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Updates on Regulatory Issues for Clinical Use of Biologics
11th Biennial ISAKOS Congress 2017, Shanghai, China
Pre-Course: The Use of Biologics to Treat Sports Medicine PathologyJune 3, 2017
Andrew G. Geeslin, MD
Purpose• Review current FDA regulation of Biologics• Describe product “risk” categories• Overview of therapies and associated category• Discuss recent regulatory updates
Note: This update is not intended to serve as a comprehensive overview of the complex regulatory framework of the FDA, nor is it intended to offer legal advice. The FDA does not specifically endorse the content of this presentation. Review of referenced FDA guidance documents is necessary prior to incorporation of these therapies into clinical practice.
Biologics•Growth Factors• Platelet Rich Plasma, isolated GF
• Cell•MSCs (BMAC, Adipose-derived)• Differentiated Cells
• Tissue• Autografts, allografts
• Scaffolds
Anz etal, JAAOS 2014
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Biologics - Cell Source
Anz etal, JAAOS 2014
Overview
• Overview of regulatory framework of FDA
• Description of three-tier system, HCT/Ps
Key Definitions• HCT/Ps: Human cellular and tissue-based products• Governed by Part 1271 of the CFR
• PHSA: Public Health Service Act • Section 361: Lower-risk products• Section 351: Higher-risk products
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Three-Tier System• Category 1: No HCT/P oversight
• Category 2: Section 361
• Category 3: Section 351
Chirba et al, J Knee Surg 2015US DHHS, 21 CFR §1271
*All must follow Current Good Tissue Practices
Current Good Tissue Practices (CGTP)• 21 CFR 1271, Subparts D and E
• Prevent the introduction, transmission, or spread of communicable diseases
• Manufacture: recovery, processing, storage, labeling, packaging, distribution, testing
• Communicable diseases: viruses, bacteria, fungi, parasites, spongiform encephalopathy agents
Category 1: No HCT/P Oversight• Whole blood and blood-
derived products
• Extracted human products such as collagen and bone marrow
Chirba et al, J Knee Surg 2015
Courtesy of RF LaPrade
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PRP and BMAC
• Considered “minimally manipulated”*
• Not regulated as HCT/Ps by FDA*
*Anz et al,JAAOS 2014
Category 2: Section 361• Four Criteria1
• Minimal manipulation• Homologous use only• No combination products• Lack of systemic effect
• Current Good Tissue Practice regulations2
2. US Department of Health and Human Services: Guidance for industry: Current Good Tissue Practice (CGTP) and additional requirements for manufacturers of human cells, tissues, and cellular and tissue-based products (HCT/Ps).
1. US Department of Health and Human Services: Human cells, tissues, and cellular and tissue-based products. 21 CFR §1271.
Category 3: Section 351• Fail to meet any one of the criteria
for inclusion in 361• Requires animal and human
clinical studies to prove safety and efficacy• Premarket approval process,
clinical studies, active IND, clearance for clinical application and marketing after approved BLA
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Category 3: Section 351• Fail to meet any one of the
criteria for inclusion in 361
Anz etal, JAAOS 2014
Examples of Products within Categories• Category 1: PRP, BMAC
• Category 2 (361): Cellular Bone Matrix (ViviGen)
• Category 3 (351): Amniotic Stem Cell Technologies, Adipose-Derived Stem Cells, cultured cells
Anz, JAAOS 2014
DePuy Synthes
InnovationPatientSafety
Clinical Efficacy RapidClinical Integration
Balance of Regulation
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• Consensus on minimum reporting requirements for clinical studies on PRP (23 items) and MSC (25 items)• Incorporation into journal submission of biologics outcome studies
https :/ /www.mibo-statem en t.o rg
• Registry of randomized clinical trials
•Good resource to identify ongoing and completed work
Marketing• Frequently requested by
patients• Direct to consumer
marketing• Not covered by insurance
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REGROW Act• Reliable and Effective Growth
for Regenerative Health Options that Improve Wellness (REGROW) Act of 2016 (S. 2689 / H.R. 4762)
REGROW Act
Anz, Am JOrtho 2016
REGROW Act
isscr.org
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21st Century Cures Act
Regenerative Medicine Advanced Therapy (RMAT) Program
blogs.fda.gov
Regenerative Medicine Advanced Therapy• Cell therapy, therapeutic
tissue engineering product, HCT/P• Treat, modify, reverse, or
cure a serious or life-threatening disease or condition• Preliminary clinical evidence
of potential to address unmet medical needs
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• Close observation of therapies awarded RMAT designation
• Must continue to focus on safety and efficacy
Regenerative Medicine Advanced Therapy
THANK YOU
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