• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Combination Products

  • Print
  • Share
  • E-mail

Section Contents Menu

Meetings, Conferences, & Workshops

Text version of PowerPoint Presentation by Zorina Pitkin, Ph.D.

Slide 1 - Public Hearing FDA Regulation of Combination Products

Risk Classification of Combination Products (Biologic/Device)

Zorina Pitkin, Ph.D.
Vice President, Regulatory Affairs & Quality Systems
Nephros Therapeutics, Inc., Lincoln, RI

November 25, 2002

Slide 2 - Overview

1. Renal Assist Device (RAD) System – biologic/ device combination product

2. Critical issues in RAD development

3. Risk-based classification of combination products

Slide 3 - Renal Assist Device (RAD) Biologic/device combination product

  • Human cells—no modifications
  • Renal cell isolation and expansion
  • Extracorporeal system based on hollow fiber membrane technology
  • Relatively short-term exposure
  • Conventional instrumentation and equipment (CVVH)

Slide 4 - RAD Regulatory Status

  • Regulated as Biologic by CBER with CDRH consults
  • Two physician-sponsored INDs
    • Phase I/II Clinical Study – ongoing
    • Targeted population:
      • Acute Renal Failure (ARF) – high predicted mortality
      • 10 patients enrolled and treated

Slide 5 - Critical Issues in RAD development

  • Quality systems
    • Product/system characterization and assurance of its safety
    • Reproducible and consistent delivery of viable and functional cells in a system to patients
  • Unique biologic/device issues
    • Complex interactions between the material and cellular processes
  • Regulatory issues
    • Applicability of specific regulations to various components of the RAD

Slide 6 - Regulatory issues in development of combination products

  • Combination products do not fit adequately into existing statutory definitions
    • Issues that are unique to combination products
  • Which GMP regulations are applicable to the manufacturing of combination products and inspection by the FDA? How will the assigned Center handle reported changes in manufacturing of combination products?
    • Lack of consistency in assigning to a Lead Center

Slide 7 - Recommendations for Regulation of Combination Products

Risk-Based Classification

Purpose

  • Identify the component of the combination product that potentially presents the highest risk
  • Create one quality system which will encompass the most appropriate regulation that could be applicable to all components of a combination product
  • Establish a common approach to similar issues

Slide 8 - Risk Classification of Combination Products (Biologic/Device)

Main assumption

Risk of combination product increases with direct long- term exposure  

Factors contributing to risk assessment:

  • Use: extracorporeal vs. implanted
  • Type of contact: through barrier vs. direct exposure
  • Exposure Time: short-term vs. long-term

Slide 9 - Risk Classification of Combination Products Limitations

  • Existing classification of devices (Classes I-III) was employed
  • Assessment of mode of action was not considered
  • No distinction was made between novel and “off the shelf” components
  • No distinction was made between autologous and allogeneic sources of cells/tissues
  • No distinction was made between human and xenogeneic sources of cells/tissues

Slide 10 - Proposed Risk Classification of Combination Products (Biologic/Device)

Biologics Risk Score (1 to 12) + Device Class (1 to 3)= Combination Product Risk Score (2 to 15)

Risk Classes of Combination Products:

Risk score from 2 to 5 – combination product risk class I

Risk score from 6 to 10 - combination product risk class II

Risk score from 11 to 15 - combination product risk class III

Slide 11 -Biologics Risk Scoring

 

Risk Factors
Risk Scores
Implanted - direct contact Long-term 12
Mid-term 11
Short-term 10
Implanted with barrier Long-Term 9
Mid-term 8
Short-term 7
Extracorporeal, direct contact
Long-Term 6
Mid-term 5
Short-term 4
Extracorporeal, contact through barrier
Long-Term 3
Mid-term 2
Short-term 1

 

Slide 12 - Classification Chart for Risk Assessment of Combination Products (CP)

 

Risk Factors
Risk Score
CP Risk Class
Type of Contact
Exposure Time
Biologics
Device Class
1
2
3
Implanted - direct contact Long-term
12
13
14
15
lll
Mid-term
11
12
13
14
lll
Short-term
10
11
12
13
lll
Implanted with barrier Long-term
9
10
11
12
lll
Mid-term
8
9
10
11
lll
Short-term
7
8
9
10
ll
Extracorporeal, direct contact Long-term
6
7
8
9
ll
Mid-term
5
6
7
8
ll
Short-term
4
5
6
7
ll
Extracorporeal, contact through barrier Long-term
3
4
5
6
ll
Mid-term
2
3
4
5
l
Short-term
1
2
3
4
l

 

Slide 13 - Summary

  • A risk assessment classification for combination products has been proposed based on risk factors associated with both biologics and device components.
  • The classification was developed under the assumption that the risk for a patient and for the public at large increases with long term direct exposure of a combination product.
  • Risk classification might eliminate the ambiguity of combination product regulation.
  • This classification system might be helpful in the decision-making process for the characterization, designation and regulation of combination products.