By 2028, the cell and gene therapy (CGT) landscape may face a crisis of its own making. Projections show that as much as half of the industry’s newly built manufacturing capacity could sit dormant. This isn’t a story of collapsing demand or a sudden freeze in capital. It’s the story of a critical, and widely underestimated, bottleneck: a profound shortage of the specialized human expertise required to develop, validate, and release these complex products.
For years, the dominant narrative in biomanufacturing has been one of physical scale. The industry mantra was simple: build more, build bigger. Companies raced to pour billions into state-of-the-art cleanrooms and bioreactors, believing that the primary constraint to meeting the promise of cell and gene therapy was a lack of square footage.
That era is over. The problem is no longer one of steel, but of talent. The new pinch point has shifted from the construction site to the quality control lab. As regulatory standards tighten and the complexity of these therapies increases, the true gatekeepers of progress are the MSAT (Manufacturing, Science, and Technology) and analytics leaders who can make these treatments real, repeatable, and defensible. Without them, the billions invested in infrastructure are just that: empty rooms waiting for a green light they may never get.
The Strategic Pivot: Smart Money Follows Talent, Not Just Footprints
The most forward-thinking players in the industry are already adapting to this new reality. A close look at recent strategic investments reveals a clear pattern: a pivot away from simply adding undifferentiated capacity and a doubling down on specialized capabilities. These companies aren’t just building bigger facilities; they’re building smarter ones, designed to solve the industry’s most pressing technical challenges.
Consider the recent moves by major CDMOs and developers:
- FUJIFILM Diosynth Biotechnologies’ Strategic Bet: In early 2025, the company’s decision to prioritize investment in its new North Carolina mega-site wasn’t just about adding volume. It was a calculated move to build a facility from the ground up with the advanced technologies and integrated quality systems needed for next-generation biologics. This signals a clear understanding that strategy is trumping raw scale, and that future success depends on having the right capabilities, not just the most space.
- Bionova Scientific Tackles the Upstream Bottleneck: Recognizing a critical vulnerability in the supply chain, Bionova Scientific (an Asahi Kasei company) opened its new plasmid DNA facility in Texas in August 2025. This is a direct bet on ensuring QA and supply reliability for a critical starting material. High-quality plasmid DNA is the foundation of any successful viral vector campaign, and by bringing this capability in-house, Bionova is addressing a major source of delays and failures before they can derail a program.
- Novartis and AGC Biologics Build for Control: Novartis’s move to bring its VIFA One site in Slovenia online in mid-2025 is a clear play to insource its AAV supply, giving it greater control over quality and timelines. Similarly, AGC Biologics’ continued ramp-up of its Yokohama facility, targeting full GMP status by 2026, is an investment in end-to-end control over the complex manufacturing process.
On paper, these massive investments should mean that the industry’s long-standing vector supply shortage is easing. But in practice, they reveal a deeper truth. The bottleneck hasn’t disappeared; it has simply migrated. The new constraint is the availability of MSAT and analytics leaders who possess the rare combination of scientific acumen and regulatory savvy needed to make vectors real, repeatable, and defensible under the harsh light of regulatory scrutiny.
Where Programs Are Breaking: The Four Horsemen of the CMC Apocalypse
The shift from a “steel” problem to a “talent” problem is being driven by a dramatic increase in regulatory expectations. For years, programs with promising clinical data could often navigate the CMC (Chemistry, Manufacturing, and Controls) process with a strategy that was “good enough.” Today, “good enough” consistently fails. The FDA and other global regulators are no longer giving the benefit of the doubt, and they are laser-focused on four key areas where programs are consistently breaking.
1. The Assay Lifecycle Gauntlet
The release of the finalized ICH Q14 and Q2(R2) guidelines in 2024, with training rolled out in July 2025, marked a point of no return for analytical development. These guidelines formalize the concept of the “assay lifecycle,” forcing companies to treat their analytical methods not as static procedures, but as products in their own right that must be understood, validated, and managed from development through commercialization. This new paradigm requires a deep, first-principles understanding of method performance, variability, and robustness. The days of simply qualifying an assay and hoping it holds up are over. Regulators now demand a comprehensive data package that proves a method is fit for purpose throughout the product’s lifecycle.
The consequences of failing to meet this new standard are severe.
Ultragenyx’s UX111 CRL in July 2025 was a wake-up call for the entire industry. Despite strong clinical data – which the FDA’s clinical reviewers acknowledged was “robust” – the program was halted by a weak CMC package. The message from regulators was unequivocal: compelling efficacy cannot rescue a poorly characterized product.
2. The Shift to Potency Assurance
For years, the central question from regulators regarding potency was, “What is your potency test?” In 2025, that question has evolved into something far more demanding:
“What is your potency assurance strategy?”
This is not a semantic shift. A “potency test” is a single analytical method. A “potency assurance strategy” is a comprehensive, multi-faceted approach that links the product’s mechanism of action (MoA) to a matrix of characterization and release assays. It requires a deep understanding of the product’s critical quality attributes (CQAs) and a suite of orthogonal methods that, together, provide confidence that every batch produced is not just pure, but biologically active and clinically effective.
The
July 2025 CRLs for both Ultragenyx and Capricor proved that potency is now a primary gatekeeper for approval. Both companies were stalled by questions surrounding their potency strategies, demonstrating that without a robust and well-justified approach, a program will not advance, regardless of how effective it appears to be in the clinic.
3. The Capsid Analytics Reckoning
July 2025 will be remembered as the month of the “CMC Reckoning,” as multiple companies, including Ultragenyx, Capricor, and (stretching back to 2024)
Rocket Pharmaceuticals, received CRLs or clinical holds directly tied to manufacturing data gaps. A central theme in these regulatory actions was the inadequacy of product characterization, particularly concerning viral capsids.
For AAV-based therapies, the ratio of full (gene-carrying) capsids to empty ones is a critical quality attribute that directly impacts both safety and efficacy. The
USP draft chapter in June 2025, which formally recognized Mass Photometry, was a landmark event. It officially raised the analytical bar, signaling that regulators expect companies to use modern, orthogonal methods to provide a more accurate and nuanced picture of their product. This puts immense pressure on analytics teams to not only implement these new technologies but also to develop the expertise to interpret the complex data they generate.
4. The Unforgiving Scrutiny of Plasmid QA
The entire gene therapy manufacturing cascade begins with a deceptively simple input: plasmid DNA. Yet, this critical starting material is increasingly becoming a source of catastrophic failure. The
August 2025 FDA 483 inspection report at the Novo/Catalent Bloomington facility read like a horror story: cat hair, pests, and microbial failures. The fallout was immediate and severe, leading to a delay for Regeneron’s Eylea HD and a CRL for odronextamab.
This event starkly illustrates the principle of “garbage in, garbage out.” A flawed starting material will inevitably lead to a flawed final product, and no amount of downstream purification can fix a problem that begins on day one.
In stark contrast, specialist suppliers are demonstrating their value. The successful inspection outcomes for
Aldevron (NAI in November 2024) and VGXI (inspection enabling a client BLA in May 2025) show that deep expertise and a relentless focus on quality are winning. These companies understand that plasmid QA is not a commodity; it is a highly specialized discipline that is fundamental to the success of the entire CGT enterprise.
The Data Doesn’t Lie: A Market Facing a Talent Mismatch
The market data paints a clear, if paradoxical, picture. The demand for cell and gene therapies is exploding, with the CGT CDMO market projected to grow to $75 billion by 2034 at a staggering 28% CAGR.
Yet, this explosive growth is happening alongside a deeply dysfunctional talent market. Broader biotech layoffs have created a superficial surplus of talent; one unverified but illustrative report from Q1 2025 suggested that while overall job postings fell by 20%, applications skyrocketed by 91%. This has created a false sense of security for some, who see a market flooded with résumés.
The reality is that this is a market of generalists. The specialists – the vector MSAT experts, the potency assay gurus, the capsid analytics wizards – remain incredibly scarce. The same report indicated that these critical hires still take an average of 78 days to fill. This is the data that matters. It proves a severe mismatch between the skills the industry has and the skills it desperately needs.
The companies that understand this – FUJIFILM Diosynth Biotechnologies, Bionova Scientific, Novartis, AGC Biologics, Aldevron, and VGXI – are the ones making the strategic investments in expertise, not just footprint. They are building a moat of talent that will be difficult, if not impossible, for their competitors to cross.
Why This Matters: The Coming Capacity Crunch
The conclusion from this evidence is both simple and alarming. A GMP suite is relatively easy to fund and build. A robust, defensible, GMP release package is not.
Billions of dollars are being poured into constructing cleanrooms. But unless the industry’s ability to execute on assay maturation, potency assurance, capsid analytics, and plasmid QA catches up, a large and growing share of that expensive new capacity will sit idle, unable to release a single batch of product.
By 2026, the winners in the CGT space will not be the companies with the most square footage. They will be the ones with the shortest validated release timelines. This is a talent problem, not a steel problem. And for any company or investor performing due diligence on a vector CDMO tomorrow, the first and most important question shouldn’t be about the size of their bioreactors. It should be a direct test for the red flags that are actually derailing programs:
- Assay lifecycle?
- Potency assurance?
- Capsid analytics?
- Plasmid QA?
The answers to these questions will determine who succeeds, and who is left with a very expensive, very empty building.
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