The USP 661 and USP 671 general chapters are effective in outlining the test requirements for a plastic container and a package system. However, there is no specific section of either test procedure chapter that dictates the testing that should be performed on the closure. This leaves even the most experienced quality and regulatory specialists at a loss as to how to qualify a closure. In this article we will outline the test options for a closure that will help insure it meets the USP qualification process.
Anatomy of a Closure
The standard closure is made of various plastic components and typically has three main parts: the outer shell, the inner screw thread section and the induction seal liner. In most cases, the outer shell is polypropylene and the inner section is polyethylene. The induction seal liner is typically a multi-layer laminate material with the product contact (the section that is heat sealed to the container land area) being some form of plastic. There are multiple variation of closures that include a simple one part screw section with no liner, closures with foam liners and unique forms like flip-top and pump systems. In essence, though, a closure is a plastic component with or without multiple parts.
Applicable USP Test Procedures for Closure Qualification
To qualify a closure as its own unique component, the test methods as outlined in USP General Chapter 661 should be the reference point. The USP 661 chapter outlines the qualification process for the five known and commonly used plastics – HDPE, LDPE, PP, PET and PETG. Also included as part of this general chapter is a test procedure simply known as USP 661 Physico-Chemical Testing Plastics. This basic extraction profile enables the testing of plastic components that may not fall into one of the five known USP plastics. It also enables the “general” qualification of components (like closures) that are not specifically outlined by the USP.
The actual test process uses purified water as the extract solvent. A sample amount equal to 600 square centimeters of surface area material is exposed to the solvent and incubated at 70 degrees Celsius for 24 hours. Upon completion of the incubation period, basic wet chemistry tests to include non volatile residue, heavy metals and buffering capacity are performed. Results obtained for the sample are compared to the established USP specification and the component either meets or does not meet the assigned spec.
How to Test the Closure
We have discussed the closure, the test procedures to use for qualification of that closure and now we need to outline a defined plan of action to insure our closure meets the basic requirements. There are two basic test options. Option one (and the most common approach) treats all plastic parts of the closure as one composite sample. Equal surface area amounts of all closure sections (outer shell, inner section and liner) are taken collectively and the USP Phys Chem test procedure is performed. The approach in option two takes each of the closure parts as its own individual samples. In this case the outer shell would be tested as one sample, the inner section would be tested as a second sample and the liner would be the third sample. With this approach, some companies may choose to go one step further and apply the plastic specific test procedures to each part. For example, for the polypropylene outer shell, instead of just performing the phys-chem plastic testing, the USP 661 test procedures for polypropylene would be followed. This would include more in depth identification testing as well as an extraction profile that includes purified water but also hexane and alcohol.
Qualification testing of a closure for a pharmaceutical use container is an area of confusion due to poor or lacking guidance in the relevant USP chapter and in the FDA guidance documents. However, there are still options that companies can follow that enable the conservative approach of qualifying a closure. The specific tests have been outlined. As a quality or regulatory person, you need to decide the most effective (and conservative) approach – test as one composite sample or treat each part of the closure as its own unique sample. Whatever approach is chosen, when the FDA inspector asks “can you please provide the qualification data for that container system” you will be prepared.