Biocompatibility is a general term used to describe the property of a material being compatible with living tissue or living system. Non- toxic, injurious, or physiologically reactive materials to the body or bodily fluids are considered biocompatible and are well sought after by medical device engineers. In simple words, biocompatibility tests are not to prove chemical compatibility; but rather confirm a lack of immune reaction to the material or device.
Choosing the right material during the design process gives manufacturers more confidence in an FDA approval. Biological reactivity testing is one such process used for determining suitability and safety. There are two main tests that indicate if a material is biocompatible or not.
USP Class VI Biocompatibility Testing
Historically, standards were set by the US Pharma Convention (USP), a non-profit organization with a focus on medications, healthcare technologies, food ingredients, and materials used in medical devices. These standards categorize materials into six classes depending on the product's specific use and duration of patient contact time (limited, prolonged, or permanent).
It includes three reactivity assessments that are usually performed in vivo on mice or rabbits to ensure accuracy.
Acute Systemic Toxicity (Systematic Injection) Test: Measures toxicity and irritation when a sample of the compound is administered orally, applied to the skin, and inhaled.
Intracutaneous Test: Measures toxicity and localized irritation when the sample is in contact with live subdermal tissue (specifically, the tissue that the medical device is intended to contact).
Implantation Test: Measures toxicity, infection, and irritation of an intramuscular implantation of the compound into a test animal over several days.
Adhesives and sealants that qualify to this designation are typically very safe for use in medical devices. However, materials passing the USP class VI tests are not guaranteed to be biocompatible for every application. It's simply a strong validation that the materials used are of high quality with low levels of toxicity.
ISO 10993 Biocompatibility Testing
With the purpose of standardizing biological evaluation of medical devices worldwide, the International Standards Organization (ISO) developed ISO 10993- a set of standards outlining material categories, tests, and test methods used to determine the biocompatibility of materials.
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, and permanent). For each resulting medical device category ISO provides a set of suggested evaluation tests. Typical tests include:
* ISO 10993-4 Hemolysis
* ISO 10993-5 Cytotoxicity
* ISO 10993-6 Implantation 14 Days
* ISO 10993-10 Intracutaneous: Sensitization and Irritation
* ISO 10993-11 Systemic Toxicity
In general, adhesives and sealants are not required to pass all ISO tests. However, it is expected that they pass the cytotoxicity test. As a fast, standardized, sensitive, and inexpensive test, the cytotoxicity test concludes if an adhesive has any adverse effect on mammalian cells. It involves culturing cells in vitro and systematically exposing them to the material in question to see if any reactions or signs of toxicity show up over a few days.
In conclusion, since the ISO system applies the USP test methods as part of a larger, more rigorous strategy, meeting ISO standards is representative of a higher level of biocompatibility than meeting USP class VI standards.