Approved CGT Products and Regulatory Process

By: Kawthar Braysh, Mohamad Toutounji, Alejandro Barquero, Lucas Klemm, Alex Prokopienko and Alvaro Eguileor Giné

To follow-up on our previous article in the ex-vivo space, we’re now diving into a landscape overview of somatic cell therapies and a brief introduction to the regulatory approval process.

Advancing cells to licensure as final products 

Somatic cell therapy includes cells modified in a way that transforms the biological characteristics of the cell population (e.g., by expansion, selection, encapsulation, activation, or genetic modification as a part of gene therapy). Here are some examples: 

(1) Autologous or allogeneic lymphocytes activated and expanded ex vivo (e.g., lymphokine-activated killer cells (LAK), tumor infiltrating lymphocytes (TIL cells), antigen specific clones).

(2) Encapsulated autologous, allogeneic, or xenogeneic cells or cultured cell lines intended to secrete a bioactive factor or factors (e.g., insulin, growth hormone, a neurotransmitter).

(3) Autologous or allogeneic somatic cells (e.g., hepatocytes, myocytes, fibroblasts, bone marrow-or blood-derived hematopoietic stem cells, lymphocytes) that have been genetically modified.

(4) Cultured cell lines.

(5) Autologous or allogeneic bone marrow transplants using expanded or activated bone marrow cells. 

Regulatory Authorities

FDA regulates products intended to prevent, treat, or diagnose diseases or injuries under legal authorities established in the Public Health Service Act (the PHS Act) and the Federal Food, Drug, and Cosmetic Act (FDCA act). Both the PHS Act and FDCA act provide authority for enforcement of the various statutory requirements. FDA is authorized to conduct inspections to determine compliance with regulatory requirements (42 U.S.C. 262(c) and 21 U.S.C. 360(h) and 374).

Section 351(a) of the PHS Act (42 U.S.C. 262-a-) identifies a biological product as "any virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product, or arsphenamine or its derivatives (or any other trivalent organic arsenic compounds), applicable to the prevention, treatment, or cure of diseases or injuries of man".

Typically, a Biologics License Application (BLA) is necessary and will be reviewed by the FDA’s Center for Biologics Evaluation and Research (CBER). BLA is a request to for permission to introduce, or deliver for introduction, a biologic product into interstate commerce (21 CFR 601.2). There are also approval designations that could be considered such as Fast Track, Breakthrough Therapy, Accelerated Approval and Priority Review. 

Table 1: Landscape of Current CGT Products

We gratefully acknowledge @Mohammed Shadid for organizing this educational initiative.