High concentration & subcutaneous. From preclinical to lifecycle.
We develop high-concentration liquid and lyophilized formulations, and the UF/DF processes behind them, for subcutaneous delivery at every stage: aseptic, non-GMP preclinical batches, clinical development, and IV-to-subcutaneous lifecycle programs. 66 programs since 2010. Clinical supply manufacturing transfers to your manufacturer-of-choice.
High-concentration work, in numbers
- Across mAbs, ADCs, and fusion proteins, from preclinical batches to lifecycle programs.
high-concentration or subcutaneous programs
ADC concentrated in liquid, no precipitation
mAb concentrated in liquid, stable and injectable
API per candidate for feasibility
from scope alignment to project start
The same protein at 15 times research concentration has entirely different problems.
In a highly concentrated liquid formulation (HCLF), antibody molecules sit close enough to attract one another through charged and hydrophobic surface patches. Viscosity rises exponentially, and self-association, opalescence, and phase separation can appear that were absent at low concentration. Each one can force reformulation, at any stage.
It changes again at scale-up.
A buffer that works at 10 mg/mL can behave differently at 150. During UF/DF, the Donnan effect shifts pH and excipient levels as the protein concentrates, so problems also surface at scale-up.
Formulated for repulsion.
We adjust pH, ionic strength, and excipients to maximize repulsive protein-protein interactions and thermodynamic stability, then measure viscosity, turbidity, osmolality, aggregation (SE-HPLC), and particle size distribution at target.
What we screen for:
- High viscosity
- Self-association
- Opalescence
- Phase separation
- Aggregation
- Sub-visible particles
What changes at each stage?
High-concentration work changes with your program’s stage. Preclinically, the question is whether the target concentration is achievable. In clinical development, it’s whether the formulation and process hold their quality through scale-up and shelf life. At lifecycle, it’s how to move an approved product to subcutaneous self-administration.
Preclinical
Formulation screening, concentration challenge, and short-term stability at target
Under 200 mg of API per candidate
Liabilities found late, after cell line and CMC commitment
Aseptic, non-GMP batches in prefilled syringes for tox studies
A defined high-concentration formulation for tox, PK, and Phase 1
Frozen liquid, −20 / −70 °C
Excipient optimization, UF/DF process development, and forced, accelerated, and in-use stability
Grams of clinical-grade material for process and stability work
pH and excipient shifts during UF/DF, and particle formation
Syringeability in-system, with break-loose and glide force
Process transferred to your manufacturer for clinical supply
Late stage and lifecycle
Reformulation, high-concentration lyophilizates, and container material compatibility
Commercial-scale material is available for development work
Comparability with the approved product, and in-syringe shelf life
Prefilled syringes, cartridges, or dual-chamber systems for self-administration
Development data to support comparability and transfer to your manufacturer
Support at every development stage
Each stage can be booked on its own. Many clients start with preclinical feasibility. Others come to us during clinical development with viscosity, stability, or syringeability problems, or at lifecycle to move an IV product to subcutaneous.
Preclinical feasibility
Whether your candidate can reach its target concentration, tested on under 200 mg of API, plus aseptic preclinical batches.
Clinical development
Excipient optimization, UF/DF process development, and forced, accelerated, and in-use stability, ready to transfer to your manufacturer.
Presentation and lifecycle
Syringeability, container material compatibility, and in-syringe shelf life in prefilled syringes, cartridges, or dual-chamber systems.
Concentration sets the dose, but viscosity and glide force decide injectability.
A concentration target matters only if the formulation passes through the needle. Viscosity rises exponentially with concentration, and subcutaneous targets typically sit at 20 cP or below. So, we measure viscosity at the target concentration and test break-loose and glide force in-system, in the intended syringe or syringe candidates. In a representative program, a mAb went from 110 to 200 mg/mL at under 20 cP, injectable through a 26G needle.
Send us four things. We’ll send back a scope.
Under a CDA: your sequence or molecular weight, pI, development stage, and target dose, volume, and device. You get a proposal with what we’d test, in what order, and how long it takes. Programs can start at any stage.
Questions we know you have, and actually helpful answers
How much material do I need for high-concentration feasibility?
“Yes. We manufacture aseptic, non-GMP preclinical batches of up to [~1,000] vials per run, depending on vial size, then transfer the process to your manufacturer for clinical supply.” (Note: [~1,000] is still a placeholder in the copy doc, client to confirm.)
How long until we know whether subcutaneous dosing is possible?
“Yes. Six of our 29 ADC programs have been high-concentration or subcutaneous, and we’ve concentrated an ADC to 100 mg/mL in liquid with no precipitation.”
Can you improve a high-concentration formulation already in clinical development?
“Yes. Sixteen of our 29 ADC programs have advanced into GMP. We tailor the cycle to your manufacturer’s freeze-dryer, including older or larger units, and mock up the fill-finish process before transfer.”
Which excipients reduce viscosity in high-concentration antibody formulations?
“Yes. Higher DAR and hydrophobic payloads raise aggregation risk, which is exactly what our stress screening targets: aggregation, charge heterogeneity, and deconjugation.”
When should I consider a lyophilized high-concentration formulation?
“Yes, that’s the usual case. If the naked antibody is available too, a side-by-side comparison shows how much the linker-payload affects stability.”
How do you handle cytotoxic material during freeze-drying?
All ADC work, including freeze-drying, runs in dedicated laboratories with cytotoxic containment.
How quickly can you start, and how long does it take?
Two to four weeks from scope alignment to project start. A lead formulation with initial stability data typically takes about three months.
Can you screen candidates for developability before nomination?
Yes. Low-material developability screening compares candidates before you nominate one.
How do you shorten an ADC lyophilization cycle?
We develop the cycle tailored to the formulation and to your manufacturer’s freeze-dryer. Highlights: [X h] to [Y h], [X h] to [Y h].
What analytical methods do you use for ADC stability?
Our panel includes detergent and excipient quantification. [Full method panel to be confirmed by the lab.]
Didn’t find your question? Conversations and quotes are always free.
Let’s talk about your molecule and what it needs to go subcutaneous.
Our calls get technical quickly. If another partner fits better, we’ll tell you.