A clinical supply chain consists of many specialized activities, each of which is dependent on the other in terms of time and success. In the process, many physical items, as well as information, need to come together at the right time from many sources, often from organizationally separated business departments.

During the set-up phase of the clinical supply chain, many of these items, starting with the drug substance (DS) through the formulated drug product (DP) and the dosage form, as well as the packaging design on a primary and secondary level, are still in technical development and the regulatory approval process. The same goes for much of the details related to the compound directly or indirectly like export documentation and labelling.

The activities are performed by many functions within and outside of the sponsor. Within the sponsor’s organization itself, the number of specialized departments span from research and development, clinical operations, technical development, finance, legal, and on to logistics.

We often find that the clinical operations function has limited awareness of the importance of the timely available information or timely fulfilment of prerequisites needed to support the preparatory activities to build a successful clinical supply chain. The same goes the other way around; for instance, for the clinical trial application (CTA), the specialized regulatory CTA department needs data about the drug which many in clinical supplies are not aware.

In the highly complex process, these interdependencies are very time-critical and often loosely coupled and managed. Changes in one often have an impact on other functions. Accordingly, a lot of effort is spent to collect the missing pieces, perform the required re-entry of data, and re-work and adapt settings for the supply chain.

The more the process proceeds towards the actual delivery to sites and being ready for dispensing to patients, the more time-critical the activities become. Only if all is complete, in the right quality and with comprehensive documentation, can the drug finally be dispensed to the patient. In assuring this, the checkpoints become more elaborate and frequent the closer the flow of goods proceeds towards patient dispensation.

Risk buffers (often called ‘overage’) are common to every clinical supply chain, if not to every demand-driven supply chain. Often misunderstood and even criticized as ‘waste’, risk buffers are a hallmark and inevitable reaction towards the inherent dynamics of clinical development, long lead times and imperfect end-to-end visibility.

Risk buffers, in a very simplified approach, are the differences between the final consumption of a material calculated by the need of the customer and the amount of material produced along the supply chain to cope with supply chain inefficiencies. In a clinical supply chain, risk buffers are applied at every material level (DS, DP, primary and secondary packed material, CFG inventories at the depots and at investigator sites). The customer need for all this is the dispensing of CFG at the investigator site to patients enrolled in the clinical trial.

The size of the risk buffers can differ substantially from one drug under investigation to another, from one study protocol to another, and from regional allocation of one clinical trial to another – all leading to the possibility of several multiples to the actual need of the enrolled patients.

Risk buffers can be expensive and their cost increases with the increasing cost of investigational drugs. Some drivers of the size of risk buffers can be influenced, some others not – at least not without jeopardizing the scientific value of a clinical trial.

The health of a clinical supply chain increases by reducing the lead time of the availability of the materials, reducing the lead time in the distribution chain until the investigator site, and increasing the flexibility in the use of particular materials in the supply chain across different study protocols and/or across different countries and regions per the study.

Moreover, key enablers for increasing the health of a clinical supply chain are enhanced end-to-end visibility, which is then often coupled with an increasing speed in re-planning and re-arranging the supply chain due to changes to the original assumptions or updated actual patient-based results of the trial.

Risk buffers, for instance, often need to be increased in case the inventories at depots and investigator sites need to cover longer periods of patient enrollment. Such periods can be reduced only by more accurate and timely visibility into the actual enrollment at the investigator site.

The longer the lead times to re-produce materials or transport the materials along the entire supply chain, the slower one can react to changes in the assumptions, the slower one can react to what really happens at the investigator site, and again the slower one can react to incidents in the supply chain. Consequently, the risk buffers need to be even higher – at worst, as high as to cover a full lead-time from DS production until the delivery of the CFG at the investigator site.

Noteworthy, risk buffers can be decreased with increased flexibility in re-planning. Timelines of several weeks or even months to finalize re-planning, and thus react to new assumptions or incidents in the supply chain, are indicators of a substantially decreased health of a supply chain. The same is true if the frequency of the re-planning is too low (weekly or even monthly cycles).

In summary, the higher the end-to-end visibility, the more actual the end-to-end information, the shorter the lead times and finally the higher the flexibility in re-planning, the lower the risk buffers in the supply chain and, consequently, the lower the costs of the entire supply chain portfolio.