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.