New regulatory efforts are placing greater strain on clinical trials and the associated labeling required during this process.

The pharmaceutical industry has undergone seismic changes during the past few decades, and the pace of those changes seems to accelerate with each passing year as new regulations are introduced. Nowhere is this more the case than when it comes to the use of labeling throughout a drug’s development.

While each clinical trial has its own unique labeling requirements, one constant remains: to ensure the validity of your study, it is important to consider as many variables as early in the process as possible.

Pharmaceutical labeling involves meeting a number of needs in order to maintain the efficacy of clinical trial results. There may be numerous trial subjects, each receiving a different dosage, frequency or duration, not to mention placebo. The amount of information that must be contained on sometimes very small labels can be staggering. There are also a large number of variations required for the different variables being tested.

Regardless of label content, however, it is important to consider the conditions to which the label may be subjected in order to ensure that it will remain adhered and legible for the length of time required. Failed labels could mean a failed trial, which would prove very costly to the developer of the drug. Consequently, it is vital to understand the individual components of the label and how each of those elements contributes to its success. For pressure-sensitive film labels, in particular, the primary components to consider are the adhesive and the film.

Selecting an Adhesive

Choosing an adhesive involves a bit of detective work regarding sterilization procedures and the end use. In most cases, there is an expectation that the label will remain adhered and legible through the sterilization process and for the life of the product or clinical trial, whether it is applied to a plastic container, glass vial or syringe containing medication.

One immediate concern is the type of container that the label must adhere to. If the drug will be contained in a plastic bottle, what type of plastic will be used? High-density polyethylene (HDPE) and polypropylene (PP) are low-surface energy plastics which require a very aggressive, permanent adhesive in order for labels to adhere to the surface.

Contrast this with high-surface energy surfaces, such as the glass used for vials and syringes, which accepts an adhesive much more readily. The shape of the container also has an impact. A very narrow syringe or vial will require a high shear adhesive to ensure that it does not lift, and if there is any coating on the syringe, the adhesive needs to be very aggressive.

Then there are the conditions under which the label is expected to perform. A trial product that a subject may take home may very well end up in a bathroom medicine cabinet where it might be repeatedly exposed to moisture in the form of steam or water. Similarly, a container that needs to be refrigerated may quickly be covered with condensation when taken out as it adjusts to room temperature. In these cases, proper adhesive testing and selection is critical to preventing label failure.

Moisture, however, is only one consideration. Temperature can also have an impact on an adhesive. In some cases, a label may be applied at room temperature and then refrigerated, while others may be applied at cold temperatures. In order for a label to succeed when applied cold, the adhesive must be able to flow at that temperature in order to achieve good wet out. Again, adhesive testing and selection is critical.

On the other end of the temperature spectrum, labeled containers going through the autoclave sterilization procedure require that the adhesive stand up to high heat (up to 250 degrees Fahrenheit) as well as high humidity and high pressure (think pressure cooker). Alternatively, ethylene oxide can react with the adhesive and cause failure, as could radiation used with gamma and electron beam forms of sterilization. Each type of exposure requires different considerations when it comes to the adhesive choice.

Choosing a Film

Just as each specific scenario has an impact on adhesive selection, so too does each one affect film selection. Unlike adhesives, however, aesthetic and function considerations can also weigh heavily when it comes time to choose.

For example, clear films are often used in conjunction with vials and syringes for the simple fact that it is often necessary to see the contents through the film. In other cases, data trumps visibility. Clinical trials may require that an enormous amount of safety and usage information be included, not to mention coded information and barcodes for tracking purposes. Expanded content labels can be the answer, allowing for more printing geography, however, the peel/reseal functionality required for this type of label may require a reconsideration of the adhesive.

As with adhesives, the container shape can be a factor in terms of selecting a film. Small-diameter containers require a very conformable film, such as a thin PP, in order to prevent flagging. Large flat panel surfaces, in contrast, can use a thicker, more rigid film, unless the panel has curves, in which case a thinner, softer film may conform better.

Then there is the issue of label production. Understanding what technology will be used to print the labels is essential to deciding upon the complete product construction. A topcoat may be required for adequate ink adhesion. Furthermore, multiple printing methods may be used on the same label, such as flexo for static information and thermal transfer for variable information, requiring a particularly versatile topcoat.

An appropriate topcoat will also ensure adequate image quality, and since one of the primary functions of pharmaceutical labels in clinical trials is the tracking of data, high image quality is critical to ensuring data integrity. Labels with print voids or that become smudged or otherwise illegible, whether to the human eye or a scanner, could have disastrous effects on the validity of study results.

The converting process of the printer creating the labels may also dictate the choice of release liner. Although it is the throw-away part of the construction, the choice of a release liner that is compatible with die-cutting and dispensing equipment is essential for efficient and precise label application to the container.

Product Security

Finally, when it comes to safety, the film can play a critical role by the incorporation of tamper-evident features into the construction. There is a variety of destructible and partially-destructible films available for this purpose, such as films that break if removal is attempted or that leave behind a visible pattern upon removal.

For example, a product manufacturer may adhere an acetate wafer seal on a medication box that must be removed in order to open the box. Through the use of a film that breaks or distorts, the label cannot be reapplied, making the removal immediately and visibly apparent, thus flagging any potential tampering.

It is always recommended that the label material be tested under the environmental conditions it will see during the life of the application, as well as on the print technology that will be used, to ensure that it will perform as required. Many substrates have been pre-tested by the film supplier to determine the parameters under which it will perform best. Should you need confirmation or additional performance testing, however, it can be facilitated through your label printer, working with their substrate provider.

In the end, selecting the right pharmaceutical labeling construction depends on your unique application requirements. Completely sharing your specifications and collaborating with your label printer and substrate supplier will ensure a recommendation of the most appropriate construction. By doing so, you can avoid potential problems before they emerge. This will ensure that your labels succeed, thus minimizing the chance that your study could be derailed, costing you precious time and expense.

This article can also be found in the October 2015 edition.