The new article provides further clarifications on the applicable classification system, as well as testing requirements to be considered.
Table of content
The Egyptian Drug Authority (EDA), the country’s regulatory agency in the sphere of healthcare products, has published a guidance document dedicated to preclinical testing and clinical investigation for medical devices. The document provides an overview of the applicable regulatory requirements, as well as additional clarifications and recommendations to be taken into consideration by medical device manufacturers and other parties involved in order to ensure compliance.
At the same time, it is important to mention that provisions of the guidance are non-binding in their legal nature, nor they are intended to introduce new rules or impose new obligations. Moreover, recommendations provided in the guidance could be subject to changes, should such changes be reasonably necessary to reflect corresponding amendments to the underlying legislation.
Medical Device Classification
The scope of the guidance covers, inter alia, the aspects related to the classification of medical devices. As explained by the authority, the classification of medical devices is based on their potential to cause harm, determined by factors such as risk level, duration of contact, invasiveness, and the part of the body affected.
Key criteria include:
- Risk Level: Ranges from low to high, depending on potential hazards.
- Duration of Contact: No contact, transient, short-term, long-term, or implantable.
- Invasiveness: Non-invasive, indirectly invasive, invasive concerning body orifices, and surgically invasive.
- Affected Body Parts: Skin, heart, blood, teeth, spinal structures, etc.
- Intended Purpose: Diagnostic, therapeutic, or monitoring.
If multiple classification rules apply, the device is assigned the highest applicable classification. Manufacturers must justify their classification decisions with supporting documentation.
Regulatory Classification Systems
Devices are classified differently across regulatory frameworks:
- IMDRF Classification System:
- Class A (Low Hazard): Bandages, tongue depressors.
- Class B (Low-Moderate Hazard): Hypodermic needles, suction equipment.
- Class C (Moderate-High Hazard): Lung ventilators, bone fixation plates.
- Class D (High Hazard): Heart valves, implantable defibrillators.
- EU MDR and EDA Classification System:
- Class I (Lowest Risk): Stethoscopes, wound dressings.
- Class IIa (Low-Medium Risk): Oxygen masks, hearing aids.
- Class IIb (Medium-High Risk): Ventilators, intensive care monitors.
- Class III (Highest Risk): Pacemakers, absorbable sutures, joint replacements.
Scientific Evidence for Medical Devices
Under the general rule, medical devices are evaluated using clinical and non-clinical testing methods to ensure safety and effectiveness:
- Clinical Testing: Includes randomized trials, case studies, human experience reports, and specimen testing (e.g., DNA, tissues).
- Non-Clinical Testing: Covers mechanical, electrical, and chemical properties through methods like performance testing, animal studies, usability engineering, and computer simulations.
Both clinical and non-clinical data are essential for understanding device risks and benefits during premarket review.
Non-Clinical Investigations and Animal Studies
The biological evaluation ensures devices do not cause adverse effects such as local/systemic toxicity, carcinogenicity, or reproductive harm.
This process is guided by ISO 10993-1:2018 standards and involves:
- Biocompatibility Testing: Evaluates the interaction between device materials and biological tissues over different contact durations (limited, prolonged, long-term). Common tests include:
- Cytotoxicity
- Sensitization
- Irritation
- Systemic toxicity
- Genotoxicity
- Implantation effects
- Chemical Characterization: Identifies and quantifies chemicals in the device to assess potential risks.
- Risk Assessment: Uses biological evaluation plans (BEP) and reports (BER) to document findings and determine the device’s safety.
In Vitro and In Vivo Testing
Biological testing follows Good Laboratory Practices (GLP) and involves evaluating devices in conditions that reflect their intended use.
Key considerations include:
- Endpoints: Relevant to device exposure, e.g., skin contact or blood interaction.
- Changes in Device Design: Require additional testing if alterations affect biocompatibility.
Animal studies may complement or replace biocompatibility tests by evaluating devices in clinically relevant settings. Control groups and sufficient sample sizes are necessary for reliable results.
Specific Testing Considerations
- Cytotoxicity
Cytotoxicity tests assess the effects of device materials on cell viability, growth, and other cellular responses. Significant findings may trigger further evaluation or chemical characterization of leachable substances.
- Hemocompatibility
Devices in contact with blood are tested for hemolysis (red cell destruction), thrombogenicity, and complement activation to ensure compatibility.
- Pyrogenicity
Devices contacting the cardiovascular, lymphatic, or cerebrospinal systems are tested for pyrogenic reactions to prevent febrile responses.
- Systemic Toxicity
Tests assess the impact of leachates on the body, focusing on acute, subacute, or chronic exposure effects.
- Irritation and Sensitization
Devices are evaluated for the potential to cause skin or mucosal irritation and allergic reactions. Testing considers manufacturing additives and sterilization byproducts.
- Implantation Effects
Implantable devices are tested in relevant anatomical sites to assess tissue responses, including during material degradation.
- Genotoxicity
Tests determine the risk of genetic damage from device materials. Genotoxicity is particularly critical for novel materials or combination products.
- Reproductive and Developmental Toxicity
Devices in contact with reproductive tissues or materials with systemic distribution are tested for reproductive harm.
- Degradation
Degradation studies evaluate how materials break down in the body and their potential release of toxic substances.
General Principles for Testing
According to the guidance, the general principles include:
- Animal Models: Selection should be scientifically justified and relevant to the device type.
- Controls: Positive and negative controls ensure data reliability.
- Comprehensive Data Submission: Complete experimental data must support testing conclusions.
- Risk-Based Approach: Testing strategies should address identified risks.
Conclusion
In summary, medical device classification and testing are critical for ensuring safety and performance. Rigorous clinical and non-clinical evaluations, guided by international standards, such as ISO 10993, provide a robust framework for assessing device risks, biocompatibility, and overall suitability for their intended use.
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