Agency official outlines quality and "sameness" priorities for generic oligonucleotides

An agency official opened a technical presentation by saying the session would cover both quality and "sameness" considerations for generic oligonucleotide drugs and why the two topics overlap. "Today, I will be discussing some, quality considerations, for generic oligonucleotides," the presenter said, framing the talk around sequence and structural comparisons to reference listed drugs.

The presenter said sameness studies should confirm sequence, chemical structures (including stereochemistry), completeness of modifications, and composition attributes such as diastereomeric distribution and duplex content. He stressed that, for some products, sameness must be demonstrated in the finished drug product before administration, because manufacturing steps can alter higher-order structures or duplex pairing. "Active ingredient sameness studies should confirm the sameness in sequence, chemical structures, which, would include but not limited to correctness in structure, location, and stereochemistry," the presenter said. The presenter also cited the preamble to proposed rules implementing the Hatch-Waxman amendments to emphasize that regulatory definitions can focus on the finished product.

This article summarizes the presenter's framing and the practical implications he highlighted for applicants preparing ANDAs: firms may need to assess finished-product changes, design orthogonal analytical approaches, and provide robust justification when relying on internal control strategies rather than direct matches to RLD analytical methods. The presenter closed by inviting panel questions and thanking colleagues for their work on generic oligonucleotide challenges.