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Navigating Clinical Holds in Cell and Gene Therapy Development

Cell and gene therapies (CGTs) are no longer the future—they’re the now. These therapies are revolutionizing medicine, offering hope to patients battling diseases once thought incurable. But as groundbreaking as CGTs are, the road from lab to market is anything but easy. One of the biggest hurdles developers face? Clinical holds.

Clinical holds can derail a promising therapy’s timeline, delaying life-saving treatments and causing significant financial and reputational setbacks. Let’s explore what causes clinical holds, why they’re so common in CGTs, and how developers can avoid them.

Why Are Clinical Holds So Common in CGT Development?

Clinical holds happen when the FDA determines that an investigational new drug (IND) application doesn’t meet the safety or regulatory requirements to move forward with clinical trials. In CGTs, they’re surprisingly frequent. While these therapies make up less than 2% of all clinical trials, they account for a staggering 40% of clinical holds. Why? It boils down to the complexity of CGT development and the stringent standards set by regulators.

One of the most common reasons for these holds is deficiencies in Chemistry, Manufacturing, and Controls (CMC), especially around potency testing. As Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, put it: “One of the key things that has delayed a fair number of approvals over the course of time has been issues related to potency.”

The Potency Testing Challenge

In simple terms, potency testing ensures that a therapy works as intended and at the right strength. Sounds straightforward, right? Not so much. For traditional drugs, potency is usually measured through a single bioassay. But CGTs are far more complex, often requiring a “matrix” of multiple assays to fully capture their biological activity.

Developing these assays is a science in itself. They need to be precise, sensitive, and reproducible, while meeting rigorous standards for validation and documentation. Skipping steps or rushing this process can lead to clinical holds—and costly delays.

Start Early to Stay Ahead

The FDA strongly recommends starting potency assay development early in the IND process. Why? Because creating and validating these assays take time—often up to 18 months. Early development allows room for refinement, data collection, and alignment with regulatory expectations.

Here’s what early preparation looks like:

  • Identifying the product’s mechanism of action and key quality attributes.
  • Developing a preliminary potency strategy, with plans to refine it as data becomes available.
  • Conducting initial tests to ensure assays are accurate and reliable.

While some developers may hesitate to invest heavily in early assay development, waiting too long can backfire. Insufficient preparation is a surefire way to end up on clinical hold, potentially costing millions in delays.

The Path to Success: A Strategic Approach

Developing CGTs is a marathon, not a sprint. To avoid clinical holds, it’s essential to have a well-thought-out strategy that addresses potential roadblocks before they arise. This means:

  1. Prioritizing early potency assay development.
  2. Conducting thorough validation and documentation to satisfy regulatory requirements.
  3. Collaborating with experienced partners who understand the nuances of CGT development.

That’s where Solvias comes in. With decades of expertise in assay development Solvias is uniquely positioned to guide CGT developers through the complexities of potency testing and CMC requirements.

Expanding Expertise in the U.S.

Solvias is taking its commitment to CGT innovation a step further with a new Center of Excellence in Research Triangle Park, North Carolina. This state-of-the-art facility, set to open in 2025, will provide tailored solutions for CGT developers, from early assay development to post-commercialization testing.

With a global network and a personalized approach, Solvias is ready to help your therapy reach the market faster—and safer.

The Bottom Line

Clinical holds are a significant challenge in CGT development, but they’re not insurmountable. With early preparation, strategic planning, and the right partners, developers can minimize risks and keep their programs on track.

If you’re navigating the complexities of CGT development, reach out to the experts at Solvias. Let’s turn challenges into opportunities—and breakthroughs into reality.

Want to learn more about CGT development? Contact us or visit us at https://www.solvias.com/