Overview of FDA regulation of combination products -- those featuring a drug and a device, a device and a biologic, or a biologic and a drug. Reviews key issues such as Primary Mode of Action, Requests for Designation, and how to handle GMPs and Adverse Event Reporting for combination products.
Herbal medicines are popular because of experience and the abundant
availability of plants in India due to its varied climatic zones. India has
around 45,000 species of plants, out of which 15,000–20,000 plants have
proven medicinal value.
Marketing Authorization Procedure in European UnionDoninder Hooda
The document discusses marketing authorization procedures in the European Union. It provides an overview of the general principles of marketing authorization and describes the key procedures including the national procedure, centralized procedure, mutual recognition procedure, and decentralized procedure. It outlines the mandatory and optional scopes of the various procedures and summarizes the timelines, responsibilities, and advantages and disadvantages of each authorization route.
GHTF group 1 is about pre market evaluation .This ppt includes brief about the group 1 , about ghtf , what it includes , study groups , definitions , classification and its rules
The document discusses the organization of the US Food and Drug Administration (FDA). It describes that the FDA regulates food, drugs, medical devices, cosmetics, and tobacco. It is organized into six product centers that regulate specific areas, a research center, and two offices. The centers regulate drugs, biologics, devices, food, veterinary medicine, and tobacco. The Office of Regulatory Affairs conducts inspections and investigations. The Office of the Commissioner provides leadership. Employment in 2013 totaled 14,589 across the various centers and offices.
CFTCC
2015 Learning about the IND/IDE Process and Reimbursements for New Drugs and Devices
Erika Segear Johnson, PhD, RAC
Regulatory Affairs Scientist
Duke Translational Medicine Institute
Introduces the basics of filing an Investigational Device Exeption (IDE) Application with the FDA
The Ministry of Health, Labour and Welfare (MHLW) is Japan's governmental authority that issues regulations and guidelines for pharmaceuticals. The Pharmaceuticals and Medical Devices Agency (PMDA) works with MHLW as Japan's main regulatory body, located in Tokyo. PMDA is responsible for reviewing marketing applications, monitoring post-marketing safety of drugs and devices, and providing compensation for adverse reactions. The drug approval process in Japan involves IND applications reviewed by PMDA and IRB, as well as regulatory reviews and approvals conducted according to a common technical document format.
Regulatory affairs professionals play a crucial role in ensuring pharmaceutical products meet regulatory standards for safety, efficacy and quality. They provide strategic guidance to various departments on regulatory requirements and work to obtain approvals from regulatory authorities. Key responsibilities include filing product registrations, tracking legal changes, and facilitating clinical trials and product approvals. Regulatory affairs has become increasingly important given historical issues that prompted stronger drug regulations to protect public health.
Regulatory requirnment and approval procedure of drugs in japan pptsandeep bansal
this ppt is about all the rules and regulations of drugs in Japan.this ppt contains the PMDA structure, DMF data, IND and NDA procedure, cosmetic regulations, post marketing survelliance etc.
Herbal medicines are popular because of experience and the abundant
availability of plants in India due to its varied climatic zones. India has
around 45,000 species of plants, out of which 15,000–20,000 plants have
proven medicinal value.
Marketing Authorization Procedure in European UnionDoninder Hooda
The document discusses marketing authorization procedures in the European Union. It provides an overview of the general principles of marketing authorization and describes the key procedures including the national procedure, centralized procedure, mutual recognition procedure, and decentralized procedure. It outlines the mandatory and optional scopes of the various procedures and summarizes the timelines, responsibilities, and advantages and disadvantages of each authorization route.
GHTF group 1 is about pre market evaluation .This ppt includes brief about the group 1 , about ghtf , what it includes , study groups , definitions , classification and its rules
The document discusses the organization of the US Food and Drug Administration (FDA). It describes that the FDA regulates food, drugs, medical devices, cosmetics, and tobacco. It is organized into six product centers that regulate specific areas, a research center, and two offices. The centers regulate drugs, biologics, devices, food, veterinary medicine, and tobacco. The Office of Regulatory Affairs conducts inspections and investigations. The Office of the Commissioner provides leadership. Employment in 2013 totaled 14,589 across the various centers and offices.
CFTCC
2015 Learning about the IND/IDE Process and Reimbursements for New Drugs and Devices
Erika Segear Johnson, PhD, RAC
Regulatory Affairs Scientist
Duke Translational Medicine Institute
Introduces the basics of filing an Investigational Device Exeption (IDE) Application with the FDA
The Ministry of Health, Labour and Welfare (MHLW) is Japan's governmental authority that issues regulations and guidelines for pharmaceuticals. The Pharmaceuticals and Medical Devices Agency (PMDA) works with MHLW as Japan's main regulatory body, located in Tokyo. PMDA is responsible for reviewing marketing applications, monitoring post-marketing safety of drugs and devices, and providing compensation for adverse reactions. The drug approval process in Japan involves IND applications reviewed by PMDA and IRB, as well as regulatory reviews and approvals conducted according to a common technical document format.
Regulatory affairs professionals play a crucial role in ensuring pharmaceutical products meet regulatory standards for safety, efficacy and quality. They provide strategic guidance to various departments on regulatory requirements and work to obtain approvals from regulatory authorities. Key responsibilities include filing product registrations, tracking legal changes, and facilitating clinical trials and product approvals. Regulatory affairs has become increasingly important given historical issues that prompted stronger drug regulations to protect public health.
Regulatory requirnment and approval procedure of drugs in japan pptsandeep bansal
this ppt is about all the rules and regulations of drugs in Japan.this ppt contains the PMDA structure, DMF data, IND and NDA procedure, cosmetic regulations, post marketing survelliance etc.
regulatory requirnment and approval procedure for drugs and cosmetics, medica...sandeep bansal
This document outlines the regulatory requirements and approval procedures for drugs, cosmetics, medical devices, biological products, herbal medicines, and foods/nutraceuticals in India. It discusses the key regulatory bodies like the Central Drugs Standard Control Organization (CDSCO) and the application processes. For drugs, the new drug approval procedure is described involving applying to the DCGI and undergoing clinical trials and reviews. For other products, the document explains the application forms and documents required for approval from bodies like FSSAI.
REGULATORY REQUIREMENTS FOR ASEAN COUNTRIESVikas Rathee
The document discusses regulatory requirements for drug registration in Asian countries. It provides an overview of the ASEAN Common Technical Dossier (ACTD) format for drug applications across ASEAN countries. It then summarizes requirements for registration in China, South Korea, and with the ASEAN region. For China, it outlines the drug classification system and two-step approval process. For South Korea, it describes the drug classification and approval process including investigational new drug applications. It also provides background on the goals and formation of the ASEAN economic alliance between Southeast Asian countries.
The European Medicines Agency (EMA) regulates medicines for both human and veterinary use across Europe. Key responsibilities of EMA include evaluating applications for new medicines and monitoring approved medicines. EMA operates through various scientific committees and follows regulatory procedures for clinical trials and marketing authorization applications. EMA helps ensure that medicines available across Europe are safe, effective and of high quality.
Fda regulations for pharmaceutical packagingPrem Patil
The document discusses guidelines for packaging and labeling of active pharmaceutical ingredients (APIs). It outlines requirements for packaging materials, labeling, storage conditions, and expiration dating to ensure quality. Proper documentation of material specifications, examination and testing is required. Labels must include accurate information and be stored securely to prevent mix-ups. APIs should be packaged and labeled in a way that protects against deterioration and contamination during transport and storage.
The document provides an overview of medical device regulations in ASEAN countries. It discusses the ASEAN Medical Device Directive (AMDD), which provides harmonized regulations across ASEAN nations. It outlines the medical device classification system and regulatory registration procedure, including requirements for quality systems and clinical evaluation/investigation. Key aspects covered are the ASEAN Common Submission Dossier Template for product registration and ISO 13485 standards for quality management systems.
The document discusses regulations for drug submissions and applications in the US and other countries. It covers the major regulatory bodies like the FDA and EMA. It then focuses on the different types of applications filed with the FDA - Drug Master Files (DMF), Investigational New Drug Application (IND), New Drug Application (NDA), and Abbreviated New Drug Application (ANDA). The ANDA process for generic drugs is summarized, including requirements for bioequivalence testing and patent certification in the Orange Book.
This document provides an overview of Vineeth Kumar Ekbote's lab presentation on new drug applications (NDAs). The presentation covers what an NDA is, the goals and process of an NDA, the forms and contents required in an NDA submission, guidance documents for NDAs, and how NDAs are reviewed and approved by the FDA. The presentation also describes the various sections required in an NDA, including the application summary, chemistry and manufacturing controls, clinical data, and labeling.
MARKETING AUTHORISATION, LICENSING AND QUALITY ASSESSMENT OF VACCINES IN INDI...Swapnil Fernandes
- European pharmaceutical legislation provides a comprehensive framework for the marketing authorisation of vaccines.
- In contrast to the European scenario, the Indian scenario for vaccines is relatively less regulated and follows the same process of approval as other biologics in spite of having a National Handbook for Vaccine Policy.
- Vaccine authorisation in the US, as is the case in EU, is a more straightforward process than in most other markets as the USFDA has provided vaccines with a distinct set of regulations in concerned areas of safety and quality.
The document provides information about the European Medicines Agency (EMA) and marketing authorization procedures in the European Union. It describes the EMA's role in evaluating and authorizing medicines, its committees and membership. Four procedures for marketing authorization are outlined: centralized, national, mutual recognition and decentralized. The centralized procedure allows marketing across the EU, while national and decentralized are for individual countries. Mutual recognition relies on an existing national authorization. Timelines for evaluation are included.
The document compares the regulatory processes for drug product submissions in the US and EU. In the US, applications are submitted to the FDA's Center for Drug Evaluation and Research and can be New Drug Applications or Abbreviated New Drug Applications. In the EU, applications are submitted through national regulatory authorities or through the centralized European Medicines Agency process. The key differences between the US and EU processes include differences in application types, approval timelines, post-approval change requirements, manufacturing standards, quality testing standards, and facility inspection processes.
TSE/BSE is a type of disease affected to the animals which may transmit to the humans if any products obtained by the disease caused animal may affect to humans also
The many biologic products are expracted from the animal source so before the extraction the animal should be tested for TSE/BSE organism in their source/Body
This document discusses various FDA approval pathways for drugs, biologics, and medical devices. It describes the New Drug Application (NDA) process for drug approval, the Biologics License Application (BLA) process for biologics approval, the Premarket Approval (PMA) process for high-risk Class III medical devices, and the 510(k) process for clearance of lower-risk Class I and II medical devices. The key FDA regulations and goals of demonstrating safety and effectiveness for intended uses are also summarized.
Risk Based Classification of Medical Devices and groupingPaulyne Wairimu
The document discusses risk-based classification and grouping of medical devices in Kenya. It describes how medical devices will be classified into categories A, B, C, and D based on factors like invasiveness and risk level. It also discusses how devices can be grouped into single devices, device families that include variations of a device, and device systems which are groups of compatible devices that serve a common purpose. Proper classification and grouping is important for the registration of medical devices in Kenya.
The document discusses regulatory requirements for bioequivalence studies from the FDA and WHO perspectives. It defines key terms like bioavailability, bioequivalence, reference product and generic products. It also outlines FDA guidelines on bioequivalence documentation for INDs, NDAs and ANDAs. Test procedures for establishing bioequivalence include pharmacokinetic, pharmacodynamic and clinical studies according to FDA regulations. Pharmacokinetic studies are emphasized for directly measuring drug absorption. Study design considerations like single vs multiple dose studies are also covered.
Regulatory requirements of row countriesDivya Pushp
This document provides an overview of regulatory requirements for pharmaceutical registration in Rest of World (ROW) countries. It begins with definitions of ROW countries and importance of harmonization. It then discusses differences between regulated and emerging markets and provides a comparative study of registration requirements across various regions including ASEAN, GCC, Latin America, CIS, Asia Pacific and Africa. Key requirements discussed include administrative documents, chemistry manufacturing and controls, specifications, stability data, packaging and labeling. Common queries from ROW countries are also summarized.
The document discusses the Common Technical Document (CTD), which provides a standardized format for submitting documentation to regulatory authorities for approval of pharmaceutical products. It describes the evolution and adoption of the CTD internationally and in India. The CTD aims to streamline the drug approval process and facilitate simultaneous reviews by different regulators. It is organized into five modules covering administrative information, summaries, quality, nonclinical data, and clinical data. Widespread use of the CTD format has allowed for greater harmonization and efficiency in global pharmaceutical development and regulation.
The Brazilian Health Surveillance Agency (ANVISA) regulates health products and services in Brazil. It oversees drug approval and registration, medical devices, food safety, tobacco and other areas. ANVISA aims to protect public health through sanitary control of production, marketing and ports of entry. It is part of the National Health Surveillance System and linked to the Ministry of Health. The registration process for new drugs involves pre-registration clinical trials, submitting documentation for approval, and post-registration monitoring and changes. ANVISA also regulates in vitro diagnostics and provides vaccination requirements for international travelers.
It contains details rules and regulations /legislation of Pharmaceuticals, Cosmetics, Active Substance Masters File, Investigational Medicinal Product Dossier for European Union
Dietary Supplements, Combination Products, and Veterinary MedicineMichael Swit
Presentation to San DIego Regulatory Affairs Network (SDRAN) Regulatory Affairs Certification (RAC) Test Review Course, on key issues relating to regulation of dietary supplements, Combination Products, and Veterinary Medicine.
regulatory requirnment and approval procedure for drugs and cosmetics, medica...sandeep bansal
This document outlines the regulatory requirements and approval procedures for drugs, cosmetics, medical devices, biological products, herbal medicines, and foods/nutraceuticals in India. It discusses the key regulatory bodies like the Central Drugs Standard Control Organization (CDSCO) and the application processes. For drugs, the new drug approval procedure is described involving applying to the DCGI and undergoing clinical trials and reviews. For other products, the document explains the application forms and documents required for approval from bodies like FSSAI.
REGULATORY REQUIREMENTS FOR ASEAN COUNTRIESVikas Rathee
The document discusses regulatory requirements for drug registration in Asian countries. It provides an overview of the ASEAN Common Technical Dossier (ACTD) format for drug applications across ASEAN countries. It then summarizes requirements for registration in China, South Korea, and with the ASEAN region. For China, it outlines the drug classification system and two-step approval process. For South Korea, it describes the drug classification and approval process including investigational new drug applications. It also provides background on the goals and formation of the ASEAN economic alliance between Southeast Asian countries.
The European Medicines Agency (EMA) regulates medicines for both human and veterinary use across Europe. Key responsibilities of EMA include evaluating applications for new medicines and monitoring approved medicines. EMA operates through various scientific committees and follows regulatory procedures for clinical trials and marketing authorization applications. EMA helps ensure that medicines available across Europe are safe, effective and of high quality.
Fda regulations for pharmaceutical packagingPrem Patil
The document discusses guidelines for packaging and labeling of active pharmaceutical ingredients (APIs). It outlines requirements for packaging materials, labeling, storage conditions, and expiration dating to ensure quality. Proper documentation of material specifications, examination and testing is required. Labels must include accurate information and be stored securely to prevent mix-ups. APIs should be packaged and labeled in a way that protects against deterioration and contamination during transport and storage.
The document provides an overview of medical device regulations in ASEAN countries. It discusses the ASEAN Medical Device Directive (AMDD), which provides harmonized regulations across ASEAN nations. It outlines the medical device classification system and regulatory registration procedure, including requirements for quality systems and clinical evaluation/investigation. Key aspects covered are the ASEAN Common Submission Dossier Template for product registration and ISO 13485 standards for quality management systems.
The document discusses regulations for drug submissions and applications in the US and other countries. It covers the major regulatory bodies like the FDA and EMA. It then focuses on the different types of applications filed with the FDA - Drug Master Files (DMF), Investigational New Drug Application (IND), New Drug Application (NDA), and Abbreviated New Drug Application (ANDA). The ANDA process for generic drugs is summarized, including requirements for bioequivalence testing and patent certification in the Orange Book.
This document provides an overview of Vineeth Kumar Ekbote's lab presentation on new drug applications (NDAs). The presentation covers what an NDA is, the goals and process of an NDA, the forms and contents required in an NDA submission, guidance documents for NDAs, and how NDAs are reviewed and approved by the FDA. The presentation also describes the various sections required in an NDA, including the application summary, chemistry and manufacturing controls, clinical data, and labeling.
MARKETING AUTHORISATION, LICENSING AND QUALITY ASSESSMENT OF VACCINES IN INDI...Swapnil Fernandes
- European pharmaceutical legislation provides a comprehensive framework for the marketing authorisation of vaccines.
- In contrast to the European scenario, the Indian scenario for vaccines is relatively less regulated and follows the same process of approval as other biologics in spite of having a National Handbook for Vaccine Policy.
- Vaccine authorisation in the US, as is the case in EU, is a more straightforward process than in most other markets as the USFDA has provided vaccines with a distinct set of regulations in concerned areas of safety and quality.
The document provides information about the European Medicines Agency (EMA) and marketing authorization procedures in the European Union. It describes the EMA's role in evaluating and authorizing medicines, its committees and membership. Four procedures for marketing authorization are outlined: centralized, national, mutual recognition and decentralized. The centralized procedure allows marketing across the EU, while national and decentralized are for individual countries. Mutual recognition relies on an existing national authorization. Timelines for evaluation are included.
The document compares the regulatory processes for drug product submissions in the US and EU. In the US, applications are submitted to the FDA's Center for Drug Evaluation and Research and can be New Drug Applications or Abbreviated New Drug Applications. In the EU, applications are submitted through national regulatory authorities or through the centralized European Medicines Agency process. The key differences between the US and EU processes include differences in application types, approval timelines, post-approval change requirements, manufacturing standards, quality testing standards, and facility inspection processes.
TSE/BSE is a type of disease affected to the animals which may transmit to the humans if any products obtained by the disease caused animal may affect to humans also
The many biologic products are expracted from the animal source so before the extraction the animal should be tested for TSE/BSE organism in their source/Body
This document discusses various FDA approval pathways for drugs, biologics, and medical devices. It describes the New Drug Application (NDA) process for drug approval, the Biologics License Application (BLA) process for biologics approval, the Premarket Approval (PMA) process for high-risk Class III medical devices, and the 510(k) process for clearance of lower-risk Class I and II medical devices. The key FDA regulations and goals of demonstrating safety and effectiveness for intended uses are also summarized.
Risk Based Classification of Medical Devices and groupingPaulyne Wairimu
The document discusses risk-based classification and grouping of medical devices in Kenya. It describes how medical devices will be classified into categories A, B, C, and D based on factors like invasiveness and risk level. It also discusses how devices can be grouped into single devices, device families that include variations of a device, and device systems which are groups of compatible devices that serve a common purpose. Proper classification and grouping is important for the registration of medical devices in Kenya.
The document discusses regulatory requirements for bioequivalence studies from the FDA and WHO perspectives. It defines key terms like bioavailability, bioequivalence, reference product and generic products. It also outlines FDA guidelines on bioequivalence documentation for INDs, NDAs and ANDAs. Test procedures for establishing bioequivalence include pharmacokinetic, pharmacodynamic and clinical studies according to FDA regulations. Pharmacokinetic studies are emphasized for directly measuring drug absorption. Study design considerations like single vs multiple dose studies are also covered.
Regulatory requirements of row countriesDivya Pushp
This document provides an overview of regulatory requirements for pharmaceutical registration in Rest of World (ROW) countries. It begins with definitions of ROW countries and importance of harmonization. It then discusses differences between regulated and emerging markets and provides a comparative study of registration requirements across various regions including ASEAN, GCC, Latin America, CIS, Asia Pacific and Africa. Key requirements discussed include administrative documents, chemistry manufacturing and controls, specifications, stability data, packaging and labeling. Common queries from ROW countries are also summarized.
The document discusses the Common Technical Document (CTD), which provides a standardized format for submitting documentation to regulatory authorities for approval of pharmaceutical products. It describes the evolution and adoption of the CTD internationally and in India. The CTD aims to streamline the drug approval process and facilitate simultaneous reviews by different regulators. It is organized into five modules covering administrative information, summaries, quality, nonclinical data, and clinical data. Widespread use of the CTD format has allowed for greater harmonization and efficiency in global pharmaceutical development and regulation.
The Brazilian Health Surveillance Agency (ANVISA) regulates health products and services in Brazil. It oversees drug approval and registration, medical devices, food safety, tobacco and other areas. ANVISA aims to protect public health through sanitary control of production, marketing and ports of entry. It is part of the National Health Surveillance System and linked to the Ministry of Health. The registration process for new drugs involves pre-registration clinical trials, submitting documentation for approval, and post-registration monitoring and changes. ANVISA also regulates in vitro diagnostics and provides vaccination requirements for international travelers.
It contains details rules and regulations /legislation of Pharmaceuticals, Cosmetics, Active Substance Masters File, Investigational Medicinal Product Dossier for European Union
Dietary Supplements, Combination Products, and Veterinary MedicineMichael Swit
Presentation to San DIego Regulatory Affairs Network (SDRAN) Regulatory Affairs Certification (RAC) Test Review Course, on key issues relating to regulation of dietary supplements, Combination Products, and Veterinary Medicine.
Key Issues in FDA & FTC Regulation of Dietary SupplementsMichael Swit
Webinar presentation sponsored by Compliance2Go, focusing on:
♦ Basics
♦ New Dietary Ingredients
♦ Claims Allowed
♦ GMPs and Other Regulatory Requirements
♦ Adverse Events
♦ The FTC Perspective
Dietary Supplements, Combination Products, and Veterinary MedicineMichael Swit
This document summarizes a presentation about solving FDA legal challenges for life sciences companies. It discusses dietary supplements, combination products, and veterinary medicine. For dietary supplements, it covers basics like definitions; new dietary ingredients and notification requirements; labeling rules for claims, ingredients, and nutrition; good manufacturing practices; and adverse event reporting. For combination products, it discusses primary mode of action determination, the request for designation process, applicable regulations, and application requirements. Veterinary medicine topics are also briefly mentioned.
Presentation to the San Diego Regulatory Affairs Network (SDRAN) RAC Review course; August 2011; covering:
♦ Basics
♦ New Dietary Ingredients
♦ Claims Allowed
♦ GMPs and Other Regulatory Requirements
♦ Adverse Events
The Impact of FDASIA on the Drug and Device IndustriesMichael Swit
March 12., 2013 presentation to the San Diego Chapter of the American Society for Quality, focusing on:
• The 2012 Election and the Political Arena
• FDASIA – The Food & Drug Administration Safety & Innovation Act of 2012
– User Fees (only briefly)
– Drug Provisions
– Device Provisions
– General Provisions
• Other Trends
Overview of FDA Regulation of Medical DevicesMichael Swit
The document is a slide presentation by Michael A. Swit, Esq. on an overview of FDA regulation, with an emphasis on medical devices. It begins with definitions of key terms under FDA regulation such as drugs, biologics, devices, foods, dietary supplements, and cosmetics. It then discusses the mission and structure of the FDA, including the different centers that regulate specific product areas. The presentation provides an overview of the classification system for medical devices and regulatory pathways for devices, including 510(k) clearance and premarket approval.
FDA Update: The Impact of FDASIA and The ElectionsMichael Swit
Presentation to the San Diego Regulatory Affairs Network (SDRAN), focusing on:
• The 2012 Election and the Political Arena
• FDASIA – The Food & Drug Administration Safety & Innovation Act of 2012
– User Fees (only briefly)
– Drug Provisions
– Device Provisions
– General Provisions
• Other Trends
This document summarizes a presentation given by Michael Swit on FDA updates and trends. It discusses the impact of the 2012 election and upcoming FDASIA legislation. FDASIA makes changes to drug, device, and supply chain regulations. It aims to expedite drug development and approval for serious diseases. The presentation also covers FDA reorganizations and other regulatory trends.
“FUNCTIONAL FOODS: CLAIMS AND LABELING” -- AN OVERVIEW OF THE LAWMichael Swit
Presentation to the Regulatory Affairs Professionals Society (RAPS) & University of Southern California School of Pharmacy conference on Dietary Supplements & Supplemental Foods." November 2000, Pasadena, CA., covering:
♦ What is a Functional Food
♦ Claims under Nutritional Labeling and Educations Act (NLEA)
♦ FDAMA Claims
♦ FTC Advertising Regulation
This document provides an overview of US FDA regulations for dietary supplements. It discusses the history and definition of dietary supplements, the governing regulatory body (FDA CFSAN), and the responsibilities of manufacturers. Key topics covered include new dietary ingredients, health and structure/function claims, GMPs, facility registration, labeling requirements, adverse event reporting, and advertising regulations. The document outlines the various FDA regulations that cover each of these areas.
Introduction to the Legal Basis for Generic Drug ApprovalsMichael Swit
Presentation at the Center for Professional Advancement (CFPA) Course on Generic Drug Approval, August 2013. New Brunswick, NJ., with a focus on how the 1984 Hatch-Waxman Act came to be enacted.
Why Compliance is a Tough Pill to Swallow – NutraceuticalsAffiliate Summit
This presentation is from Affiliate Summit West 2014 (January 12-14, 2014 in Las Vegas, NV). Session description: Discussion of strategies for manufacturers and marketers of nutraceuticals to avoid both FTC and FDA scrutiny, as well as recent FDA warning letters and trending enforcement tactics.
Keynote presentation at the Ophthalmic Drug Delivery Conference, sponsored by Pharmaceutical Education Associates, in September 2007, in San Diego. Talk focused on new drug regulatory issues, especially those arising under the 2007 Food and Drug Administration Amendments Act (FDAAA).
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.
August 29, 2012 presentation to the San Diego Regulatory Affairs Network (SDRAN) Regulatory Affairs Certification (RAC) Review Course, with a focus on:
* new animal drug applications
* generic new animal drugs applications
* species and uses
This document summarizes the current state of drug regulation in the United States. It discusses several pieces of legislation that aim to reform the FDA's drug approval process and emphasize drug safety. Key points include increased funding for the FDA through user fees, new requirements for risk evaluation and mitigation strategies from drug companies, expansion of clinical trial registration and results databases, and incentives for developing antibiotics and drugs for neglected diseases. The document also notes ongoing leadership turnover at the FDA and the political factors influencing regulatory reform under the current administration.
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
This presentation covers the essential concept of ensuring all promotional communications are on label and the safe harbors established by FDA for disseminating off-label information compliantly.
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
Similar to FDA Regulation of Combination Products (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.
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.
Corporate Governance : Scope and Legal Frameworkdevaki57
CORPORATE GOVERNANCE
MEANING
Corporate Governance refers to the way in which companies are governed and to what purpose. It identifies who has power and accountability, and who makes decisions. It is, in essence, a toolkit that enables management and the board to deal more effectively with the challenges of running a company.
Business law for the students of undergraduate level. The presentation contains the summary of all the chapters under the syllabus of State University, Contract Act, Sale of Goods Act, Negotiable Instrument Act, Partnership Act, Limited Liability Act, Consumer Protection Act.
2. www.duanemorris.com
Standard Disclaimers
• Views expressed here are solely mine and do not
reflect those of my 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.
2
5. www.duanemorris.com5
What We Will Cover on Dietary Supplements
♦ Basics
♦ New Dietary Ingredients
♦ Claims Allowed
♦ GMPs and Other Regulatory Requirements
♦ Adverse Events
6. www.duanemorris.com6
The Basics
• Pre-1994 – dietary supplements regulated as foods
• 1994 – Dietary Supplement Health Education Act
(DSHEA)
– Defined “dietary supplement” (D.S.)
– Defined “dietary ingredient”
– Required ingredient and nutrition labeling
– Delineated the claims and nutritional support statements
that could be made
– Gave FDA power to promulgate D.S. GMP regulations
– Required that any D.S. ingredient that was not on the
market on the date of enactment (October 15, 1994) had to
be subject to a New Dietary Ingredient (NDI) notification
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Definition of D.S. – Part 1
• Section 201(ff) of the Act -- The term "dietary
supplement" -
– (1) means a product (other than tobacco) intended to supplement the
diet that bears or contains one or more of the following dietary
ingredients:
(A) a vitamin;
(B) a mineral;
(C) an herb or other botanical;
(D) an amino acid;
(E) a dietary substance for use by man to supplement the diet by
increasing the total dietary intake; or
(F) a concentrate, metabolite, constituent, extract, or combination
of any ingredient described in clause (A), (B), (C), (D), or (E);
AND …
7
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Definition of D.S. – Part 2
• Section 201(ff)(2):
– …means a product that -
(A)(i) is intended for ingestion in a form described in section
411(c)(1)(B)(i); or
"(ii) complies with section 411(c)(1)(B)(ii);
(B) is not represented for use as a conventional food or as a sole item
of a meal or the diet; and
(C) is labeled as a dietary supplement;
– 411(c)(1)(B)(i) -- is intended for ingestion in tablet, capsule, powder,
softgel, gelcap, or liquid form
– 411(c)(1)(B)(ii) -- if not intended for ingestion in such a form, is not
represented as conventional food and is not represented for use as a sole
item of a meal or of the diet.
AND …8
9. www.duanemorris.com
Definition of D.S. – Part 3(A)
• Section 201(ff)(3)
– does -
(A) include an article that is approved as a new drug under
section 505, certified as an antibiotic under section 507, or
licensed as a biologic under section 351 of the Public Health
Service Act (42 U.S.C. 262) and was, prior to such approval,
certification, or license, marketed as a dietary supplement or as a
food unless the Secretary has issued a regulation, after notice
and comment, finding that the article, when used as or in a
dietary supplement under the conditions of use and dosages set
forth in the labeling for such dietary supplement, is unlawful
under section 402(f);
AND …
9
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Definition of D.S. – Part 3(B)
• Section 201(ff)(3)
– B) does not include -
(i) an article that is approved as a new drug under section 505,
certified as an antibiotic under section 507, or licensed as a biologic
under section 351 of the Public Health Service Act (42 U.S.C. 262),
or
(ii) an article authorized for investigation as a new drug, antibiotic, or
biological for which substantial clinical investigations have been
instituted and for which the existence of such investigations has been
made public,
which was not before such approval, certification, licensing, or
authorization marketed as a dietary supplement or as a food unless the
Secretary, in the Secretary's discretion, has issued a regulation, after notice
and comment, finding that the article would be lawful under this Act.
10
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The Basics
• Except for purposes of section 201(g), a dietary
supplement shall be deemed to be a food within the
meaning of this Act.
– In other words, it can be a drug also if it meets the drug
definition
• Premarket approval/clearance – not required, unless
“new dietary ingredient” …
11
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New Dietary Ingredients (NDI)
• If a dietary ingredient was not marketed before
October 15, 1994, must notify FDA before marketing
• Notice:
– Goes to Office of Nutritional Products, Labeling & Dietary
Supplements (ONPLDS)
– At least 75 days before introducing NDI into interstate
commerce
12
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NDI Notice -- Contents
• Name and address of manufacturer or distributor
• NDI name, including Latin binomial name of any herb or
other botanical
• Description of products that contain the NDI + level of
NDI in the product
• History of use or other evidence NDI is safe
• Process
– Get a filing date from FDA
– 75 days after filing date, can go to market – BUT, that does not mean
FDA agrees the NDI is safe
FDA can object
• New draft guidance – July 2011 – for comment
http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/GuidanceDocuments/DietarySupplements/ucm257563.htm
13
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Labels and Labeling
• Basics
– Statement of identity
– Net quantity of contents
– Ingredient list
– Address of mfr., packer or distributor
– Nutritional facts box
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Labeling Claims
• Nutrient content claims
– 21 CFR 101.13 – General Principles
– Types of claims governed:
“Good source,” “More” and “High Potency”
“Light” or “Lite”
Caloric claims
Sodium content
Fat, Fatty Acid and Cholesterol content
15
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Health Claims
• Possible for dietary supplements
• Petition process – for an allowable health claim – 21
CFR 101.70
• Standard for allowable claim: “significant scientific
agreement”
• Examples:
– Calcium and osteoporosis
– Sodium and hypertension
– Fiber and cancer
– Folate and neural tube defects (e.g., spina bifida)
16
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Health Claims -- FDAMA
• Basis – a published authoritative statement of a
“scientific body of the United States with official
responsibility for public health protection or
research directly related to human nutrition …”
– National Academy of Sciences
– NIH
– CDC
• Process
– 120 days notice – then can make claim
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Health Claims – “Qualified”
• Result of Pearson v. Shalala – lawsuit over First
Amendment right to make truthful commercial
speech
– FDA cannot reject a health claim that might be misleading
unless agency also finds that no disclaimer would eliminate the
potential misconception
– Examples:
“supportive but not conclusive data” shows omega-3 fatty acids
may reduce risk of coronary heart disease
Antioxidants and cancer
Nuts and heart disease
18
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Nutrient Content Claims
• These are “quasi-health” (my term) claims
• Can apply to claims relating to how the D.S:
– helps address a classical nutrient deficiency disease (e.g., Vitamin C
and scurvy); or
– helps affect or maintain the normal, healthy structure or function of
human body
but can’t be disease claim – or it’s a drug
FDA -- regulations and guidance on acceptable
structure/function claims
– helps with the “general well-being” supported by consumption
– Must bear disclaimer: “This statement has not been evaluated by the
Food and Drug Administration. This product is not intended to diagnose,
treat, cure, or prevent any disease.”19
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Limits on Structure/Function Claims
• 21 CFR 101.93(g)(2) – ten criteria that are barred;
include
– Affects a specific disease or disease class
– Affects the characteristic signs or symptoms of a specific disease
– Affects an abnormal condition linked to a natural state if the
abnormal condition is uncommon or can cause significant harm
– Affects a disease via:
Name
Contains a non-dietary ingredient that is a drug
Citation to articles that refer to diseases
Using “disease” unless general statement on disease prevention
Treats, prevents or mitigates an adverse event linked to disease
therapy
20
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Supporting Structure/Function Claims
• Must have data to substantiate the claim
• Don’t have to submit data to FDA, but you do have to
inform FDA 30 days before making any nutritional
support claims
• Must meet FTC standard – “competent and reliable
scientific evidence”
“tests, analyses, research, studies, or other evidence based on the expertise
of professionals in the relevant area, that has been conducted and evaluated
in an objective manner by persons qualified to do so, using procedures
generally accepted in the profession to yield accurate and reliable results.”
• Literature reprints – if done in their entirety, are not
considered “labeling”
21
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Other D.S. Regulatory Requirements
• Registration – mandatory -- with FDA – 21 CFR 1.232
• GMPs
– June 2007 – Final Rule published; codified at 21 CFR 111
– Examples of requirements
facility cleaning and pest control
maintaining, cleaning and sanitizing equipment
QC operations, including material review and disposition decisions
Lab operations
Manufacturing operations
Complaints
– Guidance issued
– Failure to meet GMPs – product is adulterated under § 402(g) of
Federal Food, Drug, and Cosmetic Act
22
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Adverse Events
• Labeled maker, distributor or packer must submit
serious adverse events to FDA within 15 business days
of learning
– Adverse event – “any health-related event associated with the use of a
dietary supplement that is adverse”
– Serious – an event that results in:
Death
Inpatient hospitalization
Persistent or significant disability
Incapacity
Congenital anomaly or birth defect
Medical or surgical intervention … to prevent one of the above results
• “At a Glance” on AEs – issued in 2011 –
http://www.fda.gov/downloads/Food/DietarySupplements/GuidanceComplianceRegulatoryInformati
on/UCM267417.pdf
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What We Will Cover
• A Brief History of Combination Product
Regulation
• Primary Mode of Action (PMOA) – The Key
Lynchpin to FDA’s Regulatory Regime for
Combination Products
• The Request for Designation (RFD) Process
• GMPs
• Post-Market Safety Reporting
• How Many Applications to File?
• User Fees
25
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What Is a Combination Product?
• As defined in 21 CFR § 3.2(e), the term combination
product includes:
• A product comprised of two or more regulated components, i.e., drug/device,
biologic/device, drug/biologic, or drug/device/biologic, that are physically,
chemically, or otherwise combined or mixed and produced as a single entity;
• Two or more separate products packaged together in a single package or as a
unit and comprised of drug and device products, device and biological
products, or biological and drug products;
• A drug, device, or biological product packaged separately that according to its
investigational plan or proposed labeling is intended for use only with an
approved individually specified drug, device, or biological product where both
are required to achieve the intended use, indication, or effect and where upon
approval of the proposed product the labeling of the approved product would
need to be changed, e.g., to reflect a change in intended use, dosage form,
strength, route of administration, or significant change in dose; or
• Any investigational drug, device, or biological product packaged separately
that according to its proposed labeling is for use only with another individually
specified investigational drug, device, or biological product where both are
required to achieve the intended use, indication, or effect.
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A Brief History of Combinations
• Safe Medical Device Act of 1990 -- combination
products first statutorily recognized
– Required assignment to lead center based on Primary Mode of
Action
– Implemented by Chief Mediator and Ombudsman
• Office of Combination Products (“OCP”)
– Created by Medical Device User Fee and Modernization Act
(MDUFMA) – 2002
– Office established on December 24, 2002
– OCP given broad oversight responsibilities covering the
regulatory life cycle of combination products.
Coordinate reviews among FDA Centers
Ensure consistency among similar reviews
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Section 503(g) of the Act
• FDA is required to assign a combination product to
a lead Center based on its "primary mode of action"
• PMOA was not defined in the statute or regulations
• For some products, PMOA is difficult to identify
– Early in development (just don't know)
– Products that have two (or more) completely different modes
of action, neither of which is subordinate to other
30. www.duanemorris.com30
PMOA -- Determining Which Center Leads
• PMOA = Primary Mode of Action; not defined in
statute, but in regulations
– Final Rule – 8/25/2005; 70 Fed. Reg. 49848
http://www.fda.gov/OHRMS/DOCKETS/98fr/05-16527.pdf
• Mode of Action: the means by which a product
achieves an intended therapeutic effect or action
21 CFR 3.2(k)
• Three types of modes of action:
– Biological product
– Device
– Drug
• Combination products typically have more than one
identifiable mode of action
31. www.duanemorris.com31
PMOA …
Primary mode of action is the single mode of action
of a combination product that provides the most
important therapeutic action of the combination
product. The most important therapeutic action is
the mode of action expected to make the greatest
contribution to the overall intended therapeutic
effects of the combination product.
Source: 21 CFR 3.2(m)
32. www.duanemorris.com32
Final PMOA Rule: Constituent Parts
• A constituent part of a combination product has a:
– Biological product mode of action if it acts by means of a
virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood
component or derivative, allergenic product, or analogous
product applicable to the prevention, treatment, or cure of a
disease or condition of human beings…
– Device mode of action if it meets the definition of device…, it
does not have a biological product mode of action, and it does
not achieve its primary intended purposes through chemical
action within or on the body….and is not dependent on being
metabolized for the achievement of its primary intended
purposes
– Drug mode of action if it meets the definition of drug…and it
does not have a biological product or device mode of action.
33. www.duanemorris.com
• Proposed use(s) or indication(s)
• How it achieves its overall intended therapeutic
effect(s)
• Relative contribution of each component toward the
overall intended therapeutic effect
• Duration of the contribution of each component
towards the intended therapeutic effect
• Data or information that describes and supports the
mode of action
Factors Impacting PMOA
33
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The PMOA Decision Tree –
“Assignment Algorithm”
• If unable to determine most important therapeutic
action with reasonable certainty, FDA will use the
“assignment algorithm” at 21 CFR 3.4(b).
• Two major factors, considered in order:
– Consistency: is there an agency component that regulates
other combination products presenting similar questions of S
& E with regard to the combination product as a whole?
– Safety and Effectiveness: which agency component has the
most expertise related to the most significant S&E questions
presented by the combination product?
35. www.duanemorris.com
• Intended use/indication(s)
• Overall therapeutic effect(s)
• Does a device component incorporate a novel or
complex design or have potential for significant
failure modes?
• Is drug component a new molecular entity or
formulation?
• Has a generic version of drug been approved?
• Is biological component a particularly fragile
molecule?
Assignment Algorithm – Additional Factors
35
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• How well understood are the components on a
comparable basis? Is one more risky?
• Which components raise greater risks?
• Have any components been approved/cleared?
• Is there a new indication, route of
administration, or significant change in dose or
use of component?
Assignment Algorithm – Additional
Factors …
36
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Not Sure of PMOA -- Requests
for Designations (RFD's)
• Voluntary Formal Process under 21 CFR Part 3
• Seeks to determine:
– Regulatory Identity or Classification
– Assignment of Lead Center
– Collateral issue -- clarification of regulatory pathway
• If don’t seek RFD and submit for marketing, FDA
may stay review clock while making designation
determination
• When to file RFD:
– Before filing any application for investigational or marketing
authorization
– As soon as enough info exists for FDA to make a decision
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RFD’s …
• Can meet with OCP before filing RFD -- not required
• Regulation – 21 CFR 3.7
• Guidance on How to Write a RFD
– Federal Register – Monday, April 18, 2011 – 76 Fed. Reg. 21752
– http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM25
1544.pdf
• Format – follow descriptions in 21 CFR 3.7(c)(1)-(3)
• Electronic filing – allowed, but not required
• 15-page limit (including attachments)
39. www.duanemorris.com
RFD Contents – 13 Sections
Contact Information
Product Name
Description of Product
Prior Approvals and
Agreements
Chemical, Physical or
Biological Composition
Development Work &
Testing
Manufacturing Information
Proposed use or Indications
Modes of Action (all) and
Primary Mode of Action
Schedule and Duration of
Use
Dose and Route of
Administration
Related Products
Other Relevant Information
Sponsor’s
Recommendation on
PMOA/classification and
Center with primary
jurisdiction
39
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RFD’s …
• Guidance – drills down on the 13 sections
• Some Key Points from the Guidance:
– State how you think your product should be assigned and
why
State the basis for your assertion why your selected PMOA is
most important therapeutic action for the product
Assignment Algorithm -- if you cannot determine, “with
reasonable certainty,” the PMOA, must use assignment
algorithm (Slides 34 - 36)
Even if you are sure, should address anyway
– Appropriate to file an RFD even if you believe that the
product is NOT a combination product, but uncertainty
remains
41. www.duanemorris.com41
RFD’s – OCP Process
• OCP reviews RFD’s for completeness w/in 5 work
days
• If complete, OCP sends acknowledgement letter to
sponsor, and copy of RFD’s to three Center liaisons
• Center recommendations due to OCP in 21 days
• Consultation among OCP, Centers and Office of Chief
Counsel
• Decision reached, response letter prepared, necessary
clearances obtained
• Decision must issue within 60 calendar days; if not
YOUR recommendation wins!!
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RFD’s – Process …
• Request for Reconsideration
– Submit within 15 calendar days
– Cannot exceed 5 pages in your reconsideration submission
– No new information (if you do, FDA will consider it a new
RFD)
– FDA response within 15 calendar days
– FDA has been known to change a decision upon
reconsideration
• Effect of RFD Letter – designated FDA Center can
only be changed without your consent to protect the
public health or another compelling reason.
– Source: 21 CFR 3.9(b)
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Jurisdictional Decisions -- Examples
• Breath Test Combinations
– http://www.fda.gov/CombinationProducts/JurisdictionalInformation/JurisdictionalUpdates/ucm103134
.htm
• Heparin Catheter Lock-Flush Solutions
– Federal Register of 8/17/2006 -- http://www.fda.gov/OHRMS/DOCKETS/98fr/E6-
13509.htm
– Summary --
http://www.fda.gov/CombinationProducts/JurisdictionalInformation/JurisdictionalUpdates/ucm103161
.htm
• Metered Dose Inhalers, Spacers and Other
Accessories
– http://www.fda.gov/CombinationProducts/JurisdictionalInformation/JurisdictionalUpdates/
ucm103179.htm
• Drug/Biologic Combinations
– http://www.fda.gov/CombinationProducts/JurisdictionalInformation/JurisdictionalUpdates/
ucm119233.htm
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Which GMP Rules Apply?
• What has FDA said?
– Guidance on GMPs for Combination Products
http://www.fda.gov/RegulatoryInformation/Guidances/ucm12619
8.htm
Sets forth broad framework for application of cGMP to
combination products
– Proposed Rule on GMPs for Combination Products
September 23, 2009 – 74 Fed. Reg. 48423
http://edocket.access.gpo.gov/2009/pdf/E9-22850.pdf
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Final Rules on GMPs
• January 22, 2013 – 78 Fed. Reg. 4307
https://www.federalregister.gov/articles/2013/01/22/2013
-01068/current-good-manufacturing-practice-
requirements-for-combination-products
• FDA: “The final rule is largely identical to the
proposed rule.” 78 Fed. Reg. @ 4308.
• Creates 21 CFR Part 4
• Effective date: 180 days after promulgation – July 22,
2013
45
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GMPs …
• Assumptions underlying final GMP rule:
– During and after components combined, both sets of cGMP
regulations apply (whether a single entity product or co-
packaged products)
– However, compliance with both sets of regulations can
generally be achieved by using either regulation and agency
does not see need for parallel systems
• Two options under final rule
– Parallel systems -- satisfy all requirements for both systems
– “Streamlined Approach” – full compliance with one system,
plus compliance with designated parts of other system [where
other system is not your usual system] IS full compliance with
all of second system
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Streamlined – Drug "Dominant"
• Must meet all drug GMP rules, plus these device
Quality System rules:
– 820.20 – Management Responsibility
– 820.30 – Design Controls
– 820.50 – Purchasing Controls
– 820.100 – Corrective and Preventive Action (CAPA)
– 820.170 – Installation
– 820.200 – Servicing
21 CFR 4.4(b)(1)
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Streamlined – Device "Dominant"
• Must meet all device Quality System rules, plus
these drug GMP rules:
– 211.84 – Testing and approval or rejection of components,
drug product containers, and closures
– 211.103 – Calculation of yield
– 211.132 – Tamper-evident packaging for OTC drugs
– 211.137 – Expiration dating
– 211.165 – Testing and release for distribution
– 211.166 – Stability testing
– 211.167 – Special testing requirements
– 211.170 – Reserve Samples
21 CFR 4.4(b)(2)
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GMPs – Issues Addressed in Final Rule
• What governs in investigational stage?
– Phase 1 – drug component exempt from drug GMPs
– Device component – exempt, except design controls in all
phases
• Does it apply to already approved combination
products?
– Yes; the rule does not change what applies, but creates a
system for understanding how to apply the distinct GMP rules
• Defined “convenience kits” –
“ … only kits that solely include products that are: (1) Also legally
marketed independently and (2) included in the kit as already packaged
and with the same labeling as for independent marketing.
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GMPs – Issues Addressed in Final Rule
• What if two provisions (QSR v. Drug GMP) appear
to clash?
– follow the one more “specifically applicable to the constituent
part” (if you can figure that out) – 78 Fed. Reg. at 4314
• What happens while a constituent part is being
made at a separate facility?
– all CGMP provisions applicable to that constituent part (i.e.,
drug, device, or biologic) must be satisfied at that facility
and … when it is brought to another facility where it is
combined with a different constituent part, then you have to
meet the CGMPs that apply to both …
but … you can use the “streamlined” approach
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GMPs – Issues Addressed in Final Rule
• Design controls –
– to be addressed in guidance
– “The design history file for a combination product … must
address all design issues resulting from the combination
of the constituent parts, regardless of whether” the
manufacturer picks a “drug dominant” or “device dominant”
scheme (or full implementation of both) – 78 Fed. Reg. 4315
– Examples:
document and provide objective evidence that the drug is
appropriate for use with the device – e.g., why a particular drug
will work with a drug-eluting stent
document that the device is appropriate for the drug -- e.g., that
a syringe will not interact with the drug
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GMPs -- Special Cases
• Blood and blood component products – also must
meet requirements of 21 CFR Part 606
• Human Cellular and Tissue-based Products
(HCT/Ps) – Current Good Tissue Practices apply
if product is also regulated as a drug, device or
biologic
– Section 361 of Public Health Service Act – if HCT/P is
combined with another article (other than water and certain
other agents), it is a drug, device or biologic
– 21 CFR 1271 will apply if the HCT/P is also part of a
combination product, especially the Good Tissue Practice
rules at 21 CFR 1271.145 et seq.
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GMP Final Rule – Guidance Will Issue
• FDA plans to issue a guidance on how to meet the
new rule, especially relative to:
– design controls, including coming into compliance with pre-
manufacturing design controls for products already being
marketed
– handling at multiple facilities or multiple manufacturers,
including the duties of the “central managing facility” (my term)
– conflicts between overlapping provisions of GMPs vs. QSR
– batch release testing
53
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• Initially – a “concept paper”
– http://www.fda.gov/oc/combination/adveventconpaper.pdf
• Federal Register, October 1, 2009; 74 Fed Reg. 50744
– http://edocket.access.gpo.gov/2009/pdf/E9-23519.pdf
• Basic approach
– Generally will follow the reporting system applicable to the
type of marketing application under which cleared (if single
application) -- NDA/PMA or 510(k)/BLA
– Assumption – the systems are “substantially similar”
– But, there are five types of safety reports that are unique –
have to see if one applies, in your scenario, to your
combination product
Post-Marketing Safety Reporting
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• 5-Day Report – under Medical Device Reporting (MDR) Rule –
when you learn of a reportable event associated with the device
that necessitates remedial action to “prevent an unreasonable risk
of substantial harm” to public health
• 30-Day Device Malfunction Report – under MDR, get info that
“reasonably suggests” the device has malfunctioned and, if
malfunction were to recur, the device or a similar device you
market would be likely to cause or contribute to death or serious
injury
• 15-Day Alert – for drugs and biologics – reports of a serious and
unexpected adverse event
– Note: under MDR, “serious” events are reportable in 30 days, but MDR does
not talk about unexpected, so 15-day Alert governs where a combination
product containing a device has a serious and unexpected event if you can’t
determine which component caused the AE
The Five Unique Safety Reports
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• 3-Day Field Alert – for drugs only under 21 CFR 314.81(b)(1)
– certain types of problems with drugs such as:
bacteriological contamination, failure to meet specifications
(e.g., stability) or labeling errors that could lead to product
mix-ups
• Expedited Blood Fatality Report – if blood collection or
transfusion is fatal, has to be reported in 7 days of the fatality
The Five Unique Safety Reports …
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• If a single application covers the combination:
– Use reporting rules required under the particular application
– As applicable under factual scenario, use one of Five Types
• When two applications cover the combination:
– If you can reasonably conclude which component caused the
adverse event, you can use that component’s reporting system
– If unclear which component caused AE, have to satisfy
reporting requirement of all types of application
– If other application is held by a third party, have to notify that
person within 5 days of learning of event and also satisfy your
reporting duties
The Proposed Safety Rule in Action
57
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How Many Applications?
• Concept Paper on Marketing Applications for
Combination Products
– http://www.fda.gov/downloads/CombinationProducts/RequestsforComment/UCM108197.
pdf
• Basics:
– PMOA does not ensure application status; but lead Center
– Single application usually is sufficient
– Exceptions
One component is already approved, but labeling will need to be changed
Biologics – legally can have separate apps. for components
When the components are “separate and complex” – e.g., a device in
combination with a new molecular entity drug/biologic
Where needed to “apply mechanisms to ensure appropriate regulation or
unique regulatory requirements” not available under one app.
Example: gene therapy
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How Many Applications?...
• You Might Want Two – perhaps:
– To qualify for Waxman-Hatch Exclusivity
– Orphan Drug Status
– To protect proprietary data if 2 firms are involved
• Complex decision tree suggested in concept paper
on how these are handled
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User Fees – Can I Pay the Least
Amount?
• Guidance on User Fees for Combination Products
– April 2005
– http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM147118.
pdf
• Basics
– Depends on type and # of applications
– If two applications submitted voluntarily, pay two fees
– If two applications REQUIRED, still pay two fees
• “Innovative Product Waiver” – consider seeking
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References
• Overview of the Office of Combination Products
– http://www.fda.gov/AboutFDA/CentersOffices/OC/OfficeofScienceandHealthCoordination/Officeof
CombinationProducts/default.htm
• Frequently Asked Questions on Combination
Products
– http://www.fda.gov/CombinationProducts/AboutCombinationProducts/ucm101496.htm
• Jurisdictional Determinations –
– http://www.fda.gov/CombinationProducts/JurisdictionalInformation/RFDJurisdictionalDecisions/defa
ult.htm
• Guidance on Early Development Considerations
for Innovative Combination Products (9/2006)
– http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm126054.pdf
• Final Rule on “Primary Mode of Action” –
8/25/2005; 70 Fed. Reg. 49848
– http://www.fda.gov/OHRMS/DOCKETS/98fr/05-16527.pdf
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Additional References …
• Other Types of Combinations (e.g.,
Drug/Cosmetic)
– http://www.fda.gov/CombinationProducts/AboutCombinationProducts/ucm101464.htm
• Examples of Combination Product Approvals
– http://www.fda.gov/CombinationProducts/AboutCombinationProducts/ucm101598.htm
• Articles on Combination Products – at OCP
site
– http://www.fda.gov/CombinationProducts/MeetingsConferencesWorkshops/ucm116639.htm
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Basics
• Center for Veterinary Medicine (CVM) – controls:
– New Animal Drug Application (NADA) process
Investigational
Full
Abbreviated
– Medicated Feeds
– Pet Food
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Investigational New Animal Drug (INAD)
• Must be in place before shipping an investigational
new animal drug
• Reviewed by Office of New Animal Drug
Evaluation (ONADE)
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New Animal Drug Application (NADA)
• New animal drug – Section 201(v) of the Act:
… means any drug intended for use for animals other than man, including any drug
intended for use in animal feed but not including such animal feed,—
(1) the composition of which is such that such drug is not generally recognized, among
experts qualified by scientific training and experience to evaluate the safety and
effectiveness of animal drugs, as safe and effective for use under the conditions prescribed,
recommended, or suggested in the labeling thereof; except that such a drug not so
recognized shall not be deemed to be a “new animal drug” if at any time prior to June 25,
1938, it was subject to the Food and Drug Act of June 30, 1906, as amended, and if at such
time its labeling contained the same representations concerning the conditions of its use; or
(2) the composition of which is such that such drug, as a result of investigations to
determine its safety and effectiveness for use under such conditions, has become so
recognized but which has not, otherwise than in such investigations, been used to a
material extent or for a material time under such conditions
• Safety – in target animal and humans that might
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NADA …
Identification
Table of Contents
Labeling
Components & Composition
Manufacturing Methods,
Facilities & Controls
Samples
Analytical Methods for
Residues
Safety & Effectiveness
Evidence
Applicant’s commitment to
market consistent with NADA
GMP Compliance
GLP Compliance
Environmental Assessment
(unless Categorical Exclusion
applies)
FOI Summary – of studies
serving as basis for approval –
FDA will release to public
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● Governed by Section 512(b) of Act and 21 CFR 514
● Basic sections:
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NADA -- Requirements & Processes
• Patent information – holder of approved NADA
must “list” with FDA if claims drug or a method of
use for drug
• FDA must publicize approvals monthly – “Green
Book”
• Phased submission/review – allowed by CVM –
leads to a “technical section complete” letter
– Administrative NADA – CVM then has 180 days
• Expedited Review – ERS – advances in animal
health or reduction of human pathogens
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MUMS – Minor Use/Minor Species
• Major species – horse, cattle, dog, cat, pigs,
chickens, and turkeys
• Minor species – all others
• Minor use -- major species for indication that occurs
infrequently and in only a small number of animals
or in limited geographical areas and in only a small
number of animals annually.
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MUMS – Benefits and Procedures
• “Conditional Approval” – can market after proving
safe if reasonable expectation of effectiveness
– have 5 years to collect effectiveness data via annual renewals
• “Indexing” – 21 CFR 516 – legally marketed drugs
can be used for unapproved minor species
– reviewed by expert panels
• Designation – if received, can get 7 years market
exclusivity and other monetary benefits
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Generics – Abbreviated NADA (ANADA)
• 1988 – created by Generic Animal Drug and Patent
Term Restoration Act (GADPTRA) – very similar to
Waxman-Hatch Act for human drugs
– Bioequivalence – in at least one labeled species
• Market exclusivity available for full NADAs
– 5 years – New Chemical Entity
– 3 years – New studies –
substantial evidence of the effectiveness of the drug involved, any studies of
animal safety, or, in the case of food producing animals, human food safety
studies (other than bioequivalence studies or residue depletion studies, except
residue depletion studies for minor uses or minor species) required for the
approval of the application and conducted or sponsored by the applicant
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Animal Drug User Fee Act (ADUFA)
• Initially put in place in 2003; thus, not on same
reauthorization schedule as other user fees
• Waivers or reductions – may be possible:
– application submitted under MUMS – Minor Use/Minor
Species solely for a MU or MS
– small business
– NADA solely to provide for AD’s use in a “free-choice
medicated feed”
• Technically, do not apply to Abbreviated New
Animal Drug Applications, but they have a separate
law -- AGDUFA72
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Animal Feeds
• Non-medicated – to meet animal’s nutritional needs
– includes pet food
– generally – no prior approval by CVM if made from approved
food additives or GRAS (generally recognized as safe) ingredients
• Medicated – to deliver drug to animal
• Dietary supplements marketed for animals – treated
as food and not under DSHEA
• Three types:
– Type A Medicated Articles
– Type B Medicated Feeds
– Type C Medicated Feeds
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Type A Medicated Articles
• Mixtures of one or more drug substance(s) with
appropriate vehicles
• Requires pre-approval of an NADA or ANADA
• Category I – require no withdrawal period at lowest
use level in each species in which approved
• Category II – require a withdrawal at lowest use
level in at least one species or regulated on a “no
residue” basis or with a zero tolerance
• Intended solely to manufacture another Type A or a
Type B or Type C Medicated Feed
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Type B Medicated Feed
• Contains either a Type A Medicated Article or
another Type B Medicated Feed, plus substantial
quantity of nutrients (at least 25% of total weight)
• Used solely to manufacture another Type B
Medicated Feed or a Type C
• Before being fed to animal, must be substantially
diluted to produce a Type C Medicated Feed
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Type C Medicated Feed
• Contains an active drug component – intended:
– as complete animal feed; or
– to be fed top-dressed; or
– offered free choice in conjunction with other animal feed to
supplement the animal’s total daily ration
• Produced by substantially diluting a Type A
Medicated Feed, a Type B Medicated Feed, or
another Type C Medicated Feed
• Medicated Feed cGMPs – 21 CFR 225
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Off-Label Use
• Animal Medicinal Drug Use Clarification Act of 1994
(AMDUCA)
– Allows for veterinarians to use approved animal drugs for
unapproved uses
can’t result in violative residues in food-producing animals
consistent with regulations in 21 CFR 530
– Allows for use of approved human drugs for animal uses under
certain circumstances
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Veterinary Devices
• CVM has jurisdiction, but not significantly regulated
– Adequate directions for use in target species
– Subject to adulteration and misbranding provisions of Act
– QSR for human devices not applicable
– Must meet other requirements such as laser standards
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Veterinary Biologics
• Regulated by Center for Veterinary Biologics in
Animal & Plant Health Inspection Service (APHIS)
at USDA
• Under Virus-Serum Toxin Act (VSTA) of 1913
– Pure, safe, potent and effective biologics
– Veterinary Biologics Establishment License
– Veterinary Biologics Product License
– Allows for a phased review of license applications
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Questions?
• Call, e-mail or fax:
Michael A. Swit, Esq.
Special Counsel, FDA Law Practice
Duane Morris LLP
750 B Street, Suite 2900
San Diego, California 92101
direct: 619-744-2215
fax: 619-923-6248
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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