Point-of-Care Cell Processing Devices A Manufacturer s Perspective Clinical trials, regulatory compliance, and commercialization.

Transcription

1 Philadelphia, 2013 Point-of-Care Cell Processing Devices A Manufacturer s Perspective Clinical trials, regulatory compliance, and commercialization. Brian Barnes, Ph.D. VP, Clinical and Regulatory Affairs

2 2004 Created to develop cellular therapies st FDA First-in-man Trial (Marrow-133+ in heart disease) 2007 Created Arteriocyte Medical Systems w/dwhp to acquire the Magellan Asset (Class II CBER approved device)

3 Magellan System Indication for Use The MAGELLAN Autologous Platelet Separator System is designed to be used in the clinical laboratory or intra-operatively at the point of care for the safe and rapid preparation of platelet poor plasma and platelet concentrate (platelet rich plasma) from a small sample of a mixture of blood and bone marrow. The plasma and concentrated platelets produced can be used for diagnostic tests. Additionally, the platelet rich plasma can be mixed with autograft and/or allograft bone prior to application to an orthopedic site. The platelet rich plasma can be mixed prior to application to an orthopedic site as deemed necessary by the clinical use requirements.

4 Point-of-Care Processing Devices for Cell Therapies Manufacture s Perspective Topic To discuss approaches to balancing regulatory compliance and commercial interests. To identify the challenges associated with clinical trials which use point-of-care devices.

5 Point-of-Care Processing Devices for Cell Therapies Manufacture s Perspective Point of Care Rapid, same day processing Sterile processing Targeted tissue or cell source Includes: devices for the purification or selection from preparation of whole blood, bone marrow, or adipose tissue, as well as tissue preparation devices.

6 Current Regulatory Environment Perception for POC Devices Manufacturer s perspective Exhibit SC-1: Stem Cell Therapy Market Estimates, US, Year Annual Sales ($ in 000s) Growth 2006 $16, $33, % 2008 $55,928 68% 2009 $87,483 56% 2010 $138,611 58% 2011 $148,038 7% 2012 $171,641 16% 2013 E $235,354 37% 2014 E $350,559 49% 2015 E $658,690 88% 2016 E $1,040,885 58% 2017 E $1,612,592 55% 2018 E $2,407,745 49% 2019 E $3,518,184 46% 2020 E $6,049,283 72% Robin R. Young, New York Stem Cell Summit 12 Adult Stem Cell Fact Sheet

7 Regulatory Burden of Point of Care Processing Devices Manufacturer s Perspective versus FDA perspective FD&C Sec 513(a)(2) Probable Benefit to Health vs Probable Risk of Injury or Illness Company Objectives Demonstrate Benefit to Health vs Time to Market/Reven ue

8 Point-of-Care Device Regulations Manufacturer s perspective Not Device - more than just for diagnosis Not Drug - unless articles are added that require chemistry or metabolism of the product to affect change Not Biologic unless the focus is on the biological action not the collection

9 Point-of-Care Device Regulations Manufacturer s perspective Most Point of Care Devices are focused on harnessing the body s natural power to heal itself with regenerative cells Which regulatory definition applies: Human cells, tissues, of cellular and tissue based products (21 CFR (d); HCT/P) CBER - Biologics CDER - Drugs OCTGT - Cell Therapy

10 Regulatory Pathways to Market TIME COST Exemption from premarket review + + Premarket Notification 510(k) + ++ Humanitarian Device Exemption (HDE) Premarket Approval (PMA) Biologic License Application (BLA)

11 Regulatory Conundrum Devices regulated by CDRH/CBER Autologous Marketing: PRP/Cell Concentrate Combined with Allograft bone at Bedside ALLOGRAFT CELLS POINT OF CARE DEVICES HCT/P Allograft Marketing: Stem/Progenitor Cells Combined with Allograft bone at Bedside

12 CLINICAL TRIALS USING POINT- OF-CARE PROCESSING DEVICES

13 What do you want to be able to claim? INDICATION FOR USE

14 Challenges Clinical Trials using POC Devices Manufacturer s Perspective 1. Is the focus on the device or the output? 1. What is the cell source? / How are they selected? 2. What is the cell(s) being selected? 2. Patient Population 1. No-option; pediatrics; co-morbidities, selected diseases (HDE) 3. Safety 1. Monitoring plans and Reporting requirements 4. Efficacy 1. How do I know if the product is effective?

15 Potential Risks of Cellular Therapies 1. Determine what we know 1. Is it a first-in-man trial? 2. Has the therapy or similar therapy been approved for another indication 1. Preclinical evidence, published literature, human experience with related products, etc. 2. Determine what the FDA feels risk associated with your product are 1. Trial design should minimize the risks to subjects. 1. Mode of action 2. Delivery 3. Dose

16 Potential Risks of Cellular Therapies (cont.) 3. Determine what is the worst case Scenario 1. Eg. Autologous stem cells for direct coronary infusion. 1. Electrical abnormalities 2. Generation of non-contractile or fibrotic tissue. 3. Concentration of cells in other tissues such as the lungs. 4. Determine tumorigenicity 5. Determine if delivery elicits transformation of the cells

17 Importance of preclinical data Pre-clinical Design Safety of the device Quality of the cells selected during processing Dosing and timing Cell Delivery Appropriateness of populations selected Effect on tissue (both intended and not-intended) Pre-clinical pitfalls - Post-treatment follow-up - Make sure animal cells mimic human equivalent - Limits - Catheters vs injections - Age, co-morbidities may affect translation - Ectopic growth, cell fate, tumorigenicity **Don t make the mistake of not engaging the FDA on your preclinical design.

18 Sponsor Compliance for Device Trials Warning Letters issued for: Failure to secure investigator compliance: signed investigator agreement, the investigational plan, applicable FDA regs., IRB and FDA requirements. Failure to ensure accurately quality records. Failure to ensure adequate monitoring of the investigation and to include written procedures for monitoring of the investigational plan. Failure to report: required progress reports at regular intervals to FDA and IRB. ***compliance issues for Investigators and trial sites as well. 18

19 Summary Point-of-Care Processing Devices Manufacturer s Perspective Get to know the FDA Work smart early GLP, GMP, GCP - good study, good product, good data Preclinical Animal Testing Clinical trial design Start with the Indication For Use. Risk assessment What happens if? Control How do I know if it works? Demonstrate efficacy. Choosing endpoints specifically the Primary Endpoint Monitoring safety first

20 THANK YOU FOR YOUR ATTENTION