As promised, Dr. D will kick off the New Year by beginning a new series of articles premised on understanding the complexities of the Medical Device Directive (MDD), and specifically Council Directive 93/42/EEC. A collegium of industry experts believe that complying with the Quality System Regulation (QSR) is a relatively simple task when faced with understanding and complying with the complexities and nuances associated with the MDD. One of the perceived differences between the QSR and the MDD is the enforcement approach pursued by FDA; and their being far-less forgiving then the notified bodies and competent authorities when compliance lapses occur. For some reason, a minor deviation issued by a notified body during an audit is perceived as less punitive than a Form 483 issued by the agency.

In reality, multiple minor deviations issued after a notified-body audit can result in a major deviation; or even the issuance of a stand-alone major deviation, for a significant quality system failure, can result in a notified body pulling their CE Mark from a medical device they previously approved. Can you say, “No CE Mark, no product sales in Europe?”

That said, as many of you already know, the pathway for entrance into the European Economic Community (EEC) is the affixing of the CE Mark to medical-device packaging/labeling, and in some cases, the actual medical device. The concept is surprising simple: once again repeat after Dr. D; “No CE Mark equates to no product being introduced into the European Union (EU) for sale!” Good.

Similar to the Devine Guidance (DG) series of articles exploring the virtues and idiosyncrasies of the QSR, Dr. D will dissect the MDD in 2011. The MDD is far more complex (Dr D’s opinion) and as a result, the good doctor, God willing, will pen another series of articles that reflect my poignant writing style, coupled with flights of rodomontade (look-it-up if you must) to cover the content of the Directive thoroughly. I hope you will continue to enjoy DG and the other articles depicted within the Medical Device Summit.

In this first article in the series, the doctor will present a 47,500-feet summary of the MDD. Why 47,500-feet versus the 50,000-feet colloquium most writers invoke? Because Dr. D enjoys being different!

The Medical Device Directive
Although the focus of this initial article and the subsequent articles that I will pen as part of a series will explore Council Directive 93/42/EEC, there are actually three Directives that support medical devices within the EU. As an FYI, the other two Directives are the: (a) the Active Implantable Medical Device (AIMD) Directive – 90/385/EEC; and (b) the In Vitro Diagnostic Device (IVD) Directive – 98/79/EC. Dr. D will cover these additional directives, eventually, but before Hades freezes over – I promise. 

Another FYI – just in case some of you had not emerged from your hibernaculum prior to last March, 93/42/EEC was amended by 2007/42/EC. The changes went into effect on March 21, 2010. Some of the significant changes can be found under the heading “2007/42/EC – Changes to the MDD” later in this edition of DG. That said, as a Directive, the MDD is broken down into 23-Articles and 12-Annexes. This week the doctor will provide a list of the Articles and Annexes, next week Dr D will commence with the guidance. The Articles delineated within 93/42/EEC are: 

• Article 1 – Definition, scope;
• Article 2 – Placing on the market and putting into service;
• Article 3 – Essential requirements;
• Article 4 – Free movement, devices intended for special purposes;
• Article 5 – Reference to standards;
• Article 6 – Committee on Standards and Technical Regulations;
• Article 7 – Committee on Medical Devices;
• Article 8 – Safeguard clause;
• Article 9 – Classification;
• Article 10 – Information on incidents occurring following placing of devices on the market;
• Article 11 – Conformity assessment procedures;
• Article 12 – Particular procedure for systems and procedure packs;
• Article 13 – Decisions with regard to classification, derogation clause;
• Article 14 – Registration of persons responsible for placing devices on the market;
• Article 15 – Clinical investigations;
• Article 16 – Notified bodies;
• Article 17 – CE marking;
• Article 18 – Wrongly affixed CE marking;
• Article 19 – Decision in respect of refusal or restriction;
• Article 20 – Confidentiality;
• Article 21 – Repeal and amendment of Directives;
• Article 22 – Implementation, transitional provisions; and finally,
• Article 23 – An applicability comment, “This directive is addressed to the member states.”

Wow, 23 Articles! If the readers think the Articles alone might be enough material to digest, do not forget about the12 additional Annexes, for your reading and ultimately compliance enjoyment. The Annexes dive into topics such as Essential Requirements, Quality System Requirements, and EC Declaration of Conformity. Specifically, the 12-Annexes associated with 93/42/EEC are entitled:

• ANNEX I – Essential Requirements;
• ANNEX II –  EC Declaration of Conformity (full quality assurance system);
• ANNEX III – EC Type-Examination;
• ANNEX IV – EC Verification ;
• ANNEX V – EC Declaration of Conformity (production quality assurance);
• ANNEX VI – EC Declaration of Conformity (product quality assurance);
• ANNEX VII – EC Declaration of Conformity;
• ANNEX VIII – Statement Concerning Devices for Special Purposes;
• ANNEX IX – Classification Criteria;
• ANNEX X – Clinical Evaluation;
• ANNEX XI – Criteria to be Met for the Designation of Notified Bodies; and
• ANNEX XII – CE Marling of Conformity.

2007/42/EC – Changes to the MDD
Are you overloaded yet? The reason Dr. D is asking is that there is so much more to digest in regards to the MDD. What about all of the changes that went into effect on 21 March 2010? These changes were significant and many device manufacturers were slow in responding to these changes. Thank God, Dr. D worked for an organization that began working toward compliance 18-months in advance of these changes becoming law. Oh yes, did Dr. D mention that the MDD is actually law within the EU? The doctor wonders what color the jumpsuits, for the Chief Jailable Officer (CJO), might be in the EU? Regardless, Dr. D has taken the liberty of delineating some of the major amendments made to the MDD in March of last year. I hope each of your organizations successfully incorporated each of the amendments into your quality systems.

1. Software as a medical device, depending on the application was added to the Directive.
2. All devices covered under the Directive now require clinical data to support product safety and efficacy (regardless of classification).
3. Custom-made devices now require inclusion into post-market surveillance activities.
4. Single-use devices, that are reused (never a good idea to reuse a single-use device), now require a risk assessment delineating performance issues and risk associated with potential reuse.
5. Instructions for Use (IFU) must be placed into an organization’s document control system and managed accordingly (a.k.a., controlled document – revision control is required).
6. Post-market surveillance activities must be documented by written procedure(s), for each device, including trending activities.
7. Clinical data must be included in the technical file.
8. For manufacturers located outside of the EU, they are now required to appoint an EU Authorized Representative.
9. Medical devices, which double as a protective device for the user, must be assessed against essential requirements in accordance with 89/686/EEC, the Personal Protective Equipment Directive.
10. Medical devices that can be categorized as a machine are now required to be assessed against the essential requirements delineated within 2006/42/EC, the Machinery Directive.
11. There was a reclassification of some medical devices, depending upon indication for use. In some cases, e.g., Class IIb devices were reclassified as Class III, requiring the manufacturer to compile and submit a design dossier to their notified body for review and approval.

There are a few other changes that went into effect in March 2010. Dr. D strongly suggests reading the Directive to ensure all of the changes are understood and have been adequately addressed within your respective quality systems.

Dr D.’s Rodomontade
Not wanting to state the obvious but obliged to do so, there are significant differences in the overall approach to placing product into the market in Europe and keeping it there versus the United States. Once product is approved for distribution within the states (510(k) or PMA), it is for-the-most-part there for life, unless safety and efficacy concerns (i.e., hurting patients / too many MDRs) force a market withdraw (a.k.a., the dirty six-letter word RECALL). Providing PMA supplements are filed when required (e.g., design changes), the Design History File (DHF) and Device Master Record (DMR) are maintained, and letters to file are timely, device manufacturers playing in FDA’s sandbox should be fine.

FDA’s scenario is similar for initial product approvals in the EU but simply not the case for long-term maintenance. Class III products introduced into commerce in the EU require a Design Dossier to be assembled, reviewed, and approved by a notified body (similar concept to the PMA requirement). For Class IIa and IIb devices, the assembly of a Technical File is required (similar concept to the 510(k). In the good-old days, the path of conformity for Class IIa and IIb devices was self-certification. Now notified bodies are reviewing the technical files prior to granting product approvals. Another Dr. D FYI – it is strongly recommended, although not mandated by law, European Harmonized Standards be employed in the design and testing of new products. Trust me, it will save you a bunch of time when the notified bodies commence with the proverbial; “Why wasn’t this standard considered questions.” Once the dossiers and technical files have been approved, certificates of approval are issued (e.g., Design Examination Certificate (DEC) for a Class III device). Then and only then, can the device manufacturer legally affix the CE Mark of their notified body onto the label of their product.

For long-term sustainment of product sales within the EU, once every three to five-years, depending on the notified body, the Design Dossiers (Class III Products) must be submitted to your notified body for review and approval. Why? Because in the EU all of the DECs issued, regardless of the notified body, have an expiration date. Now granted, the MDD does allow the extension of certificates; however, Dr D has seldom witnessed this practice employed. Why? Because notified bodies make money reviewing design dossiers, it is not a labor of love.

Additionally, technical files are required to be reviewed during the annual visit, to your manufacturing facility, by notified bodies performing their annual surveillance audits. In fact, one of the changes to the MDD requires the notified bodies to increase the sample size of technical files reviewed during each visit.

Furthermore, similar to the MDRs, if vigilance reports start flooding the offices of the competent authorities located within each member state, be prepared for a potential market withdraw. The competent authorities have the authority (that is why they are called the competent authority – duh, dud-duh) to ban products from entering the EU, if these products are hurting people. Finally, if your notified body pulls your organization’s certificates or the certificates expire, your organization is mandated “By Law” to remove the CE Mark from affected product. Why? Let Dr. D repeat, the MDD is law within the EU, and to play in the EU’s medical-device sandbox, compliance to these laws is mandatory.

Takeaways
Similar to the QSR, the MDD defines the framework for the levels of compliance needed for products to be distributed within the EEC. The number one takeaway from this edition of DG is that a CE Mark is required for product to enter the EU. To obtain a CE Mark, there are a number of steps that need to occur prior to affixing the CE Mark.

(a) Select a recognized notified body (TUV-R, BSI, KEMA, etc. and no Dr. D is not a paid spokesperson for these organizations). Remember this relationship is a long-term partnership; and an experienced notified body is an industry necessity needed to assist in navigating the EU regulatory arena.
(b) Establish and maintain a quality system that is compliant with EN ISO 13485 and the MDD. This should not be a problem if your organization is already compliant with the QSR. Your notified body will help with the process. Remember, the notified bodies work for you, so do not be afraid to ask for their help.
(c) Compile and submit technically accurate design dossiers and technical files to your notified body for approval. Once approval is received, ensure these files are updated regularly (e.g., harmonized and industry standards are always changing).
(d) Do not attempt to ship product into the EU until all of the certificates are received, because doing so is a violation of the Directive.
(e) Ensure an EU Authorized Representative is under written contract. A Dr. D compliance tip – the notified body will want to review this contract during their annual visit.
(f) Whenever possible, Dr D strongly suggests the use of Harmonized Standards when designing and testing products. Use of these standards, although not compulsory, will result in fewer questions from the notified bodies and faster overall product approvals.
(e) Ensure the Declarations of Conformity are accurate before having your CJO affixing their signature. Why? It just does not reflect well on the organization when the notified body finds errors in your organization’s regulatory documents that claim compliance and ask for rework.

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 1 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. 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.
3. Is your company ready for the 2010 Medical Device Directives? (2008, June). Medical Design. Retrieved December 22, 2010, from http://medicaldesign/mag/company_ready_medical_0608/
4. Medical Device Directive. (1993). Council Directive 93/42/EEC. Medical Device Safety Service. Retrieved December 21, 2010, from http://directive93-42-eec.htm.
5. Medical Devices Directive. (2010). Conformance CE Marking and product safety consultancy. Retrieved December 22, 2010, from http://www.conformance.co.uk.
6. MDD, the Medical Device Directive 93/42/EEC – introduction. (2010). Medical Device Certification. Retrieved December 22, 2010, from http://www.mdc-ce.de/cert_md1.htm
7. Schnoll, L. (1997, September). The CE Mark: Medical Device Directive. Retrieved December 22. 2010, from http://www.qualitydigest.com