Production process of weight loss peptides

The production process of weight loss peptides (such as GLP-1 receptor agonists) mainly includes two mainstream routes: biological fermentation and chemical synthesis. The specific process flow varies depending on the type of drug and enterprise strategy.

Biological fermentation method

Technological process:

Prokaryotic expression systems (such as Escherichia coli or yeast) ferment and express inclusion bodies;
Collection, rupture, inclusion body collection, renaturation, clarification;

Downstream purification: multi-step chromatography (coupling/enzyme digestion), ultrafiltration fluid exchange, sterilization filtration, etc.  ‌

Advantages: Low cost, suitable for large-scale production;

Limitations: A self built fermentation factory is required (such as Novo Nordisk not outsourcing due to technical confidentiality), and subsequent chemical modifications are needed to extend the half-life of the drug.  ‌

Chemical synthesis method

Technological process:

Solid phase synthesis:

Resin fixed amino acid C-terminus, gradually coupled to protect amino acids;

Deprotection, activation, condensation cycle to the target sequence;

Cut the resin and purify it.  ‌

Liquid phase synthesis: Similar to solid-phase method, but without the need for a resin carrier.  ‌

Advantages: Standardized process, easy to outsource (such as using this method for Eli Lilly's Tilpotide);

Limitations: High cost, but the gap with fermentation methods may be narrowed in the future due to process optimization. 

Mixed process (semi biosynthetic)

Preparation of main peptide chain by biological fermentation, and chemical modification of side chains (such as semaglutide).  ‌

Future Trends

After generic drugs are launched, chemical synthesis routes may become mainstream (such as the expiration of the domestic patent for semaglutide in 2026);
CDMO (Contract Research and Development Production Organization) production capacity is gradually expanding into the peptide field.