Label Migration Studies

Both the FDA and EMEA guidelines consider pharmaceutical labels and printing ink, although not considered as a part of the primary packaging (i.e. no direct contact with the drug product), as a potential source of drug impurities via migration through the primary packaging into the drug product.

In the general consideration regarding the safety assessment of packaging components, the FDA-guidance “Container Closure Systems for Packaging Human Drugs and Biologics” states that no harmful or undesirable amount of substances should leach from packaging components. “…This is also applicable to any component from which substances may migrate into the dosage form (e.g. an ink or adhesive)…”. In addition, the paragraph in the FDA-guidance on secondary packaging states that “…if the packaging system is relatively permeable, the possibility increases that the dosage form could be contaminated by the migration of an ink or adhesive component…In such case the secondary packaging component should be considered a potential source of contamination and the safety of its materials of construction should be taken into consideration…”.

The EMEA-guideline states in paragraph 5.1 “Migration Studies” that it should be scientifically demonstrated that no components of ink or adhesives, applied to the outer surface of the container closure system, will migrate into the medicinal product.

Although not mentioned explicitly, it could be expected that in most cases, both the FDA as well as the EMEA will establish a relationship between the concern for “label/ink migration” and the degree of concern, associated with the route of administration of the drug product. In this respect, the regulatory concern for Label/Ink migration in e.g. parenteral, ophthalmic and inhalable products is expected to be higher than for e.g. oral tablets.

Knowledge of label and printing technology – in combination with a thorough understanding of the physical properties of polymers which may impact the extent of label/ink migration – is key in understanding the risks associated with this phenomenon. It is evident that the composition of the adhesive (e.g. oil, tackifiers, PVA, Acrylics, NR), the type of ink and solvents used, the photo-initiators (UV-curing) but also the type of polymer container and contact solution will have a large impact on the nature and extent of label migration. Compounds like DCHP, TBPP, Benzophenone, Irgacure 184, Irgacure 651 or other curing agents, Irganox 1010, siloxanes and a long list of different solvents are known to be potentially present in the composition of the label or have been detected as drug impurities in final drug products as a result of label migration.

Nelson Labs Europe has an extensive experience with setting up label migration studies for a wide variety of applications (Ophthalmic containers, IV-bags, Containers used for inhalation administration, polymer vials and prefilled syringes…). In addition, Nelson Labs Europe has a long list of in-house standards which are relevant for the identification of target compounds in label migration research. Our comprehensive testing approach, using a combination of state-of-the-art analytical techniques, such as Headspace GC/MS, PTV-GC/MS, GC/MS, LC/MS, LC/MS/MS,... has been used in analytical label migration studies to support regulatory submissions.

If you would be interested to find out more about our services and testing programmes, please feel free to contact us at InfoEurope@nelsonlabs.com or call us at ++32 (0)16 400.484. 


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Contact a Study Director:


kpieters@nelsonlabs.com
avertommen@nelsonlabs.com

Nelson Labs Europe | Label Migration