Parenteral products are designed, formulated, and packaged to be sterile and to maintain sterility. One of the most important parts of the packaging of sterile drug products is the container-closure mechanism. This article examines the use of closures, for products intended for injection, in the pharmaceutical industry. The article considers the most important aspects relating to the manufacture of closures and the different physical and biological assessments required to ensure that the closures are "fit for purpose." The article does not address caps or other types of seals.Closures form part of the "container-closure system." Container-closures function to keep the contents of pharmaceutical preparations sterile (e.g., by providing a barrier between the neck of a vial and the vial contents) and to prevent ingress of contamination into a vial once a needle is inserted (e.g., by enabling resealing of the vial after the needle is withdrawn). The closure, together with a crimp that creates the container-closure, and the vial itself form the primary packaging or packaging component (i.e., the material that first envelops the product and holds it) (1). The ideal container-closure will have low permeability to air and moisture and a high resistance to aging (2).
Therefore, the manufacturers and users must have confidence in the quality control and validation of closures. It is an important part of pharmaceutical manufacturing that all information on the composition and manufacturing processes for each component type must be understood.
Pharmaceutical closures, also known as stoppers or bungs, are an important part of the final packaging of pharmaceutical preparations, particularly those that are intended to be sterile. The most commonly used type of stopper is the elastomeric closure. An elastomer is any material that is able to resume its original shape when a deforming force is removed, which is known as viscoelasticity (3).
For the manufacturing of closures, the elastomer is either natural or, as is more common, a synthetic rubber, such as butyl rubber or chlorobutyl rubber. The advantage of synthetic rubbers is that the materials are strongly resistant to permeation by oxygen or to water vapor (4).
In terms of the specification for closures and the testing and sterilization requirements, the following documents are useful as starting points:
The FDA Code of Federal Regulations (CFR) part 21 211.94 stipulates that container-closures must provide adequate protection to the product over the product shelf-life.
Before using a closure in a vial or bottle with a drug product, the closure must be assessed to determine if it is suitable for use with the product that will be filled into the glass container. The pharmaceutical manufacturer should consider the following questions relating to product compatibility, in conjunction with the manufacturer of the closure:
Once these questions have been satisfactorily answered, the pharmaceutical manufacturer can work with the manufacturer of the closure to design the optimal closure for the vial type and product.