Fill the pump using a syringe and a blunt-tipped filling tube. Holding the pump in an upright position, fill the reservoir, allowing air to escape around the filling tube.
For accurate operation, it is essential that each pump is filled completely with drug solution and that correct filling is verified by the method detailed in this section. Air bubbles trapped within the body of the pump, or failure to insert the flow moderator into the pump, may result in unpredictable pumping rate fluctuations. When filling the pump, ensure that solutions are at room temperature.
DURECT recommends that sterile technique be used during the filling and handling of ALZET pumps and during the surgical implantation procedure. Inadvertent contamination of the solution or flow moderator during filling may result in the growth of potentially activity-destroying microorganisms, tissue irritation, and erratic results. If the sterility of your solution is a concern, fill the pumps through a 0.22 µM syringe-end filter (e.g.,Millex®-GV) .
During filling and implantation, ALZET pumps should be handled with surgical gloves. Skin oils may interfere with the performance of a pump if they accumulate on its surface. If a pump becomes contaminated, its surface may be wiped with an aqueous solution of 70% isopropanol immediately before use. Do not soak the pump in isopropanol.
The following steps should be performed in a laminar flow hood using sterile technique:
- Weigh the empty pump together with its flow moderator.
- Check the instructions (supplied in each box of pumps) for the mean fill volume for the lot of pumps that will be used.
- Attach a filling tube (supplied with each package of pumps) to a syringe and draw up the room temperature solution. It is essential that the syringe and attached tube be free of air bubbles. Allow extra syringe volume for spillage. For best results, use the smallest volume syringe possible. With the flow moderator removed, hold the pump in an upright position (exit port pointed vertically).
- Insert the filling tube through the opening at the top of the pump until it can go no further. This places the tip of the tube near the bottom of the pump reservoir.
- Slowly push the plunger of the syringe, holding the pump in an upright position. A small amount of backpressure is normal, due to the tight seal at the filling port. When the solution appears at the outlet, stop filling and carefully remove the tube. (Rapid filling of ALZET pumps should be avoided because it can introduce air bubbles into the reservoir.) (refer to troubleshooting)
- Wipe off the excess solution and insert the flow moderator until the cap or flange is flush with the top of the pump. The insertion of the flow moderator will displace some of the solution from the filled pump. This overflow should be wiped off. The flow moderator must be fully inserted into the body of the pump.
- Weigh the filled pump with the flow moderator in place. The difference in the weights obtained in Steps 1 and 6 will give the net weight of the solution loaded. For most dilute aqueous solutions, the weight in milligrams (mg) is approximately the same as the volume in microliters (µl). The fill volume should be more than 90% of the reservoir volume specified on the instruction sheet. If so, the filled pump is ready for use. If not, there may be some air trapped inside the pump. Evacuate the incompletely filled pump and refill (Steps 1-6).
- If working with a catheter, a viscous solution, or an agent which may have acute toxic effects, prime the filled pumps in sterile, 37º C saline.
Troubleshooting: If you experience any difficulty filling the pumps, try filling them with the filling tube at a slight angle. This allows the air in the reservoir to escape more easily. If the filling port still seems tight, insert and remove the flow moderator several times before reinserting the filling tube.
Priming ALZET Pumps
All ALZET pumps have a start-up gradient during which the pumps soak up fluid and come to temperature. This start-up period can be accomplished by “priming” the pumps in vitro prior to implantation in vivo using the procedure below.
Priming is essential when:
- Immediate pumping is required
- A catheter is used with the pump
- A viscous solution is delivered
- The drug solution may have acute toxic effects
- Fill the pumps in the usual manner.
- Place the prefilled pumps in sterile 0.9% saline or PBS at 37º C for at least four to six hours (preferably overnight) prior to implantation. (Exception: Model 2004 requires 40 hours to prime, Model 2006 requires 60 hours to prime, Model 2001D requires 3 hours, and Model 1004 requires 48 hours.)
- If using a catheter, it is possible to drape the end of the catheter outside the beaker to avoid any mixing of solutions.
- Do not be concerned if due to evaporation, fluid is not observed dripping from the end of the catheter, as evaporative loss can occur. Remove the pump from the saline and implant immediately.
Note: While a small amount of drug solution will be expelled during priming, this will not compromise administration of your compound for the full delivery period. The pumps are manufactured such that the reservoir holds sufficient solution to deliver beyond the infusion period.