PHARMACEUTICALS
Best practices & strategies for biotherapeutics production using a stable scale-up process
Dr Anurag Dhobal and Dr Nagendra Ningaraj of Aragen Lifesciences look at the challenges and options available to improve biologics production *
Biopharmaceutical medicinal products , or biologics , are already an integral component of therapeutic strategies to treat various human diseases . 1 Biologics , which mostly consist of therapeutic recombinant proteins , are used in treating a variety of diseases , including malignancies and inflammatory disorders . 2
Developing a dependable commercial biopharmaceutical manufacturing method is logistically and technically complex , with several potential hurdles . Small biotech and major pharma businesses are constantly seeking partners to expedite the production of medications with a shorter timeline and higher yield and quality .
The main challenge with the accelerated discovery and production of biologics is exclusive dependence on live host cells that act as biological factories . Cells are sometimes unpredictable and might present technical problems . 3 Thus a robust , high-yielding cell line platform is the basis of a dependable manufacturing process .
For instance , biologic instability might occur during the development phase or during the scale-up process itself . A small change in pH or temperature , or a change in the consumables can impact the anticipated structure and function of the biologic . 4 Advance , precise prediction of the cell culture conditions on a biologic ’ s function can lead to
8 weeks
10 weeks
Stability study
effective process scale-up and greatly decrease regulatory time delays .
Many CROs face difficulties in scaling up biologics production due to inefficient analytical facilities , unstable molecules and limited process development capabilities . All these factors influence the time to market and budget outcomes of the biologic ’ s developers .
A comprehensive analytical facility requires huge capital investment , which ultimately depends on the organisation ’ s operations and commercial size . Hence , understanding and alleviating the potential barriers to efficient production and scale-up procedures
Stable transfection
Mini-pool plating & selection
Screening mini-pools & identifying best MP
Single cell printing / imaging
Expansion / Evaluation / Analytics
RCB banking
Bioreactor evaluation
Bulk pool selection
Figure 1 – Typical CLD process at Aragen with timelines
RCB testing
before starting the project is critical for the project ’ s success .
In this article , the challenges associated with the biologics production process ( cell line development , CLD ) are discussed briefly , followed by strategies to avoid these challenges , which will assist biopharma companies in derisking their production and scale-up methodologies from the drawbacks of misinformed decision-making .
Key challenges in production
Selecting the right expression platform and vector for process development at pilot-scale and commercial manufacturing is a major
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