Fall 2013 - Winter 2014RMS Quarterly Newsletter

Is Precision Important in Flow Rates?At RMS, we have devoted substantial e�ort to ensure accuracy of the �owrates achieved by the FREEDOM60® Syringe Infusion System. We were notat all surprised when the FDA, in proposed new guidance for manufacturersof infusion pumps to follow when seeking clearance to market their devices,expressed concern that �ow rate accuracy tests demonstrate that infusionpumps perform as intended. The FDA said that pumps need to maintaintheir speci�ed �ow characteristics despite changes in ambient temperature,pressure, or �uid viscosity. It said that if a pump does not maintain a constant

�ow rate during use, testing needs to be done to assess �ow rate accuracy at the minimum,intermediate and maximum �ow rates.

We manufacture FREEDOM60 Precision Flow Rate Tubing™ speci�cally for use on the FREEDOM60®.Not just any piece of medical grade tubing will do. In order to produce a precise �ow rate, the ratecontrol tubing must be manufactured to the speci�c pump system’s pressure pro�le.

One of the most di�cult aspects in manufacturing is ensuring consistent internal tubing dimensionsnot only within the same tube, but from batch to batch as well. According to Dr. Marcus Hultmark ofPrinceton University’s Department of Mechanical and Aerospace Engineering, a 5% deviation in theradius of a tube will cause a 20% deviation in the predicted volumetric �ow rate. Thus, a tiny discrepancyin manufacturing can have a huge impact on the performance which will be seen when infusing a patient.

Wide variations in delivery rates of the same medication during infusions on di�erent occasions canbe confusing to patients, add to their anxiety and discomfort, and adversely impact therapy compliance.Excessive �ow rates may exceed parameters as stated in the drug’s package insert, creating the potentialfor patient harm. If the �ow rate is too low, an infusion will take longer than expected and could lead toimpatience on the part of the patient. In a worst case scenario, the patient might terminate therapyprematurely, leading to complications from lack of medication.

Only the pump’s manufacturer knows with certainty the speci�cations and tolerances that the precision�ow tubing is required to meet, because this information is unique to the design and engineering ofthe pump. We believe there is no such thing as a “generic” �ow control tubing set that can work with anypump. We believe only �ow rate tubing speci�cally designed for the pressure pro�le would be safe touse with a constant pressure pump design, such as the FREEDOM60®.

Many factors require design consideration, some of which seem minor but can create substantialcumulative impact. For example, syringe friction is one. In the laboratory, engineers would need tomeasure many syringes on a dynamic force gauge system to determine the average syringe force

friction at each speed that the syringe is likely to operate. Also requiring consideration are items such asthe varying viscosities of the drugs likely to be used in the pump, and the likely temperatures that will beexperienced. The design must be optimized for the best compromise across these and other variables.

After the precision �ow tubing design and speci�cations are completed, the next step is to determinehow to verify the design. This is a requirement of FDA and ISO in a regulation called “Design Controls.” Precision �ow control tubes are built in the laboratory to the design speci�cations, and are then measuredagainst a standard reference to con�rm the calculations. These �ow rate measurements must be madewith precise control of the pressure and temperatures, and then veri�ed with objective data against aknown standard.

Once the �ow rate validation is completed, then the next hurdle is to determine how to maintain thesespeci�cations in full production. Some means of production measurements are necessary to ensure thatthe design intent is being met. This process, which includes patient feedback, is called “Validation.” Thevalidation of the FREEDOM60® Precision Flow Rate Tubing™ includes ensuring the �ow accuracy of tubingdelivered to patients from various production lots. The process of �ow measurements continuesthroughout the production process to verify that the �ow rates continue to meet the speci�cations(another requirement of Good Manufacturing Practices both for FDA and ISO).

If the pump is not a true constant pressure pump, then the �ow will vary as a direct function of the pumppressure. A constant �ow pump achieves the steady rate of �ow it provides by varying the pressure atwhich the medication is forced through the lines. While the �ow rate will remain as programmed, theforce of the medication going into the patient might be high enough to cause tissue or other damage.

A pump might experience the highest pressure when the syringe is full, and drop o� to the lowestpressure when the syringe is near empty. This is an example of varying pressures within a single delivery,which produces varying �ow rates. Starting with a fast �ow rate at the beginning and ending with a slowrate can be especially problematic with certain drugs such as Vancomycin, in which a rapid dose cancreate an adverse reaction. There may be pressure variations from pump to pump due to tolerances andvariations in manufacturing such as dimensional di�erences and friction. All of these factors must beconsidered and normalized (averaged) to develop the target speci�cation of the precision tubing sets.

In summary, in order for the precision �ow rate tubing sets you select not to have an adverse impact onmedication delivery rates, it should meet accuracy speci�cations, be manufactured to a speci�c pumpsystem or pressure pro�le and not just be “generic” tubing, and it should have been calibrated inlaminar �ow.