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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