Buying a Sterile Liquid Filling Line? Questions Only This Line Needs

These questions are for a supplier of a sterile liquid filling line, and only that line. The costs that apply to any machine, such as shipping, installation, training, spare parts and documents, are in a separate article: The Price on the Quotation May Not Be the Full Cost.

1. Output, at a stated container sizeAn output of 100 units per minute means nothing until you know the container size, the fill volume and the type of stopper. Ask for the output at your own container size and fill volume.
2. Vials that need washing, or ready-to-use vialsOrdinary vials, delivered in cartons and not sterile, must be washed and depyrogenated before filling. That means a washing machine and a depyrogenation tunnel in front of the filler. Ready-to-use vials arrive already sterile in sealed tubs, and need a station that opens the bags and tubs instead. These are two different lines, with different prices and different floor space. Which one is quoted? Are the washer and the tunnel included?
3. Format parts, and the price of each additional sizeWhich container sizes are included? A line delivered with one set of format parts cannot necessarily run every size. Additional sizes need additional format parts, and additional validation. What does each additional size cost, and how long does a changeover take?
4. What separates the operator from the sterile zoneAn isolator or RABS? An isolator is a fully closed box around the filling area. RABS is a partly open barrier inside a cleanroom. EU GMP Annex 1 encourages one of the two for new plants. If it is an isolator: is the decontamination generator included? And are cycle development and its validation included, or priced separately?
5. Glove testingGloves are the weak point of any barrier. Annex 1 expects isolator gloves to be integrity tested at least at the start and end of each batch or campaign, and RABS gloves at regular intervals. Is a glove tester included?
6. The dosing system, tested on a liquid like yoursPeristaltic pumps, piston pumps and time-pressure systems behave differently with thick liquids, liquids that foam, and protein products. Which dosing system is quoted? Has it been tested with a liquid like yours? Can you test it with your product, or with a placebo of the same viscosity, during the factory acceptance test?
7. The product path: single-use, or cleaned and sterilised in placeThe parts that touch the product, from the tank to the needles, are either single-use sets that arrive sterile, or stainless steel parts cleaned and sterilised in place (CIP/SIP). Single-use sets save you the cleaning validation, but you buy new ones for every batch. Which option is quoted? If single-use: who makes the sets, can you buy them from more than one source, and what does one set cost?
8. The sterile filter, and its test before useAnnex 1 expects the sterilising filter to be integrity tested after it is sterilised and before it is used (PUPSIT). The line must allow this test without opening the sterile path. Is the filter integrity tester included, and is the design ready for this test?
9. Fill accuracy, and the speed at which it is guaranteedThe fill-volume tolerance at a low speed is not necessarily the same at the operating speed you need.
10. Weighing the containers during fillingDoes the line weigh every container to confirm the fill volume is within the permitted limits, or only samples? If a container falls outside the limits, does the line remove it from the track by itself, or does that need manual intervention?
11. Stoppers: how they arrive, and how they get inReady-to-use sterile stoppers, or stoppers that must be washed and sterilised on site in a separate machine? And how do they enter the Grade A zone (the cleanest zone, where the product is open to the air) without breaking it?
12. Stoppering and cappingAfter filling, the rubber stopper is inserted, then the metal cap is crimped on. Do both steps happen inside the filling machine itself, or in one or two separate machines? Each separate machine has its own price, its own floor space, and its own qualification and validation requirements.
13. Particle and air monitoring in Grade AAnnex 1 expects the Grade A zone to be monitored for particles, and sampled for microorganisms, for the full duration of filling. Are the particle counter and air sampling points built into the line and included in the price, or left to you?
14. The link to the freeze dryerIf a freeze dryer is in the plan: how is it loaded and unloaded, automatically or by hand? And who is responsible for the link between the two machines?
15. Visual inspection after fillingEvery filled container of an injectable must be inspected for particles and defects. This is usually a separate machine or a manual inspection station. Is it part of the quotation?

A quotation that answers all these questions can be compared with another that answers them all.
A quotation that leaves half of them unanswered is not a cheaper quotation, it is an incomplete one.
The missing answers will be paid for, but after you have signed, and at a price you can no longer negotiate.