189. In mammalian cell culture based monoclonal antibody production, perfusion culture is preferred over
continuous stirred tank culture, because the process results in:
1. high volumetric productivity
2. high specific productivity per unit biomass
3. maintaining cells in active phase of production
4. retaining the product of interest in the reactor so that higher product concentration is obtained at the end
of the process.

Introduction:

In the production of monoclonal antibodies (mAbs), mammalian cell cultures are commonly used due to their ability to produce complex proteins with post-translational modifications similar to human proteins. Two common types of cell culture systems are perfusion culture and continuous stirred tank culture (CSTR). Both methods are employed to maintain cell viability and productivity, but perfusion culture is often preferred in this context.

In this article, we’ll dive into why perfusion culture is more advantageous over CSTR for monoclonal antibody production, focusing on key factors like volumetric productivity, specific productivity, and the ability to retain the product in the reactor.

Key Concepts:

1. Perfusion Culture: Perfusion culture involves continuously adding fresh medium while removing spent medium and waste products. This process allows cells to remain in the log (active) phase of growth for an extended period, maximizing productivity.

2. Continuous Stirred Tank Culture (CSTR): CSTR operates by continuously feeding medium and continuously harvesting the culture, but the cell density in the culture can be limited over time due to nutrient depletion and the accumulation of waste products.

Why Perfusion Culture is Preferred:

1. High Volumetric Productivity:

In perfusion culture, fresh medium is constantly supplied to the culture, and waste products are removed. This process ensures that cells are continuously exposed to optimal conditions, leading to higher volumetric productivity—the total amount of product (e.g., monoclonal antibodies) produced per unit of reactor volume over time.

2. High Specific Productivity per Unit Biomass:

Perfusion culture also allows cells to maintain their optimal growth conditions, which means the specific productivity (the amount of product produced per unit of biomass) remains high. This is particularly beneficial for mammalian cell cultures, which are often more sensitive to changes in the environment. Maintaining an active growth phase and avoiding nutrient starvation or waste accumulation results in a higher specific productivity.

3. Maintaining Cells in Active Phase of Production:

In perfusion systems, cells remain in the active, exponential phase of growth for a longer period. This is critical for mAb production, as the production rate of the antibody is often highest during the active cell division phase. This extended active phase leads to a continuous and robust antibody production rate.

4. Retaining the Product of Interest in the Reactor:

One of the key advantages of perfusion culture is the ability to retain the product in the reactor, thereby achieving higher product concentrations. In CSTR systems, the product is continuously removed along with the medium, which can result in lower overall product concentrations. In contrast, the perfusion process ensures that product is retained and only the medium (which has lower concentrations of antibodies) is removed, leading to more efficient and concentrated production.

Answer:

The correct answer is:

4. Retaining the product of interest in the reactor so that higher product concentration is obtained at the end of the process.