Of the two medical device regulations that are currently being debated in the European Union, the regulation covering in vitro diagnostic medical devices (IVDs) contains the more comprehensive changes to the EU IVD market access regulations. These updates set the stage for radical changes in many rules that IVD manufacturers currently use in their market access.
The reasons behind the revision
The European Commission proposed revisions to the entire medical device regulatory scheme introducing two new regulations for medical devices and IVDs in Europe.
Three overall objectives can be seen throughout the revision1 :
• Maintain the highest level of protection for human health and safety
To achieve this, the EU Commission included for economic actors a chapter on the requirements of clinical studies, increasing the post-market surveillance and vigilance activities and for competent authorities, a chapter on the traceability requirements applicable to all devices.
• Ensure the internal market continues to function smoothly “…[putting] in place a regulatory framework that is applied with consistency across the EU….”2
A consistent regulatory framework includes, for instance, the adjustments to close the legal disparities in the provisions of each member-state and the handling of borderline products and classification issues.
• Provide a regulatory framework that is not only consistent but supports innovation and competition in the industry.
A stronger version of the current third-party assessment system was seen as the most efficient way to keep innovation and competitiveness running.
A brief summary of the common changes for MDD& IVDD and specific one for IVDD only
There are common changes both in the medical devices and IVDs regulation. This is because both Regulations arise out of the New Approach and Global Approach setting the framework for the CE marking regulatory scheme and the common market. Note that a regulation is a legal European text that does not need to be transposed in all the Member States’ national legislation. The whereas-clauses identify the purposes of the changes to the legislation.
The analysis of both texts shows some common provisions/requirements:
• New definitions;
• Inclusion of the distance sales;
• Obligations for Authorised Representative, Importers and Distributors;
• Obligation for Manufacturers to have within their organisation, at least one Qualified Person responsible for regulatory compliance, holder of a specific degree and/or experience.
• Framework for the “parallel trade” situation including “Own Brand Labellers”;
• Strengthening of:
o The supervision of the Notified Bodies in particular regarding their competence and independency to carry out their tasks; and
o The provisions governing market surveillance and vigilance.
Globally, the operational authority of the European Commission increases.
The changes specifically for the IVD regulation:
• Modification of the Scope:
o Including now some high-risk devices manufactured and used within a single Health Institution, tests providing information about the predisposition to a medical condition or a disease, dedicated medical software;
• Traceability obligations;
• Addition of a Summary of Safety and Clinical Performance for Class C and D devices;
• Addition of Risk based Classification Rules;
• Contribution of reference laboratories;
• Strengthening of the provisions of unannounced factory inspections and sample checks;
• For some Class D IVDD, intervention, prior to the issuing of the certificate and in addition to the assessment procedure by the Notified Body, of a Medical Device Coordination Group (MDCG – see art 76). This group will be in charge of the review of the summary of the preliminary conformity assessment.
The MDCG may request:
o any additional information,
o an on-site visit to the Manufacturer's premises;
• Reinforcement of the requirements for Clinical Evidence for In Vitro Diagnostic medical devices proportionate to the risk class.
Taking a closer look at the IVD classification and conformity assessments:
There are a few points that are quite important for IVD manufacturers to keep track of:
• The changes in Classification Rules for IVDs
• The changes in the Conformity Assessments for IVDs and how they are being performed.
The IVD Directive classified until now IVDs in one of two Lists in Annex II of the IVDD, and had provisions for IVDs for self-testing. All other IVDs were self-certified by the Manufacturer.
The proposed IVD Regulation, however, turns the IVD classification scheme on its head by using classification rules similar to the Global Harmonization Task Force rules (GHTF).
Instead of the exclusive lists that are in the Directive, the proposed Regulation also uses a rules-based approach to classify IVDs into four classes based on the risk of the disease for which the IVD tests is meant for. Unlike medical devices, there are no additional definitions for classifying IVDs, although there are 9 implementing rules for the classification scheme similar to those used for medical devices : seven rules, all in one category, that separate IVDs into class A, B, C, or D and two specifically for class D. Class D IVDs are those that test for the most risky and life-threatening illnesses for the public, as well as for the individual.3 Class A IVDs is reserved for reagents, instruments, and specimen receptacles.4
Article 40 in the EU Commission’s proposed regulation provides a description of the Conformity Assessment. Notified Bodies and Competent Authorities have different roles in these new conformity assessments, as well as new interactions with some new players. The proposed Regulation creates for example an EU Reference Laboratories. Those laboratories are designated by the EU Commission to carry out tests, verify compliance, and provide scientific advice and technical assistance to Authorities and Industry.
One notable change applied to IVDs classified in Classes B, C, and D. Those would require the use of a Notified Body to perform the Conformity Assessment. This Notified Body can also consult with the EU reference laboratories or, in the case of companion diagnostics, with a Competent Authority or the European Medicines Agency (EMA).
The IVDs classified in Class A devices are self-certified but in some special conditions (near patient testing, sterile condition, and measuring function) some will require the involvement of Notified Body.
A flow chart for the procedure of the IVD conformity assessments can be seen below:
Part of any IVD’s conformity assessment is the Technical File. Required under the IVD Directive, many IVDs self-certified by the Manufacturers may not have been often by third parties. LNE/GMED will dedicate on May, 14th 2014 a webinar on the IVD technical file compilation and requirements. Update: click here to access to this webinar.
What can IVD manufacturers do to prepare?
IVD manufacturers should be in a position to absorb the regulatory changes and maintain their CE marking, even if they must now receive CE marking through a Notified Body. One of the ways Manufacturers can prepare themselves is to ensure they have a Quality Management System (QMS) which complies with the requirements of the future Regulations or the harmonized standard EN ISO 13485. This QMS, when implemented and running accordingly, should provide a helpful framework for Manufacturers to examine the new requirements and apply those successfully towards their company and devices.
The regulatory changes for IVD manufacturersare one of 2014’s key topics. Manufacturers watch the evolutions of the proposed IVD regulation as it makes its way through the EU Council and Parliament. Measuring and absorbing now these evolutions is essential to maintaining an IVD’s CE marking. IVD manufacturers should keep a finger on the pulse of these evolutions in order to ease their own transition. LNE/G-MED, key notified body with experience from the very beginning of the implementation of the EU regulation can guide IVD Manufacturers through their new (or different) regulatory requirements.
1 Commission Staff Working Document: Impact Assessment on the Revision of the Regulatory Framework for
Medical Devices. Part I. SWD(2012) 273 final. Pg. 22‐23.
2 Id. at 23.
3 2012/0267 Annex VII §2.1‐2.2.
4 2012/0267 Annex VII §2.5.