The quick growth of the Cell and Gene Therapy created a great deal of enthusiasm in the biopharma industry. But, despite the merits they hold for patients, there are still some challenges when it comes to minimising their risks.  

We hope you have your seat belts fastened and be ready for the take-off. On today’s journey will share some insights about how to minimise the risks of these novel therapeutics and how to manage them. Have a nice flight! 

The challenges of Cell and Gene Therapy  

When we talk about Cell and Gene Therapies, we need to remember they are more complex when compared to more conventional biopharmaceuticals.  And, despite the excitement that these new types of therapies are generating, manufacturers are facing some growth pains. 

The industry has only recently received guidelines for the development of Cell and Gene Therapies. This late clarification made the advance of these new therapies more complex and with more risks. 

So, more than everything, this complexity requires control strategies which can manage manufacturing uncertainties and risks. 

And how can we establish those control strategies? Well, let us recommend you three different focus areas that together can ensure robust process control. 

Let’s start by having a Risk-Based Approach 

We think that, in fast-paced environments like these, you need to apply two essential things: 

  • A risk-based approach. 
  • Close communication with regulatory authorities. 

Starting with a risk-based approach, you should consider it in every aspect of manufacturing. A risk-based approach in conjunction with a mature quality system in the background, can guarantee adequate and consistent product quality.    

But wait! You shouldn’t forget that your main priority is the patient safety. So, the performance of your company in the risk characterisations must be greater.  And for that, we can give you a hint! 

Try to apply a Quality by Design strategy so you can build enhanced process knowledge and support your risk-based decisions. Also, ICH Q9 guideline principles should be used as it is well known that: 

  • Approval for clinical studies may not be granted if the product didn’t demonstrate that risks to patient safety are not mitigated, or 
  • If you have a weak quality system that can compromise the approval of the clinical trial if there are unmanaged risks regarding safety of trial subjects. 
Cell and Gene Therapy_Risk-Based Approach

If you are developing a risk based QbD approach for Cell and Gene Therapies manufacturing, you are on a good path. However, as we said above, you should begin this process and product data collection as early as possible and pair it with an open dialogue with the regulators. 

And then we move to the raw and starting material quality 

We know that developing Cell and Gene Therapies under accelerated timeframes is challenging. That’s why it’s so important to establish early partnerships. Partnerships with qualified supply chains to prevent any delay when moving to clinical developments. 

When it comes to raw materials, and unlike what happens with monoclonal antibodies, it’s typically difficult to remove the impurities or to do sterilisation before the formulation of the final product. 

Nowadays, we see an increase in the number of suppliers. To avoid any kind of surprises, you should establish agreements that consider not only technical and quality specifications, but also change management details. 

In what regards Starting Materials, you must know that patient, donor, and producer cells are critical defining the quality of your final product. 

If you opt for allogeneic applications, you must use a two-tiered cell bank system manufactured according to GMP. 

The two-tiered cell banks begin with a Master Cell Bank, which works as a starting material for the whole manufacturing process. And what is a Master Cell-Bank?  

As the name says, it is a bank of cells with the same composition that derives them from a single source and where they are prepared under defined culture conditions. Then, you just need to aliquot samples in individual and cryopreserved vials to form a Working Cell Bank. 

And what about Communication with the CDMO’s? 

Well, having communication with regulatory authorities is necessary. But, in addition, we recommend a close and a proactive communication with your CDMOs as well. 

This communication is very important. Not only to create multidisciplinary teams to support your project, but also to ensure the success of regulatory inspections. 

So, overall, how can you minimise the risks of your Cell and Gene Therapy products? 

We don’t want to conclude this blog post without giving you an overview of what all Cell and Gene Therapy manufacturers should prioritise when it comes to delivering quality and success. So, at the top of your mind you should consider the following rules: 

  • The development of risk-based approaches is essential to the manufacture of these therapies. 
  • The control of raw materials is key to guarantee the product quality. 
  • Having well-characterized cell banks is a must have from a regulatory perspective.
  • Ensure a proactive Communication with your CDMOs.

We can help you manage the risks of your Cell and Gene Therapy products 

We are sure that following these approaches, your company will be able to deliver consistent and therapeutic outcomes for your Cell and Gene Therapy products. 

Besides providing end-to-end solutions, our team delivers effective 4.0 approaches that aggregate evidence and extract insights for science-based decisions. 

Also, we help you with risk-based approaches capable to identify, quantify and prioritize risk, enabling the formulation of risk mitigation strategies. So, if you think that we can be the solution for your problem, feel free to contact us

Do you want to know more about Cell and Gene Therapy? 

Have a look at our blog post: Cell and Gene Therapy: is Quality by Design ready for it?