FDA Boot Camp

The Drug Review Process

• Reviewing the fundamentals of applications; from submission, through filing and beyond
• Making sense of PDUFA Goals, fast track, break through status, and other process enhancements
• Use of administrative appeals

Rx Drugs (Small Molecules)

• Understanding the difference between “new drugs” and other drugs
• Examining the research, development, and approval process for new drugs
• Dissecting the investigational new drug application (IND) vs. the new drug application (NDA)

Biological Products (Large Molecules)

• What are biological products in relation to traditional drugs?
• Deciphering the biologics license application (BLA)
• How do the research, development, and approval process for biological products differ from the process for new drugs?
• Exploring key similarities and differences between the drug and biological product schemes

NDAs and BLAs

• Differentiating between 505(b)(1)s, 505(b)(2)s, and BLAs
• Identifying applications for fixed-dose combination drugs
• Distinguishing complex molecules regulated through NDAs from from small molecules
• Examining standards for approvals
• REMS

• Distinguishing among the different FDA programs for expedited review and approval of drug products
• Evaluating the criteria for eligibility, benefits, and limitations of each program
• Understanding accelerated approval, surrogate and intermediate clinical endpoints
• Assessing the breakthrough therapy, regenerative medicine advance therapy (RMAT), and fast track designation programs
• Reviewing priority review and the status of the Rare Pediatric Disease Priority Review Voucher (expiring December 2024, pending the Give Kids a Chance Act of 2024)
• Factoring expedited programs into your drug development strategy
• Examining recent changes to FDA’s Accelerated Approval program

• Understanding the concept of “OTC” (OTC-ness)
• Examining the OTC Review and monographs
  • Differences between approved and monographed OTC drug products pursuant to the 2020 CARES ACT reformation and modernization of the OTC drug review process
• OTC Monograph Drug User Fee Program (OMUFA)
• FDA’s Proposed Rule: Nonprescription Drug Product with an Additional Condition for Nonprescription Use (ACNU)

• Overview of clinical trials and how they are used (including different phases)
• Identifying the different parties involved (sponsors, investigators, CROs, etc.)
• Understanding human research protection (ICF, IRB)
• Enforcement
• Review of the “Right to Try” laws and their requirements during the clinical trials process
• Examining new FDA requirements for Diversity Actions Plans for clinical trials
• Delving into the categories of meetings available both prior to filing an IND and at various stages throughout a clinical trial
  • What type of meeting can you get? (in-person/written response)
  • What should you submit?
  • How to prepare for it?

Patent Protection for Drugs and Biologics

• Summarizing the patenting process for drugs and biologics
• Strategies for building patent protection for drugs and biologics
  • Understanding the potential implications of the proposed Patent Eligibility Restoration Act (PERA)
• Applying for and achieving extension of patent term for time spent in the drug approval process
  • Patent Term Extension (“PTE”)
  • Patent Term Adjustment (“PTA”)
• Reviewing the 271(e)(1) “safe harbor” provision
• Distinguishing the patenting process for drugs from that of biologics
• Identifying the respective roles of the FDA and the PTO in the protection of drugs and biological products Trademarks
• Overview of selecting a brand name for a proposed drug product
• Roles of the USPTO and FDA in the drug naming process
• Identifying the PTO and FDA clearances necessary for trade name/trademark approval on your product
• How does the branding process work for your product

Drugs

• Overview of Hatch-Waxman and reforms
  • 30-month stay; patent extensions
  • ANDA filer patent challenge and competitive generic therapy 180-day exclusivities
• Comparing the NDA, 505(b)(2), and ANDA (Abbreviated New Drug Application) drug approval routes and reviewing fundamentals of applications
• Exploring the ANDA Paragraph IV Certification, and response to Notice Letters
• Examining ANDA Standards for approval and the concepts of sameness and bioequivalence
• Special considerations: local acting drugs, labeling carve outs and other nuances
  • Understanding the role of the Orange Book in the drug approval process
  • listings, de-listings and use codes
• Market exclusivities and protection
• Identifying the different types of exclusivities
  • Regulatory exclusivity (FDA)/ (data) exclusivity, such as: NCE (new chemical entity); indication (new indication or use); NDF (new dosage formulation); ODE (orphan drug exclusivity); and PED (pediatric exclusivity)

Biologics

• Overview of biosimilar legislation and regulations, i.e., Biologics Price Competition and Innovation Act of 2009 (BPCIA)
• Understanding the rationale for safety and efficacy concerns surrounding second generation biologics
• Exploring the concepts of “biosimilarity” or “interchangeability”
• FDA rule-making and guidance relative to biosimilars
• Other points for consideration: substitution, naming, patents, and additional nuances
• Examining biosimilar exclusivities
• “Shall we dance” — weighing the pros and cons of participating in the patent dance
• Deciding when to provide notice of commercial marketing

The labeling of the drug/biologic is the final stage of the approval process. The label controls what you can do post-approval and as such it is the point of transition between the approval process and post-approval world.

• Labeling overview: key regulatory requirements, information, and contents
• Exploring the review process for labeling
• Incorporating clinical trial data on the label
• Appreciating the influence of final labeling on the scope of post-market activities
• Amending labeling post-marketing
• Using labeling as a defense in products liability litigation
• Exploring label carve outs and the 2024 Novartis v. FDA case
  • Discussing the requirements for skinny and narrow labeling

• Examining cGMPs (current Good Manufacturing Practices) and the scope of their importance in pharmaceutical/biological product commercialization
• Factoring cGMPs into the scope of the FDA’s authority
• Exploring the scope of the FDA’s cGMP Initiative and the concept of “risk-based” cGMPs
• Unpacking the FDA’s Draft Strategy Document on Innovative Manufacturing Technologies
• Conducting laboratory investigations in relation to cGMPs
• Understanding the influence of cGMPs in products liability litigation
• PFAS and the FDA’s new guidance regarding the testing of ethylene glycol (EG) and diethylene glycol (DEG) in high-risk drug components
• Evaluating the costs and impact of enforcement actions

• Overview of laws and regulations controlling the advertising, marketing, and promotion of prescription drugs and biologics
  • 21 CFR Sections 202.1, 352(n), 314.81(b)(3); Section 352(n) of FD&CA
  • Guidance documents
• Exploring the role of DDMAC (Division of Drug Marketing, Advertising and Communications)
  • What duties and responsibilities is DDMAC charged with?
  • What are its enforcement capabilities and jurisdiction?
• Identifying the role of the FTC in the advertising and promotion of drugs
  • SEC?
• Advertising requirements for prescription v. nonprescription products
Reviewing the steps which DDMAC takes for the review of launch campaigns and promotional materials
• Overview of the promotional materials submission and review process
• What constitutes a launch?
• What defines an advertisement?
  • What information must a drug advertisement include?
• Exploring the role of the label in advertising

• Clarifying FDA’s current position on First Amendment and off-label promotion
  • The 21st Century Cures Act
  • FDAMA 114
• What to expect concerning proposed legislation, rules changes and Citizen Petitions
• Cases and controversies: state AG actions and private tort claims

• 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
• Exploring protocols for Risk Evaluation and Minimization Strategies (REMS)
• Understanding the role of risk evaluation in the approval process
• Identifying risk minimization tools and when long-term safety studies are required
• Enforcing 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

• Enforcement overview—identifying the players and their positions
  • Investigations, enforcement, litigation, and defenses
• Understanding potential punishments, including civil seizure, injunction, civil money penalties, and criminal prosecutions
• Unpacking two recent SCOTUS decisions impacting FDA enforcement authority:
  • Civil monetary penalties (SEC v Jarksey)
  • Injunctions (Starbucks Corp. v McKinney)
• Exploring FDA compliance and enforcement mechanisms
  • For cause inspections vs. routine inspections and communication with the FDA during inspections
  • EIRs, Form FDA 483 observations, Untitled Letters, and Warning letters related to inspections
• Examining enforcement actions related to digital advertising and social media
  • The use of influencers for direct-to-consumer advertisements (e.g., the Untitled Letter to AbbVie Inc. regarding its UBRELVY commercial, featuring tennis-star Serena Williams)