Annex IV (EC Verification) of Council Directive 93/42/EEC, a.k.a., the Medical Device Directive (MDD) delineates the requirements for the verification of a medical device company’s checking-account balance prior to a notified body accepting a contract. Ha, ha, ha, just like the previous edition of DG, Dr. D thought he would inject some levity into a topic often deemed boring.
Now that the doctor has finally stopped laughing, there is a verification process associated with the Annex IV. It is a criminal background check to verify a device manufacturer’s Chief Jailable Officer (CJO) has never been incarcerated in The Hague, ha, ha, ha. Alright, the doctor promises to stop.
Seriously, Annex IV involves a whole bunch of trust as device manufacturers are expected to self-test and self-verify their devices meet essential requirements. Not too long ago, this process equated to the proverbial “free pass” for device manufacturers; however, today, not so much. As part of the revamped MDD, notified bodies are required to sample and exam technical files (Class IIa and IIb devices) from each product family a device manufacturer sells into the EU, during the annual audit performed by notified bodies. Additionally, Dr. D is now seeing that notified bodies are asking to review technical files prior to device manufacturers being given permission to affix the CE Marking of Conformity. Since the doctor has witnessed “The Good, The Bad, and The Ugly” (Dr. D loved this movie so he apologizes for his ongoing reference to it – but it is the doctor’s blog) when it comes to the completeness of technical files; the additional oversight by notified bodies is a good thing. Remember, Dr. D will never knowingly lead the readers of DG astray, but always attempt to present his somewhat colorful perception of the irrefragable (look-it-up) truth surrounding regulatory compliance.
The MDD – 93/42/EEC
ANNEX IV – EC Verification
1. EC verification is the procedure whereby the manufacturer or his authorized representative ensures and declares that the products which have been subject to the procedure set out in Section 4 conform to the type described in the EC type-examination certificate and meet the requirements of this Directive which apply to them.
2. The manufacturer must take all the measures necessary to ensure that the manufacturing process produces products which conform to the type described in the EC type-examination certificate and to the requirements of the Directive which apply to them. Before the start of manufacture, the manufacturer must prepare documents defining the manufacturing process, in particular as regards sterilization where necessary, together with all the routine, pre-established provisions to be implemented to ensure homogeneous production and, where appropriate, conformity of the products with the type described in the EC type-examination certificate and with the requirements of this Directive which apply to them. The manufacturer must affix the CE marking in accordance with Article 17 and draw up a declaration of conformity. In addition, for products placed on the market in sterile condition, and only for those aspects of the manufacturing process designed to secure and maintain sterility, the manufacturer must apply the provisions of Annex V, Sections3 and 4.
3. The manufacturer must undertake to institute and keep up to date a systematic procedure to review experience gained from devices in the post-production phase, including the provisions referred to in Annex X, and to implement appropriate means to apply any necessary corrective action. This undertaking must include an obligation for the manufacturer to notify the competent authorities of the following incidents immediately on learning of them:
(i) any malfunction or deterioration in the characteristics and/or performance of a device, as well as any inadequacy in the labeling or the instructions for use which might lead to or might have led to the death of a patient or user or to a serious deterioration in his state of health;
(ii) any technical or medical reason connected with the characteristics or performance of a device for the reasons referred to in subparagraph (i) leading to systematic recall of devices of the same type by the manufacturer.
4. The notified body must carry out the appropriate examinations and tests in order to verify the conformity of the product with the requirements of the Directive either by examining and testing every product as specified in Section 5 or by examining and testing products on a statistical basis as specified in Section 6, as the manufacturer decides. The aforementioned checks do not apply to those aspects of the manufacturing process designed to secure sterility.
5. Verification by examination and testing of every product
(i) Every product is examined individually and the appropriate tests defined in the relevant standard(s) referred to in Article 5 or equivalent tests must be carried out in order to verify, where appropriate, the conformity of the products with the EC type described in the type-examination certificate and with the requirements of the Directive which apply to them.
(ii) The notified body must affix, or have affixed its identification number to each approved product and must draw up a written certificate of conformity relating to the tests carried out.
6. Statistical verification
(i) The manufacturer must present the manufactured products in the form of homogeneous batches.
(ii) A random sample is taken from each batch. The products which makeup the sample are examined individually and the appropriate tests defined in the relevant standard(s) referred to in Article 5 or equivalent tests must be carried out to verify, where appropriate, the conformity of the products with the type described in the EC type-examination certificate and with the requirements of the Directive which apply to them in order to determine whether to accept or reject the batch.
(iii) Statistical control of products will be based on attributes and/or variables, entailing sampling schemes with operational characteristics which ensure a high level of safety and performance according to the state of the art. The sampling schemes will be established by the harmonized standards referred to in Article 5, taking account of the specific nature of the product categories in question.
(iv) If the batch is accepted, the notified body affixes or has affixed its identification number to each product and draws up a written certificate of conformity relating to the tests carried out. All products in the batch maybe put on the market except any in the sample which failed to conform. If a batch is rejected, the competent notified body must take appropriate measures to prevent the batch from being placed on the market. In the event of frequent rejection of batches, the notified body may suspend the statistical verification. The manufacturer may, on the responsibility of the notified body, affix the notified body’s identification number during the manufacturing process.
7. Administrative provisions
The manufacturer or his authorized representative must, for a period ending at least five years, and in the case of implantable devices at least 15 years, after the last product has been manufactured, make available to the national authorities the declaration of conformity; the documentation referred to in Section 2; the certificates referred to in Sections 5.2 and 6.4; and where appropriate, the type-examination certificate referred to in Annex III.
8. Application to devices in Class IIa. In line with Article 11 (2), this Annex may apply to products in Class IIa, subject to the following:
(i) in derogation from Sections 1 and 2, by virtue of the declaration of conformity the manufacturer ensures and declares that the products in Class IIa are manufactured inconformity with the technical documentation referred to in Section 3 of Annex VII and meet the requirements of this Directive which apply to them;
(ii) in derogation from Sections 1, 2, 5 and 6, the verifications conducted by the notified body are intended to confirm the conformity of the products in Class IIa with the technical documentation referred to in Section 3 of Annex VII.
9. Application to devices referred to in Article 1(4a)
In the case of section 5, upon completing the manufacture of each batch of devices referred to in Article 1(4a), and in the case of verification under section6, the manufacturer shall inform the notified body of the release of this batch of devices and send to it the official certificate concerning the release of the batch of human blood derivative used in the device issued by a State laboratory or a laboratory designated for that purpose by a Member State in accordance with Article 114(2) of Directive 2001/83/ EC.
What you need to know
Dr. D views Annex IV of the Directive as being broken down into six salient elements. Remember, the premise of this Annex is the device manufacturer’s ability to verify and declare that their product meets the requirements of the MDD, as applicable. Additionally, the notified bodies are required to exam and test product, on a sample basis as a minimum, prior to allowing the affixing of the CE Mark to a manufacturer’s product.
Element One – As previously stated, the device manufacturer or their European Authorized Representative has the authority to exam, verify, and declare their product (Class IIa and IIb) meets the Directive, as applicable. As part of this process, the manufacturer must ensure all of the appropriate steps have been taken in regards to documenting the design and development, verification activities, validation activities, testing, including the entire manufacturing process and sterilization. In reality, the technical file, once assembled, will look like a design dossier (Class III device). Prior to the first production device being manufactured, the device manufacturer must draw up the Declaration of Conformity, ensure that it is signed by the CJO, and send the Declaration to their notified body for review and approval. Once approved, the CE Mark can be affixed to the product. Just an FYI – chances are pretty good that the notified body is going to want to see the technical file, as well. So device manufacturers need to ensure the technical file is robust; and contains technical data supporting claims of compliance with essential requirements.
Element Two – Post-market surveillance activities, just like the United States, are applicable for the EU as well. Device manufacturers are expected to collect product performance issues, including adverse events and use this information to correct product deficiencies. Device manufacturers are required to notify the Competent Authorities when: (a) device malfunction; (b) device performance deterioration; (c) device labeling issues; or (d) device instructions for use issues; have resulted in serious injury to, or death of a patient or user. Product recalls, driven by the same reasons just given, also require notification to the Competent Authorities. Trust Dr. D when I say, “If a device manufacturer’s products are racking up a significant number of vigilant reports in the EU, they can expect a telephone call and a visit from their notified body.”
Element Three – As previously stated, the notified bodies are required to test and exam devices that were previously self-verified by the manufacturer. In pursuing this objective, notified bodies have two options; (a) 100 percent examination and test (minus sterilization); and (b) sample examination and test. Regardless, device manufacturers can expect some level of verification by their notified bodies. Remember, as a result of changes made to the MDD, there are no more free passes.
Element Four – The manufacturer or the manufacturer’s authorized rep is required to retain data associated with this Annex for a period of 5-years or 15-years (implantable). As a minimum, this data shall include:
- The Declaration of Conformity;
- Relevant documentation;
- Certificates; and
- The type-examination certificate, as appropriate.
Element Five – Is an applicability and derogation clause for Class IIa devices. As a device manufacturer, if you have been creating robust technical files for all of your Class IIa and IIb devices, including accessory technical data files, you should have no worries in regards to compliance with the Annex IV. As Dr. D stated earlier, notified bodies are now required to exam a sample of technical files from each product category during the annual audits. One additional note – the doctor has experienced the pain of having to correct and revise technical files that resided on a shelf for several years without any review or updates, including simple tasks like blowing the dust off the cover of a file. Technical files are dynamic documents requiring routine reviews and updates. Remember, if testing was performed to a harmonized standard, and that standard has changed, the technical file and applicable data must be reviewed for ongoing compliance to that change. If additional testing is required to claim compliance, manufacturers must generate the protocol and perform the testing. This is not an option but should be considered a salient requirement of the Directive.
Element Six – Is the human blood derivative clause. If a medical device contains a human blood derivative, additional testing is required by a State laboratory or other approved testing laboratory specified by a Member State.
What you need to do
Week-after-week the doctor preaches about the importance of compliance to regulations. Dr. D, based on the emails received from the readers, believes the message of compliance is being received and understood. That being said, performing device testing, executing effective verification and validation activities, and considering the influence and need to comply with applicable harmonized standards, each form a part of the foundation for a robust technical file. Device manufacturers need to concentrate on developing a robust technical file to facilitate the introduction of Class IIa and Class IIb product into the European device market. In fact, Dr. D strongly suggests creating a Standard Operating Procedure (SOP) dedicated specifically to the creation and management of technical files. This SOP should also contain a template that supports the standardization of an acceptable technical file format. The notified bodies love standardization as it makes their job easier when it comes to reviews. Remember, device manufacturers pay the notified bodies for their time and service. Call the doctor crazy but a reduction in hours expended by the notified body should equate to fewer dollars, pesos, or euros being spent by manufacturers.
For this edition of DG, Dr. D will leave the readers with three takeaways:
- Device manufacturers are empowered by Annex IV to exam, verify, and certify that their product meets essential requirements and the Directive;
- Notified bodies are required to keep the device manufacturers honest by performing examination and verification activities to ensure product does in fact meet essential requirements and the Directive; and
- If a device manufacturer’s product is deemed to be less than safe and effective and causing harm and/or death to the patient or user, these events must be reported to the Competent Authorities. Finally, device manufacturers can expect a visit from their notified body if their products are racking up the vigilant reports in the EU.
Until the next installment of DG, when Dr. D will begin providing guidance for complying with Annex V (EC Declaration of Conformity – Production Quality System) 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.