Learn more about CDMO | CMO Clinical trial material supply

Overview of the formulation development & clinical supply of small batches of drug products after lab & pilot scale up by CRO, CMO, & CDMO facilities

Q1. What are clinical trial supplies (or clinical trial materials) and services?

Clinical trial supplies or clinical trial materials pertain to the distribution of drug products that are packaged, labelled, and manufactured in compliance with cGMP practices for clinical trials. These small batches of prepackaged clinical trial supplies are then used for the clinical research of drug products via pre-clinical trials and human testing.

Prior to commercial manufacturing at a pilot or production scale, clinical trial material manufacturing services are carried out during earlier phases of scale up clinical development. As a drug progresses from the candidate drug selection phase into clinical study phases, the quantity of drug substance required increases. The early stage development phase, generally 100-1000 times lesser in quantity as compared to the production batch, takes place during the laboratory scale stage of formulation scale-up.

Laboratory scale up supports formulation development & packaging development for pre-clinical trial materials. As a result, a milligram preparative becomes a multi kg process, without impacting the quality or the performance of the active pharmaceutical ingredients (APIs). Fully integrated CDMOs offer such CDMO services for clinical trial supply.

Clinical trial supply services include, but are not limited to:

- Packaging & Labelling Services

- Clinical Supplies Management & Clinical Logistic Services

- Clinical Distribution Services

- Comparator Sourcing Services

- Tracking Services

- QP Clinical Supply Services

- Storage Services

- Clinical Trial Materials Supply Chain Management Services

Q2. How is the clinical trial materials supply chain managed?

Clinical trial materials (CTM) are defined as licensed finished dosage forms or drug products produced in small batches that are suitable for human dosing tests, but not intended for commercialization via bulk manufacturing capabilities. Clinical trial material manufacturing services are carried out in accordance with cGMP guidelines and are released by Qualified Persons (QP).

A qualified person is trained in European Union QP requirements and ensure seamless clinical supply management and transition management with external contractors. Clinical contract manufacturing of clinical trial materials (CTM) is a complex process and requires early planning, prior to commencing clinical development, in order to ensure success. Furthermore, clinical trial materials (CTM) are manufactured and supplied in required quantities through all phases of clinical testing.

- Phase I studies use clinical trial materials and supplies to test the safety of drug products.

- Phase II studies utilize clinical trial materials and supplies to test the efficacy of drug products.

- Phase III studies involve randomized, blind testing in several hundred to several thousand patients using clinical trial materials and supplies.

However, getting these packaged drug products to labs and study participants in an efficient and timely manner requires coordinated efforts by the clinical trial materials supply chain. Clinical supplies management services are therefore imperative to ensure proper functioning of the complex and global supply chain for clinical trial materials (CTM), particularly for studies requiring detailed monitoring, precise planning, and coordination between many players. The clinical material supply chain is managed in the following ways, amongst others:

- Inventory Management

- Labelling & Regulatory Support

- Temperature Data Recording Services

- Clinical Trial Material (CTM) Forecasting & Simulation

- Global Inventory Management

- QP Release Services

- Medical Packaging Design

Q3. What are some of the challenges involved in managing the clinical trial material supply chain?

Challenges faced in managing the complex & global supply chain for clinical trial materials:

The increased globalization of clinical trials has made effective management of the clinical trials material supply chain an even more crucial component of the drug-development process. A clinical supply chain is the chain for clinical materials ranging from raw products to clinical distribution.

Product development challenges have further burdened the clinical trial material supply chain due to increased regulatory requirements, new technologies, temperature deviations, changing import/export regulations, and the complexity of studies being conducted. Clinical supply management strategies are employed to combat three key challenges in clinical trial supplies management: planning, manufacturing and clinical distribution.

Clinical Trial Supply Planning Challenges:

Forecasting - clinical supply management services cannot always be accurate due to a number of reasons including the changing number of study participants (can increase or decrease compared to the predicted study population) and delays in clinical trial dates, which result in expiration of medicines, relabeling activities, and additional clinical contract manufacturing & packaging services.

Clinical Trial Materials & Manufacturing Challenges:

Making sure that clinical trial materials and supplies are regulated, and clinical trials material & manufacturing is fully compliant with cGMP guidelines are the two main concerns associated with clinical trial manufacturing services.

Clinical Trial Supplies/Clinical Distribution Challenges:

Compliant shipment of the drug substances to many clinical trial sites, which are often scattered in different countries, may seem simple, but it is difficult to achieve because of the need to comply with Good Clinical Practices (GCP) and cGMP regulations. Tracking and tracing a drug product throughout the clinical trial supply chain can also be very challenging.

Therefore, it is important to adopt strategies to optimize the clinical trial material supply chain which can be achieved via clinical supply management systems that addresses all of the above mentioned challenges faced by them.

Q4. What recent advances have been made in the technologies and logistics of pharmaceutical companies to manage clinical trial materials and manufacturing?

Technologies & Clinical Logistics

The value of some study drugs can reach tens of millions of dollars, making it essential to avoid overproduction, oversupply, and inventory expiration. With the high costs and strict handling requirements for many biopharmaceutical products entering clinical development, advancements in the technologies and logistics of pharmaceutical industries involved in clinical trial supply activities are more critical than ever. There are widespread strategies and developments that are being adopted to optimize the clinical trial supply chain, some of these advancements are explored below:

Cold chain supply management: Cold chain is a logistic system that provides a series of facilities for maintaining ideal storage conditions for perishables from the point of origin to the point of consumption. Even in refrigerated units, temperatures can vary. Temperature tracking is important to confirm appropriate temperatures throughout the clinical trial supply chain.

Outsourcing to CROs: Clinical CROs focus on clinical-trial services, such as clinical trials material & manufacturing, medical writing, data analysis, clinical research, managing regulatory-affairs processes, and other functions associated with getting new drug substances or devices to market. In recent years there has been an increasing trend towards clinical trial supply outsourcing to CROs, CDMOs, CMOs and other organizations with clinical trial supply capabilities.

Early stage storage & transportation planning: For efficient delivery of supplies, the clinical material supply team and contractors must have an established transportation and storage infrastructure that includes vetted third-party freight carriers and storage facilities.

Multi-echelon MRP tool: A time-phased, multi-echelon MRP tool should be adopted to translate study enrollment and dosing regimen projections, at the highest level, into an actionable finished good demand forecast for each clinical trial.

Personnel training: All personnel involved in the clinical trial material & manufacturing process from formulation development to packaging and clinical supply need to be properly trained in cGMP practices to reduce human errors which can slow down processes and make the clinical trial materials & manufacturing supply chain inefficient.

Track & trace systems: Advances in serialization labelling technologies make it easier to track clinical trial materials & supplies throughout the global clinical supply chain and further ensures accountability.

Centralized planning techniques: Establishing a centralized planning organization acts as a liaison to integrate clinical trial operations, the chemistry, clinical contract manufacturing, and controls team, and clinical supply managers to synchronize demand & supply activities. Through this liaison, the CMC team can better focus on clinical development and manufacturing, leveraging up-to-date demand information consolidated across all studies to drive feasible supply plans.

Q5. What is the estimated size of the clinical trial supplies market?

The clinical trial supplies market is projected to reach USD 2.5 billion by 2025 from USD 1.7 billion in 2020, at a CAGR of 7.8%. The growth of this market is majorly driven by the increasing R&D expenditure in pharmaceutical and biopharmaceutical companies, the globalization of clinical trials, and the harmonization of regulations. Advancements in clinical trial supply chain management technologies is also expected to be a major driver for the growth of the clinical supplies market. Furthermore, geographic expansion and development of Information Technology (IT) to facilitate higher integration and smooth performance of activities are other vitally impacting parameters.

The number of clinical trials conducted in the Asia Pacific is more than those in the US or Europe. This shift is ascribed to low operational costs, considerable patient recruitment potential, clinical research organizations growth, favorable regulatory environment, and better clinical trial capacity and quality. Over the next eight years, the clinical trials and pharmaceutical industry is anticipated to continue steady growth, thereby promoting the high requirement of clinical trial supplies.