fully correct the violations and
prevent their recurrence”
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LAW OFFICES OF MICHAEL A. SWIT
2014 and 2013 Inspections Statistics
2014 2013
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LAW OFFICES OF MICHAEL A. SWIT
18. Solving FDA Legal Challenges for the Life of a Life Sciences Company -18- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
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LAW OFFICES OF MICHAEL A. SWIT
How to Handle The Actual Inspection
20. Solving FDA Legal Challenges for the Life of a Life Sciences Company -20- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
How to Prepare for an Inspection
➢ Know the training and tactics of FDA Investigators
– Investigations Operations Manual (IOM)
http://www.fda.gov/ICECI/Inspections/IOM/default.htm
• See how FDA approaches inspections
– Compliance Program Guidance Manuals
http://www.fda.gov/ICECI/ComplianceManuals/ComplianceProgramMan
ual/ucm2005382.htm
– Other Guidance Documents
➢ Review other Companies’ 483s and Warning Letters –
know what the current “hot buttons” are
21. Solving FDA Legal Challenges for the Life of a Life Sciences Company -21- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Preparing for an Inspection …
➢ Have a written corporate policy for FDA inspections
➢ Establish attitude of the company – must come from the top
➢ Conduct independent external audits and internal audits
– find the problems before FDA does
– FDA policy – written audits done under a regular audit procedure are
normally not subject to inspection [see Compliance Policy Guide
#130.300); exceptions:
• “Directed" or "for-cause" inspection and investigations of a sponsor or monitor of a clinical investigation;
• In litigation
• Inspection warrant where access to records is authorized by statute; and
• Judicial search warrant.
http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm073841.
htm
22. Solving FDA Legal Challenges for the Life of a Life Sciences Company -22- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Train Personnel for Inspections
➢ Every employee must know his/her job function and
regulatory obligations
➢ Designate an inspection coordinator
➢ Document employee credentials, training and
knowledge
– QA/QC, GCP documentation
– Study, manufacturing and other protocols
– FDA program and inspection guidance documents
23. Solving FDA Legal Challenges for the Life of a Life Sciences Company -23- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Corporate Inspection Policy & Procedures
➢ Address GCP, GMP, GLP and other types of
inspections/inquiries
➢ Designate Who will interact with FDA Investigator
– Inspection Coordinator and Inspection Group
– Clinical Director Study Coordinator/Principal Investigator
– Production Employees
– Receptionist/Secretary
24. Solving FDA Legal Challenges for the Life of a Life Sciences Company -24- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Inspections of Records
➢ What records will be made available – know what you
must disclose under Section 704
➢ Have specific policies on:
– photographs
– tape recorders
– copying records (shipping, financial and business records)
➢ Questioning of personnel
– no duty to answer verbal questions, but the reality is you should
– don’t speculate; if don’t know; say you will find out
➢ Sampling –
– if FDA samples, you sample
25. Solving FDA Legal Challenges for the Life of a Life Sciences Company -25- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Personnel Interacting With Inspector(s)
➢ Receptionist/Secretary -- confirm FDA is at correct
name and institution (e.g., Par v. Parmed; Par v. Barr);
record inspector’s badge number
➢ Never leave investigator unattended
➢ Receptionist should have list of inspection
coordinator and alternate persons:
– Clinical Director / Study Coordinator / Principal Investigator
– Production V.P. / Quality Control Manager
– Executive V.P. / President
– Legal Counsel
26. Solving FDA Legal Challenges for the Life of a Life Sciences Company -26- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Duties of Inspection Coordinator
➢ Examine Credentials and 482 Forms
➢ Ask What Type of Inspection
➢ Write down all pertinent information
– contact core group
• internal
• external – you should have key experts identified in advance
– e.g., “micro” expert
– FDA attorney
– work out inspection agenda
– inform investigator of corporate policies – e.g. photographs
27. Solving FDA Legal Challenges for the Life of a Life Sciences Company -27- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
General Tactics During Inspection
➢ Designate a Conference Room
➢ Don’t Allow Access to Areas Beyond Scope of
Inspection under § 704
– You get the items if needed
➢ Never Mislead the Investigator
➢ Don’t Panic (e.g., over missing documents, or
questions you don’t know answers for immediately)
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LAW OFFICES OF MICHAEL A. SWIT
Defensive Strategies During/After
Inspection to Avoid Enforcement
➢ Draw the investigator into a conversation when a
problem is identified:
– more details (so that I may investigate);
– how/why is what we are doing (apparently) inadequate (so I may
explain to management)
➢ Daily Debriefs
– internally after each day of inspection
– try to get FDA inspector to do a daily debrief
• what is planned for next day
29. Solving FDA Legal Challenges for the Life of a Life Sciences Company -29- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
FDA Investigative Techniques for
Gathering Evidence During Inspections
➢ Questioning employees at home at night or on the
weekend
– Permitted under FDCA Sec. 704
➢ Can go through trash, obtain grand jury subpoenas
and search warrants for telephone and business
records
➢ Collaboration with FBI and FDA’s OCI
30. Solving FDA Legal Challenges for the Life of a Life Sciences Company -30- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Home Interviews …
➢ Prepare employees to contact company legal counsel
before speaking with an investigator (this assures no
waiver or corporate privilege or disclosure of
confidential information)
➢ Company SOP should reflect desire to cooperate with
FDA to the extent that company understands the
purpose of the investigation and will not waive or
jeopardize its or its employees legal rights
31. Solving FDA Legal Challenges for the Life of a Life Sciences Company -31- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Inspection Exit Interview
➢ 483 Observations
➢ Ask For:
– Explanation and Details
– Examples
➢ Write Down Exactly What Investigator Says
– some firms are videotaping (OK by FDA per IOM)
➢ If observation has been corrected, ask that to be
noted on the 483
➢ If observation is wrong, politely engage in
dialogue. If you can show, inspector may delete
32. Solving FDA Legal Challenges for the Life of a Life Sciences Company -32- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Disagreements with 483 Observations
➢ Make notes of your requested comments and
include them in your 483 response
➢ Never “argue” with inspector
➢ Never make verbal promises, only written responses
– be careful with correction timelines
➢ Affidavits
– Never sign them and don’t even listen to a reading
– If they push, ask them to send to your attorney for review
33. Solving FDA Legal Challenges for the Life of a Life Sciences Company -33- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
The Written Response to
483s & Warning Letters
34. Solving FDA Legal Challenges for the Life of a Life Sciences Company -34- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
The Response – Assessing Allegations
➢ Assess each allegation/observation
– Focus on specifics
– Focus on system-wide implications
– Focus on global implications
– Consider affected products
– Consider root-cause analysis
➢ Focus on the regulatory requirement(s) associated
with each allegation/observation
➢ Develop corrective action plan to achieve immediate,
short-term, and long-term correction and to prevent
recurrence
– Know when to seek outside assistance
34
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LAW OFFICES OF MICHAEL A. SWIT
The Written Response
➢ Provide specific evidence to minimize public health
risk
– number/scope of product’s distribution
– ability to do stock withdrawal or recall
– technical assessment
➢ If inspection follows product recall,
– Note company was “on the ball” and caught the problem, as it
was supposed to; foreclosing greater risk
– If did not catch, say what changes are being made to catch
sentinel events/data in the future
36. Solving FDA Legal Challenges for the Life of a Life Sciences Company -36- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Written Response to the 483
➢ Address each observation separately
➢ Never agree that an observation is valid:
– instead, state changes you intend to make
➢ Disagreements:
• Present your argument – remember – Science wins!!
• Be responsive, not argumentative
➢ Attach copies of changed documents
➢ Time lines –
– be specific, but be sure
– deliver what you promised when you promised it
• Send in follow-ups when due on timelines
37. Solving FDA Legal Challenges for the Life of a Life Sciences Company -37- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Keys to The Written Response
➢ Show the likelihood of recurrence of the
problem/violation is low
➢ Show the company is doing all it can reasonably to
remedy the situation: specific steps, timetable,
monitoring
➢ Problems attributable to a specific cause have/will
be fixed with permanent remedies
➢ Show that senior management understands
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LAW OFFICES OF MICHAEL A. SWIT
FDA Expectation on Your Response
➢ Wants to Hear Your D.R.U.M. – expects your response
to have these qualities:
– Direct – i.e., address the items directly raised in the 483 or
warning letter
– Related – go beyond those to potentially related problems
– Universal – expand to review those issues company-wide
– Monitoring and Management –
• show that you will stay on top of the issues
• show that senior management is involved
Source: “Compliance and Enforcement.” Presentation by David K. Elder, Director, FDA Office of
Enforcement, at the Orange County Regulatory Affairs (OCRA)/FDA Joint Educational Conference.
June 15, 2005. Irvine, California.
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LAW OFFICES OF MICHAEL A. SWIT
483/EIR: Inspection Results
➢ NAI – “No action indicated” -- no objectionable
conditions or practices were found during the inspection (or
the objectionable conditions found do not justify further
regulatory action)
➢ VAI - “Voluntary action indicated” -- objectionable
conditions or practices were found, but the District is not
prepared to take or recommend any administrative or
regulatory action
➢ OAI – “Official action indicated” -- regulatory and/or
administrative actions will be recommended
40. Solving FDA Legal Challenges for the Life of a Life Sciences Company -40- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
FDA Enforcement Discretion
➢ Prior History of Company’s Compliance
– 483’s, warning letters, recalls, etc. -- and company’s
response(s)
➢ Health risks
➢ Likelihood of recurrence
➢ Discretion in action –
– K-V vs. FDA – Makena® pharmacy compounding
41. Solving FDA Legal Challenges for the Life of a Life Sciences Company -41- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Lessons from Actual Responses
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LAW OFFICES OF MICHAEL A. SWIT
Failure to Implement Corrections
➢ 7) Failure to adequately establish procedures for corrective and preventive action;
as required by 21 CFR 820.100(a). For example, your firm's CAPA procedures, QOP-
85-04, Corrective and Preventive Action do not require written documentation when
proposing a Corrective Action Request, therefore limiting the ability to determine
recurrence of nonconforming product or quality problems. Your firm has not defined
what constitutes a sufficiently serious or recurring nonconformity'' in either your
Corrective and Preventive Action procedures or your Supplier Evaluation and Monitoring
procedure, (QOP 74-01) to define the criteria to initiate a Corrective Action Request.
Additionally, your Control of Non-Conforming Product procedures (QOP-83-01) allow
your form to close out non-conforming product reports if a disposition decision is made
to "scrap" or accept product "as is" without further evaluation to determine if a corrective
or preventive action is appropriate. Your responses, dated March 7, 2012 and May 29,
2012 were inadequate. Your promised Corrective actions have not yet been
implemented.
➢ American OptiSurgical --
http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/ucm309410.htm
43. Solving FDA Legal Challenges for the Life of a Life Sciences Company -43- www.fdacounsel.com
LAW OFFICES OF MICHAEL A. SWIT
Inadequate Corrections
➢ Failure to develop, maintain, and implement written Medical Device
Reporting (MDR) procedures, as required by 21 CFR Part 803.17.
➢ For example: Your firm’s procedure does not include the requirements for submission of
MDRs to FDA. Your firm’s procedure, (b)(4) as written, does not establish internal systems that
provide for timely and effective identification, communication, and evaluation of events that
may be subject to MDR requirements, a standardized review process or procedure for
determining when an event meets the criteria for reporting, timely transmission of complete
medical device reports, and documentation and recordkeeping requirements, as required by 21
CFR Part 803.17.
➢ We reviewed your firm’s response dated June 1, 2011, and conclude that it is not
adequate. Although you provided an English translation of your firm’s
procedure, (b)(4) it does not meet the requirements of 21 CFR Part 803.17 as
stated above.
➢ Aesculap AG
➢ http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2011/ucm
273502.htm
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LAW OFFICES OF MICHAEL A. SWIT
Repeat Violations
➢ The first postmarketing adverse drug experience (ADE) reporting
compliance inspection of Acorda Therapeutics was conducted in 2006.
Observations from the 2006 inspection included late submission of 15-day
Alert reports, failure to develop written procedures, and failure to submit
follow-up reports. A second postmarketing ADE reporting compliance
inspection of Acorda Therapeutics was conducted in 2009. Observations
from the 2009 inspection included late submission of Field Alert Reports
and the repeat findings of late submission of 15-day Alert reports and
failure to develop written procedures. Additionally, during the 2009
inspection, the FDA Investigator noted that your firm did not complete
corrective actions until 2007, even though your response to FDA, dated
January 19, 2006, stated that all corrections had been made.
➢ Acorda Therapeutics
➢ http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/u
cm303979.htm
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LAW OFFICES OF MICHAEL A. SWIT
Not Including Revised/New Procedure
➢ Failure to establish and maintain procedures for receiving, reviewing and
evaluating complaints to determine whether the complaint represents an
event which is required to be reported to FDA under 21 CFR Part 803,
Medical Device Reporting, as required by 21 C.F.R. § 820.198(a)(3). From
December 2011 - January 2012, your firm received at least 11 complaints of
artifacts associated with the use of the Bella blanket during mammography
procedures. Review of these complaints revealed that you determined an adverse
event was not required, however, your firm did not obtain the information
necessary to make this determination. For example, you did not assess whether a
mammogram needed to be repeated or if the artifacts had the potential for
misdiagnosis for each complaint. Your response did not include a revised
complaint procedure.
➢ Beekley Corporation
➢ http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/u
cm309890.htm
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LAW OFFICES OF MICHAEL A. SWIT
Failure to Address Allegation
➢ 3. Failure to document the results of finished
acceptance activities as required by 21 CFR
820.80(e)(3). We acknowledge that you have implemented
a specification that your Bella blankets to now include a
“point” pattern, however you are not recording the results
of your inspections on your weekly “Production Report
Release approval “ forms. Your response does not
address this violation.
➢ Beekley Corporation
➢ http://www.fda.gov/ICECI/EnforcementActions/WarningL
etters/2012/ucm309890.htm
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LAW OFFICES OF MICHAEL A. SWIT
Not Addressing Cause of an Observation
➢ 5. Design validation did not include adequate risk analysis, as required by
21 CFR 820.30(g). For example, the risk analysis for the Adjustable Laser Probe
was incomplete, in that the Failure Mode and Effect Analysis (FMEA) was not
assessed for new risk determinations or for the revision of risk priority numbers
following a report of a device malfunction on June 21, 2010.
We have reviewed your response and have concluded that it is not adequate.
Your response to the observation was to cease distribution of the Adjustable
Laser Probe and to voluntarily recall the product. This response does not
address the corrective action necessary to address the cause of the
observation to prevent its recurrence. The observation merely used this
device as an example of a deviation. You must assure that design control
procedures are adequately established for all of its applicable devices.
➢ Peregrine Surgical --
http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2010/
ucm238045.htm
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LAW OFFICES OF MICHAEL A. SWIT
Inspection Observations Clash with Reply
➢ 1. Failure of management with executive responsibility to establish its policy
and objectives for, and commitment to, quality. Failure of management with
executive responsibility to ensure that the quality policy is understood,
implemented, and maintained at all levels of the organization, as required by
21 C.F.R 820.20 (a).
We have reviewed your responses and have concluded that they are inadequate. Your
response of April 15 states that quality procedures have been improved over the past
11 months and that meetings are held frequently to ensure full Quality System
regulation compliance. However, evidence obtained during this inspection does
not support this assertion. You do not appear to be following your Quality
Manual, for example failing to maintain complete design controls records,
and to document verification and validation activities.
➢ Allez Spine
➢ http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2008/ucm
1048186.htm
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LAW OFFICES OF MICHAEL A. SWIT
Failure to Do Root Cause Analysis
➢ d. Your firm has failed to thoroughly investigate several
customer complaints. For example, you received complaint #(b)(4)
on March 1, 2010, citing dark particulate matter in a vial of Heparin.
You investigated and determined that the particle was most likely
due to a vendor issue; however, you did not perform an assessment
of the vial supplier.
➢ In your response, you state that you have not identified any other
defects of this nature. Your response is inadequate since you
have not addressed the potential root cause of a vial defect as
identified in your investigation.
➢ APP Pharmaceuticals
➢ http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/u
cm293068.htm
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LAW OFFICES OF MICHAEL A. SWIT
Final Sermon: Comply!
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LAW OFFICES OF MICHAEL A. SWIT
Please Teach Vigorous Risk Avoidance
Comprehensively & Corporately
➢ Thus, to ensure you comply, you must have:
– P = Procedures
– T = Training
– V = Validation
– R = Records
– A = Audits
– C = Communications – open channels
– C = Compliance Culture from the Top
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LAW OFFICES OF MICHAEL A. SWIT
Questions?
➢ Call, e-mail or write:
Michael A. Swit, Esq.
LAW OFFICES OF MICHAEL A. SWIT
San Diego, California 92130
m: 760-815-4762
e: mswit@fdacounsel.com
web: www.fdacounsel.com
➢ Follow me on:
– LinkedIn: http://www.linkedin.com/in/michaelswit
– Twitter: https://twitter.com/FDACounsel
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LAW OFFICES OF MICHAEL A. SWIT
About Your Speaker
Michael A. Swit, Esq., has been addressing critical FDA legal and regulatory issues for over 30
years. Before returning to his private law practice in late 2017, he served for 3 years as the chief
regulatory counsel at a leading developer of diagnostics and research tools. Prior to that, Swit was a
special counsel in the FDA Law Practice at the global law firm of Duane Morris LLP, in its San
Diego office. 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, therapeutic biotech products, medical devices, and IVDs.
His FDA legal and regulatory work also has included tenures 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, where he helped spearhead the
company’s emergence from the Generic Drug Scandal. 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.