Labeling is an integral part of the manufacture and sales of drugs and medial devices. The label provides product identification, instructions for use and safety information. Because the label is frequently the first point of contact for patients, medical practitioners, and many other people who handle packages throughout the supply chain, labeling for drugs and medial devices is highly regulated by the FDA and governed by a variety of standards from organizations such as ASTM and ANSI.

Brand owners need to ensure their labeling process complies with all applicable regulations and meets a high bar for quality to ensure reliable labeling throughout the lifecycle of the product. For this reason, label qualification is an essential step; executing a well-planned label material and print qualification will ensure that your product labeling remains intact during distribution, storage, and dispensing.

Planning for Label Qualification

When planning a labeling qualification, it’s important to consider the product labeling materials, the label printing and application processes, and distribution conditions that can affect label performance. Performing a risk assessment will provide clarity on the high-priority risks and provide a means to mitigate those risks during qualification testing. A pre-qualification checklist should include:

• Checking each step of the label printing process: One label may contain print generated by different types of printing methods, including laser printing, thermal transfer and ink jet technologies. Each printing method may perform differently under test conditions, and minimizing these differences is essential to creating standards by which samples can consistently be classified as acceptable or unacceptable during the inspection phase.
   
• Verifying that the label features consistent, legible print and barcodes for information such as lot code, expiration date, serial number or unique device identifier, in accordance with ISO/IEC quality standards.
   
• Confirming the label material meets the necessary standards and the specifications of the labeling process: the same label material may be applied to multiple surfaces on a product or package, and adhesives can perform differently on each surface. Qualification samples should evaluate label samples applied to all of the surfaces intended to be labeled, including curved surfaces, to confirm the label will adhere consistently.
• Establishing a testing process that is consistent with the actual process for label application, whether it’s manual or automatic.

1. Manually applied labels can introduce a high level of application pressure variation and label adhesion. If the packaging line utilizes a number of operators manually applying labels, consider using more than one operator to prepare qualification samples and introduce as much application variation into the process as possible.
2. Samples produced using an automatic label applicator should utilize the label applicator qualified process settings.

• For sterilized products, include samples exposed to the maximum number of sterilization cycles allowed in the manufacturing process.

Beyond preliminary considerations for materials and printing, the inspection process itself must be part of the qualification protocol. Both ASTM and ANSI issue standards for inspection parameters, such as lighting conditions, inspection distance and the need for clear pass/fail criteria, including:

• Quantifying the number and size of visual defects caused by loss of label adhesion.
   
• Establishing parameters for distinguishing legible versus illegible print: defects such as missing or smeared letters or numbers and extreme label or print discoloration should be identified as illegible.
   
• Defining visual acceptance criteria for label discoloration, adhesive bleed at the label edges, material delamination and surface abrasion.
   
• Determining process and pass/fail criteria for label and ink adherence in an aging study.
   
• Deciding on a bar code verifier for testing the print quality of linear and 2D bar codes.

Test Execution

Testing should represent the conditions that the labeling will be exposed to during the manufacturing process, storage, distribution, and dispensing of packaged products at the healthcare provider. The qualification process must evaluate the effects on label adhesion and print legibility due to exposure to distribution and handling conditions, including temperature exposure, shock and vibration.

Environmental simulations should represent the full range, including extremes, for temperature and humidity exposure. If possible, labels should be tested through a freeze/thaw process representative of conditions the package will be exposed to during manufacturing, transportation and dispensing. Labels should also be exposed to vibration against abrasive materials such as corrugated fibreboard and subjected to shock testing. Simulating these conditions will confirm label quality will hold up during transit without being compromised by tearing, wrinkling or other damage.

Accelerated aging and real-time studies simulate storage throughout the shelf life of the product to determine if degradation of the label material, adhesive or print will occur over time. The possibility of label adhesive or ink migration over time from a label applied to a primary drug container should be evaluated for potential risks.

An understanding of the process used for manufacturing and dispensing of a drug or device will determine if the package surface may be exposed to solvents or other chemicals. Smeared or missing print, destruction of the label surface, or removal of the label adhesive could occur. Isopropyl Alcohol, other antiseptics and surface disinfectants can come in contact with the labeling if the package is wiped down or opened by a healthcare practitioner handling an antiseptic as part of product dispensing. A test simulating the dispensing or processing conditions can confirm whether the printed labels are chemical resistant.

A diligently planned and properly executed label qualification process is one of the best investments a Life Sciences brand can make. Because of the heavily regulated nature of the industry and the brand’s responsibility to healthcare practitioners and consumers, the margin for errors and irregularities in labeling is extremely slim. Testing against a complete range of factors that can affect the quality of labeling now safeguards brand owners against the potential for compromised quality and non-compliance with important standards and regulations down the road.