Handbook
How sponsors can streamline manufacturing and speed time to market
Navigating regulatory and tech-transfer
challenges for cell and gene therapies:
How sponsors can streamline
manufacturing and speed
time to market
Custom content for ProBio from Studio by Informa TechTarget
Cell and gene therapies (CGTs) represent a new frontier in disease
treatment, offering hope to patients suffering from difficult-to-treat
cancers, genetic disorders, autoimmune diseases and previously
untreatable illnesses. And as technology continues to advance,
the demand for CGTs has surged:
You’ll learn:
• Which regulatory and tech-transfer
challenges most often affect
CGTs developers.
• Strategies and best practices sponsors
can adopt to develop a strong regulatory
strategy and scalable manufacturing plan.
$201 billion in 2034
35.60%
• How to find the right external partners
for expertise and technical support for
successful commercialization.
The global market for biologics is estimated to
reach $201 billion in 2034, growing at a CAGR
of 35.60% between 2025 and 2034.1
There are over 3,000 active clinical trials involving
cell and gene therapies (CGTs) as of Q3 2025.2
But delivering on the promise of CGTs requires developers to mitigate
and overcome several potential risks.
“Developing therapeutics within living systems requires a completely
different strategy than the chemical-based strategies sponsors
deploy for small molecules,” explained Huiyi Zhu, global viral vector
line manager at ProBio CDMO. “Cells add a number of variables to
therapeutic development, and it’s also more difficult to maintain strict
controls in cell-based assays compared with chemical-based assays.”
This playbook will discuss the regulatory challenges that often arise
throughout regulatory review for CGTs — and the steps sponsors
can take to streamline their path to market. We’ll also delve into
the unique complications for scaling manufacturing and the steps
sponsors can take to scale manufacturing from site to site.
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2
2
Regulatory challenges with CGTs:
What happens when
sponsors can’t follow
a “blueprint”
Regulatory strategy is a cornerstone of any successful therapeutic
launch, but it’s especially important when developing CGTs. The
innate variability of working within living systems poses its own
challenges, since even minute differences in cells, vectors, reagents
or other raw materials can significantly affect the quality, efficacy
and safety of the resulting therapeutic.
Making matters even more complex is the novelty of many advanced
CGTs. “We’re seeing sponsors develop therapies that are truly unique
and innovative,” said Tina Yu, senior director of regulatory affairs at
ProBio CDMO. “That’s excellent news for patients, but it can be very
difficult to navigate from a regulatory perspective. With established
therapeutics, sponsors might be able to follow existing regulations
and guidance, and call on years or decades of previous approvals
and research to support their product development. With advanced
CGTs, they’re often working without a blueprint, and it can be difficult
to know exactly what control strategy is appropriate, or whether it’s
sufficient for different phases of product, whether the clinical design
is acceptable for agencies, and etc..”
Without a body of established research to pull from, regulators look
to sponsors to provide robust scientific justification for each aspect
of process development and manufacturing. But, as Yu explained,
“without standardized benchmarks against which to evaluate safety
and potency, it’s very difficult to gauge where the bar for approval
truly is.”
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In a best-case scenario, these challenges ramp up the burden on
sponsors’ research, clinical development, operations, regulatory
and biostatistics teams, which must develop and validate processes
and build characterization and QC workflows that withstand
regulatory scrutiny.
How does ‘working without a blueprint’
affect sponsors?
1. Higher burden (and costs) on R&D
In more severe cases, these regulatory complications can bring
programs to a halt. “If regulatory agencies feel that there are gaps
in the data, sometimes those can be difficult to backfill once you’ve
already gone through process development,” Yu said. “It introduces
the risk that you’ll need to redevelop your processes or have another
batch of production — and conduct costly and time-consuming
comparability studies — before you can move forward. It can
undermine the commercial viability of your project. And, potentially
keep lifesaving treatments from reaching the patients who need
them most.”
Because CGTs are advanced, novel and unique,
sponsors must devise their own “blueprints” for process
development, manufacturing and ongoing quality control.
Since there are few (or no) established industry standards
to rely on, sponsors must invest in the required R&D to
ensure consistency.
2. Heightened regulatory scrutiny
Similarly, regulators must rely on the data in sponsors’
regulatory filings to assess safety, efficacy and
consistency. This means that sponsors must typically
conduct more research to support their filings than
they would for chemical-based therapeutics, such as
small molecules.
3. Evolving expectations from regulators
The technology around advanced CGTs is progressing
quickly — and, like sponsors, regulators are working to
evolve along with it. In practice, this means the standards
to demonstrate safety and efficacy are also evolving,
introducing another source of uncertainty and risk into
sponsors’ programs.
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Against this backdrop,
tech transfer
becomes signi icantly
more complex
Investigator-initiated trials (IITs) add another layer of complexity
to this landscape. Often conducted in geographies that offer rapid
study start-up, strong academic infrastructure and flexible innovation
environments, IITs can serve as a powerful engine for early cell and
gene therapy research. In many cases, they represent the first step
in translating novel scientific insights into clinical potential.
However, while these geographic advantages can accelerate early
progress, they may also introduce downstream challenges as
programs move toward global development. Differences in GMP
expectations, raw material acceptability, clinical data requirements
and regulatory standards across regions can complicate the transition
from locally run IITs to sponsor-led, multi-region trials.
By taking a forward-looking, platform- and geography-aware
approach from the outset, sponsors can preserve speed without
sacrificing regulatory readiness. ProBio CDMO supports IITs with
region-specific manufacturing expertise, regulatory insight across
major markets, and scalable platform design, helping ensure that
innovation achieved locally can be successfully translated into
globally viable development programs.
Once sponsors have achieved consistent processes and manufacturing
at one site, they face an even more significant challenge: how to scale
manufacturing to meet patient demand and reach patients across
target global markets.
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The sensitive nature of CGTs means that even minute differences in
processes, reagents or platforms can introduce significant variability
to the resulting therapeutic. But sites differ in their technological
capabilities as well as the reagents and raw materials available to
them. Key materials, such as plasmids, may be patent-protected in
some markets but not others, requiring sponsors to adapt or adjust
their processes around supply costs or availability. Other reagents,
such as active fetal bovine serum may be suitable to use in large
global markets, such as China, but don’t align with regulatory
standards in the U.S.
How does site-to-site variability
affect tech transfer?
1. Process redevelopment is the norm
Processes and expertise often don’t transfer easily
from site to site. Sponsors need to redevelop processes
with the resources available at each specific site and
conduct variability studies to demonstrate concordance
across sites.
Even when sponsors can use the same platforms and materials
across multiple sites, regional differences may introduce variability.
“Something as seemingly insignificant as the sugar available in one
market may differ from the sugar available in another,” said Lisa Wang,
Director of Virus MSAT at ProBio CDMO. “You might think, ‘how
different can sugar be?’ But the truth is, it can be different enough
to impact the therapeutic.”
2. Robust characterization studies
are mission critical
Of course, the reliability of variability studies depend on
sponsors’ ability to fully characterize their therapeutic.
Without a comprehensive understanding of the most
important critical quality attributes, sponsors can’t
accurately set benchmarks for consistency.
3. Global supply networks create
potential bottlenecks
Besides reworking processes around site-specific
capabilities and material availability, sponsors need
to build robust supply networks in each global market
to ensure they can consistently meet global patient
demand. Failing to source appropriate suppliers and
build sufficient redundancies into the supply chain
means sponsors risk supply interruptions that can bring
the program to a standstill.
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The challenges outlined in this playbook also reflect a broader shift
underway in advanced therapy development, one that regulators
and industry are increasingly working to address together. The FDA’s
Platform Technology Designation Program highlights a growing
regulatory emphasis on well-characterized, reproducible platform
technologies that can be applied across multiple products to
reduce development risk, streamline manufacturing and accelerate
regulatory review.
Sponsors can streamline
their path to market
by thinking proactively
While the complexity of CGT development makes it nearly impossible
to identify every risk to a program, sponsors can lay the foundation
for successful commercialization by taking a proactive approach to
risk management.
For sponsors, this creates a significant opportunity. By establishing
robust, scalable platform strategies early, teams can minimize
duplication, de-risk tech transfer and move more confidently from
development through commercialization. With deep CGT expertise,
global manufacturing capabilities, and integrated regulatory experience,
ProBio CDMO helps sponsors operationalize this platform-driven
approach, turning regulatory complexity into a competitive advantage
and enabling faster, more predictable paths to market.
“It’s important to bring in key stakeholders — especially regulatory
teams — as early as possible to help mitigate as many risks as possible,”
Yu said. “Seasoned regulatory experts can help you crystallize your
goals for the program, including the markets you eventually want to
reach, so you can develop your processes with the relevant regulatory
guidelines in mind from the start.”
The right regulatory consultants can help you identify likely bottlenecks
as you scale manufacturing from site to site across global markets and
map out the most efficient way to meet local regulatory requirements.
They can also help you streamline the shift from process development
to manufacturing — for example, by helping you select raw materials
that will most easily transition from research use only stages to GMP
manufacturing and scale-up.
Actionable takeaway:
Bring in regulatory expertise
as early as possible
When it comes to soliciting regulatory experts, there’s
no such thing as too early, Wang explained. “Any delay
introduces risk to your program, since you may need to
circle back and revalidate or redevelop processes to
withstand regulatory scrutiny. If we’re there from the outset,
we can help you work strategically from Day 1.”
External regulatory experts also bring “boots on the ground” experience
around ongoing conversations with regulators. “For CGTs, every
program needs its own unique regulatory strategy. But we can call on
our experience across hundreds of programs to curate strategies and
best practices likely to work for your therapeutic,” Yu said.
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Actionable takeaway:
Make recurring hands-on
training a priority
Take a bespoke
approach to scaling
Zhu recommended employing a number of strategies
to help new sites adhere to your processes, during
and after onboarding.
Just as a tailored approach is critical when it comes to regulatory
strategy, sponsors should also follow a site-specific approach to tech
transfer. “With CGTs, the shift from site to site requires significant
consideration, even if you’re staying in the same market,” Wang said.
1. Offer initial course-based training
to help site staff fully understand the program’s
processes and QC controls.
Ideally, sponsors will have access to the regulatory guidance they
need to optimize their processes for tech transfer — for example,
anticipating region-specific regulations and material availability,
as well as completing robust characterization studies to set strong
quality controls. However, it’s still critical to have an action plan to
onboard each site.
2. Shift to execution-based training,
allowing staff to do “trial runs” of the process to catch
errors or sources of variability early — before they affect
batches of the therapeutic.
“One often-overlooked aspect of tech transfer is communication,”
Wang said. “Your standard operating procedures [SOPs] and
processes may make perfect sense to you, but they may not translate
to a new site. So it’s important to invest in training so new sites
can familiarize themselves with your processes, ask questions and
address concerns.”
3. Provide continuing education
to refresh staff on the appropriate processes and help
ensure consistent performance over time.
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Actionable takeaway:
Find the right CDMO partner
for your needs
Finding the support
you need to streamline
time to market
Consider asking the following questions to qualify
potential CDMOs and find the best fit:
Ultimately, laying the foundation for successful regulatory filings
and successful scale-up requires a deep bench of expertise:
1. How do you support clients in developing
and executing global regulatory strategies?
• Regulatory and compliance specialists with in-depth expertise
2. What is your track record with regulatory
submissions in cell and gene therapy?
of each target global market.
• Technology and analytical experts to support process development.
• Technical and analytical experts to help ensure the process
3. How do you stay current with evolving
regulatory guidance speci ic to advanced
therapies?
consistency and method robustness.
• Communications experts to prepare regulatory findings
and other communications.
• Project managers to manage operations within and across sites.
• Training specialists to help onboard sites.
3. How do you stay current with evolving
regulatory guidance speci ic to advanced
therapies?
For many sponsors, finding a CDMO partner is critical to secure the
right expertise to set the program up for success. “One of the biggest
benefits of a CDMO partner is instant access to cross-functional
experts,” Zhu said. “You don’t need to spend months attracting the
right talent and risk bringing on expertise too late. A CDMO can bring
you the skills and insights you need from the start.”
4. What is your standard framework for tech
transfer, and how do you mitigate risk
during transitions?
5. What comparability strategies do you use to
demonstrate process equivalence post-transfer?
The ideal partner can assist in developing robust QC standards, as well
as measuring site performance to ensure consistency across the
program. It can also lead the “boots on the ground” approach to
onboarding, helping to familiarize site staff on new processes and
troubleshooting issues that may arise. Finally, it can provide regulatory
support at each stage of CGT development, laying the foundation for
a timely, cost-effective path to market.
6. How do you ensure data integrity across
systems and processes?
7. How do you track and communicate
tech-transfer progress and KPIs?
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Set your next CGT
programs up for success
with the right partner
As the CGT landscape becomes ever more complex and crowded,
sponsors need robust strategies for regulatory success and tech
transfer to gain a competitive advantage. Keeping compliance top
of mind throughout development, and taking a bespoke approach
to tech transfer, helps sponsors scale with confidence — and deliver
on their missions to change patients’ lives.
How ProBio CDMO can help
ProBio is a leading global CDMO supplier in CGTs and advanced
therapies. We are experts in the development of challenging molecules,
including proteins, bispecific antibodies and CGTs. We provide
premium end-to-end service from discovery to commercialization
with professional solutions and efficient process.
Our track record:
100+ 100+ 700+
IND
clearances
Protein and
antibody
GMP CGT
batches
CMC/CMO
projects
successfully
delivered
Learn more about how we can accelerate your path
10
ProBio, a subsidiary of GenScript, is a global CDMO offering
end-to-end services from discovery to GMP for plasmids, antibodies,
and cell & gene therapies. We bring together multidisciplinary expertise
to accelerate development and manufacturing through customized
and comprehensive services.
