Presentation to the Regulatory Affairs Certification (RAC) Review Course, sponsored by the Orange County Regulatory Affairs (OCRA) Discussion Group, on August 2, 2014, in Irvine, CA. See slides 4-58 for Labeling/Advertising Discussion; slide 59 to 72 for Imports/Exports, and 73 to end for Enforcement Actions
plasma master file is a EU requirement for the apploval of the biologics or the biosimilars to the EU in a eCTD format or Nees as per the requirement type and should contain the above given details
plasma master file in European countries and requirements in letter of intent...Sanjay batra
it includes that what is plasma master file, principles, procedure to file PMF, strategy involved, administration information, certification procedure & inspection
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 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 filing for a pharmaceutical product is done in the form of dossier. The slides explain the format and content to be included in all the formats of dossiers.
plasma master file is a EU requirement for the apploval of the biologics or the biosimilars to the EU in a eCTD format or Nees as per the requirement type and should contain the above given details
plasma master file in European countries and requirements in letter of intent...Sanjay batra
it includes that what is plasma master file, principles, procedure to file PMF, strategy involved, administration information, certification procedure & inspection
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 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 filing for a pharmaceutical product is done in the form of dossier. The slides explain the format and content to be included in all the formats of dossiers.
NSF certification, Standard for dietary supplementAtul Bhombe
Manufacturers, regulators and consumers look to NSF International for the development of public health standards and certification programs that help protect the world’s food, water, consumer products and environment. NSF is a global, independent organization, our standards team facilitates development of public health standards, and our service teams test, audit and certify products and services
It contains details rules and regulations /legislation of Pharmaceuticals, Cosmetics, Active Substance Masters File, Investigational Medicinal Product Dossier for European Union
JAPAN: ORGANISATION OF PMDA, PHARMACEUTICAL LAWS & REGULATIONS, TYPES OF REGI...anjaliyadav012327
In Japan, the pharmaceutical industry operates under strict regulatory oversight by the Pharmaceutical and Medical Devices Agency (PMDA). Established in 2004, PMDA functions within the Ministry of Health, Labour and Welfare (MHLW). The regulatory landscape is primarily governed by the Pharmaceuticals and Medical Devices Law (PMDL), which outlines the requirements for drug approval, clinical trials, manufacturing, and marketing authorization. Companies seeking to introduce pharmaceutical products into the Japanese market must navigate various types of registration applications, including New Drug Applications (NDA) for new products, Marketing Authorization Holder (MAH) Applications for market entry, and Generic Drug Applications for approval of generic versions of existing drugs. Understanding these regulations and application processes is crucial for companies operating in Japan's pharmaceutical sector.
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.
Introduction
Definition
Classification
Regulatory registration procedure
Quality system requirements
Clinical evaluation
Investigation of medical devices
Summary
Medical devices are regulated by the National Medical Product Administration (NMPA), formerly the China Food and Drug Administration (CFDA)
Manufacturers must register their devices with the NMPA before selling or distributing in China.
The NMPA reviews all device applications and has strict requirements for submission documentation, testing, and clinical data.
Any instrument, apparatus, appliance, material, or other article whether used alone or in combination, including the software necessary for its proper application.
Diagnosis, prevention, monitoring, treatment or alleviation of disease
Diagnosis, monitoring, treatment, alleviation of compensation for an injury or handicap conditions
Investigation, replacement or modification for anatomy or a physiological process
Control of conception
The Chinese authorities (CFDA/NMPA) have their own quality management system requirements.
However, these “GMP requirements” are very similar to ISO 13485.
Therefore, manufacturers usually submit the ISO 13485 certificate.
However, the audit will review this certificate against the Chinese GMP requirements.
These audits are regularly carried out during the approval procedure and/or after a recall.
NMPA issued and implemented the "Guideline on Inspection of Quality Management System for Medical Device Registration" on October 10, 2022.
Product Life-cycle Process
The guideline specifies the basic requirements for registration inspection, self-inspection, commissioned inspection, and extended inspection, etc. Applicant needs to:
Ensure the design, development, production, and other process data to be true, accurate, complete, and traceable, and consistent with the registration application materials.
Carry out the registration QMS inspection in reference to the registration application materials, and focus on the design, development, procurement, production management, and quality control of the product.
For lower-risk medical devices (Class I and Class II), clinical evaluation may not always be required. However, higher-risk devices (Class III and implantable devices) generally require clinical evaluation.
The evaluation involves reviewing existing clinical data, scientific literature, and relevant clinical research to assess the safety and performance of the device.
All clinical trials for medical devices must follow China Good Clinical Practices
Clinical investigations are required if no equivalent devices can be found and safety and efficacy cannot be proven with other clinical and non-clinical data.
For certain medical devices, the NMPA may require clinical investigations, especially for novel devices or those with significant risk.
Clinical investigations involve conducting studies on human subjects to generate clinical data on the safety and effectiveness of the device.
Biosimilars
A biosimilar is a biological medicine highly similar to another already approved biological medicine (the 'reference medicine'). (A medicine whose active substance is made by a living organism.)
Biologicals
Biological medicines contain active substances from a biological source, such as living cells or organisms and are often produced by cutting-edge technology.
Biological medicinal product
Biological Medicinal Products, also known as biologics or biologicals, are medicinal products that are manufactured using biotechnology processes and derived from living organisms or their products. They can include vaccines, blood products, gene therapies, monoclonal antibodies, recombinant proteins, and other complex biological substances.
Biological Investigational Medicinal Product
Refer to biological products that are being investigated in clinical trials or research studies to evaluate their safety, efficacy, or pharmacokinetic properties. These products have not yet received marketing authorization and are still in the experimental phase.
In the European Union, A biological substance is referred as the active ingredient in biological products.
A "biological substance" is defined as "a substance that is produced by or extracted from a biological source
That requires a combination of physico-chemical-biological testing, along with the production process and its control, for its characterization and the determination of its quality.“
Examples: Immunologic medicines
Medicines derived from human blood and plasma
Medicines developed by means of recombinant DNA technology
Hybridoma and mAb methods
Advanced therapy medicinal products
The requirements of the EU centralized procedure.
The approval standards for biotechnology products are the same as for chemically synthesized medicines.
Both types of products must be safe and effective and have appropriate quality.
MAA for a biotechnology product must meet the standard dossier submission requirements
MAA must generally comply with the CTD format, including with respect to
Module I (administrative information, including labelling)
Module 2 (various summaries)
Module 3 (chemical, pharmaceutical, and biological information)
Module 4 (nonclinical reports)
Module 5 (clinical study reports)
The EU has approved the highest number of biosimilars worldwide, and consequently has the most extensive experience of their use and safety.
EMA has issued scientific guidelines to help developers conform to the strict regulatory requirements for approving biosimilars.
The guidelines have evolved to keep pace with rapid advances in biotechnology and analytical sciences, and they take on board increasing experience of clinical use.
All medicines produced using biotechnology and those for specific indications must be approved in the EU through EMA
Some biosimilars may be approved at national level, such as some low-molecular weight heparins derived from porcine intestinal mucosa.
Medical Devices registration in Japan , quality system requirements and evaluation and investigation of medical devices in regulated countries ASEAN, China JAPAN and WHO regulations. quality and ethical considerations regulatory and documentation requirements for marketing medical devices and IVDs in regulated countries.
Clinical Research Regulation in European Union ShantanuThakre3
- On 16 April 2014, the European Commission adopted the new Clinical Trial Regulation (EU No 536/2014), repealing Directive 2001/20/EC.
- Although the Clinical Trial Regulation was adopted and entered into force in 2014, the timing of its application depends on confirmation of full functionality of the Clinical Trials Information System (CTIS) through an independent audit.
- The Regulation becomes applicable six months after the European Commission publishes notice of this confirmation.
FDA Trends in Medical Device ComplianceMichael Swit
Presentation to the Joint American Bar Association (ABA)/Medical Device Manufacturers Association (MDMA) Conference, on December 11, 2014, in Washington, D.C.. Slides focus on:
• Major Initiatives –
– Inspection Realignment
– Reporting of Corrections Guidance
• FDA Inspections –Key Observations in Device Inspections
• Marketing & Social Media –
– Intended Use Creep --Aegerion
– Space Limitation Guidance
• HHS Exclusion for FDA Violations –the Curious Case of the Purdue Pharma Executives
NSF certification, Standard for dietary supplementAtul Bhombe
Manufacturers, regulators and consumers look to NSF International for the development of public health standards and certification programs that help protect the world’s food, water, consumer products and environment. NSF is a global, independent organization, our standards team facilitates development of public health standards, and our service teams test, audit and certify products and services
It contains details rules and regulations /legislation of Pharmaceuticals, Cosmetics, Active Substance Masters File, Investigational Medicinal Product Dossier for European Union
JAPAN: ORGANISATION OF PMDA, PHARMACEUTICAL LAWS & REGULATIONS, TYPES OF REGI...anjaliyadav012327
In Japan, the pharmaceutical industry operates under strict regulatory oversight by the Pharmaceutical and Medical Devices Agency (PMDA). Established in 2004, PMDA functions within the Ministry of Health, Labour and Welfare (MHLW). The regulatory landscape is primarily governed by the Pharmaceuticals and Medical Devices Law (PMDL), which outlines the requirements for drug approval, clinical trials, manufacturing, and marketing authorization. Companies seeking to introduce pharmaceutical products into the Japanese market must navigate various types of registration applications, including New Drug Applications (NDA) for new products, Marketing Authorization Holder (MAH) Applications for market entry, and Generic Drug Applications for approval of generic versions of existing drugs. Understanding these regulations and application processes is crucial for companies operating in Japan's pharmaceutical sector.
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.
Introduction
Definition
Classification
Regulatory registration procedure
Quality system requirements
Clinical evaluation
Investigation of medical devices
Summary
Medical devices are regulated by the National Medical Product Administration (NMPA), formerly the China Food and Drug Administration (CFDA)
Manufacturers must register their devices with the NMPA before selling or distributing in China.
The NMPA reviews all device applications and has strict requirements for submission documentation, testing, and clinical data.
Any instrument, apparatus, appliance, material, or other article whether used alone or in combination, including the software necessary for its proper application.
Diagnosis, prevention, monitoring, treatment or alleviation of disease
Diagnosis, monitoring, treatment, alleviation of compensation for an injury or handicap conditions
Investigation, replacement or modification for anatomy or a physiological process
Control of conception
The Chinese authorities (CFDA/NMPA) have their own quality management system requirements.
However, these “GMP requirements” are very similar to ISO 13485.
Therefore, manufacturers usually submit the ISO 13485 certificate.
However, the audit will review this certificate against the Chinese GMP requirements.
These audits are regularly carried out during the approval procedure and/or after a recall.
NMPA issued and implemented the "Guideline on Inspection of Quality Management System for Medical Device Registration" on October 10, 2022.
Product Life-cycle Process
The guideline specifies the basic requirements for registration inspection, self-inspection, commissioned inspection, and extended inspection, etc. Applicant needs to:
Ensure the design, development, production, and other process data to be true, accurate, complete, and traceable, and consistent with the registration application materials.
Carry out the registration QMS inspection in reference to the registration application materials, and focus on the design, development, procurement, production management, and quality control of the product.
For lower-risk medical devices (Class I and Class II), clinical evaluation may not always be required. However, higher-risk devices (Class III and implantable devices) generally require clinical evaluation.
The evaluation involves reviewing existing clinical data, scientific literature, and relevant clinical research to assess the safety and performance of the device.
All clinical trials for medical devices must follow China Good Clinical Practices
Clinical investigations are required if no equivalent devices can be found and safety and efficacy cannot be proven with other clinical and non-clinical data.
For certain medical devices, the NMPA may require clinical investigations, especially for novel devices or those with significant risk.
Clinical investigations involve conducting studies on human subjects to generate clinical data on the safety and effectiveness of the device.
Biosimilars
A biosimilar is a biological medicine highly similar to another already approved biological medicine (the 'reference medicine'). (A medicine whose active substance is made by a living organism.)
Biologicals
Biological medicines contain active substances from a biological source, such as living cells or organisms and are often produced by cutting-edge technology.
Biological medicinal product
Biological Medicinal Products, also known as biologics or biologicals, are medicinal products that are manufactured using biotechnology processes and derived from living organisms or their products. They can include vaccines, blood products, gene therapies, monoclonal antibodies, recombinant proteins, and other complex biological substances.
Biological Investigational Medicinal Product
Refer to biological products that are being investigated in clinical trials or research studies to evaluate their safety, efficacy, or pharmacokinetic properties. These products have not yet received marketing authorization and are still in the experimental phase.
In the European Union, A biological substance is referred as the active ingredient in biological products.
A "biological substance" is defined as "a substance that is produced by or extracted from a biological source
That requires a combination of physico-chemical-biological testing, along with the production process and its control, for its characterization and the determination of its quality.“
Examples: Immunologic medicines
Medicines derived from human blood and plasma
Medicines developed by means of recombinant DNA technology
Hybridoma and mAb methods
Advanced therapy medicinal products
The requirements of the EU centralized procedure.
The approval standards for biotechnology products are the same as for chemically synthesized medicines.
Both types of products must be safe and effective and have appropriate quality.
MAA for a biotechnology product must meet the standard dossier submission requirements
MAA must generally comply with the CTD format, including with respect to
Module I (administrative information, including labelling)
Module 2 (various summaries)
Module 3 (chemical, pharmaceutical, and biological information)
Module 4 (nonclinical reports)
Module 5 (clinical study reports)
The EU has approved the highest number of biosimilars worldwide, and consequently has the most extensive experience of their use and safety.
EMA has issued scientific guidelines to help developers conform to the strict regulatory requirements for approving biosimilars.
The guidelines have evolved to keep pace with rapid advances in biotechnology and analytical sciences, and they take on board increasing experience of clinical use.
All medicines produced using biotechnology and those for specific indications must be approved in the EU through EMA
Some biosimilars may be approved at national level, such as some low-molecular weight heparins derived from porcine intestinal mucosa.
Medical Devices registration in Japan , quality system requirements and evaluation and investigation of medical devices in regulated countries ASEAN, China JAPAN and WHO regulations. quality and ethical considerations regulatory and documentation requirements for marketing medical devices and IVDs in regulated countries.
Clinical Research Regulation in European Union ShantanuThakre3
- On 16 April 2014, the European Commission adopted the new Clinical Trial Regulation (EU No 536/2014), repealing Directive 2001/20/EC.
- Although the Clinical Trial Regulation was adopted and entered into force in 2014, the timing of its application depends on confirmation of full functionality of the Clinical Trials Information System (CTIS) through an independent audit.
- The Regulation becomes applicable six months after the European Commission publishes notice of this confirmation.
FDA Trends in Medical Device ComplianceMichael Swit
Presentation to the Joint American Bar Association (ABA)/Medical Device Manufacturers Association (MDMA) Conference, on December 11, 2014, in Washington, D.C.. Slides focus on:
• Major Initiatives –
– Inspection Realignment
– Reporting of Corrections Guidance
• FDA Inspections –Key Observations in Device Inspections
• Marketing & Social Media –
– Intended Use Creep --Aegerion
– Space Limitation Guidance
• HHS Exclusion for FDA Violations –the Curious Case of the Purdue Pharma Executives
January 29, 2014 Presentation to Compliance2Go webinar, focusing on:
• Legal Framework for 510(k)’s
• Strategy Considerations – Claims & Functions
• Device Modifications
• Regulatory Mechanisms to Implement Changes
• The Review
• What To Do if FDA Says You’re NSE
• Key Lessons Learned
• Reform and Other Recent Trends at FDA
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
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
FDA Regulation of Advertising and Promotion -- the BasicsMichael Swit
Presentation to the November 9-10, 2017 Course sponsored by ComplianceOnline, in Boston, MA, focusing on the basics of FDA regulation of drug and device advertising.
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, March 22, 2018
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.
Internet Issues for FDA-Regulated Industry – A Review of Issues Involving Soc...Michael Swit
November 18, 2014 presentation at webinar sponsored by Compliance2Go, with a focus on:
* Legal issues involved FDA regulation of social media:
* FDA guidance on Social Media;
* FDA enforcement actions involving Social Media; and
* Best practices and other lessons learned
ANDAs, OTCs, Orphans and Cosmetics – Key IssuesMichael Swit
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
“How Do You Look in Stripes?” -- Understanding and Managing the Potential for...Michael Swit
Presentation covers:
• Strict Liability and the “Park Doctrine” – Criminal Liability for Responsible Corporate Officials
• Understanding Collateral Types of Liability That Commonly Arise When FDA Violations Occur
• Key Measures to Take to Protect Your Company and Yourself From Liability
Medical Device Advertising Law & RegulationMichael Swit
Presentation to the IVT Medical Device Conference. San Francisco. August 17, 2006. Talk focused on:
Basics of the Law
Regulation of Promotion/Advertising
Off Label Promotion & the First Amendment
Other Legal Concerns Impacting Advertising
The AdvaMed Code
Medical Device Advertising Law & RegulationMichael Swit
August 17, 2006 presentation to the IVT Medical Device Conference in San Francisco, CA, focusing on:
* Basics of the Law
* Regulation of Promotion/Advertising
* Off Label Promotion & the First Amendment
* Other Legal Concerns Impacting Advertising
* The AdvaMed Code
How to Negotiate Other Important Clinical Study Contract Terms Michael Swit
Presentation on key aspects of clinical trial agreements, with an emphasis on key clauses that may not get as much attention as normal, including choice of law, confidentiality, material transfers, record retention, termination, etc.
FDA Regulation of Promotion & Advertising Part 7: FTC RegulationMichael Swit
November 10, 2017 presentation to the ComplianceOnline course on Ensuring Compliance with FDA Regulation of Promotion & Advertising of Drugs and Medical Devices, in Boston.
Generic Drug Labeling Proposed Rule: The Generic Drug Industry PerspectiveMichael Swit
May 15, 2014 webinar sponsored by the Drug Information Association (DIA) on the November 2013 FDA proposed rule to require generic drug firms to amend their labels with new safety information even if the brand name label has not been changed with the same information.
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
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.
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.
June 14, 2018 presentation to the San Diego Regulatory Affairs Network (SDRAN) Regulatory Affairs Certification (RAC) Review Course on the basics of FDA regulation of generic drugs and biosimilars.
Recent FDA Developments in Digital Health & Clinical Decision Support SoftwareMichael Swit
June 7, 2018 presentation at the 4th Annual Medical Device Summit, sponsored by ComplianceOnline, in San Francisco, focusing on the impact of the 21st Century Cures Act and other developments on how FDA regulates software in the medical device arena, including mobile medical applications.
Synopsis On Annual General Meeting/Extra Ordinary General Meeting With Ordinary And Special Businesses And Ordinary And Special Resolutions with Companies (Postal Ballot) Regulations, 2018
In 2020, the Ministry of Home Affairs established a committee led by Prof. (Dr.) Ranbir Singh, former Vice Chancellor of National Law University (NLU), Delhi. This committee was tasked with reviewing the three codes of criminal law. The primary objective of the committee was to propose comprehensive reforms to the country’s criminal laws in a manner that is both principled and effective.
The committee’s focus was on ensuring the safety and security of individuals, communities, and the nation as a whole. Throughout its deliberations, the committee aimed to uphold constitutional values such as justice, dignity, and the intrinsic value of each individual. Their goal was to recommend amendments to the criminal laws that align with these values and priorities.
Subsequently, in February, the committee successfully submitted its recommendations regarding amendments to the criminal law. These recommendations are intended to serve as a foundation for enhancing the current legal framework, promoting safety and security, and upholding the constitutional principles of justice, dignity, and the inherent worth of every individual.
Matthew Professional CV experienced Government LiaisonMattGardner52
As an experienced Government Liaison, I have demonstrated expertise in Corporate Governance. My skill set includes senior-level management in Contract Management, Legal Support, and Diplomatic Relations. I have also gained proficiency as a Corporate Liaison, utilizing my strong background in accounting, finance, and legal, with a Bachelor's degree (B.A.) from California State University. My Administrative Skills further strengthen my ability to contribute to the growth and success of any organization.
Lifting the Corporate Veil. Power Point Presentationseri bangash
"Lifting the Corporate Veil" is a legal concept that refers to the judicial act of disregarding the separate legal personality of a corporation or limited liability company (LLC). Normally, a corporation is considered a legal entity separate from its shareholders or members, meaning that the personal assets of shareholders or members are protected from the liabilities of the corporation. However, there are certain situations where courts may decide to "pierce" or "lift" the corporate veil, holding shareholders or members personally liable for the debts or actions of the corporation.
Here are some common scenarios in which courts might lift the corporate veil:
Fraud or Illegality: If shareholders or members use the corporate structure to perpetrate fraud, evade legal obligations, or engage in illegal activities, courts may disregard the corporate entity and hold those individuals personally liable.
Undercapitalization: If a corporation is formed with insufficient capital to conduct its intended business and meet its foreseeable liabilities, and this lack of capitalization results in harm to creditors or other parties, courts may lift the corporate veil to hold shareholders or members liable.
Failure to Observe Corporate Formalities: Corporations and LLCs are required to observe certain formalities, such as holding regular meetings, maintaining separate financial records, and avoiding commingling of personal and corporate assets. If these formalities are not observed and the corporate structure is used as a mere façade, courts may disregard the corporate entity.
Alter Ego: If there is such a unity of interest and ownership between the corporation and its shareholders or members that the separate personalities of the corporation and the individuals no longer exist, courts may treat the corporation as the alter ego of its owners and hold them personally liable.
Group Enterprises: In some cases, where multiple corporations are closely related or form part of a single economic unit, courts may pierce the corporate veil to achieve equity, particularly if one corporation's actions harm creditors or other stakeholders and the corporate structure is being used to shield culpable parties from liability.
Defending Weapons Offence Charges: Role of Mississauga Criminal Defence LawyersHarpreetSaini48
Discover how Mississauga criminal defence lawyers defend clients facing weapon offence charges with expert legal guidance and courtroom representation.
To know more visit: https://www.saini-law.com/
Car Accident Injury Do I Have a Case....Knowyourright
Every year, thousands of Minnesotans are injured in car accidents. These injuries can be severe – even life-changing. Under Minnesota law, you can pursue compensation through a personal injury lawsuit.
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
Basic Concepts for Labeling, Advertising,
and Promotion
• “Label” vs. “Labeling”
– “Label” means written, printed, or graphic matter upon the
immediate container. (FDCA § 201(k)).
Information Required to be on the “label” must also be on (or
legible through) the outside container.
– “Labeling” means all labels and other written, printed, or
graphic matter:
Upon any Article or Any of its Containers or Wrappers, or
Accompanying such Article. FDCA § 201(m).
6. www.duanemorris.com6
Labeling
• FDA Interpretation of “Labeling”:
– Printed, Audio, or Visual Matter
– For Use by Medical Community or Users
– Containing Information Supplied by Manufacturer, and
– Disseminated on Behalf of Manufacturer or Distributor
– “Accompanies” – in very broad sense
• Includes: Physicians Desk Reference (PDR), Detailing
Pieces, Calendars, Price Lists, Company Publications,
Letters, Exhibits, Sound and Video Recordings (See 21
C.F.R. § 202.1(l)(2))
7. www.duanemorris.com7
Misbranding
• False or Misleading in Any Particular:
– Labeling (FDCA § 502(a))
– Restricted Device Advertising (502(q))
• Fails to Meet Rx Drug Advertising Requirements in
FDCA § 502(n):
– Established Name
– Quantitative Formula
– “Brief Summary” of Side Effects, Contraindications, and
Effectiveness
8. www.duanemorris.com8
Misbranding
• Fails to Meet Restricted Device Advertising
Requirements in FDCA § 502(r):
– Established Name
– Brief Statement of Intended Uses, Warnings, Precautions,
Side Effects, Contraindications
9. www.duanemorris.com9
Misbranding
• Includes Failure to Reveal Material Facts (FDCA
§ 201(n))
– Material in Light of Representations Made
– Material with Respect to Consequences that May Result
from Use of the Article
• Labeling must bear:
– Adequate Directions for Use (FDCA § 502(f)(1))
– Adequate Warnings (FDCA § 502(f)(2))
– Exceptions: Directions for Common Uses known to the
Ordinary Individual (21 C.F.R. §§ 201.116; 801.116)
10. www.duanemorris.com10
Fair Packaging and Labeling Act (FPLA)
• Incorporated into 21 C.F.R. Part 201, Subpart
C: OTC Drugs and 21 C.F.R. Part 801, Subpart
C: OTC Devices
– Principal Display Panel
– Statement of Identity
– Net Quantity of Contents
11. www.duanemorris.com11
Advertising and Promotion
• Advertising and Promotion not defined in FD&C Act
• Dictionary Definitions (American College
Dictionary):
– “Advertising”: “The act or practice of bringing anything . . . into
public notice.”
– “Promotion”: Furthering the “growth, development, progress,
etc.”
• Unofficial (FDA): Any Activity Used by the Sponsor
to Create an Interest in the Company’s Products.
• Advertising includes advertisements in journals and
broadcast through media (21 C.F.R. 202.1(l)(1))
– This includes the Internet
12. www.duanemorris.com12
Drug Advertising
• FDA Regulates Advertising of Prescription
Drugs (FDCA § 502(n))
– Brief Summary (including side effects, contraindications,
and effectiveness)
– 21 C.F.R. Part 202 – Prescription Drug Advertising
Regulations
– NDA Requirements for Advertising
– Pervasive, Complicated, and Highly Specific Regulatory
Scheme
13. www.duanemorris.com13
Device Advertising
• FDA can Regulate Advertising of Restricted Devices
(FDCA §§ 502 (q) and (r))
– Restricted by Regulation, PMA Approval Conditions
– Misbranded if Advertising is False or Misleading in Any
Particular (502(q))
– Section 502(r) requires “Brief Statement” of:
Intended Uses
Relevant Warnings, Precautions, Side Effects, Contraindications
– Prior Approval of Content only under “Extraordinary
Circumstances” (502(r))
14. www.duanemorris.com14
FTC Regulation of Advertising
• Regulates Advertising where FDA lacks Authority
• Looks at Overall Impression Created
• More Power to Look at Overall Marketing Scheme
• Lanham Act, Unfair Competition
15. www.duanemorris.com15
Fair Balance
• Advertising and Promotional Material (See 21
C.F.R. 202.1(e)(5)(ii))
• “Fair balance” means that Advertisements must
Communicate Fairly and in a Balanced Manner
Information Relating to Side Effects and
Contraindications and Information Relating to
Effectiveness of the Product. (See 21 C.F.R.
202.1(e)(5) and (6)).
– Information about Side Effects and Contraindications must
be Comparable in Depth and Detail with claims for Safety
and Effectiveness.
16. www.duanemorris.com16
Promotion and Intended Use
• Products are Cleared or Approved for Certain
Intended Uses
• Change in Intended Use may Require a New
Clearance or Approval
• New Intended Use Can be Created by:
– Labeling, Advertising, or Promotional Claims
– Oral Statements
– Manifestations of Objective Intent (21 C.F.R. §§ 201.128,
801.4)
Expressions
Circumstances of Distribution
Offered with Knowledge of Use
17. www.duanemorris.com17
Objective Intent
Section 801.4 Meaning of “intended uses” (for Devices)
The words “intended uses” or words of similar import in §§ 801.5, 801.119, and
801.122 refer to the objective intent of the persons legally responsible for the
labeling of devices. The intent is determined by such persons’ expressions or may
be shown by the circumstances surrounding the distribution of the article. This
objective intent may, for example, be shown by labeling claims, advertising
matter, or oral or written statements by such persons or their representatives. It
may be shown by the circumstances that the article is, with the knowledge of such
persons or their representatives, offered and used for a purpose for which it is
neither labeled nor advertised. The intended uses of an article may change after it
has been introduced into interstate commerce by its manufacturer. If, for
example, a packer, distributor, or seller intends an article for different uses than
those intended by the person from whom he received the devices, such packer,
distributor, or seller is required to supply adequate labeling in accordance with the
new intended uses. But if a manufacturer knows, or has knowledge of facts that
would give him notice that a device introduced into interstate commerce by him is
to be used for conditions, purposes, or uses other than the ones for which he offers
it, he is required to provide adequate labeling for such a device which accords
with such other uses to which the article is to be put.
18. www.duanemorris.com18
Intended Use in Premarket Approval
Conditions of Approval
• “No Advertisement or Other Descriptive Printed
Material ... shall Recommend or Imply that the
Device may be Used for any Use that is not
Included in the FDA-approved Labeling for the
Device.”
• Do not Rely on Perceived Tacit Acceptance of
Other Data in the PMA.
19. www.duanemorris.com19
New Indications for Use (510(k))
• New Intended Uses Require new 510(k)s
• Specific Indications within a General Cleared Use
may Require new 510(k)s:
– Example (FDA): “New Indications for Use Require a
510(k) Submission and Must be Based on Valid Scientific
Evidence that Provides Reasonable Assurance of Safety and
Effectiveness of the Laser for the Proposed Use. The Type
of Data that is Acceptable will Vary Depending on the
Indication.”
– E.g., Laser cleared for General Surgery but promoted for
removal of Liver Cancer
20. www.duanemorris.com20
Comparative Claims
• In general, Comparative Claims are Discouraged
• Drug – general guidelines
– Claims of Comparability (Safety or Effectiveness):
At least Two Adequate and Well-controlled Clinical Studies
– Superiority Claims
Provide Data related to the Specific Claims of Superiority
– Partial Comparisons:
Adequate and Well-controlled Studies or Substantial Clinical
Experience
Fair Balance
21. www.duanemorris.com21
Comparative Claims –
Other Considerations
• FTC -- generally silent in law; but by case, has
gone as far as 2 - RWCCT
– For Drugs, Many covered by FDA Regs at 21 C.F.R. Part
202
– For Devices, FTC is Preempted Only for Restricted Devices
– Nevertheless, FTC may Regulate some Comparative Claims
• Lanham Act — Private Right of Action (FDCA does
not have a private right of action)
22. www.duanemorris.com
Overview -- Off-Label Issues
• Tension – FDA, approved labeling and the First
Amendment
• Manifestations
– Scientific information exchange – concern – improper
influence by company on content of educational activity
– Off-Label promotion (to be discussed in Part 6)
– Our approach – disregard “Caronia” for now
• Guidance -- Industry-Supported Scientific and
Educational Activities [Hot link] -- 1997
22
23. www.duanemorris.com
1997 Scientific Exchange Guidance
• To be “safe,” must be both independent and non-
promotional
– if so, not subject to FDA jurisdiction
• Unapproved uses – not permissible if program is
subject to “substantive influence” by regulated industry
• Factors influencing “independence” determination
– Content influence -- whether and to what extent company can
speaker or moderator selection or recommendation, especially if
speaker has promoted company’s products or were subject of
complaints as to past presentations that were biased or
misleading in favor of company
» … continued …23
24. www.duanemorris.com
1997 Scientific Exchange Guidance …
• Factors influencing “independence” determination
… continued …
topic selection, e.g., via targeting points for emphasis
scripting done
– Disclosures to audience –
company funding of project
relationships between company and speakers (e.g., financial,
employee)
whether any unapproved uses would be disclosed
– Program Focus
intent to be free of commercial bias (not clear how proved)
Title and content really match24
25. www.duanemorris.com
1997 Scientific Exchange Guidance …
• Factors influencing “independence” determination
… continued …
– Program Focus … continued
Balanced discussion of all treatment modalities
– Relationship with provider –
e.g., if provider believes continued financial support is dependent
on having programs about company products
intertwining ownership or control of provider with company
– Provider involved in sales & marketing – including provider
employees
– Provider’s Demonstrated Failure to Meet Standards – of
independence, balance, objectivity, or scientific rigor
25
26. www.duanemorris.com
1997 Scientific Exchange Guidance …
• Factors influencing “independence” determination
… continued …
– Multiple presentations – of same material – could be factor;
FDA recognizes there are benefits to repeated info
– Audience selection – how done can influence
generated by company Sales & Marketing – e.g., to reward big “rx
writers” or Key Opinion Leaders (KOLs)
– Opportunities for discussion – if not present, not good
– Post-event dissemination of information – except if done via
unsolicited request or thru independent provider
– Ancillary promotional actions –
exhibit materials
Sales & marketing presentations26
27. www.duanemorris.com
1997 Scientific Exchange Guidance …
• Factors influencing “independence” determination
… continued …
– Complaints – any raised that company tried to influence content
• Document independence
– Contract between company and provider that provides for
independence and that provider will be solely responsible for
managing program
• Promotional vs. non-promotional
– If supported activity is not about the company’s products OR
competitive products, is not promotional
27
29. www.duanemorris.com
January 2009 – Guidance
• Good Reprint Practices for the Distribution of
Medical Journal Articles and Medical or Scientific
Reference Publications on Unapproved New Uses of
Approved Drugs and Approved or Cleared Medical
Devices [Hot Link]
• Genesis of guidance
– FDAMA § 401 – had added § 551 of Act (sunsetted in late
2006) – on off-label use dissemination; led to promulgation of
21 CFR Part 99 (also now void) – if complied, would not be
used as evidence of intent of off-label use – “safe harbor”
limited to HCPs and certain healthcare entities (e.g., PBMs)
sunsetting – led to guidance in 200929
30. www.duanemorris.com
Feb. 2014 – New Draft Guidance
• Distributing Scientific and Medical Publications on
Unapproved New Uses – Recommended Practices
[Hot Link]
– will replace 2009 guidance – still applies only to 3rd party pubs.
– Key differences:
Adds “clinical practice guidelines” (CPGs) to items covered by
guidance
Clarifies that it also applies to “off-label” promotion of exempt
medical devices for uses outside those covered by classification
regulation
Discusses the different types of documents separately: (1)
scientific journal articles; (2) scientific or medical reference texts;
and (3) clinical practice guidelines (CPGs)30
31. www.duanemorris.com
FDA -- Legal Analysis of Unapproved Use
• Drug
– approved drug marketed for an unapproved use is an
unapproved drug for that use – violation of § 505(a) – is a
“prohibited act” under § 301(d) of Act
– unapproved drug that is marketed lacks adequate directions for
use in violation of § 502(f) of Act – in turn, it is a prohibited
act under § 301 of Act to market a misbranded drug
• Medical Device – if promoted for unapproved or
uncleared use is also misbranded and adulterated
– Marketing an adulterated or misbranded device = prohibited
act under § 301 of the Act.
31
33. www.duanemorris.com
Scientific or Medical Journal Articles
• Requirements for Publishing Entity
– Must have editorial board of experts (‘09)
independent of the organization that publishes the article
– Public policy of full disclosure of conflicts of interest for
authors, editors, and contributors
• Article – must:
– Be peer reviewed and published per peer review procedure
– Be an unabridged reprint or copy of article
– Contain information that:
Describes adequate and well-controlled clinical investigations
that are considered scientifically sound by experts qualified to
evaluate safety or effectiveness of product33
34. www.duanemorris.com
Scientific or Medical Journal Articles …
• Article – must …:
– Contain information that is such that … :
Devices – articles on following, “also may be consistent with
this guidance:”
“significant investigations other than adequate and well-controlled
studies, such as meta-analyses, if they are testing a specific clinical
hypothesis
“significant non-clinical research” – such as well-designed bench
or animal studies
– Send with approved labeling for each product discussed in
article
– Send with a “comprehensive bibliography” of other articles
about the off-label use (pro or con) – unless the bibliography is
in article34
35. www.duanemorris.com
Scientific or Medical Journal Articles …
• Article – must …:
– Send with a “representative publication” (if existing) that
reaches contrary or different conclusions on unapproved use,
especially those calling into question the article you are sending
– Send separately from any promotional material
If a sales rep get a question on the article, rep must direct
questioner to a medical/scientific department that is
independent of sales/marketing
Can’t disseminate in the exhibit hall of a conference or during
promotion speakers’ programs
• Article – must not:
– Be false or misleading
– Suggest a use that is dangerous to health35
36. www.duanemorris.com
Scientific or Medical Journal Articles …
• Article – must not:
– Be funded, wholly or partially, be the maker of the product
– Be “marked, highlighted, summarized, or characterized” by
product maker to “emphasize or promote” the off-label use
– Be primarily distributed by product maker; rather, must be
generally available publicly where periodicals are sold
– Be written, edited, excerpted or published at request of product
maker
– Be edited or “significantly influenced”** by product maker or
any individual having a “financial relationship” to product
maker
** see discussion on influence on ISSEA (slides 3 to 7, infra)
36
37. www.duanemorris.com
Scientific or Medical Journal Articles …
• Article – must not:
– Be attached to any product info other than approved labeling
or cleared indications for use statement
• Reprint should be accompanied by a “prominently
displayed and permanently affix statement” that:
1. Lists the drugs or devices in the reprint in which product
maker has an interest
2. That some (or all) of the uses in the article have not been
blessed by FDA “as applicable to the described drug(s) or
device(s)”
I interpret that you have to say which uses are not blessed
37
38. www.duanemorris.com
Scientific or Medical Journal Articles …
• Reprint should be accompanied by a “prominently
displayed and permanently affix statement” that … :
3. Lists any author “known to the manufacturer” as having a
financial interest in the mfr. or the product of the mfr. or
receiving compensation from the mfr.; must state:
• Nature and amount of financial interest
• Affiliation of author
4. States any person known to the mfr. to have funded the study
5. All significant risks or safety concerns associated with the
unapproved use that are known to mfr., but not discussed in
article
Note: no direct mandate to do a literature search; however, one
should be done for liability reasons38
39. www.duanemorris.com
Scientific or Medical Journal Articles …
• Unacceptable Reprints
– Letters to the editor
– Abstracts of a publication
– Reports of healthy volunteer studies
– Publications consisting of statements or conclusions but which
contain little or no substantive discussion of the relevant
investigation or data on which they are based
39
40. www.duanemorris.com
Scientific or Medical Reference Texts
• Handled separately under guidance because texts
are much longer than articles, but still may discuss
off-label uses
• If disseminated in its entirety, must:
1. Be based on a systematic review of the existing evidence
2. Be published by an independent publisher that is:
• not “substantially dependent on financial support” from drug
or device mfrs.; and
• Who publishes scientific or medical educational content for
health care professional and students
3. Be the most current version
40
41. www.duanemorris.com
Scientific or Medical Reference Texts …
• If disseminated in its entirety, must …:
4. Be authored, edited or contributed by experts with
“demonstrated expertise” on subject
5. Be peer-reviewed per published peer-review procedures of the
publisher
6. Sold through “usual and customary” independent channels
directed at HCP’s and students
7. Be distributed separately from promotional materials
If a sales rep get a question on the article, rep must direct
questioner to a medical/scientific department that is
independent of sales/marketing
Can’t disseminate in the exhibit hall of a conference or during
promotion speakers’ programs41
42. www.duanemorris.com
Scientific or Medical Reference Texts …
• If disseminated in its entirety, must …:
8. Contain prominently displayed and permanently affixed
statement that:
Some of the uses may be off-label
Some of the authors might have a financial interest in the mfr.
or product being written about, unless mfr. verifies that none of
the authors has such a financial interest
9. If a text contains a chapter with a “primary substantive
discussion” to mfr.’s product, have to send with the product
labeling for each discussed product.
42
43. www.duanemorris.com
Scientific or Medical Reference Texts …
• If disseminate a single chapter, must:
1. Meet above criteria for entire text, subject to modifications
2. Be unaltered/unabridged and directly extracted from the text
in which chapter appears
3. If “necessary to provide context,” must disseminate with other
chapters from the same text
4. Contain prominent and permanently affixed statement
identifying the mfr. and disclosing:
Drug or device in which mfr. has an interest
That some or all of the uses are off-label
Disclosure of financial interests in the mfr. or product of any
author, including author’s affiliation and nature of fin. interest
43
44. www.duanemorris.com
Scientific or Medical Reference Texts …
• If disseminate a single chapter, must …:
Disclose “all significant risks or safety concerns” associated with
the unapproved uses that are known to mfr. but not discussed
in the chapter
Disseminate with the approved labeling for each product in the
chapter
• Can’t be:
1. False or misleading
2. Suggest a use that makes product dangerous to health
44
45. www.duanemorris.com
Scientific or Medical Reference Texts …
• Other restrictions:
– Must be generally available in publishing channels; can’t be
primarily distributed by the mfr.
– Can’t be edited or significantly influenced by mfr. or by
individuals have a financial relationship with the mfr.
– Can’t be marked, highlighted, summarized, etc. as to the
unapproved use, verbally (e.g., by sales rep) or in writing
– Can’t be written or published specifically at the request of the
mfr.
– Can’t be abridged or excerpted (except for sending a single
chapter consistent with the guidance)
– Can’t be attached to product information, except for approved
labeling45
46. www.duanemorris.com46
Promotion on the Internet
• Subject to the Same Regulatory and Statutory
Requirements as Materials Distributed by Other
Means.
• Issues:
– Is it Labeling, Advertising, or Promotional Material?
– Company Control or Sponsorship of Information on a Site
– Links to Sites with Unapproved Uses
47. www.duanemorris.com47
Promotion on the Internet (cont.)
• Products Sold in Foreign Countries
– Disclosure of Unapproved Status in U.S. Required on
U.S.–accessible site
– Warning Letter: A Use with only a Foreign Approval was
on Internet
– Use of Country Flags has been Allowed
48. www.duanemorris.com48
Promotion on the Internet (cont.)
• Promotion with Disclaimers has Resulted in
Warning Letters
• Links to Independent Internet sites Sponsored by
Peer-Reviewed Journals Permitted, as Long as
they do Not Violate Fair Balance
• Links to Sites Describing Off-Label Uses have
Drawn Warning Letters
– “Significant Focus” Standard
• E-commerce Internet sites must Prevent
Purchase of Prescription Products without
Physician Approval
49. www.duanemorris.com49
Do’s and Don’ts
• Do Treat Internet Like Other Media (to the Extent
Possible)
• Do Not Promote Off-label Uses
• Do Use Links to Full Labeling of Product
• Avoid Sponsoring or Linking to Internet sites
Promoting Off-Label Use
• “Fire Walls” can be Useful, if Practicable
50. www.duanemorris.com50
In Vitro Diagnostic Labeling
• 21 C.F.R. § 809.10 Contains Specific
Requirements
• Labeling Requirements for:
– Immediate and Outer Containers
– Package Insert
51. www.duanemorris.com51
IUO and RUO Exemptions —
21 C.F.R. § 812.2(c)(3)
• Exemptions from Investigational Use
Regulations for IVDs if:
– Noninvasive
– No Invasive Sampling Procedure that Presents
Significant Risk
– Does Not Introduce Energy into Subject
– Not to be Used as the Diagnostic Procedure
52. www.duanemorris.com52
RUO Exemption — 21 C.F.R.
§ 809.10(c)(2)(i)
• Research Use Only (RUO)
– Laboratory Research Phase of Development or Not
Represented as an Effective IVD (i.e., “Looking for a Use”)
– Labeled: “For Research Use Only. Not for Use in Diagnostic
Procedures.”
53. www.duanemorris.com53
IUO Exemption — 21 C.F.R.
§ 809.10(c)(2)(ii)
• Investigational Use Only (IUO)
– Testing Prior to Full Commercial Marketing
– Labeled: “For Investigational Use Only. The
Performance Characteristics of this Product have Not
been Established.”
54. www.duanemorris.com54
FDA Failure to Control IUO
and RUO Use
• E.g., Warning Letter —
– Western Blot Kits Shipped for Commercial Use Without an
Approved Market Clearance or Investigational Approval
• Draft Policy (January 5, 1998)
– 510(k)s, PMAs for IVDs
– Attempts to Prioritize, Triage
– Enforcement Categories
– New IVD’s need 510(k) or PMA before Marketing
55. www.duanemorris.com55
Prescription Drugs and Devices
• Not Safe to Use Except Under Supervision of
Licensed Practitioner (FDCA §§ 503(b)(1); 21
C.F.R. §§ 201.100, 801.109)
• Exemption from Adequate Directions for Use
• Rx Legend:
– “Caution, Federal Law Restricts this Device to Sale by or on
the Order of a ______.”
– “Rx only” allowed for drugs.
56. www.duanemorris.com56
Prescription Drugs and Devices
• Labeling must be Adequate for a Licensed
Practitioner
• Follow FDA Regulations, Product Approvals and
Clearances, and Guidances for Specific Products
57. www.duanemorris.com57
Other Exemptions from
Adequate Directions for Use
(See Applicable Regulations for Specifics)
• Retail Exemption for Rx Devices (21 C.F.R. §
801.110)
• Medical Devices having Commonly Known
Directions (Ordinary Individual) (21 C.F.R. §
801.116)
• General Purpose Laboratory Reagents (21 C.F.R.
§ 809.10(d)) – Uses generally known by persons
trained in their use
58. www.duanemorris.com58
• Intended for Processing, Repacking, or
Manufacturing Use – (21 C.F.R. § 801.122)
– “Caution: For Manufacturing, Processing, or
Repacking.”
• For Use in Teaching, Law Enforcement,
Research, or Analysis – (21 C.F.R. § 801.125)
– “Research” is nonclinical Research
Other Exemptions from
Adequate Directions for Use (cont.)
(See Applicable Regulations for Specifics)
60. www.duanemorris.com60
Import Detention
• FDA has Power to Detain on Appearance of
Violation
• Destruction, Re-exportation, Reconditioning
– Reconditioning Bond – typically three times Value of
Shipment
• Import Alerts
61. www.duanemorris.com61
U.S. Agent
• Foreign Device Manufacturers Exporting into
U.S. Must Designate a U.S. Agent
• U.S. Agent Duties
– Submit MDR Reports
– Submit Annual Certifications
– Act as Official Correspondent
– Must Submit Registration, Listing, 510(k)s
62. www.duanemorris.com62
Exports
• If a Device can be Legally Marketed in the
U.S., it can be Exported freely
• If not Legally Marketed in the U.S., must meet
the Requirements of one of the following
Sections of the FDCA:
– Section 801(e)(1)
– Section 801(e)(2)
– Section 802
63. www.duanemorris.com63
Section 801(e)(1)
• Product for Export not Adulterated or
Misbranded if:
– Accords to the Specifications of Foreign Purchaser
– Not in Conflict with Laws of Importing Country
– Shipping Container Labeled for Export
– Not Sold in Domestic Commerce
• Does not Apply to Devices that do not Comply
with §§ 514 or 515 (Performance Standard or
PMA)
– “510(k)-able” Devices Generally are Allowed to be
Exported under 801(e)(1)
64. www.duanemorris.com64
Section 801(e)(2)
• FDA Export Approval
– For Devices Not Eligible for § 801(e)(1)
E.g., Investigational Devices requiring PMAs
– FDA Can Provide an Export Approval Letter (Export
Permit)
• Standard:
– Export Not Contrary to Public Health and Safety
In practice, Standard is Similar to that for approval of
IDE
– Must have Approval of Importing Country
65. www.duanemorris.com65
Section 802
• Alternative to Section 801(e)(2)
• Applies to Drugs and Devices that would
Otherwise Need FDA Market Approval for
Export
– E.g., Unapproved Class III Devices
– Devices Not Meeting a Performance Standard
– Banned Devices
Synthetic Hair Fibers for Implant
• May be Exported to Any Country in the World if:
– The Drug or Device Complies with the Laws of the
Receiving Country, and
66. www.duanemorris.com66
Section 802 (cont.)
• May be Exported to Any Country in the World if:
– The Drug or Device has Valid Marketing Authorization by
the Appropriate authority in One of the Following Listed
Countries:
Australia, Canada, Israel, Japan, New Zealand, Switzerland,
South Africa, or
A Country in the European Economic Area (i.e., Countries in
the European Union or the European Free Trade Association)
– Labeled in Accordance with Marketing Authorization
– Substantially Meets QSR
– Not Adulterated (other than by lack of Marketing Approval)
– Not Subject to Notice of Imminent Hazard
67. www.duanemorris.com67
Section 802 (cont.)
• If not Exported to a Listed Country, FDA expects
Receiving Country to have Recognized the Listed
Country Marketing Authorization
• Any Exporter of a Drug or Device Shall Maintain
records of All Drugs or Devices Exported and the
Countries to which they were Exported
• FDA must Notify Country to which Drug or
Device will be Exported if FDA has Disapproved
an NDA, Biological License, or PMA
68. www.duanemorris.com68
Section 802 --Exports for
Investigational Use
• For Listed Countries, Compliance with Laws for
Investigational Use in the Listed Country
Sufficient for FDA
– No FDA Notification Required
• For Unlisted Countries, Need to Export under
Section 801(e)(2)
– Even if Product is Authorized for Investigational Use in a
Listed Country
– Requires FDA Permission
69. www.duanemorris.com69
Export Certificates
• Upon Request by Company
• Types of Certificates:
– Certificate to Foreign Governments (CFG) provides written
Assurance that Product can be Sold Legally in the U.S.
Drugs, Biologics, Animal Drugs, Medical Devices
– Certificate of Quality for a Pharmaceutical Product (CQPP)
provides assurance that a Human Drug Product conforms
with WHO Certification Requirements
– Certificate of Free Sale (CFS) for Food and Cosmetic products
– Certificate of Exportability (CEx) Provides Assurance that a
product that may Not be Sold in the U.S. may be Exported
under 801(e) or 802
71. www.duanemorris.com71
Export Certificates (cont.)
• Certificates are Issued by FDA, Based on
Certification by the Exporter
– CFG, CQPP, CEx Not issued if Product’s Manufacture
does Not conform with GMPs
– Various compliance issues can affect various certificates
See CPG 110.100
• Fraud relating to Certificates can result in
Criminal Action
– E.g., False Information, Substitution of Product,
Counterfeiting a Certificate
74. www.duanemorris.com74
FDA’s Mission
• To Protect the Public Health
– Included in FDAMA Mission Statement
• Inspections and Enforcement Necessary to Meet
the Mission
• Public Cannot Perform own Inspections
– E.g., Upton Sinclair, The Jungle
75. www.duanemorris.com75
Why Does FDA Use Enforcement?
• To Warn Companies
• To Stop Continuing Bad Behavior
• To Put Entire Industry on Notice
• To Control Dangerous Products
• To Establish Legal Precedent
• To Punish Wrongdoers
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Federal Food, Drug, and Cosmetic Act
• Police Act
• Coverage:
– Definitions
– Prohibited Acts
– Penalties
– Specific Provisions Regulating Foods, Drugs and
Devices, Cosmetics
– Imports and Exports
– General Authority
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Examples of Prohibited Acts
• Involving Adulteration or Misbranding:
– Introduction into Interstate Commerce
– Adulterating or Misbranding in or after I/S
• Shipment without necessary Market Clearance or
Investigational Exemption
• Refusal to Permit Access to or Copying of Certain
Records
• Refusal to Permit Inspection
• Counterfeiting Drugs
• Revealing of Trade Secret Information (by FDA
Employees)
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Examples of Adulteration
• Adulteration, e.g.,
– Filthy, Putrid, or Decomposed
– Not Made in Conformance with Current Good
Manufacturing Practice
– Prepared, Packed, or Held under Unsanitary conditions
whereby it May have been Rendered Injurious to Health
– Section 519 Violations (MDRs, Correction and Removal
Reports)
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Examples of Misbranding
• Misbranding, e.g.,
– Labeling False or Misleading in Any Particular
– Failure to have Adequate Directions for Use
– Failure to have appropriate Warnings on Labeling
– Failure to have a necessary 510(k)
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Instructions to Field Force
• Compliance Programs
– What to Inspect
– How to Make Compliance Decisions
• Investigator Operation Manual
– Tactics
– How to Behave
• Guide to Inspections of Quality Systems: Quality
System Inspection Technique (QSIT)
• Etc.
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Inspectional Authority – FDCA § 704
• Duly Designated Officers or Employees May:
– Upon Presenting to Owner, Operator, or Agent in
Charge:
Credentials
Notice of Inspection
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Inspectional Authority – FDCA § 704(cont.)
– Enter:
Factory, Warehouse, Establishment, Vehicle
In which Food, Drugs, Devices, or Cosmetics:
are Manufactured, Processed, Packed, or Held
for introduction into Interstate Commerce or after such
introduction
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Inspectional Authority – FDCA § 704 (cont.)
– Inspect:
Factory, Warehouse, Establishment, Vehicle
All Pertinent Equipment, Finished and
Unfinished Materials, Containers, and Labeling
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Inspectional Authority – FDCA § 704(cont.)
– Inspect (cont.):
For Drugs and Restricted Devices:
All Things therein bearing on whether articles are
Adulterated or Misbranded or otherwise in Violation
• Includes Records, Files, Papers, Processes, Controls,
Facilities
Exemptions: Pharmacies, Licensed Practitioners,
Research Use.
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Inspection Does Not Extend To:
• Financial Data
• Sales Data (other than Shipment Data)
• Pricing Data
• Personnel Data (other than Pertinent
Qualifications of Technical and Professional
personnel)
• Research Data (other than Research Data
regulated under rules for IND, NDA, ANDA,
Antibiotic Certifications, § 519, IDE)
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Upon Leaving:
• FDA 483 – List of Observations
– Statutory Requirement:
Report of Conditions or Practices that indicate:
Filthy, Putrid, Decomposed
Prepared, Packed, or Held under Unsanitary Conditions
Covers much more in Practice
– Some Things will Not be on FDA 483
E.g., 510(k), PMA, NDA deficiencies
Ask Specifically if there are any such things
• Receipt for Samples
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Types of Inspections
• Routine
– District Work Plan
– Preapproval Inspections
– Sample Collections
• Directed
– Complaints, MDRs, etc.
– Ongoing Investigation (of you or someone else)
– Compliance Inspection
– Sample Collection
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Inspection Techniques
• Quality System Inspection Technique (QSIT)
– QSIT:
7 Subsystems
4 Major Subsystems
Focus on Management
• Traditional
– Directed and Compliance Inspections
• See FDA’s QSIT Guide, Investigator Operations
Manual, FDA Compliance Programs, and other
FDA Guidance Documents
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Find Out:
• Reason for Inspection
• Is it For-Cause?
• What is Inspectional Plan?
• How Long will it Take?
• What can we do to Expedite it?
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Companies’ Rights
• No Photographs
• No Affidavits, No Signatures
• Statute does not provide FDA with Right to
Interview Employees – but have to handle
delicately
• Reasonable Time, Place, Manner
• Have Policies in Place to Cover these Areas
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Special Situations
• Foreign Inspections
• Inspections of Contractors and Suppliers
• BIMO Inspections: Investigators, CROs,
Sponsors, IRBs
• Portions of Plant that do Not Involve Regulated
Activities
• Visits to Employee Homes
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Enforcement Options (cont.)
• Debarment
• Consent Decree
• Withdrawal of Market Clearance or Approval
• Civil Penalties
• Criminal Prosecution
– Companies should Institute a Compliance Plan
designed to Detect Criminal Violations
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Seizure
• Purpose: To Control Bad Products
• In Rem Action
– Articles are Placed Under Custody of U.S. District
Court
– Violation of 18 USC §§ 2232 - 2233 to Move a Seized
Article
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Injunction
• Purpose: To Stop an Activity
• Temporary Restraining Order (TRO)
– Risk of Irreparable Harm if Immediate Action is Not
Taken
– Damages are Not a Sufficient Remedy
• Preliminary Injunction
– Sufficient Urgency exists to Enjoin the action until there
can be a Trial
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Injunction (cont.)
• Permanent Injunction
– (May later Petition Court for Modification)
• Consent Decree of Injunction
• Defense: Changed Circumstances
• Violation of Injunction or Consent Decree =
Contempt of Court
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Injunction: Typical Requirements
• Do Not Sell Adulterated/Misbranded Product
– Stop Sale until Pass Inspection
• Submit an Annual Certification of GMP
Compliance by an Outside Consultant
• Provisions that Cure Specific FDA
Observations, i.e.,:
– Do Not Fail to Validate Processes
– Do Not Fail to Conduct Stability Studies
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Sample Consent Decree
• GMP Deviations at Two Plants
– Four Inspections over 4½ years
Last Inspection lasted 3 months
– Two Warning Letters
– Regulatory Meeting with FDA
– Seizure of Product
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Sample Consent Decree (cont.)
• Company made “Substantial Commitments” to
FDA
– FDA “Working With Company” for eight months after last
inspection
– Company closed a portion of a plant temporarily
– Company retained Independent Expert Consultants
• FDA sought Consent Decree “to ensure the
Company keeps its Commitments”
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Terms
• Consent Decree of Permanent Injunction
• Signed by Corporation and Top Executives
• Third-party audits
– Reports given to FDA
– FDA to approve Schedule for Correcting Audit Findings
• Disgorgement and Fines
– $30,000,000 disgorgement
– $15,000 per day Fine for Failure to Meet Schedule
– Disgorgement of Profits for Products Sold after Failure to
Meet Schedule
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Terms (cont.)
• Independent Audits Yearly for Four Years
• Third-Party Experts to:
– Evaluate Quality Assurance at all facilities
– Review Manufacturing Records for products produced
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Public Health Need for Products
• Company Allowed to Make Certain Products,
that were needed to fill Critical Health Needs
– Under Third-Party Supervision
– Company had stopped production previously
• Other consent decrees have included Special
Arrangements for Medically Necessary
Products
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Other Typical Terms of Consent
Decrees
• Injunction Prohibiting Manufacturing until
Compliant with GMPs
– Certification of Compliance by Third Party
– Ship only after FDA Releases Products
– Continue shipping at Risk of Contempt Action
• Remediation or Destruction of Existing Stock
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Other Typical Terms of Consent Decrees (cont.)
• Recall
• Disgorgement Payments for Shipping before
Certified in Compliance
• Other Monetary Equitable Relief
• Individuals may be Barred from working in the
Industry
• Submission of Master Validation/Compliance
Plans
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Other Typical Terms of Consent Decrees
(cont.)
• Liquidated Damages
• Provisions allowing FDA to Order the following
in case of Future Noncompliance
– Cessation of Manufacturing
– Recall
– Notification of Users
– Additional Reports
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Other Typical Terms of Consent Decrees
(cont.)
• Company to Pay for FDA Inspections
• Consent Decree to be Posted and/or
Disseminated
• FDA Permission Required for Certain Business
Changes
• Petition to Dissolve Decree after a Certain
Time Period
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Civil Money Penalties
• Safe Medical Device Act of 1990
– $15,000 per Violation
– $1,000,000 per Person per Proceeding
– Factors:
Nature of Violations/Degree of Culpability
Ability to Pay
History of Prior Violations
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Civil Penalties (cont.)
• Exempt from Civil Penalties under SMDA:
– Good Manufacturing Practices or Device Reporting
(Unless Significant or Knowing Departure, or Risk to
Public Health)
– Device Tracking and Field Correction (Minor Violations
Exempt)
– “May” have been Contaminated or rendered injurious to
health charge (501(a)(2)(A))
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Civil Penalties Procedure
• Part 17 Civil Money Penalties Hearing:
– Complaint
– Administrative Law Judge (ALJ) assigned
– Answer or Default
– Discovery -- No Interrogatories or Depositions
– Trial-type Hearing
– Posthearing Briefs
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Civil Penalties Procedure (cont.)
• Initial Decision — 90 Days
– Standard: Preponderance of Evidence
• Appeal Initial Decision to Department Appeals
Board (DAB) of HHS
• Judicial Review of Final Decision Available to
Respondent (FDA Cannot Appeal an Adverse
Decision — DAB Decision Is Decision of the
Agency)
– U.S. Court of Appeals
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Criminal Prosecutions (cont.)
• Misdemeanor
– Up to $100,000 for Individual
– Up to $200,000 for Corporation
– Up to One Year In Jail
• Felony
– FDCA:
Intent to Defraud or Mislead
Second Offense
Up to $250,000 for Individual
Up to $500,000 for Corporation
Up to Three Years in Jail
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Title 18 Crimes
• Prosecuted under U.S. Criminal Code
• False Statements
– Knowing and Willful Coverups of Material Facts
– Materially False Representations
– False Writings or Documents
Beware of Affidavits and Certifications
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Title 18 Crimes (cont.)
• Mail Fraud, Wire Fraud
– Mail Fraud: Item Delivered by Post Office or Interstate
Carrier
– Wire Fraud: Wire, Radio, or Telephone
Communication
Includes Writings, Pictures, Sounds, Signals
• Conspiracy, Racketeering (RICO)
• Obstruction of Justice
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Factors that May Influence Sentencing
• Aggravating: Planning, Corporate Officer, Danger
to Health, Abuse of Trust, Obstruction of Justice
• Mitigating: Plead Guilty, Cooperate, Compliance
Program, Little Fish
• Fines Driven by the Loss
– E.g., Money Made not Following GMPs
• A Corporate Compliance Plan Designed to Detect
Violations Can Be a Mitigating Factor
– See PhRMA or AdvaMed Codes
– State Corporate Compliance Program Laws
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Causes of Criminal Conduct
• Productivity Incentives, Marketing Deadlines,
Funding Triggers
• Incompetent or Overbearing Bosses
• Compounding of Minor Lapses in Judgment
• Fear
• Greed
• Actual Bad Intent
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Administrative Remedies
• Warning Letter
• Administrative Detention
• Voluntary or Mandatory Recall
• Banned Devices
• Section 518 Notification, Repair, Replacement,
or Refund
– Devices
– Reasonable Probability of Serious Adverse Health
Consequences or Death
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Administrative Remedies (cont.)
• Publicity
– Imminent Danger or Gross Deception -- § 705
– Or Not:
Shall publish “all judgments, decrees, and court orders”
May “collect, report, and illustrate” the results of
investigations
Wide latitude to use other publicity
• Clinical Investigator/IRB/Animal Laboratory
Disqualification
• Civil Money Penalties
• Fraud Policy for Market Clearance Applications
– Application Integrity Policy (AIP)
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Administrative Remedies (cont.)
• Refuse, Suspend, or Withdraw Market or
Export Approvals
• Jawboning
• Voluntary Recall
• Refer to State or Local Enforcement
Increased sharing of information between
agencies – Total product lifecycle
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State Actions
• Embargo
• Product Removal
• Injunction (arguably, even if violations
corrected)
• Civil Penalties
• Direct Referral to District Attorney
• California Business & Professions Code
– False Advertising and Unfair Business Practices
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Acknowledgements
• This presentation is an amalgam of Kim Walker’s Professional
Presentations and those of the OCRA US RAC Study Group
Presentations. The following individuals have contributed to the OCRA
Study Group as sources for this presentation:
• Ginger Clasby
• Eri Hirumi
• Christine Posin
• Paul Kramsky
• Steve Lawrence
• John Spoden
• Peggy Pence, PhD
• Del Stagg, PhD
• Joyce Williams, PhD
128. www.duanemorris.com
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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