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Overview of Gravimetrics

By Dennis Tribble posted 12-01-2021 12:14


I was reviewing some old documents and ran across a slide deck that I presented a few years ago at a USP Compounding Conference on Gravimetrics. Having recently attended the ISMP Conference on Sterile Compounding Safety, I was reminded that there may still be some confusion about what Gravimetrics does and does not bring to the compounding environment. You would also find some of this in another blog (the illusion of accuracy).

I confess that I am employed by someone who sells a gravimetric solution, but this discussion is basically agnostic of that relationship. I hope you will agree when this is done.

  • Gravimetrics is a process wherein a container is weighed before and after an addition of fluids to, or removal of fluids from that container. Knowing the change in mass, and the density of the fluid, one can compute the volume of the fluid that was added to or removed from the container.
  • Any weighing mechanism can only detect a change in mass. So, knowing what substance is being moved, and knowing its density one can calculate the volume that was moved from the change in mass. So, there must be another way to verify that the correct fluid was used. Bar codes work well for that. Gravimetrics cannot tell that the wrong drug was used. An alert user might infer the wrong drug was used if the volume reported by a gravimetric system differed significantly from a volume they could physically observe.
  • The weighing mechanism doesn’t do the measurement, it only tells you how close you got. Typically, the actual measurement is performed by a sterile, disposable syringe whose accuracy is, at best, ± 4% (ISO 7886-1). While it is true that the electronic balance can probably report mass changes in very small amounts, it cannot change the accuracy of the syringe measurement. The best it can do is reject it as overfilled or report it as under-filled and suggest a correction.
  • For a change in density to make a difference, it must predict a difference in volume that we can measure with our syringes. A difference in density at 3 places behind the decimal cannot produce differences in measurements that are meaningful for any syringe size that we have. Two places behind the decimal are more than sufficient. (See examples at the end).
  • What a gravimetric system can do, that no other currently available workflow system can do, is to demonstrate that a receiving container’s mass has changed appropriately after a fluid transfer has occurred (or not). For most drugs injected into most IV bags, one cannot look at the container and verify that any amount of fluid has been added, much less that the right amount of the right fluid has been added.

So, given a system that positively identifies the medication being added to a container, the known density of the identified fluid, and a gravimetric check of the container before and after the addition occurs, one can be reasonably certain that the right amount of the right fluid was (or was not) added to the container within reasonable limits of accuracy.

  • As volumes get small, the limits of syringes themselves create limits on the accuracy a gravimetric system can verify. (ISO 7886-1, see examples at the end).
    1. For any syringe, as the volume measured in that syringe declines below 50% of its nominal volume the accuracy of the syringe measurement declines until, at 10% of nominal volume, the accuracy is about ± 16%.
    2. For a 1 mL or 2 mL syringe, the volume of the dead space in the tip of the syringe can affect the weight of the syringe enough to transgress accuracy limits.

So, Gravimetrics tells us something that we could not otherwise see without standing at the shoulder of the technician preparing the dose. And that seems useful.

Are there other technologies? Yes, one might consider analyzing the completed CSP via one of several technologies. But there are also additional variances over which we have no control that confound even that approach. Again I will refer you to the illusion of accuracy for a complete discussion of those sources of error.

One might also capture videos of the process; will a checking pharmacist have the time and energy to sit and watch a video while checking each IV? That would be inconsistent with my experience.

In my opinion, Gravimetrics provides evidence that an admixture actually occurred that is immediate, and data driven. Again, in my opinion, that is valuable.

As always, the opinions expressed in this blog are my own, and do not necessarily reflect either those of ASHP or of my employer, BD.

What do you think?

Dennis A. Tribble, Pharm.D., FASHP

Ormond Beach, FL, 32174



  1. If we believe that a fluid has a density of 1.05 and it actually has a density of 1.04, and we measure a 10 mL volume (presuming that this volume is exactly accurate), the Gravimetric system will see a change in mass of 10.4 grams where it expected a mass of 10.5 grams. Using the expected density of 1.05 g/mL, the system will compute a volume of 9.9 mL.
    1. The difference (0.1 mL) is well within the ± 4% the syringe can deliver
    2. The difference (0.1 mL) is too small to deliver with the 10 mL syringe and may not even be visible on the syringe’s scale.
    3. The difference (1%) is well within the ± 5% many gravimetric systems apply
    4. The same differences for a 50 mL measurement in a 50 mL syringe would produce a volume a mass of 52 g where the expected mass of 50 mL would be 52.5 g (a difference of 0.5 g) yielding a delivered volume of 49.52 mL (0.48 mL under-delivery). Since the smallest volume one can measure on a 50 mL syringe is 2 mL, that difference could not be seen or measured on that syringe.
    5. Thus, for any measurement we could practically make with any syringe size, the difference between two densities at 3 places behind the decimal could not possibly produce a meaningful difference in measurement.
  2. ISO 7886-1 specifies both permitted syringe accuracy and the permitted volume in the tip of the syringe (called the “dead space” because the fluid in that space never leaves the syringe).
    1. For accuracy, the permitted variance from intended volume is split up into two groups:
      1. The accuracy at 50% or more of the nominal volume of the syringe.
        1. For syringes 5 mL and larger, that accuracy is ± 4%
        2. For syringes less than 5 mL, that accuracy is ± 5%
      2. For volumes below 50% of the nominal volume, permitted variance is determined by a formula that describes a declining accuracy depending on how little is actually being measured.
        1. For syringes at or above 5 mL, the accuracy at 10% of the nominal volume (e.g., 1 mL in a 10 mL syringe) is ± 16%
        2. For syringes below 5 mL nominal volume, that accuracy is ± 17%
    2. For 1 mL and 2 mL syringes, the dead space for the syringe is 0.07 mL. For a 1 mL volume, that represents 7% of the measured volume in either syringe. Since that 0.07 mL is a permitted volume, one cannot easily determine exactly how much of the change in mass for a syringe of that size is represented by the dead space, making Gravimetrics difficult for these small doses.