Stem Cell Therapy
A Regulatory Approach
By: Gary Yingling and Karl Nobert
gary.yingling@klgates.com and karl.nobert@klgates.com
October 7, 2008
What is a stem cell?
ƒ “Serving as a sort of repair system for the body, they can
theoretically divide without limit to replenish other cells for as long
as the person or animal is still alive. When a stem cell divides, each
‘daughter’ cell has the potential to either remain a stem cell or
become another type of cell with a more specialized function, such
as a muscle cell, a red blood cell, or a brain cell.”
- Stem Cell Information, National Institutes of Health
ƒ All stem cells – regardless of source – share 3 general properties:
ƒ Capable of dividing and renewing themselves for long
periods of time
ƒ Initially unspecialized
ƒ Can give rise to specialized cell types
- Stem Cell Overview, National Institutes of Health
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Statutory Authority
ƒ Public Health Service Act (“PHS”)
ƒ “The Surgeon General, with the approval of the Secretary, is
authorized to make and enforce such regulations as in his
judgment are necessary to prevent the introduction,
transmission, or spread of communicable diseases…” Section
361, 42 U.S.C. § 264.
ƒ Biologics – Section 351, 42 U.S.C. § 262.
ƒ Federal Food, Drug, and Cosmetic Act (“FDC Act”)
ƒ Drugs – Sections 501-528 (Chap. V), 21 U.S.C. §§ 351360dd.
ƒ Devices – Sections 501-528 (Chap. V), 21 U.S.C. §§ 351360dd.
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Regulatory Authority
ƒ
Regulatory Status (HCT/P only, biologic, drug or device)
ƒ Dependent on a product’s formulation, preparation and intended use
ƒ
Human Cells, Tissues, and Cellular and Tissue-Based Products (“HCT/Ps”)
ƒ 21 C.F.R. Part 1271
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Biologics
ƒ 21 C.F.R. Pts. 600-680
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Drugs
ƒ Drugs (General) 21 C.F.R. Pts. 200-299 and
Drugs for Human Use 21 C.F.R. Pts. 300-460
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Devices
ƒ 21 C.F.R. Pts. 800-898
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Regulatory Authority (continued)
ƒ Regardless of regulatory status:
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Registration and Listing Requirements
Donor Eligibility Requirements
Adverse Event Reporting
Requirements to prevent the introduction,
transmission or spread of communicable diseases
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Criteria Considered for Determining the Regulatory
Status of a Stem Cell Product
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Degree of manipulation
Homologous use v. Non-Homologous Use
Combined with another article
Systemic effect and/or dependence on metabolic
activity (autologous use? allogeneic use in a firstdegree or second-degree relative? reproductive
use?)
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Marketing Option #1
For stem cell products that meet the criteria in 21 C.F.R. § 1271.10:
ƒ Only minimally manipulated
ƒ Homologous use
ƒ Not combined with another article (with limited exceptions)
ƒ Either (i) the product does not have a systemic effect and is not
dependent upon metabolic activity of living cells for its primary
function; or (ii) the product has a systemic effect or is dependent
upon metabolic activity for its primary function, and is for autologous,
allogeneic or reproductive use
If yes, regulated solely under PHS sec. 361 and 21 CFR Part 1271
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Marketing Option # 1
Requirements:
ƒ No pre-market review or approval
ƒ Comply with cGTPs (intended to prevent the
introduction, transmission, or spread of
communicable disease)
ƒ Reporting / Labeling
ƒ Inspections / Enforcement
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Marketing Option #2
For stem cell products that exceed the criteria in 21 C.F.R.
§ 1271.10:
ƒ More than minimally manipulated
ƒ Intended for non-homologous use
ƒ Combined with a non-cellular or non-tissue component
ƒ Either (i) systemic effect and dependent on metabolic activity
for its primary function, or (ii) systemic effect or dependent on
metabolic activity for primary function, and for autologous,
allogeneic or reproductive use.
If yes, regulated as a drug, device and/or biological product under
the FDC Act and/or Section 351 of the PHS Act.
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Marketing Option # 2
ƒ Biologics
ƒ Investigational New Drug (IND) Application / Biologic
License Application (BLA)
ƒ PHS Section 351
ƒ Manufacturer must show that the cellular or tissue
product is safe, pure, and potent and that the facility
in which the product is manufactured, processed,
packed, or held meets established quality control
standards. (42 U.S.C. § 262(a))
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Marketing Option #2 (continued)
ƒ Drugs
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IND / New Drug Application (NDA)
Requires pre-market review and approval
Must show that the product is safe and effective
Compliance with Current Good Manufacturing Practices (cGMPs)
“Well Characterized”
User Fees
ƒ Devices
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Investigational Device Exemption (IDE) / 510(k) or Pre-Market Approval
Requires pre-market clearance or approval
Compliance with Quality System Regulations (QSR)
User Fees
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FDA Issues Warning Letter
ƒ Warning Letter (July 25, 2008)
ƒ Stem cell therapy being marketed as a drug (“for
treatment of painful and debilitating orthopedic
conditions”)
ƒ Marketed therapy exceeds established criteria in 21
C.F.R. § 1271.10
ƒ Requires a BLA and IND
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Veterinary Stem Cell Therapy –
Regulatory Overview
The Therapy:
Practice of Veterinary Medicine
The Product:
1) USDA
2) FDA
ƒ
Currently, no specific
regulations governing
the practice
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Veterinary Stem Cell Therapy – Current Regulation
Biologics
ƒ USDA
ƒ The Virus, Serum, and Toxin Act of 1913 (“VSTA”)
ƒ Interstate shipment
ƒ Registration and listing requirements
ƒ U.S. Veterinary Biologics Establishment License
ƒ U.S. Veterinary Biologics Products License
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Veterinary Stem Cell Therapy – Current Regulation
(continued)
ƒ Drug
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FDA
Food, Drug, and Cosmetic Act
INADA
NADA—requires study data supporting
the safety and effectiveness of the product
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Questions?
Gary L. Yingling
gary.yingling@klgates.com
(202) 778-9124
Karl M. Nobert
karl.nobert@klgates.com
202-778-9460
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