Dr. Chris Chen is the CEO of WuXi Biologics, a leading global Contract Research, Development and Manufacturing Organization (CRDMO). Under his leadership, WuXi Biologics has built up a world-class open-access integrated platform, enabling over 800 integrated biologics projects. Dr. Chen serves on the International Board of Directors for ISPE as the first board member from Asia. He holds Bachelor’s degrees in Chemical Engineering and Automation from Tsinghua University and a Ph.D. in Chemical Engineering from the University of Delaware.
Generally speaking, how has quality
assurance in drug manufacturing evolved over the past 10 years? In the last ten
years, quality assurance in biologics drug manufacturing has greatly improved
due to several important factors:
o Regulatory Evolution: Global regulatory standards have become
stricter, with agencies like the FDA and EMA updating their guidelines to
ensure drugs are safe and effective. This has pushed drug manufacturers worldwide
to upgrade their quality systems to comply with current Good Manufacturing
Practices (cGMP) and other regulatory requirements. o Technology Advancements: New technologies, including automation
and data analytics, have enhanced the precision and efficiency of quality
assurance. Innovations such as single-use systems in manufacturing have also significantly
lowered contamination risks and improved product consistency. o Risk Management: There's an increased focus on
risk-based quality management. Principles of Quality by Design (QbD) and risk
management are now essential in both development and manufacturing, aiming to
better understand and control process variables. o Globalization: As CDMOs go globally and serve clients
worldwide, they need to standardize quality assurance across different
countries and regulatory frameworks. This has led to more unified global
quality standards. o Client Expectations: With biologics becoming more complex,
clients are seeking higher quality and greater transparency in manufacturing.
CDMOs have responded by enhancing their quality assurance systems and improving
communication with clients about quality metrics.
Overall,
the quality assurance in biologics manufacturing within CDMOs has become more sophisticated,
compliant with regulations, and aligned with technological and market changes
to meet the high standards required for biologics products.
The practicalities of managing a
multi-step quality control process are manifold and complex. What would you say
is the key to providing consistent and reliable quality across those steps, and
different locations across the world? Managing a
complex quality control process across dozens of different global sites
requires a strong and coordinated strategy to maintain consistent and reliable
quality. Here are the essential elements for success:
o
Standardization
of Processes: It's
crucial to use the same procedures and protocols at all locations. This
consistency guarantees
that each step of the quality control process is uniform, helping to meet
international regulatory standards. o
Centralized
Quality Management System (QMS):
A centralized QMS improves the oversight and management of quality at all
sites. It should include thorough documentation, data management, and
communication tools that everyone can access, helping to keep quality practices
uniform and addressing any issues quickly. o
Training and
Development:
Continuous, in-depth training for all staff involved in quality control is
crucial. Well-trained employees across all sites maintain high-quality
standards. o
Advanced
Analytical Tools and Technologies:
Modern analytical tools and technologies increase the precision and efficiency
of quality control. Automation and digital tools minimize human error and allow
for real-time data analysis, speeding up decision-making and problem-solving. o
Robust
Communication Channels:
Strong communication is essential. Regular meetings, updates, and reviews
ensure all teams are on the same page and any problems are addressed swiftly. o
Continuous
Improvement and Adaptation:
Quality control should always be evolving through ongoing monitoring,
evaluation, and enhancement. A culture of continuous improvement, where
feedback is actively sought and implemented, greatly improves quality
consistency. o
Quality Audits
and Inspections:
Frequent audits and inspections, both internal and external, ensure each site
meets quality standards. These also identify areas for improvement and
facilitate the sharing of best practices. By focusing on
these key areas, WuXi Biologics can effectively handle the complexities of a
multi-step quality control process across multiple global locations, ensuring
consistent and reliable product quality. To date, we have passed over 40
inspections by multiple global regulatory agencies, including FDA, EMA, NMPA, and
received 97 license approvals, with a 100% success rate in Pre-License
Inspection (PLI). We continue to safeguard our data integrity to maintain our
strong track record, with zero issues found regarding data integrity during
regulatory inspections. Our PPQ success rate exceeds 98%, positioning us as one
of the top performers in the industry and showcasing our premier and reliable
quality.
How are new technologies
driven/continuing to drive advances in quality? New
technologies are crucial in enhancing quality assurance across various sectors,
including the manufacturing of biologic drugs. These innovations improve
accuracy, efficiency, and adherence to regulations, ultimately boosting the
quality and safety of products. Here are some key ways new technologies are
advancing quality: o Automation and
Robotics: Automation
minimizes human errors and enhances the consistency of production processes.
Robots perform repetitive tasks with high precision, essential in settings
where small deviations can cause major quality issues. o Data Analytics: Advanced data analytics
provides deeper insights into quality control processes. Companies can leverage
datasets to foresee potential failures and deviations, enabling proactive
quality management. Real-time data analysis is crucial for making quick
corrections to maintain high-quality standards. o Internet of Things
(IoT): IoT
devices monitor and gather data from various stages of the manufacturing
process. This connectivity allows for real-time monitoring and control,
ensuring any deviations are quickly detected and corrected, thus maintaining
the quality control process's integrity. By
integrating these technologies into quality assurance processes, companies can
not only meet but surpass regulatory standards, cut costs related to quality
issues, and boost customer satisfaction by consistently delivering high-quality
products. Your proprietary bispecific antibody platform WuXiBody™ is said to
accelerate product discovery by up to 18 months; how did you calculate/estimate
that time saving, and how is it achieved with this technology platform?
The unique design of WuXiBody™ enhances the developability
characteristics of bispecifics, facilitating an accelerated development
timeline. WuXiBodyTM adopts an innovative design where the CH1/CL
region of one antibody Fab is replaced by the corresponding T cell receptor
(TCR) Cβ/Cα domains to promote correct heavy-light chain pairing. The
characteristics of this domain can differentiate the target heterodimer from
homodimers for easier removal of homodimers. The mAb-like CMC performance
accelerates the drug development process for bispecifics developed by WuXiBodyTM.
In addition, our extensive experience in CMC development could
further ensure the delivery timeline by de-risking the potential rate-limiting
steps, such as transfection ratio study, homodimer method development, clone
selection involving downstream team, and CIU low concentration
evaluation/development.
Based on the widespread adoption of WuXiBodyTM platform
in bispecific antibody discovery, we have upgraded it to deliver transformative
and customized multi-specific antibodies, addressing the growing global demand
for these complex molecules.
WuXi Biologics has patented a number of new technology platforms
over the past couple of years – this suggests that somewhere in your C-suite a
strategic decision was made couple of years ago to pursue a
pioneering path with patented technologies forming a core part of your contract
development and manufacturing business. What triggered that insight, which is
now yielding clear fruits in terms of market differentiation?
Balancing speed, quality, and cost remains one of the greatest
challenges in drug development. As a CRDMO, our continual launch of new
technology platforms comes from our drive to push boundaries and foster
innovation – all with the goal of enabling our global partners to rapidly bring
more high-quality and affordable biologics. As of December 31, 2024, WuXi
Biologics is supporting 817 integrated client projects, which is one of the
largest portfolios of complex biologics, consisting of mAbs (328), bispecifics and
multispecifics (151), ADCs (194), fusion proteins (80) and vaccines (24) as
well as other proteins (40).
Our clients are investing in next-generation biologics such as bispecific
antibodies and multispecific antibodies to provide patients with innovative
therapies that can save their lives or improve their quality of life. In
response to this demand, we have developed a universal platform, WuXiBodyTM,
to enable our partners to take any mAbs and engineer these into a
highly-functional multispecific constructs. This platform has been widely
adopted by global clients, with over 40 WuXiBodyTM
projects currently at different R&D stages.
In October 2024, Merck completed the acquisition of CN201, a novel
investigational clinical-stage CD3xCD19 bsAb for the treatment of B-cell
associated diseases, from Curon Biopharmaceutical, a client of WuXi Biologics. CN201
is one of the best examples that demonstrate how our proprietary platforms
enable our clients’ success. By combining our unique low-affinity anti-CD3 mAb,
which binds and dissociates rapidly, with the WuXiBodyTM platform,
the resulting TCE molecule CN201 showed deep and sustained B cell depletion,
along with reduced toxicity due to a lower level of cytokine release syndrome.
Other technology platforms, including TCE platform, ultra-high productivity continuous
bioprocessing platform WuXiUPTM, and the high titer production CHO
K1 cell line development platform WuXiaTM have also been applied in
the R&D of CN201, which contributes additional value to this molecule and
makes it an attractive asset for the acquisition deal.
In January 2025, we announced an agreement with Candid
Therapeutics under which Candid will have exclusive global rights to a
preclinical trispecific T-cell Engager discovered at WuXi Biologics’
proprietary universal multispecific antibody platform WuXiBody™. WuXi Biologics
is eligible to obtain an upfront payment, and development and sales milestones
totaling up to $925 million as well as royalties.
You have patented six platforms that accelerate development and
manufacturing for various types of Biologics. What are the comparative demands
for these various technologies, and do they predict future trends in
Biologics?
By leveraging a wide range of technology platforms in discovery (WuXiBodyTM,
SDArBodyTM), development (WuXiaTM, WuXianTM,
WuXiUPTM, WuXiUITM) and manufacturing, we provide reliable
and flexible services tailored to accommodate our clients’ diversified
requirements for different modalities and stages.
From
the current industry perspective, bsAb and antibody-drug conjugates (ADCs) have the best potential
growth in the biologics field over the next 5-10 years. Although the study and
commercialization of mAbs have reached a high level of maturity after decades
of development, the ongoing challenge of enhancing product safety and efficacy
continues to drive industry-wide efforts.
Many
years ago, we had foreseen this trend and accordingly built the WuXiBodyTM and WuXiDar4TM, a platform designed
to enhance DAR4 (four payload molecules per mAb) percentage in the final ADC product
and improve conjugation efficiency. Currently, 151 bsAbs/multispecific and 194 ADCs are under development at WuXi Biologics, accounting for over
40% of the total projects we serve for our global clients. The increased ratio
of new modalities in recent years is also a testament to our success in meeting our clients' needs
and predicting future industry trends.
Continuous
processing is a next-generation solution for biomanufacturing, designed to
address the production difficulty and inefficiency of either
labile/difficult-to-express or low-expressing-level proteins with minimized
environmental impact and resource demand. Our WuXiUPTM platform
employs an intensified perfusion culture process and continuous harvest,
allowing for the manufacture of different types of pharmaceutical proteins with
significantly higher productivity (10–20X greater) compared with traditional
fed-batch and perfusion culture. The WuXiUPTM platform achieves not
only higher productivity but also significantly reduces resin usage, with a
smaller facility footprint. Meanwhile, our ultra-intensified fed-batch
bioprocessing platform, WuXiUI™, has enhanced upstream productivity by 3-6
times compared to traditional fed-batch cultures, and has doubled the capacity
for downstream purification processing while achieving comparable impurity
removal. This advancement has resulted in a 50% reduction in downstream
processing time and has facilitated a 30-50% decrease in the consumption of
materials and consumables, thereby significantly reducing waste generation. All
these factors collectively lead to substantial cost savings and reduced
environmental impact on protein mass basis,which aligns with the industry trend in sustainability.
Are all of these technologies scalable for GMP
manufacturing?
Leveraging our state-of-the-art discovery and development
technology platforms, numerous clients’ projects have been advanced to GMP
manufacturing with high quality. To date, we have constructed more than 900 stable
cell lines for clinical and commercial production using WuXiaTM
platform. WuXiUPTM processes have been successfully applied to 50 different molecules (e.g., mAbs, BsAbs, fusion
proteins and enzymes) with over 20 processes scaled up to clinical and
commercial GMP manufacturing, among which 11 successful INDs and 1 BLA approval
have been achieved with an average 7-fold productivity increase. In August 2024,
we have successfully accomplished 2,000L drug substance (DS) GMP manufacturing
by utilizing WuXiUI™. The platform achieved a titer of 18 g/L, a 4-fold
increase compared to the conventional fed-batch process.
Are you able to give us a scoop on any other technologies in
development that you might be launching soon?
Derived from
the highly-vetted WuXia™ CHO-K1 cell line, we launched two new cell line
platforms, WuXiaADCC PLUS™, a superior-performing and high-yielding
mammalian cell line platform for the development and manufacturing of
afucosylated antibodies, and WuXia RidGS, a high-yield glutamine synthetase
(GS)-knockout Chinese hamster ovary (CHO) expression system platform in 2024. In
2025, we’ll launch several new cell line platforms to meet global clients’
diversified needs.
WuXi Biologics has achieved remarkable success since 2018 – it's
easy to forget what a young company it is! What is your vision for the next six
years?
Our
commitment to our clients and patients has been the cornerstone of our success.
Moving forward, we are going to intensify our efforts to expand our client
base. This means not just reaching new markets, and new segments, but creating
deeper, more value-driven partnerships. We're pushing the boundaries of what a
CRDMO can achieve by diversifying our solutions and exploring new modalities
and business avenues, to empower clients’ success and benefit patients
worldwide.