Cell and Gene Therapy (C&GT) is a fast-growing field, and that fast growth brings challenges to its development and manufacturing process.

Implementing Process Analytical Technology (PAT) and Quality by Design (QbD) might be the answer to overcome some of those challenges. How? Let’s find out!

PAT and QbD: a handful of benefits for C&GT

There are many benefits that you can get from implementing PAT and QbD in your Cell and Gene Therapy process.  

In fact, we might as well go for a list of what you can expect:

  • An increase process knowledge and help you identify the Critical Quality Attributes (CQAs) and Critical Process Parameters (CPPs).
  • A boost in process performance, caused by the implementation of automatic tools that monitor and control CQAs and CPPs.
  • The possibility to simplify the measurement of quality attributes, by developing multi-parameter sensors.
  • The enablement of real time release testing, shortening the time for quality testing.
  • A reduction in time, cost, and workload. both in the regulatory submission and in the production process.

If you aren’t yet convinced of the many benefits that PAT and QbD bring to your C&GT processes, there’s not much more we can do!

What we can do instead is to tell you how exactly these benefits optimise the C&GT processes.

Application of QbD in Cell and Gene Therapy

The QbD framework leads to the definition of the CQAs and CPPs, with a risk assessment for the process and the products.

During this risk assessment, every quality attribute needs to be enumerated and classified according to its severity (possibility to affect the product safety or efficacy). After that, you should calculate the likelihood of each quality attribute to be out of specification. Then, with these two parameters, the criticality of the quality attributes is calculated, defining the CQAs.

However, for a successful QbD implementation, it’s necessary to define the quality target product profile (QTPP). This is the set of CQAs that comprises the desired product quality attributes. For C&GT products, these fall into different categories:

  • Identity
  • Purity
  • Sterility/Safety
  • Potency
  • Formulation and Stability
  • Other

But what’s the link between PAT and QbD? We’re glad you asked!

Improving the C&GT processes

Applying PAT to your C&GT products will optimise every step of the production process. Let’s go through some of the possible CQAs and CPPs and then look at how PAT can lead to their process improvement.

When it comes to the control of media composition, which is key to guarantee cell health and product quality, you can leave the usual offline methods of measurement behind with the application of PAT. PAT will allow real-time monitoring and advanced control tools, enabling total process automation, based on the metabolites and cell concentration profile. Additionally, you can estimate endogenous factors more accurately using the real time monitoring tools together with chemometrics.

Moving on to variables such as pH, temperature, stirring rate or dissolved oxygen, with PAT you can monitor and control these important variables by using multiparametric sensors or capsules with higher lifespan and dynamic range, instead of the standard, single variable probes.

Regarding cell concentration and viability, which are critical indicators of process evolution in C&GT, PAT lets you assess not only cell number, but also cell state, such as cell physiological state or propensity to differentiate.

Finally, quality assays in C&GT are usually lengthy and operator dependent, contributing to the existing variability intra-batches. However, it’s possible to simplify the assessment of product characterisation by using multi-attribute, chemometric or automated imaging tools. Furthermore, these tools can contribute for real-time monitoring of the CQAs identified, shortening the time needed for product release.

Why isn’t everyone doing this?

Despite of all the benefits previously mentioned, a successful PAT and QbD application in C&GT requires the following:

  • Regulatory and market knowledge.
  • Knowledge of methodologies for QbD and PAT implementation.
  • Availability of a real-time monitoring tool.

We can help with your PAT and QbD implementation

Do not worry about the requirements listed above, 4TE has the necessary expertise to help you overcome these barriers. If you’re thinking of optimising your C&GT products with PAT, check out our services and feel free to contact us!

Our Work on the Topic

Interested in PAT and QbD for C&GT? We suggest you download our article on the matter:

If you want to learn more about C&GT, check our Blog post: Cell and Gene Therapy: How to minimise its risks?