An exclusive Q&A with label vendor, Schreiner MediPharm, on the supply of drugs for clinical trials, important aspects of investigational product appearance, drug labeling, clinical trial innovations, and more.

Clinical trials are a standardized (and important) element of the drug development process—their phases, design, and duration are all things that are well-monitored and well-understood. There are constantly innovations and changes implemented into the process with the hopes of improving the various aspects of clinical trials, such as patient medication adherence.

Schreiner MediPharm, a company that develops and produces specialty labels and self-adhesive marking solutions, has a hand in the pharmaceutical clinical trials, as many of their products are utilized therein.

Barbara Decker, Team Leader CTS, Schreiner MediPharm, participated in an exclusive Q&A with Pharmaceutical Processing to discuss some of the challenges with drug supply in clinical trials as well as product clarity. Her edited responses are below.

Give us an overview of clinical trials. What does the supply of drugs look like? How are they typically differentiated? How does it compare for pills vs. injectables?

Decker:

Clinical trials take place all over the world, which means you need to make sure that the Investigational Medicinal Product (IMP) as well as the Non-Investigational Medicinal Product (NIMP) are available for patients at different locations in the right quantity at the right time. In order to achieve this goal, several aspects have to be considered in the planning phase of your clinical trial supply chain, including the amount of drugs required; whether to use central and/or local depots for distribution; the inventory management system; and the storage conditions at the involved clinical sites.

As a label vendor, Schreiner MediPharm is primarily involved during the production and packaging processes concerning the investigational drug, supporting the supply chain with labeling solutions and services that allow a very flexible use of the labeled and packaged investigational drugs.

From our experience with various companies conducting clinical trials, the actual participation and allocation of patients can often vary compared to the initial recruitment planning—a factor that requires the supply of drugs to be agile and flexible. Once the investigational drugs have been manufactured, labeled, and packaged, they are transferred to central and/or local depots that supply the clinical trial sites in various countries with the required patient kits.

What are some of the greatest challenges of clinical trials and drug supply?

Decker:

The biggest challenge of clinical trials is the balancing act between the need for maximum speed and error-free processes and results. Speed is a pre-requisite since, after many years of research and big financial investments, clinical trials are the last step before approval and market launch of a new drug. Speed to market is crucial since each day that the new drug can be released earlier means earlier sales and ROI. Only a few days can be worth millions of dollars. “Error-free” means that each error within processes, documentation, or packaging/labeling of the clinical trial might imply that the trial cannot be analyzed statistically correct according to the prescribed regulations. Consequently, the drug might not get market approval, which means that the trial might have been in vain or has to be repeated, being the worst case scenario of a clinical trial.

Clinical trials, since they are usually conducted on an international scale, create a high degree of complexity when it comes to process and information flow. From our experience, the biggest challenge with regards to the clinical supply chain is to deliver products at the highest quality in order to ensure patient safety, while ensuring very short lead times and a maximum level of flexibility to react to changes in the planning process.

Obviously, it’s important that each investigational product has the same appearance. What are some of the difficulties in ensuring that the investigational product, placebo, etc. all look the same? What are some of the key steps here?

Decker:

For blinded trials, it is absolutely crucial to ensure the same appearance for the investigational product, the placebo, and/or the comparator. Some of the difficulties you might face here are:

• Different primary packaging concepts/designs (e.g. with comparator)
• Differences in the color or shape of the investigational product, compared to the placebo (for instance with liquids or tablets)

How those challenges are addressed primarily depends on whether you can change the visual appearance and the packaging concept of the investigational drug, placebo, or comparator itself, or if you need to work with the existing medication and packaging concepts. If you cannot adequately match the appearance of the different medications, you can use different secondary packaging solutions that allow for masking of, for example, differing color shades of liquids or that completely cover the appearance of the drug and/or markings on the secondary packaging. Most of these blinding options can be integrated directly into our label solutions. A label supplier with special expertise in clinical trials can customize the solution per the specific application and adapt it to the used container or packaging while ensuring safe and reliable blinding.

What are some of the important pieces of information that are required to be on the drug label?

Decker:

Some of the important pieces of information that need to be on the immediate and outer packaging are:

• Name of the substance as well as its strength/potency
• Route of administration
• Storage conditions
• Period of use (expiry date or re-test date)
• Subject number and/or treatment number
• Batch number that identifies the contents and packaging operation
• “For clinical trial use only” or a similar wording

How do companies typically ensure all of the information is compact enough to fit on a given drug product?

Decker:

The most important aspects of clinical trials are product and patient safety, both of which require extensive information on the investigational drug and its administration. To fit all the necessary information concerning the drug product, companies need sophisticated label solutions that allow for use of available space as efficiently as possible. This can be achieved by using Booklet-Labels or multi-page labels. Especially in the case of vials or syringes with small radii, this can be a real challenge since the design of the label solution must be flexible enough to be tightly wrapped around the container.

What are some of the difficulties that companies (and patients) face in clinical trials today?

Decker:

In the last few years, we’ve seen a trend toward the development of drugs that require storage at very low temperatures. This not only impacts the transportation and storage of the drug, but also the requirements for secondary packaging such as clinical trial labels.

Companies need to ensure these cold chain supplies not only throughout the transportation process but also at the investigational sites and, often, even at patients’ homes. Here, reliable adhesion becomes an issue: pharma companies must ensure that, despite these perpetually low temperatures, the labeling still sticks permanently and reliably to the investigational drug. Ensuring this requires dedicated expertise on the part of label manufacturers.

How can some of these hurdles be addressed?

Decker:

Continuing with the example of low temperature storage requirements, Schreiner MediPharm partners with our customers to develop ideal, customized labeling solutions. The ultimate goal is to ensure that each and every investigational product is labeled accurately for precise administration, avoidance of medication errors, best-possible trial results, and, of course, patient safety.

What are some of the emerging innovations for clinical trials? Do you see any of these coming into fruition in the coming years?

Decker:

One emerging trend we are seeing is digitization and connectivity playing an increasingly important role within clinical trials. The subsequent demand for smart labels based on technologies like RFID and NFC has two apparent main drivers.

The first driver is the desire to improve the supply chain as well as the packaging and distribution processes connected with it. Integrating RFID functionalities in our clinical trial labels, you can program each individual label with additional digital information that might be helpful within your supply chain or even for patient information. Having marked the primary container with a smart label that identifies each individual container, you can increase the efficiency of your packaging procedures for patient kits by automating inspection steps. You also will be able to tell which containers are inside a patient kit box without opening it.

The other driver is enhancing patient compliance to achieve clinical trial results that are increasingly precise. Therefore, Patient Compliance Monitoring Systems will be increasingly utilized in clinical trials in the coming years. Innovative functional labels with printed electronics, in combination with an integrated NFC chip, make it possible to electronically track the dispensing of medicines and even remind the patient via smartphone to take the drug at the right time and in the right dose. This supports the success of clinical trials and helps to ensure valid data, since lack of compliance might endanger clinical trials results.

A label supplier with special expertise in clinical trials should have a thorough understanding of the processes and specific requirements of clinical trial supplies and their special packaging needs. Implementing a successful clinical trial requires timeliness, accuracy, exacting documentation, and flexibility at all stages, including the packaging process.

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