1.1 This standard provides guidance on the characterization and evaluation of the decellularization processes used to produce decellularized extracellular matrix (dECM) materials that will be used as implanted medical products. 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 before 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 will require additional considerations outside the scope of this guide. 1.2 Biological tissues are composed of a structural ECM and embedded cells. The intent of a decellularization process is to disrupt or remove or both cells and cellular components from an ECM material while maintaining key structural or compositional properties or both of the material. Decellularization comprises process steps intended or expected to result or aid in the disruption of source tissue cells or removal or both of cellular content from the material undergoing decellularization. Actions that are intended to rinse or otherwise remove decellularization reagents or byproducts 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 would be outside the scope of this guide. 1.3 This guide describes relevant parameters of decellularization processes used to prepare ECM materials as medical products. 1.4 This guide 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 guide does not provide guidance on the assessment of the host response subsequent to the implantation 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 the final material is functioning in accordance with design intentions. An in-vivo model will generally be used, but cellular models may also be sufficient when appropriate. 1.6 This guide provides guidance on determining pertinent quality attributes as well as developing and assessing targets (acceptance criteria) related to the use of decellularization in manufacturing medical products. Targets should address adequacy of cellular disruption and removal of cellular remnants. Targets should define acceptable levels for retention of ECM components. Targets may place limits on damage to retained components. Targets should place limits on the persistence of decellularization reagents. This guide also provides recommendations on developing process parameters and associated process controls. 1.6.1 No consensus has been established regarding decellularization thresholds or classifications. This guide, therefore, cannot suggest targets and instead recommends commonly measured attributes to develop targets specific to the design of each unique material and its intended use. 1.7 Decellularized products will require evidence of safety or efficacy or both beyond that related to evaluating the decellularization process. These assessments are not in the scope of this guide, though they may help to identify relevant functional characteristics and test methods. 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 and health practices and determine the applicability of regulatory limitations prior to use.
Keywordsdecellularization; extracellular matrix; tissue engineering
This guide for evaluating biomaterial decellularization processes is intended to provide an approach for assessing the extent of decellularization achieved. Many TEMPs currently on the market are comprised of decellularized extracellular matrix (dECM) materials. Evaluation of the decellularization process is important from safety, regulatory, and process control perspectives. A consensus standard will provide producers, regulators, and others a common approach to apply in evaluating these products. The draft standard places emphasis on the extent of decellularization, the preservation of the original ECM properties, and the persistence of any reagents. This guide does not specify threshold levels for decellularization but does recommend product-specific target ranges.Back to Top