Article 1 of 98/79/EEC, the In Vitro Diagnostic Device Directive (IVDD), delineates the overall scope of the Directive and definitions that are pertinent to understanding and complying with the Directive; hence force the title, “Scope, definitions.” For readers that are unfamiliar with the IVDD, you will be able to quickly ascertain the similarities between the IVDD and its older brother, the Medical Device Directive (MDD). Once you have managed to navigate your way through the 35 “whereas” statements that depict all of the rationale and justification for this standard in an abridged form of legalese, the meat of the IVDD commences with Article 1.
Dr. D realizes that explaining definitions makes no sense, so I will not bother the obsequious (look-it-up) readers with the mundane explanations imbedded in each of definitions. However, the doctor will focus on a few of the salient differences specific to the IVDD and the overall scope of the Directive.
The IVDD – 98/79/EEC
Article 1 – Scope, definitions
1. This Directive shall apply to in vitro diagnostic medical devices and their accessories. For the purposes of this Directive, accessories shall be treated as in vitro diagnostic medical devices in their own right. Both in vitro diagnostic medical devices and accessories shall hereinafter be termed devices.
2. For the purposes of this Directive, the following definitions shall apply:
(a) ‘medical device` means any instrument, apparatus, appliance, material or other article, whether used alone or in combination, including the software necessary for its proper application, intended by the manufacturer to be used for human beings for the purpose of:
- diagnosis, prevention, monitoring, treatment or alleviation of disease,
- diagnosis, monitoring, treatment, alleviation or compensation for an injury or handicap,
- investigation, replacement or modification of the anatomy or of a physiological process,
- control of conception,
- and which does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its function by such means;
(b) ‘in vitro diagnostic medical device` means any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, equipment, 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:
– concerning a physiological or pathological state, or
– concerning a congenital abnormality, or
– to determine the safety and compatibility with potential recipients, or
– to monitor therapeutic measures.
Specimen receptacles are considered to be in vitro diagnostic medical devices. ‘Specimen receptacles` are those devices, whether vacuum-type or not, specifically intended by their manufacturers for the primary containment and preservation of specimens derived from the human body for the purpose of in vitro diagnostic examination.
Products for general laboratory use are not in vitro diagnostic medical devices unless such products, in view of their characteristics, are specifically intended by their manufacturer to be used for in vitro diagnostic examination;
(c) ‘Accessory` means an article which, whilst not being an in vitro diagnostic medical device, is intended specifically by its manufacturer to be used together with a device to enable that device to be used in accordance with its intended purpose.
For the purposes of this definition, invasive sampling devices or those which are directly applied to the human body for the purpose of obtaining a specimen within the meaning of Directive 93/42/EEC shall not be considered to be accessories to in vitro diagnostic medical devices;
(d) ‘device for self-testing` means any device intended by the manufacturer to be able to be used by lay persons in a home environment;
(e) ‘device for performance evaluation` means any device intended by the manufacturer to be subject to one or more performance evaluation studies in laboratories for medical analyses or in other appropriate environments outside his own premises;
(f) ‘manufacturer` means the natural or legal person with responsibility for the design, manufacture, packaging and labelling of a device before it is placed on the market under his own name, regardless of whether these operations are carried out by that person himself or on his behalf by a third party.
The obligations of this Directive to be met by manufacturers also apply to the natural or legal person who assembles, packages, processes, fully refurbishes and/or labels one or more ready-made products and/or assigns to them their intended purpose as devices with a view to their being placed on the market under his own name. This subparagraph does not apply to the person who, while not a manufacturer within the meaning of the first subparagraph, assembles or adapts devices already on the market to their intended purpose for an individual patient;
(g) ‘authorised representative` means any natural or legal person established in the Community who, explicitly designated by the manufacturer, acts and may be addressed by authorities and bodies in the Community instead of the manufacturer with regard to the latter’s obligations under this Directive;
(h) ‘intended purpose` means the use for which the device is intended according to the data supplied by the manufacturer on the labelling, in the instructions for use and/or in promotional materials;
(i) ‘placing on the market` means the first making available in return for payment or free of charge of a device other than a device intended for performance evaluation with a view to distribution and/or use on the Community market, regardless of whether it is new or fully refurbished;
(j) ‘putting into service` means the stage at which a device has been made available to the final user as being ready for use on the Community market for the first time for its intended purpose.
3. For the purposes of this Directive, calibration and control materials refer to any substance, material or article intended by their manufacturer either to establish measurement relationships or to verify the performance characteristics of a device in conjunction with the intended use of that device.
4. For the purposes of this Directive, the removal, collection and use of tissues, cells and substances of human origin shall be governed, in relation to ethics, by the principles laid down in the Convention of the Council of Europe for the protection of human rights and dignity of the human being with regard to the application of biology and medicine and by any Member States regulations on this matter.
5. This Directive shall not apply to devices manufactured and used only within the same health institution and on the premises of their manufacture or used on premises in the immediate vicinity without having been transferred to another legal entity. This does not affect the right of Member State to subject such activities to appropriate protection requirements.
6. This Directive shall not affect national laws which provide for the supply of devices by a medical prescription.
7. This Directive is a specific directive within the meaning of Article 2(2) of Directive 89/336/EEC, which shall cease to apply to devices which have complied with this Directive.
What IVD device manufacturers need to know
To adequately understand the IVDD, Dr. D will identify the salient differences employing the MDD as a frame of reference. As the doctor stated in the introduction, there are substantial similarities between the two Directives; however, there are four salient differences in regards to Article 1 of the IVDD. Probably the most salient point associated with Article 1 is the establishment of the fact that this Directive is specific for in-vitro medical devices and their accessories. In fact, the Directive specifically requires accessories to be managed as stand-alone devices, or as the Directive phrases it, “in their own right.” In the eyes of the Regulatory Gods in the European Union (EU), in-vitro medical devices and their accessories are each considered “devices.” This distinction is extremely important to understand especially when it comes to the assembly of technical data to support the application process.
Similar to the MDD, design dossiers and technical files will form the foundation for submissions to your notified bodies. One another point the doctor needs to make is that accessories under the IVDD should not be confused with the term accessories under the MDD, which in many cases just require an Accessory Technical Data File (ATDF). Dr. D will highlight the differences later in this series.
The second salient difference versus the MDD is the calibration clause. The IVDD specifically addresses calibration and the influence calibration may exude on the finished medical device and its intended use. Remember, similar to the MDD and the QSR employed in the states, device safety and efficacy are extremely important. All finished device influencers, including calibration, must be considered and addressed by the manufacturer of an in-vitro medical device.
The third salient difference versus the MDD is the removal and collection of human tissue clause. As part of the clause, there is an ethics requirement invoked. The dignified treatment of all human beings in regards to the application of biology and medicine must always be considered.
The fourth salient difference versus the MDD relates to the applicability of the IVDD when devices are manufactured and employed internally. For example, if a healthcare provider manufactures and uses a simple device, while never transferring ownership to an external source, the device is exempt from the principles of this Directive. However, the Competent Authorities located within each Member State retain the right to regulate such devices by ensuring adequate patient protections are in place.
What IVD device manufacturers need to do
Regulatory bodies like their definitions. In fact, they like their definitions so much, Dr. D always recommends that device manufacturers establish and maintain a procedure for collecting definitions relevant to their operations. Yes, the doctor understands that this just might seem like a futile effort that results in more paperwork being added to onerous volumes of procedures most device manufacturers are forced to maintain. However, it really does impress the regulatory bodies, worldwide, that you not only have a fundamental grasp of pertinent definitions, your organization has taken the time to place them in a procedure. Once a procedure is created, you have now established a platform for training to a procedure. Remember, training is a key element for any quality management system (QMS).
Dr. D also strongly recommends working with your notified bodies when applying the IVDD. Device manufacturers familiar with the nuances associated with the IVDD clearly understand some of the frustrations associated with correctly applying the classification system for in-vitro devices delineated within the Directive. Part of the Directive understanding is rooted in the correct interpretation of Article 1.
Device manufacturers that have a firm grasp of the definitions and scope of the IVDD will clearly be ahead of the pack when making application with their notified bodies for entering in-vitro devices into the European market. When in doubt, ask your notified body. Why? Because providing sound regulatory advice is one of the reasons device manufacturers pay dearly for the services of a notified body.
According to Dr. D, there are four fundamental differences associated with Article 1 of the IVDD versus the MDD. It is incumbent upon device manufacturers to comprehend these fundamental differences along with definitions specific to the IVDD to support the successful entry of in-vitro devices into the European market. When in doubt, device manufacturers should seek the advice of their notified body prior to attempting to navigate the IVDD waters alone. By the way, did the doctor mention device manufacturers pay their notified bodies for their services? Just kidding, I know I did.
Until the next installment of DG, when Dr. D provides insight and guidance into complying with Article 2 (Placing on the market and putting into service) of the IVDD, cheers from Dr. D and best wishes for continued professional success.
- Council Directive 90/385/EEC. (1990, June). Council Directive 90/385/EEC of 20 June 1990 on the approximation of the laws of the Member States relating to active implantable medical devices. Retrieved October 5, 2010, from http://ec.europa.eu.
- Council Directive 93/42/EEC. (1993, June). Council Directive 93/42/EEC concerning medical devices. Retrieved December 21, 2010, from http://eur-lex.europa.eu.
- Devine, C. (2009, July). Exploring the effectiveness of defensive-receiving inspection for medical device manufacturers: a mixed method study. Published doctoral dissertation. Northcentral University. Prescott Valley, AZ.
- Devine, C. (2011). Devine Guidance series on complying with the MDD. Published in The Medical Device Summit. http://medicaldevicesummit.com
- Directive 98/79/EC. (1998, October). Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on in vitro diagnostic medical devices. Retrieved September 12, 2011, from http://eur-lex.europa.eu.
- EN ISO 13485:2003. (2004, February). Medical devices – quality management systems – requirements for regulatory purposes (ISO 13485:2003).