Biocompatibility Testing for Medical Devices

The aim of biocompatibility testing for medical devices is to show that they are safe to use with human tissues and physiological systems. The demonstration is critical for US FDA 510k and MDR CE Marking regulatory submissions for all risk classes and types of medical devices. Analytical chemistry, in vitro experiments, and animal models are used to study system biocompatibility.

We provide a Biocompatibility Testing Service for Medical Devices applying for new MDR CE Marking and US FDA 510k Clearance. Our Labs in India, Hong Kong & Israel are accredited. We offer quick and economical pricing. Bio-compatibility refers to the interaction of medical devices with human tissues and physiological systems during the treatment process.

Biocompatibility Testing depends on the following factors:

  • Chemical and Physical nature of the materials used in the construction of the device
  • Type of patient tissue and area of exposure
  • Duration of human contact

European Harmonized Standards and US FDA recommend the current version of ISO 10993-1 (Guidelines for Biological Evaluation of Medical Devices) for regulatory compliance.

The following are the vital biocompatibility testing to be followed by medical device manufacturers according to ISO 10993-1 (Biological evaluation of medical devices, Part 1: Evaluation and testing within a risk management process )

Genotoxicity is a routine protocol that has to be performed to detect the effect of a medical device in causing genetic mutation, chromosomal aberrations and or toxicity of genetic material. It is also committed to determining the mutagenic and clastogenic materials or compounds that may be carcinogens.

The medical device genotoxicity is analyzed through in-vitro and in-vivo methods using the appropriate ISO standards as mentioned below.

  • Standard Reference: ISO 10993-3 (Tests for genotoxicity, carcinogenicity and reproductive toxicity)
  • Testing Duration = 4 Months
  • Approximate Investment Cost: 2500 – 5000 USD based on the protocol.

The interaction of devices or biomaterials with blood is an immediate and severe concern during safety assessment. The effects of the biomaterial may be broadly classified into cellular and humoral effects.

  • Standard Reference: ISO 10993-4 (Selection of Tests for Interactions with Blood, suggests areas of hemocompatibility that should be tested, including thrombosis, coagulation, platelets, and platelet function, haematology, and immunology)
  • Testing Duration = 5 Months
  • Approximate Investment Cost: 3500 – 5000 USD based on the protocol.

The medical device’s ability or the material to inhibit cell proliferation in cell lines is determined through the in-vitro cytotoxicity test. The parameters such as cell growth, cell proliferation and morphological effects of the cells are determined in this test.

  • Standard Reference: ISO 10993-5 (Tests for In Vitro Cytotoxicity)
  • Testing Duration = 3 Months
  • Approximate Investment Cost: 500 – 800 USD based on the protocol

The local effects of an implantable device or a material on tissue are assessed by implantation procedures that introduce the material or device, or a representative portion, into the tissue.

  • Standard Reference: ISO 10993-6 (Tests for local effects after implantation)
  • Testing Duration = 4 Months
  • Approximate Investment Cost: 6500 – 9500 USD based on the protocol

A sensitization test is conducted for a medical device to detect its hypersensitivity potential or allergic symptoms on the human skin.

The medical device or the material extracts are injected or topically applied to the test system and are observed for erythema and oedema at appropriate intervals for detecting the sensitizing and allergic potency of the test item (extracts).

  • Standard Reference: ISO 10993-10 (Tests for Irritation and Sensitization recommends either of these tests)
  • Testing Duration  = 4 Months
  • Approximate Investment Cost: 800 – 1300 USD based on the protocol.

Irritation tests are performed to determine the medical device’s potency to irritate dermal, ocular, and mucosal sites. The irritational effects are measured by the localized inflammatory response caused due to single, repeated, or continual exposure to the extracts from the medial device. The symptoms such as pain, oedema, and erythema are observed in this test.

  • Standard Reference: ISO 10993-10 (Tests for Irritation and Sensitization) & ISO 10993-12
    (Sample preparation and reference materials)
  • Testing Duration = 4 Months
  • Approximate Investment Cost: 800 – 1300 USD based on the protocol

Acute systemic toxicity is to be done to evaluate the medical device effect in short-term exposure. The extracts are administered one time through oral, dermal, and inhalation means within 24 hours, and various clinical signs and symptoms are observed for 14 days.

Any significant change in clinical signs and symptoms is noted, and the systemic effects are observed in detail through gross pathology and blood parameters. The test also aids in determining the lethal dose (LD50) of the extracts from the medical device.

  • Standard Reference: ISO 10993-11 (Tests for Systemic Toxicity)
  • Testing Duration = 4 Months
  • Approximate Investment Cost: 2000 – 3000 USD based on the protocol

The medical device’s potential to cause fever is determined through the Pyrogenicity test. The common pyrogen in medical devices or pharmaceutical products is bacterial endotoxins.

The contamination of the medical device or the pharmaceutical product leads to the presence of pyrogens in them. Hence the test is necessary to perform through the in-vitro or in-vivo methods to confirm it is non-pyrogenic before releasing the medical device or the product into the market.

  • Standard Reference: ISO 10993-11 (recommends testing the pyrogenicity potential of extractable substances derived from material leaching).
  • Testing Duration = 4 Months
  • Approximate Investment Cost: 200 & 400 USD based on the protocol.

Chemical characterization of the medical device is a crucial part of biocompatibility evaluation. Manufacturers should provide the composition of the medical device and its toxicity profile to prove its safety in clinical use.

The chemical characterization shall be performed through various techniques like NMR, FTIR, MS, GC-MS, etc.; the ISO 10993-18 standard is adopted to evaluate the leachable profile of the materials used in the manufacturing of the medical device.

The results obtained in chemical characterization outline the exact structural and functional properties of the medical device. It also aids in planning further in-vitro and in-vivo evaluation of the medical device.

    • Standard Reference: ISO 10993-9 (Identification & quantification of potential degradation products)
    • Standard Reference: ISO 10993-13 (Identification & quantification of degradation products from polymeric medical devices)
    • Standard Reference: ISO 10993-14 (Identification & quantification of degradation products from ceramics)
    • Standard Reference: ISO 10993-15 (Identification & quantification of degradation products from metals and alloys)
    • Standard Reference: ISO 10993-16 (Toxicokinetic study design for degradation products & leachable)
    • Standard Reference: ISO 10993-17 (Establishment of allowable limits for leachable substances)
    • Standard Reference: ISO 10993-18 (Chemical characterization of materials)
    • Standard Reference: ISO 10993-19 (Physio-chemical, morphological & topographical characterization of materials)

To investigate the biocompatibility of a medical device material used in the construction and nature of releasing leachable matters to identify and preclude subsequent toxicology problems with finished devices.

Regulatory bodies ask for analytical characterization of device materials and potential leachable per ISO 10993-17 and ISO 10993-18 testing.

CE candidates are becoming more mindful that they will be asked to provide this information by the reviewer.  
However, since this is a newer concept than biocompatibility testing, the existing requirements in this field are also a little hazy.
Our labs in Israel, Germany, Hong Kong, and India are accredited by AAALAC, NABL, ISO 9001, DSIR, US FDA, and IBSC. Before the start of the actual research, we have protocols. Our toxicologist will respond to technical questions from FDA 510k reviewers as well as concerns from Notified Bodies. There isn’t a single laboratory that does it!!! We offer Tax-Free best prices Globally!!!

Medical Device Testing

Medical devices are very critical as they have a direct impact on the lives of humans. To deliver superior and safe experiences to humans, medical device manufacturers continuously innovate the devices with State of Art technology, software, and materials. However, the benefits of improvements come with hazards and should be mitigated by taking appropriate measures. The importance of medical device testing comes in this gesture.

Medical Devices have to demonstrate safety and clinical effectiveness based on the intended purpose. Certified laboratories should perform these tests to prove that the device is safe and clinically effective both for the user and the patient.

India is one of the most economical destinations for testing globally with GLP / FDA / DEA / ISO/IEC 17025:2005 accredited Laboratories. We accept business from all over the world.

EU MDR and FDA 510k Test requirements for the below Medical Devices

  • A. Testing of Medical Equipment’s functions on electrical Energy (Active Medical Device)
  • B. Software Medical Device testing (considered under active Medical Device)
  • C. Non-Active and Implantable Medical Device testing.

A. Active Medical Device Testing

Electrical Safety & Electromagnetic Safety (IEC 60601-1 Series – Third Edition)

The third edition of IEC 60601-1 represents a significant standard in the family of IEC 60601 medical electrical equipment safety standards. First published in 1977, IEC 60601-1 has become the ‘bible’ of electromedical equipment safety and the parent standard of over 60 particular device standards ranging from diagnostic electrocardiographs to electron accelerators used in radiotherapy. These tests should be carried out on all active electrical products. Compliance with all these standards should be taken into account during the design process.

B. Software Medical Device Testing

The number of medical devices which are software-operated has been rising sharply in recent years. Malfunctions of the software may be life-risking. Therefore, software validation tests have become the most demanding. Conformity Assessment procedures require consideration of the development lifecycle procedures for document control and configuration management and control of combinations between software versions and intended hardware. Published software medical device standards (not an exhaustive list) include IEC 62304 (2006), Medical Device Software-Software Life Cycle Processes, ISO/IEC 90003 (2004), and IEC 60601 series.

C. Non-Active and Implantable Medical Device Testing

The Non-Active Medical Devices generally considered are the following

  • A device that, in whole or part, penetrates inside the body, either through a body orifice or through the surface of the body.
  • Any natural opening in the body, the external surface of the eyeball, or any permanent artificial opening, such as a stoma.
  • A device that penetrates inside the body through the body’s surface, with the aid or in the context of a surgical operation.
  • Any device which is intended to be introduced into the human body or to replace an epithelial surface or the surface of the eye by a surgical intervention that is designed to remain in place after the procedure

Biocompatibility Testing for Medical Devices is done to verify that the product is not toxic and does not cause allergic reactions. These tests are based on the ISO 10993-1 harmonized standard. Selection of tests and understanding of each test is essential.

Medical EMC and Electrical Testing

Medical electrical devices and equipment must meet the IEC 60601-1 and IEC 60601-1-2 standards for general safety and EMC. Aside from that, product-specific collateral requirements must be followed. The latest version of the specification, IEC 60601 3rd Edition, Am. 1, is accepted by medical device regulators in most markets worldwide.

Medical device regulators require electromagnetic compatibility (EMC) testing in markets such as the United States, Europe, and Australia to ensure the products are stable and perform well for consumers and patients. Regulators require EMC testing to decide whether a system can operate safely and efficiently in its intended operating environment without creating electromagnetic disruptions.

In General Safety Testing as per IEC 60601-1 following are the key test parameters:

  • Earth-bond Testing
  • Leakage Measurement including
  • Earth Leakage,
  • Enclosure Leakage and
  • Applied Part or Patient Leakage: Normal Condition
  • Patient Leakage: Single Fault Condition, Supply Open
  • Patient Leakage: Single Fault Condition, Earth Open
  • Patient Leakage F-Type
  • Patient Auxiliary Current: Single Fault, Supply Open
  • Patient Auxiliary Current: Single Fault, Earth Open

and more…

We offer Testing Services as per IEC 60601-1 requirements.

  • EMI / EMC Testing:

We offer testing services for EMC as per IEC 60601-1-2, namely:

  • Electrostatic discharge (ESD) immunity test
  • Electrical fast transient (EFT) immunity test
  • High Energy Surge immunity test
  • Damped Oscillatory waves immunity test
  • Voltage Dips and Interruptions

We can also provide Product Specific Standard testing services for Medical Electrical Devices such as Baby Warmers, Electrosurgical Cautery, Foetal Doppler, Suction Units, Hospital Furniture, Autoclaves, Beds, OT Lights, OT Tables, Centrifuges, Vital Psylogical monitors, Home Healthcare Products, and so on.

Across the Globe, IEC 60601 helps ensure the safety of electrical and electronic medical devices. Our expertise in helping ensure that your medical devices and products comply with IEC 60601 standards and are ready for export to global markets. We can help you at any stage of your medical device project, ensuring the best certification option for your product, markets, and business.

IEC60601 supports electrical and electronic equipment security around the world. Our experience will help you ensure that your medical devices meet IEC 60601 specifications and can be exported to international markets. We will assist you at any point in your project to ensure that the right certification requirements are based on your application and industry.

Some of our IEC 60601 Medical Safety Testing services include, not limited to, CE Marking class I, IIa, IIb, and III devices.

  • Risk management and integrated quality system (ISO 13485 and/or ISO 14971) assessments
  • Software and usability assessments to support various IEC 60601 clauses

Risk Assessment

We offer impartial third-party support in all aspects of the consultation, full product safety testing, and completion of a Declaration of Conformity (DoC) for Technical File compilation and review. Compliance with ISO 14971 is a crucial requirement for IEC 60601

Applying risk management to medical devices is a mandatory requirement when demonstrating compliance with the IEC 60601 series of standards. Without this documentation, compliance is not possible; we can assist you with this and provide support and guidance on ISO 14971 risk management, including:

  • Bespoke and one-to-one training
  • Documentation and procedure review
  • Production of essential documentation
  • Gap Analysis, remediation & mitigation
  • CE Marking of electrical medical devices

More information about Risk Analysis as per ISO 14971>>

I3CGlobal provides you with guidance through every step of the CE Marking process for medical devices, ensuring successful and efficient product launches.