Drug pooling's potential to reduce waste and minimize supply outage is of keen interest to biopharmaceutical companies. Yet
confusion persists about what pooling can and cannot do—and about how pooling can and cannot be done.1
Pooling, which is employed in conjunction with IVRS/IWRS, is possible when more than one protocol operating at the same depot
and/or clinical site uses the same drug. By treating identical supplies as commutable among pooled protocols, pooling allows
supply and safety stock to be shared. With pooling, dispensing units are interchangeable (indistinguishable in content, count,
and container/closure system) and while in their pooled state, they are protocol independent, with a single, shared IVRS definition.
There are three basic levels of pooling that might be of interest to clinical trial designers and managers. First, a fairly
obvious one: pooling a set of packaged kits or kit components that are not yet labeled. We might call this "Pooling Prior
to Labeling." This method is uncontroversial and is out of the scope of this article.
A second method is to deliver packaged and labeled goods to depots without a protocol number on the label. This is useful
for a variety of different simultaneous clinical trials in the same program (or at least using the same kit types). We might
call this method "Pooling at Depots." Pooling at Depots is somewhat more controversial because it requires that the protocol number be written or affixed to the
label of all kits prior to shipping, but after being requested by clinical sites (usually via IVRS) for particular trials.
Both the process around this activity and the regulations in various countries—especially in Europe—are rather unclear. However,
Pooling at Depots represents a significant clinical supply advantage over Pooling Prior to Labeling, and is thus worth consideration.
The third method of pooling encompasses Pooling at Depots but also makes the assumption that some clinical sites may be running
multiple "pooled" protocols at more or less the same time. In this type of pooling, kits may actually be shipped from the
depot without a single protocol number, although sometimes they do show a set of protocols, or a program code. In any case,
the kits remain protocol independent, even at the clinical site, until they are dispensed. At dispensing time, the IVRS marries
the protocol to the kit number and any required label modifications may be made at the site. We might call this method "Pooling
at Sites."
Pooling at Sites, done when there is more than one protocol operating at the same investigative site, is actually far more
commonly applicable than may be apparent at first blush. Although in earlier phase studies it is uncommon to have multiple
studies sharing the same formulation, in later Phase III and IV studies it is not uncommon at all. However, many clinical
supply managers interpret various European or other regulations as prohibiting the shipment of drug to sites without a protocol
number on the label. Others note that exceptions are made in cases where centralized randomization systems are used. Others
still note that regardless of the letter of the law, certain regulatory agencies will never allow pooling at sites. A common
reaction to the notion of pooling at sites is "good luck."
Pooling for Europe
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Nevertheless, Pooling at Sites does indeed occur in the biopharmaceutical world, and has indeed been shown to save significant
supply when used. We will assume that the reader accepts on some level the regulatory viability of Pooling at Sites, even
if the concept is neither universally endorsed nor applicable to all geographies. The remainder of this article will address
specific pitfalls and requirements of Pooling at Sites both in terms of electronic records and of actual labeling.
As noted above, in Pooling at Sites, the IVRS does not marry any particular kit to a protocol or subject ID until the kit
is disbursed. This allows the IVRS/IWRS to tally stock against the future needs of all the protocols at a particular location:
All projected shortfalls can be covered with a single, nonprotocol-specific shipment. That shipment will equal the location's
projected need for a specified period (minus at location and en route unexpired/ing stock). Each patient in a pooled protocol
may be dispensed the appropriate kit type from the common supply.
Traditionally, clinical supply managers package lot for a particular protocol. In a pooling scenario, they may naturally assume
that they can and should package or electronically earmark the drug for the set of protocols for which it is to be used. However,
marking drug for use electronically or on the label for a specific protocol—or even for a subset or specific group of protocols—can
compromise pooling. Only if kits are protocol independent until dispensed can an IVRS resupply algorithm consider the needs
of all protocols using a particular kit at a single location as a whole.
