USP-NF Publishes Responses to Comments on Stimuli Article on Apex Vessel Geometries

In the September 2026 issue of the Pharmacopeial Forum, PF 52(5), the USP has published its responses to comments on the Stimuli article “Characterization of Apex Vessel Geometries and Irregularities”.

The original article was published in 2025 in PF 51(1) and subsequently republished with a corrected figure in PF 51(5).

The study examined the geometrical characteristics and irregularities of commercially available apex vessels used with USP Apparatus 2 in dissolution testing. A total of 37 parameters were characterized using a coordinate measuring machine. Six vessels from each of seven manufacturers were examined. The results showed variability both between manufacturers and within the sets of vessels from individual manufacturers.

Comments were received on both versions of the article, and the USP has now considered these comments and published its responses.

In its responses, the USP explains that the geometrical characterization was the first of several planned studies. The data will be used to develop computational fluid dynamics models to investigate how changes in vessel geometry affect hydrodynamics. In addition, dissolution experiments with selected vessels are planned to assess whether the observed intra- and inter-manufacturer variability is reflected in dissolution results.

The USP intends to establish specifications only after the planned studies have been completed and the results have been comprehensively evaluated. The aim is to identify a limited number of critical geometrical parameters and irregularities, together with scientifically justified tolerances. Any future specifications should be practical, cost-effective and measurable with relatively accessible tools. A detailed characterization using a coordinate measuring machine is not expected to become a routine requirement for end users.

The responses also address the regulatory significance of apex vessels. The comments point out that apex vessels should not simply be regarded as interchangeable with standard vessels. Their use in a dissolution method should be scientifically justified with the products and samples under evaluation. In particular, agitation speed settings may need to be assessed independently because the altered hydrodynamics of apex vessels can affect both the dissolution rate and the discriminating ability of the method. A faster dissolution profile is not necessarily beneficial if the method no longer detects relevant changes in product quality.

The USP further acknowledges that the study design, which included six vessels per manufacturer, does not capture potential batch-to-batch variability. However, the purchase and detailed characterization of larger sample sets would have been prohibitively expensive. The additional CFD and dissolution studies are therefore intended to clarify which geometrical variations have a meaningful impact on hydrodynamics, dissolution performance and test robustness.

Until formal specifications are developed, the USP’s responses underline the importance of controlling the source of apex vessels and being aware of their potential geometrical variability. Variation is not automatically a risk if it is understood and controlled. The central question is which variations affect dissolution results and therefore need to be addressed through appropriate specifications.

The new USP Stimuli article containing the responses is available after registration in the Pharmacopeial Forum. Commenting is open until 30 November 2026.