The progress in understanding and addressing the challenges of impurities was a focal point of this year’s USP Therapeutic Peptides and Oligonucleotides Workshop, held virtually on February 28, March 2 and March 4, 2022.
Peptides and oligos represent rapidly growing product classes with extensive potential in a wide variety of therapeutic fields. However, they also comprise complex molecules with unique scientific and regulatory challenges in their development, manufacturing, and quality control.
Adding to the challenges is the pressing need for stakeholders to keep up with the rapid pace of innovation in the peptide/oligo arena, including: ● novel modifications, conjugations and chemistries ● novel formulations ● the emergence of platform technologies ● advanced analytical strategies and tools ● supply chain advances, and ● in the case of oligonucleotides, the emergence of generic and personalized therapies.
The USP workshop series has shed light on the emerging peptide/oligo quality issues and how they are being addressed. Originally focused solely on peptides, the workshop’s scope expanded in 2019 to include oligonucleotides – reflective of the rapidly expanding industry engagement with them. This year’s workshop marked the seventh in the series. [A link to the agenda for the 2022 workshop is provided below.]
IPQ’s coverage of the 2022 workshop is divided into the following three parts:
● PART I: US and European Regulator Perspective on the CMC Challenges of Oligonucleotides
CDER Office of Generic Drugs (OGD) Senior Chemist Deyi Zhang led off the opening, regulatory-oriented session with an overview of CMC issues for generic oligos and the development of product-specific guidances. Germany’s Federal Institute for Drugs and Medical Devices (BfArM) CMC reviewer René Thürmer then provided a European regulatory perspective on CMC experiences and expectations for oligos. Thürmer’s talk encompassed: ● control strategy development ● impurity issues, and ● future trends in the oligo field. Issues receiving additional attention during the Q&A included impurity and bioassay concerns for oligo and peptide therapies.
● PART II: USP Standards Development Efforts for Peptides and Oligos
A discussion of oligo and peptide compendial standards by two USP experts followed the FDA and EMA presentations at the opening workshop session. Senior Scientist Julie Zhang provided an overview of the USP standards-setting process and highlighted recent updates in the peptide monographs. Global Biologics Principal Scientist Sarita Acharya then discussed the development of standards for oligos and how USP has prioritized those for phosphoramidites, which serve as a critical starting material for oligo synthesis.
● PART III: Peptide and Oligo Analytical, Manufacturing and Raw Material Considerations
The third part of the story reviews the discussions held over day two and three of the workshop, which focused on analytical tools to ensure peptide/oligo quality, and manufacturing and raw material considerations, respectively. Further light was shed on impurity issues during these discussions.
LINK: ● USP Workshop Agenda