By: Gerald E. Finken
The introduction of decentralized clinical trials (“DCTs”) into clinical research has, in recent years, focused on the use of technology and telehealth to improve the clinical trial experience for patients. The proponents of the DCT model have heralded it, and rightly so, with improving study recruitment, providing better patient diversity, and reducing patient burden. By bringing clinical trials to patients, instead of requiring patients to come to clinical trials, DCTs have made the clinical trial experience more patient-centric.
Although the significance of these benefits cannot be overstated, the full potential of DCTs to make clinical trials more patient centric has not yet been realized. For decades, the traditional investigator-focused clinical supply chain model has persisted, relatively unchanged. The introduction of DCTs into clinical research, however, comes with a great opportunity for change: in addition to improving the clinical trial experience for patients, DCTs can further serve as the catalyst to also make the entire investigational drug supply chain process patient-centric.
In the traditional clinical supply chain model, investigational drugs are first manufactured, then packaged and labeled, most often at the manufacturer’s own facility. This initial step is referred to as the primary packaging of the investigational drug, and the FDA requires that this primary packaging be performed according to good manufacturing practice (“GMP”) regulations. In most cases, the primary packaging of these drugs is not suitable for immediate use in a clinical trial, as the primary-packaged drugs are typically bulk product that has not been apportioned or labeled for patient use.
Current Process
E2 Dispensing Process
Once the primary packaging is complete, the investigational drugs are then sent to a second facility, where the previously GMP-approved investigational drugs are uniquely repackaged and labeled before being GMP-approved for a second time. This further packaging step is referred to as secondary packaging, and is performed with an eye to how clinical sites will receive, store, select, and dispense the drug. For example, the decision to ship in blocks, to place multiple bottles in a kit, or to place multiple kits in a shipper is made based on the logistics of the trial and the convenience of the site. In the same manner, the decisions regarding the inclusion of the protocol number, kit number, visit number, randomization number, or color coding the label are all made for the benefit of the site when selecting the drug for dispensing. These secondary packaging inclusions are necessary in the traditional clinical supply chain model to maintain the blinding of the site when dispensing to trial patients. Planning, coordinating, and forecasting all of these items, however, is time consuming and costly. Any mistake in the process can result in trial delays, unused drug product, or, worst of all, the unblinding of the trial. In addition, from the patient’s perspective, none of the information including in this secondary packaging and labeling process is helpful to the patient – it is not patient-centric. DCTs present the opportunity to correct these issues, for both patients and investigators, just have they have for the patient’s trial experience.
DCTs, by their nature, require the shipping and dispensing of investigational drugs directly to patients, bypassing shipment to the sites. In doing so, they eliminate the need for secondary packaging and site blinding, and create the opportunity for packaging and labeling in clinical trials to become patient-centric.
The simplest way to achieve these changes is to move the shipping and dispensing of investigational drugs to a central-fill model using central-fill pharmacies. A central-fill, or mail-order pharmacy, is a pharmacy that has the licensure and operational capabilities to dispense and ship prescription drugs to patients, wherever they might live. Central-fill pharmacies are already widely used in the prescription drug setting. In that context, pharmaceutical companies manufacture and ship the prescription drugs to central-fill pharmacies, which then dispense those drugs directly to patients on a prescription from a doctor. The shipment and dispensing of drugs to patients in this central-fill model is patient-centric: patients receive drugs that have been prescribed, dispensed, and labeled specifically for them.
The use of central-fill pharmacies in the commercial setting can easily be transitioned to meet the needs of DCTs. In a clinical trial central-fill model, the manufacturing of investigational drug products remains the responsibility of the manufacturer and, as such, the manufacture and primary packaging of the investigational drugs is still subject to GMP requirements. Instead of shipping the investigational drug products to clinical sites, however, the manufacturer instead ships them to a central-fill pharmacy. Once the central-fill pharmacy receives the investigational drug, the dispensing of the drug product is governed by the practice of pharmacy, just as it is in the commercial setting, wherein central-fill pharmacies store the prescription drug product and dispense it according to a valid prescription.
Notably, moving the dispensing of investigational drugs to a central-fill pharmacy renders the secondary packaging unnecessary, as there is no longer any concerns regarding the unblinding of the sites. Unlike sites, central-fill pharmacies can be unblinded without compromising the integrity of the trial, just as a pharmacy can be unblinded at a clinical site. The central-fill pharmacy can then itself be responsible for
blinding the investigational drugs prior to shipment and dispensing. Most importantly for patients, the central-fill pharmacy labels the shipped investigational drugs in compliance with state pharmacy laws, meaning that the investigational drug products each clinical trial patient receives are labeled with individualized, patient-specific information.
Introducing central-fill pharmacies into DCTs brings into stark focus the impracticality and costs, for both patients and investigators, of secondary packaging. In the traditional model of packaging and labeling, secondary packaging is a necessary evil: it is mandatory to maintain trial integrity and blinding at the sites. Moving to a central-fill model, however, renders that secondary packaging unnecessary as blinding can now be performed by the same entity that is dispensing the investigational drugs without compromising the trial. Eliminating that packaging step not only saves investigators time and money, but it also enables the investigational drugs themselves to be packaged and labeled in a manner that speaks specifically and directly to each patient.
