A compliant quality management system is a cornerstone of most global IVD regulatory systems, whether that be the QSRs in the U.S. or ISO 13485 in the EU.  ISO13485 is the harmonized standard. However, the IVD Directive itself clearly states that all devices must have a quality system compliant with the requirements of Annex III of the IVD Directive, so a quality management system is essential to being able to place products on the European market.

A quality management system ensures that good manufacturing practices are established and maintained so that the product which is safe and effective and meets specifications is produced reproducibly.  If a manufacturer requires a notified body to CE mark their product, then the notified body is responsible for auditing to the requirements of the Directive. Companies often choose to gain certification to ISO 13485. But manufacturers may choose not to apply ISO 13485. In this scenario, they will be assessed directly to Annex IV or VII of the IVD Directive. However, they must demonstrate a system with comparable solutions to the requirements in the Directive as described in ISO 13485.

If any manufacturer does not meet the requirements of the standard, a non conformity will be raised. If this is not addressed, it could lead to first the suspension and then withdrawal of a certificate, which means that the manufacturer may no longer be able to support regulatory approval if used to support a regulatory conformity route.

It is important to remember ISO13485 is entitled “Quality Management Systems — Requirements for Regulatory Purposes” and as such is a conformity route for many countries including EU, Canada, and Australia. It is therefore not a marketing tool but it is one of the key requirements needed to gain market access in these countries. A quality system appropriately applied will enable a company to make safe reproducible products, which is why regulators use it as a key tool for entry into their markets.

The first thing to consider is ISO 13485, which states, “The type and extent of control applied to the supplier and the purchased product shall be dependent upon the effect of the purchased product on subsequent product realization or the final product.” It is therefore essential to consider, evaluate, and document the potential risk and then determine how to manage this. Risk control measures may include selecting suppliers that use validated methods under GMP. However, when this is not possible, other methods of control may need to be considered. For example, can the product be tested on receipt, and can large batches be purchased and qualified for use in the IVD application? This assumes that processes can be subsequently verified on the principle that processes that cannot be verified by subsequent monitoring or measurement should be validated. When the incoming material or product cannot be verified, and there are no validated methods, for example if the product being purchased is sterile, then an alternative supplier may need to be found.
The GHTF Document Guidance on the Control of Products and Services Obtained from Suppliers is a useful source of guidance: http://www.ghtf.org/documents/sg3/sg3final-N17.pdf

There are two important things to consider. One, does the test detect a clinical parameter which could be used to diagnose a patient. If it does not, then the test does not meet the definition of an IVD as the device must have a medical intended purpose. The other important test is how is it “placed on the market.” If it is not described for a clinical use or sold in this way, it does not meet the definition of an IVD in the IVD Directive, and the Directive therefore does not apply. If it is not an IVD, local product liability/product safety legislation will apply in the normal way. It is essential that the instructions for use clearly identify the intended use of the device and that the product is sold and advertised appropriately.  The technology alone does not make it an IVD nor determine what it is used for and how it is sold.

The labelling may change to meet new essential requirements and may now include a Notified Body number to identify that a conformity route requiring a Notified Body has now been applied. However, if neither of these are affected by the new regulations, there may be no obvious change to the labels.

Once the new IVD Directive regulations come into force, IVD manufacturers must meet any new labeling requirements. The CE mark shown on an IVD product reflects the regulations at the time the product was placed on the market, as reflected in an IVD manufacturer’s declaration of conformity. Once an IVD manufacturer applies the new IVD Directive regulations, it must meet any new labeling requirements and apply appropriate conformity routes such that the declaration of conformity denotes the regulations applied not specifically to the label.