Bioprocess Development [verified] | A Mab A Case Study In

MabSelect™ SuRe™ (MSS) Protein A resin was chosen for its high binding capacity and ability to withstand aggressive alkaline cleaning (NaOH).

: These monitor the product during manufacturing to detect deviations early.

If upstream is about growing the protein, downstream is about catching it and cleaning it. This is often the most expensive phase of production due to the high cost of resins and chromatography columns. A Mab A Case Study In Bioprocess Development

| Challenge | Finding | Solution | |-----------|---------|----------| | (pilot scale) | Shear from peristaltic pump in harvest line | Switch to low-shear diaphragm pump | | Protein A carryover | Leakage ~150 ppm | Add intermediate wash (1 M NaCl + 0.1% Triton) → reduced to 25 ppm | | Aggregate formation during viral inactivation | pH 3.5 for 60 min → 2% aggregates | Reduce hold time to 45 min, add 0.1% PS80 | | UF/DF flux drop | Concentration polarization | Increase crossflow, use 30 kDa Hydrosart membrane |

The target molecule exhibited a pI (isoelectric point) around 9.3, indicating a relatively basic molecule that influences purification strategy. MabSelect™ SuRe™ (MSS) Protein A resin was chosen

The study utilizes a Design of Experiments (DoE) approach at a 2L scale to define a "scale-independent" design space. This ensures that parameters like dissolved oxygen (set at ~60%) and nutrient feeding strategies remain effective at commercial scales. 3. Downstream Process Development a-mab-case-study-version.pdf - ISPE

The is a seminal 2009 document developed by the CMC-Biotech Working Group —a consortium including Amgen, Genentech, and Pfizer—to demonstrate how Quality by Design (QbD) principles can be applied to monoclonal antibody (mAb) bioprocessing . It serves as a practical roadmap for implementing International Council for Harmonisation (ICH) guidelines Q8(R2) , Q9 , and Q10 in a biotechnology environment. Core Framework of the A-Mab Study This is often the most expensive phase of

If you are interested in hearing more about specific parts of this process, I can tell you more about: The specific used How we scale up from benchtop to commercial production The regulatory requirements for this process

However, this initial process had limitations:

Identifying the physical, chemical, biological, or microbiological properties that must remain within defined limits to ensure safety and efficacy.

Starts with choosing a host cell (often CHO cells ) and optimizing the genetic expression of the antibody.