A key component of virtually every drug product or medical device container is the label which is typically applied to the exterior of the package system. While the FDA provides detailed guidelines for labels specific to legibility and type of information it must display, and while there are a number of ASTM procedures that address peal ability, the performance of the label to withstand the environments it may be subjected to is often overlooked. For example, ASTM D3330 Peel Adhesion Pressure Sensitive Adhesive Tapes is one of the more common standards to determine the adhesive strength of pressure sensitive labels and tapes. This standard consists of Methods A through F which identify ways to measure peel adhesion at both180 degree and 90 degree angles. In a similar manner, ASTM D6252 outlines a position-controlled 90 degree peel test method to quantify the adherence of a pressure-sensitive label to a standard steel substrate, or other surfaces. What neither the FDA guidelines or the reference ASTM methods address is the ability of the label to withstand the rigors of the environment it will be subjected to. If you think about packaged medical products in the shipment distribution cycle, what environmental factors or conditions will it be subjected to? In most cases, shipment by way of airfreight will see a wide spectrum of temperature and / or pressure changes. What will these changes do the adhesion of the label?
While there is no formal Label Adhesion test procedures to address this unique concern, the CS Analytical Team has many years of experience developing test programs that address this unique concern. As such, we have been able to develop a formal test program that can be customized for each client based upon the expected conditions encountered by labeled product through distribution and the total shelf life of the product. Distribution and storage present diverse temperature conditions for various time periods. A label must be durable enough to withstand the expected temperature range of which it may be exposed. Label adhesion testing subjects the package label to these conditions and analyzes the adhesive’s ability to withstand these expected variations. Acceptable results will verify that the packaging materials selected will effectively and adequately adhere to the bottle through distribution and shelf life.
Key Definitions for an Acceptable Label Adhesion Protocol:
Acceptable Quality Level (AQL) – The maximum percent nonconformance that, for purposes of sampling inspection, can be considered satisfactory as a process average. In many cases, a sampling plan based upon a MIL standard is used to determine the sample numbers. For most medical products, ZERO deformities will be the accepted standard.
Adhesion – The ability of a material to stick to the surface to which it is applied. The state in which interfacial forces, which may consist of valence forces or interlocking action or both, hold two surfaces together.
Adhesive – A substrate capable of holding materials together by surface attachment.
Base Label – The portion of the label that adheres directly to the container. In many instances, medical product labels are two-part – lower part that adheres to the package system and top layer that contains all printed material.
Channeling – Tunnels or void areas that have formed as a result of air entrapment or expansion of the label surface.
Defect – A departure of a quality characteristic from its intended level or state that occurs with a severity sufficient to cause an associated product not to satisfy intended normal, or foreseeable, usage requirements.
Edge Lift – The identification of adhesive failure at the edge of a label, especially in the corners, from the labeled surface by use of a pointed needle run under the label edge area. . Label edge lift is defined as greater than 1/16” wide by ½” long.
Flagging – The separation or failure of adhesion from a label’s edge that curls or moves toward the center point of application of the label.
Inspection by Attributes – Inspection whereby either the unit of product is classified simply as conforming or nonconforming, or the number of nonconformities in the unit of products is counted, with respect to a given requirement.
Label-Tear – The tearing or incomplete removal of a label as it is removed from the substrate to which it was applied.
Lay-Flat – The uniform adhesion of a label to a substrate minus the presence of channels or wrinkles on the label surface
Top Layer Label – The portion of the label that does not directly adhere to the container but adheres to a portion to the base label.
Key Critical Steps for an Acceptable Label Adhesion Study:
Sample Preparation. It is preferable that all samples be prepared in the laboratory setting to ensure an adequate Pre-testing inspection of each label, as it is applied, can be performed. Any components which show degradation should be removed and replaced before the testing is started.
Sample Quantities. While sample quantities may vary based upon a specific client need, it is common to use a set of 10 labeled containers for each storage condition that the study will use. If there are four different storage conditions, then a total of 40 labeled containers (10 for each storage condition) would be ideal.
Storage Conditions: Most label adhesion studies use four different temperature and / or temperature & relative humidity conditions. The specific conditions can be determined by the expected conditions that the package system may be subjected to. It is important that the conditions used span the temperature range from cold to hot at a bare minimum. Common conditions that ensure this requirement include: (a) negative 20º C; (b) 5º C; (c) Monitored Room Temperature/RH and (d) 38º C +/- 2º C (100º F).
Study Duration: Variability can be applied here but it is suggested that at a minimum the study run for at least a 4-week time period. I would not be uncommon for the study to run out as far as 8 or 12 weeks.
Inspection Intervals: At a minimum, labeled components shall be inspected at 24 hours, 1 week, 4 weeks, 8 weeks, and 12 weeks. The labeled components shall be removed from the storage conditions and allowed to return to room temperature, minimum of 15 minutes, before inspection. For shorter duration studies (4 weeks), weekly inspections would be ideal.
An understanding of the definitions and key concepts outlined in this article will provide you with the information you need to help define and acceptable label adhesion study program for your specific product and package system. While this type of testing is not clearly defined in guidance documents, addressing this issue as part of the system qualification process will help prevent issues, concerns and even potential recall down the road.