Eleven Manufacturing Considerations for Your MSC Program

MSC manufacturing appears straightforward on paper: initiate, expand, harvest, formulate, cryopreserve. In practice, programs derail downstream when vague assumptions are allowed to persist.

Below are eleven key considerations that determine whether MSC manufacturing remains consistent and scalable. 

1. Source strategy and donor variability 
   Define controls for biological variability, especially when scaling across donors or tissue sources.
    
2. Cell bank strategy and lifecycle 
   An MSC cell bank is not inventory. It is a control strategy for comparability, long-term supply, and regulatory continuity.
    
3. 2D versus 3D expansion pathway 
   Two-dimensional systems are often appropriate early. At scale, automated bioreactor platforms and, in some cases, 3D microcarrier-based expansion can improve consistency, provided comparability planning begins early.
    
4. Defined media exchange strategy 
   Align media changes to growth behavior using measurable signals. In-process metabolite monitoring helps detect drift before it becomes batch-limiting.
   
   
5. Predictive critical quality attributes (CQAs) 
   Surface markers alone do not define potency. CQAs must align with mechanism of action and clinical intent.
    
6. Harvest is a process, not a moment 
   Harvest and wash should be engineered unit operations with defined, controllable parameters.
   
   
7. Agglomeration control 
   Agglomeration drives downstream risk. In-line filtration and optimized wash design improve robustness and handling.
   
   
8. Automation aligned to development phase 
   Automate what reduces immediate risk, such as cell washing, while maintaining a roadmap for higher-throughput automation.
   
   
9. Cryopreservation and formulation fundamentals 
   Formulation directly impacts post-thaw viability and function. This is a frequent point of GMP translation failure if not addressed early.
    
10. DP container and fill strategy 
    Select phase-appropriate fill and finish early to avoid costly changes and comparability work later.
     
11. QC testing and stability for living products 
    MSC programs require tailored identity, potency, sterility, and stability strategies that support shelf-life claims. 

These are not optional enhancements. They are the levers that determine reproducibility, release reliability, and whether scale feels controlled or chaotic.