Since the beginning of 2011, Dr. D has been reviewing and providing guidance for the 23 Articles that form the foundation for the Council Directive 93/42/EEC, a.k.a., the Medical Device Directive (MDD). Understanding these Articles and the imbedded regulations is extremely important for device manufacturers; however, it is the opinion of the good doctor, that the Annexes associated with the MDD is where the proverbial rubber hits the road.

Device manufacturers already shipping into the European Union (EU) understand the ramifications of having product that fails to meet essential requirements or a quality system failing to meet the requirements detailed within these annexes. All one has to do is glance quickly over the certifications, issued by their notified bodies, to understand the significance of these Annexes. Since Dr. D never likes to be vituperated (look-it-up), and I am sure the readers of Devine Guidance (DG) would not enjoy being vituperated by their boss or peers; the doctor will spend the next 12 weeks enlightening readers on the salient points associated with Annexes I through XII.

This week Dr. D will commence this series of articles with the review and guidance for complying with Annex I of the MDD, “Essential Requirements.” Full text of MDD – 93/42/EEC ANNEX I – Essential Requirements can be viewed here (see pages 25-32).

What you need to know
Hopefully, you have had the chance to read the DG articles that were penned, actually typed, examining Articles 1 through 23. Several of the MDD Articles emphasize the importance of medical devices meeting their essential requirements. In fact, the need for a device to meet its essential requirements is one of the single-most important concepts device manufacturers need to understand. That being said, this edition of DG is all about understanding the importance of establishing essential requirements.

Annex I is divided into two major components, “General Requirements” and “Requirements Regarding Design and Construction.” Many of the changes to the Directive that became effective on 21 March 2010 are nestled in Annex I.  That being said, here is what device manufacturers need to know and understand.

1.    Medical devices must be designed in such a way that they are safe and effective for their intended use. Device ergonomics shall be considered in an effort to reduce risk associated with the device user.

2.    Identifying, understanding, and eliminating risk needs to be a key input into design, development, and manufacturing processes.

3.    The finished medical device must achieve its performance objectives.

4.    The finished medical device must work over its specified lifetime in its normal operating environment.

5.    The device, including its packaging, must be designed to prevent damage during transportation and storage.

6.    Undesirable side effects must be assessed for acceptable risk. It is Dr. D’s experience that device designs that result in undesirable side effects being induced, should probably be redesigned to mitigate the risk.

7.    A clinical evaluation is now required to support a device’s conformity with these essential requirements. Just a quick note: if a manufacturer is trying to obtain approval for a Class III device in the EU, this is probably not going to happen without a clinical trial.

8.    Medical devices must be designed and manufactured taking into account their chemical, physical, and biological properties. In short, little things like toxicity must be considered. Device manufacturers need to ensure their devices are not poisoning the patient. That would be a bad thing. Additionally, devices must be designed and packed to prevent contamination and residues to the person(s) transporting or storing the devices.

Furthermore, if a device incorporates a medicinal product, the device must be verified against the requirements delineated within Annex I of Directive 2001/83/EC. If a medical device contains a human-blood derivative, the notified bodies will seek a scientific opinion from the European Medicines Agency (EMEA). Finally, devices that employ liquids in their use or remove liquids (fluids) from the body should not leak. The doctor classifies the “no-leak clause” as one of the proverbial no brainers associated with Medical Device Design-101.

One additional thought, Dr. D was raised in the age of plastics and come to find out after all of the doctor’s years on this planet, plasticizers are now considered bad things. Who knew? Regardless, device manufactures must now ensure devices, which employ phthalates as part of the device construction, be properly labeled with a warning. These phthalates must not come into contact with the blood path or be used to administer or remove liquids and medicines to and from the body.

9.    Finished medical devices should not be a source for infection or microbial contamination. In fact, if a device is delivered in a sterile state, the expectation is that the device should be sterile at the time of use. Imagine that, sterile devices should be sterile, thank you Dr. D. for such a brilliant and insightful comment.

10.    If a device is intended to be used in conjunction with other devices, e.g., electrophysiological catheter and a radio-frequency generator, the device should work as advertised within that environment. If there are specific concerns or restrictions, these must be added to the device labeling. Some of the issues device manufactures must consider are: electro-magnetic interference (EMI), magnetic fields, maintenance, calibration, material aging, and other risks associated with the environment in which a device is being used.

11.    If a device performs or has a measuring function, the expectation is that the measurements made are accurate. There is an additional requirement that devices performing a measurement function express these measurements in legal limits. Can you say SI units?

12.    European’s tend to frown down upon devices that result in patients and users glowing in the dark. That being said, radiation levels must be reduced as much as practical, keeping in mind the intended use of the device.  For devices intended to emit radiation, the devices must be fitted with a visual display or be able to produce an audible warning. Although Directions for Use (DFU) are required for Class IIa. IIb, and III devices, additional instructions/warnings are required detailing the nature of the radiation being emitted and the appropriate protective actions needing to be pursued. The same salient requirements hold true for devices emitting ionizing radiation, e.g., radiology equipment.

13.    When the use of a medical device requires connection to a power source, the power supply/source must be designed in a way that ensures long-term reliability. If software is employed as an integral part of the power supply/source, the software will be validated. When a power supply’s performance is linked directly to patient safety, an alarm or other signal device shall be present, to notify the user, a power failure has occurred.  Other design considerations should include the operating environment; EMI, noise reduction, temperature, and electrical shorts resulting in electrical shock to the patient or user. Similar to having patients and healthcare professionals glowing in the dark due to exposure to radiation; shocking these same individuals with electricity is also considered a bad thing. Who knew?

14.    Device manufacturers are required to delineate general product information and ensure this information ships with each devices. As a minimum, information such as; (a) selection information, (b) indications for use, (c) contraindications, (d) compatibility data, (e) warnings, (f) sterilization, (g) single-use, (h) batch code, (i) part number, (j) expiration date, (k) manufactured by, (l) manufacturing location, (m) handling, (n) storage, and any additional relevant information pertaining to the medical device, shall be considered. One final note, once this information is loaded onto a label or placed into the DFU, device manufacturers need to translate the information. Why? Because Member States retain the right to have this information in their native tongue; and do not forget to save room for the CE Marking of Conformity.

What you need to do
Granted there is a whole bunch of information needing to be digested by device manufacturers in regards to meeting the essential requirements. The good news is the notified bodies are well-equipment to help device manufacturers navigate the Articles and Annexes collectively bundled under the MDD. The bad news is compliance is not an option. From Dr. D’s perspective, the best advice the doctor can offer is to ensure essential requirements are considered starting at the conceptual phase of the design. Effectively planning for the essential requirements will result in a medical device that is safe and effective, with performance characteristics that conform to Annex I of the MDD.

Although all of the clauses associated with Annex I are important, device manufacturers need to focus on the labeling. Labeling is reviewed as part of the overall review and approval process (design dossiers and technical files); and Dr. D has witnessed the approval delays associated with incomplete or inaccurate labeling data, translation errors, and DFUs that are missing pages. Additionally, thanks to the advent of Prop 65 (thank you California) there has been an increased awareness in materials that can be categorized as carcinogens around the globe. The EU has jumped on this bandwagon and their efforts can be seen in the phthalate warning requirement added to Annex I in March of 2010. Finally, the re-use of single-use devices has become rampant in an effort for healthcare organizations to curtail skyrocketing healthcare costs. Now Dr. D is not a proponent of re-use; however, the practice is not going to go away. That being said, reprocessed medical devices are still required to meet their essential requirements.

Takeaways
A manufactured medical device’s ability to meet essential requirements commences at the conceptual stage. All of the essential requirements must be considered as part of the design. A design and development process that results in shortcuts being taken, to improve on the speed-to-market, will result in a device manufacturer’s failure to obtain approvals for market entry into the EU, or result in significant delays as the device goes through a redesign or errors and omissions to the labeling are corrected. When in doubt, work with your notified body. You pay the notified body, so they work for you. Yes the doctor knows that some notified bodies believe the relationship is the other way around; however a quick reminder as to who signs the checks should correct the relationship issue. Until the next installment of DG, when Dr. D will begin providing guidance for complying with Annex II (EC Declaration of Conformity – full quality assurance system) of Council Directive 93/42/EEC, the MDD – cheers from Dr. D and best wishes for continued professional success.

References:

1. 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
2. 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.
3. Directive 2001/83/EC. (2001, November). Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the community code relating to medicinal products for human use. Retrieved January 7, 2011, from http://www.edctp.org