Prior to clinical trials biocompatibility testing should be completed in regards to ISO 10993. The types of biocompatible tests needed for a particular device can be determined by using the toxicity table. General biocompatible tests include cytotoxicity, genotoxicity, irritation and implantation. By completing these tests you can determine how poisonous the device is to the cells and genes. It helps determine whether or not the device will destroy blood cells, if it is implantable or if it will irritate skin cells etc. A biomaterial associated with an implant device that interacts with the bone permanently is required to have cytotoxicity, sensitization, genotoxicity, implantation, and chronic toxicity and carcinogenicity tests completed. While a surface device that only interacts with the skin for a limited time only needs to have a toxicity, sensitization, and initiation test completed prior to clinical trials.

Reference: Week Three Lecture Notes

Before biomaterials can be used for testing during clinical trials, the product must undergo specific testing verification such as using the toxicity table to ensure that the product checks off requirements based on the designated application. The toxicity table helps one know how toxic the product is based on biological effects such as cytotoxicity, genotoxicity, sensitization, irritation, systemic toxicity, hemocompatibility, carcinogenicity, and biodegradation, etc. These devices are broken into three tiers, surface devices, external communication devices, and implant devices. All three of these devices must undergo the checklist to ensure it does not pose a harm to it's patients. This toxicity table was put into place to have companies follow strict protocols to ensure the safety of the general public. In fact, implant devices is more sensitive compared to surface device but this should not be overlooked so easily, in fact surface devices can be dangerous because of irritation, allergic reaction and body rejection.

As the others have mentioned already, referencing the Toxicity Table from ISO 10993, there are different tests required for different applications. Therefore, if you know what application you are planning to use the biomaterial for, you just reference the corresponding row in the toxicity table to determine what testing will be required. Several questions I have regarding the toxicity table: What exactly is the distinction between initial evaluation tests and supplementary evaluation tests? How do you know whether it is advisable to perform the "additional tests which may be applicable?" If you don't know the specific application of the biomaterial that you are working on, or if it may be applicable to a variety of devices with different applications, how do you select which biocompatibility tests to run?

As mentioned above in the week 3 lectures as well as from bb254, biocompatibility testing should be completed in strict accordance to ISO 10993. The table dictates, in relation to its intended application and criticality to the body (ex. tooth filling vs heart valve) the number and type of testing that should be performed to ensure the product is deemed “safe”. After all, nothing is 100% biocompatible.

Also in regards to srg36 question about selecting biocompatibility test to run when unsure of the use of the product, I believe that, when in doubt, all tests in question should be performed if reasonable judgement cannot be applied. This is to say that it is always safer to error on the side of caution when designing/ implementing medical devices and take some extra time (days to months) rather than face a massive unexpected recall of the product that will both cost the parent company a significant amount of money and no doubt tarnish their reputation as a medical device supplier.

As the others stated above, its essential to follow the ISO 10993 table in regards to implants, or orthopedics. However, when it comes to neural biomaterials, or drugs used to aid in other areas of the body, you should also consider performing an ADME test. This will allow us to see whether the drugs have acceptable absorption, distribution, metabolism, and excretion. Its important to make sure that drugs can travel to its targeted place successfully and reacts the way its expected.

Apart from the ISO Standard, Carcinogenicity is a crucial test for a biomaterial.Carcinogens are classified according to their mode of action as genotoxic or nongenotoxic carcinogens. The conventional test for carcinogenicity is the long-term rodent carcinogenicity bioassay.There could be even co-carcinogens that do not necessarily cause cancer on their own, but promote the activity of other carcinogens in causing cancer.

In 2014, FDA sent a very strong warning to physicians and medical device companies, because of the risk involved with laparoscopic power morcellators(LPM) used during different types of laparoscopic (minimally invasive) surgeries like treating uterine fibroids, hysterectomy or myomectomy. These surgeries break up small bits of tissues which might spread cells from uterine cancer. Therefore, a Carcinogenicity is extremely in determining how much of a role can a particular device play when it comes to spreading cancer.

The tests to assess the biocompability of the material should follow ISO 10993. The following tests should be done on the biomaterial for verification and validation of the product: Evaluation and testing within a risk management process, tests for genotoxicity, carcinogenicity and reproductive toxicity, tests for in vitro cytotoxicity, tests for irritation and skin sensitization.

Different applications will require different types of testing. The test will depend on the material used and the process that was performed to manufacture the final product.

When we test the biocompatibility of material especially for medical devices,there are some categories depending on final usages.As mentioned above, cytotoxicity, skin irritation, sensitization, systemic toxicity, and so on.ISO 10993 describes the biocompatibility test for medical devices.However, when you chek the biocompatibility of medical devices, I recommend to start with cytotoxicity. Most of cases, if the cytotoxicity is low, it is more probable to pass the rest of categories. Biocompatibility testing must done to meet current FDA and international standards. Biocompatibility testing requirements comes into effect if a product is scheduled for Pre-Market Approval (PMA) or 510k submissions. Biocompatiblity testing determines the biological reaction of a body to a product/device that comes in contact with it for a defined duration. USP Class VI United States Pharmacopeia (USP) tests Systemic Toxicity Test,intracutaneous test, and implantation test

Various tests need to determine the safety of the product before use in clinical studies (21 CFR 312.23(a)(8)). A complete description of material composition should be made available, detailed specification for formulation and chemical composition. The preclinical data is usually derived from animal studies. The test chosen should be geared towards the safety raised by your product. The FDA encourages one to design testing strategies that incorporate both testing of cellular product and delivery system in a single study. The animal studies should include biological response to the device/product, durability response, toxicology, bacterial endotoxin, pyrogen testing, study duration, sterilization and packaging. Tests may vary depending on its application. For neural biomaterial electrode stimulation tests may be required, for orthopedic mechanical testing and for urinary liquid flow testing may be required.

As many have mentioned like @bb254 and @dag56 before testing in clinical trials many tests need to be preformed. The biocompatibility testing needs to be performed in accordance with ISO 10993 including Cytotoxicity, Genotoxicity, Irritation, Systemic Tox, Hemocompatibility, Implantation, Toxikokinetics. A urinary catheter is an example of a mucous membrane Surface Device- This would mean for limited use- Cytotoxicity, Sensation, and Irritation/Intracutaneous reaction. For an orthopedic- is a Tissue/ Bone implant device that's permanent would require Cytotoxicity, Sensation, Irritation, Systemic Toxicity, Sub-chronic toxicity, genotoxicity, implantation, hemocompatabiltiy, chronic toxicity, and carcinogenicity. For example, a laparoscope would be Tissue/Bone/Dentin communicating External Communicating Device and would require a cytotoxicity, sensation, irritation as standard ISO evaluation tests. Overall, there are different types of tests based on body contact location and body contact duration.

Determining the biocompatibility is very important in analyzing a new biomaterial for a medical device. The testing done to verify the biocompatibility has to do with the ISO 10993-1 Test Matrix. After determining they type of device being used, the device is evaluated according to various factors, including cytotoxicity, sensitization, irritation or intracutaneous reactivity, genotoxicity, and implantation, and more. All these aspects are vital in ensuring that the device can be used in clinical trials, and eventually in the market. The two main factors that are mandatory to be tested in all types of medical devices are cytotoxicity and sensitization. The rest of the evaluations are dependent on the type of body contact there is with the medical device being used, surface, external communicating, or implant, and from there the location of the device, and then the duration the device will be used.

Assessing the material biocompatibility of the product (including the material of construction and final device) is critical for successful commercialization. The tests should follow ISO 10993 and type of tests will depend on application and exposure. For example, for an implant device in contact with tissue/bone it will require cytotoxicity, sensitization, genotoxicity, implantation, chronic toxicity, and carcinogenicity. Additional tests may be applicable such as irritation or intracutaneous reactivity, systemic toxicity (acute), and sub-chronic (sub-acute) toxicity. ISO 10993 is endorsed by FDA which has published guidance with their thinking on how to comply with it (link below).
https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm348890.pdf

An animal study is one of the most important steps in the process of translating biomaterials to clinical applications. But before going further to clinical trials, ISO 10993 standard will be ran to find out the initial biocompatibility of the material. Biocompatibility of the device depends on some of these factors: the chemical and physical nature of its component material, patient tissue types that it will be exposed to the biomaterial and the life-time exposure of the biomaterial.
ISO 10993 includes the following tests Cytotoxicity, Genotoxicity, Irritation, Systemic Tox, Hemocompatibility, Implantation, Toxikokinetics Chronic toxicity and carcinogenicity that helps evaluate the biocompatibility of a material. For example, a skin surface device will require Cytotoxicity, Sensitization and Irritation evaluation testing, compare to a bone/tissue implant device that would require more testing evaluation as follow; Cytotoxicity, Sensitization, Irritation, Implantation, Chronic toxicity and carcinogenicity.

To Study the Bio-compatibility of a brand new bio-material of which our device or product has been made, I will use ISO 10993-1 Test Matrix to determine what kind of test I should perform. And the decision of the test's I should perform on my product is completely based on the use of my product, for example where in the body my product will be used, The surface of the device will be in contact with the skin or muscles and etc. So for example if I use this brand new bio-material to make a product which is an implant then I have to perform this test's in reference to different categories my device fall in, for example the device will be in contact of tissue/bone or blood then the device will be implanted in the body for prolong, limited or permanent. And there are some test mentioned ISO 10993-1 which is mandatory to perform for before clinical trials regardless of the use of the bio-material like Cytotoxicity, sensitization and Irritation. The test marked on ISO 10993-1 chart with the red cross are mandatory to perform and the test marked with a blue dot are optional.
As I said before these tests will be completely depend on the intended application of our material, for example if we use this material for some implant orthopedic application then we have to perform the test listed in the third category OF ISO 10993-1 some of the test we will perform in case are cytotoxicity, sensitization, Genotoxicity, chronic toxicity and carcinogenicity. On the other hand if I use this material to make a stent which will come in contact with a soft tissue and a circulating blood in this case I have to perform some additional testing to check the bio-compatibility of my product like Systemic Toxicity, Irritation, Sub-Chronic Toxicity(if it is Permanent use), Genotoxicity and Hemocompatibility.