Standards for biomaterials in tissue engineering

Transcription

1 Stem Cell Translation: Strategies, Best Practices and Regulatory Considerations San Francisco 28/9/10 Standards for biomaterials in tissue engineering Paul Tomlins

2 Overview Why are standards useful? Standards bodies The process of standardisation Relevant activity within the standards area Examples of the contents of an ASTM guide Where are we now with standards in tissue engineering? 2

3 What use are standards? A measure of product/data quality and consistency, valuable for: Customer confidence? Regulator confidence? Vendors liability? Standards facilitate trade Help establish emerging technologies 3

4 Standards and biomaterials Characterisation of raw materials Structure/performance assessment Assessment of product performance Detection of contaminants Sterilisation (ISO 10993/7) (Packaging) Degradation Quality management system (ISO ) 5

5 International standards bodies Thursday, September 30, 2010 International standards developed by: IEC (Int. electrotechnical committee) ITU (Int. telecommunications union) ISO (International Organization for Standardization) ASTM International 6

6 Regional standards bodies e.g. Thursday, September 30, 2010 CEN, CENELEC, ETSI, and IRMM in Europe. Pacific Area Standards Congress African Organization for Standardization (ARSO) 7

7 ISO and national standards bodies 163 national members One nation one vote system standards 8

8 ASTM International Global membership ~30,000 (>120 countries) One member one vote system standards listed in 80 volumes 9

9 ISO/TC 194: Medical devices 10

10 The role of ISO/TC 194 (Biological evaluation of medical devices) Ensuring compliance with regulatory bodies (Japan, EU, USA etc) Reducing developmental cost through harmonization Eliminating unnecessary animal testing Device quality increasingly important in litigation 11

11 Tissue engineered Medical products 12

12 ISO TC150 SC7: Tissue engineered medical products (current portfolio) Quantification of sulphated glycosaminoglycans (sgag) in regenerated articular cartilage In vivo bone formation in porous materials using rat mesenchymal cells standardisation to evaluate bone forming ability of biomaterials 13

13 ASTM International Thursday, September 30,

14 ASTM F04 Division F Classification and Terminology for TEMPs F Biomaterials and Biomolecules F Cells and Tissue Engineered Constructs F Assessment F Adventitious Agents Safety F Cell Signaling 15

15 Current standards/standard guides Area Guide Protocol Work items Terminology/ classification Assessment (preclinical evaluation) Biomaterials and biomolecules Adventitious agents safety 1 2 1G 2 5G 3P 8 6 3G 1 1G Cells and TEMPS 5 4 2G 3P Cell signalling 9P 3G 16

16 Biomaterials and Biomolecules: ASTM activity Thursday, September 30, Characterization and testing of raw or starting biomaterials for tissue engineered medical products. - Characterization and testing of alginates as starting materials -Characterization and testing of chitosan salts as starting materials - Method for in vitro biological activity of recombinant human bone morphogenetic protein-2 (RHBMP-2) using the W-20 mouse stromal cell line - Characterization and testing of biomaterial scaffolds - Characterization of type I collagen as a starting material for surgical implants and substrates - Method fordetermining the chemical composition and sequence in alginate by proton nuclear magnetic resonance ( 1 H NMR) - Method for the determination of the degree of deacetylation of chitosan salts by proton nuclear magnetic resonance ( 1 H NMR) Assessing microstructure of polymeric scaffolds - Determination of the molar mass of chitosan and chitosan salts by size exclusion chromatography with multi-angle light scattering detection (SEC-MALS). - Interpreting images of polymeric tissue scaffolds 17

17 BSI BSI CH/194 Biological evaluation of medical devices Responsible for UK input into ISO/TC 194 and CEN/TC 206 Preparation of PAS (Publicly Available Specification) documents Coordinating UK participation in ISO/TC150/SC7 work items 18

18 Relevant BSI PAS documents (1) PAS 84 Regenerative medicine glossary PAS 83:2006 Guidance on codes of practice, standardised method and regulations for cell-based therapeutics From basic research to clinical applications 20

19 Relevant BSI PAS documents (2) PAS 131 Terminology for medical, health and personal care applications of nanotechnologies PAS 132 Terminology for the bio-nano interface PAS 133 Terminology for nanoscale measurement and instrumentation PAS 134 Terminology for carbon nanostructures PAS 135 Terminology for nanofabrication PAS 136 Terminology for nanomaterials 20

20 The process of standardisation Thursday, September 30, 2010 Pre-standardisation activity round-robin VAMAS (ISO) New work item Draft standard Balloting 21

21 VAMAS Versailles project on advanced materials and standards Established 1982 Facilitates international trade of high tech products through consensus documents Biomaterials technical working area 22

22 When are standards needed? New market Single manufacturer/end user Thursday, September 30, 2010 Private agreement Consensus agreement Mature market Many manufacturers/end users 23

23 ASTM Standard Guide Monaco-Extra Summer School, Antalya

24 What characteristics do tissue scaffolds have? Biocompatible Spacious for cell mobility and proliferation Plentiful supply of nutrients Plentiful supply of oxygen Efficient removal of waste products Appropriate mechanical properties Reliable In vivo performance accommodating degradation Monaco-Extra Summer School, Antalya

25 Pore types Monaco-Extra Summer School, Antalya 2009 Open Closed Blind-end 26

26 Interconnectivity Monaco-Extra Summer School, Antalya 2009 Blind-end Open Closed 27

27 Pore size distribution and functionality Monaco-Extra Summer School, Antalya 2009 Cell conduits? Service conduits? m 1 m 100 m 28

28 Fenestrated pores? Monaco-Extra Summer School, Antalya 2009 ~30 m 29

29 Morphology of Fibrin gel and with cells Thursday, September 30, 2010 Cell Cell 30

30 Length scales accessible by different techniques Monaco-Extra Summer School, Antalya 2009 Adsorption Condensation Thermoporometry Hg Intrusion X-ray scattering (diffraction) Electron Microscopy Scanning tunnel microscopy Fluid Flow Light Microscopic Image Analysis Holography Mechanical Tracing micropores esopores macropores microcapillaries ^4 10^5 10^6 Pore Width (nm) capillaries macrocapillaries 31

31 Summary: Where are we on standards? Main focus on terminology Informative guides Still much work to be done!

32 Acknowledgements Nilofar Faruqui (NPL) Elzbieta Gurdak (NPL) Richard Leach (NPL) Melissa Mather (NPL) 34