Regulation of Regenerative Medicines: A Global Perspective
55
• January 2020 FDA guidance on testing of
retroviral vector-based human gene ther-
apy products for replication competent
retrovirus during product manufacture and
patient follow-up provides guidance on the
identification and test methods and patient
monitoring after administration of retroviral
vector-based gene therapy products.35
• September 2016 FDA guidance on recom-
mendations for microbial vectors used for
gene therapy provides recommendations on
the CMC aspects to be considered for the
dose selection and dosing schedule in ear-
ly-phase clinical trials of products containing
microbial vectors.36
• January 2011 FDA guidance on potency
tests for cellular and gene therapy products
provides detailed guidance to manufacturers
of CGT products on developing analytical
methods to measure product potency, which
are applicable to both clinical trial applica-
tion and eventual license application.37
• The European Medicines Agency (EMA)
also has provided the industry and CGT
developers with scientific guidelines on
several topics, including recommendations
on quality requirements for investigational
and commercialization of advanced therapy
medicinal products and gene therapy. In
addition to the guidelines, the EMA has
provided reflection papers and advice on
CMC considerations, such as comparability,
in a question-and-answer format.38
• Japan’s Ministry of Health, Labour, and
Welfare also has provided a guideline that
lays down basic technicalities required to
ensure the quality and safety of in vivo gene
therapy products and ex vivo genetically
modified human cell therapy and other
regenerative medical products.39
• Special designations, such as RMAT40 in the
US and priority medicines (PRIME)41 in
the EU, also provide many opportunities for
sponsors to interact with regulatory agencies
and provide tools to develop quality aspects
of their products. For instance, the EMA has
a toolbox guidance on scientific elements
and regulatory tools to meeting quality
and manufacturing controls and address
common challenges in order to support
quality data packages for PRIME marketing
authorization applications.
• The International Council for
Harmonisation of Technical Requirements
for Pharmaceuticals for Human Use (ICH)
also has provided guidance documents with
recommendations toward achieving greater
harmonization in the interpretation and
application of technical guidelines on quality
issues, including but not limited to manu-
facturing controls and good manufacturing
practices, specifications, quality risk manage-
ment, analytical methods qualification and
validation, conducting stability studies, and
defining strategies for impurities testing.42
Conclusion
This chapter reviewed the advancements in the
field of gene therapy and the landscape of vectors
used in the clinical space with a special emphasis
on viral vectors. Quality and regulatory consid-
erations for the successful development of gene
therapy also are discussed. Some of the devel-
opmental challenges for gene therapy include
safety concerns due to immunogenicity, high
manufacturing cost, and the need for long-term
follow-up. In spite of the challenges, the field
is well poised to deliver potentially life-saving
treatments for various unmet medical needs.
References
1. Approved Cellular and Gene Therapy Products.
Current as of 26 October 2021. FDA website.
https://www.fda.gov/vaccines-blood-biologics/
cellular-gene-therapy-products/approved-cellu-
lar-and-gene-therapy-products.
2. Estimates of Funding for Various Research, Condition,
and Disease Categories (RCDC). Published 25 June
2021. National Institutes of Health (NIH) RePORT
website. https://report.nih.gov/funding/categori-
cal-spending#/.
3. 2020: Growth and Resilience in Regenerative Medicine.
Alliance for Regenerative Medicine (ARG) website.
https://alliancerm.org/sector-report/2020-annual-re-
port/.
4. What is Gene Therapy? Current as of 25 July
2018. FDA website. https://www.fda.gov/vac-
cines-blood-biologics/cellular-gene-therapy-products/
what-gene-therapy.
55
• January 2020 FDA guidance on testing of
retroviral vector-based human gene ther-
apy products for replication competent
retrovirus during product manufacture and
patient follow-up provides guidance on the
identification and test methods and patient
monitoring after administration of retroviral
vector-based gene therapy products.35
• September 2016 FDA guidance on recom-
mendations for microbial vectors used for
gene therapy provides recommendations on
the CMC aspects to be considered for the
dose selection and dosing schedule in ear-
ly-phase clinical trials of products containing
microbial vectors.36
• January 2011 FDA guidance on potency
tests for cellular and gene therapy products
provides detailed guidance to manufacturers
of CGT products on developing analytical
methods to measure product potency, which
are applicable to both clinical trial applica-
tion and eventual license application.37
• The European Medicines Agency (EMA)
also has provided the industry and CGT
developers with scientific guidelines on
several topics, including recommendations
on quality requirements for investigational
and commercialization of advanced therapy
medicinal products and gene therapy. In
addition to the guidelines, the EMA has
provided reflection papers and advice on
CMC considerations, such as comparability,
in a question-and-answer format.38
• Japan’s Ministry of Health, Labour, and
Welfare also has provided a guideline that
lays down basic technicalities required to
ensure the quality and safety of in vivo gene
therapy products and ex vivo genetically
modified human cell therapy and other
regenerative medical products.39
• Special designations, such as RMAT40 in the
US and priority medicines (PRIME)41 in
the EU, also provide many opportunities for
sponsors to interact with regulatory agencies
and provide tools to develop quality aspects
of their products. For instance, the EMA has
a toolbox guidance on scientific elements
and regulatory tools to meeting quality
and manufacturing controls and address
common challenges in order to support
quality data packages for PRIME marketing
authorization applications.
• The International Council for
Harmonisation of Technical Requirements
for Pharmaceuticals for Human Use (ICH)
also has provided guidance documents with
recommendations toward achieving greater
harmonization in the interpretation and
application of technical guidelines on quality
issues, including but not limited to manu-
facturing controls and good manufacturing
practices, specifications, quality risk manage-
ment, analytical methods qualification and
validation, conducting stability studies, and
defining strategies for impurities testing.42
Conclusion
This chapter reviewed the advancements in the
field of gene therapy and the landscape of vectors
used in the clinical space with a special emphasis
on viral vectors. Quality and regulatory consid-
erations for the successful development of gene
therapy also are discussed. Some of the devel-
opmental challenges for gene therapy include
safety concerns due to immunogenicity, high
manufacturing cost, and the need for long-term
follow-up. In spite of the challenges, the field
is well poised to deliver potentially life-saving
treatments for various unmet medical needs.
References
1. Approved Cellular and Gene Therapy Products.
Current as of 26 October 2021. FDA website.
https://www.fda.gov/vaccines-blood-biologics/
cellular-gene-therapy-products/approved-cellu-
lar-and-gene-therapy-products.
2. Estimates of Funding for Various Research, Condition,
and Disease Categories (RCDC). Published 25 June
2021. National Institutes of Health (NIH) RePORT
website. https://report.nih.gov/funding/categori-
cal-spending#/.
3. 2020: Growth and Resilience in Regenerative Medicine.
Alliance for Regenerative Medicine (ARG) website.
https://alliancerm.org/sector-report/2020-annual-re-
port/.
4. What is Gene Therapy? Current as of 25 July
2018. FDA website. https://www.fda.gov/vac-
cines-blood-biologics/cellular-gene-therapy-products/
what-gene-therapy.