Nanoparticles & LNP Formulation Services

Design → GMP, without detours

Dual hubs: San Diego, CA (Southern California) & Montréal, Canada
Scope: Lipid nanoparticles (LNPs) for mRNA/siRNA/DNA, polymeric or hybrid particles where justified, process development through GMP, analytics and stability, aseptic fill–finish, and cold-chain readiness.

At MycoVista, nanoparticle work begins with one question: what must the patient receive—precisely—and what proof will convince an auditor it arrived intact? From that question, we design the formulation, the process, and the documentation as a single system. We map QTPP → CQAs → CPPs on day one, then we engineer microfluidic mixing, solvent removal, and buffer exchange so that size, PDI, encapsulation, osmolality, and potency hold from bench to batch. The result is manufacturability by default: fewer handoffs, fewer unknowns, faster learning loops, and inspection-grade outputs.

Why teams choose MycoVista for nanoparticles

Decisive. Technical. Audit-ready. That’s our operating system.

End-to-end ownership. Sequence or payload readiness → formulation design → microfluidic mixing scale-up → TFF and solvent removal → sterile filtration feasibility → fill–finish → stability—harmonized across two synchronized facilities on a unified digital QMS (ALCOA+).
Depth in the hard parts. We tune flow rate ratio (FRR), total flow rate (TFR), N/P ratio, pH, ionic strength, and temperature so the particle you characterize at 1 mL behaves at 10 L. We build solvent removal and buffer exchange to protect encapsulation and avoid dsRNA formation.
Analytics first. We set acceptance criteria before we run DoE. We trend size, PDI, zeta, encapsulation efficiency, residual solvent, osmolality, potency, and sterility as the language of truth—then we lock the design space when the evidence agrees.
Cross-modal composure. Our mammalian, microbial, vector, and small-molecule teams sit at the same table. That keeps our assumptions honest about raw materials, utilities, and release testing.

What “Nanoparticles” means at MycoVista (scope & positioning)

We focus on platforms that survive scale, validation, and inspection.

Lipid nanoparticles (LNPs): ionizable + helper + structural + PEGylated lipids for mRNA, siRNA, and plasmid DNA payloads.
Hybrid or polymeric systems: only when they win on stability, potency, or manufacturability; otherwise, we prefer the smallest credible platform that passes audit.
Use cases: vaccines, in vivo gene regulation, ex vivo transfection materials, and research-to-clinic delivery of nucleic acids.
Phase coverage: discovery material with fit-for-purpose testing → IND/IMPD readiness → clinical GMP with qualified/validated methods and aseptic presentation.

Our bias: pick the simplest recipe that delivers potency and survives the night shift. Continuous improvement is welcome; uncontrolled novelty is not.

Formulation by design: from intent to control strategy

We reverse-engineer the formulation from what patients and regulators will accept.

QTPP (what must be true): dose per vial, route (IM/IV/SC), target particle size window, acceptable PDI, osmolality range, encapsulation ≥X%, potency retention over transport and storage, and sterile presentation.
CQAs (what we will measure): hydrodynamic diameter, PDI, zeta potential (contextual), encapsulation efficiency, nucleic acid integrity (and dsRNA for mRNA), residual solvent, pH/osmolality, sterility, endotoxin, particulate counts.
CPPs (what we can control): FRR/TFR, lipid:RNA ratio and N/P, solvent content at mixing, temperature profile, pH/ionic strength at dilution, TFF parameters (TMP, shear, diafiltration volumes), hold times, and sterile filtration strategy.

Deliverable: a program-specific control strategy that ties each CQA to the unit operation and the document that proves it.

The bench-to-batch workflow (and where scale can go wrong)

We keep the physics the same while we grow volume.

1) Pre-formulation (get the payload and lipids right)

Payload assessment: for mRNA, we verify 5’ cap structure, poly(A) tail length, and integrity; for siRNA and DNA, we confirm purity/topology. We agree on acceptable dsRNA levels for mRNA early, because that decision echoes throughout analytics and immunogenicity risk.
Lipid system selection: ionizable lipid pKa, helper/structural lipid ratios, and PEG length are chosen for your route and dose. We avoid unnecessary complexity; every excipient earns its place.
Compatibility checks: we screen buffers, pH windows, and ionic strengths that allow fast, controlled self-assembly and still permit sterile filtration later.

2) Microfluidic mixing (where LNPs are born)

Device and regimen: we tune FRR and TFR to target nucleation and growth kinetics that produce the desired size and PDI. We control temperature not cosmetically but to control solvent exchange and bilayer order.
Design of experiments: we vary FRR, TFR, N/P, lipid composition, and temperature systematically. We read out size/PDI/Enc% within hours so each iteration teaches.
Scale-similarity: before we scale, we prove that channel geometry and residence times at higher flow match the small-scale energy environment. That’s how we keep 80–100 nm targets from drifting to 120–150 nm at volume.

3) Solvent removal & buffer exchange (TFF without regrets)

Tangential flow filtration: we select membranes to protect Enc% while clearing solvent and exchanging into physiological buffers. We manage TMP, cross-flow, and shear so aggregation doesn’t appear two weeks later.
Residual solvent monitoring: we monitor by suitable methods; we don’t assume it leaves because the flow sheet says so.
Diafiltration logic: we set the number of diavols by measurement, not folklore. If we can reduce diavols without compromising purity or osmolality, we do.

4) Sterile filtration feasibility (and when not to force it)

Reality check: sterile filtration drives particle size strategy. If your design consistently exceeds the practical filtration window, we either adjust size or pursue aseptic processing with validated controls.
Filter selection and recovery: we quantify pre- and post-filter Enc%, titer, and potency. We do not passively “accept” 20% loss; we learn why and fix what’s fixable.

5) Fill–finish, labeling, and cold chain

Presentation: vial or prefilled syringe with buffers that protect particle integrity and osmolality.
Cryo/lyo feasibility: when appropriate, we evaluate cryoprotectants or lyophilization. If lyophilization adds risk without clinical value, we document why we stay liquid.
Hold times & shipping: we validate holds at relevant temperatures and simulate transport. We design with operator reality in mind; three-hour limits that collapse at 2:59 are not designs.

Analytics that read the truth (not just numbers that move)

We plan orthogonal methods so one technique convinces and two techniques persuade.

Size & PDI: dynamic light scattering (or equivalent) with fixed acceptance ranges; where useful, orthogonal confirmation for outlier investigations.
Zeta potential: informative in development; we avoid over-interpreting it at release unless clinically relevant.
Encapsulation efficiency: validated fluorometric or dye-displacement methods with controls for quenching and matrix effects.
Nucleic acid quality: for mRNA—length, integrity, and dsRNA content; for siRNA—purity and strand integrity; for DNA—topology and residuals.
Residuals & safety: residual solvent, detergents (if used), endotoxin, bioburden/sterility.
Osmolality & pH: set to route and comfort; we avoid buffers that look good on paper but punish patients or filters.
Potency: cell-based or biochemical readouts aligned to mechanism. For vaccines, we map potency to expression; for gene regulation, we map to knockdown/activation.
Particulates: where route/syringe demands, we test visible/subvisible particulates to protect patients and devices.

Trending: we chart CQAs run-to-run and lot-to-lot. We lock windows when the data, not our optimism, says it’s time.

Backgrounder: why LNPs fail—and how we keep them from failing

Instability and variability usually trace back to uncontrolled assembly or uncontrolled removal. If assembly (mixing) creates wide size distributions, filtration punishes you later. If removal (TFF/solvent clearing) happens under the wrong shear or temperature, Enc% and potency leak away invisibly until stability testing embarrasses you. We avoid both failure modes by matching physics across scales and by instrumenting steps that used to be “feel.” We’d rather make one honest LNP well than create five exotic ones none of which will pass audit.

Manufacturing & GMP controls (what you’ll feel day-to-day)

QbD in practice: we document the linkage from QTPP to CQA to CPP. We place DoE results in protocols—not slide decks—and we carry ranges into batch recipes.
Digital QMS (ALCOA+): eBMR/eBR, deviation/CAPA, change control, and validated computerized systems—harmonized across San Diego & Montréal.
Material control: we qualify lipids (identity, purity, peroxide/aldehyde limits), nucleic acids (integrity, residuals), solvents, and filters. We maintain alternates for criticals with comparability on file.
Cleaning & E/L: where contact surfaces or solvents justify, we run extractables/leachables programs and cleaning validation that survive inspection.
Aseptic discipline: when filtration is viable, we filter; when not, we run in aseptic isolators/RABS with validated interventions and robust EM data.

Fill–finish: where the story lands

Container closure: vials or prefilled syringes qualified for the formulation; we manage silicone oil and surface interactions proactively.
Visual inspection: automated or manual per phase; we set clear reject criteria that operators can apply without debate.
Labeling & serialization: we embed the data you and regulators need—no scavenger hunts at release.
Cold chain: we match the chain to your stability truth. If the science supports 2–8 °C, we don’t ship at −20 °C to look “serious.” If deep-cold is warranted, we build a chain that actually works on a bad day.

Safety, immunogenicity, and regulatory posture

Immunostimulation: dsRNA and impurities drive innate responses; we minimize them and set acceptance criteria that reflect clinical reality.
Residual solvents & reagents: we control and test per applicable expectations; we don’t hand-wave because “it’s an excipient.”
Regulatory authoring: we write IND/IMPD/BLA text that quotes methods, acceptance criteria, and data—not adjectives. Reviewer Q&A comes with raw data and statistics plans.

Facilities & equipment (selected highlights)

Mixing: microfluidic platforms suitable for development through production-relevant runs; geometry chosen to preserve scale similarity.
TFF: skids with closed-system capability, recipe control, and instrumentation for TMP, cross-flow, and temperature.
Filtration: sterile filtration with integrity testing embedded in batch records; staged prefilters to protect the final membrane.
Cleanrooms: ISO 8/7, positive pressure and HEPA, unidirectional flows; BSL-2 where required. Validated utilities (HPW/clean steam/compressed air) with continuous trending.
Analytics: DLS/osmolality, fluorometric encapsulation, nucleic acid integrity assays (and dsRNA detection for mRNA), endotoxin, sterility, and potency.
Data systems: validated CDS, LIMS, ELN, and eBMR/eBR with audit trails and access controls aligned to ALCOA+.

Program Onboarding (your first 30 days)

Speed is useful only if the outputs are inspection-grade. In month one you receive:

A phase-appropriate control strategy that maps QTPP → CQAs (size, PDI, Enc%, potency, residuals, sterility, osmolality) → CPPs (FRR, TFR, N/P, pH, TFF, filtration).
A DoE plan for mixing and TFF with sampling plans, acceptance criteria, and a potency readout that matters.
A Gantt & risk map (FMEA) with decision gates to IND/registration, plus a filtration feasibility plan and a stability program aligned to your shipping reality.

Start: share payload class (mRNA/siRNA/DNA), route and dose goals, desired size window, and target presentation. We return a design space, unit-op parameters, and a documented path to GMP.

Typical timelines (indicative, biology- and physics-gated)

Feasibility (weeks): pre-formulation, initial mixing screens, Enc% and size/PDI targets achieved, early solvent removal and buffer exchange.
Development (months): DoE to lock FRR/TFR/N/P, temperature, and TFF recipe; filtration feasibility; draft formulation and stability plan.
Engineering runs: scale-similar mixing, TFF, and filtration with mass-balance and trending; hold-time studies; aseptic readiness.
Lock: process description with CPP ranges, method files with qualification/validation plans, and regulatory text.

We don’t promise calendar dates your molecule won’t keep. We show you the gates, the criteria for passing, and the fast path that stays safe.

Tech transfer & rescue programs

Most LNP projects arrive mid-story. We turn them into a narrative regulators can trust.

Document triage: methods, deviations, release history, stability, and change controls.
Gap map: which CQAs or CPPs lack controls; what fixes buy the most risk reduction fastest.
Stabilize → optimize → re-lock: we don’t ship risk; we reduce it, document it, and gate it.

ESG & supply chain (reliability is a quality attribute)

Sensible disposables: closed, single-use assemblies where they cut contamination risk and turnaround time; stainless where cleaning validation and cost win.
Criticals strategy: qualified alternates for lipids, membranes, filters, and solvents with comparability in place; stocking plans matched to campaign risk.
Utilities stewardship: oxygen, water, and solvent handling sized to route and scale; emissions managed responsibly.

Deliverables (what you can hold)

Formulation control strategy tied to patient and regulatory needs.
Process description with design space and CPP limits; validated control loops and interlocks.
Analytics package with methods, qualification/validation status, and trending; dsRNA and encapsulation data where applicable.
Stability protocols and interim data, with shelf-life rationale matched to presentation.
Batch records (eBMR/eBR) with in-line data and intervention logs; CMC text ready for IND/IMPD/BLA.

A few patterns that make us different

Headroom over hero runs. We build processes that survive shifts, solvents, and Sundays.
Orthogonal by default. Two methods for the attributes that matter most; one method for what is stable and boring—by design.
One truth, two hubs. The same control strategy follows your nanoparticle across San Diego & Montréal.
No brand worship. If a tool serves the biology and the audit, we use it. If not, we don’t.

Frequently asked (straight answers)

Can you make LNPs that filter sterile? Often yes—if we design the size window and composition accordingly. If filtration harms potency or Enc%, we move to aseptic processing with validated controls.
Do you handle dsRNA for mRNA? Yes—detection, acceptance criteria, and process levers that keep it low. We design analytics and TFF to avoid creating it in the first place.
Can you lyophilize our LNP? Sometimes. We run feasibility with cryo/lyo protectants; if the science doesn’t support it, we keep a liquid route and document why.
What about large-scale TFF? We run recipe-controlled TFF with instrumentation and PAT; we qualify membranes for fouling and recovery on real intermediates.
How do you ensure lot-to-lot equivalence across hubs? Mirrored methods, predefined transfer protocols, equivalence metrics, and shared reference standards.

Summary — why MycoVista for nanoparticles

Because LNPs and nanoparticles don’t need mystique—they need physics you can scale, analytics you can defend, and cold chain you can trust. We design the formulation, the unit operations, and the documents together. We prove sameness when you change, and we move from Design → Data → Decision without detours.

MycoVista | San Diego, CA & Montréal, Canada
Start Program Onboarding → Share payload, route, dose goals, size window, and presentation. We’ll return a design space, control strategy, and a documented path to GMP.

EN / FR support available.