In the US Food and Drug Administration's Guidance for Industry, Container Closure Systems for Packaging Human Drugs and Biologics http://www.tinyurl.com/28fxgm, the agency defines a container–closure system as "the sum of packaging components that together contain and protect the dosage form. This includes primary packaging components" (4). A similar definition is provided by the European Medicines Agency in its Guideline on Plastic Packaging Materials http://www.emea.europa.eu/pdfs/human/qwp/435903en.pdf (5). It is clear from these definitions that a prefilled syringe meets the definition of a container–closure system and thus is subject to the associated guidelines and regulations. It is noteworthy that because of its use and nature, a prefilled syringe, as an injectable product, falls into FDA's highest risk category for the likelihood of a packaging component–dosage form interaction.Foremost among these regulations and guidelines are the regulatory expectations that revolve around suitability for the intended use. As noted in FDA's container–closure guidance:
Every packaging system should be shown to be suitable for its intended use: it should adequately protect the dosage form; it should be compatible with the dosage form; and it should be composed of materials that are considered safe for use with the dosage form and the route of administration. If the packaging system has a performance feature in addition to containing the product, the assembled container closure system should be shown to function properly.
Each of these aspects of suitability for intended use will be considered in greater detail as follows.
As a packaging system, a prefilled syringe must meet all the suitability-for-intended-use expectations. Only certain aspects of a given expectation may be applicable to prefilled syringes. For example, the expectation of protection of the dosage form is interpreted to mean that the prefilled syringe should protect the dosage form from factors that may degrade the quality of the dosage form throughout its shelf life. Some commonly cited causes of such degradation for prefilled syringes include loss of solvent, adsorption of water vapor, and microbial contamination. Other potential causes of degradation, including light exposure and contact with reactive gases, are less germane to mainstream applications of prefilled syringes because such systems are not currently marketed as light or gas barriers.