LSHC Horizons Brochure 2024 - Flipbook - Page 27
Hogan Lovells | 2024 Life Sciences and Health Care Horizons | Cell, Tissue, and Gene Therapies
27
Product sameness considerations for cell, tissue,
and gene therapy products
Whether a product is considered the same as
a previously approved product has a broad
impact on a number of important regulatory
decisions, including exclusivity awards, priority
review vouchers, patent term extension, and
approval actions. Cell, tissue, and gene therapy
products challenge FDA’s existing regulatory
framework and its traditional notions of
product sameness.
FDA has issued a guidance that broadly
outlines the analytical framework for
determining when two gene therapy products
are considered the same drug for purposes of
orphan drug exclusivity. Among other things,
this general framework proposes a separate
analysis of the transgene and vector elements of
the product. However, the inherent complexity
of cell and gene therapy products means that
this general standard must be tailored on a
case-by-case basis, with a focus on components
that contribute to the overall therapeutic effect.
This analytical framework was implemented
with the licensure of the CAR-T product,
Breyanzi® (lisocabtagene maraleucel) in 2021.
FDA determined that Breyanzi® did not contain
the same drug as a previously licensed CAR-T
product for orphan drug exclusivity purposes
because the products use different transgene
hinge and transmembrane sequences. FDA
also noted that the final cell compositions of
the products are different because Breyanzi® is
administered at a defined ratio of T cell subsets.
Gary L. Veron
Partner
Washington, D.C.
This cellular composition rationale will likely
become more important as FDA analyzes more
complex cell-based gene therapy products
with differing cellular compositions. FDA has
a long history of determining sameness for
products comprised of complex mixtures in
other contexts, where it is often difficult or
impossible to determine which components
are “active” and contribute to the function
of the product.
In a December 2023 draft guidance, FDA
recognized that many cell and gene therapy
products consist of a complex mixture of
different cell types where the contribution of
each to the activity of the product is difficult
to determine. In those cases, FDA considers
the activity of the product to be based on the
totality of the cellular mixture. Importantly,
the mixture itself is considered the single
active ingredient, not the individual cell types,
and sameness determinations based on the
active ingredient generally would involve a
comparison of the mixtures.
New developments in this area are expected
in 2024. We are ever watchful of this evolving
regulatory framework and advise our clients on
when and how to engage with FDA to achieve
favorable outcomes.
Jason F. Conaty
Counsel
Washington, D.C.
Bryan Walsh
Associate
Washington, D.C.
