Design → GMP, without detours

Main hub: San Diego, CA (Southern California)
Scope: Clarification, capture, polishing, viral safety, UF/DF, and final formulation for mAbs & biologics, microbial & fungal proteins/enzymes, AAV & plasmids, and nanoparticles (LNPs) — engineered for scalability, economy, and inspection.

We built MycoVista’s purification practice around a blunt truth: upstream only matters if downstream can keep up. So we design USP and DSP together—binding capacities sized on real harvests, impurity maps that behave at scale, and documents that survive audits. The outcome is simple: higher right-first-time rate, predictable cost of goods, and fewer surprises when you switch from bench to campaign.

Why teams choose MycoVista for DSP

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

• End-to-end ownership. Clarification → capture → polishing → viral safety → UF/DF → formulation → release, harmonized in a unified digital QMS (ALCOA+) across two synchronized facilities.
• Designed with upstream. We set column sizes, residence times, and filter trains using real harvests—not buffer fantasies.
• Analytics first. Process truths come from data; we trend recovery, impurity clearance, and pressure curves every run, and we lock ranges when the evidence says so.
• Cross-modal skill. Mammalian, microbial, vectors, pDNA, and LNPs—one control-strategy template, tuned per modality, so your CMC reads like a single story.

What “Downstream” means at MycoVista

• Primary recovery & clarification: cell removal, viscosity control, DNA and lipid management, scalable flocculation/conditioning where warranted.
• Capture: bind-and-elute affinity where justified; smart flow-through for cost and robustness; multi-column capture when productivity and resin lifecycle win.
• Polishing: ion exchange (AEX/CEX), hydrophobic interaction (HIC), mixed-mode (MM), size-based options—selected using your impurity map, not fashion.
• Viral safety: low-pH inactivation studies, detergent steps where applicable, and viral filtration engineered to avoid “hockey-stick” pressure rise at PPQ.
• UF/DF & formulation: concentration + diafiltration strategies that preserve activity, control aggregates, and set you up for fill–finish.
• Analytics & release: identity, purity, potency, residuals, and stability—right-sized to your phase and risk.

Primary recovery & clarification

Goal: deliver a feed that your capture step loves.

• Cell harvest: scalable centrifugation and depth filtration trains mapped with real pressure–throughput curves; flocculation or chemical conditioning only if it de-risks fouling and doesn’t haunt validation.
• Viscosity & DNA control: DNase strategies where needed (and compatible with downstream), selective precipitations conditioned to resin and membrane specs.
• Microbial & fungal nuance: inclusion-body programs with mechanical/chemical lysis that won’t poison capture; high-solids broths from fungi with staged filters that actually de-plug.

Deliverable: a clarity and conductivity window defined for capture—no more “it depends.”

Capture

We don’t worship a platform. We prove the economics and the clearance.

• mAbs & Fc-containing proteins: classical affinity for capture when lifecycle cost, leachables, and caustic tolerance align; we run residence-time DoE and caustic-clean studies so column plans survive campaigns.
• Non-Fc proteins/enzymes: AEX/CEX/HIC/MM chosen by isoelectric point, hydrophobicity, and impurity profile; flow-through capture where clearance and capacity allow (often cheaper, more robust).
• Microbial proteins: periplasmic vs cytosolic harvests dictate the capture logic; for inclusion-body programs, we design refold alongside capture so economics add up.
• Plasmid DNA: alkaline-lysate clarification → selective precipitation/conditioning → AEX capture sized for supercoiled content and endotoxin control.
• AAV & other vectors: modality-appropriate affinity capture with salt/detergent robustness studies; pressure and lifetime planned for real cleaning cycles.
• Nanoparticles (LNPs): TFF-centric “capture” (concentration + buffer exchange) with optional orthogonal steps to control free nucleic acid or solvent carryover.

Deliverable: capture step with binding capacity, residence time, cleaning recipe, and lifecycle cost you can budget.

Polishing

The right polishing train is a function of your impurities, not ours.

• Ion exchange (AEX/CEX): remove charge variants, HCP, DNA/RNA, and endotoxin; bind-and-elute or flow-through depending on your pI and salt window.
• Hydrophobic interaction (HIC): invaluable for aggregates and misfolded species—screen salt types/strengths to minimize viscosity pain.
• Mixed-mode (MM): when single mechanisms fail, we use multi-interaction resins that can simplify the train—validated for ligand leachables and cleanability.
• Size-based options: true size-exclusion for small-scale or critical separations; membrane-based size separations for vectors where SEC won’t scale.
• AAV empty/full: ion-exchange strategies tuned to capsid surface charge; gradients validated for lot-to-lot stability.
• pDNA finishing: polishing that preserves supercoiled topology and beats endotoxin back—measured, not assumed.

Deliverable: polishing sequence with clearance claims backed by mass balance and orthogonal analytics.

Viral safety

We architect viral safety into the process—not as a last-minute patch.

• Low-pH inactivation developed on real intermediates to confirm kinetics, compatibility, and neutralization timing.
• Detergent steps where appropriate for enveloped viruses—studied for membrane compatibility down-track.
• Viral filtration: filter selection and pressure-time modeling so you avoid catastrophic flux loss; prefilters sized with real colloid loads; integrity testing embedded in batch records.

Deliverable: a viral-safety narrative tied to unit operations and supported by studies appropriate to phase.

UF/DF & formulation

We make membranes and buffers earn their keep.

• UF/DF design: staging to avoid shear and osmotic shock; hold-up and recovery quantified; aggregation thresholds found in development, not discovered at release.
• Membrane selection: MWCO chosen by hydrodynamic radius, not folklore; fouling and cleanability tested on process intermediates.
• Formulation screens: pH, excipients, ionic strength, antioxidants/surfactants where justified; stress studies that reflect shipping and storage reality.
• Vector & LNP nuance: osmolality and buffer chemistry that preserve potency and encapsulation—sterile filtration feasibility proven early.

Deliverable: final bulk specs with hold times, transfer conditions, and a buffer recipe that won’t crumble at scale.

Continuous & intensified DSP

Continuous is a tool, not a religion.

• Multi-column capture for capacity and resin economy; dynamic control proven before we scale.
• Membrane chromatography for high-throughput flow-through polishing; in-line conditioning to reduce tank farm chaos.
• PAT hooks so continuous steps remain decisional in real time—UV, conductivity, pH, and mass balance checks that trigger action, not debate.

We adopt it when: validation is clean, economics win, and operations can run it at 3 a.m. without drama.

PAT & analytics for DSP

• In-line/at-line: UV280, conductivity, pH, temperature, density; fraction analytics queued for rapid read-back.
• Orthogonal purity: SEC-MALS (size variants), CE-SDS (R/NR), icIEF/IEF (charge), LC-MS peptide mapping, binding/potency assays.
• Residuals: HCP, host cell DNA/RNA, affinity ligand residuals, detergents/processing aids, endotoxin/bioburden/sterility, mycoplasma where applicable.
• Stability: forced degradation tied to mechanism (oxidation, deamidation, clip), real/accelerated storage matched to your supply chain.

Outcome: design space and CPPs tuned by evidence, with trending that keeps lots in family.

Scalability & engineering (where columns get real)

• Column sizing: bed height, flow velocity, residence time, and pressure drop engineered for your protein and resin—verified by scale-down models that actually predict.
• Cleaning/Sanitization: NaOH tolerance verified; cleaning recipes validated; lifecycle tracking (cycles, performance decay, bioburden risk).
• Filter trains: staged depth filters with capacity models; pre-use/post-use integrity tests baked into the batch record.
• Hold-ups & transfers: line/tank hold-up volumes mapped; hold-time studies to keep potency and purity intact.
• Materials: contact materials qualified; extractables/leachables programs where risk warrants.

Facilities & equipment (select)

• Chromatography: pilot to GMP skids with gradient accuracy and automated cleaning; multi-column options; validated sensors and data capture.
• Filtration: depth, sterile, and viral filtration capabilities; high-capacity TFF skids for UF/DF with recipe control and automated diafiltration.
• Utilities & suites: ISO 8/7 cleanrooms, positive pressure and HEPA, unidirectional flows; BSL-2 where required; validated utilities (HPW/clean steam/compressed air).
• Analytics: HPLC/UPLC, LC-MS, CE-SDS, icIEF, SEC-MALS, PCR/ELISA; osmolality and DLS for LNP/vector work.
• Storage & handling: LN₂ cell banks; cold rooms/freezers aligned to stability needs; segregated staging for buffers and intermediates.

cGMP, regulatory, and QMS (what you’ll feel day to day)

• QbD: QTPP → CQAs → CPPs start at development; risk-based DoE codified in protocols.
• Digital QMS (ALCOA+): eBMR/eBR, deviation/CAPA, change control, validated computerized systems.
• Regulatory: IND/IMPD/BLA authoring support; method qual/val; viral clearance and hold-time studies planned by phase; ICH stability programs.
• Audit-ready artifacts: mass-balance tables, recovery trends, cleaning validation reports, and lifecycle summaries for filters/resins.

Program Onboarding (first 30 D)

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

1. A phase-appropriate QTPP and draft control strategy linking CQAs (purity, potency, residuals, viral safety) to unit operations.
2. A DoE plan for clarification, capture, polishing, viral filtration, and UF/DF—sampling plans, pass/fail criteria, and PAT.
3. A Gantt and risk map (FMEA) with decision gates to IND/registration, plus preliminary formulation and stability roadmaps.

Start: Share modality, dose goals, target presentation, scale, and stability intent. We return a design space, unit-op parameters, analytics map, and a documented path to GMP.

Typical timelines

• Scouting: harvest behavior, filterability, binding screens, early polishing feasibility.
• DoE & lock: residence-time/gradient studies, impurity clearance, pressure–throughput windows, cleaning recipes—then process lock when CPPs land.
• Scale-confirm: engineering runs with mass balance and recovery/purity reproducibility; documentation pack for regulatory and QA.

Tech transfer & rescue programs

We pick up mid-stream processes, stabilize them, and document the path forward.

• Triage: methods, deviations, stability, change control history.
• Gap map: which CPPs/CQAs are actually uncontrolled, what data is missing, and the fastest safe fixes.
• Stabilize → optimize → re-lock: we don’t ship risk; we reduce it, document it, and gate it.

ESG & supply chain

• Resin & membrane lifecycle: planned cycles, cleaning economies, and end-of-life criteria—no surprises in Q4.
• Single-use vs stainless sanity: disposables where they lower contamination risk and time; stainless where cleaning validation and cost win.
• Qualified alternates: for resins, membranes, and critical buffers; stocking plans matched to campaign risk and lead times.

Deliverables

• DSP process description with design space, CPP ranges, and validated cleaning recipes.
• Mass-balance & recovery tables and impurity-clearance data per step.
• Analytics package (methods; qual/val status; trending).
• Viral-safety plan with studies appropriate to phase.
• UF/DF & formulation specs with hold-times and transfers.
• Batch records (eBMR/eBR) tied to sensors, alarms, and interventions.

A few patterns that make us different

• Capture that scales. We size by pressure curves and breakthrough, not wishful titers.
• Polish to the map. Your impurity map picks the train; we don’t over-purify what regulators don’t ask for.
• Headroom over hero runs. Processes survive fouling and variability at real scale.
• One truth, two hubs. The same control strategy follows your molecule across San Diego & Montréal.

Downstream Processing & Purification Services- FAQ

Is continuous chromatography right for us?

When resin economy and throughput win—and validation/operations agree. Otherwise, robust batch runs the night shift better.

Do you support AAV empty/full separation at scale?

Yes—charge-based strategies tuned and trended; we’ll show lot-to-lot stability before lock.

Can you keep pDNA supercoiled at scale?

Yes—conditioning, capture, and polishing are designed around topology and endotoxin control.

How do you avoid viral-filter collapse?

Prefilter design, colloid control, realistic flux targets, and pressure-time modeling—validated with your feed.

Will you change the train mid-program?

Only if the data demands it—and we’ll run comparability and document the transition.

Conclusion—why MycoVista is the best CDMO

Because purification is where reality shows. Our downstream processing & purification services treat clarification, capture, polishing, viral safety, UF/DF, and formulation as a single, data-governed system. We size binding capacities on real harvests, confirm breakthrough curves and pressure–time limits, and map impurities to IEX/HIC/mixed-mode steps with validated LER. Viral clearance is proven with orthogonal steps; UF/DF locks TMP, shear, and diavolumes to protect quality attributes.

Formulation includes filtration/lyo feasibility, CCIT, and stability tied to intended logistics. PAT, mass balance, and recovery trend every run; ALCOA+ eBMR/eBR, LIMS/ELN, and CPV make the record inspection-grade by default. The outcome: higher right-first-time rates, predictable COGs, and smooth scale-up from bench to campaign. Choose MycoVista when downstream processing & purification services must deliver Design → Data → Decision → GMP—without detours.

MycoVista | San Diego, CA
Start Program Onboarding → Share modality, dose goals, scale, and stability targets. We’ll return a design space, control strategy, and a documented path to GMP.

EN / FR support available.

Contact our team today at info@mycovistabiotech.com