Day Two - Thursday August 29, 2024

8:00 am Morning Coffee & Networking

8:50 am Chair’s Opening Remarks

From Bench to CMC: Bridging the AD Gap to Simplify Development

9:00 am Balancing Resolution & Equipment Complexity to Streamline Transfer to CMC Teams

  • Huijun Tian Director, Analytical Development and Quality Control, QurAlis


  • Deliberating if small molecule principals and learnings are fit for purpose with larger oligonucleotides
  • Evaluating the value of high-resolution mass spectrometry for oligonucleotide development
  • Standardizing methods to ensure clear documentation and method validation are up to regulatory standards

9:30 am Analytical Comparability for Tech Transfer & Process Change


  • Debating how many comparability studies are necessary and which are most valuable for different oligonucleotide structures
  • Managing comparability studies for increasing batch size that detects impurities and establishes product quality for clinical manufacturing
  • Establishing best practices to ensure effective life cycle management

Charting the Uncharted: Regulatory Guidance for a New Era of Oligonucleotide Development

10:30 am Roundtable Discussion


Following a series of case studies, this is your opportunity to engage and interact with your fellow colleagues to share your ideas, challenges and seek solutions together. Select the topic of choice for a solution-led discussion, and we will feedback for Q&A towards the end of the session to create a comprehensive action plan for your team.

Topic 1: Exploring FDA Perspectives to Ensure Compliance & Clear Communication With CDER

  • Validating thorough documentation and testing of production processes
  • Gathering the latest guidance for safety, purity, and monitoring

Topic 2: Examining Structural Complexity of Oligonucleotides With the EMA

  • Navigating technical complexity of developing analytical methods
  • Improving reliability of characterization methods for oligonucleotides
  • Bringing oligonucleotides to market safely to improve future acceptance

11:00 am Coffee Break & Networking

Ensuring Reliable Product Quality to Facilitate Market Success

12:00 pm Process Development & Scale-up of GalNAc-Conjugated siRNA

  • Isaiah Cedillo Executive Director, Manufacturing & Operations, Ionis Pharmaceuticals


  • Process-related impurities associated with siRNA
  • Process development for sense and antisense stands and annealing operation
  • Analytical considerations for analyzing intermediate and annealed siRNA

12:30 pm Manufacturing Process Development for 2’-O-N-methylacetamide Oligonucleotides


  • Determining optimal storage techniques and hold times for intermediates between manufacturing unit operations
  • Optimizing preparative chromatography methods for purification that improve purity and recovery amid new impurities
  • Exploring alternative synthetic routes with modified phosphoramidites

1:00 pm Lunch & Networking

Scalability & Process Economics Considerations for Oligonucleotides to Reach Additional Patient Groups

2:00 pm Back-Tracking Oligonucleotides for Process Validation & Improving Process Economics

  • Debasis Patra Vice President, Senior Director & Head Of Chemistry, Manufacturing & Controls, OliX Pharmaceuticals


  • Exploring validated processes and manufacturing following approval as oligonucleotides enter market
  • Securing supply chains for consistent batches and ensuring quality for patients
  • Examining economic and financial considerations for market competitiveness

2:30 pm Safe-Guarding Process Efficiency & Yield to Improve Cost


  • Navigating increasingly complex chemistry through optimized synthesis
  • Streamlining downstream processing and exploring automation to integrate processes and improve efficiency
  • Implementing continuous monitoring and progressive improvements to identify patterns in production quality

Looking Long-Term: Sustainability Strategies in Oligonucleotide Manufacturing to Minimize Environmental Impact

3:00 pm Implementing Ultrafiltration/Diafiltration for Processing ASOs to Improve Efficiency


  • Examining the capabilities and limitations of UF/DF membranes to process oligonucleotides using antisense oligonucleotides (ASOs) as a model.
  • Investigating the effectiveness of UF/DF in ASO purification processing to concentrate and formulate a liquid drug substance or to prepare an ASO product for lyophilization resulting in a solid API.

3:30 pm Synthesis of RNA Fragments on a Soluble Support


  • Alternative methods to synthesize and isolate RNA are valuable to reduce the high solvent volumes and reagent amounts needed in traditional solid phase synthesis
  • Here, we describe an alternative solution-based approach to couple nucleotides on a soluble support and isolated via precipitation

4:00 pm Chair’s Closing Remarks & End of Summit