Regulation of Regenerative Medicines: A Global Perspective
57
Introduction
Given the diversity of cell-based advanced
therapies under development and the unique
challenges associated with donor consider-
ations, sourcing, transporting, manufacturing,
and testing, an entire book could be devoted to
special considerations for these novel therapies.
However, the authors have chosen to focus on
three areas that frequently present challenges for
both developers and regulators, particularly in the
context of conducting global clinical trials. The
first challenge relates to navigating the myriad
of legislative and logistical challenges of sourc-
ing the starting human cells and/or tissues and
transporting it to the site of manufacturing. The
second challenge relates to establishing compara-
bility after a planned or unplanned change in the
manufacturing process occurs. The final challenge
covered in this chapter are the considerations
for final product labeling, sampling, stability, and
handling at the clinical site.
Special Considerations for Human
Cell or Tissue-Based Starting
Materials
The following are key tenets for sourcing of
human cells and tissues as starting materials for
advanced therapies:
• Prevention of the transmission of infectious
diseases from the donor to the recipient
• Use of bidirectional tracking systems to
ensure the starting cells or tissues can be
traced back to the donor, while adhering to
privacy legislation
• Qualification of the sites involved in pro-
curement of the starting cells or tissues
• Establishing appropriate shipping condi-
tions (time and temperature) to ensure the
starting cells or tissues retain the desired
bioactivity during transport from the pro-
curement site to the location where cellular
therapy manufacturing occurs.
In the US, the Food and Drug Administration
(FDA) has comprehensive regulations, referred
to as good tissue practices (GTPs),1 govern-
ing the use of human tissues and human cells
used as starting materials in manufacturing
advanced therapies. These materials are referred
to as human cells, tissues, and cellular and tis-
sue-based products (HCT/Ps). Similar, yet not
fully aligned, regulations are in place for the EU
and other countries. In Europe, regulations for
blood and blood products are based on Directive
2002/98/EC, and the legal framework defining
the safety and quality standards for tissues and
cells is set out in Directive 2004/23/EC.2,3
7
Special Considerations for
Cell-Based Advanced Therapies
By Bridget Bulwer, Mo Heidaran, PhD, and Darin J. Weber, PhD
57
Introduction
Given the diversity of cell-based advanced
therapies under development and the unique
challenges associated with donor consider-
ations, sourcing, transporting, manufacturing,
and testing, an entire book could be devoted to
special considerations for these novel therapies.
However, the authors have chosen to focus on
three areas that frequently present challenges for
both developers and regulators, particularly in the
context of conducting global clinical trials. The
first challenge relates to navigating the myriad
of legislative and logistical challenges of sourc-
ing the starting human cells and/or tissues and
transporting it to the site of manufacturing. The
second challenge relates to establishing compara-
bility after a planned or unplanned change in the
manufacturing process occurs. The final challenge
covered in this chapter are the considerations
for final product labeling, sampling, stability, and
handling at the clinical site.
Special Considerations for Human
Cell or Tissue-Based Starting
Materials
The following are key tenets for sourcing of
human cells and tissues as starting materials for
advanced therapies:
• Prevention of the transmission of infectious
diseases from the donor to the recipient
• Use of bidirectional tracking systems to
ensure the starting cells or tissues can be
traced back to the donor, while adhering to
privacy legislation
• Qualification of the sites involved in pro-
curement of the starting cells or tissues
• Establishing appropriate shipping condi-
tions (time and temperature) to ensure the
starting cells or tissues retain the desired
bioactivity during transport from the pro-
curement site to the location where cellular
therapy manufacturing occurs.
In the US, the Food and Drug Administration
(FDA) has comprehensive regulations, referred
to as good tissue practices (GTPs),1 govern-
ing the use of human tissues and human cells
used as starting materials in manufacturing
advanced therapies. These materials are referred
to as human cells, tissues, and cellular and tis-
sue-based products (HCT/Ps). Similar, yet not
fully aligned, regulations are in place for the EU
and other countries. In Europe, regulations for
blood and blood products are based on Directive
2002/98/EC, and the legal framework defining
the safety and quality standards for tissues and
cells is set out in Directive 2004/23/EC.2,3
7
Special Considerations for
Cell-Based Advanced Therapies
By Bridget Bulwer, Mo Heidaran, PhD, and Darin J. Weber, PhD