Select Small Molecules & Process Chemistry

Design → GMP, without detours

Dual hubs: San Diego, CA (Southern California) & Montréal, Canada
Scope: Route scouting and selection, hazard assessment and safety, process development and scale-up (batch, intensified, or continuous flow), impurity control and specification setting, crystallization/polymorph/particle-engineering, kilo-lab through GMP API manufacture, cleaning validation, stability per phase, and tech transfer—executed in a unified digital QMS (ALCOA+).

At MycoVista, small molecules deserve the same decisiveness you expect from biologics: a clean route, a disciplined impurity map, a solid form that travels, and a control strategy that reads well under inspection. We tie QTPP → CQAs → CPPs on day one, then we build reactors, workups, and unit ops that operators can run at 3 a.m. without drama. We prefer headroom over hero runs. We ship processes—not just schemes.

Why teams choose MycoVista for small molecules

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

End-to-end ownership. Route design → hazard & safety → lab development → kilo-lab → GMP API → packaging and release—harmonized across two synchronized facilities with mirrored methods and documentation.
Solid-form first. We control polymorph, hydrate/solvate state, and particle-size distribution before scale conspires against you.
Impurity literacy. We make and track likely and “uninvited” impurities; then we select unit operations that clear them for real, not just on the slide.
Operations that survive reality. We pick solvents, temperatures, and unit ops that a line can hold—nights, weekends, audits included.
Regulatory spine. ICH-aligned specifications, cleaning validation with defensible MACO/PDE logic, and stability programs you can defend.

What “Select Small Molecules” means at MycoVista (scope & positioning)

We take on programs where our approach improves risk, time, or cost without compromising compliance.

API & advanced intermediates (non-stereogenic and stereoselective routes, chiral resolutions, and biocatalytic assists when they win).
Salt/solid-form selection with XRPD/DSC/TGA/DVS-driven decisions; polymorph screening that informs process, not just a report.
Crystallization & particle engineering: seeded cooling, anti-solvent, pH-shift, and continuous crystallization where justified; wet-milling or jet-milling when needed.
Impurity control: route design that avoids genotoxic liabilities; targeted synthesis of impurity markers/standards; clearance proven by mass balance and orthogonal analytics.
Process modes: batch by default; intensified or flow/continuous when validation is clean and economics win.
Scale: gram→multi-kilogram development; kilo-lab to GMP API for qualified programs; packaging and release built for clinical supply.
Potent handling: closed transfers, isolators, and containment practices suitable for OEL-banded compounds—engineered with EHS at the table.

Bias: simple beats clever. If a unit op doesn’t reduce risk or cost, we remove it.

Backgrounder: how small-molecule success actually happens

Small molecules fail for three common reasons: (1) the “best-day” route collapses at scale, (2) the impurity story reads like folklore, and (3) solid form shows up late. We counter all three—first, by picking chemistry that respects heat/mass transfer and operator reality; second, by making the impurities and proving how we clear them; and third, by putting crystallization and polymorph control into development notebooks early, so scale follows the form, not the other way around.

From QTPP to line settings (control strategy in practice)

We reverse-engineer the process from what patients and regulators must see at release.

QTPP (what must be true): route intent, target form (polymorph/salt/solvate), assay and potency ranges, acceptable residuals (solvents, reagents, catalysts), impurity thresholds (including genotoxic alerts), particle-size window (if DP-critical), packaging, and shelf life.
CQAs (what we measure): identity, assay, purity profile, specified impurities, residual solvents, elemental impurities, water content, polymorph/form, PSD (if required), microbiological where appropriate, and stability.
CPPs (what we control): stoichiometry, temperature profiles and ramps, pH windows, mixing/impeller regimes, solvent ratios, addition rates, seeding parameters, hold times, filtration/drying conditions, and cleaning recipes.

Deliverable: a control strategy that ties each CQA to an operation and an assay—codified in protocols and batch records your QA can defend.

Route scouting & selection (pick the fight you can win)

We evaluate candidate routes against safety, selectivity, step economy, impurity liabilities, and scalability—not just yield.

Disconnection logic. We favor convergent designs and avoid fragile functional groups late in the route.
Selectivity by design. We use chiral pool, asymmetric catalysis, or biocatalysis where robustness and availability align.
Red flags early. We challenge halogenations/nitrations/azides/peroxy steps with calorimetry and safer alternatives; we quantify exotherms and gas evolution before pilot.

Decision memo: one recommended route, one back-up, and the evidence for both. We commit to a path and don’t rewrite reality mid-campaign.

Safety & hazard assessment (chemistry that doesn’t surprise)

We integrate EHS and reaction calorimetry from week one.

Calorimetry & thermal analysis. RC1/DSC/ARC where prudent; we design addition/temperature ramps and quench logic that respect heat release.
Incompatibilities & off-gassing. We enumerate gas-forming pairings, incompatible reagents, and pressure-control requirements—then we pick equipment that can handle them.
Dust & solvent management. For potent or combustible powders, we design charging and dust control; for solvents, we plan ventilation, recovery, and emissions with EHS.

Outcome: safety limits in the recipe tables, not footnotes.

Lab development → kilo-lab (turn schemes into processes)

We translate the chosen route into unit operations that scale.

Reactions. We tune stoichiometry, solvent selection, and temperature/time; we lock in mixing that ensures reproducibility; we track kinetics where it shortens cycle time.
Workups. We design quenches, extractions, washes, and phase separations that don’t balloon solvent volumes; we stress-test emulsion risk.
Filtration & drying. We trial nutsche/centrifuge choices, cake resistance, and drying curves; we set endpoint criteria operators can verify (LOD/KF, torque, or temperature).
Catalysis & metals. We define catalyst loading/poison controls and plan elemental-impurity clearance without magical thinking.
In-process control. We place efficient IPCs (TLC/HPLC/GC titrations, pH, density) that make runs decisional daily.

Kilo-lab brief: scaled recipes that worked more than once, with headroom.

Impurity control & specification setting (make the map, then clear it)

We do not guess. We make impurities to learn how to remove them.

Predict & synthesize. We identify likely process and degradant impurities; we synthesize reference standards or isolate them for method development.
Clearance by design. We pick unit ops—salts, extractions, washes, absorptions, crystallizations—that clear the targeted impurities and survive validation.
Specification logic. We set acceptance criteria from development data and safety; we align with phase and clinical knowledge; we document the math, not vibes.
Genotoxic vigilance. For structural alerts, we avoid creation where possible; otherwise we control at source and apply sensitive methods with clear action limits.

Deliverable: impurity control narrative with mass balance and orthogonal confirmation.

Solid-form, crystallization & particle engineering (the heart of “manufacturable”)

Form is fate. We put solid-state at the center of development.

Screening. Salt and polymorph searches with XRPD/DSC/TGA/DVS; hydrate/solvate risk mapped.
Crystallization development. Seeded cooling, anti-solvent, and pH-shift crystallization DoE; we define metastable zones, seeding rules, and addition profiles.
Particle size. PSD by process (crystallization) first; milling only when unavoidable; we validate wet-milling/jet-milling where DP demands specific PSD.
Drying & form preservation. We pick drying conditions that preserve form and avoid transformation; we confirm form post-drying and post-milling.

Outcome: a form and PSD that travel through filtration, drying, packaging, and the clinic.

Engineering & scale-up (mixing, heat, and time that obey physics)

We size vessels and operations by heat and mass transfer, not ruler.

Mixing studies. We match impeller types, tip speeds, and baffle choices to viscosity and phase behavior; we scale by power per volume where appropriate.
Heat transfer. We calculate and verify ramp/hold profiles the jacket can actually achieve; we plan quench capacity before the worst day.
Hold times & queues. We characterize stability in hold and waiting steps; we set do-not-exceed timers in the batch record.
Closed transfers. We design powder and liquid charging to minimize exposure and variability; we qualify hoses, valves, and gaskets for chemistry and extractables risk.

Result: scale that behaves like development promised.

Continuous & flow (when it truly wins)

Continuous is a tool, not a religion.

Why we use it: hazardous chemistries (better heat removal), fast/heat-limited steps, narrower impurity spreads, or footprint and solvent savings.
How we validate: residence-time distributions, start-up/shutdown transients, in-line analytics, and batch definition that keeps QA calm.
When we don’t: when cleaning, validation, or staffing complexity outweighs the benefits. We choose what runs.

Analytical & release testing (decisions come from data)

We build fit-for-purpose → validated methods that serve the control strategy.

Identity & assay. HPLC/UPLC (and GC where appropriate), LC-MS confirmation, NMR identity when justified.
Impurities. Related substances by HPLC/GC; genotoxic alerts by sensitive methods; degradants via stability indicating assays.
Residual solvents. Headspace GC with phase-appropriate limits; solvent recovery crossover policies documented.
Water & form. KF (volumetric/coulometric), XRPD for form, DSC/TGA for thermal behavior, PSD where DP requires.
Elemental impurities. ICP-based testing aligned to risk.
Micro/bioburden. Where justified by route or use.
Stability. ICH-aligned real/accelerated with stress to map degradation pathways; packaging decisions backed by data.

Documentation: method files, qual/val reports, and CoAs tethered to batch records in the QMS.

Cleaning validation & cross-contamination control

Cleaning is chemistry too. We treat it accordingly.

Worst-case logic. We define soils, surfaces, and hard-to-clean trains; we calculate MACO/PDE with conservative assumptions.
Methods. Swab and rinse methods validated for recovery; analytical methods sensitive and specific.
Lifecycle. Periodic verification, campaign justifications, and change control tied to solvent/reagent changes.
Single-use vs stainless. We use disposables where they cut risk/time; we use stainless where cleaning validation and cost win.

Packaging, labeling & release (the last honest mile)

We pack APIs like they will travel.

Containers. Drums, liners, or bottles matched to chemistry and PSD, with moisture/oxygen barriers where needed.
Labeling. Clear identity, lot, storage, and safety; chain-of-custody documented.
Shipment. Validated lanes, temperature monitors where justified, and time-out-of-refrigeration rules that someone on a loading dock can follow.
Release. CoA and CoC aligned to specs; batch record and deviations reviewed; stability enrollment confirmed.

Facilities & equipment (selected highlights)

Development labs & kilo-lab: jacketed reactors, controlled additions, inerting, temperature-ramp control, filtration/drying trains.
GMP suites: segregated areas with unidirectional flows; validated utilities (HPW/clean steam/compressed air); closed-transfer capability.
Solid-state & particle tools: XRPD, DSC/TGA/DVS access, sieving, wet-mill/jet-mill partners as needed; PSD instrumentation.
Analytics: HPLC/UPLC, GC (including headspace), LC-MS/GC-MS access, NMR access, ICP where risk requires, KF; stability chambers.
Data systems: validated CDS/LIMS/ELN; eBMR/eBR with audit trails and access control aligned to ALCOA+.

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

QbD in practice. QTPP → CQAs → CPPs documented in protocols and transcribed into recipes and batch records.
Digital QMS. Deviation/CAPA, change control, investigations, and training—mirrored across San Diego & Montréal with shared standards and templates.
Regulatory authoring. CMC sections (specs, control strategy, impurity narratives, cleaning, stability) written from data, not adjectives.
Inspection readiness. We maintain trend reports, validation packages, cleaning files, and media to let auditors follow the story quickly.

Program Onboarding (your first 30 days)

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

A phase-appropriate control strategy mapping QTPP → CQAs → CPPs (form, assay, impurity profile, residuals, elemental impurities, PSD if applicable).
A route & hazard dossier—selected route + back-up, calorimetry and safety notes, red-flag handling, and equipment implications.
A DoE plan for key steps (selectivity, workup, crystallization/PSD), plus a preliminary specification & methods roadmap, and a Gantt & risk map (FMEA) with gates to IND/registration.

Start: share target, phase, desired form, known hazards, and time-to-clinic goals. We return a design space, unit-op parameters, and a documented path to GMP API.

Typical timelines (indicative, chemistry-gated)

Feasibility (2–6 weeks). Route confirm, early impurity map, preliminary crystallization, and first stability reads.
Development (2–4 months). DoE on selectivity and crystallization; impurity standards; draft specs; cleaning feasibility; initial stability bins.
Kilo-lab & engineering. Scale-similar heat/mass transfer, isolation/drying, and PSD lock; batch-linked analytics and mass balance.
GMP API. Validated methods (phase-appropriate), batch records, executed lots, CoA/CoC, and stability enrollment—ready to ship.

We don’t promise calendars your molecule won’t keep. We show the gates, the pass criteria, and the fastest safe path.

Tech transfer & rescue programs

Most small-molecule programs arrive mid-story. We turn them into a narrative regulators can trust.

Document triage. Route history, deviations, impurity list, solid form, cleaning files, and change controls.
Gap map. Which CQAs lack controls; which CPPs drift; what fixes buy the most risk reduction first.
Stabilize → optimize → re-lock. We do not ship risk. We reduce it, document it, and gate it.

ESG & supply chain (reliability is a quality attribute)

Green chemistry where it wins. Solvent swaps, concentration boosts, and cycle-time trims that actually reduce footprint.
Solvent recovery & emissions. Plans that survive EHS and economics.
Qualified alternates. Reagents, catalysts, membranes, filters—with comparability in the file.
Waste discipline. Segregation, neutralization, and documentation that reads well.

Deliverables (what you can hold)

Route selection memo and hazard dossier with calorimetry and safety.
Process description with design space and CPP limits; validated control loops/interlocks.
Impurity control narrative with standards, clearance data, and specification logic.
Solid-form & crystallization package with form/PSD controls and post-process confirmation.
Analytical methods (dev/transfer/qual/val), cleaning validation files, and stability protocols/data.
Batch records (eBMR/eBR), CoA/CoC, and CMC text for submissions.

Frequently asked (straight answers)

Can you control polymorph across scale? Yes—by developing crystallization like a first-class unit op, proving seeding and metastable ranges, and confirming form post-drying/milling.
Do you take on genotoxic risk? We try to avoid creation; when unavoidable, we control at source and with sensitive methods and clear action limits.
Flow or batch? Whichever runs safer, cheaper, and more robust. We justify the choice with data and validation simplicity.
How do you set specs? From development data, clinical context, and safety—mapped to ICH expectations and defended with impurity standards and mass balance.
Potent compounds? We handle select potent APIs with closed transfers and containment; we size the program to our controls and EHS comfort and decline what we cannot run safely.

Summary—why MycoVista for small molecules

Because an API is not a scheme; it is a system: route, impurities, solid form, unit operations, analytics, cleaning, stability, and documents that match reality. We design that system so it scales cleanly, reads clearly, and passes inspection—Design → Data → Decision, without detours.

MycoVista | San Diego, CA & Montréal, Canada
Start Program Onboarding → Share target, form, phase, and goals. We’ll return a design space, a control strategy, and a documented path to GMP API.

EN / FR support available.