Annex X (Clinical Evaluation) of Council Directive 93/42/EEC, a.k.a., the Medical Device Directive (MDD) delineates the need to ascertain the safety and efficacy of a medical device through the employment of clinical research and data. Depending on the device classification and intended device use, the clinical evaluation can be premised on the search and subsequent analysis of clinical data for similar or predicate devices. For Class III devices or devices categorized as implantable, device manufacturers better break out their check books and be prepared to support a complete clinical investigation (trial).
A few of the more perspicacious (look-it-up) device manufacturers will understand the need for performing a clinical trial early in the planning process. Some device manufacturers will fail to understand the Annex X requirements, delineated under the Directive, and experience first-hand the joys of having an application to market a new device, made to their notified body, rejected. Can you say, “No European market entry?” Dr. D believes the chances are pretty good that no market will open their doors to a device obviously needing a clinical investigation to support safety and efficacy; good luck in trying.
The full text of MDD – 93/42/EEC ANNEX X (Clinical Evaluation) can be seen viewed
here (pages 57-58).
What you need to know
Dr. D would like to begin this section by reiterating one of his favorite broken-record comments, “Medical device manufacturers need to design, develop, and manufacture devices that are safe and effective.” In the eyes of the regulatory folks in the EU, which include the Competent Authorities and their first line of defense, the notified bodies; conformity to essential requirements is mandatory. That being said, clinical investigations provide confirmation that devices are safe and effective in their intended use. As prescribed by Annex X of the Directive, device manufacturers are expected to execute some level of what the doctor appropriately calls “clinical due diligence.” Clinical due diligence could be as simple as a critical review and analysis of relevant literature and scientific data for similar or predicate devices, or a full-blown clinical trial. The type of clinical evaluation or investigation will be based in part on the device classification and its intended use. Regardless of the approach, the data will be required to support device application and subsequent approvals. The doctor recommends that device manufacturers work closely with their notified bodies, as they can guide you through the sometimes treacherous regulatory waters associated with entry into the European device market. If a device manufacturer’s notified body determines that a clinical investigation will be required to support the submission process, the device manufacturer better start planning for the execution of the actual trials.
In being a bit more specific, the following list captures the types of clinical assessments required by the Directive.
- The collection of relevant scientific literature and a subsequent critical analysis of this data.
- The analysis of clinical investigations performed.
- A combination of number one and number two.
If the device classification steers the device manufacturer, with a gentle nudge from their notified body, to pursue a clinical investigation; there are some basic requirements that need to be considered.
- Clear objectives of the clinical investigation must be stated, including potential risks.
- Ethical considerations in accordance with the Helsinki Declaration must be observed (an interesting read).
- Methods employed as part of the clinical investigation must be clearly delineated within a written and approved protocol. Some of the considerations are:
a. The written protocol and supporting documentation shall be appropriate for the device employed in the investigation.
b. The investigation must be performed in an environment that mimics the expected normal conditions the device will typically be employed.
c. Device features and performance characteristics must be appropriately examined for safety and efficacy while considering the overall impact to the patient, including risk.
d. Adverse events must be recorded, and reported to the Competent Authorities immediately, a.k.a., ASAP!
e. The investigation must be performed by a qualified professional. Dr. Frankenstein probably does not qualify under the Directive.
f. A signed written report containing a critical analysis of the clinical investigation and the data collected will be the salient deliverables of the clinical investigation. Without this report, device manufacturers will not be permitted to; “Pass Go and collect their €200.00.”
What You Need to Do
As always, Dr. D strongly recommends that device manufacturers hold council with their notified bodies to determine the clinical requirements to support device approvals in the EU. After all, device manufacturers pay significant coin to retain notified bodies, so it is only common sense to include them in the decision making process. Remember, it will be the notified body that is tasked with reviewing the application, declaration of conformity, technical file or design dossier, and the ultimate determination if conformance to essential requirements has been achieved.
In repeating a key element of the previous section, device manufacturers will need to ensure one of the following scenarios occur.
- The collection of relevant scientific literature and a subsequent critical analysis of this data.
- The analysis of clinical investigations performed.
- A combination of number one and number two.
- The actual performance of a clinical investigation.
Remember, the expectation of notified bodies and Competent Authorities is that some level of “clinical due diligence” is required to meet the Directive. Typically, Class III device submissions should be supported by data obtained from a well-run clinical investigation. Class IIa and IIb devices, can generally be supported through the collection and critical analysis of scientific data and previous clinical investigations performed. However, Dr. D strongly recommends working with your notified body prior to deciding on the appropriate path to meet the clinical investigation requirement. By the way, did the doctor mention you actually pay your notified bodies? Just kidding, of course I did.
Takeaways
The takeaway for this edition of DG is eloquently simple. The expectations of the Competent Authorities are that medical devices should always be safe and effective while conformity to essential requirements is achieved. Under Article X of the Directive, safety and efficacy are assessed through the employment of what Dr. D calls, “clinical due diligence.” The clinical requirement can be achieved by: (a) the collection and critical analysis of scientific data for similar or predicate devices; (b) a review of clinical investigation data; (c) the actual performance of a clinical investigation; or (d) a combination of a, b, or c.
Until the next installment of DG, when Dr. D will provide guidance for complying with Annex XI (Criteria to be met for the Designation of Notified Bodies) of Council Directive 93/42/EEC, the MDD – cheers from Dr. D and best wishes for continued professional success.
References:
- 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.
Related Articles
-
The new guidance is intended to establish confidence in automation used for production or quality assurance systems and describe various methods and testing activities that may be applied to establish computer software assurance and meet regulatory software validation requirements.
-
The updated guidance document clarifies what constitutes a statement of the basis for the deficiency and includes examples of well-constructed deficiencies and industry responses to facilitate a more efficient review process.
-
The revised cybersecurity draft publication is not intended to be a checklist for healthcare organizations to follow, but rather a guide to help them comply with the HIPAA Security Rule.
-
The draft guidance proposes updates to clarify how the Breakthrough Devices Program may be applicable to certain medical devices that promote health equity, as well as considerations in designating eligible devices that may benefit populations impacted by disparities in health…
About The Author
Dr. Christopher Joseph Devine
President
Dr. Christopher Joseph Devine is the President of Devine Guidance International, a consulting firm specializing in providing solutions for regulatory compliance, quality, supplier management, and supply-chain issues facing the device industry. Dr. Devine has 32 years of experience in quality assurance, regulatory compliance and program management. He is a senior member of the American Society for Quality (ASQ), a member of the Regulatory Affairs Professionals Society (RAPS), and a member of the Project Management Institute, and resides on several technical advisory boards. Dr. Devine received his doctorate from Northcentral University, with his doctoral dissertation titled, “Exploring the Effectiveness of Defensive-Receiving Inspection for Medical Device Manufacturers: A Mixed-Method Study.” Dr. Devine holds a graduate degree in organizational management (MAOM) and an undergraduate degree in business management (BSBM).
