Container closure system of a drug-device combination product

Biological evaluation and management of changes for a container closure system of a drug-device combination product: case study of a wearable injector

Lucie Armand1, Nastassja Bidaubayle2, Nicolas Farion1

1 Becton Dickinson, 11 Rue Aristide Berges, 38800 Le Pont-de-Claix, France

2 Efor Group Consulting Life Sciences, 19 r Rosiéristes, 69410 Champagne au Mont d'Or, France

Container closure system of drug-device combination product (DDCP) is a combination of primary packaging and injection system of pharmaceutical products that are regulated by US regulation 21 CFR part 4 and Medical Device Regulation (EU) 2017/745. DDCP safety implies a biological evaluation conducted within a risk management process following ISO 10993-1(2018)standard.

As per this standard, the first step is material characterization of the container closure system through material selection, information gathering from material suppliers and/or extractables chemistry studies on the finished final product. If applicable, a toxicological risk assessment of extractables is then performed as per ISO 10993-17 standard taking into account DDCP intended clinical use. The local and systemic toxicity endpoints that could not be covered by chemical characterization and that are relevant for the DDCare assessed through biological testing defined in accordance with ISO 10993-1 and sub-parts.

After this first step, every change in the materials, design, packaging, shelf-life, intended use, manufacturing processes, equipment or environment is evaluated for its potential impact on the product safety. The need to conduct further evaluation and/or testing is assessed.

The wearable injector is composed of multiple components made of various material types and with various contact categorizations as per ISO 10993-1. Thus, the evaluation appropriate to each category shall be carried out to perform the biological evaluation of the full product. For this case study, several examples of changes on various component types will be illustrated, including manufacturing change (molder change), material change (ingredient, plastic resin, printing ink changes, packaging), regulation change (new classification of a chemical). The assessments regarding potential impact on extractables profiles and the overall biological evaluation, as well as the testing strategies will be presented. For a multi-component product, specific and pragmatic strategies are defined to avoid tests multiplication and limit animal use.