BX LAB TECHNICAL ARTICLE
Oligonucleotide Capacity Is Measured in Moles, and the Numbers Are Small
What a $126 million plant expansion buys, and why that constrains everyone upstream of it.
Key takeaways
The largest oligonucleotide CDMOs report annual capacity in single- or low-double-digit moles.
ST Pharm went from 1.5 to 6.4 moles a year by retrofitting, then committed $126m for a second plant.
Treat any capacity figure with care: published numbers differ by more than tenfold and rarely define terms.
An odd unit, and a revealing one
Most chemical manufacturing is measured in tonnes. Oligonucleotide manufacturing is measured in moles per year — and once you convert, you see why. A therapeutic oligonucleotide has a molecular weight around 7,000. A mole of it is about seven kilograms. So a plant advertising single-digit moles of annual capacity is talking about tens of kilograms of finished drug substance a year. That is the scale the entire modality runs on.
What a large expansion actually buys
ST Pharm gives the clearest public numbers. Its first oligonucleotide plant at the Banwol campus opened in 2018 with about 1.5 moles a year of capacity. A retrofit took that to roughly 6.4 moles. The company then committed about $126 million to a second plant with four to six large production lines, targeting around 14 moles a year — a figure it said would make it the largest oligonucleotide CDMO in the world by capacity. Read that again: nine figures of capital expenditure, for roughly eight additional moles a year, to lead the field.
Treat the published numbers with suspicion
Capacity figures in this industry are not comparable and are frequently wrong. Market-research summaries currently circulate a figure of 180 moles a year for one Chinese facility — more than ten times the capacity of a plant whose owner claims to be the world leader. Both cannot be right. Nobody defines whether they mean crude or purified, which sequence length, which chemistry, or synthesiser occupancy versus theoretical throughput. If a capacity number matters to your planning, get it from the company, in writing, with the assumptions attached. We have not been able to reconcile the public figures either, and we would rather say so than repeat one.
Why this constrains everyone upstream
A 20-mer needs 19 couplings, each consuming an excess of amidite. The building-block requirement per mole of finished oligonucleotide is therefore large, and it lands before the oligonucleotide plant runs, not after. When a late-stage programme scales, its amidite demand arrives as a step change with a fixed date. Reagent lead times reported in this industry are already measured in months at peak. That is a planning problem, not a purchasing problem, and it is usually discovered too late to solve by ordering harder.
What to do with this
If you are running a programme that could reach commercial scale, the useful question is not "can I buy this amidite" but "who is making it, at what scale, and what happens to my timeline when three other programmes want it in the same quarter". Ask a supplier what they make themselves and what they buy in. Ask what the lead time looks like when the answer is not "in stock". The chemistry is the easy part; the queue is not.
Turn the product name into a decision-ready specification
A purchasing name is only the starting point for a research material. Build the specification around exact chemical identity, form and assay basis. Define how identity will be confirmed and distinguish chromatographic purity from assay, concentration or active-content measurements. Add the attributes that could alter use, such as water, residual solvent, counterion, residual metals, known related substances or storage sensitivity. Acceptance limits should reflect the intended function rather than copying every available analytical result into a specification. Where a method is critical, record the technique, column or detection principle and sample preparation assumptions. This gives chemistry, analytical and procurement teams one shared definition of the material and reduces the chance that a technically correct but operationally unsuitable lot enters the project.
Qualify the material in the workflow that matters
A CoA can establish lot results against an agreed specification, but it cannot by itself prove performance in the intended research workflow. Plan a small, controlled qualification using a representative substrate, sequence, enzyme, reaction or analytical method. Include a suitable reference or previously accepted lot when available, keep preparation conditions comparable and predefine the observations that will trigger acceptance or investigation. Useful endpoints can include conversion, coupling efficiency, impurity formation, recovery, transcript integrity, conjugation yield or downstream signal, depending on the material. Record both the chemical result and practical behavior such as dissolution time, foaming, color change, precipitation or instrument delivery. This separates a material-quality question from a process-compatibility question and creates evidence that can support later lot-to-lot comparison.
Review process and scale risks before increasing quantity
Scale changes can expose risks that are not visible in a small research batch. For a research material, review handling, purification, analysis and scale-up before committing to a larger campaign. Estimate concentration, heat and mass-transfer needs, hold times, mixing limits, filtration area and the stability window of intermediates or prepared solutions. Identify the operations that control impurity rejection rather than assuming reaction yield alone will predict an acceptable isolated product. Raw-material availability and variability should be included in the route review, especially when a protecting-group reagent, specialty precursor or purification medium has a long lead time. A staged plan—feasibility, confirmation batch and then larger manufacture—provides checkpoints for analytical comparability, safety review and yield reconciliation while there is still room to adjust the process.
Build an analytical package that answers buyer questions
The useful documentation package should connect identity, purity and intended use. At minimum, align the specification and lot-specific Certificate of Analysis; then identify which supporting data are appropriate for the chemistry, such as HPLC or UPLC, LC-MS, high-resolution MS, NMR, water, residual solvents or inorganic-ion analysis. Chromatograms and spectra are most helpful when the material form, sample preparation and acceptance logic are clear. For complex or highly polar materials, a single percentage may not describe all relevant attributes, so note whether the result represents area purity, assay, concentration or another basis. Change control should cover shifts in route, critical starting material, purification approach, analytical method or manufacturing site when those changes could affect comparability. This framework helps technical, QA and procurement reviewers reach the same conclusion from the same evidence.
Use a structured request to shorten technical review
A complete inquiry for a research material should include the structure or unambiguous identifier, desired form, target quantity, expected future scale, intended use, target date and required documentation. Add known constraints: sensitive functional groups, prohibited solvents, metal limits, water sensitivity, shipping temperature, packaging preference or compatibility with an established method. If the request supports a regulatory submission, state the development stage and the documents expected, but do not assume that research-use or non-GMP material carries a qualification it does not have. Ask the supplier to identify open assumptions in the quotation and to separate confirmed specification items from values that still require method development. The resulting technical exchange is more efficient, and the final quotation can be tied to a material definition that is meaningful to scientists, procurement and quality reviewers.
Build a fit-for-purpose request
Before sourcing or scale-up, align the exact structure, intended workflow, target purity and assay basis, required form, storage conditions, quantity, timeline and documentation. If a catalog item does not match those requirements, a related analog, impurity standard, reference material or research-use custom route can be reviewed.
References
Technical context is supported by the peer-reviewed literature below.
- ST Pharm (2021) ST Pharm announces expansion of oligonucleotide facility, taking a leap towards the world largest oligonucleotide CDMO — company announcement
- Contract Pharma — ST Pharm to expand oligonucleotide facility
- DCAT Value Chain Insights — ST Pharm investing to expand oligonucleotide manufacturing capacity
- Christensen et al. (2025) Current industry practices for therapeutic siRNA and ASOs. Nucleic Acids Research