www.biopharminternational.com March 2021 eBook BioPharm International 13
then early-phase clinical studies
could provide early evidence of the
gene therapy's effectiveness.
The draft guidance further rec-
ommends that sponsors of neuro-
degenerative-disease-focused gene
therapy candidates consider con-
ducting additional product char-
acterization studies to establish
acceptance limits for CQAs (1).
Because gene therapy products
in herent ly have more va r iable
quality attributes than small-mol-
ecule drugs or more familiar and
well-characterized biological prod-
ucts, further characterization stud-
ies may be necessary, especially
because product CQAs could influ-
ence final formulation parameters.
Formulation aspects may need to
be decided on early in the manu-
facturing process development.
Mea nwh i le, pro duc t- sp e c i f ic
considerations may include the
design of the gene therapy prod-
uct, product purity, product iden-
tity, potency assays, and product
strength. In addition, FDA sug-
gests that sponsors evaluate any
effects that manufacturing process
changes may have on the product's
CQAs; demonstrate compatibility
of any drug delivery device used
with the investigational product
before initiating Phase I studies;
and discuss plans for pharmaceuti-
cal quality development with FDA
early, for example, at the pre-in-
vestigational new drug application
meeting as well as maintaining
continuous engagement with the
agency throughout the drug devel-
opment process.
EMPHASIS ON GUIDANCE FOR
NEURODEGENERATIVE DISEASES
Having regulatory guidance spe-
cifically focused on gene therapy
development for neurodegenera-
tive diseases is an important effort
on FDA's part. Megan Canniere,
head of Regulatory Affairs at Spark
T he rap eut ic s, says t hat, g ive n
the significant unmet need that
neurodegenerative diseases col-
lectively represent, the agency's
ef for ts to prov ide g u ida nce to
therapeutic developers in this area
is laudable.
"Regulatory guidance is a valu-
able tool in supporting therapeu-
tic developers to understand the
agency's latest think ing and to
facilitate streamlining of develop-
ment efforts," she states.
I n pa r t ic u la r, t he new d ra f t
guidance recommends that spon-
sors developing gene therapy prod-
ucts targeting neurodegenerative
diseases get in contact with the
Office of Tissues and Advanced
Therapies (OTAT) in the Center for
Biologics Evaluation and Research
(CBER) early in the process, pref-
erably before submitting an IND.
Sponsors are also encouraged to
maintain communications with
O TAT a l l t h roug hout pro duc t
deve lopme nt to d i s c u ss pro d -
uct-specific considerations.
"Gene therapy as a modalit y
presents nu merous oppor t u n i-
ties to meet areas of large unmet
need in neurodegenerative dis-
eases," Canniere points out. This
modality of treatment also creates
unique considerations in the con-
text of targeting the central ner-
vous system (CNS), she adds.
To expedite the regulatory pro-
cess for sponsors of gene therapy
products, FDA has made several
programs available that address
unmet medical needs for serious or
life-threatening conditions. These
programs include breakthrough ther-
apy designation, fast track designation,
accelerated approval, priority review, and
regenerative medicine advanced therapy
designation (3,4), all intended to facil-
itate and expedite development and
review. Specifically, the regenerative
medicine advanced therapy desig-
nation and breakthrough therapy
designation call for increased FDA
attention on potentially promising
therapies and offer a pathway to
sponsors for more frequent interac-
tions with the agency. The aim is
for sponsors to develop more effi-
cient trial designs and to streamline
overall drug development.
"Having a guidance dedicated to
gene therapies for neurodegenerative
diseases provides a unified source
of multi-disciplinary (pre-clinical,
clinical, and CMC) information on
such unique considerations, and
may preempt the agency needing to
respond to identical questions from
many different sponsors, each tar-
geting distinct neurodegeneration
indications, with CNS-directed gene
therapies," says Canniere.
REFERENCES
1. FDA, Draft Guidance for Industry:
Human Gene Therapy for
Neurodegenerative Diseases (CBER,
January 2021).
2. FDA, Guidance for Industry: Guidance
for Human Somatic Cell Therapy and
Gene Therapy (CBER, March 1998).
3. FDA, Guidance for Industry: Expedited
Programs for Serious Conditions—Drugs
and Biologics (CDER,CBER, May 2014).
4. FDA, Guidance for Industry: Expedited
Programs for Regenerative Medicine
Therapies for Serious Conditions (CBER,
February 2019).
BP
Regulatory Sourcebook Quality
"Gene therapy as a
modality presents
numerous opportunities
to meet areas of
large unmet need in
neurodegenerative
diseases."
—Megan Canniere,
Spark Therapeutics
