In today’s competitive drug development market, investing precious resources in moving a drug candidate from the lab to a first-in-human, phase I clinical trial can represent a significant gamble for sponsors.

Building integrated clinical supply chains, designed for speed, agility and performance, helps to facilitate improved visibility, better management of risk and effective contingency planning as programs evolve. This creates strong foundations and scalable operations that support expedited transitions into later phases and successful commercialization.

To build speed, agility and performance into supply chains, we must first identify and dismantle the risk factors capable of preventing early phase supply chains operating to their full potential. To achieve this, early planning, clear communication and a willingness to break with clinical supply convention must reign supreme. 

Plan to succeed
To build strong foundations that are scalable through the phases, key data must be gathered to inform an optimized supply chain plan, at the earliest opportunity.

Gathering the necessary data at the right time will help sponsors understand requirements and appropriately design strategy, while mitigating risks of delay and disruption.

Defining requirements means analyzing a range of factors and liaising with numerous stakeholders.

The study’s title provides a basic overview of blinding status, the trial’s overarching objective, therapeutic area and potential use of comparator products. More in-depth clinical requirements can be found in the clinical protocol’s synopsis, study drug and study conduct sections, including stratification factors, study design and visit schedules. This data will assist in decisions surrounding kit design and patient dosing requirements; this in turn informs production campaign and distribution strategies.

The clinical team represents another knowledge base; providing valuable insight into the number of participating countries, start dates, when individual sites will come online, enrolment projections and patient assumptions.

Communication with pharmaceutical development and comparator procurement teams will also provide detail on drug characteristics, manufacturing timing and stability and flag any potential constraints. Collaboration with these teams provides clear visibility over a bulk manufacturing plan and the kind of stability program available to establish shelf life. They will also confirm if expiry extensions are planned, the required storage conditions and whether stability memos and time out of temperature data is available.

Establishing supply and demand
Once key data is understood, sponsors can focus on developing supply chains that are underpinned by speed, agility and performance.

Balancing how much drug product is required for early phase trials can be particularly problematic but can be overcome if the ethos of ‘plan early and plan often’ is adopted. It can also be made easier by looking to the future and communicating with CMO partners to ensure alignment and ability to produce greater quantities as the trial progresses.

Flexibility is another key factor, as early phase studies regularly need to be extended to hit required patient numbers, so factoring in expiry update requirements pro-actively will minimize delay and disruption further down the line.

Working with data gathered will also help establish the requirements for material and production planning and for creating a drug demand forecast, based on enrolment forecasts.

With little product data to inform early phase supply chain operations, tasks like managing expiration and defining transport and storage criteria can be more complex to manage. While early phase trial sponsors focus on recruitment and establishing the most appropriate dosing regimens, striking the right balance between producing too much and not enough can introduce additional forecasting challenges. This makes supply chain agility all the more important to achieve and should influence the production approach taken.

Selecting the best fit production approach
While standard bulk manufacturing will often keep initial costs down for early phase sponsors, it’s important to be open to the benefits of using less conventional manufacturing strategies to drive speed, agility and performance. Although such strategies may incur additional overheads initially, they can reduce waste and promote enhanced patient centricity and retention longer term.

Just in Time Manufacturing (JTM) is the full late-stage customization of clinical kits and can add value to early phase operations; helping sponsors respond quickly to shifting demand, while preserving drug product.  If an early phase study faces enrolment challenges or limitations with drug availability, JTM can represent a cost-effective solution in appropriate scenarios.

JTM can be utilized to help facilitate drug supply for trials involving treatments designed around niche patient groups and disease types that typically deal with high-value, limited supply. Although patient populations are smaller, forecasting supply and demand can be more difficult, due to the reduced patient pool that comes with developing highly targeted medicines.

It’s also important to remember that issues can sometimes arise with APIs, when new drugs are being tested in early phases, which can create additional risk for bulk manufacturing methods.

Understanding packaging anD labelling requirements
Before deciding on packaging design, early phase trial sponsors must consider the drug’s form requirements, the volume needed, temperature constraints (including freeze/thaw cycles and handling) and light protection factors.

Maintaining product stability and drug integrity is mission critical so packaging and labelling operations must be designed to promote compliance with stability criteria and maximize patient safety.

It’s also important that sponsors select a supply partner that is able to meet precise packaging needs through all phases—not just the early phase. Creating scalable packaging operations that not only deliver for phase I but are able to stand up to demands of later phases is key to ongoing success. If sponsors opt to work with a CMO that can accommodate bottling production for a phase I study but is unable to accommodate alternative packaging types, such as blister packs, as requirements evolve in later phases, time and resources can be wasted sourcing a new partner.

Designing distribution
Distribution is the final step on the critical path towards creating early phase supply chains that operate with speed, agility and performance. 

An optimized distribution strategy is one that places enough IMP (and ancillaries of the correct type), at the correct place, in an acceptable condition and in time to meet patient need.

Despite the emerging trend of early phase trials involving increasing numbers of sites across multiple countries, often combined with the development of next generation, temperature-sensitive products, most early phase studies operate with significantly fewer sites, patients and countries. While this makes distribution a more straightforward proposition, sponsors should prioritize the development of future-proof strategies during early phases that can be built upon, as demands increase, to facilitate smooth transitions into later phases.

Strengthening early phase distribution strategy with access to a global depot network and single inventory database, biological, controlled and ambient product delivery, import/export, courier management and shipping lane data analysis will ensure bigger picture supply chain success. As will utilizing shipping and monitoring technology, particularly for trials involving complex biologics and gene therapies that need to maintain a complete cold chain from production line to patient.

Flexibility in distribution approach should also be a key consideration, especially for sponsors keen to maximize patient centricity and enhance recruitment and retention for fledgling early phase studies. In applicable countries, direct to patient distribution models can lower the cost per patient for sponsors, take pressure off sites and—most importantly—make participation more convenient for patients.

One way to access such broad and future-proof distribution capability is by partnering with CMOs with extensive coverage in all key markets and a track record of managing distribution for small phase I studies right through to global phase III mega trials.

Break down the silos
Gathering data, using it to inform streamlined and agile production schedules, and designing cost-effective and patient-centric packaging and distribution strategies are made infinitely more difficult if the physical supply chain fails to align with the digital.

If the network of manufacturing facilities, buildings, warehouses, trucks, planes and people through which drugs are produced and distributed are not unified with the systems that capture, store and disseminate supply chain data to power, monitor and track ordering, movement and administration of clinical supplies, gaps appear that can have disastrous consequences. And what starts as little more than an affordable annoyance during an early phase study, can quickly escalate into a big and expensive problem as operations grow in scale and complexity in later phases.

By reducing the number of stakeholders involved, these silos can be removed.

For example, early phase sponsors that opt to partner with a single vendor, with dual expertise in clinical supplies and technology, notice a typical five-fold reduction in errors, when releasing inventory and raising shipment orders. They also benefit from process automation to drive efficiency and a unified view of data, which facilitates smart decision making and continuous improvement through each trial phase.

Ultimately, by harnessing available data, planning early and often, selecting the best-fit production, packaging and distribution strategies, harmonizing the physical and digital supply chain and prioritizing effective communication with CMO partners, strong and scalable supply chains can be constructed. If approached with these factors in mind, supply chains are more likely to function with the speed, agility and performance needed to maintain supply to patients and successfully transition through the phases to meet key milestones. 

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Caitlyn Clauss is Supply Chain Solutions Manager at Almac Clinical Services, responsible for supporting and enhancing the Almac Supply Chain Management consultation service. In her role, Caitlyn ensures the cohesive delivery of new services and products, positive and collaborative partnerships among supply chain stakeholders, development and delivery of training material, and the deployment of improvement efforts for optimal service quality and client experience. She joined Almac in 2015.