Innovative Systems for Delivery of Drugs and Biologics
1 / 17

Innovative Systems for Delivery of Drugs and Biologics Drug-Eluting Stents Current Approach to Review - PowerPoint PPT Presentation

  • Uploaded on

Innovative Systems for Delivery of Drugs and Biologics Drug-Eluting Stents Current Approach to Review. Ashley B. Boam, MSBE Division of Cardiovascular Devices Office of Device Evaluation Center for Devices and Radiological Health. What is a Drug-Eluting Stent (DES)?.

I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
Download Presentation

PowerPoint Slideshow about 'Innovative Systems for Delivery of Drugs and Biologics Drug-Eluting Stents Current Approach to Review' - matt

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.

- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

Innovative Systems for Delivery of Drugs and BiologicsDrug-Eluting Stents Current Approach to Review

Ashley B. Boam, MSBE

Division of Cardiovascular Devices

Office of Device Evaluation

Center for Devices and Radiological Health

What is a drug eluting stent des
What is a Drug-Eluting Stent (DES)?

Example:Cordis’ Cypher™ Sirolimus-Eluting Coronary Stent


  • Stent Platform & Delivery System

  • Carrier(s)

  • Drug


Des and the regulatory process
DES and the Regulatory Process

Three Component System

Stent Platform & Delivery System

[CRDH Review]





Agent (‘Drug’)

[CDER Review]

Carrier (e.g., Polymer)

[CDRH Review]


Overview of review challenges for des
Overview of Review “Challenges” for DES

  • Regulatory jurisdiction

  • Inspectional authority & site readiness

  • Disparity in statutory & regulatory requirements between CDRH & CDER

  • Appropriate leveraging of information from INDs, NDAs, DMFs, MAFs, etc.

  • Appropriate pre-clinical testing & clinical trial design

  • Post-market studies and surveillance

Regulatory jurisdiction
Regulatory Jurisdiction

  • Combination Products (21 CFR Part 3)

  • CDRH lead center with CDER consultation

  • Divisions involved include…

    • Cardiovascular Devices (ODE/CDRH)

    • Cardio-Renal Drug Products (OND/CDER)

    • New Drug Chemistry I (OPS/CDER)

    • Pharmaceutical Evaluation I (OCP/CDER)

    • Mechanics & Materials (OST/CDRH)

  • Submissions: IDEs & PMAs


Regulatory review team for des

Expertise required…

Regulatory Review Team for DES

Mechanical Performance

& Testing Regimes

Animal Experimentation

& Evaluation

Clinical Trial Design

& Methodology


[Drug Substance & Carrier(s)]


Pharmacokinetics /




Inspectional authority and site readiness
Inspectional Authority and Site Readiness

  • Inspections conducted by CDRH with CDER/ONDC participation

  • Validations should be complete prior to inspection

  • Subsequent manufacturing changes may require reinspection

Information to support des applications
Information to Support DES Applications

* Refer to CDER Guidance, “Content & Format of INDs for Phase 1

Studies of Drugs…”;

* Refer to CDRH Guidance, “…Interventional Cardiology Devices:

…Intravascular Stents”;


Approved vs unstudied drug substances
Approved vs. UnstudiedDrug Substances

  • Potential Sources for Safety Data (Phase 1 IND)

    • Approved drug – NDA

    • Drug under IND investigation

    • “Unstudied” – New Molecular Entity (NME)

  • Analog of Approved Drug is an NME

  • Necessary Categories of Safety Information

    • Chemistry, Manufacturing & Controls (CMC)

    • Systemic Pre-clinical Pharmacology/Toxicity

    • Systemic Clinical Exposure

  • Potentially Influences Clinical Trial Design

Preclinical testing objectives
Preclinical Testing Objectives

  • Characterization of finished, sterilized product to be studied is essential

    • Coating/drug loading characteristics – drug and carrier content, uniformity, abrasion resistance (if coating), particulate

    • In vitro/ in vivo elution

    • Methods and initial specifications for stability testing

  • Adequate animal studies needed to assess safety prior to human studies


Common preclinical testing deficiencies
Common Preclinical Testing Deficiencies

  • Inadequate Stent Platform Testing

    • Fatigue and corrosion testing

  • Inadequate Analysis of Surface Modifications

    • Coating integrity/durability

    • Drug content/uniformity

  • Incomplete In vitro Pharmacokinetics

    • Methodology and IVIVC, if possible

  • CMC Issues Inadequately Addressed

    • Stability/shelf life

Common animal study deficiencies
Common Animal Study Deficiencies

  • Inadequate Reports to Assess Safety

    • Lack evaluation of doses intended for clinical evaluation &/or overdosage at appropriate time points

    • Lack evaluation of serial sections of myocardium

    • Lack description of arterial histopathology

    • Lack necropsy reports (especially important for unexpected deaths)


Clinical evaluation of des
Clinical Evaluation of DES

  • Reasonable Assurance of Safety and Effectiveness

  • Clinical Study Needs to Be Designed for Both Objectives

  • Usual Standard of Evidence is RCT

  • Study Endpoints for Coronary DES

    • Primary – Clinically Meaningful

    • Use of surrogate and/or co-primary endpoints?

    • Non-inferiority trial - appropriate delta

  • Use of Independent Core Labs, CEC & Active DSMB


Des post market
DES Post-Market

  • TPLC is critical for DES!

  • 5 year follow-up of all patient cohorts (feasibility, pivotal, any supportive)

  • Additional data collection post-market to gain further understanding of rates of drug-related adverse events

  • Approval for new indications, new study populations through IDE

  • Adverse events are reported through MDR

    • reports to CDRH, data shared with CDER

Questions talk to us
Questions? Talk to us!

  • Coronary DES

    • Ashley Boam, Branch Chief (

    • Joni Foy, Ph.D., Lead Reviewer (

  • Peripheral DES

    • Elisa Harvey, DVM, Branch Chief (

    • Jennifer Goode, Lead Reviewer (