Considerations for manufacturing of cell and gene medicines for clinical development.

The global changes from 2001 that elevated substantially modified cell therapies to the definition of "medicinal product" have been the catalyst for the dramatic expansion of the field to its current and future commercial success. Europe was the first to incorporate human somatic cells into drug legislation with the medicines directive of 2001 (2001/83/EC), which led to the development of the term "advanced therapy medicinal products" (ATMPs) to cover all substantially modified products, tissue-engineered products and somatic cells that are not substantially modified but that are used non-homologously. For convenience, I use the term "ATMPs" throughout this review. The transition from "cell therapy" to "cellular medicine" coincided with changes in clinical trial legislation in Europe and, subsequently, across many drug jurisdictions throughout the world. As medicines, there is a clear path through multiple phases of trials and associated requirements for compliance with the good practice standards of drug development, and manufacturability is central to this development.