Annex VIII (Statement Concerning Devices for Special Purposes) of Council Directive 93/42/EEC, a.k.a., the Medical Device Directive (MDD) delineates the requirements for custom-made devices and/or investigational devices intended specifically for employment in clinical investigations. Similar to the Investigational Device Exemption (IDE) category used for devices intended for a clinical trial application in the United States, the MDD has specific requirements to ensure product safety and efficacy is sustained for similar devices used within the European Union (EU).
By now, the frequent readers of Devine Guidance (DG) are used to Dr. D’s occasional sprinkling of homiletic aphorisms (look-it-up) throughout each of these articles. This edition of DG will be no different. Remember, “Hindsight is always 20/20.”
The full text of MDD – 93/42/EEC ANNEX VIII – Statement Concerning Devices for Special Purposes can be viewed here (pages 50-51).
What you need to know
No surprises here, but device manufacturers need to work through their notified bodies to ensure the basic requirements associated with Annex VIII are achieved prior to shipment into the EU. For custom-made devices and investigational devices, the process commences with the generation of a statement of conformance that contains product-specific information. For custom-made devices, this statement must contain:
- The name and address of the actual manufacturer;
- Data that can be employed to quickly identify the custom-made device;
- A written statement that clearly defines that the custom device is intended for use on a specific patient, including the patient’s name;
- The name of the clinician prescribing the device and the address of the healthcare facility where the procedure will take place;
- The operating / performance characteristics of the custom-made device, as delineated by the prescription; and
- A statement that delineates the custom-made device meets essential requirements, as applicable.
For devices intended to be used in clinical investigations (trials), written statements, from the device manufacturer, are also required prior to these devices being given access to the EU. As a minimum, data needing to support the approval of devices intended for clinical use are:
- Data that can be employed to quickly identify the investigational device;
- The protocol to be employed in the clinical trial;
- Insurance confirmation for clinical trial participants;
- Informed consent documentation;
- Statements acknowledging the human-blood derivatives or tissue of animal origin within the investigational device, if applicable;
- Opinion of the ethics committee (from the applicable institution) pertaining to the actual protocol; and
- The actual name of the practitioner responsible for clinical trial oversight, execution, the address of the clinical trial location, starting date, and expected duration of the clinical trial; and
- A statement to the fact that the clinical device meets essential requirements and the device is safe and effective for its intended use.
Data and documentation requirements
For custom-made devices and investigational devices, there is also a requirement for specific pieces of data to be retained, just in case the Competent Authorities want to take a look. For custom-made devices, examples of data and documentation requiring to be retained are:
- Manufacturing location(s);
- Design documentation;
- Manufacturing documentation e.g., manufacturing processes;
- Inspection and testing methodologies applied to ascertain custom-made device performances; and
- Any and all documentation that supports claims of conformance to the Directive.
For investigational devices, additional data requirements are mandated by the Directive. In fact, these additional requirements mimic those of a technical file and/or design dossier. Since a positive outcome is always the hope of any clinical trial, Dr. D recommends just biting the bullet and doing the right thing from the start; and commence with the assembly of the technical file and/or dossier at inception. If this approach is followed, then upon conclusion of the trial, only the clinical data will need to be added. That being said, as a minimum, the documentation needed to support the investigation device are:
- The description of the medical device, including the intended use of the device;
- Design drawings (including design calculations), manufacturing processes, sterilization, critical components, subassemblies, inspection activities, and testing;
- Application of risk analysis (make sure to employ ISO 14971:2009);
- A compiled list of applicable standards, e.g., essential requirements checklist;
- Additional testing performed, if the device contains a human blood derivative; and
- Identification and risk assessment of animal tissue, if employed as part of the investigational device.
Remember, just because devices covered under Annex VIII have been given special names, their own Annex, and some dispensation in regards to regulatory requirements, the expectation is that the same inherent controls applied as part of routine manufacturing of approved medical devices are applicable to these devices. This includes audits to ensure the overall effectiveness of the tools employed in the design, manufacture, inspection, and testing of investigational devices.
Identical to the other Annexes, there is a data retention requirement for data used to support declarations. For most devices the standard requirement is five years. For implantable devices, the retention period is 15-years. Finally, and identical to previous Annexes, there is a post-market surveillance requirement. Manufacturers are expected to pursue appropriate corrective action when: (a) device malfunctions occur; (b) device performance characteristics have deteriorated; and (c) device performance has resulted serious injury or death of the patient or user. Remember, these adverse events must be reported in accordance with the European Vigilance Reporting process. Failure to report will surely agitate the Competent Authorities. Devices that fail to meet expected safety and efficacy requirements should be withdrawn, a.k.a., RECALLED!
What you need to do
Once again, Dr. D will share a not so well-kept secret. For medical device that are safe and effective, it is all about a robust design anchored in the application of adequate design verification and design validation methodologies. You can quote the doctor when I say; “A crappy design equates to a crappy device.” As an old quality guy, Dr. D has experienced, first-hand, the results of custom-made and clinical devices, regardless of the robustness of the design, being built on prototype production lines with limited controls in place. For some reason device manufacturers often equate “prototype” to “no quality oversight required.” Granted, this approach may be effective for building the initial path-finder units prior to design transfer. However, for building units that will be used on patients, quality oversight is required. This includes the use of calibrated instrumentation, trained operators, and manufacturing processes that have been appropriately validated. Why? Because under Annex VIII of the Directive, device manufacturers cannot build custom-made or investigational devices in the proverbial garage. Accuracy and documentation count!
One aspect of Dr. D’s business is the performance of supplier audits and internal audits. I always cringe when I peek into the engineering lab or assess prototype manufacturing lines for the same reasons depicted in the previous paragraph. That being said, the doctor has a solution. Device manufactures should have a dedicated pilot line for the manufacturing of custom-made and/or investigational devices. This line may not be operational 24/7; however, when needed, device manufacturers can quickly reassign assemblers, inspectors and technicians for brief periods of time to meet short-term demand. The pilot line should be considered a controlled line with all of the device manufacturer’s assembly, inspection, testing, training, calibration, and validation procedures in full-force. All product manufactured on this pilot line should have the appropriate manufacturing travelers, inspection results, test results, and associated documentation that will form the foundation of the device History Record (DHR). One final note; do not forget about including the pilot line into the internal audit program.
As you can gather from the previous section, manufacturing special devices always strikes a chord with the doctor and sometimes the notes are sour. Just because Annex VIII delineates requirements for custom-made and investigational devices in a way that can be interpreted as manufacturing a device in a less than compliant environment, nothing could be further from the truth. Climbing back onto my pulpit to pontificate, Dr. D will once again emphatically state, “Medical device must be safe and effective in their intended use!”
In reviewing Annex VIII, although the requirements have been tailored for custom-made and investigational devices, there is nothing nestled in the Annex that remotely indicates exceptions from the level of quality in the design, manufacturing, inspection, or testing of medical devices. That being said, the doctor will close out this week’s guidance with just one takeaway. Custom-made and investigational devices are used to treat patients. They must be designed, manufactured, inspected, and tested in a manner that results in a device that is safe and effective. That means adequate controls must be in place.
Until the next installment of DG, when Dr. D will begin providing guidance for complying with Annex IX (Classification Criteria) 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.
- EN ISO 13485:2003. (2004, February). Medical devices – quality management systems – requirements for regulatory purposes (ISO 13485:2003).