MANUFACTURING ARTICLES

• Rethinking ATMP Assurance When Sterility Timelines, Reality Misalign

  The compendial 14-day sterility testing window exposes product and patient to numerous risks, but settling on a rapid alternative also presents its own set of challenges.

• The Potency Chains Of Events For mRNA/LNP Therapeutics

  Potency in mRNA/LNP therapies depends on two chains: manufacturing/cold chain integrity and complex in vivo delivery. Breakdowns at any step — from stability to translation — can limit efficacy and safety.

• How Informal FDA Feedback Is Quietly Driving RNA Capital Allocation

  Subtle FDA signals — especially in pre-IND talks — are quietly shaping RNA investment. Early regulatory feedback on CMC and comparability now drives how investors assess risk and allocate capital.

• Inside Alnylam's Playbook For High Volume siRNA Production

  As one of the first companies to establish a chemoenzymatic ligation platform, Alnylam's Maines and Nechev are in the perfect position to espouse wisdom on the practical aspects and remaining challenges of implementing enzymatic ligation at a large scale. Here in this installment, Maines and Nechev outline what they’ve learned thus far about the science of enzymatic ligation, while also paying credence to the unknowns and existing barriers that, as a frontrunner, Alnylam will inevitably (but willingly) be tasked with facing in the future.

• The "Middle Ground" Advantage: Why Alnylam Is Betting Big On Chemoenzymatic Ligation

  Though conversations are picking up around this hybrid approach, we aren’t exactly known as an industry that embraces risk no-holds barred. While there are a handful of manufacturers and CDMOs who are embracing the hybrid model today, there are many more that are likely to hold out for the next-next gen approach: Fully enzymatic oligo production. However, as Alynlam’s CTO and Chief Quality Officer Tim Maines argued, embarking into the “middle ground” of enzymatic ligation is essential for garnering the step-by-step learnings needed to help us unlock even bigger manufacturing wins in the future. 

• The Evolution Of Oligonucleotide Manufacturing: Engineering Considerations For Scale, Efficiency, And Facility Design

  As oligos move toward larger indications, manufacturing shifts from chemistry alone to facility design—balancing scale, solvent safety, cost, and flexibility as SPOS, slurry, and enzymatic paths converge.