Incorporating new approach methodologies into regulatory nonclinical pharmaceutical safety assessment

© 2023 The Author(s). ALTEX. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/New approach methodologies (NAMs) based on human biology enable the assessment of adverse biological effects of pharmaceuticals and other chemicals. Currently, however, it is unclear how NAMs should be used during drug development to improve human safety evaluation. A series of 5 workshops with 13 international experts (regulators, preclinical scientists, and NAMs developers) was conducted to identify feasible NAMs and to discuss how to exploit them in specific safety assessment contexts. Participants generated four “maps” of how NAMs can be exploited in the safety assessment of the liver, respiratory, cardiovascular, and central nervous systems. Each map shows relevant endpoints measured and tools used (e.g., cells, assays, platforms), and highlights gaps where further development and validation of NAMs remains necessary. Each map addresses the fundamental scientific requirements for the safety assessment of that organ system, providing users with guidance on the selection of appropriate NAMs. In addition to generating the maps, participants offered suggestions for encouraging greater NAM adoption within drug development and their inclusion in regulatory guidelines. A specific recommendation was that pharmaceutical companies should be more transparent about how they use NAMs in-house. As well as giving guidance for the four organ systems, the maps provide a template that could be used for additional organ safety testing contexts. Moreover, their conversion to an interactive format would enable users to drill down to the detail necessary to answer specific scientific and regulatory questions.Peer reviewe

Alpha-L-fucosyltransferases in human submaxillary gland and stomach tissues associated with the H, Lea and Leb blood-group characters and ABH secretor status

Schemes for the biosynthetic steps in the formation of the blood group active glycoproteins in secretions postulate that α-Image -fucosyltransferases specified by the Image and Image genes control the addition of Image -fucose to different acceptor sites in a precursor substance to give H, Lea and Leb serologically active structures. 1,2. The presence of 2-, 3- and 4-α-Image -fucosyl-transferases in submaxillary glands and stomach mucosal linings from persons who are secretors of ABH, and of 3- and 4-α-Image -fucosyltransferases in tissues from non-secretor persons, is described in this paper