A Deep Dive into the Quality Cornerstone of GLP-1 drug

  GLP-1 receptor agonist drugs, represented by semaglutide and tirzepatide, have faced intensified scrutiny and warnings from regulatory agencies worldwide.

  In January of this year, the UK‘s Medicines and Healthcare products Regulatory Agency (MHRA), based on over 1,200 reports of GLP-1-related pancreatitis received since 2007—including 19 fatal cases—strengthened safety warnings and mandated updates to product labeling. Subsequently, the U.S. FDA issued an official warning letter to Novo Nordisk, citing systemic serious violations within its pharmacovigilance system, including failures to timely report severe adverse events such as disabling strokes and suicidal ideation.

  Prior to this, the FDA had initiated an investigation in 2024 into the potential risks of suicidal ideation and behavior associated with this drug class. Furthermore, in April 2025, the FDA explicitly prohibited compounding pharmacies from manufacturing and selling direct copies of branded GLP-1 drugs to address quality and safety risks from non-standard supply channels.

  This series of events once again underscores the paramount importance of drug safety. Consequently, in-depth and systematic impurity studies, as critical factors impacting drug safety and efficacy, have become even more crucial.

  For GLP-1 drugs, which are complex peptides manufactured via chemical synthesis or biotechnology, the impurity profile is extremely intricate. Taking semaglutide as an example, its impurities are primarily categorized into two major classes:

  •   Process-related impurities: These include deletion peptides, insertion peptides, peptides with incorrect sequences, and incomplete deprotection products generated during synthesis.

  •   Degradation products: These may form during production and storage through processes such as oxidation, deamidation, and hydrolysis.

  Global regulatory authorities have established stringent control standards for these impurities. For instance, the United States Pharmacopeia (USP) and the Chinese Pharmacopoeia typically require semaglutide active pharmaceutical ingredient (API) to have a main component purity of not less than 98.0%, total impurities not exceeding 2.0%, and any single unknown impurity not exceeding 0.10%, with even stricter limits set for known specified impurities. The Technical Guidelines for Pharmaceutical Research of Chemically Synthesized Peptide Drug Substances (Trial) issued by China‘s National Medical Products Administration (NMPA) also clearly defines these control standards.

  SZEB  supplies a comprehensive series of semaglutide impurity reference standards. We are committed to supporting pharmaceutical companies in placing impurity control at the core of their R&D and production processes, thereby helping to build a robust, end-to-end quality assurance system from drug development to patient administration.