6/2/17. Updates on Regulatory Issues for Clinical Use of Biologics. Purpose. Biologics. Andrew G. Geeslin, MD

Transcription

1 Updates on Regulatory Issues for Clinical Use of Biologics Andrew G. Geeslin, MD Pre-Course: The Use of Biologics to Treat Sports Medicine Pathology June 3, th Biennial ISAKOS Congress 2017, Shanghai, China 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 t he cont ent of t his present at ion. 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 et al, JAAOS

2 Biologics - Cell Source Anz et al, 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 2

3 Three-Tier System Category 1: No HCT/P oversight Category 2: Section 361 Category 3: Section 351 *All must follow Current Good Tissue Practices Chirba et al, J Knee Surg 2015 US DHHS, 21 CFR 1271 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 bloodderived products Extracted human products such as collagen and bone marrow Chirba et al, J Knee Surg 2015 Courtesy of RF LaPrade 3

4 PRP and BMAC Considered minimally manipulated * Not regulated as HCT/Ps by FDA* *Anz et al, JAAOS 2014 Category 2: Section 361 Four Criteria 1 Minimal manipulation Homologous use only No combination products Lack of systemic effect Current Good Tissue Practice regulations 2 1. US Department of Health and Human Services: Human cells, tissues, and cellular and tissuebased products. 21 CFR 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). 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 4

5 Category 3: Section 351 Fail to meet any one of the criteria for inclusion in 361 Anz et al, 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 Balance of Regulation Patient Safety Clinical Efficacy Innovation Rapid Clinical Integration 5

6 Consensus on minimum reporting requirements for clinical studies on PRP (23 items) and MSC (25 items) Incorporation into journal submission of biologics outcome studies / 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 6

7 REGROW Act Reliable and Effective Growth for Regenerative Health Options that Improve Wellness (REGROW) Act of 2016 (S / H.R. 4762) REGROW Act Anz, Am J Ortho 2016 REGROW Act isscr.org 7

8 6/2/17 21st Century Cures Act Regenerative Medicine Advanced Therapy (RMAT) Program blogs.fda.gov Regenerative Medicine Advanced Therapy Cell therapy, therapeutic tissue engineerin g product, HCT/P Treat, modify, reverse, or cure a serious or lifethreatening disease or condition Preliminary clinical evidence of potential to address unmet medical needs 8

9 Regenerative Medicine Advanced Therapy Close observation of therapies awarded RMAT designation Must continue to focus on safety and efficacy THANK YOU 9