FDA Regulatory Pathways for Medical Devices

Overview of FDA Regulation of Medical Devices

• 1976 Amendments: Expanded FDA's responsibilities to medical devices under the CDRH.
• Regulatory Similarities: Both medical devices and pharmaceuticals share regulatory frameworks, yet differ in innovation speeds:
  • New drug approval: 10-15 years.
  • New medical devices: 3-7 years.

Definition of Medical Devices

• FD&C Act Definition: Devices include instruments, apparatuses, machines, implants, or in vitro reagents meeting three criteria:
  1. Recognized in the National Formulary or US Pharmacopoeia.
  2. Intended for diagnosis, treatment, prevention of disease.
  3. Affects body structure/function without chemical action/metabolism.
• Examples: Tongue depressors, stethoscopes, surgical instruments, pacemakers, and inert biological materials.

Device Development Process

• Development typically starts with a concept from a physician or bioengineer.
• Stages of Development:
  1. Prototype development.
  2. Patent Process initiated.
  3. Preliminary bench testing followed by animal testing.
  4. Iterative cycles of testing and redesign.

Key Steps to Market Device in the US

1. Classify the Device: Based on risk; devices categorized into three classes:

   • Class I (Low Risk): General controls adequate
     • Example: Bandages (exempt from PMN and QS regulation).
   • Class II (Moderate Risk): Requires pre-market notification (510(k)).
   • Class III (High Risk): Life-supporting devices requiring PMA approval.

2. Select Regulatory Pathway: Four primary pathways:

   • PMA (Pre-Market Approval): For high-risk devices requiring substantial clinical data.
   • 510(k) (Pre-market Notification): Must show substantial equivalence to existing devices, fewer requirements for clinical studies.
   • De Novo: For novel devices lacking predicates; offers a streamlined pathway for regulatory burden reduction.
   • HDE (Humanitarian Device Exemption): Devices for rare diseases affecting fewer than 4,000 individuals annually; efficacy not needed but safety must be demonstrated.

3. Register and List the Device:

   • Manufacturers must register with the FDA and comply with annual verification.
   • Foreign manufacturers need a US agent for correspondence.

Post-Market Regulations

• Compliance with labeling, advertising, and manufacturing surveillance is mandated.
• Surveillance Sources include:
  • MDR: Reports on malfunctions, injuries, or deaths.
  • MedSun: High-quality reports from hospitals on device use.
  • Post-Approval Studies: Required post-market for some devices.
  • FDA Discretionary Studies: Conducted by FDA to monitor device performance.

Case Study: Eluvia Drug-Eluting Stent

• Condition: Peripheral arterial disease (PAD), affects 8-12 million in the US.
• Product Overview: Eluvia stent developed by Boston Scientific.
  • Initially received CE Mark in February 2016.
  • Obtained FDA approval for PMA in September 2018.
• Trials:
  1. MAJESTIC trial (CE approval based on safety/performance).
  2. IMPERIAL trial (FDA approval with 309 patients).
• Market Timing: Historically, longer delays for US approvals compared to Europe, highlighting evolving regulatory environments.

Conclusion and Resources

• The FDA provides numerous guidance documents to support device manufacturers navigating the approval processes.
• Recommended practice includes scheduling meetings with FDA officials for clarifications and support.