Within the scope of Medical Device Risk Assessment manufacturers must, inter alia, define the shelf life of the device. However, there are some divergences in the interpretation of the applicable essential requirements by manufacturers and Notified Bodies. With respect to the relevance of the information contained and the formal aspects, some manufacturer documentation does not meet the criteria that TÜV SÜD considers essential for validation. Based on an expert opinion by the Central Authority of the German Länder for Health Protection with regard to Medicinal Products and Medical Devices (Zentralstelle der Länder für Gesundheitsschutz bei Arzneimitteln und Medizinprodukten, ZLG), TÜV SÜD gives helpful tips on what manufacturers should look out for, particularly in the validation of shelf life.
Depending on the device, technological, chemical, physical, microbiological and/or toxicological aspects of the device and its packaging may have to be considered to determine shelf life. Directive 93/42/EEC, Annex 1, defines the essential requirements in this context, while the normative requirements made on the control of documents and records are set forth in EN ISO 13485.
Realistic scenarios for significant test results
Some of the requirements prone to frequent divergences in interpretation concern the selection of the production batches to be tested. In TÜV SÜD‘s opinion, testing should be carried out on a minimum of three batches to eliminate variability caused by the production process and raw materials. In accordance with GMP requirements, the test intervals must be risk-based and distributed across the entire shelf-life period. The test parameters selected must significantly reflect the relevant characteristics of the Medical Device up to the end of the shelf life. If the manufacturer submits (historical) data, these data must show that they are valid and applicable to the current validation.
The same applies to the storage and climatic conditions in which testing is performed. TÜV SÜD critically reviews whether these conditions comply with the actual market conditions and the climate zones in the target markets. Parties wishing, for example, to place a catheter-lock solution on the market which will be stored in air-conditioned hospitals but also in emergency vehicles without air-conditioning need a regulation aligned to their specific situation.
Manufacturers that use artificial ageing must describe the extent to which the selected parameters permit realistic statements to be made about the product, its packaging and the period in question. After all, common calculation procedures in accordance with Arrhenius‘s law do not per se take into account the combination of individual materials in a device and its packaging. Artificial ageing at high temperatures of a dental instrument made of steel in blister packing, for example, supplies information about the ageing of the packing material rather than about the ageing of the instrument itself. The Arrhenius equation, furthermore, is not suitable for use in temperature ranges in which a Medical Device undergoes changes caused by thermal impact, i.e. through deformation or phase transformation. As a general rule the following applies: The data obtained with accelerated ageing must be verified by comparing them against the data obtained with normally aged products later on.
First the criteria – then the test
As a Notified Body TÜV SÜD validates "Shelf-life determination within the scope of certification in accordance with Annex II (3), Annex II (4) and Annex III". To ensure rapid processing, the experts advise discussing and agreeing the criteria for shelf-life determination at an early stage to avoid further demands and tests later on. In this context, TÜV SÜD supports manufacturers, offering review of the solutions and validation plans even before the start of the shelf-life tests.
”Shelf life“ refers to the durability under specified storage and transport conditions defined by the manufacturer until the immediate packaging is opened for the first time.
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