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Scale-up and tech transfer Proposed capability Models labeled

Scale-up works when each unit is sized on the right quantity, the powder flows and the knowledge travels

Processability tests, published scale-up rules and the technology-transfer package, shown as figures with their sources.

Status. EUTECNIQ has no plant, pilot equipment, staff or data. Every plan here is proposed.

Academy and related: flow agents and glidants (Course 12) · process engineering

23.6%powder per kg of pine bark in a published pilot extraction and spray drying
17-foldsupercritical CO₂ scale-up predicted by keeping the solvent-to-feed ratio constant
9.5 W/Lultrasonic power per liter in a 100 L pilot, against 225 W/L at 200 mL
3stages of process validation in FDA's 2011 guidance

Grau Baquero et al., Materials 2025; Prado et al., J Food Eng 2012; Withouck et al., Foods 2023; FDA, Process Validation (2011). Published results, not EUTECNIQ data.

From receipt to packed extract

Each step of an extract train is scaled on, or tested for, its own quantity

A proposed ethanol-extraction and spray-drying train, with the quantity that governs each step at scaleSchematic, not to scale
Proposed botanical extract train from raw-material receipt to packed powder, with the quantity each step is scaled on or tested for: particle size, solvent-to-feed ratio and power per volume, heat-transfer area per volume, droplet size and outlet temperature, glass transition and water uptake, and powder flowExtraction and solvent recoveryPurification, drying and packingQCReceiptidentity, moistureMillingparticle sizeSievingMExtractionsolvent-to-feed ratio;power per volume ortip speedFiltrationspent marcsteamEvaporationheat-transfer area pervolumecooling waterSolvent recoveryrecycled solventaqueous concentrateResincolumnSpray dryingdroplet size, outlet temperature andhumidityair heaterexhaustpowderglass transition, water uptakeBlendingSievingPackingpowder flow,hygroscopicityQC releasespecification, certificate ofanalysisDownstream: capsule ortabletcompressibility andcompactibility
Accent labels are explained in the sections below, with sources. Moving lines show the direction of flow. No vendor design is implied.
Text version of the train

Receipt and quarantine (identity and moisture) → milling (particle size) → sieving → stirred, jacketed extraction (solvent-to-feed ratio; power per volume or tip speed) → filtration (spent marc out) → evaporation (heat-transfer area per volume), with vapor condensed and the solvent recycled to the extractor → resin column → spray drying with air heater, cyclone, bag filter and fan (droplet size, outlet temperature and humidity) → powder (glass transition, water uptake) → blending → sieving → packing (powder flow, hygroscopicity) → QC release against the specification. Downstream, a capsule or tablet maker depends on compressibility and compactibility.

Published mass balance

In a published pine-bark extraction, water was 83% of the input and the dried powder 3.9%

Per 2 kg of bark: 12 kg in, 0.47 kg of powder out, and 8.5 kg of water evaporatedPublished data, our arithmetic
23.6%powder per kg of bark
18.1 kgwater evaporated per kg of powder
5.3 MJnatural gas per kg of water evaporated in the dryer trial
2.3×the latent heat of water (2.257 MJ/kg)
Grau Baquero G, Sorolla S, Casas C, Bacardit A. Materials. 2025;18(5):1000, Tables 1 and 2 (aqueous autoclave extraction of Pinus by-products; pilot spray dryer rated at 20 kg/h). Our arithmetic: the 8.38 kg bark-extract trial (438.6 g powder, 52.7% tannins, 10,056 kcal natural gas) is scaled to the 9 kg of liquid extract; evaporated water by difference.
Data table (every number in the figure)
Flowkg per 2 kg barkBasis
Pine bark in2.00Table 1
Water in10.00Table 1
Solubilizing agent in0.03Table 1
Moist residue out3.00Table 1
Liquid extract out9.00Table 1
Not closed (inputs 12.03, outputs 12.00)0.03Table 1, difference
Powder from the spray dryer0.471438.6 g per 8.38 kg (Table 2) × 9/8.38
Tannins in the powder (52.7%)0.248Table 2
Other powder solids0.223difference
Water evaporated8.53difference (trial: 7.94 kg; reported condensate 7.9–8.5 kg)
Natural gas, bark trial42.1 MJ10,056 kcal × 4.184 kJ/kcal
Dryer feed rate, bark trial5.3 kg/h8.38 kg in 95 min
Extraction electricity5.607 kWhTable 1

Table 2 prints the bark-extract feed as "8380 kg"; with 438.6 g of powder and 7.9–8.5 kg of condensate the feed must be 8.38 kg (8,380 g), and we read it that way.

Most of the mass a plant moves is solvent, so evaporation and solvent handling set the energy bill, not the product.

Explanation, details and sources

The study is a life cycle assessment of tannin extracts made from pine bark, cones and pruning. The moist residue weighs 3 kg against 2 kg of bark fed, so it holds liquid, and that liquid carries extract away unless the cake is pressed or washed. The dryer used 5.3 MJ of natural gas per kilogram of water removed, 2.3 times water's latent heat at its normal boiling point; the difference left as heat in the exhaust air and as equipment losses.

The extract is a tannin for leather tanning, used here only for its published balance. Our own illustrative balance of a 1,000 kg ethanol batch is on the process engineering page.

Processability: powder flow

Two volume readings classify how a powder flows, and above a compressibility index of 25% USP calls it poor

USP <1174>Compressibility index
 = 100 (V0 − Vf) / V0
Hausner ratio = V0 / Vf
Bulk density
Tapped density
Compressibility index
Hausner ratio
Flow class, by index
Flow class, by ratio

Where the sample falls on USP's seven-class scale of flowabilityCalculator on the USP scale
USP general chapter <1174> Powder Flow, Table 2, Scale of Flowability (USP 38–NF 33 text). Inputs are free choices, not measurements.
Method, assumptions and limits
What it calculates
Bulk and tapped density, the compressibility index and the Hausner ratio of one sample, and the flow class each index falls in.
Equations
Compressibility index = 100 (V0 − Vf)/V0 = 100 (ρtapped − ρbulk)/ρtapped; Hausner ratio = V0/Vf = ρtapped/ρbulk; ρ = m/V (USP <1174>).
Variables and units
Mass in g; volumes in mL of the same sample; densities in g/mL.
Classes
Index ≤ 10 excellent, 11–15 good, 16–20 fair, 21–25 passable, 26–31 poor, 32–37 very poor, > 38 very, very poor; ratio 1.00–1.11, 1.12–1.18, 1.19–1.25, 1.26–1.34, 1.35–1.45, 1.46–1.59, > 1.60. The tool rounds the index to a whole number and the ratio to two decimals before classing, and places 38 and 1.60, which the table leaves unassigned, in the last class.
Valid range
10–200 g; 50–250 mL; the tapped volume is held at or below the bulk volume.
What it does not establish
The result depends on the cylinder, the tapping method and the sample's history, so powders are compared only under one method. Flow under consolidation, as in a hopper, is characterized by the shear-cell method.
Verification
Unit tests in tests/unit/proc_su.test.js; independent Python reference in tests/numerics/ref/technologies-scale-up-tech-transfer.py.
USP lists four flow tests; its angle-of-repose scale runs from 25° (excellent) to above 66°Compendial classes
USP chapter 1174 lists four ways to characterize powder flow: angle of repose, compressibility index or Hausner ratio, flow through an orifice and shear cell; its angle-of-repose scale runs from excellent, 25 to 30 degrees, to very, very poor, above 66 degreesαAngle of reposeV₀Vf​tapCompressibilityindex, Hausnerratiog/sFlow through anorificeστShear cellAngle of repose and flow (USP <1174>, Table 1)Excellent: 25–30 degreesExcellent25–30°Good: 31–35 degreesGood31–35°Fair, aid not needed: 36–40 degreesFair, aid not needed36–40°Passable, may hang up: 41–45 degreesPassable, may hang up41–45°Poor, must agitate or vibrate: 46–55 degreesPoor, must agitate or vibrate46–55°Very poor: 56–65 degreesVery poor56–65°Very, very poor: > 66 degreesVery, very poor> 66°Schematics, not to scale. The compressibility index and Hausner ratio classes are in the classifier above.
USP <1174> Powder Flow, Table 1 (angle of repose) and the four methods named in the chapter.

A blend that drifts from fair to poor flow fills capsules and dies unevenly, which shows up as weight variation.

Explanation, details and sources

For the compressibility index and Hausner ratio, a sample of known mass is poured into a graduated cylinder (unsettled volume V0) and tapped until the volume stops changing (Vf). A powder that packs down a lot under tapping has strong interparticle forces and flows poorly. Carriers, granulation or a glidant can change the class. Silicon dioxide as a flow agent is covered in Course 12, other ingredients.

Processability: hygroscopicity

A hygroscopicity class is one weight gain at 80% humidity; a sorption isotherm shows the whole curve

European Pharmacopoeia hygroscopicity classes: weight gain after 24 h at 25 °C and 80% relative humidityCompendial classes
European Pharmacopoeia hygroscopicity classes by weight gain after 24 hours at 25 degrees C and 80% relative humidity: under 0.2% non-hygroscopic, 0.2 to under 2% slightly hygroscopic, 2 to under 15% hygroscopic, 15% or more very hygroscopic, and deliquescent when enough water is absorbed to form a liquidWeight gain after 24 h at 25 ± 1 °C and 80 ± 2% relative humidity (log scale)Non-hygroscopic: under 0.2%Non-hygroscopicunder 0.2%Slightly hygroscopic: 0.2 to under 2%Slightly hygroscopic0.2 to under 2%Hygroscopic: 2 to under 15%Hygroscopic2 to under 15%Very hygroscopic: 15% or moreVery hygroscopic15% or more0.2%1%2%10%15%100%Deliquescentabsorbs enough waterto form a liquidThe test does not account for the water already in the sample, so a pre-dried and an as-received lot can class differently.
Ph. Eur. 5.11, as described by Allada R. Asian J Pharm. 2016;10(4) (25 ± 1 °C, 80 ± 2% RH, 24 h; 0.2, 2 and 15% thresholds); the same wording with "deliquescent" appears in the Chinese Pharmacopoeia guideline.
Water held at equilibrium, 25 °C: maltodextrin raises the humidity at which mango solids turn rubbery from 7% to 35%Published parameters
GAB isotherms with the parameters of Kashiwakura Y, et al. J Appl Glycosci. 2024;71(1):15–21, Table 1, plotted over 2–70% RH, inside the measured range. Markers: measured critical water activities 0.074, 0.345 and 0.575 (glass transition at 25 °C).
Data table (g water per 100 g dry matter)
MaterialWmCK10% RH30% RH50% RH70% RHCritical RH, measured
Mango solids16.11.6860.9202.68.717.634.17.4%
Mango : maltodextrin 20 : 806.42.3030.9221.34.17.914.634.5%
Maltodextrin4.39.1920.9952.44.97.713.557.5%

The class is a single test point; the isotherm tells a plant what room humidity keeps the powder glassy while it is blended and packed.

Explanation, details and sources

The pharmacopoeial test stores the material at 25 °C and 80% relative humidity for 24 hours and classes it by weight gain: slightly hygroscopic from 0.2% to under 2%, hygroscopic from 2% to under 15%, very hygroscopic at 15% or more, deliquescent when it takes up enough water to form a liquid. It does not account for the water already in the sample. An isotherm gives equilibrium water content across humidity; the data used here stop at 70%, so the 80% test point lies outside them. Storage and packaging consequences are on the drying and particle engineering page.

Processability: stickiness in the dryer

A spray-dried powder sticks to the chamber when it leaves hotter than its glass transition, and a carrier raises that transition

Gordon–TaylorTg = wsTgs + k wwTgwws + k ww
Mango solids
Mango : maltodextrin 20 : 80
Maltodextrin
Glass transition against water content, with the dryer outlet temperatureModel output, published parameters
Gordon–Taylor parameters: Kashiwakura et al. 2024, Table 1 (Tgw = 136 K). Sticky-point offset: Roos and Karel (1991) put the sticking point about 10–15 °C above Tg, as summarized by O'Donoghue (2019), who also lists 14–34 °C for skim milk powder depending on the test.
Method, assumptions and limits
What it calculates
The glass-transition temperature of each material at the chosen water content and its difference from the outlet air temperature.
Equations
Gordon–Taylor as shown, with ws = 1/(1 + W/100) and ww = 1 − ws, W in g water per 100 g dry matter; Tgs 310.4, 366.1 and 435.8 K and k 3.86, 7.18 and 9.00 (Kashiwakura et al. 2024).
Assumptions
The outlet air temperature is taken as an upper bound for the particle temperature at the dryer exit; amorphous powder; the 10 °C line marks where reported sticky points begin, not a design limit.
Valid range
Outlet 40–110 °C; 1–8 g water per 100 g dry matter.
What it does not establish
Whether a given extract deposits in a given dryer: wall deposition also depends on particle velocity, contact time and the dryer's airflow, and is measured in trials.
Verification
Unit tests and the independent Python reference named above.

At the defaults, 70 °C and 4 g of water per 100 g, mango solids sit 56 °C above their glass transition, the blend 28 °C above, maltodextrin 13 °C below.

Explanation, details and sources

Sugar-rich extracts have a low glass transition, so they turn sticky in the hot, humid lower part of a spray dryer and coat its walls (Bhandari et al. 1997). Adding a high-Tg carrier such as maltodextrin, lowering the outlet temperature or drying further all move the particle below the sticky point. Each costs something: carrier dilutes the active, a cooler outlet leaves more water, and drier air needs more energy.

Processability: compaction

Tablet strength at production speed is predicted best from tensile strength against solid fraction

Three compaction profiles link pressure, solid fraction and tensile strength; one of them ignores press speedPublished finding
Three compaction profiles relate compaction pressure, tablet solid fraction and tensile strength. Tye, Sun and Amidon found compressibility and tabletability speed dependent for some materials, and compactibility essentially independent of tableting speedCompaction pressurepunch force ÷ punch areaSolid fraction1 − porosity of the tabletTensile strengthdiametral test: σ = 2F / (πDt)Compressibilityspeed dependent for some materialsCompactibilityessentially independent of speedTabletabilityspeed dependent for some materialsWhy it matters at scale: a production press runs faster than a development press. Tye et al. (2005) proposed the compactibility profile, tensile strength versussolid fraction, as the speed-independent predictor of tablet strength during scale-up. USP <1062> (official December 1, 2017) describes all three profiles.
Tye CK, Sun CC, Amidon GE. J Pharm Sci. 2005;94(3):465–472; USP <1062> Tablet Compression Characterization (official December 1, 2017); Fell JT, Newton JM. J Pharm Sci. 1970;59(5):688–691 (diametral compression test).

Measure all three profiles on the development press, then carry the compactibility curve to the production press.

Explanation, details and sources

Compressibility is solid fraction against compaction pressure, tabletability is tensile strength against pressure, and compactibility is tensile strength against solid fraction. Tye, Sun and Amidon tested four direct-compression excipients and a placebo: tabletability and compressibility of some changed with tableting speed, while compactibility of all of them was essentially speed independent. Tensile strength comes from the force F that breaks a tablet of diameter D and thickness t across its diameter: σ = 2F/(πDt).

Scale-up: geometric similarity

A larger, geometrically similar tank cannot hold power per volume, tip speed and Reynolds number constant at once

Scale-up rulesk = D2/D1 = (V2/V1)1/3
P/V: N2 = N1k−2/3
tip speed: N2 = N1k−1
Re: N2 = N1k−2
blend time: N2 = N1
Scale ratio k
Lab power per volume
Lab tip speed
Lab Reynolds number
Plant value ÷ laboratory value under each scale-up rule (log scale)Model output
Plant speed, power, power per volume, tip speed and Reynolds number under each rule
Rule held constantPlant speedPowerP/VTip speedRe
Paul EL, Atiemo-Obeng VA, Kresta SM, eds. Handbook of Industrial Mixing. Wiley; 2003; Rushton J, Costich E, Everett H. Chem Eng Prog. 1950;46:467–476 (Po ≈ 5, Rushton turbine).
Method, assumptions and limits
What it calculates
The plant impeller speed under four scale-up rules and the resulting power, power per volume, tip speed, Reynolds number and blend time relative to the laboratory; the same model draws the 3D map below.
Equations
k = (V2/V1)1/3; P = PoρN³D⁵; tip speed πND; Re = ρND²/μ.
Variables and units
Volumes in L; N in rpm (÷ 60 to s⁻¹); D = (D/T)·T in m with T = (4V/π)1/3; ρ = 998 kg/m³; μ 1.002–100 mPa·s (logarithmic slider).
Assumptions
Geometric similarity, baffled tanks, one impeller, liquid height equal to diameter; constant power number, which needs turbulent flow (Re above about 10⁴, flagged otherwise). Turbulent blend time scales as 1/N in a fixed geometry, so only its ratio is shown.
Valid range
Laboratory 1–50 L; plant 100 L to 20 m³ (logarithmic slider, two significant figures).
What it does not establish
Solids suspension, gas dispersion and heat transfer have their own correlations; local shear near the impeller differs from the averages shown.
Verification
Independent Python reference in tests/numerics/ref/technologies-scale-up-tech-transfer.py.
Power per volume over vessel volume and impeller speed, with the path each rule takes from the laboratoryModel output
Same model and inputs as the calculator above. Amber: turbulent region where a constant power number holds. Drag to rotate.
Data table: power per volume, W/m³, at the calculator's D/T and Po
Volume50 rpm100 rpm200 rpm400 rpm800 rpm

Constant power per volume keeps droplet and suspension behavior closer; it lengthens blend time and lowers tip speed.

Explanation, details and sources

In turbulent flow the impeller draws power P = PoρN³D⁵. With every length scaled by k, holding one quantity fixes the plant speed and moves the rest. The rule is chosen by what the step is sensitive to: dispersion and mass transfer follow power per volume, shear-sensitive material follows tip speed, and a reaction that needs fast mixing follows blend time, which is usually the most expensive to hold.

Scale-up: heat transfer

A thousandfold larger vessel has a tenth of the jacket area per liter, so it heats and cools more slowly

Jacket area per volume falls with the cube root of volumeGeometry, H = T
Wetted wall plus flat bottom of a cylinder with liquid height equal to diameter: A/V = 1.25πT²/V. Heat-up times at three scales are computed on the process engineering page.

Where a step is temperature critical, coils or external exchangers restore the area that scale removes.

Scaled from 1 L to 1,000 L with the same shape, a vessel keeps a tenth of the jacket area per liter, from 46 to 4.6 m² per m³Drawn to scale · computed geometry
Three geometrically similar, baffled, jacketed stirred vessels of 1 litre, 100 litres and 1,000 litres drawn in isometric projection to one scale, each cut away to show four baffles and a six-blade disk turbine. A table gives each vessel's diameter, jacket area and area per volume, which falls from 46 to 4.6 square metres per cubic metre, and how impeller speed, tip speed and Reynolds number change when power per volume is held constant.
Standard stirred-tank geometry: Paul EL, Atiemo-Obeng VA, Kresta SM, eds. Handbook of Industrial Mixing. Wiley; 2003. Diameters, areas and speed ratios computed here (H = T, flat bottom, turbulent flow). Generated illustration, EUTECNIQ. Full-size SVG
Scale-up: extractors and dryers

Each unit operation has its own published scale-up basis, and one pilot study shows what happens when it is not held

What is held constant across scales, and what the studies foundPublished evidence
Scale-up basis by unit operation with the published evidence: stirred vessel, jacketed vessel, supercritical CO2 extractor, ultrasonic extractor, spray dryer and tablet pressStepHeld constant across scalesWhat changes, or what the study foundSourceStirred vesselOne of: power per volume, tip speed,Reynolds number or blend timeThe other three move; the calculator above shows byhow muchPaul et al. 2003Jacketed vesselGeometric similarityJacket area per volume falls with the cube root ofvolume, so heat-up and cool-down slowGeometry; Bergman et al.2011Supercritical CO₂extractorSolvent-to-feed ratio (kg CO₂ per kgplant)Predicted the pilot extraction curve over a 17-foldscale-up (0.29 → 5.15 L)Prado et al. 2012Ultrasonic extractorNot held: acoustic energy densityFell from 225 to 9.5 W/L; yield fell at one solid ratioand rose at anotherWithouck et al. 2023Spray dryerDroplet size distribution, outlettemperature, outlet humidityDroplet size matched alone was not enough: gasmixing and residence time differ by dryerPoozesh and Bilgili 2019;Thybo et al. 2008Tablet pressCompactibility profileHigher press speed can change tabletability andcompressibilityTye et al. 2005
Paul et al. 2003; Bergman TL, et al. Fundamentals of Heat and Mass Transfer. 7th ed. Wiley; 2011; Prado JM, et al. J Food Eng. 2012;109(2):249–257; Withouck H, et al. Foods. 2023;12(17):3142; Poozesh S, Bilgili E. Int J Pharm. 2019;562:271–292; Thybo P, et al. Pharm Res. 2008;25(7):1610–1620; Tye et al. 2005.
Ultrasonic extraction of applewood: energy density fell 24-fold from flask to 100 L pilotPublished data
Applewood ultrasound-assisted extraction: acoustic energy density fell from 225 W/L in 200 mL and 45 W/L in 1,000 mL to 9.5 W/L in the 100 L pilot (Withouck et al. 2023)1101001,000acoustic energy density, W per liter (log scale)200 mL laboratory50 W probe200 mL laboratory: 225 W/L225 W/L1,000 mL laboratory50 W probe1,000 mL laboratory: 45 W/L45 W/L100 L pilot950 W probe100 L pilot: 9.5 W/L9.5 W/LEnergy density fell 24-fold from 200 mL to 100 LPolyphenol yield at the pilot scale:• lower than in the laboratory at a solid-to-solventratio of 1 : 33• at least 30% higher at 1 : 20, where the stirred100 L vessel kept the wood suspended and the 200mL flask did not
Withouck H, Paelinck A, Foubert I, Fraeye I. Ultrasound-assisted extraction of applewood polyphenols at lab and pilot scales. Foods. 2023;12(17):3142 (30% ethanol, 10 min, 25 °C; 26 kHz laboratory and 20 kHz pilot probes).
Data table
ScaleProbe powerAcoustic energy density
200 mL laboratory50 W225 ± 5 W/L
1,000 mL laboratory50 W45.0 ± 0.1 W/L
100 L pilot950 W9.5 ± 0.1 W/L

A scale-up basis is chosen from the mechanism, then confirmed at pilot scale; matching one variable is rarely enough.

Explanation, details and sources

For supercritical CO₂ extraction of grape seed, keeping the solvent-to-feed ratio constant predicted the 5.15 L pilot curve from the 0.29 L laboratory one at 35 MPa and 313 K (Prado et al. 2012). For spray drying, Poozesh and Bilgili review rules for atomization, drying and gas–solid separation; Thybo et al. matched droplet size between a pilot and a production dryer and still needed production trials, because mixing and residence time differed. In the applewood study the pilot yield was lower at a solid-to-solvent ratio of 1 : 33 and at least 30% higher at 1 : 20, which the authors attribute to energy density and to suspension of the wood.

Technology transfer

Technology transfer moves product and process knowledge, with the documents, from the unit that developed a process to the one that will run it

Who does what in a transfer: sending, receiving and quality unitsProposed workflow
Technology-transfer swimlane across sending, receiving and quality units: scope, transfer package, protocol with acceptance criteria, gap and risk assessment, method transfer, master and batch records, engineering runs, qualification, quality review, then knowledge management and continued verificationSending unitReceiving unitQuality unitScopeteam,timeline,criteriaPackageprocess,CQAs, CPPs,specificationsProtocolacceptancecriteria setfirstGap andriskequipmentand scale(ICH Q9)MethodsUSP <1224>transferRecordsMMR 111.205,BPR 111.255Engineeringrunsconfirmranges andbalancesQualificationbatches; PPQwhere drugrules applyQA reviewreport andapprovalKnowledgehistory andmodels (ICHQ10)Verificationtrend CPPsand CQAs
ICH Q10 Pharmaceutical Quality System (Step 4, June 4, 2008), sections 1.6.1 and 3.1.2; WHO TRS 1044, Annex 4 (2022); USP <1224> Transfer of Analytical Procedures; 21 CFR 111.205 and 111.255.

ICH Q10 names the goal: transfer knowledge "to achieve product realisation", forming the basis for the process, control strategy and validation approach.

Explanation, details and sources: the transfer package
ElementContentAnchor
Process descriptionRoute, unit operations, sequence, set points and ranges, in-process controls, hold timesWHO TRS 1044 Annex 4
CQAs and CPPsCritical quality attributes and the process parameters that move them, with the evidence behind each linkICH Q8(R2) definitions
SpecificationsRaw material, in-process and finished specifications with justification21 CFR 111.70 (supplements)
Analytical method transferComparative testing, covalidation, revalidation or a justified waiver, under a pre-approved protocolUSP <1224>
Risk assessmentEquipment and scale gaps between sending and receiving units, ranked with mitigationsICH Q9(R1)
RecordsMaster manufacturing record for each formulation and batch size; batch production record for every batch21 CFR 111.205, 111.255
Run evidenceEngineering runs, then qualification batches (process performance qualification where drug rules apply)FDA Process Validation guidance (2011)
Knowledge managementDevelopment history, deviations and model data kept usable across the lifecycleICH Q10

ICH Q10 defines knowledge management as a "systematic approach to acquiring, analysing, storing and disseminating information related to products, manufacturing processes and components". For dietary supplements the receiving unit's master manufacturing and batch production records are requirements of 21 CFR Part 111.

Process validation

FDA's process-validation guidance runs in three stages and covers drugs, not dietary supplements

Design, qualify, then verify for as long as the process runsFDA guidance
FDA's 2011 process validation guidance in three stages: process design; process qualification, with facility, utility and equipment qualification followed by process performance qualification; and continued process verification. The guidance does not cover dietary supplementsStage 1 · Process designStage 2 · Process qualificationStage 3 · Continued process verificationThe commercial process is defined fromknowledge gained in development and scale-up.The design is evaluated for reproduciblecommercial manufacture: (a) facility design andqualification of utilities and equipment, then (b)process performance qualification. It mustsucceed before commercial distribution.Ongoing assurance during routine productionthat the process remains in a state of control.knowledge from routine production feeds back into the process designScopeCovers human and veterinary drugs, biological products, APIs and the drug part of combination products. It does not cover dietary supplements,which follow 21 CFR Part 111 (master manufacturing record, 111.205; batch production record, 111.255).
U.S. FDA. Process Validation: General Principles and Practices. Guidance for industry, January 2011, Revision 1 (scope; sections III.B and IV.B–D). Nonbinding recommendations; status checked October 24, 2026.

EUTECNIQ would borrow the lifecycle logic for supplement processes while meeting Part 111's own record requirements.

Explanation, details and sources

The guidance defines process validation as "the collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality product." Products made during Stage 2 can be released if acceptable, and Stage 2 must succeed before commercial distribution.

Comparability

After a process change, products are compared against criteria set in advance, and there are five possible outcomes

The ICH Q5E comparability outcomesICH guideline
ICH Q5E comparability: compare pre-change and post-change quality attributes against predefined criteria; five possible outcomes from comparable to not comparableCompare pre- and post-changeproductquality attributes against criteria set inadvance: batch analyses, in-processcontrols, validation, characterization,stabilityHighly similarComparable: no adverse impact on safety orefficacy foreseenHighly similar, but the methods cannot detectrelevant differencesMore characterization, or nonclinical orclinical studiesSome differences; no impact on safety orefficacy can be justifiedComparable, on accumulated experienceand dataSome differences; an adverse impact cannot beexcludedNonclinical or clinical studiesNot highly similarNot comparable (outside the guideline'sscope)
ICH Q5E Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process (Step 4, November 18, 2004), section 1.4 and glossary.

Q5E was written for biotechnological products; for a botanical extract EUTECNIQ would apply its logic with fingerprints, marker assays and stability.

Explanation, details and sources

Q5E defines "comparable" as "a conclusion that products have highly similar quality attributes before and after manufacturing process changes and that no adverse impact on the safety or efficacy, including immunogenicity, of the drug product occurred." The comparison draws on routine batch analyses, in-process controls, validation data, characterization and stability. How fingerprints and markers are compared is on the purification and standardization page.

Readiness gates

Six proposed gates would move a process from grams to routine production, each released only by evidence

The evidence that releases each gate, and the scale at which it is typically producedProposed stage gates
Six proposed readiness gates from feasible to routine production, each with the evidence that releases it and its typical scaleG0 FeasibleG1 DefinedG2 PilotedG3 Transfer-readyG4 QualifiedG5 RoutineGramsTarget constituentsextracted andmeasured with afit-for-purposemethod; no safety orregulatory stopperfoundLitersDesigned experimentsidentify theparameters that moveeach CQA; rangesproposed; stabilityscreening startedTens to hundreds oflitersMass and energybalances close withinan agreed tolerance;heat-up, filtration anddrying parametersmeasured; material forcustomer and safetystudiesPilot to plantProcess description,CQAs and CPPs,specifications, riskassessment, mastermanufacturing recordand transferredmethods approved bythe quality unitCubic metersQualification batchesat commercial scalemeet all specifications;deviations investigatedand closedCommercialTrends of CPPs andCQAs show theprocess stays incontrol; changes gothrough changecontrolSix proposed readiness gates from feasible to routine production, each with the evidence that releases it and its typical scale0G0 Feasible · GramsTarget constituents extracted and measured with afit-for-purpose method; no safety or regulatorystopper found1G1 Defined · LitersDesigned experiments identify the parameters thatmove each CQA; ranges proposed; stabilityscreening started2G2 Piloted · Tens to hundreds of litersMass and energy balances close within an agreedtolerance; heat-up, filtration and drying parametersmeasured; material for customer and safety studies3G3 Transfer-ready · Pilot to plantProcess description, CQAs and CPPs, specifications,risk assessment, master manufacturing record andtransferred methods approved by the quality unit4G4 Qualified · Cubic metersQualification batches at commercial scale meet allspecifications; deviations investigated and closed5G5 Routine · CommercialTrends of CPPs and CQAs show the process stays incontrol; changes go through change control
EUTECNIQ's proposed internal gates, not a regulatory classification. Thresholds such as balance-closure tolerance or the number of qualification batches would be set per product before work starts.
Text version: gates, evidence and typical scale
GateEvidence required to passTypical scale
G0 FeasibleTarget constituents extracted and measured with a fit-for-purpose method; no safety or regulatory stopper foundGrams
G1 DefinedDesigned experiments identify the parameters that move each CQA; ranges proposed; stability screening startedLiters
G2 PilotedMass and energy balances close within an agreed tolerance; heat-up, filtration and drying parameters measured; material for customer and safety studiesTens to hundreds of liters
G3 Transfer-readyProcess description, CQAs and CPPs, specifications, risk assessment, master manufacturing record and transferred methods approved by the quality unitPilot to plant
G4 QualifiedQualification batches at commercial scale meet all specifications; deviations investigated and closedCubic meters
G5 RoutineTrends of CPPs and CQAs show the process stays in control; changes go through change controlCommercial

Moving a botanical process toward manufacturing?

Describe the material and the step; EUTECNIQ would respond with a proposed processability and transfer plan and its limits.