By David Gilliland
It is critical to maintain patients on drug supplies during clinical trials, both for the success of the study and for the health of the patient. In this second part of this series on ensuring adequate drug supply, we will look at some specific strategies for successfully managing the clinical supply inventory.
While Part 1 of the series provided insight into some of the logistical challenges pharma/biotech companies face in conducting clinical studies, there is one very clear common denominator: the need for accurate and strategic management of the clinical supply inventory. How can this be achieved?
Technology Solutions Lend Support
Technologies are currently in place that support the process — including IRT (interactive response technologies), which support patient dispensing and control the available site inventory such that the correct kits are referenced to the investigator to dispense to the patient. The IRT system has records of available inventory down to the site level, it provides information as to when patients are forecasted to arrive for resupply, and it monitors the expiry dating of the supplies so that no expired or expiring product will be dispensed to patients. In addition, some companies offer software programs that are essentially simulation tools that can help CSO project managers assess forecasting requirements, and, if used, can provide the probability of the potential for stockouts. Whether you use such systems or not, you need to confirm that the strategy being used ensures ongoing study supply from start to finish, and that can only be achieved by adequately trained and skilled CSO PMs.
Project Management Skills Are Key
Clinical supply PMs should be able to address ongoing recruitment and related demand, oversee existing patients and ongoing demand, and monitor drop-out rates. In setting up the triggers for site resupply in the IRT systems, the PM should review the ongoing patient recruitment against depot inventory within the various regions and plan global distribution needs accordingly. This should link back to the planned manufacturing strategy related to both availability of supply and expiry dating of existing supplies. In such situations, the forecasted bulk drug product needs are easily captured and the added benefit is that costs are relatively easy to maintain against budget.
This is by no means the end of the matter. As mentioned previously, recruitment rates are not 100 percent accurate, so project managers need a way to deal with this. I recall coming across a scenario in which the study end dates kept dragging out, but no additional bulk drug was being made available. By looking at the regional variability in the study, rather than at recruitment across the entire study, we were able to evaluate which regions were actively recruiting and which were not. In so doing, we could reconfigure the entire distribution strategy to ensure that the drug supply went where it was in large demand, while significantly reducing supply to low-demand areas. Again, this is only feasible if you are actively reviewing, on a regular basis, the recruitment and drug supply needs across regions, rather than as a study-based need. The cost savings resulting from being actively involved in reviewing the demand consistently can be significant and, in many cases, can ensure ongoing supply to patients. I cannot emphasize enough the need to ensure there is optimal expiry dating, sufficient volume on the import license is approved, and all logistical considerations are taken into consideration when preparing your strategy, as were discussed in Part 1.
Additional Considerations For Oncology Studies
The oncology challenges, and indeed biologicals in general, require additional consideration. For the most part, conventional preparation of clinical supplies may no longer be adequate. What I mean by this is that labeling of supplies with booklet labels and having bulk inventory sitting in one part of the world with short expiry dating is no longer practical in many situations. This is due to small patient numbers at sites, with uncertainty as to when the patients will actually be recruited. While for other therapeutic indications — such as cardiovascular studies — there is enough bulk supply to support a strategy where depots can be preloaded to meet regional demand, this may not be the case for these cancer studies due to low yields from manufacture and the speed required to ensure aggressive timelines can be met.
Hence, regional labeling may be the optimal choice, but it needs to occur in a very reduced timeline, while linking with existing technologies, including IRT, and complying with regulations, including QP release within the EU. Oftentimes, the applicable terminology gets mixed up. I refer to this as just in time (JIT), but to many, IRT is JIT. I tend to think of IRT as being conventional nowadays, as it is very much a commonplace approach, while what I refer to as JIT applies to a system in which the product is sitting in inventory as unlabeled bulk stock and once a request comes it, it is then labeled, released, and at the site within a matter of a few days. That process is feasible, but I fear it will take too long to become established and we will find ourselves developing these processes as a result of study failures rather than proactively planning.
Innovative Process, Technologies Support Patients, Studies
Another process in place to support clinical projects and patients is direct to patient (DTP) shipment, which continues to grow. This is where patients have their drug supply delivered to their homes in a manner that complies with all regulations and maintains patient confidentiality. Conventionally, supplies are at the site and couriers are organized to pick up the product as needed. The product is maintained at required temperature controls right through to patient receipt, and support can be organized as needed at the patient’s home for additional services, sample collections, and transportation, etc. The benefits of this include better patient retention or even patient recruitment and, obviously, it gives patients access to clinical programs that they otherwise could not take part in.
New technologies are emerging, such as liquid paper, where it is feasible to carry out expiry update of patient supplies remotely and instantly, through a simple “wave of the wand” (only somewhat of an exaggeration). Why is this important? In many instances, materials are at the site, and it can take several months to conduct expiry updates as the process requires batch records, at the sites, and for the most part there are no GMP qualified operators on hand, so the staff requires training on how to properly label supplies. There is always concern that the incorrect products could be pulled from shelves and wrongly labeled and, of course, in these types of operations all labels must be 100 percent accounted for. In short, it is time-consuming and leaves inventory at sites unavailable for patients for as much as several months.
Ensuring adequate drug supply for any clinical study, outside of all the regulatory requirements, bulk drug availability, etc., requires a “reasonable” clinical forecast and a skilled CSO PM with the ability to design a strategy that covers the supply process from start to finish, ensuring patients always have access to drug, all while dealing with limited storage capacity at sites, expiry date issues, and amending the distribution strategy based on ongoing study progression.
About The Author:
David Gilliland earned his Ph.D. from the School of Pharmacy at Queens University Belfast, Northern Ireland. He has worked for more than 20 years on both sides of the Atlantic in support of clinical programs, in both pharma and vendor roles. Most recently David worked as the director of clinical supply operations at Daiichi Sankyo, leading the team in support of all phases of clinical studies, including several mega-trials, and covering cardiovascular, oncology, and pain therapeutic areas. He is currently looking for his next leadership opportunity. You can connect with David on LinkedIn.