As Dr. D. stated in the previous edition of Devine Guidance (DG), the Medical Device Directive (MDD) encompasses a far more complex array of documents (my humble opinion), than the Quality System Regulation (QSR). Employing my less than aureate but somewhat colorful prose, I will begin breaking down the MDD into smaller sound bytes in the hopes that each of you can takeaway a better understanding of the regulatory requirements and the potential compliance pitfalls associated with complying with the Directive.

Article 1 of the scope is appropriately entitled “Definitions, scope.” Guess what – that is exactly what is disseminated in the first Article, the applicability and scope of the Directive. As many of you are already aware the doctor is always attempting to proselytize (look-it up if you must) to the readers the need for ongoing compliance with regulations, regardless of the regulations being mandated by law within the United States, or in the case of the MDD, the European Union (EU). That said, please read on, and enjoy.

Welcome to the MDD: Article 1 – Definitions, scope
1. This Directive shall apply to medical devices and their accessories. For the purposes of this Directive, accessories shall be treated as medical devices in their own right. Both 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, software, material or other article, whether used alone or in combination, including the software intended by its manufacturer to be used specifically for diagnostic and/or therapeutic purposes and 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 of 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 maybe assisted in its function by such means;

(b) ‘Accessory’ means an article which whilst not being a device is intended specifically by its manufacturer to be used together with a device to enable it to be used in accordance with the use of the device intended by the manufacturer of the device;

(c) ‘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;

(d) ‘Custom-made device’ means any device specifically made in accordance with a duly qualified medical practitioner’s written prescription which gives, under his responsibility, specific design characteristics and is intended for the sole use of a particular patient. The above-mentioned prescription may also be made out by any other person authorized by virtue of his professional qualifications to do so. Mass-produced devices which need to be adapted to meet the specific requirements of the medical practitioner or any other professional user shall not be considered to be custom-made devices;

(e) ‘Devices intended for clinical investigation’ means any device intended for use by a duly qualified medical practitioner when conducting investigations as referred to in Section 2.1 of Annex X in an adequate human clinical environment. For the purpose of conducting clinical investigation, any other person who, by virtue of his professional qualifications, is authorized to carryout such investigation shall be accepted as equivalent to a duly qualified medical practitioner;
 
(f) ‘Manufacturer’ means the natural or legal person with responsibility for the design, manufacture, packaging and labeling 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 a device 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) ‘Intended purpose’ means the use for which the device is intended according to the data supplied by the manufacturer on the labeling, in the instructions and/or in promotional materials;

(h) ‘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 clinical investigation, with a view to distribution and/or use on the Community market, regardless of whether it is new or fully refurbished;

(i) ‘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;

(j) ‘Authorized representative’ means any natural or legal person established in the Community who, explicitly designated by the manufacturer, acts and maybe addressed by authorities and bodies in the Community instead of the manufacturer with regard to the latter’s obligations under this Directive;

(k) ‘Clinical data’ means the safety and/or performance information that is generated from the use of a device. Clinical data are sourced from: clinical investigation(s) of the device concerned; or clinical investigation(s) or other studies reported in the scientific literature, of a similar device for which equivalence to the device in question can be demonstrated; or published and/or unpublished reports on other clinical experience of either the device in question or a similar device for which equivalence to the device in question can be demonstrated;

(l) ‘Device subcategory’ means a set of devices having common areas of intended use or common technology;

(m) ‘Generic device group’ means a set of devices having the same or similar intended uses or commonality of technology allowing them to be classified in a generic manner not reflecting specific characteristics;

(n) ‘Single-use device’ means a device intended to be used once only for a single patient.

3. Where a device is intended to administer a medicinal product within the meaning of Article 1 of Directive 2001/83/EC (1). That device shall be governed by this Directive, without prejudice to the provisions of Directive 2001/83/EC with regard to the medicinal product. If, however, such a device is placed on the market in such away that the device and the medicinal product form a single integral product which is intended exclusively for use in the given combination and which is not reusable, that single product shall be governed by Directive 2001/83/EC. The relevant essential requirements of Annex I to this Directive shall apply as far as safety and performance-related device features are concerned.

4. Where a device incorporates, as an integral part, a substance which, if used separately, maybe considered to be a medicinal product within the meaning of Article 1 of Directive 2001/83/EC and which is liable to act upon the body with action ancillary to that of the device, that device shall be assessed and authorized in accordance with this Directive.

4a. Where a device incorporates, as an integral part, a substance which, if used separately, maybe considered to be a medicinal product constituent or a medicinal product derived from human blood or human plasma within the meaning of Article 1 of Directive 2001/83/EC and which is liable to act upon the human body with action ancillary to that of the device, hereinafter referred to as a ‘human blood derivative’, that device shall be assessed and authorized in accordance with this Directive.
 
5. This Directive shall not apply to:

(a) In vitro diagnostic devices;
(b) Active implantable devices covered by Directive 90/385/EEC;
(c) Medicinal products covered by Directive 2001/83/EC. In deciding whether a product falls under that Directive or this Directive, particular account shall betaken of the principal mode of action of the product;
(d) Cosmetic products covered by Directive 76/768/EEC (1);
(e) Human blood, blood products, plasma or blood cells of human origin or to devices which incorporate at the time of placing on the market such blood products, plasma or cells, with the exception of devices referred to in paragraph 4a;
(f) Transplants or tissues or cells of human origin nor to products incorporating or derived from tissues or cells of human origin, with the exception of devices referred to in paragraph 4a;
(g) Transplants or tissues or cells of animal origin, unless a device is manufactured utilizing.  

6. Where a device is intended by the manufacturer to be used in accordance with both the provisions on personal protective equipment in Council Directive 89/686/EEC (1) and this Directive, the relevant basic health and safety requirements of Directive 89/686/EEC shall also be fulfilled.

7. This Directive is a specific Directive within the meaning of Article 1(4) of Directive 2004/108/EC of the European Parliament and of the Council (2).

8. This Directive shall not affect the application of Council Directive 96/29/Euratom of 13 May 1996 laying down basic safety standards for the protection of the health of workers and the general public against the dangers arising from ionizing radiation (3), nor of Council Directive 97/43/Euratom of 30 June 1997 on health protection of individuals against the dangers of ionizing radiation in relation to medical exposure (4).

Directive applicability
Simply put, this Directive is all encompassing for medical devices except when exclusions are noted within the Directive or one of the other two Directives apply. What does that mean Dr. D? Basically, this Directive (minus exclusions) is applicable for medical devices and their accessories.

I am sure most of you are familiar with the practice of listing applicable accessory devices within your design dossiers and technical files. In fact, the listing of ancillary and accessory devices is a mandatory requirement. Additionally, you should be managing accessory-technical-data files (ATDF) as a subset to dossiers and technical files. Yes, that is a whole lot of documentation to create and manage; however, it is just part of the price of admission into the medical device market within the EU.

Dr. D will let you in on a little secret, “the notified bodies will review your ATDFs as part of their annual friendly visit to your facilities; and they are not being managed, your organization will receive deviations.” The notified body expectation is that an ATDF should be sustained as meticulously as a standard technical file. That is also Dr. D’s expectation as well, as I have spent way too many years bringing technical files and ATDFs into compliance with this Directive. 

Directive definitions
Since the definitions provided within the Directive are for the most part self explanatory, Dr. D is not going to dwell to much on this section of Article 1. However, there are a few definitions, changes to definitions, and new definitions, that you should be keenly aware of because of the amendments to the Directive made in March of 2010 (Directive 2007/47/EC). Some of the Dr D watch outs are:

• Software has been added to the medical device definition;
• There were significant changes to the in-vitro diagnostics definition (a must read);
• Custom-made device inclusions into the Directive;
• Expansion of the clinical investigation requirements;
• Authorized Representative (new definition) – required for all device manufacturers located outside of the EU;
• Clinical Data (new definition) – the additional requirement for clinical data to support product submissions (clinical data must be included in dossiers and technical files);
• Device Subcategory (new definition);
• Generic Device Group (new definition); and
• Single-use device (new definition).

As the doctor previously said, the definitions are very well defined. Device manufacturers just need to ensure all of the changes are understood and incorporated into their technical documentation and day-to-day activities, as appropriate.

Devices administering medicinal product (a.k.a., Combination Devices)
For devices categorized as administering a medicinal product (sections 3 and 4), the Directive establishes the need to consider and comply with two directives. Directive 2001/83/EEC delineates the requirements in regards to the medicinal aspects associated with this type of device; however, the MDD establishes the need for complying with specific Essential Requirements defined within Annex I of the MDD. The primary factors for the need to comply with Annex I are ensuring safety and performance features are achieved and sustained during the life of the product. Remember, safety and efficacy always counts.

Medicinal Product Derived from Human Blood (Combination Device)
Once again, the MDD requires the employment of two Directives to correctly assess and qualify a device. For starters, Article 1 of Directive 2001/83/EC should be employed for definition assessment of the device. If the device is correctly categorized as a “human blood derivative,” the device needs to be assessed in accordance with this Directive.

Directive Exclusions
The device and category exclusions delineated within this Directive are clearly depicted under Section 5 of Article 1 of the MDD. However, please keep in mind that just because a particular device is listed as an exclusion under this Directive, it will be covered under one of the other two Directives. Dr. D strongly recommends, actually Dr. D emphatically recommends, working with your notified body to ensure devices being designed, qualified, and approved for distribution in the EU are qualified under the correct Directive; and the appropriate path for conformity in regards to applicable Annexes. Dr. D will expand on paths of conformity, device categories, etc. in the very near future, so please keep reading DG.

Personal Protective Equipment
Since when did devices, categorized as Personal Protective Equipment (PPE), require the consideration of two Directives? Effective 21 March 2010, premised on the amendments made to the MDD, in accordance with 2007/42/EC, devices that can be categorized as PPE, require compliance with Essential Requirements delineated within this Directive and Directive 89/686/EEC. In short, this is somewhat of a regulatory double whammy, as multiple Directives need to be considered. In fact, there is a unique Essential Requirements Checklist (ERC) required for claiming conformity to the PPE Directive. So what can be construed as PPE? For example, if the healthcare facility is located in undesirable and dangerous location, somewhere within the EU, and a physician needs to wear a Kevlar vest for safety, during his or her trek to work; this bulletproof vest does not qualify as personal protective equipment under the Directive. However, if a physician in a catheter lab requires special gloves to protect his or hers hands from radiation, then these special gloves would be considered PPE in accordance with this Directive; and require health and safety requirements associated with 89/686/EEC to be achieved. 

Specific directive
Section 7 of Article 1 is a simple clause (just kidding – there is nothing simple about the Directive) that identifies the MDD as a Directive within the meaning of Article 1(4) of another Directive (2004/108/EC). Directive 2004/108/EC is the governing document for controlling electromagnetic energy and compatibility (a.k.a., EMC). The link is being made between these Directives because capital equipment employed as a medical device or forms an integral part of a medical device requires testing and evaluation against the EMC Directive. For example, an RF generator employed as part of an ablation system, for treating arrhythmias, would require EMC testing and certification. The testing would have to include the RF Generator and the disposable catheter that actually provides the therapy. I know, enough with all of the Directives Dr. D. Unfortunately folks, I did not author the Directives. Remember, the doctor previously issued a subtle warning that in his honest opinion, the MDD is far more complex than the QSR. Just wait until I start diving into each of the Annexes, it is going to make your head spin if you are not familiar with the MDD.

Directive effect on other directives – Ionizing Radiation
Exposure to ionizing radiation and the dangers to exposure continue to problematic for healthcare workers and even the patient. That said, safety standards and the overall protection of healthcare workers and other individuals potentially exposed to ionizing radiation are protected, from a regulatory standpoint under the guise of Council Directive 96/29/Euratom. The MDD shall not affect that Directive in regards to safety standards and protection from ionizing radiation as a result of exposure during a medical application.

Dr D’s Weekly Rodomontade
During a long-flight home, last Friday, I had the opportunity to sit next to an individual who was employed by a small medical device company located on the left coast. We talked at length about the trials and tribulations associated with placing product into the US market and touched on product entry into the EU. One of the concerns raised by this individual was the amount of work required to not only comply with the MDD; but all of the work required in preparation of that first notified body audit. Yes, it takes a substantial amount of work to achieve and sustain compliance to the MDD; however, there are ways to ease the overall pain when deciding to enter the European Market. Dr. D will share some of the free advice offered to this individual.

1. Selecting a competent Notified Body i.e., TUV-R, BSI, KEMA, (Dr D is not a paid spokesperson for this organizations) will help organizations, large and small, navigate the regulatory waters associated with the complexities of the MDD and doing business within the EU.
2. Do not be afraid to hire consultants to assist in establishing a compliant quality system. Organizations such as the Emergo, Regulatory Compliance Associates, Validant, and Goode Consulting Industries (once again not a paid spokesperson) can help build the initial foundation for your quality system or install the entire system. Now granted, using consultants can be expensive; however, considering the time saved and the expertise they bring to the table, it is well-worth the dollars spent, to have professionals on board working in your best interest.
3. Ensure that once your have selected a European Authorized Representative, make sure you define the relationship in a contract. The notified bodies will ask to see the contract during their annual audit.
4. Read the Medical Device Summit and Devine Guidance weekly. Did you know that all of the ranting of Dr. D are available at The Summit and are absolutely free to download?

Takeaways
The major takeaways from this edition of DG are: (a) significant changes made to the definitions of the MDD (21 March 10) should be clearly understood; (b) PPE requires a stand-alone and unique ERC; (c) depending on the application, software is now in scope of the MDD; and (d) combination devices require compliance to requirements delineated in multiple Directives. Additionally, Dr. D recommends printing out a copy of each of the Directives, mentioned in this article (a list of the Directives can be found in the Reference Section); and the reading of each Directive carefully. There is just so much information to be gleaned from these Directives. Furthermore, selecting a recognized notified body can ease the challenges associated with navigating the regulatory waters of the EU. Finally, if your organization does not have the bandwidth or resources to design and implement a quality system that complies with all aspects of the MDD, do not be afraid to hire competent consultants. They are well worth the money spent.

In closing, thank you again for joining Dr. D and I hope you find value in the guidance provided. Until the next installment of DG, when Dr. D will provide guidance for complying with Article 2 (placing on the market and putting into service) of Council Directive 93/42/EEC, the MDD – cheers from Dr. D. and best wishes for continued professional success.

References:

1. Code of Federal Regulation. (2010, April). Title 21 Part 820: Quality system regulation. Washington, D.C.: U. S. Government Printing Office.

2. Council Directive 89/686/EEC. (1989, December). Council Directive 89/686/EEC on the approximation of the laws of the member states relating to personal protective equipment. Retrieved January 11, 2011, from http://www.emergogroup.com

3. 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

4. Council Directive 96/29/EURATOM. (1996, May). Council Directive 96/29/EURATOM – laying down basic safety standards for protection of the health of workers and the general public against the dangers arising from ionizing radiation. Retrieved January 7, 2011, from http://eur-lex.europa.eu

5. Council Directive 97/43/EURATOM. (1997, June). Council Directive 97/43/Euratom of 30 June 1997 on health protection of individuals against the dangers of ionizing radiation in relation to medical exposure, and repealing Directive 84/466/Euratom. Retrieved December 21, 2010, from
   http://eur-lex.europa.eu 

6. 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.

7. Directive 2001/83/EC. (2001, November). Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the community code relating to medicinal products for human use. Retrieved January 7, 2011, from http://www.edctp.org

8. Directive 2004/108/EC. (2004, December). Directive 2004/108/EC of the European Parliament and of the Council of 15 December 2004 on the approximation of the laws of the member states relating to electromagnetic compatibility and repealing Directive 89/336/EC. Retrieved January 7, 2011, from http://eur-lex.europa.eu

9. Directive 2007/47/EC. (2007, September). Directive 2007/47/EEC of the European Parliament and of the Council of 5 September 2007 amending Council Directive 90/385/EEC on the approximation of the laws of member states relating to active implantable medical devices, Council Directive 93/42/EEC concerning medical devices and Directive 98//8/EC concerning the placing of biocidal products on the market. Retrieved December 21, 2010, from http://eur-lex.europa.eu

10. Medical Device Directive. (1993). Council Directive 93/42/EEC. Medical Device Safety Service. Retrieved December 21, 2010, from http://directive93-42-eec.htm