In-Vitro Devices and CE Marking
In the dynamic landscape of medical technology, the regulatory framework plays a pivotal role in ensuring the safety and efficacy of diagnostic devices. Particularly, the CE marking process stands as a beacon for manufacturers of in vitro diagnostic devices (IVDs), indicating compliance with European Union (EU) regulations. As the demand for cutting-edge diagnostic solutions continues to surge, understanding the intricacies of CE marking for in vitro diagnostic devices becomes imperative.
Within the realm of in vitro diagnostic test kits, the significance of CE marking is particularly pronounced. These kits, designed for rapid and accurate diagnosis of various medical conditions, must undergo meticulous scrutiny to meet the rigorous standards imposed by regulatory bodies. The process of obtaining CE marking involves a comprehensive evaluation of the design, manufacturing processes, and performance characteristics of in vitro diagnostic test kits.
What are In-Vitro Diagnostic Devices?
As per Article 2 of REGULATION (EU) 2017/746 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL (IVDR), an In-Vitro Diagnostic Device (IVD) can be defined as
“any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, piece of equipment, software or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally for the purpose of providing information on one or more of the following:
- concerning a physiological or pathological process or state;
- concerning congenital physical or mental impairments;
- concerning the predisposition to a medical condition or a disease;
- to determine the safety and compatibility with potential recipients;
- to predict treatment response or reactions;
- to define or monitoring therapeutic measures.
Specimen receptacles shall also be deemed to be in vitro diagnostic medical devices;”
Apart from the devices covered in the above definition, In-Vitro Diagnostic Devices (IVDs) can also be made available in various types that may include but not be limited to the following:
1. Specimen Receptacle:
- Definition: A device intended by its manufacturer for the primary containment and preservation of specimens derived from the human body. It is used for in vitro diagnostic examination.
- Example: Containers, whether vacuum-type or not, designed for holding and preserving human body specimens for diagnostic testing.
2. Accessory for an In Vitro Diagnostic Medical Device:
- Definition: An article that, while not being an in vitro diagnostic medical device itself, is intended by its manufacturer to be used together with one or more specific in vitro diagnostic medical devices. Its purpose is to enable the intended use of the diagnostic devices or to directly assist in the medical functionality of those devices.
- Example: Reagents, calibration solutions, or additional components used in conjunction with a specific in vitro diagnostic medical device.
3. Device for Self-Testing:
- Definition: Any device intended by the manufacturer for use by laypersons. This includes devices used for testing services offered to laypersons through information society services.
- Example: Over-the-counter pregnancy tests or home blood glucose meters designed for use by individuals without professional medical training.
4. Device for Near-Patient Testing:
- Definition: Any device not intended for self-testing but designed to perform testing outside a laboratory environment. These tests are generally conducted near or at the patient’s side by a healthcare professional.
- Example: Point-of-care diagnostic devices used by healthcare professionals in settings outside a traditional laboratory.
5. Companion Diagnostic:
- Definition: A device essential for the safe and effective use of a corresponding medicinal product. It identifies patients who are likely to benefit from the medicinal product or identifies patients at increased risk of serious adverse reactions due to treatment with the medicinal product.
- Example: A diagnostic test that helps determine whether a patient’s genetic makeup is suitable for a specific targeted therapy.
6. Generic Device Group:
- Definition: A set of devices with the same or similar intended purposes or a commonality of technology. These devices can be classified in a generic manner that does not reflect specific characteristics.
- Example: A group of diagnostic devices with similar intended uses or based on a common technological platform, allowing them to be classified together.
The classification rules for these IVD devices have been laid out in the Annex VIII of the IVDR which states seven rules for classification along with guidance on implementing the rules to help IVD manufacturers identify the risk class of IVD devices.
Critical points for CE marking of IVD devices under the new IVDR
The CE marking process for in vitro diagnostic test kits under the new In Vitro Diagnostic Regulation (IVDR) involves several critical points to ensure compliance with the regulatory requirements. Here are key considerations:
1. Classification:
- Critical Point: Accurate classification of the IVD device is crucial as it determines the conformity assessment route.
- Action:
- Refer to Annex VIII of the IVDR for classification rules.
- Seek guidance from competent authorities or notified bodies if classification is uncertain.
2. Conformity Assessment:
- Critical Point: Choose the appropriate conformity assessment route based on device classification.
- Action:
- Understand the conformity assessment procedures (Annexes IX-XI).
- Engage a notified body early in the process, especially for higher-risk devices.
3. Clinical Evidence:
- Critical Point: Robust clinical evidence is essential for demonstrating the device’s performance and safety.
- Action:
- Conduct a comprehensive clinical evaluation based on clinical data.
- Document the clinical evidence in accordance with the requirements (Annex XIV).
4. Performance Evaluation Report (PER):
- Critical Point: Prepare a PER demonstrating conformity with performance requirements. Scientific Validity Report which is a new and critical addition to the regulation will impact the effectiveness of the qualification.
- Action:
- Address specific requirements outlined in Annex XIII.
- Thorough literature review and demonstration of equivalence.
- Ensure data on analytical and clinical performance is comprehensive.
5. Quality Management System (QMS):
- Critical Point: Implement and maintain an effective QMS.
- Action:
- Comply with ISO 13485:2016 requirements.
- Demonstrate conformity with the IVDR’s QMS requirements (Annex XI).
6. Post-Market Surveillance (PMS) and Post-Market Performance Follow-Up (PMPF):
- Critical Point: Establish robust PMS and PMPF systems for ongoing monitoring.
- Action:
- Implement systems for data collection and analysis.
- Report any emerging risks or non-compliance promptly.
7. UDI (Unique Device Identification):
- Critical Point: Implement UDI requirements for traceability.
- Action:
- Assign UDIs to devices.
- Ensure compliance with UDI database requirements.
8. Technical Documentation:
- Critical Point: Maintain comprehensive technical documentation.
- Action:
- Assemble and update technical documentation as required (Annex II).
- Ensure documentation is readily available for inspection.
9. Labeling and Instructions for Use:
- Critical Point: Ensure accurate and compliant labeling and instructions for use.
- Action:
- Comply with labeling requirements (Annex I).
- Provide clear and comprehensive instructions for use.
10. Economic Operators:
- Critical Point: Clearly define roles and responsibilities for economic operators.
- Action:
- Establish agreements with importers and distributors.
- Ensure traceability and compliance throughout the supply chain.
11. Notified Body Interaction:
- Critical Point: Engage with notified bodies for conformity assessment.
- Action:
- Communicate effectively with the notified body.
- Address any findings or requests promptly.
12. Transition Period:
- Critical Point: Be aware of transition timelines and deadlines.
- Action:
- Plan and execute activities to meet IVDR requirements within the transition period.
13. Training and Competence:
- Critical Point: Ensure personnel are trained and competent.
- Action:
- Provide training on IVDR requirements.
- Maintain records of personnel competence.
Adherence to these critical points will contribute to a successful CE marking process for IVD devices under the new IVDR. It’s essential to stay informed about updates, seek expert guidance, and engage with competent authorities and notified bodies throughout the regulatory journey.