Sourcing a comparator drug for global trials can be challenging when navigating this process for the first time. Companies often adopt a ‘one-pot-fits-all’ approach that could expose them to operational, regulatory and financial risks, which could threaten the integrity of study results.

The great complexity of today’s international clinical trials means there are numerous issues surrounding the organisational, operational and financial performance of clinical trial materials (CTM). This has gradually become a significant problem for trial sponsors and contract manufacturers as well.

The globalisation of clinical trials can present cost savings and advantages for trial sponsors when sourcing from more cost-efficient markets or from a single global supplier. But this requires detailed knowledge of the differing regulations specific to countries, as well as the ability to meet them. We shouldn’t forget that there are an increased number of new countries where clinical trials are taking place.

Bear in mind that the environment might not be the most favourable at the beginning, due to its stage of maturity for conducting clinical trials. The key is to make the sourcing process as streamlined as possible, while using a sourcing specialist to make it cost-effective and maximise return on investment. Trial sponsors must select the right supplier based on the certain trial needs.

Associated risks

The process of supplying comparator drugs for global clinical trials presents numerous obstacles, such as the inability to obtain relevant documentation, minimal supply chain security and delays in resupply. To overcome these challenges, it is crucial for drug developers to adopt a strategic approach comprising two elements: understanding global regulations governing sourcing, and developing a risk-driven demand plan that can rapidly accommodate changes in the quantity of comparators.

What’s important to note is that the risks associated with comparator sourcing can increase without a well-planned supply strategy. When procurement teams are tasked with sourcing comparators at short notice, wholesalers or suppliers must be quickly identified and appraised – a process that can be challenging in a compressed time frame.

The major risk it presents is that there can be great variability in supply and no security to deliver on time. Wholesalers may not be able to provide large single-lot batches with long expiration dates. The trial sponsor may have to buy the comparator in multiple lots, leading to clinical inconsistency. This can create significant operational challenges, as well as more paperwork to address audits or even recalls.

Additionally, wholesalers may not be compliant with sourcing regulations and the logistics necessary to deliver the comparator to sites worldwide. Suppliers should know the import and export requirements for each country, and the specific handling criteria necessary for every type of delivery, including cold chain and controlleddrugs requirements, plus the special nature of the sources.

Most of the time, a short lead time may prevent sponsors from sourcing directly from the manufacturer through a sourcing specialist, which takes more time than usual. Therefore, robust relationships between sponsors and suppliers should be built to address this complex process.

Local sourcing considerations

A local sourcing specialist can liaise directly with the manufacturer to schedule production runs to meet either short or long-term comparator requests. This demand planning not only secures the reliability of a supply with quality material, but also helps it to maintain flexibility, should a study be extended.

In addition to effective demand planning, sourcing directly from a manufacturer enables access to large, single lots of the comparator with maximum shelf life and specific batch numbers. Securing comparators with the former provides time for characterisation, demonstrating bioequivalence, relabelling and repackaging. It also minimises resupply costs and avoids any regulatory burden when submitting investigational new drug or new drug applications.

Getting the appropriate paperwork from manufacturers is very important. They can provide full-pedigree documentation reflecting the chain of custody, from the source to the designated point of delivery. The availability of these documents is not guaranteed when sourcing via wholesalers, putting a company at risk of not complying with regulatory requirements. While the offer of the comparator is at the lowest product cost initially, the lack of robust networking and supply restrictions may result in an unreliable supply, along with a sizeable acquisition cost.

The supply chain strategy requires meticulous planning in advance. It should preferably be established when the protocol design is drafted.

Since comparator drugs come from a wide variety of sources across a number of countries, attention should be paid to regional variations and differing trade regulations of governance, prior to selecting the most appropriate source. This planning will be imperative for assessing options and limitations for sourcing the chosen comparator; reviewing sourcing options, in terms of regulatory requirements; packaging; reformulation and relabelling needs; determining the required volume and delivery schedule; evaluating the price and total cost of acquisition; confirming the availability of the required pedigree and product documentation; and bringing the right drug to the correct site on time.

For a successful trial, the ultimate goal of comparator sourcing is to get the appropriate drug to a suitable site promptly and in the right quantities. Nevertheless, with significant growth in clinical research expected in emerging regions like Russia, Asia, South America, the Middle East and Africa, sponsors and drug manufacturers must be prepared for the geographical challenges that lie in wait.

The increased burden on supply and clinical operation teams will, therefore, lead to a push towards the establishment of a compliant and efficient supply chain across borders. Requirements set by local regulatory agencies, regarding the source of comparators and the trade regulations governing import and export, must be understood and adhered to. Another factor to consider is that some comparators demand special handling, such as products with specific cold chain requirements.

If not managed effectively, these factors can result in the delayed delivery of a comparator to a site, which, in turn, can lead to costly delays for a trial. Agile, global inventory and logistics management is critical to ensure compliance, supply chain security, prompt delivery and global batch traceability. In such cases, it’s essential to have country-specific regulatory expertise on either the manufacturer or trial sponsor side, as regulations are constantly evolving.

Once the desired comparator has been identified, the task turns to finding the source. Having global knowledge of the comparator sourcing landscape makes it possible to assess the options available. However, caution must be exercised when evaluating sources for a comparator. Only those that are audited should be used to ensure supply chain security and minimise the risk of counterfeiting.

Single sourcing versus decentralised sourcing

When it comes to sourcing, many trial sponsors are interested in single sourcing from one geographic area to trial sites in multiple countries. When considering this in relation to a trial, it is important to weigh the associated pros and cons.

Advantages include the management of one comparator source; a reduction in local supply cost; consistency in the data collected across trial sites; and greater flexibility to shift comparator supply from one site to another.

When obtaining the required documentation, a lack of formal guidance and taking a case-bycase basis approach are some of the challenges to consider.

A trial sponsor should carefully evaluate single-sourcing options from a regulatory standpoint and understand what is required, in terms of supporting documentation. The US FDA, for example, provides no formal guidance on single sourcing, so it is best to consult your comparator sourcing specialist, who will have the ability to advise on specific cases and be in direct contact with agency officials on your behalf.

While single sourcing can ease the demands on internal supply and logistics departments, the dependency on one source for a drug comparator presents a number of risks and necessitates the careful verification of a supplier. A sourcing specialist can ensure that these risks are quantified and mitigated, but adopting decentralised sourcing through different suppliers will address this issue.

Clinical trials can come to a halt if the comparator drug is not available throughout the study, affecting timelines and bringing about substantial costs for the sponsor. A transactional approach to sourcing, where the focus is on finding a comparator as quickly as possible, can increase the likelihood of these risks, prior to and during the course of a trial. Comparators that are sought via a ‘last-minute’ approach can expose a company to high risks.

Comparator sourcing should be an important strategic element in the planning and preparation of clinical trials. The goal for the procurement team should be to clarify the needs for a comparator and the time required to properly evaluate all sourcing options. Close communication between the supply chain and clinical teams enables better planning and will minimise a company’s exposure to avoidable risk, unexpected problems and large costs.