In this blogpost, we want to make you think about the application of the Quality By Design for Cell & Gene Therapies.

Over the past century, lifecycle management of biotechnology products and biopharmaceutical industry has been founded on principles from the pharmaceutical small-molecule industry. But are they suitable for it? Let’s find out!

The current model and its risks

One of the paradigms of the pharmaceutical small-molecule industry is its definition of clinical programs. These programs are capable of establishing risk-benefits of a dosage and its delivery system on healthy individuals and patients.

In terms of efficacy and safety, we expect that product quality attributes to be a guarantee for patient outcomes. Also, they need to deliver the clinical performance that was designed. This clinical performance is irrespective of both:

  • Patient-to-patient differences;
  • Variability in manufacturing operations over a product’s lifecycle.

However, if we talk about Cell & Gene Therapy, that model brings potential risks for patients. When we try to transport the pharmaceutical model to biopharmaceutical operations, we verify fundamental insufficiencies and inadequacies on it.

In general, biologics have more quality attributes than small molecules. In fairness, not all of them are clinically relevant. But those that are, are so in great contrast to those observed for small molecules.

Because of that, new therapies and new product specifications for biologics can be complex and extremely patient-specific. We need to assure quality compliance during the whole manufacturing process. Otherwise, we may risk the product efficacy and patient safety.

This idea has worked out for the last few years, but it is highly inefficient! The trial-and-error during product development is not a solution anymore. Today, we need to take a different approach to the subject.

Does it suit Cell & Gene Therapy products?

When it comes to terminally ill patients, we don’t have second attempts nor time for classical QbD experiments. Although an optimal solution for C&GT products may be far away, why can’t we streamline practices of the current model?

Throughout the years, pharmaceutical industry considered and introduced many concepts like:

  • Progress Analytical Technology (PAT).
  • Quality by Design (QbD).
  • Lifecycle Management (LCM).
  • Continuous Process Verification (CPV).

All of these are included into specific ICH guidelines. However, they were built for small molecules and there is significant uncertainty in the proposed science-based framework. This uncertainty justifies prescribing a risk management framework across the different guidelines.

Risk management is the priority!

As mentioned, biologics have more CQA’s when compared with small molecules. And here is the point: defining a control strategy for biologic products requires a lot of effort. And, not only that, we acknowledge that uncertainty will be present in all stages of development and manufacturing.

How do we tackle this? We propose a solid and structured risk-based approach across the development lifecycle. We believe this will ensure the delivery of consistent product quality and patient safety.

What about Quality by Design?

Quality by Design keeps patients out of the equation and the quality is the surrogate for efficacy. The quality targets used for biologics are designed for an average unspecific patient response. This can be an inadequate way to deliver ensured outcomes to small, differentiated patients’ populations.

Will that be enough for Cell & Gene Therapies?

Short answer: No! Using a patient profile and corresponding outcomes information will not deliver the required predictive framework. So, what do we need?

  • Effective end-to-end integration of operations over products’ lifecycle.
  • Define a true endpoint on operations at patient outcomes.

We combine evidence-based and risk-based approaches together with the needs we indicate above. And this has a dramatic impact on delivering predictive clinical outcomes.

But there’s more! This will not only accelerate the access to new therapies, but it will also enable an industry 4.0 integration. We will be able to bring together the explicit and the tacit knowledge. And, with that, improving biopharmaceutical industry agility.

Setting up Risk Management Processes for Cell & Gene Therapies

If you’d like to have a deeper understanding of this topic with further details on:

  • FDA’s Guidelines for Cell and Gene Therapies;
  • Process development for CGT products;
  • CQA evaluation through Design of Experiments Studies (DoE);
  • Process characterization studies;

We suggest that you download this article of ours:

CGT Article

On the same subject and in this blog, we have another recent publication on the topic.

How can we help you?

4TE and its team have worked with biopharmaceutical companies across different areas like End-to-End Lifecycle Management, Qbd Frameworks and QRM process Optimisation.

We developed commercial validated tools which can help your business in this journey of biologics manufacturing and its potential risks. If you think that we can be the solution for your problem, feel free to contact us.