Medical device biological testing is a critical part of the regulatory approval process. In this blog, we have discussed the various medical device biological testing methods. Additionally, we have mentioned the parameters used to choose the appropriate test method for your device.
What is biological testing of medical devices?
Biological testing of medical devices is a series of laboratory and in-vivo tests performed to evaluate how a device and its materials interact with the human body. The goal is to ensure the device is safe for its intended use and does not produce toxic, allergenic, or other adverse biological reactions. Medical device biological testing is a mandatory requirement for most regulatory authorities. These tests are aimed to ensures medical devices do not cause harmful biological responses, such as irritation, cytotoxicity, systemic toxicity, upon use.
Key aspects of medical device biological testing methods
- Material characterization: The device’s materials are identified and analyzed. Additionally, its potential to release compounds into the body is evaluated.
- Biological testing (In Vitro/In Vivo): Laboratory tests are performed to assess effects on biological systems. Cytotoxicity tests evaluate if the material will kill cells. Irritation tests focus on chances of skin or tissue irritation. Sensitization tests determine whether the device will trigger an allergic response. Systemic toxicity tests are performed to assess if it causes harm to the entire body.
- Biological evaluation report: The medical device biological testing has to be properly documented. A document summarizing the findings is required to demonstrate compliance with standards and regulations.
Important role of medical device biological testing
Biological testing of medical devices is vital for patient safety. Additionally, it is a crucial regulatory requirement.
- Product reliability: Medical device biological testing methods are aimed at ensuring your device performs safely throughout its lifecycle.
- Risk management: By ensuring biological safety, these tests reduce chances of product recalls and reputational damage.
- Patient safety: The primary goal of medical device biological testing is to ensure the device will not release toxic or harmful substances and harm the patient.
- Regulatory compliance: Most regulatory bodies, such as the FDA, EU MDR, CDSCO, require mandatory biological testing of medical devices.
- Market approval: Biological testing of medical devices is mandatory in most countries to secure market approval.
8 top medical device biological testing methods
- Sensitization testing: This test assesses the potential for a device to cause allergic reactions or hypersensitivity. The aim is to detect the potential for delayed, dose-independent allergic responses from repeated or prolonged exposure. The test involves exposing test animals, such as guinea pigs, to the device’s materials or extracts during both an induction and a challenge phase. The animal’s skin is then scored for signs of an allergic reaction, such as swelling and redness. The guideline followed is ISO 10993-10.
- Cytotoxicity testing: This is a baseline test performed for almost all medical devices. Cytotoxicity test is the basic test among all medical device biological testing methods. The aim is to determine whether the device’s materials or the chemicals they release are toxic to living cells. A sample of the device is placed in contact with cultured mammalian cells. Then, the cells are observed for damage or death. The assessment performed can be qualitative (visual observation of cell morphology) or quantitative (using dyes to measure cell viability).
- Irritation testing: This test determines if a device will cause localized inflammation or irritation. The aim is to evaluate a device’s potential to cause localized skin or mucous membrane irritation. The test involves applying extracts from the device to animal tissue, such as skin. Then, signs of irritation, like erythema and edema, are looked for. In-vitro methods using reconstructed human epidermis models are also increasingly being used. The guideline followed is ISO 10993-23.
- Systemic toxicity testing: This test assesses the device’s potential to cause harmful effects to the entire body. Systemic toxicity testing aims to evaluate the effect of extractable and leachable substances on the body’s major organ systems. Device extracts are administered to test animals, which are then monitored for acute, sub-chronic, or chronic effects.
- Implantation testing: This test is specifically for devices that are implanted into the body. The aim is to assess the local tissue response to the implanted device material and how it degrades over time. A sample of the device material is implanted into living tissue (e.g., bone or muscle) for a set duration. Then, the implantation site is evaluated macroscopically and microscopically for inflammation or tissue necrosis.
- Hemocompatibility testing: This hemocompatibility test is performed for devices that come into contact with blood. The goal of the test is to ensure the device does not cause blood clots, damage red blood cells (hemolysis), or activate the immune system (complement activation). In-vitro tests are conducted to evaluate the device’s interaction with blood components.
- Genotoxicity and carcinogenicity testing: The test examines whether device materials can damage DNA or cause cancer. Assays, such as Ames test, are used to check for DNA mutations. Long-term studies are performed on animals to detect tumor formation. Genotoxicity and carcinogenicity tests are required for medical devices intended for chronic or lifetime exposure.
- Subacute and chronic toxicity testing: These tests evaluate long-term exposure effects of the medical device. The period ranges from weeks to months. The tests aim to evaluate prolonged effects of material exposure. They provide data on cumulative toxicity, carcinogenicity, or organ damage. Notably, these tests are mandatory for long-term implants and permanent devices.
Factors affecting medical device biological testing methods
We have discussed the different medical device biological testing methods. The type and extent of biological testing required will depend on various factors. Regulatory authorities want manufacturers to assess these factors and choose the applicable biological tests accordingly. Hence, it is important to carefully consider the below mentioned factors before choosing the test method.
- Type of device (implant, disposable, diagnostic, etc.)
- Nature of body contact (skin, blood, bone, tissue, etc.)
- Contact duration (short-term, long-term, permanent implant)
- Device materials (metal, polymer, ceramic, silicone, etc.)
- Sterilization process (gamma, EtO, autoclave, etc.)
International standards for biological testing
International standards have been formulated for biological testing of medical devices. These standards provide guidelines on selecting tests based on device category and contact type. ISO 10993 is accepted by most global regulatory authorities. We have presented some of the important guidelines mentioned in ISO 10993:
- ISO 10993-1: Evaluation and testing within a risk management process
- ISO 10993-5: Tests for in vitro cytotoxicity
- ISO 10993-10: Tests for irritation and sensitization
- ISO 10993-11: Tests for systemic toxicity
Common challenges faced
Challenges in the biological testing of medical devices range from scientific and technical complexities to regulatory, and ethical hurdles. These issues often delay market entry.
- Scientific and technical challenges: Medical devices are made of numerous, highly complex materials. Identifying and quantifying all potential toxic compounds can be difficult, especially when they are present at trace levels. Moreover, in vitro tests are designed for short-term exposure. They cannot adequately simulate the long-term or cumulative biological effects that implanted or long-term devices may have. Furthermore, detecting and quantifying potentially harmful chemicals at very low levels is challenging. It requires highly sensitive and precise analytical methods and complex data interpretation.
- Regulatory and documentation challenges: The international standards for biological testing, such as the ISO 10993, are constantly being updated. It is difficult to keep up with the changes. Moreover, comprehensive, enhanced documentation and traceability for every stage of the testing lifecycle is required. Furthermore, testing drug-device combination products can be difficult, as the two have distinct regulatory pathways.
- Ethical concerns: Animal experiments remain a critical and often necessary part of medical device biological testing methods. This raises ethical concerns and pushes for the development and validation of alternative in-vitro and in-silico biological testing methods.
Biological testing of medical devices is required by most regulatory authorities. Need help choosing the appropriate medical device biological testing methods for your device? Drop an email at [email protected] or call/Whatsapp on 9996859227 and we will be more than happy to help.
