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.
FDA Regulation of Combination ProductsMichael Swit
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.
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.
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.
In our post about the nutraceuticals industry, dietary supplements as a category of nutraceuticals are subject to compliance with FDA regulations under the Dietary Supplement Health and Education Act of 1994 (DSHEA).
FDA Regulation of Combination ProductsMichael Swit
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.
FDA Regulation of Combination ProductsMichael Swit
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.
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.
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.
In our post about the nutraceuticals industry, dietary supplements as a category of nutraceuticals are subject to compliance with FDA regulations under the Dietary Supplement Health and Education Act of 1994 (DSHEA).
FDA Regulation of Combination ProductsMichael Swit
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.
1.b alcances de la nueva ley de inocuidad de alimentos del fdaProColombia
The document summarizes the Food Safety Modernization Act and the FDA's proposed produce safety regulations. It discusses why the law was needed due to issues like globalization and the increasing complexity of the food supply. It then outlines key provisions of the law around prevention, inspections/compliance, imports, and partnerships. It focuses on new requirements for importers to verify the safety of foreign suppliers and facilities. Finally, it discusses the FDA's approach to implementing the new rules through education, outreach, and flexibility.
The Federal Food, Drug, and Cosmetic Act (FFDCA) was enacted in 1938 and gave the U.S. Food and Drug Administration (FDA) authority to oversee food, drugs, and cosmetics. It was passed in response to the 1937 Elixir Sulfanilamide tragedy that killed over 100 people. The FFDCA introduced requirements for pre-market approval of new drugs and mandated that labels disclose ingredients and directions for safe use. It has since been amended multiple times to both strengthen and clarify the FDA's regulatory authority.
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.
The document provides background information on the U.S. food safety system. It discusses the main federal regulatory agencies that oversee food safety - the USDA and FDA. The USDA regulates meat and poultry products while the FDA regulates all other foods, including imports. Other agencies like CDC and EPA also play roles. The agencies have different statutory authorities that influence their oversight approaches. The U.S. system relies on cooperation between federal, state, and local authorities.
The document discusses the Federal Food, Drug, and Cosmetic Act (FFDCA) and the Kefauver-Harris Amendments of 1962. The FFDCA was passed in 1938 in response to tragedies from unsafe drugs and gave more authority to the FDA. The Kefauver-Harris Amendments of 1962 required drug manufacturers to prove a drug's efficacy and safety before approval in response to the thalidomide crisis. The amendments strengthened pre-market drug approval processes and mandated new drug efficacy studies.
Manufacturers that export FDA-regulated products such as drugs and medical devices from the US are oftentimes required to provide a certificate prepared by the FDA which confirms the product’s regulatory and marketing status...
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).
This document provides guidance on submitting a New Drug Application (NDA) in India. It defines key terms like new drugs and outlines the regulatory agencies and rules involved. The summary requirements for an NDA include chemical and pharmaceutical information on the active ingredient and formulation, results from animal and human clinical studies in phases I-III, and details on manufacturing and quality controls. Supporting documents like a license, drug samples, and prescribing information must also be provided. The review process involves examination by regulatory authorities and subject matter experts.
HIGHLIGHTED: Guidance for Industry: Fulfilling Regulatory Requirements for Po...NextWorks
This is the highlighted version of FDA's Guidance for Industry
Fulfilling Regulatory Requirements for Postmarketing Submissions of Interactive Promotional Media for Prescription Human and Animal Drugs and Biologics from January 2014.
When these guidances come out, I typically go through them and highlight the most relevant portions for those who need to skim through or refresh their memory.
HIGHLIGHTED: Guidance for Industry: Internet/Social Media Platforms: Correcti...NextWorks
This is the highlighted version of FDA's Guidance for Industry
Internet/Social Media Platforms: Correcting Independent Third-Party Misinformation About Prescription Drugs and Medical Devices
When these guidances come out, I typically go through them and highlight the most relevant portions for those who need to skim through or refresh their memory.
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.
- A new dietary ingredient (NDI) is defined as a dietary ingredient that was not marketed in the United States before October 15, 1994. Manufacturers and distributors must submit a notification to the FDA at least 75 days before marketing a dietary supplement containing an NDI.
- The notification must include a description of the NDI, the manufacturing process, a safety narrative explaining why the supplement is reasonably expected to be safe, and a description of the supplement and its conditions of use.
- Certain dietary ingredients that have been present in the food supply are exempt from the notification requirement if they have not been chemically altered. However, all dietary supplements containing an NDI, including exempt ones, must not cause the product
This document summarizes amendments made to Administrative Order 56 s. 1989 regarding rules and regulations on licensing drug establishments and other authorizations in the Philippines. The amendments were made to align drug establishment licensing with recently passed laws, streamline regulatory processes, and promote electronic transactions. Key changes include expanding the scope to various entities involved with pharmaceutical products, defining important terms, and requiring licenses or permits for various activities involving pharmaceuticals.
Overview of the Veterinary Feed DirectiveCari Rincker
This presentation was prepared for the 2016 American Agriculture Law Association Annual Educational Symposium. This presentation will be given on October 6, 2016. It first lays the background of the Veterinary Feed Directive ("VFD") and then delves into the requirements of various stakeholders including (1) veterinarians, (2) livestock producers, (3) feed distributors, and (4) drug manufacturers.
The document summarizes the historical aspects of the new drug approval process in the United States. It outlines the key events and legislation that established regulations for drug safety, including the 1906 Food and Drug Act, the 1938 Food, Drug, and Cosmetic Act, the 1962 Kefauver-Harris Amendments requiring proof of efficacy, and the 1992 Prescription Drug User Fee Act expediting the review process. The document provides an overview of the clinical trial phases and FDA review process required to demonstrate a drug is safe and effective before approval and public use.
drug registrastion requirements in china ...sonali mishraSonaliMishra64
The document discusses regulatory highlights and drug development in China. It provides an overview of the Chinese regulatory authority, currently called the National Medical Products Administration (NMPA), which oversees drug registration and clinical trials. It also summarizes the drug registration process in China, including requirements for imported drugs. This involves submitting clinical trial applications, conducting clinical trials, and obtaining an imported drug license. The document outlines categories for drug registration and review timelines, as well as opportunities for accelerated approval in China.
I. INTRODUCTION
II. DEFINITIONS
III. TYPES OF DRUG MASTER FILES
IV. SUBMISSIONS TO DRUG MASTER FILES
V. AUTHORIZATION TO REFER TO A DRUG MASTER FILE
VI. PROCESSING AND REVIEWING POLICIES
VII. HOLDER OBLIGATIONS
IX. CLOSURE OF A DRUG MASTER FILE.
The Hatch-Waxman Act established an abbreviated approval pathway for generic drugs that relies on the safety and efficacy evidence of the branded reference drug. It aims to balance incentives for innovation and generic competition. The Act created ANDAs that allow generics to enter the market after patents and exclusivities expire. It also provides the branded drug up to 30 months to litigate patents against Paragraph IV ANDA challenges and restores some patent term lost during regulatory review.
This document discusses drug scheduling and regulation in various countries. It begins by explaining the roles of pharmaceutical companies, regulatory bodies, and how drugs reach consumers. It then discusses the risks of self-medicating and outlines the role of regulatory bodies in protecting public health and safety. The document goes on to provide histories of drug regulation in India, the United States, and other countries. It explains the various drug schedules used to classify medications based on their risks and medical usefulness. The remainder of the document discusses the specific drug schedules outlined in the Drugs and Cosmetics Act and Rules of India.
Dietary Supplements, Combination Products, and Veterinary MedicineMichael Swit
Presentation to San DIego Regulatory Affairs Network (SDRAN) on key issues relating to regulation of dietary supplements, Combination Products, and Veterinary Medicine.
1.b alcances de la nueva ley de inocuidad de alimentos del fdaProColombia
The document summarizes the Food Safety Modernization Act and the FDA's proposed produce safety regulations. It discusses why the law was needed due to issues like globalization and the increasing complexity of the food supply. It then outlines key provisions of the law around prevention, inspections/compliance, imports, and partnerships. It focuses on new requirements for importers to verify the safety of foreign suppliers and facilities. Finally, it discusses the FDA's approach to implementing the new rules through education, outreach, and flexibility.
The Federal Food, Drug, and Cosmetic Act (FFDCA) was enacted in 1938 and gave the U.S. Food and Drug Administration (FDA) authority to oversee food, drugs, and cosmetics. It was passed in response to the 1937 Elixir Sulfanilamide tragedy that killed over 100 people. The FFDCA introduced requirements for pre-market approval of new drugs and mandated that labels disclose ingredients and directions for safe use. It has since been amended multiple times to both strengthen and clarify the FDA's regulatory authority.
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.
The document provides background information on the U.S. food safety system. It discusses the main federal regulatory agencies that oversee food safety - the USDA and FDA. The USDA regulates meat and poultry products while the FDA regulates all other foods, including imports. Other agencies like CDC and EPA also play roles. The agencies have different statutory authorities that influence their oversight approaches. The U.S. system relies on cooperation between federal, state, and local authorities.
The document discusses the Federal Food, Drug, and Cosmetic Act (FFDCA) and the Kefauver-Harris Amendments of 1962. The FFDCA was passed in 1938 in response to tragedies from unsafe drugs and gave more authority to the FDA. The Kefauver-Harris Amendments of 1962 required drug manufacturers to prove a drug's efficacy and safety before approval in response to the thalidomide crisis. The amendments strengthened pre-market drug approval processes and mandated new drug efficacy studies.
Manufacturers that export FDA-regulated products such as drugs and medical devices from the US are oftentimes required to provide a certificate prepared by the FDA which confirms the product’s regulatory and marketing status...
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).
This document provides guidance on submitting a New Drug Application (NDA) in India. It defines key terms like new drugs and outlines the regulatory agencies and rules involved. The summary requirements for an NDA include chemical and pharmaceutical information on the active ingredient and formulation, results from animal and human clinical studies in phases I-III, and details on manufacturing and quality controls. Supporting documents like a license, drug samples, and prescribing information must also be provided. The review process involves examination by regulatory authorities and subject matter experts.
HIGHLIGHTED: Guidance for Industry: Fulfilling Regulatory Requirements for Po...NextWorks
This is the highlighted version of FDA's Guidance for Industry
Fulfilling Regulatory Requirements for Postmarketing Submissions of Interactive Promotional Media for Prescription Human and Animal Drugs and Biologics from January 2014.
When these guidances come out, I typically go through them and highlight the most relevant portions for those who need to skim through or refresh their memory.
HIGHLIGHTED: Guidance for Industry: Internet/Social Media Platforms: Correcti...NextWorks
This is the highlighted version of FDA's Guidance for Industry
Internet/Social Media Platforms: Correcting Independent Third-Party Misinformation About Prescription Drugs and Medical Devices
When these guidances come out, I typically go through them and highlight the most relevant portions for those who need to skim through or refresh their memory.
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.
- A new dietary ingredient (NDI) is defined as a dietary ingredient that was not marketed in the United States before October 15, 1994. Manufacturers and distributors must submit a notification to the FDA at least 75 days before marketing a dietary supplement containing an NDI.
- The notification must include a description of the NDI, the manufacturing process, a safety narrative explaining why the supplement is reasonably expected to be safe, and a description of the supplement and its conditions of use.
- Certain dietary ingredients that have been present in the food supply are exempt from the notification requirement if they have not been chemically altered. However, all dietary supplements containing an NDI, including exempt ones, must not cause the product
This document summarizes amendments made to Administrative Order 56 s. 1989 regarding rules and regulations on licensing drug establishments and other authorizations in the Philippines. The amendments were made to align drug establishment licensing with recently passed laws, streamline regulatory processes, and promote electronic transactions. Key changes include expanding the scope to various entities involved with pharmaceutical products, defining important terms, and requiring licenses or permits for various activities involving pharmaceuticals.
Overview of the Veterinary Feed DirectiveCari Rincker
This presentation was prepared for the 2016 American Agriculture Law Association Annual Educational Symposium. This presentation will be given on October 6, 2016. It first lays the background of the Veterinary Feed Directive ("VFD") and then delves into the requirements of various stakeholders including (1) veterinarians, (2) livestock producers, (3) feed distributors, and (4) drug manufacturers.
The document summarizes the historical aspects of the new drug approval process in the United States. It outlines the key events and legislation that established regulations for drug safety, including the 1906 Food and Drug Act, the 1938 Food, Drug, and Cosmetic Act, the 1962 Kefauver-Harris Amendments requiring proof of efficacy, and the 1992 Prescription Drug User Fee Act expediting the review process. The document provides an overview of the clinical trial phases and FDA review process required to demonstrate a drug is safe and effective before approval and public use.
drug registrastion requirements in china ...sonali mishraSonaliMishra64
The document discusses regulatory highlights and drug development in China. It provides an overview of the Chinese regulatory authority, currently called the National Medical Products Administration (NMPA), which oversees drug registration and clinical trials. It also summarizes the drug registration process in China, including requirements for imported drugs. This involves submitting clinical trial applications, conducting clinical trials, and obtaining an imported drug license. The document outlines categories for drug registration and review timelines, as well as opportunities for accelerated approval in China.
I. INTRODUCTION
II. DEFINITIONS
III. TYPES OF DRUG MASTER FILES
IV. SUBMISSIONS TO DRUG MASTER FILES
V. AUTHORIZATION TO REFER TO A DRUG MASTER FILE
VI. PROCESSING AND REVIEWING POLICIES
VII. HOLDER OBLIGATIONS
IX. CLOSURE OF A DRUG MASTER FILE.
The Hatch-Waxman Act established an abbreviated approval pathway for generic drugs that relies on the safety and efficacy evidence of the branded reference drug. It aims to balance incentives for innovation and generic competition. The Act created ANDAs that allow generics to enter the market after patents and exclusivities expire. It also provides the branded drug up to 30 months to litigate patents against Paragraph IV ANDA challenges and restores some patent term lost during regulatory review.
This document discusses drug scheduling and regulation in various countries. It begins by explaining the roles of pharmaceutical companies, regulatory bodies, and how drugs reach consumers. It then discusses the risks of self-medicating and outlines the role of regulatory bodies in protecting public health and safety. The document goes on to provide histories of drug regulation in India, the United States, and other countries. It explains the various drug schedules used to classify medications based on their risks and medical usefulness. The remainder of the document discusses the specific drug schedules outlined in the Drugs and Cosmetics Act and Rules of India.
Dietary Supplements, Combination Products, and Veterinary MedicineMichael Swit
Presentation to San DIego Regulatory Affairs Network (SDRAN) on key issues relating to regulation of dietary supplements, Combination Products, and Veterinary Medicine.
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.
“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
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.
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.
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.
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
As defined by Congress in the Dietary Supplement Health and Education Act, which became
law in 1994, adietary supplement is a product (other than tobacco) that
-- is intended to supplement the diet;
-- contains one or more dietary ingredients
(including vitamins; minerals; herbs or
other botanicals; amino
acids; and other substances) or their constituents;
-- is intended to be taken by mouth as a pill, capsule,
tablet, or liquid; and
-- is labeled on
the front panel as being a dietary supplement.
http://ods.od.nih.gov/
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.
DIETARY SUPPLEMENT
The purpose of dietary supplements, is to enhance or supplement the diet. Even though a product is marketed as a dietary supplement, it is still considered a medicine to the extent that it is meant to treat, diagnose, cure, or prevent diseases.
Tablets, capsules, soft gels, powders, bars, gummies, and liquid supplements are just a few of the many different forms that supplements can take.
It is a product that is intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin, a mineral, an herb or other botanical, an amino acid.
A dietary substance use by human to supplement the diet by increasing the total daily intake, or a concentrate, metabolite, constituent, extract, or combinations of these ingredients.
FDA Role
Companies can often introduce a dietary supplement to the market without notifying FDA.
FDA’s role in regulating dietary supplements primarily begins after products enter the marketplace.
If a product is found to be unsafe or not otherwise in compliance with the law, FDA can work with the company to bring the product into compliance or possibly remove it from the market.
FDA regulates both finished dietary supplement products and dietary ingredients.
FDA regulates dietary supplements under a different set of regulations than those covering "conventional" foods (edible fruits and vegetables) and drug products.
Role of DSHEA
Manufacturers and distributors of dietary supplements and dietary ingredients are prohibited from marketing products that are adulterated or misbranded.
That means that these firms are responsible for evaluating the safety and labelling of their products before marketing to ensure that they meet all the requirements of the Federal Food, Drug, and Cosmetic Act (FFDCA) as amended by DSHEA and FDA regulations.
FDA has the authority to take action against any adulterated or misbranded dietary supplement product after it reaches the market
The Dietary Supplement Health and Education Act of 1994 was enacted to prohibit
Dietary supplement manufacturers and distributors from making false claims (such as "natural" and "therapeutic," on supplement labels)
The law also prohibits the manufacture and sale of adulterated dietary supplements.
Aim of these act:
To make dietary supplements safer by forbidding manufacturers and distributors from producing and selling mislabelled or adulterated products.
Act requires that the manufacturer of the dietary supplement ensures their product meets DSHEA and FDA regulations.
Table of Contents
Short Title Reference Table Of Contents
Findings
Definitions
Safety of Dietary Supplements and Burden of Proof on FDA
Dietary Supplement Claims
Statements of Nutritional Support
Dietary supplement ingredient labeling and nutrition information labeling
New dietary ingredients
Good manufacturing practices
Conforming amendments
Withdrawal of the regulations and notice
Commission on dietary supplement labels
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
Successfully Navigating U.S. FDA Requirements when Importing a new Dietary Supplement into the U.S. Presented by Nutritional Products International,Scott Gould and Rosemarie Sunderland on a live Webinar. For more information on marketing your product in the US visit www.nutricompany.com
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
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
First Amendment's Impact on Federal Regulation of Advertising and PromotionMichael Swit
This document summarizes the impact of the First Amendment on the regulation of advertising and promotion by the FDA. It discusses key court cases that have established protections for commercial speech related to pharmaceutical products. It outlines the Central Hudson test for evaluating restrictions on commercial speech and describes FDA guidance and regulations regarding off-label promotion as well as industry-supported medical education. The document focuses on lawsuits brought by the Washington Legal Foundation challenging FDA restrictions as violating the First Amendment.
The document provides an overview of the Waxman-Hatch Act of 1984, which established the modern generic drug approval pathway in the United States. It discusses the reasons for its creation, key provisions such as bioequivalence standards and patent certification requirements, and subsequent amendments. The Act sought to balance increased availability of low-cost generic drugs with incentives for continued pharmaceutical innovation.
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Pedal to the Court Understanding Your Rights after a Cycling Collision.pdfSunsetWestLegalGroup
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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.
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Genocide in International Criminal Law.pptxMasoudZamani13
Excited to share insights from my recent presentation on genocide! 💡 In light of ongoing debates, it's crucial to delve into the nuances of this grave crime.
सुप्रीम कोर्ट ने यह भी माना था कि मजिस्ट्रेट का यह कर्तव्य है कि वह सुनिश्चित करे कि अधिकारी पीएमएलए के तहत निर्धारित प्रक्रिया के साथ-साथ संवैधानिक सुरक्षा उपायों का भी उचित रूप से पालन करें।
The presentation deals with the concept of Right to Default Bail laid down under Section 167 of the Code of Criminal Procedure 1973 and Section 187 of Bharatiya Nagarik Suraksha Sanhita 2023.
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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.
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What We Will Cover on Dietary Supplements
♦ Basics
♦ New Dietary Ingredients
♦ Claims Allowed
♦ GMPs and Other Regulatory Requirements
♦ Adverse Events
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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 …
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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
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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 …
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Definition of D.S. – Part 3(B)
• Section 201(ff)(3)
– B) does not include – “Prior Market” Clause
(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.
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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” …
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New Dietary Ingredients (NDI)
• If a dietary ingredient was not marketed before
October 15, 1994 and (a) not present in the food
supply or (b) chemically altered even if present in
the food supply or as a pre-DSHEA dietary
ingredient), 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
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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
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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
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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)
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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
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Nutrient Content &
Structure/Function 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.”
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Limits on Structure/Function Claims
• 21 CFR 101.93(g)(2) – ten criteria that are barred;
include
– Effects a specific disease or disease class
– Effects the characteristics signs or symptoms of a specific disease
– Effects an abnormal condition linked to a natural state if the
abnormal condition is uncommon or can cause significant harm
– Effects 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
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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”
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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
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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
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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 (“PMOA”)
– Implemented by Chief Mediator and Ombudsman
• Office of Combination Products (“OCP”)
– Created by Medical Device User Fee and Modernization Act
(MDUFMA) – 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
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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)
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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.
• Three types of modes of action:
– Biological product
– Device
– Drug
• Combination products typically have more than one
identifiable mode of action
Source: 21 CFR 3.2(m)31
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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.
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• 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
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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?
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• 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
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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 …
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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
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RFD’s …
• 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
• 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/UC
M251544.pdf
• Format – follow descriptions in 21 CFR 3.7(c)(1)-(3)
• Electronic filing – allowed, but not required
• 15-page limit (with attachments)
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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 jurisdiction
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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 12 - 14)
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
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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
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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
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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
The Five Unique Safety Reports
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• 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
• 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
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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
• Combination Products Main Homepage
– http://www.fda.gov/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 …
• SMG 4011 – Intercenter Consultative/Collaborative
Review Process
– http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/StaffManualGuides/UCM28356
9.pdf
• 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
• AliveCor – Vet app marketed before human use
510(k) cleared …
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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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