What is Clinical Trial Supply?

Introduction: Understanding the general concept of clinical trial supply

Clinical trials and clinical research studies involve complex supply chains – the dynamic coordination of many moving parts is essential for keeping operations running smoothly across sites and without interruptions. Clinical trial supply can be conceptualized as involving three parts:

1. Clinical trial supplies (material supplies)
2. The clinical supply chain (logistics)
3. Clinical trial supply management (coordination)

Clinical trial supplies include study-related materials like the study drug, devices needed for procedures, and generic medical supplies such as gloves and syringes. The logistics aspect encompasses everything from planning and sourcing materials to the manufacturing, packaging, labeling, and distribution of supplies to individual study sites. All of these factors change dynamically as the study progresses from the planning stage through to completion, and thus coordination of trial supply and the supply chain is an essential underlying component. Clinical trial supply management thus refers to the coordination of all the logistical and material considerations necessary to keep the study running efficiently, to adhere to timelines, and to optimize the use of resources, while simultaneously ensuring patient safety and regulatory compliance.

In this article, we will dive into the topic of clinical trial supply and clinical supply chain management.

Clinical trial materials

Clinical trial materials range from investigational medicinal products (IMPs; aka investigational products, IPs) – which could be either drugs or devices that are under evaluation – to comparator drugs or placebos used in control groups. Other trial-specific materials could include promotional/advertising materials, rescue medications to be used in case of any anticipated adverse effects, physical copies of informed consent forms (ICFs) and patient surveys, etc. The range of possible materials that might be needed for a trial is nearly unlimited, as each trial varies as per its unique design and needs.

Apart from study-specific materials, clinical trial supply also considers ancillary supplies.

What are ancillary supplies in clinical trials?

Ancillary supplies are another integral part of clinical trial operations. Ancillary supplies include standard medical equipment and consumables, like syringes, gloves, etc., that are necessary for performing medical diagnostics, tests, or procedures, and even things like ordinary stationery used by investigators for paperwork. The availability of such rudimentary supplies has to be ensured across sites and throughout the duration of the trial to ensure its smooth operation and preventing unforeseen delays that could jeopardize a study’s timeline or outcomes.

The importance of quality control and assurance for clinical trial materials

Quality control (QC) and quality assurance (QA) are two aspects of oversight that are necessary for ensuring that all clinical trial materials meet stringent safety standards before reaching study sites or patients. QC checks typically involve monitoring processes at various stages – such as during manufacturing, packing, or labeling – to catch any potential deviations from set specifications. QA, on the other hand, refers to the oversight of this entire process, verifying consistent adherence to protocols to mitigate any existing potential risks to quality or safety.

Distribution and logistics: The clinical supply chain

Actors involved in the clinical supply chain

The clinical supply chain involves multiple stakeholders with different responsibilities. The main players typically involved include:

• The sponsor (i.e., pharmaceutical or biotech companies, academic institutions, etc.)
• Contract research organizations (CROs), who may be tasked with various aspects of trial operations (optional)
• Drug manufacturer(s), which could be a contract manufacturing organization (CMO)
• Packaging and labeling vendors (might be integrated into the manufacturing service)
• Logistics providers (i.e., drug and trial supply distribution, transfer of patient samples, etc.)
• Software/non-physical service providers
• Regulators
• Trial sites, where investigators/staff interact directly with patients

The interactions between these different actors are many, consistently changing, and vary in nature. For example, some interactions require shipment of physical goods, whereas others may be characterized by period reporting, and others by training or performing maintenance on software or devices. Because of the complex nature of clinical trial logistics, and especially its non-static nature, solid clinical management is vitally important. We will touch more on the management aspect of clinical trial supply chains in the next section.

Logistical operations

The types of logistical operations that may be necessary for setting up and conducting a trial commonly include things such as:

• Getting the drug manufactured in sufficient quantities for the trial protocol (i.e., considering the number of patients, dosing schedule, trial duration)
• Getting the study drug packaged and labeled appropriately as an investigational product, as per applicable regulations
• Shipping/distributing the drug to trial sites
• This may involve special storage conditions (i.e., cold transport), and strict timelines (to ensure supplies are constant and to make sure the product does not expire)
• Collection, organization, and timely and appropriate transfer of laboratory samples required for medical tests/procedures

Beyond the aspects related to the study drug, medical supplies, and samples taken from patients, there are also logistical considerations related to documentation, protocols, training, site activation, and devices:

• Signing clinical trial agreements (CTA) with sites and performing site initiation visits (SIV), including reviewing SOPs and conducting any necessary staff training
• Obtaining informed consent for all participants and collecting ICFs (or electronic versions, i.e., eConsent) in one location/database
• Organizing all study documentation, including paper records collected at individual sites – nowadays, most sponsors emply some sort of electronic platform to gather everything in one place, such as a clinical trial management system (CTMS)
• Distribution, setup, training, and eventual recollection of any connected devices or wearable devices used for at-home measurements or electronic clinical outcome assessments (eCOA)

These different logistical considerations need to be organized, coordinated, and overseen by a dedicated person or team, which is where clinical trial supply management comes in.

What is clinical trial supply management?

Clinical trial supply management is the comprehensive, ongoing organization and oversight of the procurement, tracking, and distribution of all materials necessary for conducting a clinical study. It may also involve coordination between different stakeholders and providers, and is usually closely related to other facets of trial management. For example, as more patients are enrolled at a given site, that information might be entered into the CTMS, which could then relay information to trial supply management, indicating that additional study drug shipment needs to be made to that site.

The roles and responsibilities within clinical supply management can vary with the size and complexity of the trial, and the practices and organizational structures (both internal and external) of the sponsoring organization.

Stages involved in clinical trial supply management

Management of the clinical trial supply chain might commonly begin with an extensive planning stage, forecasting the quantities of required materials based on study design and enrollment numbers. The procurement phase comes next, where resources are sourced from one or more manufacturers, and study drugs must also be packaged and labeled as per regulatory guidelines. For international trials, this will require consideration of the varying regulations applicable in different areas of the world. The distribution stage involves careful coordination to ensure the right materials reach the intended study sites on time, in the right quantity, without any wastage or mishandling. Another critical aspect is tracking and monitoring trial progress and the status of trial supplies across sites, to properly program any refill shipments and ensure sites are properly equipped at all times, especially as the study progresses and new participants may withdraw from or be added to the study.

Ensuring proper manufacturing and handling of the study drug(s), particularly “current good manufacturing practices” (cGMP), may also fall under the responsibility of the clinical supply management team.

How clinical supply management contributes to efficient clinical trials

Efficient clinical supply management profoundly supports adherence to timelines and budgets, and overall is important for smooth and successful trials. Good planning prevents overstocking, which would lead to waste and wasted resources, or undersupply, with may cause costly delays. Both of these scenarios have the potential to incur major financial losses as well as detrimental effects on patient safety and data integrity. Efficient coordination between stakeholders and management of the logistical aspects of a trial, while often invisible to patients, could be thought of as the backbone of a successful clinical trial.

Legislation and regulatory compliance related to clinical trial supply

The legislation and regulations pertaining to clinical trials differs around the world. As nearly every stage of the clinical supply chain must comply with applicable regulations, such as cGMP, the regulatory aspect becomes central to proper clinical supply management. Potential aspects to be addressed in this regard can include dealing with import/export restrictions regarding investigational medicinal products (IMPs), cold-chain storage/shipping requirements, differing labelling norms, and ensuring safe and high-quality manufacturing practices that comply with local regulatory frameworks. Compliance issues can cause major setbacks and financial losses, or in the worst case can lead to the early termination of a trial, and thus this area demands consistent vigilance along the entire supply chain and throughout the trial.

Potential challenges encountered in clinical trial supply chain management

Due to the complexity of clinical supply chains and the amount of actors and operations involved, this may be a particularly challenging aspect of trial management. Difficulties in forecasting patient enrollment rates, managing divergent legislation in multinational trials, last-minute or mid-trial protocol changes, shipment delays, and non-compliance instances are just a few of the potential complicationsd that may be encountered. The clinical supply management plan should attempt to account for problems with a higher likelihood of occurring, and establish protocols for addressing those issues. While the supply management team requires agility and expertise for quickly resolving or adapting to any such issues, thorough planning remains the most important tool for preventing setbacks and being prepared to addressed them if they do occur.

The advantages of technology: Current trends and strategies used in clinical supply management

Clinical supply management teams are increasingly leveraging technology to enhance operational efficiency and flexibility. Artificial intelligence (AI) and machine learning algorithms can assist with more accurate forecasting, helping to optimize the planning phase. The use of interactive response technology (IRT) enables real-time tracking of supplies, providing real-time data for quick and proactive decision making.

Another trend is the shift towards decentralized trials (DCTs) or virtual trials, which may not involve study sites at all, and wherein patient-centric strategies like direct-to-patient (DTP) shipping of trial materials are commonly adopted. This approach minimizes site visits for patients, but requires a different approach to drug distribution logistics, particularly concerning the legal complexities of shipping controlled or not-yet-approved drugs to patients, as well as related privacy concerns and issues with maintaining blinding while still labelling the shipment as per legal regulations. In cases where DTP shipments are not permitted, structures such as local pharmacy partners or dedicated pick-up points may be used.

Blockchain technology offers potential solutions for thorough, secure, and transparent documentation of all supply chain operations and interactions, supporting high degrees of traceability and accountability throughout the supply chain.

Another trend is the move toward end-to-end integrated models, where all stages of clinical supply – from drug manufacturing through to distribution – are managed cohesively by a single partner organization. This reduces the number of hand-offs along the chain, offering improved control and streamlined coordination. This trend is reflected in the increasing prevalence of clinical development and manufacturing organizations (CDMOs), which evolved from CMOs to integrate further aspects od drug development. Some CROs may also offer clinical supply services, even beginning from drug development or manufacturing.

Conclusion

In conclusion, efficient and organized clinical trial supply management is vital for smoothly operating and successful clinical research studies. Good clinical supply management begins with thorough planning, and involves the coordination of multiple stakeholders and suppliers and constant attention to stay on top of unexpected events. The complexity of trial supply management calls for a dedicated manager or team, and aspects of clinical supply and logistics can also be outsourced to an experienced CRO, CDO, or CDMO. However, modern software also offers greatly enhanced capacity for sponsor organizations to undertake this aspect of trial operations themselves, leveraging real-time data, streamlined coordination between sites and providers, automated alerts, and other benefits that advanced eclinical technologies offer.

Other innovations within the area of clinical supply management have further improved the capacity for efficient and streamlined trial logistics, supporting the increasing complexity of clinical studies while helping sponsors optimize resource allocation, adhere to timelines and budgets, and navigate and remain compliant with differential regulations across geographical areas in complex international or remote studies.