Regulation of Regenerative Medicines: A Global Perspective
49
Introduction
The field of regenerative medicine focuses on the
development of curative processes or therapeu-
tics, with the end products replacing diseased
components or restoring normal function.
Advances in our basic understanding of the
molecular underpinnings of normal physiology
and disease pathophysiology, combined with
advances in technology, have paved the way
for 22 approved cell and gene therapy (CGT)
products developed by academic and industry
sponsors.1 According to the National Institutes
of Health (NIH) Research Portfolio Online
Reporting Tools (RePORT), funding for regen-
erative medicine-enabling research (Table 6-1)
has increased over the years.2
Gene therapy remains an active field of
research, making significant strides with 114
Phase 1, 237 Phase 2, and 72 Phase 3 gene
therapy-based clinical trials in 2020.3 However,
the future of gene therapy hinges on the success
and safety of the methods by which potentially
life-changing technologies are introduced to
patients. To this end, this chapter will focus on
gene therapy products, with an emphasis on the
selection of vectors as a method to deliver genetic
material to patients and the regulatory consider-
ations associated with such choices.
Gene Therapy
Gene therapy products intended for human
use are regulated by the US Food and Drug
Administration’s (FDA) Center for Biologics
Evaluation and Research (CBER). Within
CBER, the Office of Tissues and Advanced
Therapies (OTAT), previously known as the
Office of Cellular, Tissue, and Gene Therapies
(OCTGT), evaluates these products. Gene ther-
apy products include4,5 but are not limited to:
• Non-viral vector-based therapies
• Viral vector-based therapies
• Patient-derived gene-modified cellular
products, such as chimeric antigen receptor
(CAR) T-cells
• Clustered regularly interspaced short pal-
indromic repeats (CRISPR)/Cas-mediated
gene editing
• Oncolytic viruses
• Bacterial vector-based therapies
These gene therapy products encompass the two
primary delivery methods to date: ex vivo and in
vivo. With an ex vivo delivery strategy, cells are
harvested from a patient or donor and subse-
quently modified or re-engineered (typically by
viral vector transduction) and then administered
to the patient. In contrast, an in vivo delivery
system introduces gene therapy products, such
6
Gene Therapy and Viral Vectors:
An Overview on Current Trends
By Marites T. Woon, PhD and Rajesh L. Thangapazham, PhD, RAC
49
Introduction
The field of regenerative medicine focuses on the
development of curative processes or therapeu-
tics, with the end products replacing diseased
components or restoring normal function.
Advances in our basic understanding of the
molecular underpinnings of normal physiology
and disease pathophysiology, combined with
advances in technology, have paved the way
for 22 approved cell and gene therapy (CGT)
products developed by academic and industry
sponsors.1 According to the National Institutes
of Health (NIH) Research Portfolio Online
Reporting Tools (RePORT), funding for regen-
erative medicine-enabling research (Table 6-1)
has increased over the years.2
Gene therapy remains an active field of
research, making significant strides with 114
Phase 1, 237 Phase 2, and 72 Phase 3 gene
therapy-based clinical trials in 2020.3 However,
the future of gene therapy hinges on the success
and safety of the methods by which potentially
life-changing technologies are introduced to
patients. To this end, this chapter will focus on
gene therapy products, with an emphasis on the
selection of vectors as a method to deliver genetic
material to patients and the regulatory consider-
ations associated with such choices.
Gene Therapy
Gene therapy products intended for human
use are regulated by the US Food and Drug
Administration’s (FDA) Center for Biologics
Evaluation and Research (CBER). Within
CBER, the Office of Tissues and Advanced
Therapies (OTAT), previously known as the
Office of Cellular, Tissue, and Gene Therapies
(OCTGT), evaluates these products. Gene ther-
apy products include4,5 but are not limited to:
• Non-viral vector-based therapies
• Viral vector-based therapies
• Patient-derived gene-modified cellular
products, such as chimeric antigen receptor
(CAR) T-cells
• Clustered regularly interspaced short pal-
indromic repeats (CRISPR)/Cas-mediated
gene editing
• Oncolytic viruses
• Bacterial vector-based therapies
These gene therapy products encompass the two
primary delivery methods to date: ex vivo and in
vivo. With an ex vivo delivery strategy, cells are
harvested from a patient or donor and subse-
quently modified or re-engineered (typically by
viral vector transduction) and then administered
to the patient. In contrast, an in vivo delivery
system introduces gene therapy products, such
6
Gene Therapy and Viral Vectors:
An Overview on Current Trends
By Marites T. Woon, PhD and Rajesh L. Thangapazham, PhD, RAC