Sterility Assurance-Current and Future State.

Abstract

Manufacture by aseptic processing accompanied by end product compendial sterility testing has been the predominant means of production and disposition of therapeutics requiring the critical quality attribute of sterility. Despite significant advancements in microbiology and epidemiology and innovations in therapeutic products and engineering, there have been minimal advancements in the standards and regulations governing the assurance of sterility. Furthermore, the assurance of sterility of current and future therapies are not well served in a singular fashion, rather therapies occupy optimal locations in a sterility assurance design space within which parametric release is the default and expected mode of product disposition. Indeed, recent chimeric antigen receptor T-cell therapies (CART) for all intents and purposes conform to the principles and requirements for parametric release; its disposition is parametric in all but words. This article offers a new direction including a "road map" for the future of sterility assurance paved through a sequence of ongoing changes to the United States Pharmacopeia (USP) informational chapters. The future state of design-space provides optimal assurance of sterility and expanded opportunities for parametric release is explored by introduction of candidate modalities for sterile manufacture per recently revised USP <1211> and <1222>.