1.1 This document provides guidance on the characterization and evaluation of the decellularization processes used to produce decellularized extracellular matrix (dECM) materials which will be used as medical products in direct or indirect contact with the body. The decellularization process may be performed on tissue from human or other mammalian sources or produced in vitro from human or other mammalian cells. The dECM may or may not be recellularized prior to use. Decellularized ECM material derived from non-mammalian tissue or cells and decellularized ECM material used for non-medical purposes may follow the framework provided but may require additional considerations outside the scope of this document.

1.2 Biological tissues are composed of a structural extracellular matrix (ECM) and embedded cells. The intent of a decellularization process is to disrupt and/or remove cells and cellular components from an ECM material while maintaining key structural and/or compositional properties of the material. Decellularization comprises process steps intended or expected to result or aid in the disruption of source tissue cells and/or removal of cellular content from the material undergoing decellularization. Actions that are intended to rinse or otherwise remove decellularization reagents or by-products should also be considered in that context as part of the decellularization process. Purifications or other isolations of specific ECM components are not considered decellularization and are outside the scope of this document.

1.3 This document describes relevant parameters of decellularization processes used to prepare extracellular matrix materials as medical products.

1.4 This document provides guidance on the measurement of specific and general properties of dECM. This includes both the analysis of cellular material as well as the assessment of the effects of decellularization on dECM properties such as composition, structure, and material properties.

1.5 This document does not provide guidance on the assessment of the host response subsequent to the implantation or other in vivo placement of dECM medical products. Such assessments should instead be conducted as part of biocompatibility studies or other safety and efficacy studies. At a minimum it is recommended that the finished product composed of dECM material shall be assessed in a relevant model that represents the biological responses that the product is expected to experience to ensure that the final material is functioning in accordance with design intentions. An in vivo model will generally be used, but cellular or ex vivo models may also be satisfactory when appropriate.

1.6 This document provides guidance on determining pertinent quality attributes as well as developing and assessing acceptance criteria related to ensuring the consistent evaluation and use of decellularization in manufacturing medical products. Acceptance criteria should address the adequacy of cellular disruption and removal of cellular remnants. Acceptance criteria should define acceptable levels for retention of extracellular matrix components. Acceptance criteria may place limits on damage to retained components. Acceptance criteria should place limits on the persistence of decellularization reagents. This document also provides recommendations on developing process parameters and associated process controls.

1.7 Decellularized products will require evidence of safety and/or efficacy beyond that related to evaluating the decellularization process. Commonly referenced standards include the ISO 10993 series (see ISO 10993-1) for biocompatibility of medical devices and the ISO 22442 series for medical devices utilizing animal tissues and their derivatives. These assessments are not in the scope of this document, though they may help to identify relevant functional characteristics and test methods as discussed in 5.2.9.

1.8 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use.

1.9 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.