Understanding the biocompatibility of silicone can help you ensure product compliance and quality, thereby avoiding overseas entry risks, stabilizing cooperation and expanding the market. This article will focus on introducing the relevant regulations and tests for silicone biocompatibility, as well as related applications. We hope it will be helpful for your business.
What is Silicone Biocompatibility?
When your product comes into contact with human tissues or body fluids, biocompatibility refers to the ability of a material to perform with an appropriate biological response under its intended use conditions. This implies that when choosing materials, it needs to:
- Chemical Inertness: No harmful chemical reactions with biological environments
- Non-cytotoxicity: Does not cause unacceptable cell damage or reduced cell viability
- Non-sensitization: No allergic immune reactions
- Systemic Non-toxicity: Does not cause harmful systemic effects after exposure
Silicone has many inherent advantages, such as chemical inertness, temperature resistance, anti-aging properties, and low surface energy. However, not all silicone meets the biocompatibility standards; its performance depends on:
- Raw material quality
- Type of additives (Coloring agents, fillers, etc.)
- Curing system (Platinum vs Peroxide Curing)
- Production process and post-treatment steps
Only medical-grade silicone materials manufactured under controlled formulations and processes are suitable for biocompatible applications.
Regulations for Silicone Biocompatibility
ISO 10993 Series
If you are involved in the production of silicone products related to medical devices, ISO 10993 is the globally recognized biological evaluation framework for medical devices and is widely used to support EU MDR biological safety requirements. This standard adopts a modular testing strategy based on risk assessment and has extremely high flexibility.
You can customize the corresponding testing items according to the actual application of your products. However, its testing period has a wide range, usually spanning from 2 to 24 weeks, and the testing cost ranges from $5,000 to over $100,000, which may increase your production costs.
However, this standard is applicable to all types of medical device products and supports compliance with EU MDR biological evaluation requirements. It serves as the core compliance guarantee for the products to be sold globally and in the EU market.
USP Class VI
If your main target market is the United States, then understanding the USP Class VI is even more important. It is a material classification of the US Pharmacopeia and is commonly referenced in FDA submissions. It is applicable for the medical device approval reviews in the US market.
This standard testing mode is fixed and only includes three core tests: full-body injection, intradermal injection, and implantation. The flexibility is extremely low, and a uniform testing standard is applied to all materials.
The testing period is relatively stable, concentrated in 4 to 6 weeks, and the cost is controlled between $8,000 and $12,000. Compared to ISO 10993, your production cost is lower.
However, you should be aware that passing the standard test only meets the basic entry requirements of the United States, and it does not necessarily meet the compliance standards of the EU MDR. USP Class VI alone is generally insufficient to meet the biological evaluation requirements of the EU MDR for finished medical devices.
Test Standards for Silicone Biocompatibility
ISO 10993 Series Test Standards
Basic Tests
The table below lists the general basic tests. These are the most common biological tests for medical silicone products. Based on your device class and risk assessment, you may need to conduct part or all of them to complete ISO 10993 biological evaluation. In basic tests, silicone typically performs well and passes.
| Test Item | Standard | Purpose | Typical Performance of Silicone |
| Cytotoxicity | ISO 10993-5 | Evaluate whether the material causes cell damage or death | Passed (Platinum-cured silicone generally achieves a cell survival rate of ≥70%) |
| Sensitization | ISO 10993-10 | Evaluate potential allergic reactions | Negative (No sensitization response) |
| Irritation / Intracutaneous Reaction | ISO 10993-23 | Evaluate local irritation risks | Low irritation potential, irritation index ≤ 1.0 |
Extended Tests
The table below summarizes the advanced extension test. You can choose to conduct it based on the contact duration and usage type of the medical device as needed. This can further comprehensively verify the biocompatibility of your product and meet higher compliance requirements.
| Test Item | Standard | Application Type | Description |
| Acute Systemic Toxicity | ISO 10993-11 | All contact types | Toxic reactions caused by single exposure |
| Subacute / Subchronic Toxicity | ISO 10993-11 | Long-term / permanent contact | Cumulative effects after repeated exposure |
| Chronic Toxicity | ISO 10993-11 | Permanent contact (>30 days) | Effects from long-term exposure |
| Genotoxicity | ISO 10993-3 | Permanent contact | Detect DNA damage, e.g. Ames test |
| Carcinogenicity | ISO 10993-3 | Permanent contact | Assessment of long-term carcinogenic risks |
| Implantation Reaction | ISO 10993-6 | Long-term / permanent contact | Histological evaluation of local inflammation and fibrosis |
| Hemocompatibility | ISO 10993-4 | Blood-contacting devices | Hemolysis, thrombosis and platelet adhesion |
| Pyrogenicity | ISO 10993-11,or related pyrogen testing methods | Implants / blood-contacting products | Check for pyrogenic reactions |
USP Class VI
USP Class VI is the highest biological reactivity classification under the USP plastic testing
system. You can consider it as an important evaluation point for screening silicone raw materials.
While ISO 10993 is the complete assessment for final medical device products. USP Class VI certification may support material selection, but finished device biocompatibility evaluation is still required. The following table summarizes the 3 testing methods and standards of USP Class VI for you:
| Test | Method | Pass Standards |
| Systemic Injection Test | Inject material extract into mice and observe toxic reactions | No abnormal toxicity, no death and no significant weight loss |
| Intracutaneous Test | Perform intracutaneous injection on rabbits and examine local irritation | No erythema, edema or other irritation reactions |
| Implantation Test | Implant materials under rabbit skin and conduct histological examination weeks later | No obvious tissue abnormalities; the difference in capsule thickness compared with control materials ≤ 1.0 |
Applications of Biocompatible Silicone in Medical Devices
Limited Contact
If your medical silicone products are used for limited contact, with a contact duration of no more than 24 hours, three basic tests are required: cytotoxicity, sensitization, and irritation. The typical applications of such products are as follows:
- Syringe plunger
- Mask sealing ring
- Vial stopper
- Medical suction bulb
- Tourniquet
- Stethoscope ear tips
- Thermometer probe cover
Prolonged Contact
The duration of prolonged contact usually refers to 24 hours to 30 days. If you produce such silicone medical products, in addition to undergoing basic tests, you also need to pass the subacute/subchronic toxicity to ensure the safe use of the products. Typical applications are as follows:
- Medical catheter
- Endotracheal tube cuff
- Scar patch
- Insulin pump tubing
- Ostomy bag sealing ring
- Orthopedic pad
Permanent Contact
Because the contact duration exceeds 30 days, the permanent contact type medical silicone products have the strictest requirements. To produce such products, you need to pass all tests, including chronic toxicity, genotoxicity, carcinogenicity, and implantation reactions. The main typical applications are as follows:
- Pacemaker insulation layer
- Artificial joint cushion
- Cochlear implant coating
- Cranial repair plate
- Drug sustained-release carrier
FAQ
What Are Extractables and Leachables in Silicone Biocompatibility?
Extractables refer to the chemical substances that precipitate from silicone under strict laboratory conditions, while leachables are the substances that precipitate during normal clinical use.
Commonly precipitated substances from silicone include low-molecular cyclic siloxanes, residual catalysts and colorants, as well as processing additives and other additives.
Does Sterilization Affect the Biocompatibility of Silicone?
Yes, there will be a significant impact. And different sterilization methods have different effects on silicone. Although ethylene oxide is basically suitable, residual substances need to be tested; gamma rays and electron beams may alter the properties of silicone and cause the release of oligomers.
Most medical silicone products can be sterilized by steam high-pressure methods. However, if you use them repeatedly, the silicone will age. The impact of dry heat sterilization depends on temperature and exposure duration.
Can Original Silicone Biocompatibility Data Be Used for FDA Submissions?
Yes, but there are conditions. You need to do the following three things:
First, the formula of this silicone material must be exactly the same as the one you are using. Second, no new migratable substances should be produced during your manufacturing process. Finally, you need to use compatible sterilization methods because ethylene oxide, gamma rays or steam sterilization may alter the biocompatibility.
How Long Does Silicone Biocompatibility Testing Take?
The three basic tests: cytotoxicity, sensitization, and irritation, usually take 4 to 6 weeks; if further subacute/subchronic toxicity tests are conducted, all together they may take 8 to 12 weeks. The complete chronic toxicity test combined with genotoxicity and implantation test could take 4 to 6 months.
What Are the Differences in Biocompatibility between Platinum-Cured Silicone and Peroxide-Cured Silicone?
Because platinum-cured silicone has no cross-linking by-products and very little residue, it has a low risk of biocompatibility issues. Therefore, it is mostly used for implants and long-term contact devices.
However, peroxide-cured silicone will produce small molecule residues. You need to perform a secondary curing process. Thus, the risk of biocompatibility is higher, and it is only suitable for short-term and common medical products.
Does Silicone Require Separate Biocompatibility Testing for Each Specific Device?
Yes. Because different surface areas and thicknesses will affect the release amount of the extractables. Moreover, different processing conditions, disinfection methods, and the contact duration with different equipment will all influence the biocompatibility of the silicone.
Final Thoughts
Legensilico, as a silicone manufacturer with over 20 years of experience, can provide you with high-quality medical silicone products. If you are interested in our silicone products or want to learn more about silicone biocompatibility, please feel free to contact us at any time.
