MEDICAL DEVICES
AUGUST 2011 Vol. 1 No. 32
IRISH MEDICINES BOARD, KEVIN O’MALLEY HOUSE, EARLSFORT CENTRE, EARLSFORT TERRACE, DUBLIN 2 TEL: 01 676 4971 FAX: 01 634 4033 EMAIL: MEDICALDEVICES@IMB.IE
Letter from the Editor
Welcome to the second edition of the medical devices
newsletter for 2011.
2 011 continues to be another busy
year for medical devices at the
Irish Medicines Board (IMB) and in
Engineering Research Group of the
Royal College of Surgeons in Ireland
(RCSI), which provides an overview CONTENTS
this edition of the newsletter, we fea- of tissue engineering and the research
ture articles on the recently pub- being undertaken by this multidisci-
lished IMB safety notices relating to plinary group in this emerging field.
medicine feeders and the safe use of Updates on the range of European
blood glucose monitoring systems. meetings attended by the IMB are
An update is also provided on recent also provided.
changes to the EUDAMED medical As always, readers are encouraged
device registration data require- to provide feedback, particularly in Editorial
ments. relation to articles that may be of
We are also pleased to feature an interest, by contacting us at
article from The Bone and Tissue medi cal device s@ imb.ie EUDAMED Medical Device
Registration Data Requirements
Overview of Tissue Engineering
Medicine Feeders
Safe Use of Blood Glucose
Monitoring Systems
Regulatory Update
PAGE 2
EUDAMED Medical Device Registration Data Requirements
The Irish Medicines Board (IMB) has operated and maintained a medical device registration database since
2001 which captures data relating to Irish based medical device manufacturers and authorised representatives
of Class I and custom-made medical devices, system or procedure packs and all classes of
in vitro diagnostic medical devices (IVDs).
C ommission Decision 2010/227/EC,
adopted on 19th April 2010, con-
cerning the European Databank on
must be provided, where the model
refers to the reference of the device
model as assigned by the manufactur-
Medical Devices (EUDAMED), came er. In the case of general category IVDs,
into effect on the 1st May 2011, which either the generic name or the
obliges Member States to capture, and name/make of the device must be pro-
upload, additional information to that vided. The most notable change fol-
which was previously required. It lowing the implementation of
should be noted that only data gener- EUDAMED is that the transitional pro-
ated from the 1st May 2011 will be vision in Article 10(6) of Directive
affected by these changes; manufactur- 98/79/EC, which obliges IVD manufac-
ers may, however, amend any data turers to give notification to every
existing prior to May 1st by submitting Member State concerned by the plac-
an amendment to the IMB. ing on the market of devices, now ceas-
In the case of general medical es to apply. As such, in cases where a
devices, registration with the IMB is non-Irish based IVD manufacturer or
required under Article 14 (1, 2) of authorised representative wishes to
Council Directive 93/42/EEC. There are place an IVD device on the Irish mar-
no changes to the organisation details;
they remain as per the current registra-
tion system i.e. name, role, contact
details, etc. The changes brought about
by Commission Decision 2010/227/EC
relate to the device details which must
be supplied to the Competent Authori- or authorised representative is based
ty. All medical device registrations as of within Ireland. As with general med-
1st May 2011 must be accompanied by ical device registrations, IVD registra-
either the Global Medical Device tions made from 1st May 2011 must
Nomenclature (GMDN) or another also be accompanied by either the ket, the IMB does not require notifica-
internationally recognised nomencla- GMDN or another internationally tion prior to doing so, provided that all
ture. Additionally, device registrations recognised nomenclature. In the case relevant registration information has
must also refer to either the generic of Annex II List A, Annex II List B and been uploaded to EUDAMED. Howev-
name or the name/make of the device. self-test IVDs, both those which have er, if the manufacturer or authorised
The generic name refers to the generic been CE marked or are undergoing per- representative is aware that such infor-
name of the device as assigned by the formance evaluation, either the mation is not already present or in the
manufacturer, whereas the name/make name/make or model information process of being uploaded to the
refers to the brand name (trademark) EUDAMED system, the IMB would be
under which the medical device is mar- grateful if it could be provided on a
keted. With regard to system or proce- voluntary basis.
dure packs, the IMB will also be All data contained on the
requesting that the classification of the EUDAMED system is accessible to both
device be supplied in the cases where the national Competent Authorities
the packs are CE marked as a device in and to the European Commission. This
their own right (i.e. in cases where the information is not publically available.
component devices have not already As part of the IMB registration system
been individually CE marked). Data redesign, a validation project concern-
relating to custom-made medical ing all registered details currently on
devices are neither captured by, nor the system has recently commenced.
uploaded to, the EUDAMED system All registrants will be contacted shortly
and as such, are not covered in this via post/email and asked to confirm
article. their registered details. Details con-
As per Article 10 (1), (3) and (4) of cerning the process of confirmation
98/79/EC, IVDs must also be registered will be contained in that communica-
with the IMB where the manufacturer tion.
PAGE 3
Overview of Tissue Engineering
Prof. Fergal O’Brien, Dr. Tanya Levingstone, Dr. Ciara Murphy, Dr. Orlaith Brennan
Everyday thousands of surgical procedures are performed to replace or repair tissue that has been damaged
through disease or trauma.
advantage over these cell types. The matrix. Scaffolds can therefore be used
C urrent clinical approaches focus on
the transplantation of tissue from
one site to another in the same patient
current clinical standard involves
autologous cells from patient’s bone
as delivery systems for growth factors,
adhesion peptides and cytokines.6
(autograft) or from one individual to marrow, which are either directly Another area of importance is the host
another (allograft). Both techniques implanted or cultured in vitro prior to immune response to implanted tissue
have associated disadvantages. Auto- implantation. However, the risk of engineered constructs. The incorpora-
grafts are expensive to harvest and complications following the bone mar- tion of drugs, such as inflammatory
cause pain and donor site morbidity row harvesting procedure has led to inhibitors, into scaffolds in order to
due to inflammation and hematoma the search for alternative sources of control the host response is another
formation. Allografts have limited stem cells that can demonstrate the major area of research within the field
availability and additional constraints potential for therapeutic use. Sources and provides the opportunity for tar-
relating to the risk of rejection and that have shown potential include geting drug delivery directly to dis-
transfer of disease from donor to peripheral blood, adipose tissue, eased tissue to provided localised treat-
patient. The demand for new therapies umbilical cord blood and amniotic ment.7 Scaffolds have also shown
has led to the emergence of the field of fluid-derived stem cells. potential for use as delivery systems for
Tissue Engineering (TE), a term used Cells derive a vast wealth of infor- therapeutic genes.8 The gene therapy
interchangeably with regenerative mation from their environment. The approach utilises DNA encoding for
medicine, which is an interdisciplinary microstructure, composition and therapeutic genes to potentially pro-
area comprising different specialties mechanical cues provided by the scaf- vide a more stable and effective
such as medicine, materials science, fold influence cell behaviour. It is approach to allow sustained and con-
cell biology, genomics and chemical essential that the scaffold is biocom- trolled release of therapeutic factors.
engineering. TE offers a paradigm shift patible, biodegradable and has Promoting vascularisation of scaf-
in medicine: rather than simply replace mechanical properties consistent with folds and tissue engineered constructs
damaged tissues, it aims to regenerate the anatomical site into which it is following implantation is a major chal-
the tissue through the use of biological being implanted. Scaffold stiffness has lenge in the field of TE. Lack of vascu-
substitutes that restore, maintain or also been shown to direct the differen- larity leads to the problem of core
improve tissue function.1 Researchers tiation lineage of stem cells.3 Scaffold degradation which is one of the pri-
have been developing tissue engi- architecture is also of critical impor- mary causes of graft failure post-
neered constructs for the regeneration tance, with porosity, pore interconnec- implantation. One approach currently
of practically every tissue and organ in tivity and pore size all influencing cel- under investigation by a small number
the body.2 lular infiltration, nutrient diffusion of groups, including the group based at
TE technologies are based on a bio- and ultimately the survival of cells.4,5 RCSI, is the development of a pre-vas-
logical triad which involve the success- In addition to biomechanical sig- cularised construct that can support
ful interaction between three compo- nals, cellular behaviour is strongly blood flow and thus improve oxygen
nents: (1) the cells that create the tissue influenced by biological and biochem- and nutrient delivery throughout the
(2) the scaffold that holds the cells ical signals from the extracellular tissue engineered construct (fig.1).
together to create the tissue’s physical Additionally, a range of bioreactor sys-
form and, (3) the biological signalling tems are being utilised in the culture of
molecules, such as growth factors, that constructs pre-implantation to
direct the cells to express the desired improve cell distribution, and to pro-
tissue phenotype. In selection of the vide biophysical stimulation to
cellular component of the triad it is increase levels of differentiation and
essential to select cells that can facili- matrix deposition within the scaffolds.
tate matrix deposition and integration Alternatively, developing scaffolds
of the scaffold with host tissue in vivo. with embedded pro-angiogenic signals
The choice of cells includes primary (such as growth factors or genes) might
cells, cultured from explants of tissue, also provide a solution.
cells from an immortalised cell line, or In the Royal College of Surgeons in
stem cells. Stem cells, under appropri- Ireland, regenerative medicine is one of
ate conditions, can differentiate into the key research pillars i.e. an area of
different cell types such as osteoblasts, strategic research importance within
chondrocytes and adipocytes. Stem the College. The Bone and Tissue Engi-
cells have shown significant potential neering Research Group is headed by
as they have a higher proliferative Prof. Fergal O’Brien and carries out
capacity than cells from adult tissue Figure 1:
(primary cultures) which gives them an Microvessels in a collagen-GAG scaffold continued on following page
PAGE 4
Overview of major importance are our links with in our lab. The group has numerous
the medical community and we typi- national and international collabora-
Tissue Engineering cally have a number of surgical trainees tions, most significantly with the Cen-
continued from previous page carrying out research in our group at tre for Bioengineering in Trinity Col-
any time. At present there are over 40 lege Dublin.
researchers encompassing principal
research in areas including tissue engi- investigators, postdoctoral researchers, 1. Langer, R., Acc Chem Res (2000) 33, 94.
neering of bone, cartilage and cardio- graduate and undergraduate students 2. Atala, A., Rejuvenatation Res (2004) 7, 15.
vascular tissues. Research is ongoing in working in the group. The group main- 3. Engler, A.J., et al., Cell (2006) 126, 677.
the areas of biomaterial development, tains very much a translational focus 4. Murphy, C.M., et al., Biomaterials (2010) 31,
461.
stem cell biology, drug delivery, gene and two recently patented technolo- 5. O’Brien, FJ., et al., Technol Health Care (2007)
therapy, mechanobiology and bioreac- gies, HydroxyColl,9 a bone repair tech- 15, 3.
tor development, translating to in vivo nology, and ChondroColl,10 a cartilage 6. Place, E.S., et al., Nat Mater (2009) 8, 457.
models. The group is truly multidisci- repair technology, are being commer- 7. Huang, D., et al., J. Biomater Sci Polym Ed (2010)
plinary with physicists, material and Jun 21.
cialised through a spin-out campus
8. Endo, M., et al., Tissue Eng (2006) 12, 489.
life scientists, engineers and veterinary company, which is focused on clinical 9. O’Brien, F.J., et al., W02008096334, (2008).
surgeons all working together. Of translation of technologies developed 10. Gleeson, J.P, et al., WO 2010/084481, (2010).
Medicine Feeders
Medicine feeders, including spoons, droppers, syringes, cups and pacifiers/soothers, which are intended for use
for administration of medicines, are classified as medical devices.
devices are required to bear a four devices have already been issued by
S uch devices can be categorised as:
digit notified body number under
the CE mark on the device and its
individual manufacturers/suppliers.
Copies of these customer communica-
(1) Medicine feeders with volumetric packaging. tions accompany the IMB Safety
markings or specifications and Notice SN2011(16) on medicine feed-
(2) Medicine feeders without volu- 2. Medicine feeders provided without ers on the IMB website w ww.i mb.i e.
metric markings or specifica- volumetric markings/specifications The IMB is advising pharmacists,
tions. hospital personnel and retailers to
Medicine feeders without volu-
metric markings or specifications ensure their staff is made aware of
Medicine feeders without volumetric IMB Safety Notice SN2011(16) on
markings or specifications are not are classified as class I medical
devices. These devices are not medicine feeders, to be aware of the
intended to provide a measuring func- differences between the above prod-
tion or to accurately measure medi- intended to provide a measuring
function or to accurately measure ucts and consider the intended pur-
cine doses. pose/accuracy of these products prior
For companies wishing to place medicine doses. These devices are
also required to bear a CE mark on to use. In instances where a device is
medicine feeders on the Irish market, not supplied to the consumer with its
they must be in compliance with both the device and its packaging.
However, according to Medical original packaging/labelling, ensure
Medical Devices Directive 93/42/EEC that the use, accuracy, cleaning, etc. of
and S.I. No. 252 of 1994, as amended. Devices Directive 93/42/EEC and
S.I. No. 252 of 1994, as amended, the device is clearly outlined to the
As such, these devices and their customer.
labelling are required to bear a CE there is no requirement for a noti-
fied body to review any aspect of The IMB is advising consumers to
mark. There are two categories of ensure that they have confirmed with
medicine feeders: these devices and as such, they
will not bear a four digit notified the pharmacist how a medicine
body number. should be administered before using
1. Medicine feeders provided with
it, particularly an oral liquid. It is
volumetric markings/specifications
The IMB has become aware of a num- important that consumers understand
Medicine feeders with volumetric ber of non-compliant medicine feed- the dosage required and how best to
markings or specifications are ers (including spoons, droppers, measure the dose. Consumers with
classified as class I medical devices syringes, cups and pacifiers/soothers) any concerns or questions should
with a measuring function. Noti- that have been provided to pharmacy consult with their pharmacist or gen-
fied body assessment is required outlets, retail outlets and hospitals in eral practitioner.
for the aspects of manufacture Ireland. The non-conformances noted Should you notice any further non
concerned with the conformity of have varied from inadequacies in the compliant products on the Irish mar-
the metrological requirements as labelling, to products that have not ket, please contact the medical device
outlined in the Medical Devices been assessed by a notified body. A vigilance and compliance team by
Directive 93/42/EEC and S.I. No. number of customer communications email at v i gi la nce @ imb .i e or by tele-
252 of 1994, as amended. These regarding these non-conforming phone +353-1-6764971.
PAGE 5
Safe Use of Blood Glucose Monitoring Systems
A new safety notice, SN2011(06), has been published on the IMB website, www.i mb.ie, to highlight the risk of
transmission of blood borne agents associated with the use of blood glucose monitoring systems.
cose test strips are only used once and
B lood glucose monitoring systems
generally consist of a blood glucose
meter, test strips, lancing device and
(ii) single patient use devices such as
lancing devices are only used on a sin-
control solution. These devices may be gle patient. Examine the guidance pro-
intended by the manufacturer to be vided by the manufacturer in the user
used by a single patient for self-moni- manual before use. Follow the manu-
toring or by healthcare professionals facturer’s instructions in relation to the
for the monitoring of multiple proper cleaning of the device as out-
patients. lined in the user manual. Ensure that
Where a blood glucose meter is facilities are in place to ensure the safe
used for the monitoring of multiple disposal of these devices in accordance
patients, it is crucial to ensure that the with the manufacturer’s directions.
device used is intended by the manu- The IMB is advising members of
facturer to be used by healthcare pro- by the manufacturer to be used once the public to talk to a healthcare pro-
fessionals in a multi-patient setting by an individual patient or more than fessional, such as a GP, before buying a
and that recommended precautions for once by a single patient. Lancing medical device. Members of the public
the prevention of transmission of devices should not be used on more should ensure that the devices that
blood borne pathogens are adhered to. than one patient. The use of these they are planning to buy bear the CE
When using devices intended to be devices on multiple patients could mark. Follow the manufacturer’s guid-
used with multiple patients, it is essen- potentially result in the transmission ance with regard to cleaning both the
tial to follow the manufacturer’s guid- of blood borne pathogens to patients blood glucose meter and lancing
ance in relation to the proper cleaning who use the same lancing device, even device. Follow the manufacturer’s
of the device, as outlined in the user when the lancet is changed between guidance with regard to the safe dis-
manual. patients. posal of lancets and blood glucose test
Similarly, where a blood glucose When using a lancing device for strips. Complete the warranty form (if
meter is used by a single patient for self-testing, users should not re-use the provided) so that the manufacturer can
self-testing, users should follow the same lancet or share their lancing make contact if they need to (e.g. if
manufacturer’s instructions regarding device with others. Users should refer they need to recall the product). If
the proper cleaning of the device to the user manual for guidance on the members of the public are concerned
which can be found in the user manu- safe use of lancing devices and the safe about a result given by a medical
al supplied with the meter. disposal of lancets. device, seek medical advice. Lancing
Blood glucose test strips are single The IMB is advising hospital / devices should not be shared with any-
use only devices that should only be healthcare professionals to ensure one else due to the risk of transmitting
used once and then disposed of follow- that this notice is communicated to infection.
ing the manufacturer’s instructions for the appropriate personnel within your In addition, the safety notice pro-
use supplied with the test strips. organisation. Ensure that procedures vides a useful list of reference docu-
Lancing devices are single patient are put in place so that (i) single use ments, including relevant standards,
use only devices that may be intended devices such as lancets and blood glu- codes of practice and guidance.
Regulatory Update
COMPLIANCE AND consistent application of the medical UDI System to improve patient safety
ENFORCEMENT WORKING device legislation across Member States. by enhancing the identification of
Updates were provided by a number of devices, especially in the case of
GROUP (COEN) Member States on specific market sur- adverse events, and to facilitate trace-
veillance projects and various issues of ability of devices in the event of a field
A meeting of the COEN Working
Group was held in Brussels on 25th
May 2011. Discussion took place
mutual interest. The next meeting of
the COEN group is scheduled for Octo-
safety corrective action. The work
which has been done at the Global Har-
among Member States on enhancing ber 2011. monisation Task Force (GHTF) level in
cooperation between market surveil- UNIQUE DEVICE the UDI Working Group was consid-
lance authorities and customs authori- ered as a foundation for the European
I D E N T I F I C AT I O N ( U D I )
ties. The role of economic operators in initiative.
WORKING GROUP At the June meeting, the UDI Work-
the context of Regulation 768/2008
was also discussed. Progress was made
on the market surveillance frequently
asked questions (FAQ) guide to ensure
T he UDI Working Group met in June.
The goal of the group is to further
discuss the development of a European continued on following page
PAGE 6
Regulatory Update continued on documents relevant to the medical included discussion on resourcing,
devices sector. New work items were assessment of drug-device combination
ing Group reviewed recent changes also discussed and agreed including a products, companion diagnostics and
proposed by the GHTF to the draft proposal to revise the designation clinical research of both medicines and
guidance document ‘GHTF Draft Pro- process for notified bodies. Further devices. The workshop was successful
posal for Guidance on Unique Device details of these work items and a meet- and a further work programme and
Identification (UDI) System for Med- ing note will be published on ongoing cooperation is envisaged.
ical Devices’. The revised guidance doc- www.cmc-md.eu.
ument was reviewed and Member MEDICAL DEVICE EXPERT
States discussed similar systems that C L I N I C A L I N V E S T I G AT I O N & GROUP (MDEG)
have already been implemented in
Member States.
E VA L U AT I O N ( C I E ) W O R K I N G
GROUP T he MDEG met in Brussels in June.
Discussions included an update on
key medical device issues. Updates
N O T I F I E D B O D Y O P E R AT I O N S
GROUP (NBOG) T he Clinical Investigation & Evalua-
tion Working Group met in Brus-
sels. The group finalised its review of
were provided on the progress of
new/revised legislative measures on e-
T he Notified Body Operations Group
met in June both for its normal
meeting and also to conduct a work-
comments on the draft MEDDEV guid-
ance on post-market clinical follow up.
labelling of medical devices, devices
incorporating animal tissues and leg-
islative revisions relating to the inclu-
In addition, the draft GHTF guidance
shop on the peer review system for document on serious adverse event sion of provisions for screening assays
authorities responsible for designation reporting during clinical investigations for new variant CJD in the IVD Direc-
and monitoring medical devices. The was also reviewed. Of key interest were tive. In addition, discussions took place
peer review system allows opportunity presentations made to the group on on the progress made to resolve issues
for European colleagues to accompany the number of pre-market clinical relating to the formal objections on
national authorities while they are investigations currently being conduct- harmonised standards and also on the
auditing a notified body and aims to ed in Europe, a presentation from a next steps for the recast of the medical
ensure that the same criteria and stan- European clinical society on implant devices directives. A presentation was
dards are being applied to notified bod- registers and a paper on pre-market made by the notified body association
ies across Europe. The workshop in evaluation of medical devices recently on their proposed Code of Conduct for
June allowed an opportunity to discuss published by the Belgian Health Tech- notified bodies. In addition, significant
how the peer review system may be nology Assessment agency. discussions took place on the future
further developed and improved and role for the GHTF and on the develop-
also to discuss some of the main chal- ment of Unique Device Identifiers
lenges that had been encountered by HEADS OF MEDICINES AGENCY (UDI) for medical devices.
authorities and peer reviewers while (HMA) – COMPETENT
participating in this system to date. AUTHORITIES FOR MEDICAL RECAST WORKING GROUP
The IMB have participated in peer DEVICES (CAMD) WORKSHOP
review system on five occasions to
date, being reviewed twice and acting
A workshop was hosted by the Hun-
garian Presidency on 27th April
T he recast working group was estab-
lished by the CAMD in February to
provide detailed input to the Commis-
as a peer reviewer on three occasions.
2011 to increase mutual understanding sion and specific suggestions as to how
and explore potential collaborations the legal texts might be struc-
CENTRAL MANAGEMENT
between the network of the Heads of tured/changed for the purposes of the
COMMITTEE
Medicines Agency (HMA) and the recast. The meetings afford a key
T he Central Management Commit-
tee for medical devices held its third
meeting in Brussels in June. Work
Competent Authorities for Medical
Devices (CAMD) network. In approxi-
mately 20 Member States, single agen-
opportunity for Member States to dis-
cuss together and with the Commis-
sion the various elements of the med-
items underway include: development cies are responsible for both medicine ical devices regulatory system which
of specific criteria for notified body and medical device regulation and so may be subject to revision. The meet-
designation; to define the contents of these 20 agencies are already represent- ings to date have allowed for detailed
notified body certificates; to define the ed by their Chief Executives on the technical, clinical and regulatory
contents of a manufacturer’s declara- HMA. An overview of the different reg- aspects of the proposed recast to be
tions of conformity; to improve the ulatory systems and related structures considered. Topics highlighted by the
readability of instructions for use; to was provided, the Commission updated group may be considered by the Com-
agree on periods of grace for manufac- on the recast and key discussions were mission for inclusion in the impact
turers correcting non-conforming held on resourcing and funding of assessment report and in the legislative
product (e.g. after an up-classification) device authorities and exploring alter- proposals which are expected to be
and the coordination of consultations native fee models. Specific work items published in 2012.
Bulletin of the Medical Devices Department is designed by Ashfield Press Publishing Services for
IRISH MEDICINES BOARD, KEVIN O’MALLEY HOUSE, EARLSFORT CENTRE, EARLSFORT TERRACE, DUBLIN 2
tel: +353 1 6764971 fax: +353 1 6344033 email: medicaldevices@imb.ie: http://www.imb.ie