Case Studies for Regenerative Medicine Standards

Development and Use Anthony Ratcliffe

Synthasome Inc, San Diego, CA

Scope of ASTM International Division IV (Medical and Surgical Materials and Devices): TEMPs

• The development of standards and promotion of related materials for tissue engineered medical products focusing on components of combination medical products intended to repair, replace or regenerate human tissue.

• These comprise the biological components such as the cells, tissue, cellular products, and/or biomolecules and biomaterials used in combination, including biologic, biomimetic and/or synthetic materials.

Articular Cartilage Repair and Regeneration

Synthasome, Inc

• Clinical Need • Research Need • Product Development Need • Manufacturing Need

Some features to Consider for Articular Cartilage Repair and

Regeneration

• Biomaterials • Cell culture and proliferation

• Product characterization (mechanical, biochemical etc)

• Product delivery

• Fixation in situ • Integration with host tissue • Pre-clinical study design • Pre-clinical outcomes • Clinical study design • Clinical outcomes

Applications for Articular Cartilage Repair Constructs

• Trauma • Focal articular

defects • Degenerative

joint disease

• Knee • Hip • Shoulder • Ankle • Digits

Synthasome, Inc

Carticel for Articular Repair • Autologous cell transplantation

– Tissue harvest – Cell culture and expansion – Re-implantation

• Clinical outcome is good to excellent – Similar to microfracture

• Expensive, profitability??? • Second generation products being developed

Synthasome, Inc

Tissue Engineered Articular Cartilage

HAO = 0.166 MPa

Et = 0.35 MPa

Synthasome, Inc

F2451 – SG for in vivo Assessment of Implantable Devices Intended to Repair

or Regenerate Articular Cartilage

• Products included may be composed of – Natural or synthetic biomaterials – Cells – Biologically active agents (growth factors, synthetic peptides,

plasmids, etc)

• Description and rationale of various animal models using a range of species

• Outcome measures –histologic, biochemical and mechanical – are briefly described

WK31014 – Standard test method using a goat in vivo model for testing articular

cartilage repair or regeneration • NIH funded project • Preliminary studies complete • Experimental design complete • Study to characterize model

ongoing • Model will allow for product

assessment for repair of small and large defects

• Model contains negative and positive controls

• Participation of industry, academia and FDA

Rotator Cuff Surgical Repair

• Clinical need – 4 million doctor visits per year

for rotator cuff problems – ~400,000 surgeries per year

in US – 30 - >90% failure rate

• R&D need – Multiple products on the

market, more being developed

Synthasome, Inc

Products for Reinforcement of Tendons and Soft Tissue

• Restore (DePuy)

• GraftJacket (Wright)

•ZCR Patch (Zimmer)

• TissueMend (Stryker)

• X-Repair (Synthasome)

Synthasome, Inc

F2903 – SG for Tissue Engineered Medical Products for Reinforcement of Tendon and Ligament Surgical Repair

• For the development, production and delivery of TEMPS intended to provide mechanical (functional) reinforcement of surgical repair of tendons and ligaments

• Products included may be composed one or combinations of two or more of matural ECM, synthetic biomaterials, cells, molecular mediators

• Products may be rapidly degrading, slowly degrading, or non-degrading

• Surgical repair may to tendon – tendon, tendon – bone, tendon – muscle, ligament – ligament, ligament – bone

Reinforcement of Tendon and Ligament Repair

X-Repair – Augmentation of Surgical Repair for Tendons and soft tissues

ASTM D2579 ASTM D3786 ASTM D5035 ASTM D5587 ASTM F1635 ISO 10993 ISO 11135

ASTM F2211 ASTM F2312 ASTM F2027 ASTM F2150 ASTM F2903

F2212 – SG for Characterization of Type I Collagen as Starting Material for Surgical

Implants and Substrates for TEMPs

• Provides guidance on Collagen Type I analysis

• Serves as key document in guiding the development of TEMPs products under development

• Allows objective comparison with products on market

Summary

• Standards provide a rationale approach to assess and compare technology safety and effectiveness

• Use of standards can increase efficiency of regulatory submissions