Dr. Christopher Joseph Devine, President, Devine Guidance International
Devine Guidance

IVDD – An Introduction

By Dr. Christopher Joseph Devine
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Dr. Christopher Joseph Devine, President, Devine Guidance International

This series of articles will be premised on the IVDD.The primary takeaway from this week’s edition is that there are significant similarities between the MDD and the IVDD. However, there are also several differences that make the IVDD appear quirky. With revisions to the IVDD looming on the horizon, ongoing compliance with this Directive will continue to be a challenge.

Dr. D received several requests in regards to the next series of articles the good doctor should pen. The three finalists were: (a) the Canadian Medical Device Conformity and Assessment System (CMDCAS); (b) Japan’s Ministry of Health, Labor, and Welfare’s (MHLW) Ministerial Ordinance 169 – Standards for Manufacturing Control and Quality Control for Medical Devices and In-vitro Diagnostic Reagents; and (c) Directive 98/79/EC – The European Directive on In Vitro Diagnostic Medical Devices (IVDD). 

Although all three of these pieces of medical device regulation are worthy of Dr. D’s weekly tirades, the doctor does not have enough hours in a week to tackle all three. That being said, this series of articles will be premised on the IVDD. The IVDD is actually one of three recognized device Directives in Europe; the first Directive being 93/42/EEC, a.k.a. the MDD, which was the topic of the previous series of Devine Guidance. In fact, if you have not had the pleasure of reading the previous series, feel free to do so. They are available at MedicalDeviceSummit.com

The other Directive is Active Implantable Medical Device (AIMD) Directive – 90/385/EEC, which Dr. D will eventually cover in a series.

Just contemplating the need for three Directives governing medical devices in the EU can make one’s head spin. In fact, the use of some kind of mnemonic (look-it-up) device just might be helpful in trying to memorize and retain all of the data imbedded in these Directives. Regardless, just like the MDD and the AIMD, the IVDD is law in the EU (enough acronyms already) and compliance is mandatory.

The IVDD – 98/79/EEC
Dr. D would like to begin this new series of DG by providing a definition for the term “in vitro.” According to Merriam-Webster’s on-line dictionary, the Latin translation for “in vitro” is “in glass.” Now the doctor understands that not many folks are walking around speaking Latin anymore; so the English translation is “outside the living body and in an artificial environment.” Now for the Latin translation, the only thing that Dr. D prefers in vitro is good bourbon. However, if Dr. D walked up to the bar and asks for; “Jack on the rocks – in vitro,” I am sure the bartender would quickly show the good doctor the door.

Getting back to the IVDD, the readers are going to find a significant amount of similarities between the IVDD and the MDD. The IVDD is equally verbose and is broken down into Articles and Annexes, just like the MDD. In fact, many of the Articles and Annexes share the same titles as the MDD. So why bother with a stand-alone Directive Dr. D? It seems the regulatory folks in the EU could have easily expanded on the virtues of the MDD and save themselves the time and effort of creating another Directive.

That being said folks, is not the doctor’s call, besides another Directive gives Dr. D the chance to continue writing so the readers can enjoy his colorful approach to analyzing the IVDD and providing some useful guidance.

IVDD Basics
The IVDD was ratified by the European Parliament on 28 October 1998. There are 24 Articles and imbedded in the body of the IVDD. The Articles are:
  1. Article 1 – Scope, definitions
  2. Article 2 – Placing on the market and putting into service;
  3. Article 3 – Essential  requirements;
  4. Article 4 – Free movement;
  5. Article 5 – Reference to standards;
  6. Article 6 – Committee on Standards and Technical Regulations;
  7. Article 7 – “No title” A continuation of Article 6;
  8. Article 8 – Safeguard clause;
  9. Article 9 – Conformity assessment procedures;
  10. Article 10 – Registration of manufacturers and devices;
  11. Article 11 – Vigilance procedures;
  12. Article 12 – European databank;
  13. Article 13 – “No title” Protection of public health and safety clause;
  14. Article 14 – Amendments to Annex II, and derogation clause;
  15. Article 15 – Notified bodies;
  16. Article 16 – CE marking;
  17. Article 17 – Wrongly affixed CE marking;
  18. Article 18 – Decisions in respect of refusal or restriction;
  19. Article 19 – Confidentiality;
  20. Article 20 – Cooperation between Member States;
  21. Article 21 – Amendment of directives;
  22. Article 22 – Implementation, transitional provisions;
  23. Article 23 – “No title” Publication into the Official Journal clause; and
  24. Article 24 – “No title” Directive addressed to Member States clause.
The Annexes associated with the IVDD are:
  1. Annex I – Essential Requirements;
  2. Annex II – List of Devices Referred to in Article 9(2) and (3) – Lists A & B;
  3. Annex III – EC Declaration of Conformity;
  4. Annex IV – EC Declaration of Conformity (Full Quality Assurance System);
  5. Annex V – EC Type-Examination;
  6. Annex VI – EC Verification;
  7. Annex VII – EC Declaration of Conformity (Production Quality Assurance);
  8. Annex VIII – Statement and Procedures Concerning Devices for Performance Evaluation;
  9. Annex IX – Criteria for the Designation of Notified Bodies; and
  10. Annex X – CE Marking of Conformity.
What IVD device manufacturers need to know
As most device industry professionals realize, the introduction of new regulations or changes to regulations always creates an elevated level of angst. Guess what? The IVDD is no exception. The reason Dr. D is saying this is because changes to the IVDD are on the horizon. In June of 2010, the European Commission made the decision to ask for public comments in regards to proposed revisions to the Directive. The Commission was very specific when drafting a series of questions applicable to current sections in the Directive and potential additions to the Directive. Early in 2011, the Commission published the results. A few of the key areas where opportunities for change and improvement were noted:
  1. The Classification System, specifically clarity surrounding List A and List B devices depicted under Annex II (expanded risk-based classification to be considered);
  2. Revision and/or potential deletion of Annex VI – EC Verification; 
  3. Clarification of device testing modalities;
  4. Clinical requirements; and
  5. The addition of an option to obtain a Conditional CE Marking of Conformity.  
In short, it is inevitable that revisions to the IVDD will happen. Some of the notified bodies the doctor has spoken with expect these changes to become effective in 2015. A final draft should be available next year. 
Now granted, change is inevitable so what else do the manufacturers of IVD medical devices need to know? 
  1. For starters, the Quality Management System (QMS) should still be premised on ISO 13485:2003. 
  2. The IVDD is the law of the land for the 27-Member States comprising the EU. 
  3. The path for conformity and the obtainment of the CE marking of conformity is defined within the IVDD.
  4. IVD medical devices need to conform to their essential requirements.
  5. Technical documentation, including design dossiers, is still required as part of the approval process through the notified bodies.
  6. Devices categorized under List A (high-risk) requires a mandatory examination of the technical documentation by a notified body (prepare the dossier).
  7. The establishment of a European Authorized Representative is still a requirement.
  8. IVD devices still require a CE Mark reflecting the registration number of the manufacturer’s notified body.
  9. The establishing of a post-market surveillance program remains a salient requirement.
  10. The Chief Jailable Officer (CJO) still needs to sign the Declarations of Conformity.
What IVD device manufacturers need to do
The late Al Davis, National Football League Hall of Fame Member and the long-time owner of the Oakland Raiders always used to say, “Just win-baby-win!” Dr. D would like to borrow his tag line and say, “Just comply-baby-comply!” Regardless of the perceived idiosyncrasies associated with 98/79/EC, compliance to this Directive is mandated by law within the EU. The similarities to 93/42/EEC should make compliance to the IVDD a relatively simple task for device manufacturers with experience introducing medical devices into the EU, under the MDD. However, there are some subtle differences that can make attempts at complying with the IVDD a frustrating experience. For example, correctly identifying the appropriate classification of a device in accordance with List A versus List B (Annex II) appears to pose a significant challenge for IVD device manufacturers. Dr. D always recommends holding court with the notified body to ensure the correct device classification is selected in accordance with Annex II. 
Similar to the MDD, IVD device manufacturers are required to comply with basic requirements delineated throughout the directive. For example IVD device manufacturers: 
(a) Shall have an approved QMS; 
(b) Shall employ effective design control tools when developing devices; 
(c) Shall manufacturer in a controlled environment; 
(d) Shall employ a validated sterilization method, if deemed appropriate; 
(e) Shall package devices in a way that protects the product from damage;
(f) Shall properly label each device, including the CE Mark; 
(g) Shall perform appropriate testing and inspection of each device; 
(h) Shall construct Instructions for Use for device; 
(i) Shall compile and retain technical documentation (notified bodies will review the technical documentation as part of the application approval process); 
(j) Should consider employing the Harmonized Standards (not required but strongly recommended); 
(j) Shall notify the notified body of significant changes to a device;
(k) Shall contract with a European Authorized Representative;
(l) Shall prepare a design dossier for Annex II, List-A devices.
(m) Shall expect annual audits from the notified body;
(n) Shall establish and maintain a program for post-market surveillance; and
(o) Shall have the CJO sign the Declaration of Conformity.
Takeaways
The primary takeaway from this week’s edition of DG is that there are a significant amount of similarities between the 93/42/EEC (the MDD) and 98/79/EC (the IVDD). However, there are also several differences that make the IVDD appear quirky. The employment of List A versus List B has resulted in much angst for IVD device manufacturers. Finally, with revisions to the IVDD looming on the horizon, ongoing compliance with this Directive will continue to be a challenge.

Until the next installment of DG, when Dr. D provides insight and guidance into complying with Article 1 (Scope, definitions) of the In Vitro Diagnostic Medical Device Directive, a.k.a., IVDD – cheers from Dr. D and best wishes for continued professional success.

 
 
References: 
  1. 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
  2. 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
  3. 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.
  4. Devine, C. (2011). Devine Guidance series on complying with the MDD. Published in The Medical Device Summit; http://medicaldevicesummit.com
  5. 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 
  6. Retrieved September 12, 2011, from http://eur-lex.europa.eu
  7. EN ISO 13485:2003. (2004, February). Medical devices – quality management systems – requirements for regulatory purposes (ISO 13485:2003).
  8. Merriam-Webster On-line Dictionary. (2011). In vitro. Retrieved 08 October 2011, from http://www.merriam-webster.com/medical/in%20vitro
  9. Stynen, D. (2011, July). Revision of Europe’s IVD directive 98/79/EC – lessons and results from public consultation document. Retrieved 03 October 2011, from http://www.ivdtechnology.com
  10. The EU In-Vitro Diagnostic Directive. (1998, December). Retrieved 10 October 2011, from http://www.bioingegneria
  11. Williams, S. (2010, February). Understanding the EC directive 98/79/EC on in vitro diagnostic medical devices. Retrieved 08 October 2011, from http://www.sgs.com/ivd-medical-devices-white-paper

 

Dr. D’s first book “Devine Guidance for Complying with the FDA’s Quality System Regulation” has finally been published.
Visit http://devineguidanceinternational.com or Amazon to obtain a copy. 
(ISBN: 9781466358768)

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Dr. Christopher Joseph Devine, President, Devine Guidance International

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