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Presenter warns impurities and immunogenic motifs can complicate ANDA approvals
Summary
Using a hypothetical case, the presenter showed how different synthetic routes can generate distinct impurity profiles — including fragments with immunomodulating motifs — and recommended thorough risk assessments in ANDA submissions.
The presenter raised impurity-profile differences as a central regulatory risk for generics, saying new impurities or levels higher than the RLD could create immunogenicity or off-target concerns that require thorough assessment. "Apart from typical considerations for impurities, the risk in immunogenicity, information and of target effect, should be considered for, oligonucleotide impurities, especially for those that are new or at much higher levels than the R and D," the presenter said.
He illustrated the point with a hypothetical: Company A makes a 23-mer by linear synthesis, conducts nonclinical and clinical studies, and could receive approval; Company B using a convergent route could produce different impurities, potentially introducing known immunomodulating motifs. The presenter said such differences mean ANDA applicants must assess impurity profiles, synthetic-route design, and the implications for safety and comparability rather than assuming identical risk profiles.
