Drug pooling takes time and expertise to set up, but when implemented correctly, it can substantially reduce costs and increase efficiency.
Pooling is an option whenever more than one protocol draws from the same drug supply at the same site or depot. It saves money and maximizes supply, but it is not for everyone. Pooling requires research, the right systems and procedural controls. Should your company dip into pooling?
For those dealing with an expensive or hardto- obtain drug, using a common inventory across multiple drug programs is practically a must. There is no better way to maximize the available supply. For others, the rigor involved in setting up the system must be weighed against the benefits
Traditionally, if a company has three protocols using the same drug, it assigns a certain number of kits to each protocol. Each drug kit is then produced for a specific protocol. It is packaged, labeled with the assigned protocol number and then shipped accordingly. This may lead to considerable waste of available investigational materials, increased cost, and it might result in sponsors being unable to meet aggressive clinical study timelines.
As an example, let us suppose that Protocol A is assigned 20 drug kits. The kits are shipped, but the study is delayed or under-enrolled and ultimately utilizes only twelve of these kits. The remaining eight kits must then be made unavailable for use.
Now, let us suppose that Protocol B expands more quickly than anticipated and immediately needs four more units to continue. The remaining kits from Protocol A cannot be reallocated, so Protocol B ends up being delayed until more supply can be produced, packaged, labeled, released and delivered to the site.
During that same period, the company has also launched Protocol E. Since Protocol A could not share its oversupply with other protocols, a different supply must now be created and allocated to Protocol E, which means Protocol E won’t get off the ground until the new supplies are ready.
Additionally, production of individual lots for each protocol will require more line clearances, generation of additional batch records, more individual reviews by the quality units and will result in multiple storage locations for the warehousing and distribution of finished goods.
The concept of pooling solves all of these problems. For example, the drug is produced in large batches and packaged so that it is completely interchangeable in terms of container, count and content (with a shared IVRS definition). It is stored in a centralized location and then labeled and shipped as needed. In a pooled system, Protocol A won’t receive those last eight units until the moment they’re needed—and when they aren’t needed, they remain in the pool and are available for Protocol B or even Protocol E.
As clinical supply program professionals, our single, critical goal is to make absolutely certain that all patients receive the correct medication, at the correct location, and at the correct time—produced according to the appropriate quality and safety standards. From this perspective, drug pooling is the best supply approach out there. It enables us to ensure that the drug is where it needs to be when it is needed for use.
The other challenge is keeping costs to a minimum. Pooling can meet this challenge in several ways; it reduces the amount of API required, it requires standardized packaging, it allows for fewer set ups/lots due to longer production runs, and fewer supplies are shipped to each site because shipments include only what is needed. This is particularly important when dealing with controlled-temperature products.
Less tangible cost savings come from reduced administration. Fewer packaging runs using larger quantities means fewer RFPs and fewer batch records associated with such administrative tasks. Fewer label proofs are required and label information becomes standardized. Companies can save time on all associated administrative activities required to support the supply chain.
There are various levels of pooling. Pooling can be done at the packager by producing primary packaged materials to be utilized for more than one protocol. Some do not consider this to be real drug pooling, however, it is generally included as a starter concept for students of drug pooling, because it helps them to understand how one unit of a drug can be used across many sites or countries.
The remaining levels of drug pooling are depot (or hub) pooling, and site pooling.
Most often, depots are contracted out to a third-party CMO, which inputs data directly into the company IVRS. Celgene, for example, uses Xcelience to produce clinical packaging, then uses Xcelience’s temperature controlled warehouses as depots. Xcelience has been known to dedicate individual rooms to labeling specific protocols—sometimes leaving those rooms dedicated and ready to label for weeks at a time.
Depot-level pooling usually begins by labeling the kits with a protocol-specific and/or country label at the depot. This type of label makes for a very easily-identifiable kit. Such an approach reduces the burden on site personnel, reduces the risk of site mistakes in managing the drug supply, and ensures supplies are labeled in a manner acceptable to the sponsor. However it does not allow for pooling at the site, and it requires a little extra time to label and QP release supplies at the point of distribution. If the various sites deal with only one protocol each, then there is no need for site pooling and this method could be attractive.
Applying a multi-country booklet label at the time of distribution—or an ancillary label with the protocol-specific details—can create a more flexible supply, allowing new protocols to be added as needed, but this type of label still does not allow for complete pooling at the site, and extra time is needed for QP release at the point of distribution.
It is also possible to list multiple protocols on a label (with or without a checkbox), to use program codes, or to leave a space to write-in the protocols. Multi-protocol labels maximize flexibility since site pooling is possible, and QP release can often be accomplished right at the depot. No late-stage customization is required. The drawback associated with this method is that it becomes difficult to add new protocols to the pool.
When several protocols are being dispensed at a single site, then site-level pooling is the most flexible type of pooling and yields the highest cost savings. In this case, labeled kits (not protocol specific) are shipped to the sites and the protocols are assigned through IVRS at the site. With no late-stage customization required, this method is very flexible and it is easy to add new protocols.
Alternatively, just the program ID may be listed on the label, and the protocol itself can be left unspecified, to be associated at the time of dispensing.
It is important to know a country’s regulations before choosing one of these methods. Australia and the US, for example, do not require protocol-specific labels when the drug leaves the depot. EU countries require protocol specification and QP release before the drug is shipped to sites. Regulations throughout Europe vary, with some regulatory agencies never allowing drugs to be shipped without a protocol number on the label. Others make exceptions, such as with the use of centralized randomization systems. Despite these hurdles, many pharma and biotech companies have managed to find ways of pooling their supplies to meet country requirements.
Should your company take the plunge into pooling?
Pooling saves time, money, and maximizes supply. But it also takes time and money to set up your system. You have to evaluate the different pooling methods, research regulatory requirements and make sure your IVRS/IWRS system is up to the task. You also need to ensure that you have buy-in from all stakeholders: study managers, sites, QA, regulatory, and your vendors. There are risks associated with a pooling strategy. Packaging and labeling is the easy part; the implementation and maintenance of the pooling system is the tricky part.
In the vast majority of cases, a rock-solid IVRS/IWRS is indispensable. As the drug is being dispensed to a patient, the IVRS assigns the protocol number to the kit with any necessary label adjustments noted. It also keeps track of everything, from what drug is available where, to what has been dispensed and to whom, right down to the patient detail, shipping detail and inventory detail. The system also allows manual ordering for non-IVRS protocols, configures max quantity for shipments, allows CMOs or sites to request the drug in a controlled matter, and reports across multiple clinical trials for demand forecasting and actual data analyses.
There are a few instances in which companies have chosen to do without an IVRS/IWRS, but only when the study has been particularly simple and the sponsor has been comfortable with the level of risk associated with not having such a system.
Even with a pooling plan in action, rigorous attention to supply is necessary. Clinical plans change, affecting the drug supply requirement. Study and production timelines can lead to bottlenecks—particularly where supply is limited. Lots expire. Sponsors must continually use and track data against the existing and forecast strategy.
Despite all the headaches and hassles associated with ensuring a compliant system, in most cases, the cost savings and efficiencies of pooling will outweigh its challenges.