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PIP "stress test" 01.02.



Working document for meeting on medical devices 4.5.2012

PIP case EU legislation applicable at EU legislation applicable Envisaged amendments to be

the time of the facts since March 2010 presented in the Commission
Chronology of facts35 proposals38
(Directive 93/42/EEC on (amendments introduced by
medical devices, hereafter Directive 2007/47/EC) (already envisaged prior to
MDD36 37) PIP; additional amendments
due to lessons learned from
PIP are marked with an *)

1. Pre-market

1.1. Conformity assessment

In July 1997, the notified body For the conformity assessment of The conformity assessment On a case-by-case basis,
TÜV Rheinland39 (identification breast implants, notified bodies as process for class III MD has not individual conformity assessment
number 0197) carried out the first independent third parties must be procedures for high risk or novel

According to the information at the disposal of the Commission.
National transposition measures to be applicable as of 1 January 1995.
The transitional provisions for devices in conformity with preceding national regulations do not seem to be relevant for this case.
Subject to adoption by the Commission after completion of the internal procedures (inter-service consultation etc.).
TÜV Rheinland Product Safety GmbH, now TÜV Rheinland LGA Product GmbH.

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audit of the manufacturer PIP in involved prior to implants being been significantly amended. devices shall be subject to
the context of the conformity placed on the market. scrutiny by a committee of
assessment regarding soft tissue Manufacturers may choose any But is has been reinforced for IIa national experts (with rapporteur
breast implants. notified body that is designated forand IIb devices for which, in and co-rapporteur system) prior to
the required tasks. addition to the quality system, the issuance of certificates by the
In 1997, TÜV Rheinland issued a notified bodies must examine the notified body.
quality system certificate in Until 2003, breast implants were design documentation on a
accordance with Annex II MDD. classified as class IIb devices representative basis (sampling Possibility to adopt, by
After recertification audits in July (Annex IX, rule 8, MDD). The regime). implementing or delegated acts,
2002 and Sept. 2007 , TÜV notified body's involvement was mandatory requirements for
Rheinland renewed the quality thus limited to verification of the certain devices regarding the
system certificate. manufacturer's quality system documentation to be submitted by
(Annex II, without sect. 4, MDD). manufacturers to notified bodies
In 2004, after the reclassification Certificates issued in accordance and their assessment.
of breast implants, TÜV with Annex II have a validity of 5
Rheinland issued also a design years. * Notified bodies, in the context of
dossier examination certificate in the design dossier examination,
accordance with Annex II, sect. 4, In 2003, on the request of France should carry out adequate
MDD. This certificate was and UK, breast implants were physical or laboratory tests of
renewed in 2009. reclassified as class III devices the device or of its crucial
by Commission Directive components or require
2003/12/EC. manufacturers to carry out such
tests under their supervision (and
Since 1.9.2003 (or since 1.3.2004 possibility to consult reference
regarding breast implants already laboratories where those are
on the market), the conformity designated for specific risks or
assessment by notified bodies devices).
consists of the assessment of
* Manufacturers should have
- the manufacturer's quality available in their organisation a
system and qualified person responsible for
According to the information the regulatory compliance of the
provided by the German - the design dossier related to device released on the market with
authorities, the assessment teams the device. appropriate qualification, legal
consisted of several auditors (lead status and personal liability.
auditors and auditors) and It is required that the body's
included qualified personnel for assessment team includes at least

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the device group "soft tissue one member with past experience
implants". of assessments of the technology

1.2. Safety and performance

requirements, incl. clinical

PIP's technical documentation is Annex I MDD lays down the The essential requirements were The essential requirements shall be
not available to the Commission. essential requirements to be met reviewed and several amendments further updated in the light of
But according to information at its by medical devices. The basic introduced such as the technological progress and
disposal, PIP declared using requirement is that "devices must requirements to take into account international guidance.
silicone gel approved for medical be designed and manufactured in results of validated biophysical or
use (e.g. Nusil©). There is no such a way that […] they will not modeling research or to pay Moreover, there shall be the
evidence that at the moment of the compromise the clinical condition special attention to CMR possibility to adopt, by
first and subsequent conformity or the safety of patients, or the substances. implementing or delegated acts,
assessments, the breast implants safety and health of users […] mandatory requirements for
did not comply with the legal provided that any risks which may certain devices, incl. the required
requirements. be associated with their intended clinical evaluation.
use constitute acceptable risks
It is not clear at what moment and when weighed against the benefits
during which periods PIP changed to the patient and are compatible
the design of and the material used with a high level of protection of
for the implants in a way that the health and safety".
safety and performance
requirements expected from such a Specific requirements exist
medical device were not met any regarding the chemical, physical
more (e.g. use of industrial grade and biological properties of

In 2001, the Commission published Communication COM(2001)666 on Community and national measures in relation to breast implants. Among others, it
contains detailed guidance on essential safety requirements and conformity assessment schemes of Directive 93/42/EEC in relation to breast implants.
See EN ISO 14607 which addresses in particular intended performance, design attributes, materials, design evaluation, manufacturing, sterilization,
packaging and information supplied by the manufacturer.

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silicone instead of medical devices (e.g. toxicity and

silicone, increased and premature biocompatibility of used material,
rupture, oozing of silicone). minimization of risk due to
leakage of substances).

There are no specific requirements

for implants. As regards breast
implants, in 2001, the Commission
provided guidance40 as to which
aspects should be particularly
looked at and issued a mandate for
a standard that lays down detailed
specifications regarding breast
It shall be further clarified in the
According to Annex X MDD, as a legislation that "equivalence" with
general rule, demonstration of The requirements regarding another implantable or class III
conformity with the characteristics clinical evaluation have been device is not a sufficient
and intended performances must significantly strengthened. justification to omit clinical
be based on clinical data, in investigations.
particular in the case of It is now always required that
implantable and class III devices. demonstration of conformity with Furthermore, manufacturers shall
the essential requirements must make publicly available a
include a clinical evaluation summary of the safety and
(Annex I, sec. 6a MDD). performance data, incl. the
relevant clinical data.
In the case of implantable and
class III devices, clinical Criteria for the manufacturer's
investigations must be conducted post-market clinical follow-up
to obtain the data for the clinical (PMCF), as part of his post-
evaluation, unless it is duly market surveillance plan (PMS),
justified to rely on existing clinical shall be laid down.
data (Annex X, sec. 1.1a MDD).

Manufacturers are obliged to

conduct a post-market clinical
follow-up as part of the post-

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market surveillance regarding their

devices (Annex X, sec. 1.1c

1.3. Designation and monitoring

of notified bodies

In 1994, TÜV Rheinland has been Member States are responsible for The minimum criteria for notified The minimum requirements to
designated by Germany as notified the designation and monitoring of bodies and the designation process be met by notified bodies laid
body in the field of medical notified bodies in accordance with have not been amended. But the down in Annex XI MDD shall be
devices; the designation scope the minimum criteria laid down in Commission has been empowered reinforced and made more
includes soft tissue implants. Annex XI MDD, but they are to adopt, by Comitology detailed.
vague. procedure and in the light of
Between 1994 and 2011, the technical progress, detailed Moreover, the designation and
German authorities conducted at In 1998, the requirement was measures necessary to ensure monitoring process shall
least once a year surveillance added that notified bodies need to consistent application of the fundamentally be revised. In the
assessments (with 2-6 assessors).have "sufficient scientific staff minimum criteria to be met by future, a Member State shall only
In 2002 and 2003, the assessment within the organisation who notified bodies for their designate a body after a 'joint
was 'peer reviewed' by an assessor
possess experience and knowledge designation by the Member States. assessment' conducted with
of, respectively, the Dutch and the
sufficient to assess the medical experts from the Commission and
Danish authorities. functionality and performance of However, efforts had been other Member States. The draft
devices for which it has been focussed on a systematic revision designation shall be submitted to a
There is no evidence that TÜV notified". of the entire regulatory framework committee of national experts that
Rheinland lacked the necessary where the designation and can issue a negative opinion.
competence to conduct conformity No provisions exist as to how the monitoring process should be
assessments related to breast Member States must conduct the addressed. The monitoring of notified bodies
implants. control on notified bodies. shall also regularly be conducted
by a 'joint assessment team'.
Since 2000, designating
authorities of the Member States
meet in the Notified Body
Operations Group (NBOG) to
improve the overall performance
of notified bodies in the medical
devices sector by promulgating
examples of best practice to be
adopted by both notified bodies

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and supervising authorities. In

2003, NBOG adopted a
Designating Authorities Handbook
to provide guidance for
designating authorities in the
execution of their responsibilities
for the designation and monitoring
of notified bodies.

2. Post-market

2.1. Surveillance by notified


As mentioned above, it is unclear As part of the surveillance, the For the surveillance by the notified
The role of notified bodies in the
as of when and in which periods notified body must periodically body, the manufacturer must vigilance system shall be clarified
PIP silicone breast implants did no carry out appropriate inspections provide it, among others, with
(e.g. obligation of manufacturers
longer meet the safety and and assessments. It may pay clinical evaluation and the results
to inform their notified body about
performance requirements of the unannounced visits to the of the post-market clinical follow-
incidents; access of notified bodies
MDD. There is no evidence that manufacturer and may carry out up. to the future EU vigilance
PIP informed TÜV Rheinland or ask for tests in order to check database; obligation of notified
about changes to the design of But there is still no legally defined bodies to analyse vigilance data
that the quality system is working
silicone breast implants such as properly. role of notified bodies in the and to take appropriate action in
the change of the design of the vigilance system (only addressed relation to audits and certificates).
The manufacturer is required to in some guidance documents).
devices or the material used for the
filling. inform the notified body of any In addition, there shall be the
changes to the approved quality possibility to set mandatory
Between 1998 and 2010, TÜV system and/or product design. criteria for surveillance audits.
Rheinland conducted 9 regular
surveillance audits (plus 2 * In the context of their
recertification audits). Moreover, surveillance over manufacturers,
an extraordinary audit (observed notified bodies shall randomly
by the German authorities) was perform unannounced factory
conducted in February 2001 inspections and, in this context,
further to the UK's Medical check adequate samples from the
Device Alert 2000(07) of production or the manufacturing

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December 2000 regarding PIP process. The frequency of

hydrogel breast implants. unannounced visits should be
defined in a subsequent
As a result, hydrogel implants implementing measure to ensure a
were withdrawn from the scope of level playing field.
the certificate by TÜV Rheinland.
But the findings did not have an * Notified bodies should be
impact on the certification of required that the composition of
silicone breast implants. their assessment teams assures
continuous objectivity and
neutrality including a rotation of
auditors at appropriate intervals.

* It could also be foreseen that, at

least for crucial components, a
notified body should check
coherence between quantity of
purchased raw material/
components and quantity of output
of finished products. The problem
is that such obligation comes close
to accountability check which
does not fall in the competence of
notified bodies.

* Negative results of an audit shall

be communicated to the Member
State where the manufacturer or
authorised representative is

2.2. Market surveillance by


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In 2000 and 2001, the French There is a general requirement that This situation has not changed. Specific provisions regarding
authorities took a number of Member States must ensure that market surveillance shall be
measures regarding breast only compliant devices are placed introduced in the medical device
implants, such as a temporary or put into service on their markets legislation, such as the obligation
suspension of their placing on the (Article 2 MDD). But there are no to conduct periodic inspections
market and putting into service specific requirements in the (physical or laboratory checks on
and the request to all medical device legislation as to samples) and the coordination of
manufacturers to provide how Member States should surveillance programmes.
additional documentation for their conduct the surveillance. Negative findings should be
reintroduction on the market. communicated to the responsible
Further to correspondence Regulation 765/200842 (applicable notified body.
between the French authorities and since 1.1.2010) provides general
PIP, AFSSAPS conducted an requirements as regards Member Member States shall also be
inspection of PIP in June 2001 in States' market surveillance obliged to set "effective,
the context of the 'breast implant' obligation (including proper proportionate and dissuasive"
campaign and found several non- powers and resources of national penalties in case of violation of
conformities. Further to extensive authorities and appropriate the legal obligations and notify
correspondence and submission of measures such as physical or them to the Commission.
additional reports by PIP, laboratory checks).
AFSSAPS concludes in Dec. 2001
that the non-conformities have In addition to the product related
been remedied. AFSSAPS then conformity assessment, a
conducted inspections of the other 'manufacturing authorisation' by
breast implants manufacturers. an authority is not required by EU

On 29 March 2010, the French Article 8 and Article 18 require This situation has not changed. The legal instruments for Member
authorities (AFSSAPS) adopted a Member States to take action States to take restrictive measures
decision to recall PIP silicone against unsafe and/or non- against unsafe and/or non-
breast implants from the market compliant devices. compliant devices shall be

Regulation (EC) No 765/2008 of the European Parliament and of the Council setting out the requirements for accreditation and market surveillance relating
to the marketing of products.

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and to suspend their placing on the clarified to enhance legal certainty

market, distribution, export and for authorities when applying
use. restrictive measures.

On 9 April 2010, the French National measures that restrict or In Article 8 (safeguard clause), an Clarification of the conditions
authorities formally notified the prohibit the placing on the market empowerment has been added to when the Commission shall be
Commission of their decision of of unsafe and/or non-compliant enable the Commission to adopt, empowered to take a restrictive
29 March. On 26 April 2010, the devices must be notified to the by Comitology procedure, measure against unsafe and/or
Commission informed all EU Commission and the other measures regarding the prohibition non-compliant devices.
Member States (PermReps) about Member States. The Commission or restriction of unsafe products.
the situation and requested them to shall keep Member States Expertise shall be available to the
take the necessary measures to informed about progress and Commission (in house and
prohibit any placing on the outcome of the safeguard clause external experts, e.g. Medical
market, distribution, putting into procedure. (Article 8 and Article Advisory Board) to help to take a
service or use of the PIP implants 18(b)). decision on a safeguard clause and
as well as to alert the medical to take a measure against unsafe
professionals. and/or non-compliant devices.

In the following weeks and

months, Member Sates adopted
measures at national level to
withdraw the devices from their

2.4. Vigilance

A high number of ruptures of PIP Manufacturers must have a The provision regarding the The obligations regarding the
implants occurred. Only a limited systematic procedure in place to manufacturer's obligation to have reporting of incidents and the
number seemed to have been review experience gained from a PMS has been reinforced and follow-up shall be clarified.
reported to national authorities, in their devices on the market (post- extended to post-market clinical
particular the French AFSSAPS market surveillance plan, PMS) follow-up as a continuous and In the future, incidents shall be
reported by manufacturers to a

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and the UK's MHRA, that found and are obliged to report active update of the clinical central vigilance database (part
unusual high rate (but still below incidents43 to the national evaluation. of Eudamed, managed by the
1%) of premature rupture. authorities. Commission) accessible to
Member States and notified
On the basis of incident reports National authorities are obliged to bodies. The public shall have
from healthcare professionals in record and evaluate centrally the access to information about
France in 2007 (8 incidents = incidents brought to their measures taken.
0.11%), 2008 (27 incidents = attention. But these only concern
0.41%) and 2009 (29 incidents = the incidents reported at national Manufacturers shall also be
0.56%), AFSSAPS investigates level. obliged to report "trends", i.e.
the trend of higher than usual accumulation of adverse events
ruptures of PIP implants. Member States are obliged to that individually do not need to be
ensure that manufacturers are reported.
But PIP seemed to have received informed about incidents reported
complaints from users (found by by healthcare professionals (no Notified bodies would be obliged
AFSSAPS during their inspection EU obligation for healthcare to analyse vigilance data and to
in March 2010) that had not been professionals to report). take appropriate action in relation
reported to AFSSAPS. This data, to audits and certificates.
after analysis by AFSSAPS, shows The problem in the present case is
rupture rates of between 3.5% (in that from the current 'incident' Furthermore, in the case of
2007) to 9.39% (in 2009). definition in the legislation, it is incidents that occur in several
not clear if the individual rupture Member States, authorities shall
In parallel, on the basis of incident of a breast implant is to be coordinate their assessments
reports in the UK, MHRA considered as a "serious under the lead of a coordinating
investigates and concludes that the deterioration of the state of health" authority and with support of the
ruptures of PIP implants (in and therefore subject to the Commission.
absolute terms still below 1%) reporting requirement or not.
occur unusually early after The Commission shall have the
implantation. MHRA contacted Currently, there is no legal necessary resources to analyse
PIP on 22.1. and 18.3.2010. obligation of manufacturers to reported incidents to identify

Incidents are defined in Directive 93/42/EEC as "(a) any malfunction or deterioration in the characteristics and/or performance of a device, as well as any
inadequacy in the labelling or the instructions for use which might lead to or might have led to the death of a patient or user or to a serious deterioration in
his state of health; (b) any technical or medical reason in relation to the characteristics or performance of a device for the reasons referred to in subparagraph
(a), leading to systematic recall of devices of the same type by the manufacturer".

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AFSSAPS is informed by MHRA report 'trends', i.e. the signals and trends which would
on 6.4.2010. accumulation of adverse events need action at EU level (e.g.
that individually do not need to be harmonised product requirements).
In February 2010, PIP claims in a reported.
letter to MHRA that the rupture Commission shall be empowered
rate was only 0.3% and provides Moreover, there is no legal to adopt EU wide measure to
statistics about sales, ruptures and obligation of manufacturers to ensure uniform reaction to
explantations regarding UK. inform their notified body about incidents.
incidents or field safety corrective
There was likely significant actions (some notified bodies * Measures could be introduced
underreporting by plastic surgeons oblige manufacturers in their enhancing the reporting of
to the national authorities. contracts to notify them of suspected incidents by healthcare
vigilance issues). professionals and patients (in
analogy to the new
The operation of the vigilance pharmacovigilance provisions in
system has already been further Art 107a Dir. 2001/83/EC and Art
detailed by non-binding guidelines 25 Reg. 726/2004).
(MEDDEVs) which address the
issue of trend reporting and the
role of notified bodies.

On 30 March 2010, the French Member States are obliged to Article 10 MDD has been A process for the coordination of
authorities alerted the other inform the other Member States reworded and now requires the assessment of vigilance cases
Member States about increased and the Commission about information about measures taken affecting several Member States
frequency of incidents in relation outcome of evaluation of incidents or contemplated to minimise shall be established (see above).
to PIP silicone breast implants and (Article 10(3) MDD). recurrence of incidents. In
about their decision of 29 March addition, the Commission is
2010 to recall PIP silicone breast empowered to adopt, by
implants from the market and to Comitology procedure, the
suspend their placing on the procedures to implement the
market, distribution, export and Article on vigilance.

In 2010 and 2011, exchange of MDEG, vigilance and other This situation has not changed. A committee of medical devices
views and update of state of play Commission working groups do experts designated by the Member
during informal meetings of the not have any statutory basis. States shall be set up and
Medical Device Expert Group supported by the Commission; a

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(MDEG) and Vigilance working sub-group should be dedicated to

group vigilance and market surveillance

2.5. Traceability

PIP did not keep records of the No traceability requirements in the This situation has not changed. Traceability requirements shall be
whereabouts of their products. legislation. introduced in the new legislation.
Member States have difficulties Economic operators shall ensure
identifying the women who traceability up and down the
received PIP implants. distribution chain. In addition,
based on a risk-based approach,
traceability of devices shall
gradually be implemented by
means of a Unique Device
Identification (UDI) system.

* Patients should obtain an

"implant card" with key
information about the implanted
device, incl. warnings or
precautions to be taken (e.g.
compatibility with diagnostic
devices) and expected life cycle
and recommended regular follow-
up checks.

It seems that PIP produced An OBL is considered a A provision has been introduced OBL shall continue to be
silicone breast implants also for manufacturer in terms of the MDD extending the conformity considered as manufacturer. They
other companies that marketed and must meet all the relevant assessment procedure regarding shall be required to provide
them with another name under requirements. The Commission the manufacturer's quality system information about the original
their own names (so called "Own has clarified this with an to third parties that carry out the equipment manufacturer (OEM)
Brand Labellers", OBL). interpretative document in 2008. design, manufacture, testing etc. and about identical devices placed
on behalf of the manufacturer. on the EU market under different
E.g. the Dutch company Rofil sold names.
implants made by PIP under its

PIP "stress test" 01.02.2012

own name as "M-Implants". The

company went bankrupt but seems
to have been reestablished in
Cyprus. Company structures,
bankruptcies and marketing
practices are dubious and create
additional confusion as to the
identification of women having
received implants made by PIP.

On 20 January 2012, the German

authorities informed that the
German company GFE
Medizintechnik GmbH
presumably during the period
September 2003 and August 2004
purchased PIP silicone breast
implants, processed them with
titan and sold them under the
name "Tibreeze". The company
also went bankrupt.

3. Risk management and

recommendations to patients

Between 21 December 2011 and 4 No provisions in the medical This situation has not changed. A committee of medical devices
January 2012, meetings (by devices legislation. experts designated by the Member
teleconference) of the Health States shall be set up and
Security Committee were The EU Health Security supported by the Commission.
organized by the Commission to Committee was set up by the Besides its regular meetings, it
exchange information and Council of Health Ministers in would also be convened in crisis
coordinate follow-up by national 2001. It is chaired by the situations and provide the platform
authorities. Commission and made up by for regular and structured
officials from national information exchange between
governments. national authorities.

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Different recommendations to No provisions in the medical This situation has not changed. A Medical Advisory Board (with
patients by Member States. In devices legislation. possibly specialised expert panels)
January 2012, Commission has composed of external scientific
given a mandate to SCENIHR to The mandate to SCENHIR is experts in the field of different
provide a common risk assessment given in accordance with Article medical disciplines shall be set up
with regard to PIP breast implants, 2(3) of Commission Decision to provide scientific advice to the
based on information provided by 2008/72144 (urgency procedure). Commission, Member States,
the Member States But there is no scientific EU body notified bodies and manufacturers.
specialised in medical devices45.
Also EU reference laboratories
and a network of national
reference laboratories shall be set
up for certain hazards or products

4. International

Between 1996 and 2005, the US No international treaty in place International cooperation and The legal basis should be
Food and Drug Administration regarding international information exchange remains reinforced for the international
(FDA) conducted several cooperation. The Global voluntary. According to the new cooperation and the exchange of
inspections of PIP with regard to Harmonization Task Force Article 20a about cooperation at information with 3rd country
saline breast implants. Some of the (GHTF) for medical devices EU level, such cooperation may regulatory authorities, e.g.
inspections detected major (AUS, CAN, EU, JPN, US) is a be part of initiatives developed at regarding audits and incidents.
deficiencies regarding quality voluntary regulatory cooperation. international level.
system and manufacturing. On the basis of reciprocity, 3rd
Confidentiality arrangements countries shall be given access to
Neither the French nor the German between FDA and European the future EU vigilance database.
authorities were informed of the authorities were agreed only later
FDA inspections and their (e.g. with AFSSAPS in 2005 with

Commission Decision setting up an advisory structure of Scientific Committees and experts in the field of consumer safety, public health and the

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findings. DG ENTR, now DG SANCO, in


On 10 January 2012, an At international level, cooperation The current NCAR exchange

information note was sent to 3rd is voluntary. In 2005, a National programme shall be further
countries about available Competent Authority Report deepened and extended in the
information regarding PIP. (NCAR) exchange programme has context of the new International
been set up by the GHTF with Medical Device Regulators' Forum
some other participating 3rd (IMDRF).
countries in order to facilitate the
dissemination of important The UDI system shall be based on
information regarding adverse a globally recognized standard
events related to medical devices. (currently being developed in the
context of the GHTF and further
No traceability requirements as pursued by the new IMDRF).
regards exported products.