Adhesives and sealants are often considered for use within a medical device. However, finding the right material and supplier can be an incredibly difficult job. Medical device engineers must achieve specific physical, chemical, thermal, and electrical properties while simultaneously ensuring that the end product will receive FDA approval for the appropriate degree of biocompatibility.
This blog post is designed as a guide to help engineers (or other interested individuals) navigate the market of medical adhesives and sealants and further understand the types of certifications a "medical grade adhesive" might receive. Specifically we will explain and compare USP class VI and ISO 10993 certifications.
What Is Biocompatibility?
A material is considered biocompatible if it lacks any interaction (toxic, injurious, or otherwise reactive) with living tissue or living systems. Essentially, the living tissue keeps on living just as if the material were never introduced.
For obvious reasons biocompatibility is of the utmost importance for medical devices, and the FDA requires that engineers prove a certain degree of biocompatibilty prior to a product's introduction to the market. As a result medical device engineers will strategically design their products with medical-grade components -- components that have individually exhibited levels of biocompatibility.
An important point for our conversation, however, is that the FDA only approves the final device, not individual components or materials. Therefore, adhesives and sealants used in medical devices are not individually required to pass the same set of tests and standards. However, testing adhesive and sealant materials for biocompatibility helps medical device manufacturers select the correct materials during their design process. By choosing adhesives and sealants that have been proven to meet USP class VI and ISO 10993 protocols, medical device manufacturers can increase their confidence that their final product will gain FDA approval.
USP Class VI Biocompatibility Testing
The U.S. Pharmacopeial Convention (USP) is a non-profit organization that creates standards for medications, food ingredients, healthcare technologies, and plastics/ polymers used in medical devices. Depending on the product’s specific use and duration of patient contact time (limited, prolonged, or permanent), materials are broken down into six classes -- USP class VI being the highest and most demanding class. Adhesive and sealant materials that qualify to this designation are generally considered very safe for use in medication devices.
USP class VI testing involves three reactivity evaluations. All three evaluations are preformed in vivo (latin for “within the living”) on mice or rabbits. Tests preformed in vivo are generally more predictive than tests preformed in vitro (latin for “in glass”). The three evaluations preformed for the USP class VI testing are:
- Acute Systemic Toxicity Test: Material is administered orally, applied to the skin, and inhaled. Toxic or irritation response is measured.
- Intracutaneous Test: Material is applied to sub-dermal tissue. Toxic or irritation response is measured.
- Implanation Test: Material is implanted into intramuscular tissue. Toxic or irritation response is measured.
It should noted, however, that passing the USP class VI tests does not guarantee a material will be safe for use in all medical devices or all applications. But this makes sense. Materials that fail to meet these standards are conclusively toxic or irritable. However, the USP class VI testing can not perfectly test for every possible interaction and, therefore, materials that pass these tests can not conclusively be considered biocompatible for every application.
Passing the class VI designation is simply a strong indicator of material’s quality and is correlated with low levels of toxicity. Some medical devices may be required to meet even higher standards than those provided by USP class VI. Enter ISO 10993…
ISO 10993 Biocompatibility Testing
The International Standards Organization (ISO) developed ISO 10993 in an effort to standardize biological evaluation of medical devices worldwide. This set of standards outlines material categories, tests, and test methods that can be used to determine the biocompatibility of materials.
It is interesting to note that ISO 10993 actually refers to methods described in the USP. However, because the ISO system applies these methods as apart of a larger, more rigorous strategy, meeting ISO standards is representative of a higher level of biocompatibility than meeting USP class VI standards.
The ISO strategy categorizes medical devices by type of body contact (surface device, external communicating device, and implant device) and by contact duration (limited, prolonged, permanent). For each resulting medical device category ISO provides a set of suggested evaluation tests.
Adhesives and sealants are generally not required to pas the full battery of ISO tests for a related application. As mentioned earlier, only the final medical device is submitted for approval. As a result many adhesives and sealants are only tested for cytotoxicity -- a test required for all types of devices -- in order to prove the material meets the minimum standards.
The cytotoxicity test determines whether a given material will have an adverse effect on mammalian cells (normally mouse or human cells). Cells are cultured in vitro, systematically exposed to the material in question, and observed over several days for signs of toxicity. There are a few major benefits to this method. The cytotoxicity test is fast, standardized, sensitive, and inexpensive.
USP vs. ISO For Adhesives & Sealants
The short answer is that ISO 10993 is a more rigorous system and thus carries more authority than a USP class VI certification. Medical adhesives and sealants that pass the ISO standards have proven to meet the highest standards of biocompatibility, and will probably not pose an issue once the final medical device applies for approval.
However, full ISO 10993 certification is generally unnecessary for adhesive and sealant products, and many material formulators may avoid the full certification due to prohibitively high costs. Furthermore medical devices aren’t required to test all their individual components, only the end product. Additionally, depending on the device structure and application, the adhesive component may only make limited contact with human tissue.
As a result we would encourage medical device manufacturers to consider adhesives and sealants that pass USP class VI requirements or only pass aspects of the ISO 10993 protocol, such as the ISO 10993-5 test for cytotoxicity. Depending on your application these products may provide superior performance properties and allow for more convenient assembly procedures, without compromising the biocompatibility of the end device.
Cova Advice For Selecting A Medical Grade Adhesive & Sealant
- Don't limit yourself to fully ISO 10993 certified materials - Depending on your application, using materials that have been either USP class VI or ISO 10993-5 tested may be sufficient. Especially if these materials provide important performance properties to the end product.
- Don't be afraid to pursue a custom product - Often times applications can not be solved with an off-the-shelf product. Many formulators will develop or modify products specifically for your application, providing you with a medical grade adhesive that meets your design and assembly specifications. Custom formulations will always meet your needs better than an off-the-shelf alternative.
- Talk to us! We can help you connect to a variety of formulators - At Cova Scientific we help engineers identify and connect with formulators across the country. Don't be afraid to reach out and tell us a little bit about your application. We can help you take the next steps forward.