To: drkaz who wrote (10326 ) 5/23/2018 7:01:22 PM From: HardToFind 2 RecommendationsRecommended By
Respond to Scale-up is intrinsically tricky to even talk about:Scale-up is done for each stage and each step of production (micelle formation stage, ligand formation stage, micelle and ligand attachment stage), and each of these stages has multiple steps. Some stages and steps scale up better than others. (I think Seymour once told me there were 14 steps to scale up for FluCide...but my memory may be weak on that matter.) Initially, the company thought scale-up to 2.5 kg batches was quite doable. But scale-up has proven to become more difficult than expected, and there may be practical limits above about 1 kg for even the easiest steps. We may not make it past that batch size in the next few years. This reality has caused the company to go back and revise the ligands to become more effective...i.e., to require less drug material. The micelle backbone has also changed over time to support better oral and topical drug delivery. Each time the backbone or the ligand changes, two of the three stages of the scale-up have to be re-done. (Hopefully, we're getting better and faster at redoing scale-up.)
