Biological Evaluation is the series of tests which is performed pre-clinically either in-vivo or in-vitro techniques to protect the patient from any biological risk and to assess the safety of the medical device. It is mainly performed to measure the bio compatibility of medical device or any material with the biological system. As the medical device comes in contact with any part of the body, it should be assessed for its safety upon use.
The word Biocompatibility means the interaction between a medical device and the tissues and physiological systems of the patient treated with the device. It is one of the method to assess the safety of the device. The Device evaluation is based on invitro tests, invivo tests (animal models) or analytical chemistry.
The biocompatibility of any device depends on various factors, like
- Physical and chemical nature of the device and its materials
- Types of patient tissue that is exposed to the device
- Duration of the exposure
As there is no risk free medical device or device material available so, the manufacturer’s goal is to minimize the risk and increase the benefits to the users. Thus Biological evaluation plan is an essential element with weighing the risks and benefits of medical devices and to prove the safety of the device by complying to the relevant standards.
As the ISO procedures tend to be more stringent, so companies planning to register their product in both Europe and the U.S. should follow ISO test methods i,e ISO Standard 10993
[Testing policies which comply with the ISO 10993 family of documents are acceptable in Europe and Asia]
Selection of tests in biocompatibility matric which categorize the medical devices based on the type and duration of the body contact. Potential biological effects also listed. In ISO 10993 -1 does not give specific tests for any particular medical device but framework to design the biocompatibility tests. The tests are listed to be performed based on area of contact between medical device and patient and its duration of contact. The first step in this is to characterize the device and device components chemically.
Chemical characterization will reflect the nature and duration of the clinical exposure and evaluate the biological safety of the device. It mainly depends on the nature of the materials used, e.g. polymers, gels, liquids, metals, ceramics, composites or biologically sourced materials.
The below are the available biocompatibility tests.
- Irritation Tests
- Acute Systemic Toxicity
- Sub chronic Toxicity
- Implantation Tests
- Carcinogenesis Bioassay
- Reproductive And Developmental Toxicity
- Preclinical Safety Testing
- Histopathology Services
Cytotoxicity: It is an invitro test used to assess the biocompatibility of a material or extract through the use of isolated cells. These are used mainly in evaluating the toxicity or irritancy potential of materials and chemicals and help to screen the materials prior to in vivo tests.
Sensitization: Sensitization will be performed using specific chemicals and help to determine whether the material or device contains any chemicals which cause any adverse local or systemic effects after repeated or prolonged exposure.
Irritation tests: These tests will determine the local irritation potential of devices, materials or extracts, using sites such as skin or mucous membranes in animal models.
- Intracutaneous test mainly for externally communicating or internal contact with the body or body fluids.
- Skin Irritation test for devices that have external contact with intact or breached skin like topical devices
- Mucous Membrane Irritation tests for externally communicating contact with intact natural channels or tissues.
Acute Systemic Toxicity: Which mainly detects leachable that produce systemic toxic effects. In the Biocompatibility Matrix this test is recommended for all blood contact devices. Material Mediated Pyrogen test will assess the material for pyrogenic response, or fever, after introducing into the blood.
Sub-Chronic Toxicity: These tests are used for devices to determine harmful effects for longer-term or multiple exposures to test materials. These tests are required for all permanent devices which have prolonged contact with internal tissues.
Genotoxicity: These evaluations used in both in vitro and in vivo tests to detect mutagens, substances which can directly or indirectly induce genetic damage. As per ISO 10993-1 this assessment of genotoxic potential is used for permanent devices and devices with prolonged contact (>24 hours) with internal tissues and blood
Implantation Tests: These evaluations used in devices or materials which are in direct contact with living tissue other than skin ( e.g. implantable devices, surgical sutures, surgical ligating clips etc..). These tests used in devices which are implanted for either short-term or long- term periods.
Hemocompatibility: These evaluations done for blood compatibility in Devices or Materials which used in blood contacting devices like intravenous catheters, blood transfusion sets, hemodialysis sets to establish their safety.
Carcinogenesis Bio-assay : These assays are used to evaluate the tumorigenic potential of device or test materials and/or extracts in single or multiple exposures
Reproductive And Developmental Toxicity : These evaluations used to determine the potential effects in devices or materials and/or extracts on fertility, reproductive function, and prenatal and early postnatal development. It will done for mainly devices which has permanent contact with internal tissues.
Pharmacokinetics: These studies used to investigate the metabolic process of absorption, distribution, metabolism and elimination of toxic leachable and potential degradation products from device or test materials and/or extracts. These are mainly used in bio-absorbable materials
Preclinical safety Testing: These evaluations will determine pharmacological and toxicological effects in animals and it is base for initiation of human studies.
Histopathology: These evaluations mainly for Implant studies as device or test material is placed in direct contact with living tissue.