Functionality Testing For Plastics Used In Injectable & Implantable Devices
How are plastic materials used in injectable products?
Many product-packaging systems use elastomeric materials. Elastomeric materials are plastics that can resume their original shape after experiencing tension or compression. Plastics are used in injectable products such as vials, bottles, prefilled syringes, flexible bags, and blow-fill-seal containers. Stoppers, cap liners, plungers, needle shields, tip caps, seal liners, and injection ports are all examples of injectable product components that utilize plastics. Implantable devices also use plastics and require plastics testing (often from plastics testing labs). Any plastic with direct or transient contact with a pharmaceutical product or medical product formulation must pass certain regulatory requirements before being used as a device or packaging material. Polymer coatings also fall under the assessment criteria for elastomeric materials for polymers & plastics testing. Information on a polymers’ composition, manufacturing, and use can be found in USP 1381.
What are the regulatory tests needed for the elastomeric packaging used in injectables?
As mentioned earlier, elastomerics (a subset of plastics) in direct or indirect contact with a medical or pharmaceutical product must be assessed for their safety before use. Plastic materials can vary widely in their purity, meaning that intentionally or unintentionally added elements exist in manufactured plastics. Thus, baseline physiochemical and biological reactivity requirements for plastics used in injectable packaging-delivery systems must be met, in addition to functional requirements. Depending upon the elastomeric material, USP 1663 extractables testing may be needed. Overall, safety tests for elastomeric plastics fall under two primary categories: package integrity testing (e.g., functionality, seal quality, and leak testing) and cytotoxicity testing (e.g., biological reactivity and physiochemical testing).
What is package integrity testing?
Package integrity testing is testing how well a package stays complete and undivided to keep wrapped objects protected and sterile. Package integrity and container-closure integrity are terms that are used interchangeably. These terms are the same, depending upon the definition of container-closure integrity. In the past, container–closure integrity referred to a package that had passed or could pass a microbiological challenge test. However, package integrity and container-closure integrity are synonymous under the USP 1207 definition of container-closure integrity. In the context of package integrity and package integrity testing, a product package is considered both the product packaging and the product. Package integrity testing includes leak testing, seal quality testing, and other assessments such as the functionality testing described below.
How do you determine elastomeric plastic suitability for medical product packaging?
First, plastics of interest undergo an elastomeric screening process to verify a lack of biological or chemical reactivity with the product formulation or pharmaceutical agent. Next, extraction studies and pharmaceutical assessments are performed to identify any leachable agents in the product-packaging system. Any identified leachables are measured. Then their product compatibility is determined. Once identified, product-compatible plastics undergo a series of functionality tests to verify their mechanical performance in use.
What are the functionality tests For pharmaceutical-grade plastics Testing?
Functionality tests are performed on plastic closures that a hypodermic needle will pierce. These tests ensure that the plastic closures can adequately seal product containers and provide effective product delivery through needles. Self-sealing functionality tests are needed only for multi-dose containers. The elastomeric plastic closures being tested should mimic those used in the final product-package system, including any terminal sterilization processes (e.g., steam, ethylene oxide) or surface modifications (e.g., siliconization, fluoropolymer coatings). Multiple 21-gauge hypodermic needles with a 12° long-bevel are used for the following functionality tests.
#1: Penetrability Testing
Procedure: Ten vials are filled with water and fit with elastomeric closures. Closures are then examined by measuring the force required to pierce the plastic closure with a sterile hypodermic needle repeatedly.
Acceptance criteria: Piercing force is no greater than ten Newtons for each closure. Penetrability testing is needed for implantable devices (such as thermal polymerizing gels) that are implanted via fluid injections. Penetrability testing for polymers & plastics testing is a common assay for plastics testing labs since it evaluates how easily a product can be removed from its plastic packaging.
#2: Fragmentation Testing
Procedure: Fragmentation testing for dry preparations involves first fitting twelve clean vials with plastic closures. For liquid preparations, twelve vials are filled with water within four milliliters of their capacity before being fit with closures. All vials stand for sixteen hours after preparation. Next, a hypodermic needle is used to inject one milliliter of water and remove one milliliter of air. The water injection and air removal process is completed four times for each elastomeric closure, piercing in a new location with each injection and using a new needle for each closure. Once all four piercings are complete, vial liquid is filtered through a membrane with a pore size of half a micron or less. Rubber fragments visible to the naked eye are then counted after filtration for each of the twelve vials.
Acceptance criteria: No more than five fragments with a diameter greater than 50 microns (μm) are visible. Particles can be examined microscopically for size verification.
#3: Self-Sealing Capacity Testing
Procedure: Ten vials are filled with water and fit with elastomeric closures. Closures are then pierced ten times each with a new hypodermic needle. Each needle piercing is at a different location on each plastic closure. Next, all ten vials are immersed in a 0.1% (1 gram/Liter) methylene blue solution for forty minutes. The external pressure is reduced by 27 kilo Pascals for the first ten minutes before being restored to atmospheric pressure for the remaining thirty minutes of immersion. Finally, the vials are removed, rinsed, and visually inspected for any trace of blue within the filled vials.
Acceptance criteria: All vials contain no trace of blue solution. Self-sealing capacity testing is needed for implantable devices (such as thermal polymerizing gels) that are implanted via fluid injections from a multi-dose vial. Many contract testing labs can perform the same functionality testings for polymers & plastics testing as plastic testing labs.
Plastics Testing Summary
Overall, many product-packaging systems use plastic materials known as elastomers. Plastics are used in injectable products such as vials, bottles, prefilled syringes, flexible bags, and blow-fill-seal containers. Stoppers, cap liners, plungers, needle shields, tip caps, seal liners, and injection ports are all examples of injectable product components that utilize plastics. Any plastic with direct or transient contact with a pharmaceutical product or medical product formulation must pass certain regulatory requirements before being used as a device or packaging material. Safety tests for elastomeric plastics fall under two primary categories: package integrity testing (e.g., functionality, seal quality, and leak testing) and cytotoxicity testing (e.g., biological reactivity and physiochemical testing). This article describes three functionality tests performed on elastomeric closures intended for needle piercing. These functionality tests are penetrability, fragmentation, and self-sealing capacity testing. Self-sealing capacity testing is only needed for multi-dose containers. Many contract testing labs can perform the same functionality testings for polymers & plastics testing as plastic testing labs. All in all, ensure you choose a contract manufacturing organization that can support you with appropriate package integrity testing for your unique implantable device or injectable needs.
MycoScience is a contract manufacturing organization specializing in sterile syringe and vial filling. MycoScience also offers Preservative Efficacy Testing, Cytotoxicity Testing, Bioburden Testing, Cleaning Validations, Microbial Aerosol Challenge Testing, Accelerated Aging, Microbiology Testing, EO Residual Testing, Bacterial Endotoxin Testing, Package Integrity Testing, Sterilization Validations & Environmental Monitoring services medical devices and allied industries. MycoScience is an ISO 13485 certified facility.
References
Michael J. Akers. Sterile Drug Products Formulation, Packaging, Manufacture, and Quality. Drugs and the Pharmaceutical Sciences. Informa Healthcare. 2010.
United States Pharmacopeial Convention. <381> Elastomeric Components In Injectable Pharmaceutical Product Packaging/Delivery Systems (USPC <381>).
United States Pharmacopeial Convention. <1207> Package Integrity Evaluation- Sterile Products. Rockville, MD, USA. 2021. (USPC <1207>).
