Thanks again to Rob Packard for providing another guest post. Rob is a Regulatory Affairs and Quality Management System expert whose specialty is helping companies with regulatory submission of a Design Dossiers for CE Marking of high-risk Class III medical devices. You can read more of Rob’s work at QC is Dead and RA Review blogs.
Thank you for reading my previous posting on Creo Quality, “Canadian Licence Process for Medical Devices – A Step by Step Example” from July 30th. This second posting in the series explains the process for obtaining CE Marking approval for a Medical Device.
For our example, we will be using the same hypothetical client for Jon to help.
Jon’s client called to ask if he could help them expand into the European market. As with the Canadian Market, Europe also considers cyanoacrylate a medical device when it is used as a topical adhesive. Jon’s first step is to determine the device classification as per Annex IX in the Medical Device Directive (93/42/EEC as modified by 2007/47/EC). Instead of relying solely upon the Directive, Jon also uses guidance documents published on the Europa website–specifically MEDDEV 2.4/1 rev 9 (the following link explains the European MEDDEV guidance documents – http://wp.me/p2DThn-1r).
Jon identifies three potential device classifications: 1) Class 1 as per Rule 4 (a non-invasive device which comes into contact with injured skin, if the device is intended to be used as a mechanical barrier, for compression or for absorption of exudates); 2) Class 2a as per Rule 7 (a surgically invasive device intended for short-term use [i.e. - < 30 days] are in Class 2a; and 3) Class 2b as per Rule 8 (an implantable device). These three applications match the three possible applications that Jon identified when he was reviewing Canadian Device licenses.
If this device were not required to be “sterile”, then a Class 1 device could use the Annex VII route of conformity (i.e. – self-declaration). However, even generic bandages are sold as sterile devices. Therefore, whether the device is a sterile Class 1 device or a Class 2a device, obtaining CE Marking approval will still require a Notified Body’s review and approval. The most common route would be the Annex V route of conformity. If Jon’s client were to launch their product as a “glue” for internal use, then the device would require an Annex II.3 Full Quality System Certificate or the combination of an Annex V Certificate and a Type Examination Certificate (i.e. – Annex III).
The previous paragraph was hard to understand, but the source of this jargon is Article 11 of the Medical Device Directive. This one section is best practices in European legalese. If you want to make something almost unintelligible, copy Article 11. If you want to understand this stuff, a flow chart of the various routes to conformity is as good as it gets (still hard to understand, but fewer words).
What you need to know…
Jon’s client only has one product family and they are currently selling the product in Canada for external use by healthcare professionals—not as an implant. Therefore, the device is a Class 2a device requiring an Annex V certificate. Jon’s client will need to do the following:
1) Select a Notified Body
2) Submit a Technical File for review and approval
Fortunately, Jon’s client already obtained an ISO 13485:2003 certificate with CMDCAS from their current registrar as part of the Canadian Licensing process. Therefore, the changes required for the Quality System consist of adding a few work instructions to meet European-specific requirements, such as vigilance reporting, creating a technical file and performing clinical evaluations. Jon’s client also needs to add the European Requirements as an applicable regulatory requirement in the Quality Manual.
The bigger challenge is assembly of a Technical File for submission. Since the product is already on the market in Canada, all of the technical requirements have been met. The documentation of these requirements now needs to be converted into a format acceptable to a Notified Body. There are three recommended strategies:
- What ever the Notified Body prefers. Some of the Notified Bodies have a checklist of requirements for a Technical File. If such a checklist exists, the client should organize the Technical File in exactly the same order.
- The GHTF STED format (GHTF/SG1/N011:2008). The Global Harmonization Task Force (www.ghtf.org) published this guidance document in an effort to standardize the format for submission of regulatory submissions. This is the format required for Class 3 and 4 Canadian medical device license applications.
- The NB-MED recommended format (NB-MED 2.5.1/rec 5). This document was created by the “Big 5” Notified Bodies. It provides a template in a two-part format for submissions. This is the format I use most often for auditing files and for creating new files.
Jon’s client chose option 3 for organizing their Technical File, because they have full reports for each of the verification and validation tests that were performed, but creating summaries for each report would take longer than assembling a Technical File with copies of each of these full reports.
In all, Jon estimates that his client can complete their preparations in about 60 days. Therefore, Jon suggested that the client obtain a quotation from their registrar for an Annex V Certificate. In addition, Jon suggested hiring a consultant to help them with preparation of a Clinical Evaluation. Prior to 2010, Clinical Evaluations were only required for high-risk devices. As part of the new MDD, clinical evaluations are now required for all devices. Since the use of and risks associated with cyanoacrylates is well characterized in published literature, Jon’s client may use a literature search method for preparing a Clinical Evaluation as per MEDDEV 2.7/1 rev 3.
The company hired an authorized representative to handle European registration, receive customer complaints and to act as a liaison with the Competent Authority in the event of an adverse event. An Authorized Representative Agreement was signed, and the Authorized Representative recommended a few corrections to procedures they reviewed as part of entering the contract with a new client.
The company also hired a regulatory consultant that was able to complete a literature search and write a Clinical Evaluation within 4 weeks. The complete Technical File was assembled and submitted to the Notified Body electronically with 7 weeks of starting the project. The Notified Body’s first round of questions were received within 6 weeks. Jon and the client prepared responses to the questions in a week and submitted them to the Notified Body. Fortunately, the responses were thorough and the Technical File was well-organized from the start. The Notified completed their final review and recommended the product for CE Marking within 3 more weeks. The Notified Body conducted two panel reviews to verify the technical, regulatory and risk aspects of the submission. Finally, the Annex V certificate was received 12 weeks after initial submission of the Technical File.