Annex III (EC Type – Examination) of Council Directive 93/42/EEC, a.k.a., the Medical Device Directive (MDD) delineates the requirements for having one’s head examined in the European Union (EU). In short, the Annex III requirement clearly states that one must definitely have their head examined if they choose to work in quality or regulatory in the medical device industry.
Ha, ha, ha, I hope Dr. D has captured your attention with my attempt at some levity. All kidding aside, there is an examination associated with the Annex III requirement; however, it deals with a medical device manufacturer’s notified body and the examination of their device application and technical data for entry into the EU’s medical device market. The doctor’s experience in regard to the application submission and review process just might lead some device industry professionals to form the conclusion that maybe having one’s head examined might not be too far off base. Regardless, this Annex is a salient requirement of the Directive. Not unlike the game of Monopoly, where one must “pass go to collect $200.00,” notified bodies will not issue an EC Type Examination Certificate if device manufacturers are not able to “pass the device examination process.” Simply put, no certificate equates to no sales; a.k.a., no revenue stream coming from the European market.
By now, I hope the readers of DG realize that although Dr. D lays no claim to being an overly sagacious (look-it-up) disciple of medical device regulations, my belief in compliance is driven by the underlying principle that medical devices must be safe and effective, regardless of market.
The MDD – 93/42/EEC
ANNEX III – EC Type – Examination
1. EC type-examination is the procedure whereby a notified body ascertains and certifies that a representative sample of the production covered fulfills the relevant provisions of this Directive.
2. The application includes:
- the name and address of the manufacturer and the name and address of the authorized representative if the application is lodged by the representative,
- the documentation described in Section 3 needed to assess the conformity of the representative sample of the production in question, hereinafter referred to as the ‘type’, with the requirements of this Directive. The applicant must make a ‘type’ available to the notified body. The notified body may request other samples as necessary,
- a written declaration that no application has been lodged with any other notified body for the same type.
3. The documentation must allow an understanding of the design, the manufacture and the performances of the product and must contain the following items in particular:
- a general description of the type, including any variants planned, and its intended use(s),
- design drawings, methods of manufacture envisaged, in particular as regards sterilization, and diagrams of components, sub-assemblies, circuits, etc.,
- the descriptions and explanations necessary to understand the above- mentioned drawings and diagrams and the operation of the product,
- a list of the standards referred to in Article 5, applied in full or in part, and descriptions of the solutions adopted to meet the essential requirements if the standards referred to in Article 5 have not been applied in full,
- the results of the design calculations, risk analysis, investigations, technical tests, etc. carried out,
- a statement indicating whether or not the device incorporates, as an integral part, a substance, or human blood derivative, referred to in Section7.4 of Annex I, and the data on the tests conducted in this connection which are required to assess the safety, quality and usefulness of that substance, or human blood derivative, taking account of the intended purpose of the device,
- a statement indicating whether or not the device is manufactured utilizing tissues of animal origin as referred to in Directive 2003/32/EC,
- the solutions adopted as referred to in Annex I, Chapter I, Section 2,
- the preclinical evaluation, —the clinical evaluation referred to in Annex X,
- the draft label and, where appropriate, instructions for use.
4. The notified body must:
- 4.1. examine and assess the documentation and verify that the type has been manufactured inconformity with that documentation; it must also record the items designed inconformity with the applicable provisions of the standards referred to in Article 5, as well as the items not designed on the basis of the relevant provisions of the above mentioned standards;
- 4.2. carryout or arrange for the appropriate inspections and the tests necessary to verify whether the solutions adopted by the manufacturer meet the essential requirements of this Directive if the standards referred to in Article 5 have not been applied; if the device is to be connected to other device(s) in order to operate as intended, proof must be provided that it conforms to the essential requirements when connected to any such device (s) having the characteristics specified by the manufacturer;
- 4.3. carry out or arrange for the appropriate inspections and the tests necessary to verify whether, if the manufacturer has chosen to apply the relevant standards, these have actually been applied;
- 4.4. agree with the applicant on the place where the necessary inspections and tests will be carried out.
5. If the type conforms to the provisions of this Directive, the notified body issues the applicant with an EC type-examination certificate. The certificate must contain the name and address of the manufacturer, the conclusions of the inspection, the conditions of validity and the data needed for identification of the type approved. The relevant parts of the documentation must be annexed to the certificate and a copy kept by the notified body.
- In the case of devices referred to in Annex I, Section 7.4, second paragraph, the notified body shall, as regards the aspects referred to in that section, consult one of the authorities designated by the Member States in accordance with Directive 2001/83/EC or the EMEA before taking a decision. The opinion of the competent national authority or the EMEA must be drawn up within 210 days after receipt of valid documentation. The scientific opinion of the competent national authority or the EMEA must be included in the documentation concerning the device. The notified body will give due consideration to the views expressed in this consultation when making its decision. It will convey its final decision to the competent body concerned.
- In the case of devices referred to in Annex I, Section 7.4, third paragraph, the scientific opinion of the EMEA must be included in the documentation concerning the device. The opinion of the EMEA must be drawn up within 210 days after receipt of valid documentation. The notified body will give due consideration to the opinion of the EMEA when making its decision. The notified body may not deliver the certificate if the EMEA’s scientific opinion is unfavorable. It will convey its final decision to the EMEA.
- In the case of devices manufactured utilizing tissues of animal origin as referred to in Directive 2003/32/EC, the notified body must follow the procedures referred to in that Directive.
6. The applicant must inform the notified body which issued the EC type-examination certificate of any significant change made to the approved product. Changes to the approved product must receive further approval from the notified body which issued the EC type-examination certificate wherever the changes may affect conformity with the essential requirements or with the conditions prescribed for use of the product. This new approval must, where appropriate, take the form of a supplement to the initial EC type-examination certificate.
7. Administrative provisions
- 7.2. Other notified bodies may obtain a copy of the EC type-examination certificates and/or the supplements thereto. The Annexes to the certificates must be made available to other notified bodies on reasoned application, after the manufacturer has been informed.
- 7.3. The manufacturer or his authorized representative must keep with the technical documentation copies of EC type-examination certificates and their additions for a period ending at least five years after the last device has been manufactured. In the case of implantable devices, the period shall beat least 15years after the last product has been manufactured.
What you need to know
Since the EC Type – Examination is so dependent on the notified bodies, device manufacturers need to select a notified body they are comfortable working with, which should include familiarity with the manufacturer’s device technology. That being said, Annex III is all about the notified bodies and their authority to review and certify products. Under the requirements of Annex III, the device manufacturer must file an application and provide relevant device technical information (design dossier) to their notified body for review. As a minimum, the application shall include:
- The manufacturer’s name and address;
- The name and address of their European authorized representative;
- The appropriate technical documentation (design dossier); and
- A written declaration that clearly states that a similar application has not been filed with another notified body. Remember, only one device application, for each device type, is permitted in the EU.
The documentation will vary depending on the medical device being submitted for review. For example, if a device incorporates a human blood derivative, additional testing will be required. In general, the following pieces of information will need to be incorporated into the technical documentation:
- Device description, including variations of the device that are being planned (a.k.a., product-line extensions);
- The intended use of the device;
- Device design drawings (including component drawings);
- Manufacturing / production drawings;
- Method of sterilization;
- A list of applicable standards employed (hopefully, European Harmonized Standards);
- The results of design and development activities, including testing performed;
- The application of risk analysis tools;
- A statement indicating the presence, or lack of, human blood derivatives;
- A statement indication the presence, or lack of, animal tissues;
- Pre-clinical and clinical evaluations performed; and
- A copy of the device’s draft label and instructions for use, containing English and 135 languages and dialects (just kidding about the 135; however, translation for applicable languages spoken within the EU, minus the dialects will be required for product distribution within non-English speaking Member States).
Notified Body Requirements
Under the requirements delineated within Annex III, the notified bodies are required to make their clients miserable by rejecting applications multiple times and by asking silly questions that have intuitively obvious answers to the most casual observers. Sorry, if Dr. D has a jaded view of this process; however, the doctor has experienced “The Good, The Bad, and The Ugly” – great movie – when working with notified bodies and their review of technical data. That being said, the notified bodies are required to:
- Exam the technical documentation and verify that the manufactured medical device in in conformance with its specifications and standards claimed;
- Arrange for inspections and testing, as applicable, to verify device conformance to essential requirements;
- Arrange for inspection and testing to ascertain correct selection and use of standards, chosen by the manufacturer;
- Work in conjunction with the device manufacturer in selecting an appropriate location for additional inspection and test, if deemed necessary and appropriate; and
- Issue a certification upon the successful review and acceptance of the application and technical documentation.
Device Manufacturer (a.k.a., the applicant)
Once the device manufacturer receives the certificate of examination, the overall process does not end. In fact, as long as the approved medical device remains on the European market and for a time after the device is no longer available on the market; there will always be additional requirements needing to be met. One of the more salient requirements is the need to submit all proposed device changes, deemed as significant, to the notified body for review and approval. What is the heck does “significant change” mean Dr. D? The doctor likes to categorize “significant change” as a change that influences device form, fit, function, or performance against the originally approved product specification. When in doubt, play it safe and ask your notified body for guidance. Not unlike the submission of a Class III device change in the United States, where a 30-day PMA supplement is required by the FDA, the same concept holds true for the EU.
Two key provisions associated with Annex III relate to the rights of other notified bodies to obtain copies of examination certificates and the retention of examination certificates. (1) Other notified bodies may request a copy of any examination certification and their additions, by making a formal request through application. If the reason depicted is deemed reasonable, a copy of the examination certificate will be supplied, after the manufacturer has been notified. (2) The retention period for examination certificates will be a minimum of 5-years (after last device is manufactured) or 15-years for implantable devices. The device manufacturer or the device manufacturer’s EU authorized representative shall be tasked in retaining these copies.
What you need to do
The single most important thing that device manufacturers need to do is prepare a design dossier that is clear, concise, and complete. Early in this guidance, the doctor poked fun at notified bodies and their notoriously painful review process. Device manufactures can easily fall prey to the infinite “do-loop” if key components of the dossier are missing. Believe it or not, leaving out little things like sterilization, shelf-life testing, and package-integrity testing can result in significant delays to the approval process.
Additionally, not unlike the FDA, notified bodies do not like surprises. Yes, the notified bodies work for the device manufacturers; and the device manufacturers pay for this service. The service provided is not cheap. Remember, protracted reviews due to the inadvertent omission of technical data equates to more money being spent as a result. One more thing to remember is the potential for revenue lost as a device application remains in limbo due to an incomplete design dossier or errors in technical documentation. These problematic issues force the notified body’s reviewer to play a game of 50-questions. It is just not worth the pain not to get the submission right the first time. Will there be questions surrounding the submission? Absolutely, but the hope is that the amount of questions generated are just a handful needing to address minor details.
Finally, never forget about the need to retain the examination certificate and the technical documentation (a.k.a., the design dossier) for the required length of time. The doctor has experienced on a couple of occasions requests for the dossier being made by a Competent Authority, shortly after device production has officially stopped.
For this edition of DG, there are just two takeaways device manufacturers need to clearly understand and remember. The application process begins with an application supported by a clear, concise, and complete design dossier. Device manufacturers want to ensure all of the technical documentation is readily available for their notified bodies during the examination process. A poorly constructed and/or incomplete design dossier will result in an initial rejection, the proverbial game of “50-questions” and a protracted review and approval process, keeping the device out of the European market. The second takeaway is the responsibilities associated with certificate and data retention. Just because a device manufacturer stops manufacturing a device does not mean it is ok to toss out the certificates or design dossier. There is a mandatory retention period of either 5 or 15 years, depending on the application of the device.
Until the next installment of DG, when Dr. D will begin providing guidance for complying with Annex IV (EC Verification) of Council Directive 93/42/EEC, the MDD – cheers from Dr. D and best wishes for continued professional success.
- 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.
- Annex II (EC Declaration of Conformity – full quality assurance system) of Council Directive 93/42/EEC, a.k.a., the Medical Device Directive (MDD) delineates the regulatory requirements necessary for compliance with the Directive employing an acceptable quality assurance system. Additionally, applications required by notified bodies for the quality management system (QMS) and device review and approval are included as part of Annex II.