Desalination 199 (2006) 265–267

Presented at EUROMEMBRANE 2006, 24–28 September 2006, Giardini Naxos, Italy.

Biomaterial regulations for tissue engineering

Ulrich GrosskinskyLSMW GmbH Total Life Science Solutions, Regional Office, Alte Jakobstrasse 79/80, 10179 Berlin, Germany

email: ulrich.grosskinsky@lsmw.com

Received 20 October 2005; accepted 1 March 2006

1. Introduction

The development of (bio)materials used forgrowing human tissue is a long-term process ofmultidisciplinary research activities. Materialsare selected and tested according to the intendedapplication. Criteria for material selection canbe toxicology, biocompatibility, biostability orbiodegradability, mass transfer, surface proper-ties, hygienic design, scale-up, costs and otherphysical or (bio-) chemical properties. Theresulting, and generally the most importantcriteria for material selection are quality andsafety of the final tissue engineered product.Thus, regulations of legal authorities, for safetyand quality in general and also specific forbiomaterials should be followed.

2. Results and discussion

The quality and safety of human tissue engi-neered products (hTEPs) are subject to differentregulatory requirements. Depending on thecountry of distribution and the kind of producthTEPs are regulated as tissue, drug, biologic,medical device or combination product. Consid-ering just the European Union (EU) and theUnited States (US) hTEPs are subject to currentGood Manufacturing Practice (cGMP) [1–4],current Good Tissue Practice (cGTP) [5], other

regulations [6–8] or/and quality managementsystems [9–11]. These regulations are of generalnature and thus no specific requirements forbiomaterials are listed. General requirementsare for instance: “The parts of the productionequipment that come into contact with the prod-uct must not be reactive, additive or absorptiveto such an extent that it will affect the qualityof the product and thus present any hazard” [1].For selection of materials in contact with productmore specific regulations must be considered.

Types of biomaterials and materials ofconstruction of equipment and componentsare polymers, metals, glasses, ceramics andcomposite materials.

Biomaterials such as scaffolds or membranesusually should be porous, nontoxic, nonimmuno-genic, biocompatible, adhesive, growth promot-ing and, in case of scaffolds biodegradable orresorbable. Degradation products also must benontoxic and nonimmunogenic [12]. Dependingon the material of interest several standards fortesting of material properties including biocom-patibility are available: United States or EuropeanPharmacopoeia (USP, EP) [13–16], standards bythe International Organization for Standardiza-tion (ISO), Association for the Advancementof Medical Instrumentation (AAMI), AmericanSociety for Testing of Materials (ASTM);

doi:10.1016/j.desal.2006.03.1720011-9164/06/$– See front matter © 2006 Published by Elsevier B.V.

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National Institute of Standards and Technology(NIST) [17–20] and others.

Materials of construction of equipment andcomponents should be compatible with the bio-processing conditions, cleaning solutions andsterilizing conditions. Material characteristicsaccording to the American Society of MechanicalEngineers (ASME) are homogenous in nature,impervious, inert, nonabsorbent, nontoxic, insol-uble by process or cleaning fluids, capable towithstand temperature, pressure, resistant to cor-rosion, scratching, scoring and distortion [22,23].

Generally, materials having product contactshall be certified by an industry recognized stan-dard such as Pharmacopoeias [14–16], Food andDrug Administration (FDA) [21] or standards fore.g. stainless steel [24].

3. Conclusion

For development of biomaterials likescaffolds, membranes and materials having prod-uct contact specific (user) requirements should beclearly defined. Accordingly material propertiesand their variability indirectly result from these(user) requirements. Safety and quality issues aresubject to regulations and should be evaluated bya risk based approach. A risk assessment shouldbe based on user requirements, data from materialsafety data sheets, toxicology data or resultsobtained from material testing. During develop-ment phase several changes relating to selectionor preparation of (bio)material might be neces-sary to fulfill quality and safety requirements.Success in development, clinical trials and appli-cation of final product is ensured by compliancewith regulations for (bio)materials from thebeginning of development.

Acknowledgement

The present study is part of the Livebiomatproject STRP contract No. 013653 granted bythe European Commission.

References

[1] EU directive 2003/94/EC on good manufacturingpractice, 8 October 2003.

[2] US FDA; Current good manufacturing practice inmanufacturing, processing, packing, or holding ofdrugs, 21CFR Part 210.

[3] US FDA; cGMP for finished pharmaceuticals, 21CFR Part 211.

[4] US FDA; Regulations for biological products, 21CFR, Part 600–680.

[5] US FDA. 21 CFR Parts 16, 1270 and 1271 Cur-rent good tissue practice for manufacturers ofhuman cellular and tissue-based products, 2004.

[6] EU Directive 2004/23/EC on quality and safetyfor the donation, procurement, testing, processing,preservation, storage, distribution of human tis-sues and cells, 31 March 2004.

[7] EU Proposal for a Regulation of the Europeanparliament and of the council on advanced ther-apy medicinal products, 16.Nov. 2005.

[8] EU Directive 93/42/EEC of 14 June 1993 con-cerning medical devices.

[9] ISO EN DIN 9001 Standard, Quality managementsystems, 2000.

[10] ISO EN DIN 13485 Standard, Medical devicesquality management systems, 2003.

[11] US FDA, Quality system regulation. 21 CFR Part820.

[12] G.L. Griffith, Emerging design principles in bio-materials and scaffolds for tissue engineering,Ann. N.Y. Acad. Sci., 961 (2002) 83–95.

[13] Chapter 1031, The biocompatibility of materials usedin drug containers, medical devices and implants,United States Pharmacopoeia, USP 28, 2005.

[14] Chapter 87, Biological reactivity tests in vitro;USP 28; 2005.

[15] Chapter 88: Biological reactivity tests in vivo;USP 28; 2005.

[16] Chapter 3: Materials for Containers, and Contain-ers; E.P., 4th edition, 2002.

[17] ISO EN AAMI DIN 10993 Standard: Biologicalevaluation of medical devices.

[18] ASTM D1239-98, Test method for resistance ofplastics films to extract by chemicals.

[19] ASTM F2150-02e1, Guide for characterizationand testing of biomaterial scaffolds used in tissue-engineered medical products.

[20] National Institute of Standards and Technology(NIST), Polymers Division; Biomaterials Group;

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http://polymers.msel.nist.gov/researcharea/biom-aterials/index.html

[21] US FDA. Indirect food additives: Polymers. 21CFR, Part 177.

[22] Part PM- Polymer based materials, PM-2.6 Mate-rials of construction; Standard ASME BPE-a-

2004 Add. to ASME BPE-2002 BioprocessingEquipment, ASME, 2005, p 84.2.

[23] Part SD- Design for sterility and cleanability, SD-3.4Materials of Construction, Standard ASME BPE-2002 Bioprocessing Equipment, ASME, 2002, p 10.

[24] EN DIN 10088 Standard: Stainless steel, 1995.