The Open Path
One foundation, bench to filing - one qualified GMP foundation taken up in three opt-in stages that never change the chemistry underneath it.
A programme's cost and risk do not sit only in the molecule. They sit in how it is resourced and de-risked across the journey to the clinic - and the usual mistake is to pay for every layer of assurance on day one, or to scramble for it at filing. The Open Path resolves that: one qualified GMP foundation, taken up in three stages matched to where a programme is. Stage A - establish the process on in-stock GMP material (speed). Stage B - upgrade the water to WFI Beyond as the product nears the patient (safety). Stage C - add DMF and stability support as you approach filing (formalities). The chemistry never changes from the first stage to the last; only the assurance around it grows.
In-Depth · Industry Edition C05 · Rev 1.0 · 19 Oct 2026 · Author: Jens Hartmann, CEO, PAN-Biotech & PAN-Celltech · a briefing for pharma, biotech & CDMO teams.
Key takeaways
- One foundation, three stages. A single qualified GMP supply base, taken up as a programme earns it - Stage A establish, Stage B upgrade, Stage C file - each stage opt-in and on request.
- The chemistry never changes. The buffers and media you develop on in Stage A are the same material you scale and file with - no RUO-to-GMP switch, no comparability gap. Only the layer of assurance around them grows from stage to stage.
- Stage A - Speed. Build on existing GMP-grade CT catalogue buffers and media, held on stock and immediately shippable, CoA per lot. On-shelf means you win on price and availability at once - the two levers that dominate total cost of ownership (TCO).
- On the shelf, across the whole bioprocess. Upstream, PAN's catalogue runs to roughly 1,800 listed products (~85% on stock); downstream, the standardized Open Downstream program is a compact, still-growing shelf - some 35-40 GMP stock products - engineered so a few dozen universal stocks cover close to 90% of what a process needs, every item on stock. Breadth upstream, precision downstream.
- Stage B - Safety. Upgrade the water base of the medium or buffer to WFI Beyond - metal-controlled (all 24 ICH Q3D elements by ICP-MS, plus copper and iron on a dedicated oxidation-metals addendum), nuclease-free and ultra-low in endotoxin: the insurance against the silent, late failure. Stage B is also where you scale the fill format (1 ml vials up to 1000 L bags) and add customized products where a standard needs tailoring.
- Stage C - Formalities. Add DMF support and a stability study - reference the filed FDA Type IV (excipient) DMFs (WFI Beyond MF044505, DPBS MF044371), with a custom DMF written and filed by PAN's expert team in weeks, not months, and ICH Q1A(R2) stability on request. The dossier, carried on the supply side.
- Spend staged to risk. You take only the layer each phase needs - the result is the lowest total cost of ownership across the programme and a faster path to the patient, not the lowest sticker price on any one line.
- It works for every modality. The same path underlies monoclonal antibodies, cell & gene therapy, mRNA, vaccines and liposomes/LNP, on a foundation that spans both upstream and the standardized downstream range - one engagement model across the portfolio.
Research to filing, spend staged to risk
You take only the layer each phase needs - and the chemistry underneath never changes.
Where the cost and the risk really sit
Every programme spends enormous effort on the molecule. Far less is spent, deliberately, on the supply and assurance that carry it - and that is where a surprising share of the cost and the risk actually accumulates. The chain of buffers, media, solvents and excipients a process runs on has to be qualified, documented, scaled and defended in a filing, and sourcing it badly - from a fragmented base, at the wrong grade, with the paperwork left to the end - is what quietly adds months and multiplies the chance of a late, expensive failure.
The usual responses are both wrong in opposite directions. One is to gold-plate everything from day one: buy the highest grade, the fullest documentation and the regulatory backing before the programme has earned any of it - paying for assurance the molecule may never reach. The other is to defer all of it and then scramble at filing: changing a material late, re-qualifying, opening comparability work exactly where it hurts most. Neither matches spend to risk.
The question is not "what is the cheapest input" or "what is the most complete dossier" - it is "what does this phase actually need, and can I add the rest later without changing anything underneath?"
The Open Path is PAN's answer: one qualified foundation you build on from the first research run, and two further layers of assurance you add on request as the programme matures - without ever re-sourcing or re-qualifying the chemistry you started on.
Section 2One foundation, three stages
The model is deliberately simple. The same qualified GMP material carries the programme the whole way; three stages differ only in the layer of assurance wrapped around it, and you take each one only when the phase calls for it.
Establish the process
Build and establish your process on existing GMP-grade CT buffers and media - held on stock and immediately shippable, released with a CoA per lot. No custom-manufacturing wait, and you develop on the exact material you will scale and file with.
What it gives you: Speed - start now, off the shelf.
Upgrade to WFI Beyond
As the product moves toward the patient, upgrade the water base of the medium or buffer to WFI Beyond where the molecule earns it - metal-controlled (24 ICH Q3D elements plus copper and iron), nuclease-free, ultra-low endotoxin. It is also where you scale the fill format (1 ml vials up to 1000 L bags) and add customized products where a standard needs tailoring. The safety layer that removes the silent, late failure modes before they can reach a clinical batch.
What it gives you: Safety - insurance on the inputs.
DMF & stability support
As the programme moves toward filing, add DMF support and a stability study: either reference a DMF PAN has already filed (WFI Beyond MF044505, DPBS MF044371), or have PAN's expert team file a new custom DMF for your product in weeks, not months - plus ICH Q1A(R2) stability data on request. The paperwork and regulatory know-how, carried on the supply side.
What it gives you: Formalities - the dossier, handled.
Each stage is opt-in and on request; a programme can stop at any stage or take all three. Because the buffers are GMP grade from Stage A, nothing about the chemistry changes as the assurance layers are added.
Section 3Stage A - establish the process
The first stage is about moving. The whole PAN catalogue a programme needs - buffers, stock solutions, upstream media and the standardized downstream range - is GMP-grade (CT-series), held on stock and immediately shippable, released with a Certificate of Analysis per lot. A team orders what the step needs and starts, with no custom-manufacturing slot, no multi-week lead time and no project set-up to clear first.
The depth behind that is real, and it runs across the whole bioprocess. Upstream, PAN's established catalogue runs to roughly 1,800 listed products, around 85% of them held on stock. Downstream, the newer, deliberately standardized program takes the opposite route to the same place: a compact, still-growing shelf - on the order of 35 to 40 GMP stock products today, and expanding as each application is added - built so that a few dozen universal stocks cover close to 90% of everything a downstream process needs, every item on stock. Breadth upstream, precision downstream, immediate availability on both. The downstream foundation is set out in full in In-Depth D01 - The Open Downstream.
The quiet advantage is that you develop on the very material you will scale and file with. Because it is already GMP grade, there is no RUO-to-GMP switch to revalidate later and no comparability gap opening up when the programme crosses into the clinic - a research-grade (RUO, P-) version can still be produced on request where a project wants one for higher-volume early work. And because every item is on the shelf, procurement wins on price and availability at once - the two levers that dominate total cost of ownership (TCO), well beyond the unit price on any one quote.
Section 4Stage B - upgrade to WFI Beyond
As a product moves toward the patient, the margin for error on the inputs narrows. Stage B upgrades the water base of the medium or buffer - the single largest component of almost every medium, buffer and formulation - from standard GMP WFI-quality water to WFI Beyond, PAN's beyond-compendial Water for Injection, where the molecule earns it. It is opt-in and made to order, produced through PAN-Celltech's Custom Solutions program with a Certificate of Analysis per lot.
What the upgrade adds, proven lot by lot: all 24 ICH Q3D elemental impurities measured by ICP-MS, plus copper and iron reported on a dedicated oxidation-metals addendum (iron sits outside the monograph and ICH Q3D, so PAN reports it as a beyond-compendial characterisation); nuclease-free (RNase and DNase not detected); and endotoxin more than 50x below the Ph. Eur. Water-for-Injection limit. It is the one upgrade that lifts the quality ceiling of the whole process at once, because everything is built on water.
Stage B is also where a programme scales and tailors. The same qualified material can be filled to whatever format the step needs - from 1 ml vials through tubes, bottles and single-use bags, up to 1000 L - so the move from a small early prep to full process volumes never means re-sourcing or re-qualifying. And where a standard product does not fit a process exactly, PAN-Celltech will supply a customized product on request - for example, optimising the recipe or performance of a Stage A standard to a programme's own process - built from the same qualified, in-stock building blocks, so a tailored product is a refinement of the foundation, not a departure from it.
Built on WFI Beyond
For a programme heading to the patient, WFI Beyond is the recommended, on-request safety standard: it removes the contaminant classes that quietly destroy a product in storage - trace metals that drive oxidation, nucleases that degrade a nucleic-acid payload, endotoxin that cannot be cleared from an injectable - at the cheapest layer to control. The full water story is In-Depth · Industry Edition D02 · Water: The WFI Beyond Standard.
Built on WFI Beyond the mark for the water beneath a molecule that earns it.
Honest boundary: the figures above are release values, proven on every lot; the stated shelf life rests on stability studies for the microbiological parameters (sterility and endotoxin). WFI Beyond is an excipient for further manufacturing, not for direct human use.
Section 5Stage C - DMF and stability support
The last stage is about the dossier, and there are two routes to it: use a DMF PAN has already filed, or have PAN file a new one for your product. Route one - two of the universal utilities are already backed by filed FDA Type IV (excipient) Drug Master Files - DPBS (MF044371) and WFI Beyond (MF044505) - which you cross-reference in your IND/BLA through a Letter of Authorization, so the material is referenceable as exactly what it is in the product without rebuilding a dossier or re-proving it, taking months of independent testing off the critical path. PAN's proprietary detail stays in the FDA's confidential file.
Route two - where a specific product you rely on is not yet filed, PAN-Celltech's regulatory experts will write and file a new custom DMF for it on request, drawing on the extensive in-house expertise behind our own filed Type IV DMFs to get a dossier written and submitted in weeks, not months, and provide an ICH Q1A(R2) stability study to support your shelf-life claim. It is a maintained, living dossier - annual updates, change control - which is why Stage C signals a long-term supply relationship rather than a spot buy. DMF and stability support are optional, on-request services.
Section 6The through-line - spend staged to risk
Put the three stages together and the logic is one sentence: take only the layer each phase needs, on a foundation whose chemistry never changes. Stage A gets you moving on in-stock material; Stage B buys the safety insurance as you approach the patient; Stage C carries the regulatory load toward filing. Because nothing underneath is re-sourced between stages, there is no comparability work, no re-qualification, no restart - the assurance grows, the material does not.
That is why the Open Path is both the lower-cost and the faster-to-patient decision: it removes the hidden tail of TCO (qualification labour, incoming QC, and above all the cost of a late failure or a forced material change) while keeping the programme moving. It also collapses the supply base to one vendor, one audit, one purchasing process across the whole path, upstream and downstream - fewer suppliers to qualify, assess and transact with at every stage. And because it is one engagement model over a single foundation, it applies the same way whether you are making a monoclonal antibody, a cell or gene therapy, an mRNA product, a vaccine or a liposome / LNP - all on one foundation that spans upstream and the standardized downstream range set out in In-Depth D01 - The Open Downstream.
Assurance is a thing you add, not a thing you gamble on
The fear I hear most across the industry is not a slow buffer order - it is a programme that fails late on something avoidable: a material changed under qualification, a storage surprise in a nearly-finished batch, a dossier gap found at submission. Every one of those is an assurance failure, not a molecule failure, and the cheapest time to prevent them is before they can happen.
The Open Path is built so a team never has to gamble on that. You start on material that is already GMP grade and already filed-ready beneath; you add the water-quality insurance when the molecule earns it; you add the regulatory dossier as you approach filing - each layer on request, none of it forcing a change to what came before. Controlling the inputs up front, and upgrading where a molecule earns it, is among the cheapest insurance a programme can buy against its most expensive kind of late failure.
- A personal note from the author, drawn from the interview programme behind this In-Depth series.
The partner behind the path
The Open Path is only as good as the operation behind it - a GMP operation proven at commercial scale, GMP-compliant and audit-proven in an EU Annex 1 facility (a capability, not a certification):
Track-record figures are anonymised; capacity figures are stated as "up to".
What the Open Path means for you - by function
The model is shared. The sections below translate it into the terms of a specific role - read yours, skip the rest.
Develop on the material you will file with
Start at Stage A: build your process on in-stock GMP-grade buffers and media, shippable now, so development is not gated on a manufacturing slot. Because the material is GMP from the outset, the chemistry you develop on is the chemistry you scale and file with - no RUO-to-GMP switch, no comparability gap. The WFI Beyond upgrade (Stage B) and DMF / stability support (Stage C) layer on later, as the programme reaches the clinic, without changing anything you developed on.
On-stock material, no re-qualification between stages
Stage A in practice: GMP buffers and media you can order and run today, with a CoA per lot, scaling from a small prep to process volumes - up to single-use bags of 1000 L - without re-qualifying the supply. The later assurance layers (WFI Beyond, then DMF) are added without changing the chemistry on your floor, so a stage change never means a line change.
Qualify once; pay for assurance when it is earned
The three stages are a procurement advantage in themselves: qualify the GMP foundation once (Stage A), then add the WFI Beyond upgrade (Stage B) and DMF / stability (Stage C) only as a programme earns them - assurance paid for when it is needed, not before, and no re-sourcing between stages. And because every Stage A product is on the shelf - roughly 1,800 upstream products (~85% on stock) and a standardized downstream shelf of some 35-40 products covering close to 90% of a process - you win on price and availability at once, the two levers that dominate total cost of ownership (TCO), well beyond the unit price on any one quote. And consolidating the whole path onto this one foundation means one vendor, one audit, one purchasing process - fewer suppliers to qualify, assess and raise orders against, the TCO most procurement teams never get onto the quote.
One audited source; documentation that deepens, never changes
One audited GMP source across the foundation collapses the QA load - one documentation and packaging standard, one EU Annex 1 site to assess, a CoA on every lot. The value concentrates in Stages B and C: the WFI Beyond upgrade documents the metal (24 ICH Q3D elements plus copper and iron), nuclease and endotoxin attributes on the CoA and its oxidation-metals addendum, and DMF plus ICH Q1A(R2) stability put the dossier on file - both added without re-qualifying the underlying GMP material, so comparability is preserved by design.
Reference our filings; add the dossier as you approach submission
This is where Stage C pays off. DPBS and WFI Beyond are backed by filed FDA Type IV (excipient) DMFs (MF044371, MF044505) you cross-reference through a Letter of Authorization - months off the critical path. Because the material in your control strategy has not changed since Stage A, nothing shifts under you late in development, and where a product you rely on is not yet filed, PAN-Celltech's expert team will write and file a custom DMF - in weeks, not months - and provide ICH Q1A(R2) stability on request.
Spend staged to risk - lower cost, faster to patient
The strategic case is one line: take only the layer each phase needs, on a foundation that never changes underneath. Stage A gets you moving on in-stock material; Stage B buys the safety insurance as you approach the patient; Stage C carries the regulatory load toward filing. Judged on total cost of ownership rather than sticker price, a single on-stock, GMP-grade, DMF-supported source across the whole path is both the lower-cost and the faster-to-patient decision - and exactly the CMC and supply-chain diligence investors and partners look for.
Run it yourself - and offer the same path to your sponsors
For a contract manufacturer, one qualified foundation with a CoA per lot and DMF-backed key utilities lets you standardise incoming materials across every client programme rather than re-qualifying a different base for each. And you can offer the same three stages to your sponsors: establish on in-stock GMP material (Stage A), upgrade to WFI Beyond for the clinic (Stage B), add DMF / stability (Stage C). For you that is ease of doing business - one qualified supplier, one documentation standard, on-shelf availability - and a lower total cost of ownership (TCO) across every programme you run.
In one arc
One qualified GMP foundation → establish the process on it, on stock, immediately (Stage A, speed) → upgrade the water to WFI Beyond as the molecule nears the patient (Stage B, safety) → add DMF and stability support as you approach filing (Stage C, formalities) → with the chemistry never changing from first stage to last. Spend staged to risk, across every modality - the lowest total cost of ownership and the faster path to the patient, from a single partner whose reason for building the path is to take time and risk out of yours to the clinic.
What to ask your PAN contact for - by stage
Each stage has a short list of things to request; you only ever need the ones for where your programme is.
The buffers and media are GMP-grade CT catalogue products, manufactured by PAN-Celltech, released with a Certificate of Analysis per lot; a research-grade (RUO, P-) equivalent can be produced on request. Manufactured to GMP in an EU Annex 1 facility (a capability, not a certification), within an ISO 9001-certified quality system. WFI Beyond, custom DMF and stability support are opt-in, on-request Custom Solutions services.
The Open Path, answered
Do I have to take all three stages?
No. Each stage is opt-in and on request. Many programmes run entirely on Stage A; others add Stage B (WFI Beyond) as they approach the clinic, and Stage C (DMF + stability) as they approach filing. You take only the layer each phase needs, and you can stop at any stage.
What does "the chemistry never changes" mean in practice?
The buffers and media you develop on in Stage A are GMP grade from the outset, so they are the same material you scale and file with. Adding Stage B (a water-base upgrade) or Stage C (DMF and stability documentation) does not re-source or re-formulate that material - it wraps more assurance around it. So there is no RUO-to-GMP switch and no comparability gap opening up later.
How does this lower total cost of ownership?
Because you qualify the foundation once and pay for the WFI Beyond and DMF/stability layers only when a programme earns them - not up front, and not in a late scramble. Stage A material is on the shelf, so you win on price and availability at once; and avoiding a forced late material change removes the most expensive line in the hidden tail of TCO. The result is lower total cost and a faster path to the patient.
What exactly is the Stage B WFI Beyond upgrade?
WFI Beyond is PAN's beyond-compendial Water for Injection, opt-in and made to order. Every lot is proven on its Certificate of Analysis to carry all 24 ICH Q3D elemental impurities by ICP-MS, plus copper and iron on a dedicated oxidation-metals addendum, to be nuclease-free (RNase and DNase not detected) and to run more than 50x below the compendial endotoxin limit. It is backed by a filed FDA Type IV (excipient) DMF (MF044505). The full story is In-Depth Edition D02 - Water.
What does Stage C cover, and is stability included?
Stage C is DMF support plus a stability study. You can reference the filed FDA Type IV DMFs for DPBS (MF044371) and WFI Beyond (MF044505) through a Letter of Authorization; where a product you use is not yet filed, PAN-Celltech's expert team will write and file a custom DMF on request - in weeks, not months - and provide an ICH Q1A(R2) stability study to support your shelf-life claim. Both are optional, on-request services.
Does the Open Path apply to my modality?
Yes - it is modality-agnostic. The same three stages underlie monoclonal antibodies, cell and gene therapy, mRNA, vaccines and liposomes/LNP, all on the downstream foundation in Edition D01. The application-specific editions (A02-A06) show the material set for each; the Open Path is the engagement model that runs across all of them.