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Devices incorporating human or animal tissues

Regulatory basis

MDR Annex VIII Rules 17–18 (classification); MDR Annex I §13 (GSPR); EN ISO 22442 series (animal tissue requirements); European Pharmacopoeia Chapter 5.2.8 (TSE risk minimisation). Devices made from non-viable human tissue are Class III; non-viable animal tissue devices are also Class III (with some Class IIb exceptions).

Disclaimer

This site provides general information only and does not constitute legal or regulatory advice. Always consult the official regulation text and a qualified regulatory professional.

Definition and scope​

MDR Rules 17 and 18 apply to devices that are manufactured using tissues or cells of human or animal origin, or their derivatives, where those tissues/cells are non-viable or rendered non-viable.

Important scope boundary: this applies to MDR medical devices only. Living cells and tissues used therapeutically are typically governed by ATMP legislation (Regulation (EC) 1394/2007) rather than MDR, unless the living cell component is ancillary to a device that is the principal element.

Examples in scope​

DeviceOriginRule
Decellularised pericardial patchBovine pericardiumRule 18
Collagen membrane for guided bone regenerationPorcine collagenRule 18
Human-derived fibrin sealantHuman plasma proteinsRule 17
Hyaluronic acid dermal filler (biologically derived)Bacterial fermentation product — not in scope of Rule 17/18N/A
Xenograft heart valve (glutaraldehyde-fixed porcine)PorcineRule 18
Processed human bone allograftHumanRule 17

Classification​

Rule 17 — Human tissues (Class III)​

All devices manufactured using non-viable human tissues or cells, or their derivatives, are Class III — unless they contact only intact skin.

Rule 18 — Animal tissues (Class III / IIb)​

Devices manufactured using non-viable animal tissues or cells, or their derivatives, are:

  • Class III if they contact the heart, central circulatory system, or CNS or are intended to be absorbed by the body
  • Class IIb if they are intended for other contact (e.g. intact skin only)
  • Class IIb for animal-derived dental restorative materials contacting intact mucosa

GSPR §13 — Key requirements​

Annex I §13 sets out specific requirements for devices made from tissues of human or animal origin:

Viral safety and TSE risk​

  • Viral inactivation: manufacturing processes must include validated steps to inactivate or remove potential viral contaminants
  • TSE (transmissible spongiform encephalopathy) risk: animal-derived materials must meet the requirements of the European Pharmacopoeia Chapter 5.2.8 — which specifies:
    • Approved species (cattle, sheep, goat — high risk; pig, horse — lower risk)
    • Approved geographical sourcing (countries with controlled BSE/scrapie status)
    • Approved tissues (muscle, hide, bone — risk tiered by TSE susceptibility)
    • Validated removal/inactivation steps

Biocompatibility​

  • Full EN ISO 10993 biological evaluation
  • For implantable devices: chronic toxicity, implantation testing, carcinogenicity assessment
  • Tissue fixation methods (e.g. glutaraldehyde crosslinking) must be validated for efficacy and biocompatibility

Donor screening and traceability (human-derived materials)​

  • Human-derived materials must comply with Directive 2004/23/EC (standards for donation, procurement, and testing of human tissues)
  • Donor infectious disease testing and traceability records
  • The finished device manufacturer must have traceability back to the donor (anonymised)

Stability and sterility​

  • Tissue-based devices must demonstrate stability under defined storage conditions
  • Sterility must be validated and maintained through the shelf life

Regulatory pathway implications​

Class III classification under Rules 17/18 means:

  • Annex IX conformity assessment (cannot use Annex X + XI)
  • Full notified body technical documentation review
  • Clinical evaluation with clinical investigation data expected for novel products
  • Where devices incorporate human blood derivatives: additional consultation with EMA required (parallel to drug-device combination procedure)

Official references​

ReferenceDescription
MDR Annex VIII Rules 17–18Classification rules for tissue-derived devices
MDR Annex I §13GSPR for tissue-derived devices
EN ISO 22442-1:2015Medical devices utilising animal tissues — risk analysis and management
EN ISO 22442-2:2015Controls on sourcing, collection, and handling
EN ISO 22442-3:2007Validation of elimination/inactivation of viruses and TSE agents
Ph. Eur. 5.2.8Minimising the risk of transmitting TSE via medicinal products
Directive 2004/23/ECQuality and safety standards for human tissues