IVD DIRECTIVE REVISION

3 April 2013 Erik Vollebregtwww.axonadvocaten.nl

Future regulatory framework

• Since the IVDD was published there have been changes in technology and experience with the

legislation and its implementation.

• There will be more focus on

• Genetic tests• Point of Care testing devices• Companion Diagnostics• Software as an IVD• In house tests and testing services provided directly to patients

2

Leveraging existing infrastructure

• GHTF Principles have been the inspiration for many of the fundamental changes in the new

proposal

• New rules based risk classification• Conformity assessment procedures• Clinical evidence requirements and concepts

3

IVDD will become a Regulation

Impact of becoming a regulation

• Direct entry into force

• No transposition period

• i.e. no transposition into national law • although there will probably be a transition period

• Shorter timeline

• A regulation should result in more consistent application

Quantum leap in regulatory burden

Source: BSi

Scope

• Scope changes concern extension and clarification, mainly as with respect to:

• high-risk devices manufactured and used within a single health institution, which are subject to most of the requirements set out in the proposal;

• tests providing information about the predisposition to a medical condition or a disease (e.g. genetic tests) and tests providing information to predict treatment response or reactions (e.g. companion diagnostics), which are considered as in vitro diagnostic medical devices ;

• medical software, which is explicitly mentioned in the definition of IVDs.

MAID

• Implementation of decision 768/2008 methodology

• Economic operators must identify who supplied them and to whom they have supplied IVDs;

• Manufacturers must fit their devices with a Unique Device Identification (UDI) which allows traceability

• The UDI system will be implemented gradually and proportionate to the risk class of the devices;

• Manufacturers/authorised representatives and importers must register themselves and the devices they place on the EU market in Eudamed

• Not new

MAID overview

Manufacturer Importer Distributor

EndUserPost market surveillance and vigilance

Regulatory compliance of device

Verify compliance Verify compliance

Supplier

Supplier

Subco

ntra

ctor

s

Qualified person / parallel trade

• Manufacturer's organisation must have access to a 'qualified person’ responsible for regulatory compliance.

• Similar requirements exist in EU legislation on medicinal products and in the national laws transposing the Directive on medical devices in some Member States.

• A distributor, importer or other natural or legal person shall assume the obligations incumbent on manufacturers if he does any of the following:

a) makes available on the market a device under his name, registered trade name or registered trade mark;

b) changes the intended purpose of a device already placed on the market or put into service;

c) modifies a device already placed on the market or put into service in such a way that compliance with the applicable requirements may be affected.

Parallel trade• Modification of a devices already placed on the market does not include:

• translation of IFU• repackaging for parallel trade purposes

HOWEVER (part implementation of pharma repacking case law ECJ)

• Repackaging must not affect the condition of the device• Repacker must indicate the activity carried out together with his name,

registered trade name or registered trade mark and the address at which he can be contacted and his location can be established on the device or, where that is not possible, on its packaging or in a document accompanying the device

• Quality management system for translation and preservation of original condition of the device and that the packaging of the repackaged device is not defective, of poor quality or untidy

• QS must be certified by notified body• QS must include vigilance feedback to manufacturer• prior notice and mockups must be supplied to authorities and manufacturer

if requested

Qualified person

• The qualified person shall at least [?] be responsible for ensuring the following matters:

a) that the conformity of the devices is appropriately assessed before a batch is released;

b) that the technical documentation and the declaration of conformity are drawn up and kept up-to-date;

c) that the reporting obligations in accordance with Articles 59 to 64 are fulfilled.

d) in the case of devices for performance evaluation intended to be used in the

e) context of interventional clinical performance studies or other clinical performance studies involving risks for the subjects, that the statement referred to in Section 4.1 of Annex XIII is issued;

Qualified person

QP qualification

• University level in natural sciences, medicine, pharmacy, engineering or another relevant discipline, and at least two years of professional experience in regulatory affairs or in quality management systems relating to medical devices; OR

• five years of professional experience in regulatory affairs or in quality management systems relating to medical devices

What do we know?

• Function may be outsourced• Not the same autonomous obligations as AR (terminate / notification) but

is “responsible” – only to manufacturer or also to authorities?• What is a batch? Depends on context and is 1 or more devices

Traceability, registration, summary of safety and performance, Eudamed• Aim Commission: address one of the main shortcomings of the current system:

lack of transparency:

• a requirement that manufacturers fit their devices with a Unique Device Identification (UDI) which allows traceability.

• UDI system will be implemented gradually and proportionate to the risk class of the devices;

• a requirement that manufacturers/authorised representatives and importers shall register themselves and the devices they place on the EU market in a central European database;

• an obligation for manufacturers of high-risk devices to make publicly available a summary of safety and performance with key elements of the supporting clinical data;

Conformity assessment

• Biggest changes because of implementation of GHTF classes A-D• The existing modules established under the 'New Approach’ do not change –

see annexes VIII to X, however

• EC verification module was deleted • The concept of batch testing has been clarified

Source: BSi

Conformity assessment

• See GHTF SG1-N46:2008 “Principles of Conformity Assessment for In Vitro Diagnostic (IVD) Medical Devices” for model

• Class A devices : sole responsibility of the manufacturer, except if intended for near-patient testing, have a measuring function or are sold sterile

• Classes B, C and D : notified body involvement

• Class D: explicit prior approval of the design or of the type of the device and of the quality management system before they may be placed on the market

• Class B and C devices : the notified body checks the quality management system

• Class C: in addition of QMS notified body check the technical documentation of representative samples.

• After initial certification, notified bodies shall regularly conduct surveillance assessments in the post-market phase.

Scrutiny procedure It’s a trap!!!

• Will apply to class D devices but potentially to many others

• Any specific categories or group of devices that Commission determines by implementing act justified only by one or more of following criteria:

a) the novelty of the device or of the technology on which it is based and the significant clinical or public health impact thereof;

b) an adverse change in the risk-benefit profile of a specific category or group of devices due to scientifically valid health concerns in respect of components or source material or in respect of the impact on health in case of failure;

c) an increased rate of serious incidents reported in accordance with Article 59 in respect of a specific category or group of devices;

d) significant discrepancies in the conformity assessments carried out by different notified bodies on substantially similar devices;

e) public health concerns regarding a specific category or group of devices or the technology on which they are based.

Scrutiny procedure

Common Technical Specifications

• Where no harmonised standards exist or where relevant harmonised standards are not sufficient, the Commission shall be empowered to adopt common technical specifications (CTS) in respect of

• the general safety and performance requirements set out in Annex I, • the technical documentation set out in Annex II or the clinical evidence and • post-market follow-up set out in Annex XII.

• Compliance with CTS is presumption of compliance with Annexes• Like with standards, diverge allowed but must be justified

Clinical

• Clinical data requirements depend on risk class of IVD• Annex XIII : rules for the conduct of interventional clinical performance studies

and other clinical performance studies where the conduct of the study, including specimen collection, involves invasive procedures or other risks for the subjects of the studies

• applies only to clinical performance studies carried out for regulatory purposes

• The concept of 'sponsor’ introduced and aligned with proposal for Clinical Trial Regulation

Vigilance and market surveillance

• Vigilance

• Introduction of EU portal for reporting of serious incidents and corrective actions taken by manufacturers.

• Information will be automatically made available to the national authorities concerned

• Coordinating authority that takes direction in coordinating the analysis of the case in multinational matters

• Market surveillance

• Emphasis on work-sharing and coordination• Use of pan-EU electronic system on market surveillance• Procedures for compliant and non-compliant devices presenting a risk to

health and safety at national level• Procedure for national preventive measures with respect to potential risk

related to a device or a specific category or group of devices

Governance

• New kids on the block

• MDCG• Reference laboratories

Governance

• MDCG tasks

a) to contribute to the assessment of applicant conformity assessment bodies and notified bodies pursuant to the provisions set out in Chapter IV;

b) to contribute to the scrutiny of certain conformity assessments pursuant to Article 42;

c) to contribute to the development of guidance aimed at ensuring effective and harmonised implementation of this Regulation, in particular regarding the designation and monitoring of notified bodies, application of the general safety and performance requirements and conduct of the clinical evaluation by manufacturers and the assessment by notified bodies;

d) to assist the competent authorities of the Member States in their coordination activities in the fields of clinical performance studies, vigilance and market surveillance;

e) to provide advice and assist the Commission, at its request, in its assessment of any issue related to the implementation of this Regulation;

f) to contribute to harmonised administrative practice with regard to in vitro diagnostic medical devices in the Member States.

Governance• Reference laboratories

• For specific devices, or a category or group of devices, or for specific hazards related to a category or group of devices, the Commission may designate one or more European Union reference laboratories with the following tasks:

a) to verify compliance of class D devices with the applicable CTS, when available, or with other solutions chosen by the manufacturer to ensure a level of safety and performance that is at least equivalent, as provided for in the second subparagraph of Article 40(2);

b) to carry out appropriate tests on samples of manufactured class D devices or batches of class D devices, as provided for in the Section 5.7 of Annex VIII and in Section 5.1 of Annex X;

c) to provide scientific and technical assistance to the Commission, the Member States and notified bodies in relation to the implementation of this Regulation;

d) to provide scientific advice regarding the state of the art in relation to specific devices, or a category or group of devices;

e) to set up and manage a network of national reference laboratories and publish a list of the participating national reference laboratories and their respective tasks;

Governance

• Reference labs continued

f) to contribute to the development of appropriate testing and analysis methods to be applied for conformity assessment procedures and market surveillance

g) to collaborate with notified bodies in the development of best practices for the performance of conformity assessment procedures;

h) to provide recommendations on suitable reference materials and reference measurement procedures of higher metrological order;

i) to contribute to the development of standards at international level;j) to provide scientific opinions in response to consultations by notified

bodies in accordance with this Regulation.

Companion Dx

• New regime

• New definition “a device specifically intended to select patients with a previously diagnosed condition or predisposition as eligible for a targeted therapy”

• Class C risk classification

• Design or type examination

• whereby the notified body shall consult one of the competent authorities designated by the Member States in accordance with Directive 2001/83/EC or the European Medicines Agency (EMA) in accordance with the procedures set out in Section 6.2 of Annex VIII and in Section 3.6 of Annex IX.

• Also consultation in case of changes affecting the suitability of the device in relation to the medicinal product concerned are made

Timelines

Transitional regime

• Complex• Sunshine clause – you can comply prospectively• Certificates issued by notified bodies under old IVD directive

• prior to the entry into force of this Regulation shall remain valid until the end of the period indicated on the certificate

• except for certificates issued in accordance with Annex VI of Directive 98/79/EC which shall become void at the latest two years after the date of application of this Regulation.

• after the entry into force of this Regulation shall become void at the latest two years after the date of application of this Regulation.

• ALL notified bodies will be decertified and have to be recertified under new requirements during transition period

Unannounced factory inspections

• Minimum once per 3 years, more frequent for high

risk devices, timing to be unpredictable

• Checks will look at:

• Manufacturing in line with documentation?• At least one critical process out of:

• Design control, purchasing, incoming materials, assembling, sterilisation, packaging product QC

• Design Examination/Type Examination sample several products at end of line or warehouse

• Test in house or in external labs• Sampling and test criteria determined in advance• If impossible take samples from market, where needed supported by CA• Compare with existing technical documentation, test protocols and results

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Thanks for your attention

Erik VollebregtAxon LawyersPiet Heinkade 1831019 HC AmsterdamT +31 88 650 6500F +31 88 650 6555M +31 6 47 180 683E erik.vollebregt@axonlawyers.com @meddevlegalB http://medicaldeviceslegal.com

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