Cell & Gene Therapies Are Under the Microscope—And Few Are Passing

Cell & Gene Therapies Are Under the Microscope—And Few Are Passing

FDA Uncertainty: Why First-Cycle Approval Is Now a Matter of Survival

Leadership shake-ups, budget cuts, and philosophical shifts inside the FDA have pushed the review process for biologics, advanced therapies, and any cold-chain-sensitive product into uncharted territory. Predictability is gone, reviewer experience is thinning, and the agency’s tolerance for ambiguity has dropped to near zero. In this six-part series we expose the new flashpoints that can sink a submission—and show you how to bullet-proof yours before it ever reaches the agency’s desk.

Cell and gene therapies (CGTs) represent some of the most groundbreaking science in modern medicine. But in the eyes of regulators, they also represent some of the highest-risk products on the market—logistically complex, temperature-sensitive, and operationally fragile from end to end.

Recent developments have sent a chilling message across the advanced therapy landscape: the FDA is no longer extending flexibility to sponsors with gaps in their cold chain, manufacturing, or chain-of-custody strategy. In fact, applications are being declined at alarming rates—not because the therapies don’t work, but because logistics risk hasn’t been fully mitigated.

Here’s what could be fueling these shifts:

• CGT applications are being turned away due to inconsistencies in transport protocols and chain-of-custody procedures
• Regulators are demanding real-time visibility and control from collection to administration—especially for autologous and cryogenic products
• Sponsors who merely acknowledge cold chain risks are no longer getting the benefit of the doubt—they must eliminate or engineer around them

This is particularly devastating for smaller biotech firms, where a single failed review can decimate timelines, funding, and credibility. Even firms with strong clinical data discover that regulatory approval can still fall apart at the cold chain.

Modality Solutions specializes in making sure that it doesn’t happen to you.

We help CGT developers proactively engineer shipping and storage strategies that are defensible from day one. Our work integrates cold chain validation into the therapy’s entire vein-to-vein control architecture—so the FDA sees not just a product, but a complete and robust delivery system.

We support sponsors with:

• Thermal packaging qualification, including LN2 and dry ice conditions
• Real-world deviation testing aligned to clinical logistics (e.g., airport tarmac delays, customs bottlenecks)
• Simulated transport route stress profiles for critical nodes in the supply chain
• Submission-ready documentation that ties shipping validation to FDA CMC expectations and IND/BLA frameworks

For example, one CAR-T developer faced a catastrophic review risk due to SOP inconsistencies across clinical trial sites. There was no harmonized process for shipper reuse, packaging inspection, or time-out-of-environment tracking. Modality Solutions was brought in just weeks before submission. We standardized procedures, validated transport tolerances, and built a unified data package that told a clear and compelling regulatory story. The application was approved—cold chain risks neutralized.

The takeaway is stark: No matter how effective your therapy, if your cold chain strategy raises doubt, it can—and will—stop your submission cold.
Regulators do not want assumptions. They want proof.

• Proof that your product survived its journey intact
• Proof that every temperature deviation was modeled and mitigated
• Proof that your chain of custody is airtight from the patient to the vial and back again

With Modality Solutions, you’re not just responding to the new regulatory climate—you’re mastering it.
Because in the world of CGT, logistics failure isn’t a setback—it’s a death sentence for your approval.

How Modality Solutions Can Help You
From cryogenic shipper qualification to chain-of-custody analytics, we integrate logistics validation into your therapy’s entire control architecture. Reviewers get airtight proof that the product remains potent from collection to infusion—turning a perceived weakness into a decisive competitive advantage.

Frequently Asked Questions:

Q: Why are cell and gene therapies facing stricter FDA reviews?
A: They are logistically complex, fragile, and highly temperature-sensitive. Regulators no longer grant flexibility for gaps in cold chain or chain-of-custody strategies.

Q: What specific risks are causing CGT applications to fail?
A: Inconsistent transport protocols, weak chain-of-custody procedures, and inadequate real-time visibility across the supply chain.

Q: What level of proof does the FDA now require for CGTs?
A: Proof that the product remains potent end-to-end, every deviation is modeled and mitigated, and chain of custody is airtight.