This is a ready-to-use worksheet for translating a process step across scale during a technology transfer: identifying which engineering parameter actually governs the critical quality attribute at risk, calculating that parameter at both the sending and receiving scale, and recording the evidence that confirms the translation held. It is the supporting technical basis behind section 8, Scale effects, of the paired technology transfer risk assessment; that risk assessment asks for a named scale-up model and a predicted effect, and this worksheet is where that model actually gets worked out with real values rather than asserted in a sentence. Replace every <<FILL: ...>> placeholder with your own specifics. The formulas below are standard chemical and bioprocess engineering relationships, not copyrighted standard text; the numeric values in the filled specimen are an invented illustration of the method, not a reported result from any real process.
Document control header
| Field | Entry |
|---|---|
| Document title | Scale Translation Worksheet for <<FILL: process step / unit operation>>, Transfer <<FILL: transfer ID>> |
| Document number | <<FILL>> |
| Linked transfer risk assessment | <<FILL: ref>> |
| Prepared by | <<FILL>> |
| Date | <<FILL>> |
| Sending site, equipment ID | <<FILL>> |
| Receiving site, equipment ID | <<FILL>> |
1. Purpose
This worksheet documents the engineering basis for moving <<FILL: process step>> from the sending scale to the receiving scale: which physical parameter was chosen to govern the translation, why, what the sending-scale and receiving-scale calculated values are, and what evidence confirmed the choice held once the process actually ran. A scale-up or scale-down model named without this detail is an assumption, not a verified basis.
2. Scope: process step and scale change
| Field | Entry |
|---|---|
| Process step | <<FILL: e.g. cell expansion bioreactor, viral vector production bioreactor, chromatography step, UF/DF step, single-use mixing step>> |
| Sending scale | <<FILL: volume, column diameter, or membrane area, with vessel/equipment geometry>> |
| Receiving scale | <<FILL: volume, column diameter, or membrane area, with vessel/equipment geometry>> |
| Geometric similarity confirmed | <<FILL: height-to-diameter ratio, impeller type, baffle configuration, sparger design, same or different>> |
3. Governing parameter selection
Evaluate every candidate parameter below against the process step named above. Mark each as the primary basis, a secondary parameter that must be checked, or not applicable, and state why.
| Candidate parameter | Applies to this step | Role (primary basis / secondary check / not applicable) | Rationale |
|---|---|---|---|
| Power per unit volume (P/V) | <<FILL: Y/N>> | <<FILL>> | <<FILL>> |
| Impeller tip speed | <<FILL: Y/N>> | <<FILL>> | <<FILL>> |
| Volumetric mass transfer coefficient (kLa) | <<FILL: Y/N>> | <<FILL>> | <<FILL>> |
| Mixing time | <<FILL: Y/N>> | <<FILL>> | <<FILL>> |
| Reynolds number | <<FILL: Y/N>> | <<FILL>> | <<FILL>> |
| Linear velocity and bed height (chromatography) | <<FILL: Y/N>> | <<FILL>> | <<FILL>> |
| Membrane loading and per-area crossflow (UF/DF) | <<FILL: Y/N>> | <<FILL>> | <<FILL>> |
A parameter marked “not applicable” still needs one line of stated reasoning; a row left blank reads as a parameter nobody considered, not a parameter correctly ruled out.
4. Calculated values at each scale
Use the standard engineering relationship for the chosen parameter. N is impeller rotational speed, D is impeller diameter, Np is the impeller’s power number (empirical, specific to impeller geometry and flow regime), rho is fluid density, mu is fluid viscosity, V is working volume.
| Parameter | Formula / method | Sending-scale value | Receiving-scale value | Delta | Within acceptable range |
|---|---|---|---|---|---|
| Power per unit volume | P/V = Np x rho x N^3 x D^5 / V | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL: Y/N>> |
| Impeller tip speed | Tip speed = pi x D x N | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL: Y/N>> |
| Volumetric mass transfer coefficient (kLa) | Empirical, measured by a gassing-out or oxygen-balance method at each scale; not reliably predicted from P/V alone | <<FILL: measured>> | <<FILL: measured>> | <<FILL>> | <<FILL: Y/N>> |
| Mixing time | Empirical, measured by a tracer or pH-indicator homogenization test at each scale | <<FILL: measured>> | <<FILL: measured>> | <<FILL>> | <<FILL: Y/N>> |
| Impeller Reynolds number | Re = rho x N x D^2 / mu | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL: Y/N>> |
| Linear velocity (chromatography) | Linear velocity = volumetric flow rate / column cross-sectional area | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL: Y/N>> |
| Membrane loading (UF/DF) | Loading = batch volume / membrane area | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL: Y/N>> |
kLa and mixing time do not have a reliable first-principles formula across arbitrary vessel geometries; treat the “formula” column for those two rows as a measurement method, not a calculation, and measure both at the receiving scale rather than inferring them from a matched P/V.
5. Secondary parameters: checked, not assumed
List every parameter marked “secondary check” in section 3 and state the evidence confirming it did not drift outside what the process can tolerate, even though it was not the chosen basis.
| Secondary parameter | Expected behavior if basis parameter is held constant | Actual value or trend observed | Consistent with expectation |
|---|---|---|---|
<<FILL>> | <<FILL>> | <<FILL>> | <<FILL: Y/N>> |
6. Scale-down model qualification (if this worksheet supports a small-scale model, not a direct production transfer)
| Field | Entry |
|---|---|
| Is a scale-down model being qualified here | <<FILL: Y/N>> |
| Studies the model will support | <<FILL: e.g. raw material variability, resin or filter lifetime, failure-mode characterization feeding PPQ>> |
| CQA comparison, model vs. commercial scale | <<FILL: attach or summarize side-by-side CQA data, not just matched CPPs>> |
| Basis accepted as representative | <<FILL: Y/N, with the data reference supporting it>> |
| Re-qualification trigger | <<FILL: e.g. any change to commercial-scale equipment, operating range, or raw material source>> |
A scale-down model qualified on matched critical process parameters alone, with no critical quality attribute comparison, is not qualified; see the scale-down model qualification discussion for why CPP matching alone does not establish representativeness.
7. Verification evidence from the engineering run
| Evidence type | What it confirmed | Result | Reference |
|---|---|---|---|
<<FILL: e.g. dissolved oxygen trend through peak growth>> | <<FILL>> | <<FILL>> | <<FILL>> |
<<FILL: e.g. mixing-time tracer study>> | <<FILL>> | <<FILL>> | <<FILL>> |
8. Disposition
| Field | Entry |
|---|---|
| Scale translation basis accepted | <<FILL: Y/N>> |
| Open items carried to the risk assessment or MPI | <<FILL>> |
| Approved to proceed to the next engineering run or PPQ | <<FILL: Y/N, with conditions>> |
9. Approvals
| Role | Name | Signature | Date |
|---|---|---|---|
| Preparer (process/bioprocess engineer) | <<FILL>> | ||
| Reviewer (process science SME) | <<FILL>> | ||
| Approver (Quality) | <<FILL>> |
Filled specimen
Extract from an invented transfer of a CAR-T cell expansion step from a 2 liter benchtop bioreactor to a 50 liter single-use production bioreactor. Numbers are illustrative only.
| Parameter | Sending scale (2 L) | Receiving scale (50 L) | Delta | Within acceptable range |
|---|---|---|---|---|
| Power per unit volume | 15 W/m3 | 15 W/m3, agitation setpoint re-derived to match | 0 percent, matched by design | Yes |
| Impeller tip speed | 0.55 m/s | 0.95 m/s, higher at matched P/V due to larger impeller diameter | Plus 73 percent | Flagged for secondary check, within the cell line’s established tip-speed tolerance from prior characterization |
| Volumetric mass transfer coefficient (kLa), measured | 4.2 per hour | 2.6 per hour at initial sparging setpoint, measured by gassing-out method during engineering run | Minus 38 percent | No, below the minimum kLa the peak growth phase oxygen demand requires |
Section 7 evidence: a dissolved oxygen trend during the engineering run showed DO sagging to 18 percent of setpoint during peak growth against a lower control limit of 30 percent, confirming the kLa shortfall was real rather than a measurement artifact. A sparging-rate adjustment, tested in a second engineering run, raised measured kLa to 4.0 per hour and held dissolved oxygen above 35 percent through peak growth for the remainder of the run.
Disposition: scale translation basis accepted only after the sparging-rate adjustment; the adjustment was written into the receiving site’s master production instructions and the risk assessment’s section 8 was updated to reflect the corrected kLa value and its verification data, not the originally assumed P/V-only basis.
Common findings this worksheet prevents
- A scale-up model named in a risk assessment as “power per volume” with no record of which secondary parameters were checked or what their values turned out to be.
- Tip speed, kLa, or mixing time assumed to scale proportionally with the chosen basis parameter, with no measurement confirming it.
- A scale-down model accepted on matched critical process parameters with no critical quality attribute data comparing it to the commercial-scale process.
- An engineering-run deviation traced to a scale effect with no documented scale translation basis to compare it against, so the investigation has to reconstruct the engineering logic after the fact.
How to adapt this worksheet
- Complete section 3 for every process step affected by the scale change before running the engineering run, not after a deviation forces the analysis.
- Use a validated measurement method for kLa and mixing time; both require real data at the receiving scale, not a value inferred from the sending scale.
- Feed the accepted basis and its verification evidence directly into section 8 of the technology transfer risk assessment so the two documents stay consistent.