Public Hearing FDA Regulation of Combination Products November 25, 2002 Risk Classification of...
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Public Hearing FDA Regulation of Combination Products
November 25, 2002
Risk Classification of Combination Products (Biologic/Device)
Zorina Pitkin, Ph.D.Vice President, Regulatory Affairs & Quality Systems
Nephros Therapeutics, Inc., Lincoln, RI
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Nephros Therapeutics,
Inc.
Overview
1. Renal Assist Device (RAD) System – biologic/ device combination product
2. Critical issues in RAD development3. Risk-based classification of combination
products
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Nephros Therapeutics,
Inc.
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)
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Nephros Therapeutics,
Inc.
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
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Nephros Therapeutics,
Inc.
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
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Nephros Therapeutics,
Inc.
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
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Nephros Therapeutics,
Inc.
Recommendations for Regulation of Combination Products
Risk-Based ClassificationPurpose
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
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Nephros Therapeutics,
Inc.
Risk Classification of Combination Products (Biologic/Device)
Main assumptionRisk 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
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Nephros Therapeutics,
Inc.
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
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Nephros Therapeutics,
Inc.
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 IRisk score from 6 to 10 - combination product risk class IIRisk score from 11 to 15 - combination product risk class
III
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Nephros Therapeutics,
Inc.
Biologics Risk Scoring
Risk Factors Risk Score
Implanted - direct contactLong-term 12Mid-term 11
Short-term 10
Implanted with barrier Long-term 9Mid-term 8
Short-term 7
Extracorporeal, direct contact
Long-term 6Mid-term 5
Short-term 4Extracorporeal, contact through barrier
Long-term 3Mid-term 2
Short-term 1
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Nephros Therapeutics,
Inc.
Classification Chart for Risk Assessment of Combination Products (CP)
1 2 3Long-term 12 13 14 15 IIIMid-term 11 12 13 14 IIIShort-term 10 11 12 13 IIILong-term 9 10 11 12 IIIMid-term 8 9 10 11 IIIShort-term 7 8 9 10 IILong-term 6 7 8 9 IIMid-term 5 6 7 8 IIShort-term 4 5 6 7 IILong-term 3 4 5 6 IIMid-term 2 3 4 5 IShort-term 1 2 3 4 I
CP Risk ClassDevice Class
Risk score
Implanted - direct contact
Risk Factors
Biologics
Implanted with barrier
Extra-corporeal,
direct contact Extra-
corporeal, contact
through barrier
Exposure Time
Type of Contact
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Nephros Therapeutics,
Inc.
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.