Arc Nouvel works with biotechnology and pharmaceutical companies at inflection points, pre-IND preparation, early clinical transitions, manufacturing evolution, and regulatory engagement. At these moments, scientific promise alone is not enough. What determines whether a therapy advances efficiently or stalls under regulatory pressure is often the unseen structure beneath it: CMC.
To understand what that structure requires in today’s advanced therapy landscape, we spoke with Dr. Gavin Liu, CMC and technical development leader and Consultant at Arc Nouvel. His career traces the full arc of modern cell therapy development, from academic immunology research to hands-on CAR-T manufacturing, platform leadership, GMP execution, regulatory package strategy, and CDMO oversight.
In this article we will explore not just the technical depth of his journey, but a disciplined way of thinking about risk, scalability, and regulatory consequence.
From Academic Immunology to CMC
Dr. Liu began his career in academic immunology, earning his PhD from Peking University before completing postdoctoral training at UCSF. He later joined the University of Washington, where his research focused on tumor biology and immune modulation, particularly strategies to reactivate NK cells and T cells against cancer.
At the time, the work was intellectually rigorous and scientifically exciting. The goal was clear: understand how to manipulate immune responses to eliminate tumors. But translation into real therapies still felt distant.
That changed in 2016–2017, when the first CAR-T therapies began entering clinical practice.
“When I saw the first CAR-T product entering the clinic, it was a very exciting moment,” he recalls. “I realized what we had been working on in the lab could truly change a patient’s life.”
The shift was profound. Immune engineering was no longer theoretical. It was therapeutic.
“I saw that the work in the lab was not just publications anymore,” he says. “It was something that could directly impact patients.”
That realization prompted a decisive move into industry. Dr. Liu joined one of the early CAR-T pioneers, stepping into an environment where scientific elegance had to be matched by reproducibility, control, and regulatory defensibility.
There, he learned not only how to culture cells at scale, perform viral transduction, and manage harvest and formulation, but how those activities must integrate with analytical development, quality systems, and regulatory expectations.
“In industry, you cannot just show that it works once,” he explains. “You have to show that it works consistently, that it is controlled, and that you can explain it to regulators. Manufacturing is evidence generation,” he says. “Every decision you make will eventually be reviewed.”
That realization marked the beginning of his evolution, from immunologist to CMC expert.
Thinking Two Steps Ahead
In early-stage development, process adjustments often feel incremental. A change in activation time improves expansion. A different reagent enhances transduction efficiency. An additional assay provides more data.
But Dr. Liu saw how these “small” decisions reverberate.
“That experience taught me to always think two steps ahead,” he explains. “How will today’s decision affect GMP manufacturing? How will it affect comparability? How will regulators view this six or twelve months from now?”
He experienced firsthand the consequences of early shortcuts. A material substitution introduced unexpected variability during tech transfer. An assay lacking mechanistic alignment became difficult to justify in an IND. Documentation gaps created avoidable questions in agency meetings.
These lessons shaped a habit of structured anticipation. Before approving a change, he evaluates scalability, controllability, and long-term regulatory perception.
Building From Scratch
As he advanced into leadership roles, including platform development for CAR-NK therapies, Dr. Liu encountered environments with limited precedent. Emerging cell therapy modalities lacked established best practices. Processes had to be designed from first principles.
“We had very few references,” he says. “We had to think carefully about scalability and robustness from the beginning.”
Without historical templates, foresight became even more critical. The team needed to define critical quality attributes, align potency assays with mechanism of action, and anticipate how processes would evolve as programs progressed from preclinical work to Phase I.
This experience reinforced an essential lesson: you do not need a commercial-ready process on day one, but you must design a process capable of evolving without structural disruption.
Framework first. Optimization later.
CMC is a Strategic Enabler
The most defining realization in Dr. Liu’s career did not come from a scientific breakthrough. It came from watching strong science struggle.
He recalls observing programs with compelling biological rationale and even encouraging early clinical activity fail to maintain momentum because the CMC foundation was fragile.
“It became clear to me that CMC is not just operational support,” he reflects. “It is a strategic enabler.”
In these cases, the biology generated enthusiasm. Early patient responses created optimism. But when the program moved into regulatory dialogue, structural weaknesses surfaced. Control strategies were loosely defined. Potency assays were insufficiently aligned with mechanism of action. Specifications lacked clear scientific justification. Process evolution plans were unclear.
“The science was strong,” he says. “But the CMC package was not ready to support it.”
In advanced therapies, regulators understand early-phase uncertainty. They do not expect commercial perfection at Phase I. But they do expect coherence.
“They expect logic. They expect consistency. They expect a clear risk mitigation strategy,” Dr. Liu explains. “They want to see that you understand your product and that you know how it will evolve.”
When that clarity is present, regulatory discussions become constructive. When it is absent, they become corrective.
“A strong CMC strategy accelerates development because it builds confidence,” he says. “When regulators see a structured plan, they are more comfortable with the uncertainty.”
Conversely, gaps in CMC create friction. Programs must pause to generate additional comparability data. Assays must be redesigned. Specifications must be rejustified. Documentation must be restructured. These are not minor adjustments, they affect timelines, capital allocation, and investor confidence.
“You can have promising biology,” he adds, “but if your manufacturing is unstable or your assays are not well justified, the program can slow down very quickly.”
Move Fast Without Accumulating Technical or Regulatory Debt
Oncology today moves at extraordinary speed. New cell therapy programs emerge almost weekly. Patients urgently need new options. Investors demand progress that is visible and defensible. Competitive positioning can shift within months.
Yet cell therapies do not tolerate recklessness.
“Speed doesn’t come from cutting corners,” Dr Liu says. “It comes from making informed decisions.”
That distinction is critical. In his experience, the illusion of acceleration often produces delay. Programs that rush into regulatory interactions without structured CMC planning frequently encounter requests for additional information. Missing justification for potency assays triggers agency questions. Incomplete comparability strategies lead to bridging studies that were never budgeted.
“Acceleration without structure creates rework,” he explains. “And rework is the slowest path.”
He has seen companies believe they are moving quickly, only to discover that incomplete CMC planning forces them backward. Regulatory questions surface not because the science is weak, but because the supporting framework lacks clarity.
“If you define your critical quality attributes early, align potency with mechanism of action, and design a scalable process from the start, you actually move faster,” he says. “You prevent the problems that cause delay.”
Importantly, he emphasizes that regulators are not adversaries. They understand early-stage uncertainty. They do not expect perfection in Phase I.
“They expect logic. They expect consistency. They expect a clear risk mitigation strategy,” he notes. “If you can show that you understand your risks and how you will manage them, the discussion becomes constructive.”
His objective, as he frames it, is to help teams “move fast without accumulating technical or regulatory debt.”
That debt, he explains, is rarely visible at first. It accumulates quietly in documentation gaps, assay immaturity, and loosely defined control strategies. But once regulatory review begins, it becomes expensive.
“Every shortcut has a cost,” he adds. “The question is whether you pay it early with planning, or later with delay.”
For emerging sponsors, that distinction can determine survival.
GMP Manufacturing
If early development is where strategy is designed, GMP manufacturing is where it is tested.
The transition from development to GMP is one of the most fragile stages in cell therapy programs. It is where theoretical control must become operational control.
Dr. Liu has observed recurring vulnerabilities at this stage.
One of the most common is potency assay design that lacks mechanistic grounding.
“In cell therapy, potency must reflect biological function,” he explains. “You cannot use a generic assay and assume it will satisfy regulatory expectations.”
Different modalities require different logic. A CAR-T cell, a bispecific antibody, and a vaccine operate through distinct mechanisms. Potency assays must align with that biology.
“FDA may not require a perfect assay early,” he says, “but they require a meaningful design. You must show why this assay reflects how your product works.”
Another vulnerability is inadequate specification definition. Target product profiles and quality attributes must be anchored in product understanding.
“Specification is not just a number,” he notes. “It must be scientifically justified. Otherwise, it becomes very difficult to defend.”
Without clear linkage between quality attributes and clinical relevance, specifications appear arbitrary, and arbitrary thresholds invite scrutiny.
Perhaps the most underestimated challenge is tech transfer to CDMOs.
“Tech transfer is not document sharing,” he says. “It is a data-driven exercise.”
Differences in facility configuration, equipment, materials, and analytical methods require structured evaluation. Comparability studies are not optional formalities, they are the evidence regulators will expect.
“If you don’t plan comparability properly, FDA will ask for that evidence,” he explains. “Consistency and robustness are fundamental.”
He has seen scenarios where performance metrics shift significantly between facilities, raising questions that could have been anticipated earlier.
“You cannot have seventy percent performance in one facility and thirty percent in another without explanation,” he says. “That creates concern immediately.”
At the GMP stage, regulatory expectations are heightened and timelines compressed. Planning gaps that were tolerable in development become consequential.
GMP does not expose new problems. It exposes unaddressed ones.
The Underestimated Variable: Patient Variability
Autologous cell therapies introduce a layer of complexity that is fundamentally different from traditional biologics: the starting material is human, and every human is different.
“Each patient is different,” Dr. Liu emphasizes. “That is something we often underestimate.”
Differences in immune cell composition, prior therapies, disease progression, and overall health affect the quality of starting material. That variability influences expansion kinetics, transduction efficiency, and final product characteristics.
“You cannot assume that what works for one patient will work exactly the same for another,” he says. “You must design your process to absorb variability… It’s not only about the process, it’s about materials, logistics, operator training, facility validation, documentation, and GMP technique. Everything must work together.”
Mitigation strategies for starting material variability must be considered early. Without them, downstream inconsistency becomes inevitable.
“If you don’t have a comprehensive CMC mindset,” he says, “you will face challenges later, especially when you combine clinical development and manufacturing.”
In cell therapy, clinical and CMC functions are inseparable. Safety signals, product variability, and process controls intersect directly.
“CMC is not one workflow,” he adds. “It is an interconnected ecosystem.”
That ecosystem must be designed deliberately, not patched reactively.
The Future of CAR-T and the Expanding Role of CMC
CAR-based therapies are evolving rapidly. Beyond oncology, applications in autoimmune diseases are expanding. Construct designs are progressing from early generations to more sophisticated configurations aimed at durability, safety, and scalability.
As innovation advances, CMC complexity increases. Manufacturing must support increasingly engineered constructs. Global scalability becomes essential. Cost considerations grow.
“The field is maturing,” Dr. Liu observes. “CMC is playing an increasingly central role in enabling this process.”
At the conclusion of our discussion, Dr. Liu offered a concise recommendation.
“Before you engage regulators, have experienced eyes review your CMC strategy.”
CMC is structurally complex and unforgiving of oversights. Early decisions shape downstream obligations. Some changes are manageable. Others are difficult to reverse.
In advanced therapies, innovation captures attention. Structure earns approval.
Why Arc Nouvel
Arc Nouvel had an increasing need for advanced therapy CMC expertise to complement its strong oncology and biologics leadership. At that time, Dr. Liu was introduced through a mutual connection and quickly became a valuable addition to the team.
Dr. Liu was particularly impressed by the firm’s regulatory pedigree and practical orientation.
“It’s about helping sponsors make decisions that stand up to regulation and move programs forward efficiently,” he says.
Arc Nouvel does not offer theoretical templates. It offers experience grounded in real regulatory interactions and global oncology development.
Filling a Market Gap
Today’s biotech environment is capital constrained. Many companies reduce internal headcount and rely heavily on external vendors. Few can justify building full in-house advanced therapy CMC leadership.
Dr. Liu believes Arc Nouvel is especially valuable for small and mid-sized biotech companies approaching critical regulatory milestones such as pre-IND meetings or early clinical development.
“These companies often have strong science,” he explains, “but they may not have experience across regulatory expectations in different functions.”
Arc Nouvel establishes the structural framework. Sponsors then populate it with their data. This integrated guidance prevents costly missteps and reactive remediation.
For emerging companies, that difference can determine survival.
