Stability and durability requirements for pharmaceutical packagings
In February 2019, the Delegated Regulation (EU) 2016/161 entered into effect . The objective of the Regulation is to increase the anti-falsification security of pharmaceutical products and to reduce the entry of falsified medicinal products into the legal supply chain. The Regulation provides that the packaging must carry a unique identifier in addition to an anti-tampering device. The anti-tampering device can for instance comprise a safety label which can be checked to verify whether the packaging was opened before being supplied to the patient. Typically, codes are used as unique identifiers. The information contained therein must be present on the packaging both in plain text and in a data matrix code in order to ensure machine readability of the information. The identifier code, which is unique for each secondary packaging (or folding box), can be applied by different marking technologies such as inkjet printing methods (thermal inkjet – TIJ, continuous inkjet – CIJ), thermal transfer printing (TTP) or laser marking technologies (inverse codes by laser ablation or laser marking on thermochromic surfaces).
According to the Regulation, the applied codes must be unique and readable “for a minimum of one year after the expiry date of that medicinal product or five years after the pack has been released for sale or distribution” . This provision implies requirements regarding the stability and durability of the data matrix codes or anti-tampering devices. Defined storage conditions for the medicinal products are not specified in the Regulation. Even in case of thoroughly monitored storage and transport conditions for pharmaceuticals (Good Distribution Practice), the safety features must withstand different climatic conditions (transport chain or e.g. refrigerated medicinal products) and ageing processes.
The readability of the codes can be impaired by abrasion or vibration, e.g. between several folding boxes in a secondary packaging, during the transport of medicinal products. The codes’ resistance to abrasive processes at a defined weight load can be determined by a rub-fastness test (refer to Fig 1).
Further factors influencing the stability of the codes are water and moisture They can be relevant in the supply chain because of different transport and storage conditions of the medicinal products. Water resistance is tested after ISO 18935 and classified in three categories: “water resistant”, “moderately water resistant” or “not water resistant” (refer to Fig 2). The test can be carried out, as appropriate, either with a drop of water or by adjusting the ambient moisture. Another option is to load the codes such that they are subjected to a rub-off test immediately after exposure to water or moisture.
Furthermore, the light-fastness of codes may be important. Here, the code is subjected to accelerated light ageing, and the change in readability is recorded. Depending on the ink and the substrate, there may be a reduction in contrast due to fading of the ink or yellowing of the paperboard (refer to Fig 3). The minimum requirements may be different according to the specific application.
The Regulation (EU) 2016/161  provides, as mentioned above, that the safety features must remain readable for a minimum storage time of 5 years. Without long-term testing, it is difficult for pharmaceutical companies to verify compliance with this legal obligation. The new PTS method PTS DF 109/2019  demonstrates a concept for the testing of codes and packagings by accelerated ageing, except for exposure to light, according to DIN ISO 5630-3 or DIN 6738.
In this method, codes and folding boxes undergo accelerated ageing at 80°C and 65 % relative humidity for the evaluation of their (shelf) life. The methodology was transferred to the FFPI Specification for paperboard for pharmaceutical folding boxes FFPI-SP 08/2019 .
Testing the safety features for their resistance to various ambient conditions and for their ageing behaviour can furnish proof of legal compliance and facilitate the selection or optimization of the materials and processes. We would be glad to support you in this matter.
Dr.-Ing. Martina Härting,