A promising fermentation result has to become a process that another operator can understand, test and run. The receiving facility has its own equipment, controls and constraints. That makes the transfer package part of the next experiment, rather than paperwork to complete after development.
For an R&D lead preparing an external trial, the useful starting point is a comparison: what generated the internal result, what changes at the receiving site, and which changes could affect the accepted product? The comparison should cover the organism and medium, vessel geometry, mixing, oxygen transfer, controls, downstream equipment and release specification.
A strong package makes the gaps visible. If shear sensitivity has not been investigated, record it as an open question. If a recovery estimate comes from literature rather than a run, keep its source and uncertainty beside the number. The operator can then discuss a scoped trial instead of interpreting an apparently complete process description.
That gap can delay a production trial and consume cash. This article examines the mechanism; it does not rank it above every regulatory, supply-chain or consumer risk in the sector.
A delay can remain invisible in a headline milestone until a receiving operator asks for the missing evidence.
The assumption to test
Discovery and translation can both constrain a food biotech business. This article focuses on the translation problem that remains after a promising laboratory result.
The translation questions include process robustness, tech transfer, reproducibility at scale, contamination control and performance on equipment operated outside the founding team.
Closing a process-transfer gap requires the right industrial skills, documentation and external testing. Treat it as a defined part of development, alongside other material risks.
Leaving transfer planning until after a financing milestone can create a mismatch: the financial model assumes a production capability that the next operator has not yet assessed. The remedy is to put the receiving equipment and evidence needs into the development plan while changes remain possible. It does not require every early research team to have a commercial process already validated.
Biology, engineering and operating practice remain connected throughout this work. A transfer can reveal a biological limit, an equipment mismatch or a poorly specified procedure. Investigate the cause before choosing the remedy.
The molecular result and the production result answer different questions. A target molecule may be expressed successfully while recovery, functional performance or operating consistency still needs development. Progress in one area provides evidence to use in the others; it does not close them automatically.
Producing a target molecule is not the same as producing a saleable ingredient reliably and economically. Biology and process engineering remain connected. The target scale and target cost must be defined for the actual product, rather than assumed to be solved across the sector.
One-minute brief
R&D leads: distinguish repeated observations under the same conditions from evidence of performance after equipment or operator changes. Give the receiving team enough context to assess both.
For founders: identify the transfer expertise and records needed before selecting a receiving operator. Contracting that work early can reveal dependencies while the plan can still change.
Investors -the scale-up question belongs in the first meeting, not after the term sheet; if the valuation assumes pilot performance will survive transfer unchanged, that assumption needs to be priced, not assumed
What the evidence needs to show
Which inputs belong in the model
Use published techno-economic work to identify variables worth examining, then trace them to the process under review. A review of heterogeneous models can guide questions without supplying a cost estimate for your own ingredient.
GFI’s techno-economic review identifies feedstocks, capital costs and process performance as important drivers. It compares models with different products and assumptions. A biomass fermentation cost range should not be recast as a universal precision-fermentation benchmark or attributed to one process variable.
Funding totals describe a market, not the technical readiness of each recipient. A company’s cost and transfer claims still need their own evidence. This analysis does not infer a causal investment trend from aggregate funding figures.
Recruitment and access to industrial process experience belong in the milestone plan. Obtain realistic lead times for the roles or contractors you need; a fixed hiring delay is not established here.
Compare the skills in your team with the work ahead. The question is whether someone can plan, operate and document the transfer, rather than how many people hold a particular degree.
Why scale-up fails - the mechanism, not just the pattern
Transfer risks become more useful when described as mechanisms that can be tested. A generic warning about scale says little about which experiment, control or equipment comparison the team should fund next.
Laboratory, pilot and commercial operation each require checking how the process behaves under the receiving equipment and operating conditions. Some parameters transfer; others need adjustment and validation.
Changes in vessel geometry, mixing, gas delivery, heat removal and control can alter the conditions experienced by the culture. Their importance depends on the process. Compare relevant equipment and operating conditions directly; volume alone does not specify oxygen transfer, shear or mixing performance.
Titre, productivity or recovery can change during transfer. Measure the change and investigate its cause. A universal 30-60 percent performance loss is not established and should not be used as an expected result for every process.
Unplanned troubleshooting can consume both campaign time and cash. Include an investigation allowance and an explicit decision about what happens if the trial misses its acceptance conditions.
A larger failed batch can involve more material, utilities, downtime and investigation work. Calculate that exposure for the actual batch and recovery plan rather than assuming it exceeds every company’s annual R&D budget.
Keep contamination events and investigations in the development record. Ask the receiving operator what history, root-cause work and controls it needs before accepting the process. Requirements vary by process and facility.
The record should show what was observed, how it was investigated and which uncertainty remains. An unexplained deviation and a resolved event have different implications for the next run.
Downstream recovery can materially change the economics. Show the recovery train and its assumptions alongside upstream titre and productivity. The cost share must come from the process model, rather than a sector-wide percentage.
Illustrative mass balance: one original litre of broth containing 30 g of target product, with 45 percent overall recovery, yields 13.5 g of recovered target product before any additional specification losses. That is mass per original litre of broth, not the concentration of the final stream. Recalculate each cost line on its correct basis; the example does not imply that every component of total COGS doubles.
A useful skills review starts with the actual work: transferring the process, selecting and operating separation equipment, investigating contamination, interpreting variation and recording changes. Experience with a large vessel matters only insofar as it is relevant to the material, equipment and constraints in this programme.
Relevant experience may come from food fermentation, biopharmaceuticals, chemicals, equipment suppliers or existing food biotech teams. Evaluate the work each person has actually done.
Look for experience with relevant equipment, failure investigation and process documentation. Availability and cost need direct confirmation. Practical knowledge complements published methods; it does not make published engineering evidence irrelevant.
Related analysis: How to choose a fermentation production site
Examples of project and facility planning
Regulatory permission and production readiness
A regulatory authorisation and a successful production transfer answer different questions. Consider them separately in the development and financing plan.
If commissioning or validation takes longer than the financial plan allows, the funding requirement changes. Model that dependency explicitly, rather than attributing a named company’s insolvency to an unverified technical cause.
Regulatory permission concerns the product, intended use and market under the applicable conditions. Production readiness concerns reliable output, specification and economics on the intended equipment. Progress on one does not prove the other. This distinction does not diagnose the outcome of a named company.
Keep regulatory, technical, commercial and financing milestones separate when reviewing the next commitment.
Planning examples: Solar Foods and BFF-Ede
Solar Foods’ public Factory 02 planning shows that a location decision can involve electricity, infrastructure, construction, permitting and financing. A project plan is not proof of achieved commercial output. The example is relevant to the questions a receiving site raises, not proof that every transfer risk has been solved.
NIZO’s January 2025 BFF-Ede announcement described an open-access scale-up project up to 10,000 litres supported by a EUR 12.5 million grant. Its June announcement concerned the future site. Confirm current operating status and process compatibility with the operator.
A practical transfer plan tests equipment, operator and documentation assumptions before committing to the next production milestone. Include the possibility of a failed trial and the time and cash needed to investigate.
Before buying a facility, compare ownership with suitable external or shared capacity. The result depends on process compatibility, schedule, know-how, demand and financing. A universal vessel-volume cutoff or three-to-fivefold capital saving is not established here.
For R&D teams
A publication and a transfer package can overlap substantially, but their intended users may need different information. A paper reports the question, methods and results within its scope. A receiving operator also needs executable instructions, material specifications, equipment comparisons, operating limits and deviation handling. Describe what is missing instead of labelling research inherently unsuitable for industrial work.
Repeatability within one team and reproducibility under changed operating conditions provide different evidence. Record which parameters were held constant, which changed and how performance varied. Neither three runs nor twelve runs alone establishes a process as ready for transfer.
Use these three checks to prepare a useful operator discussion. They are a starting structure, not universal intake requirements or a validated transfer standard.
1. What does the run history establish?
Distinguish sequential optimisation from repetition of a defined procedure. Record changes between runs, variation within each run and the relevant product outputs. Agree the number and design of further runs from observed variability, the risk of a wrong decision and the receiving operator’s requirements. Three runs can be informative without being a universal validation threshold.
Second: does a contamination event log exist, with root-cause analysis for each incident?
Keep a dated event and deviation log with vessel identity, observations, investigation, corrective action and evidence of effectiveness. If no contamination has been observed, examine run history and detection methods. An absence of recorded events does not by itself prove either poor tracking or an immature process.
Third: are critical process parameters documented with acceptable ranges - not target values, but ranges within which performance holds?
For illustration only, a target of pH 6.8 describes a setpoint. A tested operating interval would additionally identify the conditions studied, the observed performance, the runs supporting that conclusion and uncertainty at the boundaries. An example such as pH 6.8 ± 0.2 is not a recommended range for another process. Setpoints and acceptable ranges must come from the relevant development work.
Prepare a batch record covering media and supplier specifications, inoculation, critical process parameters, in-process checks, expected performance and deviation handling. Review it with the receiving operator. Questions during transfer are expected; the purpose is to make the process and its limits explicit.
Start drafting the batch record early and use it in the operator discussion. Writing it can expose missing instructions or unsupported assumptions; targeted bench work may still be needed to resolve them. An initial conversation can help establish what evidence the operator requires before accepting a campaign.
For founders
Founders need to decide which transfer capability to own, which to access through a partner and when to commit. That decision should follow the process requirements and cash plan, rather than a general rule about the right size of an industrial team.
Secure process-transfer expertise before it becomes a schedule dependency. Compare internal hiring with qualified contractors and the receiving operator’s support. Build realistic lead times into the milestone plan.
Match the resourcing model to the work. A contractor, a receiving operator and a permanent manufacturing role have different costs and responsibilities. Choose the arrangement that covers the next milestone and preserves the knowledge needed later.
NIZO’s BFF-Ede announcements describe a planned open-access scale-up project, not a confirmed production slot for this team. Other potential development partners, including 21st.BIO, need the same direct checks: current equipment, permitted processes, support scope, confidentiality, schedule and commercial terms. A capability description should remain a lead to investigate until the operator confirms a compatible offer.
Three kinds of evidence can make a scale-up discussion more specific. Their relevance and required depth depend on the proposed commitment; none eliminates execution risk.
External operating evidence
An external trial can test equipment, operator and documentation assumptions that repeated internal work does not. Set acceptance criteria for the actual process; a fixed 15 percent tolerance is not a universal standard or a substitute for sufficient replication.
Measure downstream recovery across repeated independent runs using a defined input/output basis and product specification. Set the number of runs according to variability and the decision, rather than treating three as a universal validation standard.
State which values are measurements and which remain assumptions. Both can appear in an early cost model, provided their uncertainty and sensitivity are visible.
A defined operator discussion
Record the facility, equipment, material reviewed, feedback received and decisions still outstanding. An introductory conversation can be useful without establishing a partnership. A confidentiality agreement protects a discussion; it does not itself confirm technical acceptance or a production booking.
A useful technical review asks for recovery measurements, external operating experience and sensitivity to lower yields. The depth of evidence should match the process, its stage and the commitment under review.
Add the dependencies that determine whether the next milestone is executable: equipment, evidence, operator acceptance, materials, budget and time for investigation.
For investors
Scale-up introduces material execution risks that should be made explicit in the operating plan. Assess them alongside regulatory, market, supply and financing risks instead of assigning a universal sector ranking.
Five questions to ask in the first meeting - before any due diligence, before any technical advisor is brought in.
One. What is the highest scale at which this process has run, and who operated it?
Ask for vessel volume, facility, operator, protocol version, run count and performance on a consistent basis. Internal and external runs answer different questions. A single successful external run can expose new information without establishing reproducibility or an acceptable universal tolerance.
Two. What was the last contamination event, and what caused it?
Review contamination history alongside batch counts, detection methods, deviations and investigations. A documented event can provide useful learning. No observed event is not evidence, by itself, of either insufficient experience or poor records.
Three. What happens to your cost model if DSP yield drops from X% to Y%.
Use measured recovery and variation where available. Where they are not, retain the assumption, explain its basis and test a justified range. A cost model built partly on assumptions is still a model. Its decision value depends on those assumptions being inspectable and on a plan to test the consequential ones.
Four. Who on your team has transferred a process to commercial scale?
Ask who has transferred a comparable process and what evidence they can share about the conditions, deviations and resulting performance. Previous failures may provide useful learning, but a successful transfer does not require a prior failed one.
Five. What single milestone reduces your scale-up risk the most, and what does it cost and take how long?
A useful plan names the receiving facility, trial scale, process package, acceptance criteria, quotation and lead time. Use a current written operator quotation; an illustrative trial cost or lead time is not an available commercial offer.
Prompts for further investigation
A single blended COGS number with no separation between upstream fermentation cost and downstream processing cost
- Missing run, deviation or detection records that prevent a reviewer from assessing the operating history.
Pilot data generated only at lab geometry - no external vessel, no different impeller, no different operator
No named DSP vendor or separation equipment supplier despite a downstream process described as defined and costed
A scale-up timeline structured in years with milestone labels and no listed dependencies or risk-reduction triggers
“We have spoken to several CDMOs” with no named facility, no process package submitted, and no written feedback received
Before the next financing or campaign commitment, test a downside case with additional transfer work and delayed acceptable output. The number of extra iterations is a scenario assumption. Ask whether the cash and timetable can support it, then identify the result that would justify changing that assumption.
The next watchpoint is the receiving operator’s evidence: after the trial, compare recovery, specification and variability with the acceptance conditions agreed beforehand. If the result changes the cost or timing assumptions, change the operating plan before repeating them in the financing case.
Sources and scope
This is an edited adaptation of the author’s full Substack essay, first published 2026-04-02. Examples and editorial frameworks are distinguished from measured evidence. Source checks and editing: 16 October 2026.
- GFI, techno-economic insights
- NIZO, BFF project announcement, January 2025
- NIZO, future-site kick-off, June 2025
Read the original Substack version. Read the FoodEdge editorial standards or suggest a correction.
Cover photograph: Photo by Julia Koblitz / Unsplash. Context image, not a photograph of a company or experiment discussed here. Photo licence.
