American Conference Institute's 24th FDA Boot Camp

FDA Regulatory Fundamentals 101 With Ethics Session

1:00 Fundamentals of FDA Regulatory Law

Aimed at providing a primer to professionals who have limited or no experience working with FDA on regulatory matters, this workshop will provide you with a basic overview of FDA regulations and will prepare you for the more in-depth discussions that will take place throughout the conference. Topics addressed during this workshop will set the stage for the main conference by helping you thoroughly comprehend the structure of the FDA and walk you through the preapproval, approval, and post-approval process. Get the background you need to flow seamlessly into the conversations at FDA Boot Camp.
Topics to include:

• FDA Mission
• FDA Organization
• History of FDA Laws
• Acronyms and Terminology
• Clinical Trials Process
• Types of New Drug Applications
• The Review Process
• The Hatch Waxman Act
• Legal Barriers to Approval
• Biological Products
• The Basics of Device classification and approval
• Post-marketing issues and enforcement, including recalls

4:00 Resolving Ethical Challenges Encountered During the Drug Approval Process

This one hour program will explore ethical issues that may arise in the context of communications with FDA on behalf of clients. The program is based on scenarios involving situations in which FDA requires full disclosure of adverse information and authority. For example:

1. In the context of citizen petitions FDA requires certification that the petition includes all information and views on which
   the petition relies as well as data and information known to the petitioner which is unfavorable to the petitioner. 21 CFR 10.30. The discussion will cover the implications of that certification upon an attorney in light of Rules 1.6, 1.7 and 1.8 of the Rules of Professional Responsibility.
   
   
2. In the context of an Advisory Committee meeting at which counsel is present, Committee members ask whether all data
   regarding adverse events have been reported to FDA. The discussion will cover the implications of the lawyer’s participation in light of the requirements of Rules 1.3, 3.4, and 4.1.
   
   
3. Your client has retained a former FDA official and tells you that he will be contacting FDA to discuss a pending NDA. The discussion will cover the implications of Rule 1.11.

Registration and Continental Breakfast

Co-Chairs’ Opening Remarks and Brief Overview of FDA Practice

The Nature of the Approval Process

Rx Drugs

• Understanding the difference between “new drugs” and other drugs
• Overview of the research, development, and approval process for new drugs
• The investigational new drug application (IND)—timing, content, and purpose
• The new drug application (NDA)—timing, content, purpose, and review process
• Accelerated approval (fast track)
• Different uses of the REMS process in new drug approvals

Biological Products

• What are biological products? What does it mean to say that they are also “drugs”?
• Which “new drugs” require BLAs instead of NDAs?
• How do the research, development, and approval process for biological products differ from the process for new drugs?
• The biologics license application (BLA) —timing, content, purpose, and review process
• Key similarities and differences between the drug and biological product schemes

OTC Products

• The concept of “OTC” (OTC-ness)
• The OTC Review—identifying covered drugs and defining a “monograph”
• OTC versus Rx
• Overview of how old and new OTC drugs come to market

PREAPPROVAL AND APPROVAL

Morning Coffee Break

Understanding the Clinical Trial Process for Drugs and Biologics

• Outlining the phases of clinical trials (I-IV)
• Regulatory requirements (e.g., informed consent, IRBs, sponsor obligations, investigator obligations, etc.)
• FDA authority
• Discussing the roles and obligations surrounding CROs and SMOs
• Identifying major differences between clinical trials for drugs and biologics
• Disclosure of clinical trial information
  • FDA Amendments Act of 2007
  • FDAMA § 113
  • clinicaltrials.gov
  • PhRMA policies

Drugs and Biologics: Labeling

The labeling of the drug/biological product is the final stage of the approval process. The labeling affects what you can do post-approval. It is the point of transition between the approval process and post-approval world.

• Labeling overview: key regulatory requirements, information, and contents
• Review process for labeling
• How does the final labeling control the scope of post-market activities?
• How can and when should the labeling be amended post-market?
• How is the labeling a defense in products litigation?
• When can punitive damages may be rewarded with respect to labeling
• Assessing the impact of labeling on reimbursement

Networking Luncheon

Patent and IP Overview for Drugs and Biologics: Understanding The Connection Between FDA Regulation and IP and Related

Part 1 – Patents, Trademarks and Other IP Protections and Mechanisms

• Summarizing the patenting process for drugs and biologics
• Strategies for building patent protection drugs and biologics
• Seeking extension of patent term for time spent in the drug approval process (Patent Term Extension, Supplemental Protection Certificates), and/or time spent obtaining a patent at the United States Patent Office (Patent Term Adjustment)
• 271(e)(1) “safe harbor”
• Identifying the respective roles of the FDA and the PTO in the patenting of drugs and biological products
• Determining whether to seek a trademark or a patent for a product

Afternoon refreshment break

Part 2 – Hatch-Waxman and BPCIA Overview

Drugs

• Comparing the NDA, 505(b)(2) and ANDA (Abbreviated New Drug Application) drug approval routes
• ANDA filing: what does the FDA require?
• Showing bioequivalence in an ANDA
• ANDA Paragraph IV Certification, and response to Notice Letters
• The role of the Orange Book in the drug approval process: what is it, why is it Orange, and why is it important?
• Regulatory Exclusivity (FDA)
  • Categories of regulatory (data) exclusivity—NCE (new chemical entity); new indication; NDF (new dosage formulation);
    ODE (orphan drug exclusivity); PED (pediatric exclusivity)’ New antibiotic exclusivity
  • overview of Hatch-Waxman and reforms under MMA
  • the role of Orange Book under Hatch-Waxman vis-à-vis the MMA
    • 30-month stay
    • patent extensions
    • ANDA-filer exclusivity (180 day)

Biologics

• Identifying products approved/regulated as biologics
• Overview of biosimilar (FOB) legislation and regulations
• The rationale for safety and efficacy concerns surrounding second generation biologics

Exclusivity for Combination Products

• Exploring exclusivities for combination products comprised of two new Orange Book listed drugs, two old drugs, a new and an old, a listed drug and device, and a listed drug and biological product

The Drug Supply Chain Security Act – Summarizing the Act and Its Effect on FDA Practice

• The executive branch’s strategy and FDA’s pathway for global product supply chain security, safety, and quality
• Overview of the Drug Supply Chain Security Act (Title II of the Drug Quality and Security Act of 2013)
• FDA’s Implementation Plan, including timeline for Guidance
• Identifying the scope of the DSCSA
• Outlining the specifics:
  • obligations to create a unique product identifier;
  • establishing tracing and monitoring systems;
  • developing detection and response protocols regarding counterfeit materials;
  • understanding notification obligations;
  • evaluating the effect of the act on the recall process; and
  • penalties.

Conference Adjourns to Day Two

Continental Breakfast

Co-Chairs’ Opening Remarks and Recap of Day One

​POST-APPROVAL

cGMPs: Drugs and Biologics (current Good Manufacturing Practices)

• Examining cGMPs (current Good Manufacturing Practices) and the scope of their importance in pharmaceutical/biological product commercialization
• Looking at how cGMPs factor into the scope of the FDA’s authority and history
• Exploring the scope of the FDA’s cGMP Initiative and how the concept of “risk-based” cGMPs is defined
• Defining the concept of validation
• How are laboratory investigations in relation to cGMPs conducted?
• Defining the term “quality systems”
• How are cGMPs factoring into products litigation?
• Evaluating the cost of enforcement actions: what happens to company stock when there is an announcement of an enforcement action?

Medical Devices: Classifications, the Essentials of the Premarket Review Process, and Post-Market Requirements and Concerns

FDA’s Risk-Based Classification Scheme

• Understanding the concept of risk-based classification
• Three main classes of medical devices
• Device reclassification

The Premarket Review Process

• Potential changes to 510(k) process and changes to diagnostics
• 510(k) exemptions for low risk devices and the role of the
• Investigational Device Exemption (IDE)
• Understanding the selection of “predicate” devices when 510(k) submissions are made and the consequences of choosing the wrong predicate
• Premarket approval (PMA) process

Post-Market Requirements and Concerns

• What is the scope of the Quality System Regulation (QSR)?
• What are the reporting requirements under the Medical Device
  Reporting (MDR) and Reports of Corrections and Removals regulations?
• What other types of post-market requirements can FDA impose on medical devices, e.g., tracking?
• What claims can device manufacturers make regarding cleared/ approved devices, devices with pending 510(k) notices, and investigational devices?
• What are the consequences of illegal promotion of a device?
• What medical device recalls need to be reported to FDA?
• FDA seizure and injunction power
• When can product be reintroduced to the market?

​MEDICAL DEVICES

Morning Coffee Break

Using FDA’s Citizen Petition Process and Litigation to Achieve Market Success

• Overview of FDA’s Citizen Petition process
• Market exclusivities and other issues that can be addressed in a petition
• Maximizing your chance of success before FDA
• To sue or not to sue FDA
• Strategies for prevailing in Court against FDA
• Recent court decisions involving FDA issues

How to Respond to FDA: Best Practices, Tips, Tricks, and Pitfalls to Avoid

Companies will sometimes receive a written communication from FDA regarding either a pending product submission (e.g. a request for additional information), a compliance related matter (e.g. a 483 or a Warning Letter), or some other type of general communication (e.g. a letter to the industry regarding a policy change). It is important for companies to know how to go about responding to such communications in a way as to provide them with the best opportunity for successfully dealing with the issue at hand. 6 Join the Conversation ACI: Pharmaceutical/Biotech/Life Sciences @ACI_Pharma / #ACIFDA There is no one set of answers for every response. Often times the specifics of the response depend upon the type and substance of the communication, who in FDA sent it, the circumstances surrounding the issuance of the communication, as well as the regulatory history of the company. This presentation will provide valuable insights, gained from years of experience, and will cover the following topics:

• Who at FDA is the response to be addressed to?
• Who should the response be written for?
• How do you assure that you have addressed all of the issues FDA is concerned with (and it’s not always the issues that are articulated in the FDA communication)?
• At what level of complexity/specificity should the response be written?
• Who should be the signatory of the response?
• What if any follow-up should the company engage in?

Adverse Events Monitoring, Pharmacovigilance, Risk Management, and Recalls

• What is pharmacovigilance?
• How pharmacovigilance uses adverse event reports
  • direct versus indirect reports
  • causality assessments
  • labeling changes
  • pre- and post-market ADE reporting requirements
  • how regulatory agencies use ADE reports
• Risk Evaluation and Minimization Strategies (REMS)
• Risk evaluation in the approval process
• Risk minimization tools
• Enforcement of ADE reporting and REMS requirements
• Examining the relevance to product liability risks, including innovator and co-promoter liability risks
• What is the FDA’s recall and oversight authority (overview of 21 CFR Part 7)?
  • guidance versus regulation
  • voluntary recalls versus mandatory recalls
  • market withdrawals and stock recoveries
• Interaction between recalls and corrective and preventive action

Conference Concludes*

​* Luncheon will be served for delegates attending the afternoon Mater Classes beginning promptly at 12:15

Hatch-Waxman and BPCIA: Overview of Biosimilars and Life Cycle Planning for Drugs and Biologics

1:15 Biosimilars

James Czaban
Partner
Wiley Rein LLP (Washington, DC)

• Overview of Title VII of the Patient Protection and Affordable Care Act (PPACA, P.L. 111-148), i.e., Biologics
  Price Competition and Innovation Act of 2009 (BPCIA)
• Biosimilar pathway vs. 505(b)(2) and BLAs
• Defining “biological” and “biosimilars” under BPCIA B Post-Approval Marketing Guidance and Preemption Protocols
• Exploring interchangeability requirements
• Understanding the significance of the methods of making claims in this legislation
• Examining the effect of this abbreviated approval pathway on innovation
• A look at FDA Rule making and guidance relative to biosimilars
• How will biosimilars fit in with life cycle strategies?
  • targeting R&D efforts
  • re-examining prosecution efforts
  • anticipating vulnerable patents and litigation

2:30 Bioequivalence and the “Same Active Ingredient” vis-à-vis Patentability

Clark G. Sullivan
Partner
Troutman Sanders (New York, NY)

• Small molecule patent strategies and their application to biologics (e.g., active ingredient claims, purity claims, formulation claims, method claims, etc.)
• Extra hurdles for patenting biologics (enablement, written description, subject matter eligibility)
• Bioequivalence v. biosimilarity
• What lessons can be applied to biologics from FDA’s rating precedent for 505(b)(2) products?
• What lessons can be applied to biologics from FDA’s same labeling precedent for small molecules?

3:30 Afternoon Refreshment Break

3:45 Marketing Exclusivities (Non-Patent): Challenges, Opportunities, and Current Controversies

David Adams
Partner
Venable LLP (Washington, DC)

There are a number of different modes and methods of exclusivity (non-patent). This session will outline what they are and what
challenges, opportunities, and current controversies arise in relation to them, including the role that the FDA plays in regulating these modes of exclusivity. Modes and methods of exclusivity to be discussed include:

• Orphan Drug Exclusivity (7 years)
• New Chemical Entity Exclusivity (5 years)
• New Clinical Study Exclusivity (3 years)
• Pediatric Exclusivity (6 months)
• First Generic Applicant Exclusivity (180 days)
• New Antibiotic Exclusivity

5:00 Master Class B Concludes