CDMO Blog

Implementation of a manufacturing process that assures a predefined quality of product is a critical requirement for the licensing and marketing of every cell and gene therapy (CGT) product.

When we think about cell and gene therapies (CGTs) what most often comes to mind is the early stage scientific innovation responsible for finding new ways to treat diseases. A lot of complex research and testing is performed to confirm Proof of Concept and that the therapy performs as desired. 

In an introductory post on lentiviral vector (LVV) manufacturing for cell and gene therapies (CGTs) we touched upon the challenges with transfection-based protocols for producing LVVs at large scale. Here we will take a closer look at the use of stable producer cell lines as an alternative to transient transfection for the manufacture of LVVs.

Compliance with quality control (QC) standards is a basic requirement for products manufactured under good manufacturing practices (GMP) conditions. In this post we will explore the main compendial QC tests that ensure cell and gene therapies are safe for use in patients, and important considerations for integrating QC testing into the manufacturing process.

Lentiviral vectors (LVV) are a key component in the production of cell and gene therapies. They are most often used to deliver genetic material that will modify cells and confer therapeutic properties. Today, even with the proliferation of cell and gene therapies in development, LVV is still produced using legacy methods employed in basic research. Overcoming technical challenges in the scale-up of LVV production is a major focus for the industry. Scalable LVV production platforms are critical for manufacturing affordable cell and gene therapies and making them more widely available. For an overview of LVV manufacturing and process optimization considerations see our previous post.

Understanding the cell and gene therapy (CGT) development process from start to finish often comes down to learning the language. For individuals more familiar with the early R&D steps in this process, terms like IQ, OQ and PQ – associated with later manufacturing steps – may be completely new. To get us started: IQ stands for installation qualification; OQ is operational qualification; and, PQ is performance qualification. Simply put, these are three steps in a validation process that ensures the equipment used in manufacturing works the way it’s supposed to. 

In the field of cell and gene therapy, there are two main types of viral vectors: adeno associated virus (AAV) and Lentivirus (LV). The manufacture of these vectors is dependent on the regulatory requirements dictated by its end use. AAVs are most commonly used to deliver gene therapies – meaning they will be administered directly to a patient. In contrast, LV is typically used as an input material to genetically modify cells used for cell therapies (e.g. CAR-Ts) and is not included in the final product delivered to the patient.

Conventional cancer treatments (e.g. surgery, chemotherapy/radiation) do not specifically target cancer cells and, as a result, can cause extensive off-target damage, and complications for patients.