Background

An in-vitro diagnostic (IVD) manufacturer was not familiar with the EU regulations and wanted to understand the general requirements that were needed to be fulfilled in order to market their products. The device utilized cardiac enzymes, also referred to as cardiac biomarkers, to identify and treat certain cardiovascular ailments. The quantification of these biomarkers was used to predict and diagnose the progression of certain cardiac conditions. 

The regulations for the EU are quite extensive when it comes to IVDs, and hence the manufacturer contacted Elexes to seek some regulatory counsel for marketing their devices in the European Union (EU).

Problem Statement

Following were the main issues the manufacturer ran into

1. The manufacturer was unsure about the labeling requirements for IVDs, as per the EU regulations.
2. The manufacturer was uncertain of the risk control measures that need to be adopted for the device according to the EU guidelines. 
3. The client also lacked clarity over what, in general, must be included in the IFU.

Approach and Solution

1. Elexes advised on the labeling requirements for the in-vitro diagnostics, as per the latest EU 2017/746, and provided clarity to the client. 

A few of the most significant details that had to be included on the labels of the devices are highlighted below.

• The name of the device, intended use
• The name, registered trademark of the manufacturer, and registered address
• Identification as an In Vitro Diagnostic device (IVD symbol) or, alternatively, identification as a “device for performance study”
• The Unique Device Identifier (UDI) of the device
• The serial number and/or the lot number of the device
• Warnings or Precaution statements to bring to the user’s notice
• The expiry date until when the device can be used without any degradation in performance of the device
• Mention of net quantity of contents in terms of numerical count, weight, or volume.
• Indication of applicable handling and/or special storage conditions, if any.
• Indication of the device’s state of sterility
• Indication if the device is intended for single use or is reusable

2. Elexes analyzed the overall risk management requirements that are to be considered by the manufacturer. 

The client was advised to take the following things into consideration while documenting and establishing a risk management file for the device:

• Identification of the foreseeable and known hazards associated with the device
• Risk estimation and evaluation associated with the intended use of the device
• Elimination or reduction of the identified risks to the best extent through safe design
• Adequate precautions and protection measures
• Information for safety (Warnings/Precautions/Contra-indications) and necessary training for users
• Information regarding residual risks 

The entire risk assessment process was explained in detail to the Client, also in line with the ISO 14971 standard. 

3. Elexes considered various device-specific requirements and applicable harmonized standards along with the IVDR and summarized some of the key requirements that should be included in the instructions for use.

• Basic information which was also relevant for other labels
• Principle of the assay
• A description of the reagents used in the device and limitations if any
• Special storage indications (e.g. temperature, light, humidity, etc.), handling and operating conditions
• Information on warnings, precautions, measures to be taken, and limitations of use regarding the device
• Indication if the device is intended for single use or is reusable
• Instructions for reprocessing/sterilization methods if the device is reusable
• Conditions for sample collection, handling, and sample preparation
• Appropriate symbols and their abbreviations
• Result Interpretations and/or expected values

Some relevant warnings and precautions that the Client was advised to include based on the reviews performed by the Elexes team were as follows: 

Key Takeaways

1. Identifying the correct labeling requirements for a product goes a long way in ensuring that the product is marketed in the European Union or worldwide markets without any hurdles or back and forth with the regulators. 
2. Various warnings and precautions that need to be in the user manual, to ensure safe and effective use of the product, should be identified in the course of thorough risk management and product performance evaluation.
3. Risk Analysis and mitigation are important steps in a product’s lifecycle, and a risk management file should be continuously updated even after the product is marketed.  
4. The manufacturer is responsible for providing accurate information to the users for the proper use of the device. Elexes made it easy for the client to understand the information that needs to be included in the labels and eased the process of regulatory approval.

Benefits delivered