Table 1.

Key concepts and definitions in the US FDA and EMA cell-based therapy regulations

General concept	US FDA terminologya	US FDA definition	EMA terminologyb	EMA definition
Cell-based interventions	human cells, tissues, and cellular and tissue-based products (HCT/Ps)	products “containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion or transfer into a human recipient”	somatic cell therapy medicinal product	somatic cell therapy medicinal product is a biological product that contains or consists of cells/tissues that have been subjected to substantial manipulation or are not intended to be used for the same essential function in the recipient as the donor, but is intended to be used for therapeutic purposes
	HCT/Ps	see above	tissue-engineered products	a product contains or consisting of engineered cells and/or tissues, and is presented as having properties for, or is used in or administered to regenerate, repair or replace human tissue
Homologous use	homologous use	the cells have the same basic function(s) in the recipient as donor	same essential function	the cells when removed from their original environment in the human body are used to maintain the original function(s) in the same anatomical or histological environment
Autologous use	same surgical procedure	related to HCT/Ps, an establishment removes HCT/Ps from an individual and then implants, infuses, or transfers those cells/tissues into the same individual. Furthermore, the HCT/Ps are in their original form	N/A
Manipulation	minimal manipulation	processing does not alter the relevant original/biological characteristics of the cell/tissue. For structural tissues, this includes its utility for reconstruction, repair, or replacement. Examples include rinsing, cleansing, sizing, or shaping	substantial manipulation	the cells/tissue have been manipulated during the manufacturing process so that their biological characteristics, physiological functions, or structural properties have been modified to be relevant for their intended function. Examples of substantial manipulation includes cell culture expansion, enzymatic digest, genetic modification of cells, and differentiation with growth factors. Examples of non-substantial manipulation include cutting, grinding, shaping, centrifugation, sterilization, irradiation, cell separation, filtering, and freezing
Structural tissue		HCT/Ps that physically support or serve as a barrier or conduit, or connect, cover, or cushion. Examples include bone, skin, amniotic fluid, umbilical cord, blood vessel, adipose tissue, cartilage, and tendon or ligament	N/A
Nonstructural tissue		HCT/Ps that serve metabolic or other biochemical roles in the body are considered cells/nonstructural tissues. Examples include reproductive cells and tissues; hematopoietic stem/progenitor cells and lymph nodes	N/A

N.A, not applicable—the concept was not described or was relevant to the policy.

^aUS FDA. 2017 “Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-based Products” and “Same Surgical Procedure Exception under 21 CFR 1271.15(b)” (U.S. Food and Drug Administration, 2017a, U.S. Food and Drug Administration, 2017b).

^bRegulation (EC) No. 1394/2007 and 2015 “Reflection paper on classification of advanced therapy medicinal products” (European Medicines Agency (EMA) Committee for Advanced Therapies (CAT), 2015; The European Commission, 2007).