Assumptions in a URS are not a defect. Every specification written before the process is fully characterised contains them. The defect is an assumption that is invisible — inherited from the previous project, never written down, and discovered at qualification when changing it costs six figures.
These six recur on nearly every vial filling project.
1. Fill volume tolerance
Almost always copied from the last URS as "±2%". The number that matters comes from the label claim, the pharmacopoeial uniformity of delivered dose requirement for the presentation, the overfill already granted in the batch record, and the site's demonstrated process capability. For a high-value biologic, tightening from ±2% to ±1% can pay for itself in yield within a year; for a low-cost diluent it is money spent on nothing.
State the tolerance, the basis, and the measurement method — gravimetric at what sampling frequency, on what balance resolution, corrected for density at what temperature.
2. Container and closure dimensional range
A machine is set up for a vial, not for a nominal size. Two suppliers' 10R vials differ in flange thickness, overall height tolerance and glass distribution. If the URS says "10R vial", the change-parts are designed for whichever drawing the supplier had to hand. Specify the full dimensional envelope, including the tolerance range across every approved container supplier, and state whether dual sourcing must run without change-parts.
The same applies to stoppers: lyophilisation stoppers, serum stoppers, the durometer, the siliconisation level and whether they are supplied ready-to-sterilise.
3. Product characteristics at the point of fill
Viscosity, density, surface tension, foaming tendency, shear sensitivity, particulates, and whether the product is a suspension that will settle in the buffer vessel. These decide pump technology — peristaltic, rolling diaphragm, rotary piston, time-pressure — and pump technology is not a change you make later.
If any of these are unknown at URS stage, say so explicitly and specify the range the design must tolerate. A requirement to handle 1–50 mPa·s is honest; silence is an assumption of water.
4. The environmental and containment concept
Open RABS, closed RABS or isolator is often decided by capital budget and then rationalised. It is a requirement driven by the product, the intervention profile and the site's contamination control strategy — and it changes almost everything downstream: decontamination cycle time, glove port count and position, transfer systems, environmental monitoring points, gowning, and the achievable line efficiency used in the capacity calculation.
Decide it in the URS, with the rationale, or accept that the capacity numbers are provisional.
5. Intervention list
Every planned and unplanned intervention the line must support — weight check retrieval, stopper bowl refill, format part cleaning, jam clearance, sampling for sterility, first-air corrections. This list determines glove port positions, tooling access, and whether an intervention can be performed at all without stopping the line or breaching first air.
Suppliers do not know your intervention list. If it is not in the URS, the machine will be designed for theirs.
6. Data, records and audit trail scope
Which parameters are critical, which records are the GMP record, how long they are retained, who may change a recipe, how electronic signatures are applied, and how data leaves the machine. This is the requirement set that most often reaches Site Acceptance Test unresolved, because it is written as "shall comply with 21 CFR Part 11" — a sentence a supplier cannot design against.
Write it as function: role-based access with named roles, a time-stamped audit trail of parameter changes that cannot be modified by any user role, retention for the record's stated life, and a defined export format the site can read without the supplier's software.
Handling them properly
The mechanism is simple and it is what an assumptions register is for:
| Field | Purpose |
|---|---|
| Assumption | The value taken, in the form used in the requirement |
| Basis | Where it came from — comparable equipment, development data, engineering judgement |
| Owner | The named person who must confirm it |
| Confirm by | The gate at which it must be resolved: enquiry, purchase order, FDS approval, FAT |
| Impact if wrong | What has to change, and what that costs |
Nothing should reach approval with unconfirmed assumptions still open. The register makes them visible enough that closing them becomes somebody's job rather than everybody's hope.