Quality Management in Cell and Gene Therapy: Common Challenges and Solutions

This is one of the biggest risks I see in small biotech companies—especially in cell and gene therapy. These teams are small, often just 15 to 20 people, and each person holds a tremendous amount of knowledge about the product. I’ve seen companies where someone who has been with the team for five years leaves, and suddenly, all of that knowledge about the product’s raw materials, processes, and development stages is gone. The replacement might have similar qualifications, but they’re not going to come in with that specific knowledge, and that can lead to major disruptions in clinical or manufacturing phases. I had a client who lost their most important manufacturing person in the middle of phase II trials, and it set them back months.

 

Now, that turnover doesn’t just happen because of external opportunities. In this field, you’ve also got a lot of pressure—sometimes the work environment becomes toxic because companies are up against tight deadlines. I’ve seen cases where people are burned out from pushing to meet impossible timelines. You’ll have CEOs or shareholders demanding that the product hit the market by a specific date, and that creates a fast-paced, high-pressure environment that’s hard to sustain.

 

You’ve got to focus on knowledge transfer and employee retention strategies. First, document everything. And I don’t just mean the SOPs—sure, you need those—but also informal knowledge. Why certain decisions were made, what went wrong in trial runs, and how the team adjusted. You should be recording that in a way that’s easy for new people to access. One client of mine used a digital platform to store these decisions, including video walkthroughs and meeting notes, so the new hires could quickly get up to speed.

 

Mentorship is also key. You want your senior people passing that knowledge down to newer team members. If you’re not creating a culture where people are actively sharing knowledge, you’ll lose it the moment someone walks out the door. And look, in the early stages, you might not need a full-time replacement right away. Bringing in part-time consultants can fill that gap. I’ve seen it work really well—consultants come in with specific expertise in cell and gene therapy and can help maintain continuity while you build out your team.

That’s a huge issue. I’ve seen it time and time again. You’ve got departments like IT, CMC, regulatory, and clinical all working together on the same project, but they’re not necessarily speaking the same language regarding compliance. One team might be hyper-focused on hitting their own goals but overlook the bigger picture of how their work fits into the regulatory framework.

 

For example, I’ve seen IT teams make changes to data management systems without understanding the FDA’s requirements for data integrity, or a CMC team tweak a manufacturing process without realizing it could put the entire project out of compliance. One company I worked with had this exact problem—they changed their clinical development without considering how it would affect their regulatory submissions. They had to go back and redo much of the work because they missed critical GCP requirements.

 

The first step is to provide cross-functional GCP training. Every department needs to understand how GCP applies to their specific role. It’s not enough for the regulatory team to handle it. CMC needs to know how its manufacturing processes impact clinical data, and IT needs to understand how to protect data integrity. Tailor the training to each department’s needs and show them real-world examples of where a lack of compliance derailed a project. I’ve seen companies use case studies where non-compliance led to regulatory delays—it helps bring the message home when people see how easily things can go wrong.

 

Also, it’s essential to create formal communication channels between departments. I always recommend setting up a quality review board with representatives from each team—IT, CMC, regulatory, and clinical. They should meet regularly to discuss any compliance issues or upcoming projects. This way, everyone is on the same page, and potential compliance risks are flagged early on.

Managing CMOs and raw materials is one of the biggest headaches in cell and gene therapy. You’re often working with multiple suppliers, and it can go south very quickly if you don’t stay on top of things. I’ve seen companies waiting weeks for batch records only to find out that the CMO had an issue they didn’t report. By the time the company found out, it was already too late to meet their submission deadlines, and that’s a nightmare when you’re under pressure to get to the next phase of your clinical trial.

 

Another problem is that a lot of CMOs have multiple clients, and your project might not always be their top priority. If you’re a small company, you could end up at the back of the line while they focus on their more prominent clients. That’s why I always tell companies, ‘Be a pain in the neck if you have to!’ Stay on top of your CMOs. Keep that dialogue open, and make sure you’re always on their radar.

 

The solution here always starts with a robust quality agreement. Your agreement needs to detail how and when the CMO must notify you of any issues. I recommend requiring them to notify you within one business day of any critical deviation. You also need to include performance metrics—things like batch record turnaround times and communication timelines—so that both sides know what’s expected. If those expectations aren’t met, there need to be consequences.

 

And it’s not just about the paperwork. You’ve got to stay engaged with your CMO and suppliers. I suggest having regular, structured weekly or biweekly meetings. These meetings should go over everything—progress, any issues that have come up, and what’s next. Both sides need to have someone responsible for communication, and if something goes wrong, you need to address it immediately.

 

I’ve also seen companies struggle with fragmented supply chains—where different stages of manufacturing are handled by different CMOs. The communication gets complicated, and it’s hard to maintain accountability. You need someone at your company who’s managing all of those relationships, ensuring that everything is coordinated smoothly.

Auditing is expensive, no doubt about it, especially when you’re dealing with cell and gene therapy. You’re not just auditing a chemical process—you’re dealing with live cells, bioreactors, and specialized cleanrooms. These audits need to be thorough because even a small issue can have a big impact on product quality or compliance. But with the costs of on-site audits, you’ve got to be strategic.

 

What I recommend is a risk-based approach to auditing. Not every supplier is equally critical to your success. Focus your audits on the suppliers that are handling your most important materials—viral vectors, biologics, and cleanroom management. Those are the ones where failure can cause the biggest problems. These critical suppliers should be audited more frequently and more thoroughly.

 

For less critical suppliers, you can consider remote audits. This is a growing trend in the industry, and it allows you to save on travel and time costs while still maintaining oversight. Remote audits can include things like virtual facility tours, documentation reviews, and video calls with key personnel. They’re not a substitute for on-site audits but can be a good way to keep track of non-critical suppliers without breaking the bank.

 

I once worked with a company that had a critical supplier for viral vectors. When we conducted the audit, we found that their cleanroom protocols weren’t stringent enough for the type of work they were doing. By catching that early, the company was able to avoid a potential contamination issue that could have set them back months.

Contamination is always a huge concern in cell and gene therapy. The biggest source of contamination is people. Even with the best-trained staff, human error can happen, and bacteria can get into your cleanrooms. But one of the growing issues we’re seeing now is mold contamination. It’s becoming more common in cleanrooms, and most companies aren’t prepared for it. Standard cleaning agents target bacteria but don’t always eliminate mold spores effectively. I’ve seen cleanrooms shut down for weeks because of mold, and once it’s there, it’s hard to get rid of.

 

The best approach is to have a rigorous environmental monitoring program. Regularly test your cleanrooms for both bacteria and mold. You can’t just assume everything is fine because your air samples came back clear. Mold spores are tricky, and they can sneak in without showing immediate signs. That’s why I recommend using sporicidal cleaning agents specifically designed to kill mold spores, not just the standard cleaners used for bacteria.

 

Training is another big part of this. Your staff needs to be well-versed in aseptic techniques. I’ve seen companies get lax with this over time, assuming that their staff knows the protocols. But you need to reinforce proper gowning procedures and aseptic behavior constantly—especially when you have new hires. I recommend regular refresher training for all staff, not just the new ones. This helps maintain the standards needed to avoid contamination.

 

And don’t forget deep cleaning schedules. Daily cleaning isn’t enough to control contamination long-term. You need to schedule regular deep cleans that go beyond the surface level and follow them up with thorough environmental monitoring to make sure your cleanroom stays free of contaminants.