myRIS MEDICAL DEVICES & COSMETICS/BIOCIDES

Friday December 19, 2014 (SW51 2014)
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GLOBAL NEWS
GLOBAL REGULATORY AFFAIRS
EUROPEAN UNION
FRANCE
EUROPE
MIDDLE EAST
RUSSIA & RELATED COUNTRIES
NORTH AMERICA
LATIN AMERICA
AUSTRALIA & NEW ZELAND
INDIA & ASIA
DISCOVERY - DESIGN - DEVELOPMENT
COSMETICS & BIOCIDES
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Parmi les sujets sélectionnés dans ce numéro :
Medtech’s Biggest Moves in 2014
p.3
Molecular Testing To Drive Infectious Diseases
Diagnostics Market
p.5
The methodological guideline on “Meta-analysis of
diagnostic test accuracy studies” now available
p.9
8 FDA Guidance Documents You Need to Know p.34
The Top 15 Medical Device Deficiencies Cited by FDA in
2014
p.37
PCORI and NIH Partner on Request for Applications to
Study How to Improve Blood Pressure Control in HighRisk Individuals
p.46
CHINA - Potential New Tool for Cervical Cancer
Detection and Diagnosis
p.52
La notification des produits cosmétiques
p.62
L’ISO 27001: une norme pour encadrer les systèmes
qualité liés à la sécurité de l’information
p.10
ANSM - Risques liés aux prothèses de hanche à couple
de frottement métal-métal: Recommandations
d’utilisation et de suivi des patients
p.24
ANSM - Les logiciels dispositifs médicaux
p.25
Rapport nano 2014
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p.64
© Adrien Tillet
«Beyond words, the world »
Season’s Greetings and Best Wishes
Yves Tillet and Associate Consultants & Experts
Cabinet WHITE-TILLET
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GLOBAL NEWS 
 Medtech’s Biggest Moves in 2014
(Source: MD+DI)
 The Worst Performing Medical Device Companies of 2014
Koninklijke Philips Electronics: –20.5%
Getinge AB: –22.5%
Drägerwerk AG & Co.: –14.4%
General Electric: –8.7%
Siemens: –6.2%
(Source: Qmed)
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 Why Women Are Embracing Biomedical Engineering
Shreya Chandrasekhar, a graduate student in SJSU's biomedical engineering program, says many women are drawn to the field out of
altruism.
Is it possible that women could end up dominating biomedical engineering—or at least gain some
workforce parity with men in coming years?
It is still a pretty open question. But one had to at least hope for more gender diversity after a recent
informal talk with about a dozen San Jose State University biomedical engineering students at
BIOMEDevice San Jose.
The biomedical engineering program has a stronger female presence than male at the university. One
student, who was obtaining a master’s at the university, said he noticed that women outnumbered men
when attending the bioengineering program at the University of California, Berkeley as well. Syracuse
University professor Andrew Darling, PhD, said in a report earlier this year that women outnumber men in
the freshmen class of that university as well.
Nationwide, however, one gets the impression that there are still more men than women in biomedical
engineering—albeit by a fairly narrow margin. In 2000, some 39% of BME bachelor degrees were awarded
to women, which is the highest percentage of any engineering discipline, according to the American
Society for Engineering Education. A source pointing to 2011 numbers says 40% of graduates earning BME
degrees were women.
At present, women remain underrepresented in the biomedical engineering workforce as well as in
academic positions. More striking, in 2012, Forbes put biomedical engineering on its top 10 list of the
worst jobs for women. Coming in at No. 8 on the list, biomedical engineers fared slightly better than
secretaries. In that article, the percentage of professional women biomedical engineers was cited as
18.2%.
Nationwide, a growing number of women are beginning to make a name for themselves in the medical
device industries. For instance, Elizabeth Holmes (30), the founder of Theranos (Palo Alto, CA), happens to
be the youngest recipient of 2015 Horatio Alger Award for exceptional leadership. Her blood diagnostics
company also has helped her become the youngest female billionaire in the United States.
The field of biomedical engineering is relatively new, and is quickly growing, making the field potentially
attractive to a growing number of students, including women, who have outnumbered men on college
campuses for decades.
A paper published in 2010 by the American Society for Engineering Education acknowledges hurdles in
academia for females entering biomedical engineering—especially at the post-graduate level—but
suggests that “the field is inherently appealing to women, especially in comparison to the more traditional
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disciplines such as mechanical and electrical engineering.” It continues: “[Women] are more connected to
the biological and medical sciences, which have greater gender equity than engineering sciences.”
A similar theme also emerged from the discussion with SJSU students. The students state that one of the
main things that drew them to the field was the overarching desire to help others, a theme that also
emerged in a survey of the BME student body. … (Source: Qmed)
 Molecular Testing To Drive Infectious Diseases Diagnostics Market
A new Frost & Sullivan reports predicts that molecular testing will be one of the foremost drivers of the
overall growth of the global infectious diseases diagnostics market.
The report states that the market will be worth $12.78 billion in 2018 growing at an compound annual
growth rate of 10% from $7.92 billion last year.
The increase is partially being fueled by greater demand for a new diagnostic regime that is more
decentralized than the traditional centralized lab testing methodology. Molecular diagnostics remains the
fastest growing segment of the overall infectious diseases diagnostics market.
Large diagnostics players are keenly aware of both these trends - the demand for both decentralized
testing and the prevalence of molecular diagnostics. In April, Roche bought point-of-care molecular
testing company iQuum For $275 million in cash and the potential for an additional $175 million in
milestone payments. The Marlborough, Massachusetts company has FDA-cleared and CE Marked
diagnostic tests that can be performed at the point of care with minimal training.
They have a "lab-in-a-tube" technology, explained Aish Vivekanandan, an analyst with Frost & Sullivan.
Tests for Hepatitis B and C, tuberculosis and sepsis are the largest revenue generators. The growth of the
worldwide infectious diseases diagnostics market is being driven by increased prevalence of some of
these diseases in the developing world, according to the report.
Companies like Roche, Qiagen, Abbott and others are taking advantage of the opportunity in these
relatively under penetrated emerging markets by striking partnerships with local companies as well as by
making acquisitions.
For instance, Qiagen, the Dutch company, inked a deal with Tokyo-based Astellas Pharmaceuticals to
develop companion diagnstics paired with Astellas drugs for cancer and other diseases.
"Another example is Enigma diagnostics collaboration with China's ICDC to develop and commercialize
their molecular diagnostic test to detect infectious disease pathogens," Vivekanandan says. … (Source :
MD+DI)
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 What the Medtech Giants Expect from Start-Up Partnerships
The bigger companies get, the more they usually rely on outside sources for innovation. So, they
increasingly develop systematic approaches to monitor and evaluate start-ups and their technologies. The
goal is to be up to speed on the latest developments in the sector and to have a foot in the door at an
early stage if the start-up evolves into a worthwhile acquisition target.
Some companies are setting up accelerators around the world in order to get hold of the most innovative
ideas. Becton Dickinson, for example, has started two accelerator programs in the US and one in Israel in
2014 and is planning to add further programs next year. In Israel, BD cooperates with Microsoft Ventures
that provides office space and the infrastructure for the start-ups and Healthbox which appropriates
funding.
“The BD accelerator program is an innovation experiment with the primary objective of ‘organization
learning’; learning about new technologies, capabilities and business models that may enable future
opportunities for BD. In partnership with investors and infrastructure providers, we recruit, evaluate and
select startups based on the uniqueness of their technology and capability of their team. In return, BD
provides these startups with business mentors and subject matter experts to better understand market
needs, customer requirements and regulatory, clinical and reimbursement hurdles,” Al Lauritano, director
strategic technology partnerships for BD Technologies told EMDT. “We do not charge for these support
services but do it to help them be successful to raise further capital. It’s also important to note that we
are typically not taking equity stakes in these companies (at this stage) nor are we co-inventing.”
Those activities are rather strategically than financially motivated. The companies use the experience to
study the implications of new technologies, the reactions of customers and potential business models.
The start-ups that participate in BD’s accelerator programs are are typically pre-seed or seed stage. “[…]
We are not considering acquisition at this stage. We are more likely to establish a research collaboration,
license agreement or incubation relationship with accelerator graduates,” Lauritano said. “Presently, we
are looking to accelerate startups that are combining medtech and high tech to make medical devices
smarter. We are also looking at Big Data opportunities that will help improve clinical decision making and
healthcare outcomes.”
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 C.R. Bard Could Face Billions in Damages from Mesh Lawsuits
A federal judge has warned C.R. Bard Inc. (BCR) to settle outstanding pelvic mesh lawsuits or face billions
of dollars in jury awards to plaintiffs, according to a report by Bloomberg.
“I can’t imagine a corporation facing potentially billions of dollars in verdicts wouldn’t find it advisable to
try to achieve a settlement for a much lesser sum,” U.S. District Judge Joseph Goodwin, sitting in
Charleston, WV, said at a December 9 hearing, according to a transcript obtained by Bloomberg. “I base
that billions of dollars business on some of the rather large verdicts that we’ve had.”
Goodwin is overseeing all federal-court litigation involving the implants.
The Murray Hill, NJ-based company faces more than 12,000 lawsuits filed by women who claim the
implants have damaged their organs, made sexual intercourse painful, and left them in constant pain,
Bloomberg said.
Transvaginal mesh implants are used in the treatment of pelvic organ prolapse, pelvic floor repair, and
stress urinary incontinence. Potential causes for these conditions include childbirth, hysterectomy,
obesity, and normal aging. In order to treat them, a transvaginal mesh is surgically attached to or
implanted, using the vaginal wall as an anchor point. However, several meshes used in the procedure
have been found to cause complications in some patients, including erosion of internal tissues and
organs, painful sexual intercourse, infection, and urinary problems.
Plaintiffs have won multi-million-dollar awards in cases against C.R. Bard and other medtech companies.
In August 2013, a federal jury in West Virginia ordered C.R. Bard to pay $2 million to a woman who was
allegedly injured by the company’s vaginal mesh device. Bloomberg reported that the company agreed in
October to settle 500 suits for about $21 million, in its first large-scale resolution of vaginal-mesh cases,
people familiar with the accord said.
In an SEC filing in July, the company said that it was facing personal injury claims filed by approximately
12,445 plaintiffs in state and federal court over its women’s surgical continence products. It also
acknowledged facing “material additional costs” if ordered by the District Court in West Virginia to
prepare for trials.
“The company anticipates that multiple additional trials, including a possible consolidated trial, may occur
in early 2015,” Bard said in the SEC filing. “Additional state court trials are scheduled throughout the
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second half of 2014…. it cannot give any assurances that the resolution of these claims will not have a
material adverse effect on the company’s business, results of operations, financial condition and/or
liquidity.” … (Source: Qmed)
AUDIT & OUTSOURCING in CHINA
The Cabinet WHITE- TILLET is now present in China with Alban Tacquet who took
the general direction of our local representation in order to:
• Conduct audits secured at a reasonable cost according to GMP standards (Drugs
and API), ISO 9001, ISO 13485 (MD) , GMP Cosmetics;
• Complete outsourcing assignments in the areas of active ingredients of drugs,
medical devices and cosmetics;
• Support for legal and regulatory approaches to the authorities.
Alban Tacquet (41) has made a career in quality management and regulation of
health products in France before running a business in China. Married to a Chinese
wife, Alban lives in Beijing (Pekin) for 7 years.
For more information, please contact Yves TILLET CEO/CSO to:
White-tillet@white-tillet.com
 Medtronic launches new sinus surgery device
Medtronic said that it's launching a new sinus surgery device, NovaShield, for functional endoscopic sinus
surgery.
The NovaShield device consists of a chitosan-based injectable nasal packing and a stent, according to a
press release. The FDA granted 510(k) clearance for the device in October, Medtronic said.
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"NovaShield is Medtronic's first chitosan-based nasal packing," ENT biomaterials product manager Lisa
Sapp said in prepared remarks. "With the benefits of chitosan and its unique design, NovaShield is helpful
for both surgeons and patients." … (Source: Massdevice)
GLOBAL REGULATORY AFFAIRS
Government and Regulatory Bodies
http://www.pharmweb.net/pwmirror/pwk/pharmwebk.html
http://www.who.int/en/
www.imdrf.org
 The methodological guideline on “Meta-analysis of diagnostic test
accuracy studies” now available
Diagnostic tests are used for a variety of purposes including to: determine whether or not an individual
has a particular target condition; provide information on a physiological or pathological state, congenital
abnormality, or on a predisposition to a medical condition or disease; predict treatment response or
reactions; define or monitor therapeutic measures. Ideally an evaluation should be undertaken to assess
the clinical utility of a test. Such an assessment is generally not supported by appropriately designed
studies or by long term outcome data. In the absence of clinical utility data, diagnostic tests are evaluated
on the basis of test accuracy: the ability of the test to correctly determine the disease status of an
individual. Test accuracy is not a measure of clinical effectiveness and improved accuracy does not
necessarily result in improved patient outcomes. A number of metrics are available to describe the
characteristics of a diagnostic test, such as the sensitivity, specificity, diagnostic odds ratio, predictive
values, likelihood ratios, and the receiver operator characteristic (ROC) curve. Diagnostic tests may also be
subject to a threshold effect, whereby the translation of a test result into a dichotomous
positive/negative result is not uniform across studies.
Meta-analysis of Diagnostic Test Accuracy Studies.pdf
 Report highlights hip, knee revision rates
The American Joint Replacement Registry's 1st-ever annual report on hip and knee implants underscores
the relatively high incidents of problems involving hip replacement surgeries relating to malfunctioning
implants.
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Out of more than 43,823 hip and knee procedures performed in 2013, there were 1,510 hip revisions –
just 3.4% of the total. Knee revisions came in at 1,367, or 3.1% of the total number, the AJRR found.
Those results point to revision surgeries as a relatively small number out of the total performed. But the
AJRR's look at revision surgeries from 2012-2013 involving implants 3 months old or less paints a different
picture.
The most frequently reported diagnosis code for hip revision surgeries involved infection and
inflammatory reaction to the implant (37.8% of the time). The next biggest complication centered on
periprosthetic fractures, where a bone breaks around the implant (31.7%). After that, dislocation of the
prosthetic joint was next biggest diagnosis for revision surgery (14.6%), then "other" mechanical
complications of the joint implant" (8.5%) or "mechanical loosening" of the prosthetic joint (7.3%).
For knee revision surgeries, the results are somewhat better in terms of malfunction problems. … (Source:
MassDevice)
 ISO 80369-20
ISO 80369-20 Small-bore connectors Part 20 Common test methods - Final vote.pdf
 L’ISO 27001: une norme pour encadrer les systèmes qualité liés à la
sécurité de l’information
La norme ISO 27001 permet aux entreprises et aux administrations d'obtenir une certification qui atteste
de la mise en place effective d'un système de management de la sécurité de l'information (SMSI). Cette
norme garantit aux parties prenantes (clients, actionnaires, partenaires, autorités de tutelle, etc.) que la
sécurité des systèmes d'information a été pleinement prise en compte et que l'organisme s'est engagé
dans un processus d'amélioration continue.
La norme ISO 27001 définit les tâches et actions à respecter pour qu'un processus "Plan-Do-Check-Act" ou
"Roue de Deming" soit en place dans l'organisme, typiquement sous la responsabilité du RSSI
(Responsable de la Sécurité des Systèmes d'Information).
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Cette démarche ISO 27001 apporte l'amélioration continue de la sécurité de l'information, l'universalité
et la complétude des pratiques, une approche axée sur les processus et le développement du dialogue et
de la communication entre les interlocuteurs sur les problématiques de sécurité. … (Source: LNE)
ACCREDITATIONS
 Accords de reconnaissance mutuelle (ARM):
Le LNE/G-MED est organisme d’évaluation de la conformité dans le cadre des accords de reconnaissance
mutuelle signés entre l’Union Européenne et respectivement les Etats-Unis d’Amérique, l’Australie et la
Nouvelle Zélande.
>> Pour en savoir plus, consultez nos pages accès au marché USA et accès aux marchés Australien et NéoZélandais
Taiwan
Le LNE/G-MED est accrédité par le ministère de la santé de Taiwan pour la réalisation des audits suivant la
norme ISO 13485.
>> Pour en savoir plus, consultez notre page accès au marché taiwanais
Food and Drug Administration (FDA)
Le LNE/G-MED est accrédité par la FDA en tant qu’organisme tierce partie (programme IAP) pour
effectuer des inspections autorisées par la FDA.
>> Pour en savoir plus, consultez notre page accès au marché USA
Brésil
Le LNE est accrédité par l'INMETRO en tant qu'OCP (Organisme de Certification Produits)
>> Pour en savoir plus, consultez notre page accès au marché brésilien
Japon
Dans le cadre d'un accord de reconnaissance avec le JQA (Japan Quality Assurance organization), le
LNE/G-MED est organisme autorisée JPAL pour les audits système de gestion de qualité (SGQ)
>> Pour en savoir plus, consultez notre page accès au marché japonais
Programme CB-Scheme
Dans le cadre des accords internationaux du CB Scheme (Schéma OC), le LNE est reconnu par l'IECEE en
tant qu'organisme de Certification (National Certification Body) et comme Laboratoire d'Essais
(Certification Body and Testing Laboratory, CBTL).
>> Pour en savoir plus, consultez notre page certification CB Scheme
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 ACTUALITES
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Guide relatif à l'implémentation de la norme EN 60601 3ème édition
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Guide sur la compatibilité électromagnétique (CEM) des dispositifs électro-médicaux
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Enregistrement des dispositifs médicaux au Brésil
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Enregistrement des dispositifs médicaux au Japon
 L’ISO 50001: une solution performante pour améliorer la gestion
énergétique des bâtiments
Dans le cadre de la mise en application des dispositions de la directive européenne "Efficacité
énergétique", les entreprises doivent prendre des dispositions pour évaluer leur consommation d'énergie
en vue d'améliorer leur performance énergétique.
D’ici le 5 décembre 2015, les grandes entreprises devront soit réaliser un audit énergétique, soit se faire
certifier suivant la norme ISO 50001. … (Source: LNE)
EUROPEAN UNION
 Retour sur les révisions des directives
européennes sur les dispositifs médicaux
Le 26 septembre 2012, la Commission européenne a publié les 2 textes de révision des directives
européennes sur les dispositifs médicaux qu’elle a soumis au Parlement européen et au Conseil de
l'Union européenne.
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Ils prennent la forme de 2 propositions de règlements européens qui viendront remplacer les
directives actuellement en vigueur (90/385/CEE – 93/42/CEE – 98/79/CE).
Ces révisions, après leur adoption, auront un impact important et pérenne sur l’ensemble des
opérateurs économiques (fabricants, mandataires, importateurs et distributeurs) qui intervient dans la
mise sur le marché des dispositifs médicaux au sein de l’espace économique européen. Elles vont
également modifier les missions et responsabilités de la Commission Européenne, des autorités de
santé et des organismes notifiés.
La Commission indique que les deux propositions de règlement pourraient être adoptées en 2014 et
mise en application entre 2015 et 2019.
Les 3 objectifs majeurs de ces révisions
La Commission européenne donne trois objectifs globaux pour les révisions, qui sont déclinés au sein
des deux propositions de règlements 1.
Premier objectif : s'assurer d’un niveau élevé de la protection de la santé humaine et de sécurité. Pour
atteindre cet objectif, la Commission a inclus, entre autres, un chapitre sur les exigences des
évaluations cliniques, le renforcement de la surveillance post-commercialisation et les activités de
vigilance pour les acteurs économiques et les autorités compétentes, ainsi qu’un chapitre sur la
traçabilité pour tous les dispositifs.
Deuxième objectif : garantir le fonctionnement du marché intérieur. La Commission précise que cet
objectif est atteint par "... [mettre] en place un cadre réglementaire qui s'applique avec cohérence à
travers l'UE ....2" Un cadre réglementaire cohérent comprendrait par exemple les clauses visant à
combler les disparités des dispositions légales propres à chaque État membre ou à harmoniser la façon
dont sont traités les produits-frontières et les questions de classification. En outre, l'annexe XV de la
proposition de règlement relatif à la révision des dispositifs médicaux énumère les produits qui sont
inclus dans le champ d'application élargi de la définition de «dispositif médical», fournissant des
précisions.
Troisième objectif : fournir un cadre réglementaire qui est non seulement cohérent, mais qui soutient
également l'innovation et la concurrence dans le secteur européen des dispositifs médicaux. La
Commission a examiné différentes options pour faire évoluer le système actuel et a décidé que des
dispositions renforcées apportées au système d'évaluation par tierce partie en vigueur actuellement
serait la solution la plus efficace, permettant de préserver l'innovation et une forte compétitivité.
Un bref aperçu des nouvelles exigences introduites par les deux propositions de règlements
La révision comporte deux propositions de règlements. L’un est applicable aux dispositifs médicaux de
diagnostic in vitro et le second à tous les autres dispositifs médicaux. Il est à noter que le règlement
est un texte juridique européen qui n'a pas besoin d'être transposé dans la législation nationale de
chaque État-membre.
Les «attendus», présentés en début des textes de révision, identifient les objectifs des modifications
apportées à la législation. Il est toujours très intéressant de les lire, au moins une fois, parce qu’ils
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fournissent l’argumentaire de ces changements et des pistes d'interprétation du texte lui-même. Selon
les dispositions transitoires proposées, dans l'hypothèse d'une adoption par le Parlement européen en
2014, les deux règlements pourraient être strictement obligatoires en 2017 pour les dispositifs
médicaux et en 2019 pour les dispositifs médicaux de diagnostic in vitro.
> L’analyse des deux textes montre des exigences / dispositions communes, en particulier :
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Art 2 – Nouvelles définitions
Art 5 – Prise en compte de la vente à distance
Art 7 – Ajout de Spécifications Techniques Communes pour les dispositifs médicaux (elles existent
déjà pour les dispositifs médicaux de diagnostic in vitro)
Art 9 à 12 – Exigences pour les mandataires, les importateurs et les distributeurs
Art 13 – Obligation pour les fabricants de disposer au sein de leur organisation d’au moins une
personne qualifiée possédant des connaissances spécialisées dans le domaine des dispositifs
médicaux (diplôme et/ou expérience spécifique)
Art 14 – Cadre pour le « commerce parallèle » (ce qui inclut les distributeurs à marque propre)
Chapitre IV – Renforcement de la supervision des organismes notifiés en particulier en ce qui
concerne leur compétence et leur indépendance pour la réalisation de leur mission
Chapitre VII – Renforcement des dispositions relatives à la surveillance du marché et à la
vigilance.
Globalement, l’autorité, en terme opérationnel, de la Commission Européenne est elle aussi
renforcée.
> Et des exigences / dispositions spécifiques à chaque secteur concerné, en particulier :
Pour la proposition de règlement sur les dispositifs médicaux (en remplacement de la directive
90/385/CEE sur les dispositifs médicaux implantables actifs et la directive 93/42/CEE sur les dispositifs
médicaux)
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Art 1 et 2 – Modification du champ d’application (qui inclut à présent certains dispositifs
implantables ou invasifs (voir annexe XV) même s’ils ne sont pas destinés à un usage médical et
également certains dispositifs fabriqués à partir de tissus ou de cellules d’origine humaine rendus
non-viables)
Art 23 et 24 – Obligation de traçabilité
Art 26 – Ajout d’un résumé des caractéristiques de sécurité et des performances cliniques pour
les dispositifs médicaux de classe III
Art 21 – Ajout de règles de classification
Art 42 – Renforcement des dispositions relatives aux inspections inopinées et aux contrôles par
sondage
Art 44 – Pour certains dispositifs médicaux de classe III, intervention, avant l’émission du certificat
et en sus de la procédure d’évaluation réalisée par l’organisme notifié, d’un Groupe de
Coordination des Dispositifs Médicaux (GCDM voir art 78) chargé de la revue du rapport
d’évaluation préliminaire. Le GCDM peut demander des informations complémentaires, des
contrôles par sondage ou des audits sur site
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Art 49 à 60 – Renforcement des exigences relatives à l’évaluation clinique au cours de la vie du
dispositif médical
Pour la proposition de règlement sur les dispositifs médicaux de diagnostic in vitro (en remplacement
de la directive 98/79/CE sur les dispositifs médicaux de diagnostic in vitro)
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Art 1 et 2 – Modification du champ d’application (qui inclut à présent certains dispositifs à haut
risque fabriqués et utilisés dans un seul et même établissement de santé, les dispositifs qui
renseignent sur la prédisposition à une affection ou à une maladie, les logiciels médicaux dédiés)
Art 21 et 22 – Obligation de traçabilité
Art 26 – Ajout d’un résumé des caractéristiques de sécurité et des performances cliniques pour
les dispositifs médicaux de classe C et D
Art 39 – Ajout de règles de classification basées sur le risque
Art 40 – Contribution de laboratoires de référence
Art 40 – Renforcement des dispositions relatives aux inspections inopinées et aux contrôles par
sondage
Art 42 – Pour certains dispositifs médicaux de diagnostic in vitro de classe D, intervention, avant
l’émission du certificat et en sus de la procédure d’évaluation réalisée par l’organisme notifié,
d’un Groupe de Coordination des Dispositifs Médicaux (GCDM voir art 76) chargé de la revue du
rapport d’évaluation préliminaire. Le GCDM peut demander des informations complémentaires,
des contrôles par sondage ou des audits sur site
Art 47 à 58 – Renforcement des exigences relatives à la preuve clinique en fonction du risque
L’étape suivante : comment les propositions deviennent des règlements
La Commission européenne est la branche exécutive de l'Union européenne (UE), responsable de la
réalisation et de l'exécution des règlements de l'Union et des lois.
A ce titre et en tant que représentante des intérêts de l'UE dans son ensemble, c’est elle qui propose
de nouvelles lois et réglementations au Parlement, représentant les citoyens de l'Union européenne et
au Conseil de l’Union européenne, représentant les gouvernements des États membres.
Ensuite, grâce à la procédure législative ordinaire, le Parlement et le Conseil étudient le projet de
règlement et en discutent, éventuellement à deux reprises, pour trouver un accord avant que le vote
formel au Parlement n’ait lieu.
Une fois voté au Parlement, le règlement devient d’application obligatoire dans tous les pays de
l’Union européenne.
Pour en savoir plus sur le processus législatif, consultez le site de l'Union européenne.
Pour toute question relative à la commercialisation de votre dispositif en Europe, ainsi qu’aux
conséquences de ces révisions sur votre dispositif, n’hésitez pas à nous contacter. Nous pourrons vous
guider pour obtenir ou maintenir la certification en vue du marquage CE de votre dispositif. (Source:
Gmed)
15
1 - Commission Staff Working Document: Impact Assessment on the Revision of the Regulatory
Framework for Medical Devices. Part I. SWD(2012) 273
 Rôles, responsabilités, nouveaux acteurs…
les changements proposés dans la révision des directives
(Source: GMED)
 Europe Edges Towards a New Understanding on HTA
The European Union is moving ahead, in its own slightly crabwise fashion, with its attempts to work out
what healthcare budgets should be used for. The characteristic sideways gait results from the fact that
this isn't strictly speaking an EU issue. The EU treaty preserves health spending decisions as a matter for
national governments, and they have long-defended this approach in custom and practice. But health
services in Europe are, as in so many other parts of the world, at serious risk of imploding under their
own weight in these budget-constrained time. In consequence, any close observer of EU machinations
can perceive one new group breaking fresh ground by looking at how to make national health services
more efficient and sustainable, while another group looks at health technology assessment as it as about
to take on a new lease of life.
Lengthy courtship
The EU has been flirting with health technology assessment (HTA) for some time now, but for a long while
the relationship was conducted in the EU's usual hands-off "don't look at me while I'm doing this"
approach to pharmaceuticals and money. It took a bold step in 2011, when it adopted the cross-border
patients' rights directive— which was really a Trojan horse designed by the European Commission to
penetrate the camp of national regulators, while masquerading as a simplification of rules for the benefit
of citizens. Artfully concealed inside the longwinded rhetoric about equality of opportunity and individual
rights were a handful of hardcore institutional innovations, and the chief interloper among those
meticulously disguised fifth columnists was the first legal base for HTA. No imposition, of course. That
would be unthinkable. But a carefully crafted provision for a voluntary network of national HTA bodies,
conveniently covering all member states, plus Norway and Iceland, and supported by an EU-funded
organization with the unpronounceable title of EUnetHTA.
After a couple of years probing carefully and discreetly at how individual member states make their
judgments on new drugs or devices or medical procedures, the EU is now getting ready for the next
stage. Not quite an ambush, but definitely a fastidiously prepared convergence of thinking about the idea
of something more systematic. Still voluntary, of course. The EU is the EU. But there are unmistakable
indications of EU aspirations to shift to a higher gear. At the end of October, delicate manipulations of
circumstance persuaded members of the HTA network to adopt —unanimously—a "strategy for EU
cooperation on HTA."
Vision embraced
16
What this amounts to is an acceptance by national authorities of a strategic vision for HTA—something
unthinkable only a few years ago, but now less rebarbative as a concept because of the hard times that
austerity has forced upon healthcare planners. And to serve the development of that strategic vision, EU
officials have convinced national officials that they should identify priority areas to be addressed through
the network.
It is all still carefully wrapped around with allusions to the treaty's ban on any interference with areas of
national competence or any harmonization of national laws or regulations, and explicit opt-out clauses
making clear that "individual member states are free to decide the level at which they are willing to
participate in cooperation efforts." But it is a real advance towards developing a European approach,
rather than leaving all these decisions to the whims, caprices, and local priorities or vested interests of
member states. If it is to be a single market for medicines, then there must be some common elements in
deciding which products merit reimbursement across that market, the logic runs.
HTA, says the new strategy, is "a useful tool to help decision makers achieve sustainable healthcare
systems, in the best interest of European patients." The goal of this new degree of European cooperation
is "to increase use, quality, and efficiency of HTA production in Europe and to promote HTA in decisionmaking." Cooperation can "promote more consistent approaches to HTA as a health policy tool to
support evidence-based, sustainable, equitable choices in healthcare and health technologies." And it can
develop "shared know-how" among national bodies working together to produce and apply shared
methodologies.
 Changement d’organisme notifié: les points clés pour rejoindre le
LNE/G-MED
Le transfert ou le changement d’organisme notifié (ON) n’est pas une décision facile à prendre pour un
fabricant de dispositifs médicaux. L’ON est un partenaire accompagnant le fabricant dans la certification
de ses dispositifs médicaux. La relation entre le fabricant et l’ON est donc cruciale. Toutefois,
indépendamment des raisons amenant au transfert, le fabricant peut changer d’ON librement. … (Source:
LNE)
 Cybersécurité des dispositifs médicaux: un
enjeu majeur pour les acteurs de la santé et les patients
17
Principalement commercialisées dans les magasins d’applications de smartphones, les applications
mobiles dédiées à la santé et les logiciels de dispositifs médicaux représentent un marché en plein boom.
Dans le même temps, de plus en plus de dispositifs médicaux sont connectés aux réseaux des hôpitaux à
des fins de télémaintenance ou de contrôle périodique de leur fonctionnement. Ces technologies ont
régulièrement fait parler d’elles dans les médias ces dernières années, avec notamment l’affaire du
Hacking d'une pompe à insuline en 2011, l’arrêt du support technique du système d'exploitation Windows
XP, ou plus récemment la vulnérabilité logicielle Heartbleed, une faille de sécurité sur OpenSSL.Tous ces
exemples soulignent l’importance de la cybersécurité des dispositifs médicaux.
Mais, lorsque l’on parle de cybersécurité des dispositifs médicaux, qu’entend-on exactement? La sécurité
de l'information vise à garantir la disponibilité, l'intégrité et la confidentialité des données stockées,
traitées ou transmises. … (Source: LNE)
 Risques liés à l’introduction de dispositifs médicaux en IRM : une
évaluation désormais exigée
L'Imagerie par Résonance Magnétique (IRM) est aujourd'hui un dispositif majeur dans le domaine du
diagnostic médical. Elle complète et se substitue même parfois à des examens de radiologie
conventionnelle (scanner), limitant d'autant l'exposition du patient aux rayonnements ionisants. Le
nombre d'équipements est en forte croissance, et chaque année, 7% de la population des pays de l'OCDE
passe un examen IRM. L'acquisition des images IRM nécessite la combinaison d'ondes
électromagnétiques de puissance élevée : champs magnétiques statiques, gradients de champs
magnétiques et radiofréquences. Ces ondes interagissent avec tout élément introduit dans
l'environnement IRM, engendrant parfois des risques pour le patient et le personnel médical. Une
évaluation des risques liés à l'introduction du dispositif médical en IRM est aujourd'hui exigée par la
plupart des organismes notifiés pour la mise sur le marché d'un dispositif médical. … (Source: LNE)
 The European Union's response to Ebola emergency
West Africa is currently facing the largest and most complex Ebola epidemic on record. Guinea, Liberia
and Sierra Leone are the most affected countries. The disease has already claimed more than 6 000 lives
and has seen over 17 000 cases.
The European Union has been monitoring its spread and taken collective action at home and abroad. It
has mobilised political, financial and scientific resources to help contain, control, treat and ultimately
defeat Ebola. On 24 October 2014 the European Council appointed Christos Stylianides, EU Commissioner
for Humanitarian Aid and Crisis Management, as EU Ebola Coordinator. Between 12 and 16 November, he
travelled to the three most affected countries together with the EU Commissioner for Health Vytenis
Andriukaitis. On 5-7 December EU Commissioner for International Cooperation and Development, Neven
18
Mimica, followed up with a visit to Guinea Conakry to reaffirm the EU’s medium and long term support to
affected and at-risk countries.
Financial assistance
The EU's total financial contribution to fight the epidemic is over €1.1 billion. This includes funding from
the Member States and the European Commission.
The Commission has given €434 million to fight the disease - covering emergency measures and longerterm support.
Since March 2014, the European Commission has allocated close to EUR 60 million in humanitarian
funding to addresses the most urgent needs. These funds are channelled through humanitarian partner
organisations, such as MSF, the International Federation of the Red Cross and Red Crescent societies,
IMC, Save the Children, IRC, Alima, WFP’s Humanitarian Air Service, UNICEF and WHO. EU aid contributes
to epidemic surveillance, diagnostics, treatment and medical supplies; deployment of doctors and nurses
and training of health workers; raising awareness among the population and promotion of safe burials.
In addition to existing EU and bilateral development partnerships, the Commission is also providing some
€210 million in development and early recovery assistance. The funds are thus being delivered now and
into 2015. The objectives are to reinforce the capacity of governments to deliver vital public services,
notably health care, and maintain macro-economic stability. These funds are also used to strengthen food
security and improve water and sanitation. Mobile laboratories for the detection of the virus and training
of health workers are also funded through the development assistance. Furthermore, the EU supports the
African Union's medical mission in West Africa.
To reduce the risk of further spread of Ebola, EU funding has also been allocated to countries neighboring
the affected region where we support early detection and awareness building.
Emergency supplies and expertise
The EU is also sending emergency supplies and experts. The EU Civil Protection Mechanism facilitates the
coordinated delivery of material support from the Member States through the Emergency Response
Coordination Centre (ERCC).
EU Member States have provided mobile laboratories, treatment centers, ambulances and field hospitals.
The EU has organized logistical support including multiple airlifting operations and supports the
deployment of navy ships to transport emergency supplies provided by the Member States, such as food
aid, medical kits, clean blankets and chlorine for sanitations. EU humanitarian experts, including
specialists in hazardous diseases, have been deployed to the three most affected countries.
Medical evacuation
International health workers operating directly on the ground are the backbone of the response to the
Ebola epidemic. More health workers are needed. To support their mobilization, a European medical
evacuation system has been established to ensure they would get appropriate treatment and would be
transported to hospitals in Europe in case of an infection. Member States are making capacity available
for this. The medevac system ensures evacuation within 48 hours to an equipped hospital in Europe for
international health workers and other EU nationals diagnosed with the virus. Evacuation requests are
received through the ERCC and assessed by the World Health Organisation (WHO).
19
Research
There is currently no specific treatment or vaccine available against Ebola. To address the urgent need
for research into new treatments, the EU has been stepping up its efforts to look for new effective
vaccines and medication. Through a partnership with the European pharmaceutical industry under the
Innovative Medicines Initiative, a €280 million call for proposals has been launched to support research
projects involving clinical trials of new vaccines in Ebola-affected countries, the development of fast
diagnostic tests and new approaches to manufacture, store and transport vaccines. The call, to which the
Commission has contributed half of the budget, will use a new fast-track procedure to get successful
projects up and running early next year.
This comes on top of the previously mobilised €24.4 million from Horizon2020 that will fund five projects
ranging from large-scale clinical trials to tests of existing and new Ebola compound treatments.
The EU is also helping to fight infectious diseases in sub-Saharan Africa, including Ebola, within the
European and Developing Countries Clinical Trials Partnership programme (EDCTP2). This partnership will
work with a budget of €2 billion over the next ten years, with nearly € 700 million coming from
Horizon2020 and a €1.5 billion contribution from EU countries.
Preparedness
The risk of Ebola to the general public in the EU is very low. Transmission of the virus requires direct
contact with a symptomatic patient’s body fluids. Furthermore, the EU has very high standards of
healthcare infrastructures and preventive care. Nevertheless, there is a small possibility of individuals
arriving in the EU with potential Ebola virus infection.
Since the outbreak of the Ebola virus disease, the Commission and the Member States have also been
working on preparedness and coordination of risk management in close cooperation with of the
European Centre for Disease Prevention and Control (ECDC) and the WHO.
The Health Security Committee (HSC), bringing together EU Member States and the Commission, meets
regularly to coordinate Ebola prevention and readiness. It surveys Member States' preparedness and has
established a list of available Ebola assets which could be shared, including high security laboratories,
hospital capacity and medical evacuation equipment. The EU's Early Warning and Response System for
medical emergencies has been activated. HSC is also providing information for travellers in all EU
languages and establishing procedures for airports and health authorities on handling possible Ebola
cases.
In addition, the Commission has launched the 'Ebola Communication Platform for Clinicians' - an online
platform enabling the rapid exchange of information on the treatment and prevention of the Ebola
disease. The platform brings together EU hospitals and physicians recognised as reference centres for the
treatment of Ebola patients. This network further boosts the level of preparedness and response against
Ebola by linking together expertise on treatment of Ebola patients between health care specialists.
Exit screening
The WHO has recommended exit screening of travellers leaving the affected countries in order to reduce
the risk of spread of Ebola. Since the disease's incubation period is up to 21 days, it is widely recognised
that such screening can be only partially effective.
The Commission in partnership with the WHO has proposed to carry out an audit of the exit screening
measures in the three most affected countries. Its goal is to assess current exit screening practices and
identify any gaps. The audit report is due at the beginning of December.
20
Advocacy and diplomatic outreach
From the outset of the crisis, the EU has been supporting and calling for a strong international response
coordinated by the United Nations. The EU is in constant contact with the governments of the region
through its Delegations as well as with regional organizations such as the African Union and ECOWAS.
The appointment by the European Council of an EU Ebola Coordinator, Commissioner Christos
Stylianides, aims to ensure that EU institutions and Member States act in coordination with each other
and with international partners. To this end, an EU Ebola Task Force has been set up, bringing together
Member States, Commission services, the European External Action Service (EEAS) and representatives of
the UN, the Red Cross and NGOs. The Task Force meets daily in the Commission'sERCC, which serves as a
platform for coordination of the European response. … (Source: EC)
 DG Sanco clarifies scope of Joint Procurement Agreement
The Commission’s Health and Consumers Directorate (DG Sanco) has clarified the scope of the Joint
Procurement Agreement that allows EU member states to jointly negotiate the price and supply of
vaccines and antiviral medications. The joint procurement procedure can be launched with the agreement
of a minimum of 4 member states and the Commission. … (Source: EC)
 Roche's HIV and HCV MDx Get CE Mark
Roche said that its Cobas HIV-1 and HCV next-generation viral load monitoring assays have received CE
marking.
The Cobas HIV-1 assay simultaneously amplifies and detects two separate regions of the HIV-1 genome to
quantify the amount of viral RNA in the patient's blood. The Cobas HCV assay employs the firm's dualprobe approach to detect hepatitis C RNA. Both assays are available for use on the Cobas 6800 and 8800
systems.
The two molecular diagnostic systems are fully automated platforms for blood donor screening, viral load
monitoring, women's health, and microbiology testing. Roche said in a statement that the viral load
portfolio on the 6800 and 8800 systems "will provide laboratories with improved productivity and the
ability to deliver results for rapid clinical decisions." … (Source : Genomeweb)
 CVRx's Barostim neo gets CE Mark for use with MRIs
CVRx said its Barostim neo system was granted expanded CE Mark approval in the European Union for use
with MRI procedures.
Barostim neo is used to help regulate blood flow in patients suffering from heart failure or drug-resistant
hypertension. The system uses a small pulse generator, which is implanted under the collarbone, to
activate the body's blood-pressure sensors, or baroreceptors. The device can also be used with
implantable cardio-defibrillators and cardiac resynchronization therapy.
CVRx said that the expanded approval allows for the system to be used during MRIs under certain
conditions.
In September, European regulators awarded expanded approval for Barostim neo for the treatment of
heart failure. The product first received CE Mark clearance in 2011 for the treatment of high blood
pressure.
21
CEO Yadim Nared told MassDevice.com in September that the Barostim neo device is designed to
influence both the sympathetic and parasympathetic systems, reducing sympathetic activity and
increasing parasympathetic activity. … (Source: MassDevice)
22
 Abbott Pathogen Detection Platform Obtains CE Mark
Abbott announced today that its pathogen detection platform, Iridica, has obtained CE marking and is
now available in Europe and other countries that recognize CE mark.
The diagnostic platform uses a combination of PCR and electrospray ionization mass spectrometry to
amplify and detect pathogens directly from patient samples without the need for culture. It can currently
distinguish over 1,000 bacteria, viruses, and fungi, according to a statement, allowing for unbiased
screening of patient samples in less than six hours.
Previously called Plex-ID, the next generation platform debuted in July, and has been praised for its ability
to detect and identify pathogens that are rare or difficult to grow in culture.
Preliminary data from a study of the platform showed an independent panel of physicians would have
prescribed a different course of treatment in about 60 percent of cases if they'd had the Iridica-based
diagnosis. That study, called Rapid Diagnosis of Infections in the Critically Ill, or RADICAL, also suggested
the platform could reduce healthcare costs and length of hospital stays, according to the statement.
There are currently five panels available on the Iridica platform, including one for bloodstream infections
that detects more than 780 bacterial strains along with four antibiotic resistance markers, and a fungal
panel that detects more than 200 types of fungi and yeast, according to the company website. … (Source:
GenomeWeb)
NBOG
http://www.nbog.eu/
 NBOG reports & News
http://www.nbog.eu/5.html
 NBOG issues 2014 Progress Report
The NBOG Progress Report for 2014 submitted to the Medical Devices Expert Group (MDEG) highlighted
meetings held in February and June concerning the performance and designation of Notified Bodies, with
representatives from more than 20 EU Member States, European Free Trade Area (EFTA) countries, MRA
partners and the European Commission (including representatives from FVO, the Food and Veterinary
Office). … (Source: NBOG)
France
http://ansm.sante.fr/
23
 Risques liés aux prothèses de hanche à couple de frottement métalmétal: Recommandations d’utilisation et de suivi des patients
Les prothèses de hanche sont des dispositifs médicaux dont le rôle est de remplacer l'articulation
naturelle de la hanche lorsque celle-ci ne fonctionne plus correctement, du fait principalement d’une
usure (coxarthrose) ou d’une fracture du col fémoral. Les prothèses dites "à couple de frottement métalmétal" sont inscrites au plan de surveillance renforcé des dispositifs médicaux[1] . C’est dans ce cadre que
l’Agence nationale de sécurité du médicament et des produits de santé (ANSM) a récemment participé à
des travaux européens sur ces dispositifs et qu’elle en a initié au niveau national. Au vu des nouveaux
résultats qui en sont issus, l’ANSM publie aujourd’hui une mise en garde à l’attention des chirurgiens
orthopédistes et de nouvelles recommandations de suivi des patients porteurs de ces implants.
Une prothèse totale de hanche (PTH) se compose de trois parties, une partie qui vient s'insérer dans le
fémur, une partie qui se fixe sur le bassin, appelée cotyle, et une partie qui fait la jonction appelée tête
fémorale. Le couple de frottement d’une PTH est défini par l’ensemble de la tête fémorale et du
cotyle. Il existe différents couples de frottement.[2]
En France en 2013, environ 140 000 PTH de première intention ont été implantées dont 3000 (2%)
sont de type "à couple de frottement métal-métal"[3] . Il existe trois catégories de prothèses de hanche
à couple de frottement métal-métal : celles à tête fémorale de petit diamètre (<36mm), à tête
fémorale de grand diamètre (≥36mm) et les prothèses dites de "resurfaçage"[4] .
Le dysfonctionnement ou la rupture de l’implant peuvent être à l’origine d’une consultation voire
d’une réintervention chirurgicale appelée "révision". Le taux de révision chez les patients porteurs de
prothèses de hanche à couple de frottement métal-métal est ainsi supérieur aux autres couples de
frottement, cette tendance étant plus marquée pour les implants de grand diamètre.
Contexte de l’évaluation des risques
En mars 2012, la revue Lancet a publié une analyse des résultats d’une étude observationnelle[5]
réalisée entre 2003 et 2011 montrant des taux de révision très supérieurs chez les patients porteurs
des prothèses métal-métal notamment par rapport au couple céramique-céramique. Suite à cet
article, la Commission européenne a mis en place une action coordonnée à l'échelle européenne sur le
sujet pour faire un constat des bénéfices et des risques de chacune des catégories des PTH à couple de
frottement métal-métal et pour évaluer plus avant les effets à moyen et long termes, locaux et
systémiques, liés à ces dispositifs.
Les récents résultats d’évaluation européens ont été présentés à la Commission de suivi du rapport
bénéfice/risque des produits de santé au cours de sa séance du 1er juillet 2014. Suite à cette séance, un
rapport de la Société Française de Chirurgie Orthopédique et Traumatologique (SOFCOT) a été
présenté à la Commission suivante du 14 octobre 2014. Celle-ci a alors émis des avis concernant le
devenir des produits et les recommandations de suivi proposées par la SOFCOT. Par ailleurs, les
investigations sur l’éventuelle toxicité liée à ces dispositifs médicaux seront poursuivies dans le cadre
d’un groupe de travail pluridisciplinaire.
24
Recommandations de l’ANSM pour l’utilisation des PTH et le suivi des patients : les points clés
L’ANSM attire l’attention des chirurgiens orthopédistes quant à l’utilisation de ces produits.
Les recommandations de l’ANSM sont les suivantes :




Pour toutes les catégories de prothèses de hanche à couple de frottement métal-métal : ne pas
les utiliser chez les femmes en âge de procréer et chez les patients allergiques à des métaux.
Pour les prothèses de resurfaçage ,pour éviter toute perte de chance à une catégorie de patients
(homme jeune, avec une activité physique très intense, au ratio tête/col adapté, et un diamètre
de tête fémorale ≥ 48 mm), il est recommandé de restreindre l'utilisation de ces prothèses à ces
indications très ciblées. Il existe en effet un intérêt fonctionnel pour ce type de prothèses dans
ces quelques rares situations cliniques très précises. De plus cette chirurgie doit être réservée à
quelques chirurgiens maîtrisant la technique opératoire spécifique à cet implant ainsi que le
parfait positionnement de celui-ci. L’ANSM recommande de se référer aux indications de pose
ainsi qu’aux conditions d’encadrement mises en place par la HAS (http://www.has-sante.fr )
Pour les têtes fémorales de petit diamètre (<36mm) à faible teneur en carbone [6] et les têtes
fémorales de grand diamètre (≥ 36mm) , on constate qu’à ce jour il n’existe plus aucun produit
de ce type sur le marché français. Néanmoins, il convient de noter une balance bénéfice /risque
négative de ces produits qui conduirait à ne pas recommander leur utilisation.
Pour les têtes fémorales de petit diamètre (<36mm) à haute teneur en carbone [7] , ces
prothèses sont équivalentes aux alternatives non métalliques ; elles peuvent continuer à être
utilisées dans les indications et en fonction des modalités recommandées par la HAS.
Par ailleurs, l’ANSM en partenariat avec la SOFCOT et la société française de chirurgie de la hanche et
du genou (SFHG), a mis à jour les modalités de suivi des patients implantés publiées par l’agence en
mars 2012.
Ces recommandations seront susceptibles d’évoluer en fonction des résultats des travaux qui seront
mis en place dans le cadre de la problématique globale des implants métalliques.
Modalités de suivi des patients porteurs de prothèse totale de hanche à couple de frottement métalmétal -Recommandations ANSM et SOFCOT (17/12/2014)
(96 ko)
Mise en garde concernant les prothèses de hanche à couple de frottement métal-métal (17/12/2014)
(368 ko) - Information de sécurité
Prothèses de hanche à couple de frottement métal-métal : information patient - Questions/Réponses
(17/12/2014)
(34 ko)
 Les logiciels dispositifs médicaux
L’Agence nationale de sécurité du médicament et des produits de santé (ANSM) a pour mission de
favoriser un accès rapide, encadré et large à l’innovation et à l’ensemble des produits de santé pour les
patients.
Dans le cadre de cette mission, l’ANSM a organisé une réunion d’information « Innovation » (7e édition)
sur le thème des logiciels dispositifs médicaux le vendredi 28 novembre 2014, de 10h00 à 13h30 dans ses
locaux.
25
Après des retours d’expérience dans le développement de logiciels en santé par différents acteurs
industriels et académiques, l’ANSM a présenté la qualification et la classification des logiciels médicaux et
le cadre réglementaire applicable. Des échanges avec la salle se sont également déroulé sous la forme
d’une table ronde.
Les interventions :
Le logiciel « dispositif médical » à l’ANSM – ANSM (03/12/2014)
(264 ko)
Quelques exemples de qualification de logiciels – ANSM (03/12/2014)
Etude « Sécurité des logiciels » – ANSM (03/12/2014)
Le projet Diabeloop – CEA (03/12/2014)
(442 ko)
(199 ko)
(2194 ko)
Développement de logiciels en santé : Retour d’expérience -VOLUNTIS (03/12/2014)
Au cœur de l’imagerie numérique des laboratoires – TRIBVN (03/12/2014)
(762 ko)
(1478 ko)
Développement de logiciels en santé : retour d’expérience – SNITEM (03/12/2014)
(292 ko)
Documents de référence
 Amalgames dentaires à base de mercure: Recommandations pour
les professionnels de santé et information des patients
L’Agence nationale de sécurité du médicament et des produits de santé (ANSM) affirme sa volonté de voir
diminuer de façon importante l’utilisation des amalgames à base de mercure dans le traitement de la
carie dentaire.
Elle émet à cette fin des recommandations à destination des chirurgiens-dentistes afin de préciser les
situations cliniques limitées dans lesquelles l’amalgame peut encore être employé et en rappelle les
précautions d’emploi. En parallèle, une information est également délivrée aux patients sur la place des
amalgames à base de mercure parmi les matériaux d’obturation disponibles. Il leur est également rappelé
l’importance du respect des règles d’hygiène bucco-dentaire et du traitement précoce des caries
dentaires.
Suite à l'actualisation de ses travaux sur les amalgames dentaires présentée à la commission de
prévention des risques du mois d’octobre 2014, l’ANSM a réaffirmé sa volonté de voir diminuer de façon
importante l’utilisation des amalgames à base de mercure dans le cadre du traitement de la carie
dentaire.
Elle émet ainsi des recommandations à la fois auprès des chirurgiens-dentistes et des patients sur
l’utilisation de ce matériau d’obturation.
Il est rappelé aux professionnels que l’amalgame dentaire doit être réservé à des situations cliniques
limitées et justifiées comme la restauration des dents permanentes postérieures (molaires et
prémolaires) en cas de prévalence carieuse élevée et de lésions multiples et étendues. Les mesures de
précaution d’utilisation à prendre en compte et les règles de bonnes pratiques sont également
mentionnées.
26
L‘Agence réaffirme également la nécessité de renforcer l’information des patients vis-à-vis des différents
matériaux de restauration disponibles en amont de la réalisation de l’acte conservateur.
Par ailleurs, il est à noter que la première des préventions contre la carie dentaire reste les règles
d’hygiène buccodentaire (promotion des bonnes habitudes d’hygiène bucco-dentaire, actes de
prophylaxie) qui doivent être rappelées systématiquement aux patients.
De plus, l’ANSM tient à sensibiliser à la fois les professionnels de santé et les patients sur l’importance de
la déclaration de tout effet indésirable en relation avec l’utilisation d’un matériau d’obturation.
L’Agence a d’autre part rappelé, au cours de la commission de prévention des risques du mois d’octobre
2014, la nécessité de promouvoir la recherche dans le domaine des biomatériaux afin d’élargir l’offre de
solutions alternatives aux amalgames dentaires disponibles. … (Source: ANSM)
Amalgames dentaires : Recommandations à l’attention des professionnels de santé à respecter lors de
l’utilisation des amalgames dentaires - Recommandations (11/12/2014)
(118 ko)
Informations à l’attention des patients sur les amalgames dentaires - Recommandations (11/12/2014)
(128 ko)
http://www.has-sante.fr/portail/jcms/j_5/accueil
 Enjeux actuels de l’évaluation médico-économique - une
comparaison avec le NICE
Les questions d’organisation et de soutenabilité des systèmes de santé ainsi que l’évaluation économique
des traitements ne sont plus des sujets purement nationaux. Plusieurs sujets d’actualité récents ont
montré que les pays européens sont confrontés aux mêmes difficultés et aux mêmes problématiques et
ce malgré des systèmes de santé différents. La HAS fait aujourd’hui le point sur ses derniers travaux et «
dialogue » avec le NICE*, institution britannique homologue, à l’occasion d’un colloque intitulé «
Contribuer à la qualité et l’efficience », tenu à la Cité internationale.
Poursuivre l’exploration de la dimension économique dans nos évaluations, notamment des
médicaments et dispositifs médicaux
Depuis plus d’un an, la HAS met en œuvre l’évaluation de l’efficience des médicaments et dispositifs
médicaux. Sont concernés par ce dispositif les produits de santé qui ont « un impact significatif sur les
dépenses de l’assurance maladie compte tenu de [leur] incidence sur l’organisation des soins, les
pratiques professionnelles ou les conditions de prise en charge des malades et, le cas échéant, de [leur]
prix ». Les avis d’efficience, par les nouvelles données qu’ils apportent au Comité Economique des
Produits de Santé (CEPS), participent à la définition du prix des produits concernés. La négociation du prix
des traitements très innovants mais coûteux présentés au remboursement s’appuie désormais
également sur des données de rapport coût-avantages ou sur des données d’efficience. En pratique, 26
produits de santé (25 médicaments et 1 dispositif médical) ont été éligibles à une évaluation médicoéconomique par la HAS. Actuellement, 15 avis d’efficience ont été rendus par la Commission Évaluation
27
Économique et de Santé Publique (CEESP). Trois avis d’efficience sont aujourd’hui disponibles sur le site
de la HAS, les autres le seront dans les prochaines semaines.
Parallèlement à ces avis d’efficience, la HAS a poursuivi son évaluation de l’efficience des stratégies
diagnostiques et thérapeutiques et a publié au cours du dernier trimestre les évaluations relatives à la
prise en charge de l’apnée du sommeil et de l’insuffisance rénale terminale.
Une comparaison avec le système anglais via les activités du NICE
Dans l’objectif d’améliorer ses méthodes de travail et de répondre à sa mission d’aide à la décision, la HAS
entend constamment s’enrichir des apports des expériences étrangères. Une réflexion comparative des
modes de fonctionnement et de travail entre la HAS et son homologue britannique, le NICE, s’inscrit dans
cette perspective. Elle doit toutefois tenir compte des différences profondes d’organisation entre les deux
systèmes de santé et des différences culturelles entre les deux pays.
Au niveau des avis d’efficience, si des points de concordance existent, des différences notables subsistent.
Par exemple, ces avis ont en France vocation à aider les décideurs (CEPS, ministère) à affiner leurs prises
de décision concernant le prix. Ils ne constituent pas un avis conforme de remboursement ou non comme
c’est le cas outre-manche.
En France, aucune valeur de référence n’est à ce jour spécifiée. Ainsi, il est possible de déterminer le coût
du gain en santé produit par une innovation mais il n’est pas possible de dire si ce coût est acceptable
pour la collectivité. Si la HAS n’est pas légitime pour édicter seule cette valeur, elle est en situation de
fournir les éléments qui permettront à terme d’initier un débat démocratique sur ce sujet et a engagé un
travail de recherche et d’analyse documentaire sur ce thème.
Plusieurs autres différences sont à souligner, par exemple :
- la hiérarchisation des recommandations cliniques du NICE par une analyse coût/avantage établit ainsi un
lien mécanique et démontré entre efficience et pertinence des soins ;
- les liens entre le NICE et les universités, la recherche académique ou encore les organismes de
professionnels permettent une synergie plus grande pour produire des synthèses des connaissances
scientifiques ;
- la stratégie de diffusion des productions et de leur appropriation auprès des professionnels très aboutie,
qui permet une meilleure appropriation par les professionnels britanniques, domaine où la HAS poursuit
ses efforts;
- la grande sélectivité dans les évaluations à mener tant dans leur nombre que dans leur thématique
conférant une plus grande force aux positions du NICE ;
- enfin, le rôle des usagers en tant que contributeurs pleins et entiers plus affirmé notamment au travers
de la définition de choix de valeurs mais également avec la mise en place d’un conseil permanent des
citoyens au sein de l’institution.
Des parcours de soins pour garantir l’efficience des prises en charge
La HAS a initié plusieurs travaux destinés à mieux coordonner les parcours de soins des patients et éviter
les ruptures de suivi entre les prestations : structuration des soins primaires et organisation de la sortie
d’hospitalisation par exemple, notamment appliquées au parcours de santé des personnes âgées, travaux
sur le repérage et la prise en charge des personnes âgées fragiles, prévention des événements
indésirables liés aux médicaments, coordination des acteurs dans les territoires.
28
La pertinence des pratiques professionnelles pour dépenser mieux
La HAS a entrepris de travailler sur la pertinence des actes et des pratiques en analysant la variabilité des
pratiques. En effet, si les bonnes pratiques professionnelles sont définies, comment identifier et réduire
ces variabilités, sources potentielles de problèmes de sécurité des soins et du patient mais également de
coûts supplémentaires ? L’analyse approfondie de plusieurs situations (césarienne programmée, chirurgie
bariatrique, etc.) via les bases de données disponibles (PMSI, SNIIRAM…) devraient permettre de
progresser dans ce domaine. L’expérience du NICE, comme d’autres institutions internationales en charge
de garantir la qualité et l’efficience du système de santé (freins et facteurs clés de succès) et ses
méthodes peut apporter des éléments d’éclairage pour les actions actuelles et futures de la HAS. …
(Source: HAS)
CNEDiMTS
 Derniers Avis de la
CNEDiMTS



Les Avis sur les dispositifs médicaux (et les synthèses)
Rapports d'évaluation des technologies de santé.
L’Évaluation des technologies de santé et des actes
CEPS
L’objet du site est :




de décrire les missions du CEPS,
de décrire son organisation et son fonctionnement,
de retracer son activité,
de fournir les informations de base concernant le prix des médicaments et les tarifs des dispositifs
médicaux ainsi que les informations pratiques relatives au dépôt et au traitement des demandes.
http://www.sante.gouv.fr/comite-economique-des-produits-de-sante-ceps.html
EUROPE
29
http://www.mhra.gov.uk/#page=DynamicListMedicines
 Final reminder to cancel licences by the end of December 2014
Periodic fees and cancellation of licences - holders of authorisations, registrations and licences are
required to notify the MHRA by 31 December 2014 to cancel authorisations, registrations and licences
from 31 March 2015. If you have not cancelled them yet please do so as soon as possible.
This will ensure that you are not liable for a periodic fee in connection with a specific licence for the fee
period 1 April 2015 to 31 March 2016.
Regulation 37 (5) (a) of the Medicines (Products for Human Use) (Fees) Regulations 2013 SI 2013 No.532
requires authorisation, registration or licence holders to give three-months notice to the licensing
authority before the beginning of a fee period (ie 1 April) if they wish to cancel a licence. They will then
not be liable for the periodic fee. … (Source: MHRA)
 Guide to the systematic design, construction, and description of
synthetic biological systems using digital biological information
Draft PAS 246 synthetic biological systems - for comment.pdf
 Medtech Start-Ups: Point-of-Prescription Test to Fight Antibiotics
Resistance
While currently the media is mainly concerned with the Ebola crisis in Africa, probably the more
dangerous development, at least for the developed world, is the emergence of antibiotic-resistant
bacteria. According to the European Commission, more than 25,000 people die every year because of
drug-resistant infections.
“Ever since antibiotics were invented we have known that pathogens will develop antibiotic resistance as
a classic example of Darwinism. In fact bacteria, with a reproductive cycle of less than a hour in some
cases, can demonstrate Darwin’s theory in a finite time period far better than humans,” explained Neil
30
Butler, CEO of the start-up Spectromics. According to Butler, there are a number of mechanisms of
resistance. If the bacteria comes into contact with a non-lethal dose of antibiotic it has the opportunity to
develop resistance strains in it’s natural reproductive cycle. If a patient stops taking the antibiotics half
way through the course of medication, before the infection is cleared this can result in resistance.
“For a number of infections where resistance is slow to develop a suitable diagnostic solution is to ID the
bacteria and treat with an antibiotic that is known to be effective. Molecular Diagnostic solutions are very
effective in such cases because their inbuilt amplification capability together with specific DNA
recognition allow them to be both sensitive and specific,” said Butler. “There are however gram negative
bacteria, where the resistance is encoded by hundreds of genes, and where new mutations are constantly
developing.”
Such a complex and moving target is difficult to configure a molecular test for and it would require
constant updating and requalifying through regulatory processes, according to Butler. “The alternative
approach is to use phenotypic testing, which has been the cornerstone of microbiological testing since the
introduction of antibiotics. The problem with the classical method of culturing (growing) bacteria in the
presence of different antibiotics and monitoring how each drug influences the growth of bacteria is that
it’s slow. A 1- 2 day test isn’t tolerable when patients have infections that require urgent treatment, and
many of the antibiotics don’t work.”
The Manchester based Spectromics has developed a 10 minute phenotypic test that determines which
drugs work best against the particular bacteria. “As the test works by combining the patient sample with a
panel of antibiotics and determining which kill or inhibit the pathogen. To address the issue of how do we
stop patients taking half the course of medication, then a follow up test could be performed to ensure the
infection has been effectively treated,” Butler said.
Spectromics is a spin-out of the Manchester Institute of Biotechnology where the researchers started
working on pathogens associated with Urinary Tract Infection (UTI) and their response to antibiotics. After
having tested over 200 strains of bacteria with a number of antibiotics and achieving a highly reproducible
susceptibility prediction accuracy (88-98%), they decided to commercialize the tests they developed. A
patent application was filed in February 2014 and the company was formed 2 months later.
“The unmet need [for the technology] is that in the community antibiotics are prescribed by doctors
based on clinical assessment,” said Butler. “ In the US, there are 16million suspected UTI’s treated every
year, but only half those patients have actual UTI’s, so there is 100% overtreatment with unnecessary use
of drugs, and the consequential opportunity to develop new resistances.” … (Source : EMDT)
http://www.nice.org.uk/
http://www.hpra.ie/
BfArM http://www.bfarm.de/DE/Home/home_node.html
31
 List of safety measures updated
BfArM has updated the list of safety measures taken with respect to medical devices through December
12, 2014. … (Source: BfArM)
 Autumn Symposium 2014: papers and posters online now
On the occasion of its 10th anniversary, IQWiG’s symposium took a look into the future. Discussion
centered around the direction that evidence-based care should take, and what IQWiG can contribute to
the challenges ahead. The presentations from the symposium are now available online. … (Source:
IQWIG)
http://www.fagg-afmps.be/fr/
http://www.agenziafarmaco.it/
http://www.aemps.gob.es/en/home.htm
 AEMPS hosts technical workshop for development of arthroplasty
register in Spain
AEMPS and the Spanish Society of Hip Surgery (SECCA) organized a Technical Seminar in order to share
experiences on existing Arthroplasty Registers in Europe, with a view to developing a National
Arthroplasty Register to monitor the behavior of implants during the time they are in place. The
Conference was held on December 3, 2014 at the AEMPS headquarters. … (Source: AEMPS)
http://www.legemiddelverket.no/English/Sider/default.aspx
http://www.lakemedelsverket.se/english/
SWISSMEDIC
http://www.swissmedic.ch/index.html?lang=fr
Ministry of Health of Ukraine
32
http://www.kmu.gov.ua/control/en/publish/article?art_id=88456
MIDDLE EAST
 TITCK updates certified testing centers
The TITCK has updated the list of testing centers that have been inspected and certified to conduct
bioavailability and bioequivalence testing, and Phase I clinical testing. … (Source: TITCK)
RUSSIA & RELATED COUNTRIES
Ministry of Healthcare of the Russian Federation
http://government.ru/eng/power/23/
NORTH AMERICA
 CDRH issues final guidance on passive implants in MR environment
The CDRH has released final guidance on labeling and testing passive implants in the magnetic resonance
(MR) environment identifying the main safety and compatibility issues as magnetically induced
displacement force and torque, radio frequency (RF) heating, and image artifacts. The guidance applies to
premarket approval application (PMA), Investigational Device Exemption (IDE), and premarket notification
(510(k)) submissions. … (Source: FDA)
 FDA Upbeat about Medical Device Approval Times
Earlier this week the science chief of the U.S. Food and Drug Administration spoke about the agency’s
efforts to improve the process it uses to clear and approve medical devices. Bill Maisel, deputy director of
science at the FDA’s Center for Devices and Radiological Health, said in Cambridge, MA that the agency
had made progress in the area.
Maisel spoke on the topic to members of MassMEDIC. His speech was one of several events put on by the
FDA intended to provide an overview on topics in regulatory approval for the coming year. The agency’s
priorities entering the new year include strengthening the clinical trial process for devices, according to a
news release from the Boston Business Journal.
“We want patients in the U.S. to have access first in the world to the technology,” Maisel said. “That
means timely approval trials.”
33
To illustrate the agency’s commitment, Maisel noted that the agency has cut down the average length of
time from the submission of an application to run a trial, to a decision on the application by 75% in the
past three years. In 2011, it took an average of more than 400 days for such an application to be
processed. This year, Maisel reports that the average application is now processed in 101 days.
The FDA has also taken strides to sort through the categories of medical devices in an effort to identify
devices considered high-risk, for which the most data is required for approval. The agency has already
reviewed half of the high-risk devices as they look for any that can be downgraded in order to speed up
the approval process.
Maisel also says that the agency is working to improve its level of customer service by collecting feedback,
with the goal of reaching a 70% satisfaction rate among industry representatives and other government
agencies that work alongside the FDA. Maisel noted that the Center for Devices and Radiological Health
received an 84% approval rating, surpassing its goals.
In related news, the FDA has been criticized for not disclosing the extent of its financial ties to industry.
The Wall Street Journal recently explained that a number of doctors sitting on FDA review panels also
have links to device makers—connections that the agency doesn’t disclose publicly.
In panels evaluating devices involved in cardiology, orthopedics, and gynecology from 2012 through 2014,
a third of 122 members had received compensation (in the form of money, research grants, or food and
travel) from medical device companies, according to The Wall Street Journal. Nearly 10% of the FDA
advisors received something of value from the specific company whose product they were evaluating, but
the FDA only disclosed roughly 1% of these corporate connections. … (Source: Qmed)
 8 FDA Guidance Documents You Need to Know
Mobile Medical Applications (Apps)
One year after its publication in late 2013, this guidance remains unclear to many manufacturers.
What FDA says: A continuum of mobile medical apps exists ranging from those that are clearly not
medical devices to those that are distinctly medical devices and thus require regulation. For apps in the
gray area of regulation, FDA will exercise enforcement discretion. This means that as long as no safety
issues arise, it will not require pre-market submissions or compliance with FDA medical device
requirements.
The Good: The guidance provides a shorter, easier path to market for low-risk apps.
The Bad: The industry is worried that the increased cost and time to market associated with FDA
regulation will stifle innovation.
The Path Forward: FDA manages mobile medical apps within the existing regulatory framework and has
been doing so for years. The software that conducts and analyzes CT scans is a great example.
Manufacturers should make an informed decision regarding their place in the regulation continuum. For
those apps that will be subject to FDA enforcement, and which represent a novel approach for which
there is no predicate, the de novo classification guidance may be applicable.
Framework for Regulatory Oversight of Laboratory Developed Tests
The most sweeping changes FDA announced in 2014 were for laboratory developed tests (LDTs).
What FDA Says: FDA is ceasing enforcement discretion and establishing active oversight to ensure the
validity and safety of LDTs, which have grown increasingly complex and critical to diagnosis.
34
The Good: For IVD developers that compete against LDTs, the playing field may soon be more level. LDTs
can remain on the market during the new registration and approval processes.
The Bad: More than 11,000 laboratories currently regulated under CLIA must quickly register and list tests
performed and begin reporting adverse events, which may be difficult to precisely define. That, combined
with a relatively short 1 to 5-year horizon for institution of approval processes for most LDTs, as well as
the new quality systems requirements, will place significant demands on industry resources.
The Path Forward: As this is a draft guidance, significant uncertainty remains and particularly so for DNA
sequencing-based and rare disease LDTs. However, increased regulation of LDTs, whether through FDA or
CLIA reform, is inevitable. Advance preparation is required to reduce barriers to rapid, efficient, and costeffective LDT development and marketing.
In Vitro Companion Diagnostic Devices
The companion diagnostic devices (CDx) guidance is an example of FDA’s effort to accelerate access to
treatment by improving the development process.
What FDA Says: A CDx provides information for the safe and effective use of a corresponding therapeutic.
Ideally, a CDx and its corresponding therapeutic should be developed and approved or cleared
contemporaneously. FDA will use a risk-based approach to determine the regulatory pathway. In general,
the agency will not approve a new therapeutic or new indication if an already cleared/approved CDx does
not exist.
The Good: CDx and potential regulatory pathways are now clearly defined.
The Bad: Codevelopment may require a longer upfront planning period and strain the resources of small
manufacturers. Sponsors must now meet with both the drug and device divisions of FDA.
The Path Forward: The CDx developer should partner with the therapeutic manufacturer as early as
possible, stay involved in decision making, and meet regularly with FDA to ensure development is on
course.
De Novo Classification Process (Evaluation of Automatic Class III Designation)
510(k) clearance hinges on a device’s substantial equivalence to an existing product. Novel devices with a
risk profile consistent with a Class I or II designation are classified as Class III, which requires approval via a
PMA if a predicate device cannot be identified.
What FDA Says: The de novo pathway allows FDA to clear new technology devices with low or moderate
risk via a 510(k)-like process, instead of a PMA.
The Good: This guidance streamlines the de novo process.
The Bad: The review timeframe is uncertain. Prior to FDA’s recent efforts to streamline the process,
manufacturers waited a year or longer to complete the de novo process.
The Path Forward: Manufacturers with new technology devices should use the Pre-Submission process to
determine if de novo designation is applicable.
IDEs for Early Feasibility Medical Device Clinical Studies, Including Certain First In Human Studies
Many U.S. device manufacturers conduct first in human (FIH) studies offshore because of stringent IDE
requirements.
35
What FDA Says: This guidance was designed to introduce flexibility into the IDE process, in a manner that
will not impact patient safety. Depending on risk profile FDA may be more flexible about technical aspects
or gaps in the submission, provided a sponsor is clear on how it will manage the design process.
The Good: Sponsors can collect the clinical data needed to make design decisions even though the device
design is not finalized.
The Bad: FDA will not compromise patient safety. Thus, a company considering a U.S. FIH study must
perform a thorough analysis of the risks to health and controls introduced to mitigate these risks.
The Path Forward: Schedule early conversations with FDA to determine the applicability of U.S.-based FIH
studies.
Presubmission Program and Meetings with FDA Staff
FDA has held presubmission meetings for 20 years, but this guidance formalizes the process.
What FDA says: This guidance provides specific information and illustrative examples of the meeting
process, including the types of meetings, when to request a meeting, and materials to submit prior to the
meeting.
The Good: Sponsors have successfully used these meetings to obtain informal scientific input from FDA
before engaging in expensive animal and/or clinical testing.
The Bad: A presubmission meeting, or any other type of FDA meeting, can add three to four months to a
timeline.
The Path Forward: Straightforward devices for which FDA requirements are known do not require
presubmission meetings. However, novel devices without a clear regulatory path should be discussed in a
Pre-Submission Meeting.
Refuse-to-Accept Policy for 510(k)s
Though the current refuse-to-accept (RTA) policy described in this guidance has been in effect for nearly
two years, FDA reports that approximately 50% of 510(k) submissions are still rejected during RTA review.
What FDA Says: The RTA review is an administrative “pre-review” to ensure completeness of a 510(k)
submission prior to substantive review. Within 14 calendar days of submission a document is either
approved for regulatory review or it receives an RTA designation due to a missing component.
The Good: This process helps sponsors ensure their applications are complete. Also, as part of its MDUFA
III performance goals, FDA pledges to review compliant submissions in 60 days. It’s a win for sponsors and
FDA.
The Bad: It is no longer a viable strategy to submit while testing is in progress or to omit certain tests from
a submission. Sponsors must complete all testing and supporting information and submit their 510(k)
when the design validation is complete. In addition, though the RTA review is intended to be
administrative, some reviewers may ask out of scope questions.
The Path Forward: Follow the checklist exactly and leave nothing open to interpretation. Use the
comments section to inform FDA of the rationale for anything outside of the norm. Be prepared to make
revisions and address any out of scope questions.
eCopy Program for Medical Device Submissions
36
The eCopy is a significant step on the road to fully electronic premarket device submissions. In fact, FDA is
now running a pilot program for fully electronic 510(k) submissions.
What FDA Says: A paper submission must be accompanied by an electronic copy that is its exact
duplicate—an eCopy.
The Good: Sponsors are no longer required to submit two paper copies.
The Bad: Any discrepancies between the paper submission and the eCopy will lead to rejection. Minutiae
such as file naming conventions are also strictly controlled.
The Path Forward: Follow the rules. There is no other choice. Use FDA’s free eCopy validation tool before
submission. Avoid the electronic 510(k) submission program until it progresses past the pilot stage. …
(Source: MD+DI)
 The Top 15 Medical Device Deficiencies Cited by FDA in 2014
The US Food and Drug Administration (FDA) has released data on the observations it makes during
inspections of medical device facilities, indicating the most common issues faced by medical device
companies.
Total 483s Issued Declines for First Time in Six Years
In its most recent report, FY 2014 Inspectional Observation Summaries, FDA said it issued 972 Form
483s—forms indicating areas of noncompliance at a facility—to medical device companies in fiscal year
2014.
The number of 473s issued (972) marked the first year since FY 2008 that FDA has issued fewer 483s than
the year prior, and is the least issued since FY 2010 when FDA issued 976.
The Top 15 Medical Device Deficiencies in FDA's 483 Reports
FDA's inspections also noted common deficiencies at medical device manufacturers.
Regulatory
Short Description
Long Description
37
Frequency
Citation
21 CFR 820.100(a) Lack of or inadequate Procedures for corrective and preventive 360
procedures
action have not been [adequately]
established.
21 CFR 820.198(a) Lack of or inadequate Procedures for receiving, reviewing, and 251
complaint procedures
evaluating complaints by a formally
designated unit have not been [adequately]
established. Specifically,***
21 CFR 820.50
Purchasing controls, Lack Procedures to ensure that all purchased or 129
of
or
inadequate otherwise received product and services
procedures
conform to specified requirements have not
been [adequately] established.
21 CFR 820.75(a)
Lack of or inadequate A process whose results cannot be fully 122
process validation
verified by subsequent inspection and test
has not been [adequately] validated
according to established procedures.
21 CFR 803.17
Lack of Written MDR Written MDR procedures have not been 117
Procedures
[developed] [maintained] [implemented].
21 CFR 820.100(b) Documentation
Corrective and preventive action activities 101
and/or results have not been [adequately]
documented.
21 CFR 820.90(a)
Nonconforming product, Procedures have not been [adequately] 100
Lack of or inadequate established to control product that does not
procedures
conform to specified requirements.
21 CFR 820.30(i)
Design changes - Lack of Procedures for design change have not 95
or Inadequate Procedures been
[adequately]
established.
Specifically,***
21 CFR 820.22
Quality audits - Lack of or Procedures for quality audits have not been 90
inadequate procedures
[adequately] established.
21 CFR 820.198(c) Investigation of device Complaints involving the possible failure of 68
failures
[a device] [labeling] [packaging] to meet any
of its specifications were not [reviewed]
38
[evaluated] [investigated] where necessary.
21 CFR 820.25(b)
Training - Lack of or Procedures for training and identifying 61
inadequate procedures
training needs have not been [adequately]
established.
21 CFR 820.40
Procedures
not Document control procedures have not 61
adequately established or been adequately [established] [maintained].
maintained
Specifically,***
21 CFR 820.20(c)
Management review - Procedures for management review have 60
Lack of or inadequate not
been [adequately] established.
procedures
Specifically,***
21 CFR 820.181
DMR
not
or A device master record has not been 58
inadequately maintained [adequately] maintained.
21 CFR 820.80(d)
Lack of or inadequate Procedures for finished device acceptance 55
final
acceptance have not been [adequately] established.
procedures
(Source: RAPS)
 FDA seeks input on changes to Adverse Event Reporting Forms
The FDA is seeking input on its proposed changes to the adverse event reporting forms 3500, 3500A and
3500B. Changes would make it easier for FDA to scan in forms using optical character recognition
software. Comments are due February 9, 2015. … (Source: GPO)
 Implementing the Unique Device Identifier System into health care
systems is critical for reaching its potential to benefit public health
As the FDA works with manufacturers to launch a new system of identifying medical devices using
standard bar codes and numbers, we look forward to the day when the system, called the Unique Device
Identifier (UDI) system, will be fully set up— with identifiers on device labels and a corresponding
database of identifying information about most of the devices in the U.S. marketplace.
But why does that matter?
Much like vehicle identification numbers (VINs) for automobiles, UDIs are intended to streamline the
monitoring of devices, improve safety tracking and recall efficiency, and even make it easier to evaluate
device performance over time. So while there’s little doubt that UDI can improve patient safety,
modernize how we evaluate devices once they are in use, and facilitate future device innovation, these
benefits will only become a reality when the UDI system is adopted and integrated into the health care
system—when hospitals, doctors’ offices, patient registries, heath care insurance companies, and others
incorporate UDI as part of their standard electronic health information systems.
39
Without the practical implementation on the clinical side, UDI will be codes and a database with limited
utility to improve patient care or reach its other critical goals.
The FDA is thinking about this now—not later. While going full steam ahead to fulfill our responsibility for
implementing UDI regulations for medical device manufacturers, we are doing everything we can to
promote the widespread adoption of UDI in the U.S. health care system.
We commissioned the Brookings Institution to create a “roadmap” for provider systems, patients, payers,
supply chain personnel, and many others, to adopt and utilize UDIs. This report, released on Friday,
December 5, provides 17 recommendations for adopting UDIs across three major intersections of the
health care system—providers (e.g., electronic health records, hospital inventory management, billing
records); administrative transactions (e.g., claims data and payment information); and patient-directed
tools (e.g., mobile apps and public awareness campaigns).
We’re working hard to create and populate an efficient and useful UDI system for medical devices. But
even the perfect system will fail to improve patient care if it’s not properly integrated into electronic
health information systems. That process has to start now.
Today, we are co-sponsoring with Pew Charitable Trusts and the Department of Health and Human
Services Office of the National Coordinator (ONC) a meeting where some 400 experts are convening to
discuss changes that are needed to store and share UDI information throughout the health care system,
with the ultimate goal of improving patient care.
The goal is to have the UDI system not only up and running—but actually used as the key to unlock
important data that can help patients.
But how does such a system really help patients and the providers who care for them? Consider a possible
scenario where the connections made via UDI could make an important difference in patient care.
A patient undergoing knee surgery—we’ll call him John—has the UDI of his knee implant scanned and
electronically recorded into his clinical record.
When John is discharged, he can also register the UDI into his personal health record (PHR), available
from his provider, through a variety of mobile apps that can enable two-way communication with his
provider.
Having the UDI recorded will help John to know if safety alerts apply to his specific implant. It will also
help him accurately report any potential adverse event to the provider, the FDA, or the manufacturer,
with the confidence that the UDI ensures that all parties know what the type of device may be causing
John—and possibly other patients—problems. Importantly, if John hears about knee implants being
recalled, he will be able to quickly pinpoint, by using his UDI, if his particular type of implant is involved in
that recall. If it’s not, John may avoid needless anxiety; if it is, he can take any necessary action, such as
following up with his orthopedic surgeon.
The UDI from John’s surgery is also available to be transmitted to a total joint replacement registry,
without any of his personal information. Data from the registry may then be used to support the
development of innovative implants and reduce the data requirements for — or replace altogether —
postmarket studies conducted by the device manufacturer to demonstrate long-term performance.
The possibilities of UDI are exciting—better and more precise information can lead to better care and
better awareness of how medical devices work in the general population. The FDA is working to set up
the system, but implementation and integration are critical. The question is—if we build it, will people
adopt it?
40
Jeffrey Shuren, M.D., J.D., is Director of FDA’s Center for Devices and Radiological Health (Source: FDA)
 FDA - Advisory Committee Calendar
 January 22, 2015: Anti-Infective Drugs Advisory Committee Meeting Announcement
 January 12, 2015: Endocrinologic and Metabolic Drugs Advisory Committee Meeting Announcement
 January 7, 2015: Oncologic Drugs Advisory Committee Meeting Announcement
 CDRH updates approvals/clearances
The CDRH has posted the 510(k) final decisions that were made in November 2014. … (Source: FDA)
 CDRH updates advisory committee meeting information
The CDRH has issued a notice of the postponement of the Orthopedic and Rehabilitation Devices Panel
December meeting and the addition of the transcript to the November meeting of the Ophthalmic
Devices Panel.
Federal Register: Orthopaedic and Rehabilitation Devices Panel of the Medical Devices Advisory
Committee; Notice of Postponement of Meeting
Transcript posted for November 14, 2014 Ophthalmic Devices Panel of the Medical Devices Advisory
Committee Meeting
 FDA honcho Maisel: Study could downgrade some high-risk devices
The FDA is about halfway through a retrospective study of its pre-market approval program, a review that
could result in some devices being removed from the highest-risk category, according to Dr. Bill Maisel,
deputy director for science at the FDA's Center for Devices & Radiological Health.
Maisel, speaking before a group of medtech executives in Waltham, Mass., yesterday, said the FDA would
be completing its review of the PMA program in 2015.
"We're going to see if we can shift some of the pre-market data to post-market," he told the crowd at
MassMEDIC's annual FDA update.
Maisel said the FDA is conducting a review of the PMA process back to its inception in 1976, including
whether or not some devices, which were once classified as "high risk" can be reclassified in order to
improve the process of approving medical devices for market.
Maisel also highlighted the agency's improvements in speeding up timelines for both PMAs and 510(k)
clearances, saying the FDA has done a better job of improving its customer service. … (Source:
MassDevice)
 Alere Gets FDA Waiver for Rapid HIV Test
The FDA has granted a waiver under the Clinical Laboratory Improvement Amendments for expanded use
of the Alere Determine HIV-1/2 Ag/Ab Combo test for HIV infection. The point-of-care rapid diagnostic
test, previously only available to hospitals and laboratories licensed to conduct moderate complexity
tests, can now be used in doctor’s offices, clinics and public health settings.
41
The test, first approved in August 2013, is capable of detecting HIV-1 and HIV-2 antibodies and free HIV
p24 antigen, which appears just days after infection and before the HIV antibody is detectable. This helps
healthcare providers detect HIV infection earlier in the course of the disease, which in turn can improve
clinical outcomes and patient treatment, the Waltham, Mass.-based Alere says. … (Source: FDAnews)
 Screening Test Approved for Viruses That Cause Blood Cancer
The U.S. Food and Drug Administration today approved MP Diagnostics HTLV Blot 2.4, the first FDAlicensed supplemental test for Human T-cell Lymphotropic Virus-I/II (HTLV-I/II). This test is intended for
use as an additional, more specific test for human serum or plasma specimens that have previously tested
positive on an FDA-licensed HTLV-I/II blood donor screening test. The MP Diagnostics HTLV Blot 2.4 is a
qualitative enzyme immunoassay test intended to confirm infection with HTLV and to differentiate
between HTLV-I and HTLV-II.
The Human T-cell Lymphotropic viruses (HTLV) are a group of human retroviruses known to cause
diseases such as adult T-cell leukemia/lymphoma (a rare form of blood cancer) and inflammation of the
nerves in the spinal cord (myelopathy), as well as other conditions. HTLV can be transmitted from person
to person through breastfeeding, unprotected sexual contact, or transfusion of blood from an infected
donor.
Because HTLV can be transmitted through blood, the FDA requires that donated blood be tested for HTLVI/II antibodies. Currently there are two FDA-licensed screening tests for HTLV-I/II. If the test is positive,
the donation is discarded and the donor is notified of his or her deferral. The MP Diagnostics HTLV Blot
2.4 provides blood establishments with additional information to convey to the donor; specifically, the
test can confirm HTLV infection and determine which virus type is causing the infection, HTLV-I or HTLV-II.
“The approval of MP Diagnostics HTLV Blot 2.4 will help blood establishments better counsel donors who
have had positive results on an FDA-licensed HTLV-I/II screening test,” said Karen Midthun, M.D., director
of FDA’s Center for Biologics Evaluation and Research.
Many people who are infected with HTLV are unaware of the infection because the virus may not cause
any symptoms or signs of infection. Additionally, many people infected with HTLV-I or HTLV-II may never
develop any disease caused by the viruses. However, these asymptomatic carriers can still transmit the
viruses to others.
MP Diagnostics HTLV Blot 2.4 is manufactured by MP Biomedicals Asia Pacific Pte. Ltd. Singapore, a
company of MP Biomedicals LLC, Santa Ana, California. … (Source : FDA)
 Cianna Medical wins FDA nod for breast surgery device
Cianna Medical said it reached a new milestone, winning FDA clearance for new surgical guidance tech
designed to boost precision in breast biopsies and lumpectomies. Plans call for a slow rollout, with a
gradual expansion in 2015 beyond 2 medical centers in Florida and Tennessee currently involved in a pilot
study, the company said.
"We believe it has the potential to reduce surgical delays, improve patient satisfaction and optimize
surgical planning," CEO Jill Anderson said in prepared remarks.
The Savi Scout surgical guidance system is designed to produce audible and visual indicators surgeons can
use to tag cancerous tissue during lumpectomy and biopsy procedures.
42
The surgeon uses a hand piece that emits infrared light and electromagnetic waves to locate a reflector
placed in target tissue as long as a week before surgery. After reaching the surgical bulls-eye, the surgeon
takes out the target tissue and the reflector, according to the company. No radiation is involved. It is
designed for breast conservation surgery, where surgeons remove all detectable cancer cells. … (Source:
MassDevice)
 FDA Clears Quidel's MDx for Bordetella Pertussis
Quidel said after the close of the market on Wednesday that the US Food and Drug Administration has
cleared the company's AmpliVue Bordetella Assay.
The assay detects Bordetella pertussis nucleic acids isolated from nasopharyngeal swab specimens from
patients suspected of having a respiratory tract infection due to the bacteria, which causes whooping
cough.
Quidel's test is a self-contained handheld molecular diagnostic that requires no upfront DNA extraction
and can generate results in about 75 minutes. The AmpliVue Bordetella Assay is CLIA-classified as
moderately complex. It is the fifth assay in the AmpliVue format, the San Diego-based company said. In
July the FDA cleared the AmpliVue GAS Assay for detection of Group A Streptococcus. In late 2013, it
cleared the AmpliVue Group B Strep Assay, and in 2012, it cleared the AmpliVue C. difficile assay.
The AmpliVue technology was developed by BioHelix which Quidel acquired last year. Even before
the acquisition, though, Quidel had been using the technology, dubbed helicase-dependent
amplification (HAD), under a collaborative R&D agreement forged by the two firms in 2009. …
(Source: GenomeWeb)
 FDA Approves Blood Test That Gauges Heart Attack Risk
The U.S. Food and Drug Administration on Monday approved a new blood test that can help determine a
person's future odds for heart attack and other heart troubles.
The test is designed for people with no history of heart disease, and it appears to be especially useful for
women, and black women in particular, the agency said.
"A cardiac test that helps better predict future coronary heart disease risk in women, and especially black
women, may help health care professionals identify these patients before they experience a serious
[heart disease] event, like a heart attack," Alberto Gutierrez, director of the Office of In Vitro Diagnostics
and Radiological Health in the FDA's Center for Devices and Radiological Health, said in an agency news
release.
The test tracks the activity of a specific biological signal of vascular inflammation, called Lp-PLA2. Vascular
inflammation is strongly associated with the buildup of artery-clogging plaques in blood vessels, the FDA
explained. As plaque accumulates, arteries narrow and the chances of a serious cardiovascular event
increase.
"Patients with test results that show Lp-PLA2 activity greater than the level of 225 nanomoles per minute
per milliliter are at increased risk for a [heart disease] event," the FDA said.
The FDA said its approval of the new blood test comes from data compiled in a study funded by the U.S.
National Institutes of Health. Almost 4,600 people aged 45 to 92 with no prior history of heart disease
took part in the study, and were followed for an average of just over five years.
43
In subgroup analyses, the test seemed especially sensitive for black women, because they experienced a
"higher jump" in the rate of heart attack and other heart disease events when their blood levels of LpPLA2 exceeded a certain level.
"As a result, the test's labeling contains separate performance data for black women, black men, white
women and white men," the FDA said. … (Source : HealthDay)
 Brainsway wins FDA nod for PTSD test
Israel's Brainsway will commence a 166-patient trial at 15 medical centers to test whether its deep
transcranial magnetic stimulation device can treat patients with post-traumatic stress disorder.
Brainsway said it won an investigational device exemption from the FDA to get the neurostimulator trial
going.
The company's Deep TMS technology has had Israeli regulatory approval since October 2011 to treat
major depression, bipolar disorder and negative impairment in schizophrenia patients. It has FDA
clearance to treat patients with depression who haven't responded to medication treatments in the
current depressive episode.
Brainsway CEO Uzi Sofer noted in prepared remarks that this is the 5th FDA approval for a pivotal
multicenter trial, 4 of which will be held simultaneously. This new IDE zeroes in specifically on Brainsway's
H-Coil technology, which Sofer said was specifically developed to treat PTSD. … (Source: MassDevice)
 CenterVue Gets FDA Nod for True-Color Confocal Scanner
CenterVue Tuesday announced the launch of its Eidon true-color confocal scanner following FDA 510(k)
clearance. The device is the first retinal imaging system to combine confocal scanning with true-color
imaging capabilities, according to the Fremont, Calif., firm.
The fully automated Eidon’s combination of confocal imaging technology and white light illumination
provides superior contrast and image quality over a traditional fundus camera, simplifying the diagnosis
of retinal diseases, CenterVue says.
The scanner allows for both central and outer retinal imaging, providing a viewing angle of up to 110
degrees, and its multiple imaging methods — true color, red-free and infrared — yield information on
different layers of the retina, the company notes. … (Source : FDAnews)
 FDA Clears Additional Flu Strains for Focus' MDx Assay
Quest Diagnostics business Focus Diagnostics today said that the US Food and Drug Administration has
cleared eight additional influenza strains on the Simplexa Flu A/B & RSV Direct kit.
The kit originally received 510(k) clearance in 2012. The additional flu strains cleared by the FDA are
H7N9; H3N2 (both the Minnesota and Indiana strains; H1N1 (2011); H3N2 (the Ohio and Texas strains);
and influenza B (Brisbane and Wisconsin strains).
Focus said that the novel avian influenza A strain H7N9, which can kill as many as one-third of people
it infects, and H3N2, which infects people more easily than other swine influenza virus according to
the Centers for Disease Control and Prevention, are of particular concern.
44
"Influenza viruses constantly evolve, and virus subtypes can quickly develop and infect large populations,"
Hollis Batterman, medical director for infectious diseases at Focus, said in a statement. "It is vital that the
tests can detect the recently circulating and geographically diverse strains." … (Source: GenomeWeb)
 Siemens files 510(k) for CT lung cancer screening
Siemens Healthcare has filed a 510(k) application with the U.S. Food and Drug Administration (FDA) to
market CT lung cancer screening on its entire line of CT scanners.
Siemens made the submission because current FDA clearances for CT scanners cover their use as
diagnostic tools rather than for screening applications. Receiving a specific 510(k) clearance will allow
Siemens to market its scanners as screening tools.
The Siemens submission is for its Lung Low Dose protocol, which enables technologists to perform
automated lung studies simply by selecting the protocol from a drop-down menu. The tool uses
anatomical landmarks found on a patient to select the appropriate scan range.
The radiation dose generated by the protocol varies by scanner, but Siemens is reporting an average dose
across all of its systems of 0.8 mSv per scan. Siemens believes the radiation dose on its flagship Somatom
Force scanner is even lower.
This compares to an average dose of 1.5 mSv in the landmark National Lung Screening Trial, which
established the clinical effectiveness of lung cancer screening with low-dose CT. That trial was performed
in 2000 with CT equipment that was nearly 15 years older than today's technology. … (Source:
AuntMinnie)
 Assistance with U.S. FDA Regulations
Registrar Corp provides Registration, U.S. Agent, and Compliance Assistance for U.S. and Non-U.S.
Companies in the Food and Beverage, Medical Device, Drug, and Cosmetics Industries. … (Source :
Registrarcorp)
 NIH Awards $640K Grant to Rutgers Researcher for Rapid Ebola Dx
The National Institutes of Health has awarded Rutgers New Jersey Medical School researcher David Alland
a $640,000 grant to develop a rapid detection test for the Ebola virus.
The amplicon-nested PCR-based assay is designed to be performed on Cepheid's GeneXpert platform
using the firm's assay cartridges.
The Ebola test would analyze small amounts of patients' blood or samples taken from cheek swabs. Alland
said in a statement that he hopes to develop the assay within the next 15 months.
45
In collaboration with Sunnyvale, Calif.-based molecular diagnostics firm Cepheid, Alland's team had
previously developed a rapid detection test for tuberculosis. "The beauty of this approach is that there's
already a substantial supply of these instruments in developing countries because of the TB tests, so we
can piggyback," Alland said.
Cepheid, which markets the TB test, said more than 3,500 of the GeneXpert systems are now in use in the
developing world, including 1,000 in Africa.
The new award is a supplement to a five-year NIH grant awarded to Alland's team and Cepheid in 2012 to
develop sample prep methods and nested PCR assays to detect bloodstream infections. … (Source:
GenomeWeb)
http://www.pcori.org/
 PCORI and NIH Partner on Request for Applications to Study How to
Improve Blood Pressure Control in High-Risk Individuals
The National Institutes of Health (NIH), as part of a research partnership with the Patient-Centered
Outcomes Research Institute (PCORI), issued a Request for Applications (RFA) to study how to improve
blood pressure control among populations at highest risk for suffering hypertension-related strokes, heart
attacks, and other cardiovascular events.
PCORI has committed up to $25 million to fund up to two patient-centered trials through the
Hypertension Disparities Reduction Program Partnership (HDRPP) with NIH’s National Heart, Lung, and
Blood Institute (NHLBI) and National Institute of Neurological Disorders and Stroke (NINDS).
PCORI’s Addressing Disparities program and NIH agreed to collaborate on this patient-centered research
initiative to fill important evidence gaps on what works best to control high blood pressure, a leading
cause of cardiovascular disease, among high-risk populations. Approximately 67 million U.S. adults have
hypertension, more than half of whom do not have it under control. More than three-quarters of people
who have suffered a stroke have high blood pressure, as do nearly 70 percent of those who have had a
heart attack.
Hypertension disproportionately affects certain populations, including racial and ethnic minorities,
individuals with low socioeconomic status, and those who live in rural communities. For example, AfricanAmerican men were 30 percent more likely to die from heart disease than white men in 2007, and rural
residents are more likely to be diagnosed with heart disease than urban dwellers. Moreover, African
Americans’ rate of stroke is more than double that of Caucasians, and this disparity is most pronounced in
middle-aged black men. Previous research studies have rarely targeted these high-risk populations
exclusively nor fully engaged patients and clinicians in the research.
“We’re excited to work with our colleagues at NIH on this initiative to address the burden of high blood
pressure among patients at highest risk for heart failure, heart attacks, and other hypertension-related
events,” said Romana Hasnain-Wynia, MS, PhD, Director of PCORI’s Addressing Disparities program. “By
focusing our efforts on these populations, we expect to generate useful evidence that will fill important
46
gaps in our knowledge of prevention and treatment and help these patients and their clinicians to gain a
better understanding of how to manage their blood pressure.”
“If we are able to understand how to effectively treat hypertension in high-risk populations, we are
certain to realize reductions in cardiovascular disease among all Americans,” said NHLBI Director Gary
Gibbons, MD. “High blood pressure damages the entire circulatory system. This initiative could help us
learn how to better control high blood pressure and reduce patient’s risk for heart disease, heart failure,
and other serious events, thereby improving the lives of 33 percent of adults in this country living with
high blood pressure.”
“Hypertension is the largest cause of stroke, but it is also mostly controllable with appropriate
treatment,” said NINDS Acting Director Walter Koroshetz, MD. “NINDS research has shown that there are
major disparities in stroke in the U.S., particularly in the southeastern U.S., which has been called the
‘Stroke Belt.’ By working with PCORI, we are hopeful that these disparities can finally be eradicated
through better blood pressure management.“
The HDRPP funding announcement seeks proposals for comprehensive comparative effectiveness studies
to test a variety of methods and combinations of methods and interventions to improve blood pressure
control, such as self-measured blood pressure monitoring, lifestyle modification, and patient counseling.
Proposals must demonstrate strong patient and stakeholder engagement.
Letters of Intent (LOIs), though not required, may be submitted to NIH by Tuesday, Jan. 13, and
applications are due by Friday, Feb. 13. Interested applicants should consult the full RFA, titled "Testing
Multi-Level Interventions to Improve Blood Pressure Control in Minority Racial/Ethnic, Low
Socioeconomic Status, and/or Rural Populations (UH2/UH3),” for eligibility requirements, application
criteria and instructions, deadline updates, and other details. … (Source: PCORI)
 PCORI Board Approves Providing Up to $50 Million for CER on
Hepatitis C
The Patient-Centered Outcomes Research Institute (PCORI) Board of Governors today approved the
development of a PCORI Funding Announcement (PFA) providing up to $50 million for up to four
comparative clinical effectiveness research (CER) studies on the best ways to diagnose and treat
hepatitis C virus infection.
The Board also approved the issuance of two PFAs totaling up to $150.7 million to support the second
phase of development of PCORnet, PCORI’s initiative to improve the efficiency of health research
nationwide by harnessing the power of data from electronic health records and other sources.
With the Board’s approval, PCORI will develop a PFA focused on hepatitis C virus (HCV) research
questions that emerged as the highest priorities during a multi-stakeholder workshop PCORI hosted on
October 17. The four priority topics are:



Finding out which screening methods and testing strategies in which settings lead to the best
detection rates.
Assessing alternative ways to deliver care to high-risk populations.
Exploring the trade-offs between long-term virologic response and adverse effects associated
with different regimens of new oral antiviral medications.
47

Comparing the benefits and harms of starting treatment immediately after a diagnosis versus
active surveillance, in which treatment starts once a patient shows progression to liver disease or
other manifestations of infection.
Hepatitis C affects more than 3 million people in the United States, the majority of whom are
undiagnosed. About one-third of these individuals will develop chronic liver disease if untreated.
“HCV is a major health threat that can have devastating consequences for infected people and their
families,” said PCORI Executive Director Joe Selby, MD, MPH. “Recently approved medications are
immensely promising and offer vast improvements over previous therapies, but as yet there’s no ‘realworld’ evidence of their long-term effectiveness nor comparative evidence to help inform decisions
about screening, diagnosis, and treatment of HCV.
“In response to the feedback we’ve received from many healthcare stakeholders, and with the
approval of our Board, PCORI will issue a funding announcement in the next few months to support
CER that will build the evidence needed to better inform practice and address questions important to
patients,” Selby said.
PCORI also will issue two funding announcements later this month to support the next stage of
PCORnet’s development, funding up to 13 of the Clinical Data Research Networks (CDRNs) and up to
22 of the Patient-Powered Research Networks (PPRNs) that make up PCORnet. PCORI will provide up
to $8.75 million for each CDRN and up to $1.68 million for each PPRN over the three-year second
phase of PCORnet’s development, which will begin in September 2015 at the end of the 18-month first
phase. All of the 11 current CDRNs and 18 PPRNs are eligible to apply as are new networks that can
meet the baseline requirements within six months of the beginning of Phase II.
In other business, the Board discussed PCORI’s proposed research strategy for the next five years.
PCORI plans to continue to fund research under its broad funding announcements at a reduced level,
and shift funding toward a smaller number of larger studies focused on specific high-priority topics.
PCORI will make extended funding commitments to select topics and in some cases fund clusters of
studies around a particular topic to produce more comprehensive findings that will have greater
impact.
The strategy builds on PCORI’s previous investments and leverages the topic prioritization process
facilitated by its six multi-stakeholder advisory panels. The plan also encourages research that will tap
into PCORnet once it is fully operational.
Presentation materials and an archive of the webinar from today’s Board meeting are available on
PCORI’s website. … (Source : PCORI)
http://www.ahrq.gov/
48
http://www.iom.edu/
SANTE CANADA/HEALTH CANADA
http://www.hc-sc.gc.ca/index-fra.php
 Aurora Spine receives Canadian medical device license for ZIP fusion
system
Aurora Spine received the Health Canada Medical Device License for its ZIP Interspinous Fusion System.
The fixation implant intended for spinal fusion, consists of a ONE-STEP locking mechanism, articulating
spikes and various sizes to accommodate variations in patient anatomy. Aurora Spine received clearance
from the U.S. Food and Drug Administration for the system in November 2013.
"As a company traded on the TSX Venture Exchange, this is a significant milestone for Aurora Spine and its
global growth. We are pleased to offer the ZIP MIS Interspinous Fusion System in Canada and introduce
Aurora Spine's advanced, innovative, minimally invasive spine surgery technologies which are designed to
improve spine patient outcomes, drive continued surgeon interests and provide unique benefits that
deliver value to hospitals and patients," said Trent J. Northcutt, president and CEO of Aurora Spine. …
(Source : Becker’sSpine)
LATIN AMERICA
SSA http://www.salud.gob.mx/
http://portal.anvisa.gov.br/wps/portal/anvisa/home
AUSTRALIA & NEW ZELAND
http://tga.gov.au/
 Business gateway to eBusiness Services - launching in early 2015
In early 2015, the TGA will be launching the first of a series of upgrades to its existing eBusiness Services.
49
The first upgrade will allow eBS clients to access a user-friendly gateway to:

access and manage (where appropriate) their contact details and other information held by TGA,
and

view and pay invoices.
All current eBS functions will still be available through the new gateway and you will still be able to submit
applications and provide information to the TGA through eBS.
The new gateway is undergoing extensive user testing with current eBS users to make sure we deliver the
most user-friendly system.
We will communicate with you via email and website updates so you can stay up to date with any actions
that need to be taken before the launch. If you wish to receive emails about any changes to the current
eBS please subscribe to the TGA eBS Notices email list.
Throughout 2015 more improvements will be made to eBS and we will keep you informed about these
upgrades.
This work is being completed as part of our efforts to reduce regulatory burden and in line with our TGA
Business Plan 2014-2015 which outlines one of our major priorities which includes enhancing our business
capability and improving business processes and systems for our clients. … (Source: TGA)
 Declaration that certain IVDs are medical devices
In December 2014 the National Manager of the Therapeutic Goods Administration signed the Therapeutic
Goods (Articles that are Medical Devices) Specification 2014. The Specification ensures that pathology
tests and related instrumentation, that are used for the purpose of predicting the susceptibility or
predisposition of persons to a disease or ailment, are medical devices for the purposes of the Therapeutic
Goods Act 1989 and the Therapeutic Goods (Medical Devices) Regulations 2002.
The Specification also corrects a drafting oversight by specifying that pathology tests and related
instrumentation, that are used to test for pregnancy in persons, are medical devices.
The Specification was recommended in the Regulation Impact Statement proposing amendments to the
new regulatory framework for in vitro diagnostic medical devices (IVDs).
The Specification is intended to put beyond doubt that such goods are medical devices and to ensure that
these goods can be regulated under the Therapeutic Goods Act 1989 and the Therapeutic Goods (Medical
Devices) Regulations 2002 as IVD medical devices, consistent with other medical devices of comparable
risk.
A copy of the instrument can be found on the Medical devices notices & standards orders page. (Source:
TGA)
 TGA - presentation on CTs
TGA - Clinical trials - 3 Dec 2014.pdf
50
 TGA presentation given at the Australasian Ethics Network
Conference workshop, 3 December 2014
(Source: TGA)
 Schedule of fees and charges
The TGA has successfully transitioned from Westpac Banking Corporation (Westpac) to the
Commonwealth Bank of Australia (CBA) for all transactional banking services, including all payments for
services provided by the TGA.
The Westpac account will be closed on 23 December 2014 and payments to the TGA through that
account will no longer be accepted after this date.
For your reference, all EFT payments should be made to:
Bank: Commonwealth Bank of Australia
BSB: 062-909
Account: 10215498
Payments by credit card should be made through https://www.bpoint.com.au/payments/TGA (link is
external).
Assistance
TGA Accounts Receivable: Ph. +61 2 6221 6900 OR email accountsrec@tga.gov.au (link sends e-mail) …
(Source: TGA)
 ACMD meeting statement, Meeting 17, 28 November 2014
ACMD meeting statement, Meeting 17, 28 November 2014
 ACMD meeting statement, Meeting 16, 26 September 2014
ACMD meeting statement, Meeting 16, 26 September 2014
 Meeting dates for 2015 now available
Advisory Committee on the Safety of Medicines (ACSOM)
Advisory Committee on the Safety of Medical Devices (ACSMD)
INDIA & ASIA
51
China SFDA | Hong Kong MDCO & PSDH | India CDSCO | Japan MHLW | Korea KFDA | Malaysia MOH | Philippines DOH
| Singapore HSA | Taiwan TFDA | Thailand FDA | Vietnam MOH
http://www.pmda.go.jp/english/
 Japan hosts 15th global health meeting
The European Commission participated at the 15th ministerial meeting of the Global Health Security
Initiative (GHSI) hosted by Japan in Tokyo, on December 11, which brought together health ministers and
representatives from Canada, France, Germany, Italy, Japan, UK, US, Mexico, and the World Health
Organization. The aim of the GHSI is to forge stronger global collaboration on health security by
addressing health threats from chemical, biological and radio/nuclear agents and by collaborating on the
development of preparedness and response on pandemic influenza.
Communiqué setting out the achievements of the Global Health Security Initiative - 15th Ministerial
meeting on the GHSI (December 11, 2014)
http://www.sfdachina.com/?gclid=CIes_4rZnrMCFe_MtAod_0gAeA
 Potential New Tool for Cervical Cancer Detection and Diagnosis
Cervical cancer is, in many ways, a shining example of how successful the war on cancer can be. Thanks
largely to the advent of Pap smear screening, U.S. cervical cancer deaths decreased dramatically, by more
than 60 percent, between 1955 and 1992. In the last two decades, better treatment outcomes and more
powerful imaging techniques have steadily pushed 5-year survival rates ever higher. The latest weapons
in modern medicine's arsenal are two new vaccines that were recently approved by the U.S. Food and
Drug Administration for preventing this type of cancer altogether.
As rosy a picture as that paints, cervical cancer continues to claim far too many lives. Thousands of
American women still die from the disease every year, and hundreds of thousands of other women
around the world suffer the same fate -- sad, stark statistics that showcase the continued need for more
advanced screening methods to catch more cases of the disease early, when it is most treatable.
Now a team of researchers from Central South University in China have demonstrated that a technique
known as photoacoustic imaging, which is already under investigation for detecting skin or breast cancers
and for monitoring therapy, also has the potential to be a new, faster, cheaper and non-invasive method
to detect, diagnose and stage cervical cancer with high accuracy. Their work appears in a new paper in
The Optical Society journal.
52
In this paper, the researchers describe how they examined 30 cervical tissue samples with photoacoustic
imaging. Some were taken from healthy women and some of the samples contained the cancerous cells
of a cervical tumor. They found that photoacoustic imaging could distinguish the cancerous from the
normal tissue and had the potential to evaluate the stage of the cancer.
Our results show that the photoacoustic imaging may have great potential in the clinical diagnosis of
cervical cancer, said Jiaying Xiao, an assistant professor of biomedical engineering at Central South
University, who led the research. The technique is non-invasive and can detect the lesions in the cervical
canal, an area conventional methods fail to observe. The photoacoustic imaging can also evaluate the
invasion depth of cervical lesions more effectively. … (Source : PMPnews)
MFDS
http://www.kfda.go.kr/eng/index.do;jsessionid=8WaGRaioTcYSanehB1hMj6KOHjYV58zMGvaefbMlRWUQqdgxsIWA05GwBX1zZoJG
WHITE-TILLET Partner in South Korea
 MFDS soliciting input on tissue bank safety management guidance
The MFDS seeks input on tissue bank safety management guidance designed to ensure there is no risk of
cross-contamination in tissue processing rooms and facilities. … (Source: MFDS)
 MFDS posts GMP seminar materials
The MFDS has posted presentations made at the November Medical Device GMP Certification
International Seminar. … (Source: MFDS)
 MFDS designates public institutions for device trials
The MFDS has posted the names of the public institutions that are designated to conduct medical device
clinical trials.
 MFDS designates public institutions for device trials
The MFDS has posted the names of the public institutions that are designated to conduct medical device
clinical trials.
53
HSA
http://www.hsa.gov.sg/publish/hsaportal/en/home.html#page=tab1
CDSCO
http://www.cdsco.nic.in/
 Indian regulator soliciting feedback on regulatory system upgrade
plan
India's Central Drugs Standards Control Organisation is soliciting feedback on a Ministry of Health and
Welfare plan to upgrade the country's regulatory system at both national and state levels over the next
three years. The goal of the upgrade is to "facilitate expeditious consideration and faster decision making
and testing of medical products wherever required and serve the objective of the quality, safety and
efficacy of drugs and other medical and cosmetics products."
On both state and national levels, the plan calls for setting up new drug testing laboratories and
upgrading those already running; creation of new lab and regulatory positions, with appropriate training
for new hires; and strengthening enforcement mechanisms. The plan also proposes the establishment of
a Training Academy and implementation of an e-Governance mechanism and networking of CDSCO and
State Drugs Control Departments.
Comments on the proposed plan can be submitted until December 22, 2014. … (Source: CDSCO)
 IISc scientists help peer into insides of HIV-infected cell
A new biosensor can measure what is going on within HIV-infected cells in real-time and also provide
insight on the interactions between the AIDS virus and the tuberculosis causing bacteria within the cells.
Researchers from IISc, Bangalore, the International Centre for Genetic Engineering and Biotechnology,
New Delhi and Jamia Millia Islamia, New Delhi have exploited this non-invasive biosensor that can
measure what is going on within HIV-1 infected cells in real-time. This technology can offer insights which
can help in controlling the AIDS infection besides insight on the interactions between HIV-1 and TBcausing bacteria, Mycobacterium tuberculosis (Mtb), says a release by Gubbi Labs.
Since its discovery, Acquired Immune Deficiency Syndrome or AIDS has caused an estimated 36 mn
deaths worldwide (as of 2012). Its causative agent, the Human Immunodeficiency Virus (HIV), has thus
been a hot topic of research. Human body produces oxygen free radicals called Reactive Oxygen Species
or ROS, during routine cellular metabolism.
When not regulated properly, accumulation of these ROS can lead to oxidative stress. Heightened
oxidative stress is one of the primary causes of reactivation of HIV-1 in infected cells. Oxidative stress also
decreases proliferation of disease fighting immune cells; besides, it causes loss of memory in immune
cells. These factors reduce the efficiency of the immune response toward the HIV. A major cellular
54
antioxidant called glutathione (GSH) functions as a protective shield against the oxidative stress.
GSH levels in infected cells and tissues are indicators of the level of infection. The team has devised a noninvasive biosensor methodology for precise measurements of GSH levels within HIV-1 infected cells.
Earlier methods use whole cell or tissue extracts, which destroy detailed information related to the GSH
levels in different areas within an infected cell.
Study discovered that a modest increase in oxidative stress is sufficient to reactivate virus from latency.
This may allow researchers to adopt a "shock-and-kill" strategy in which virus could be reactivated by
oxidative stress inducing compounds and subsequently killed/flushed by current anti-HIV drugs. The
fluctuation of GSH levels detected by the biosensor also helps understand the expression of antioxidant
genes and related pathways during latent and active stages of infection. … (Source: BS)
DISCOVERY - DESIGN - DEVELOPMENT
 Key Considerations for Designing Neurovascular Microcatheters
Significant technological progress, favorable reimbursement conditions, and the medical device industry's
windfall—the massive army of aging baby boomers—will spur the U.S. neurovascular market to exceed
$600 million by 2020, according to market research firm iData Research.
And a critical driver of growth in this sector has been the various advancements in microcatheter design
and development. "Almost every device placement or therapy taking place in or above the neck will
require a microcatheter to support the intervention," comments Steven W. Berhow, president of Rogers,
MN-based Biomerics Advanced Catheter.
The increasing move to minimally invasive surgical procedures has motivated medical tubing and
extrusion experts to test the boundaries of miniaturization. Specialists have sought to strike a delicate
balance in terms of achieving the smallest possible outside diameter for a catheter without compromising
performance characteristics for a given application.
Designing microcatheters for neurovascular interventions takes these demanding requirements a step
further, however. Beyond shrinking profiles, these microcatheters pose additional challenges because
they must be able to carefully navigate the winding, delicate anatomy of the tiny blood vessels that run
through the head and neck.
"Devices used in the neurospace require microcatheters that can transverse very tortuous anatomies
while maintaining pushabilitiy and the lumen itself," Berhow says. "The design must have characteristics
constructed into the shaft and tip that allow the microcatheter to reach its intended work site and deliver
the therapy without damaging the vessels it is moving through."
55
To this end, microcatheters must possess the following traits, according to Berhow:
1. Good torque within the shaft from the proximal to the distal end
2. Flexibility in the distal portion of the catheter
3. Kink resistance
4. Visibility under fluoroscopy
5. Low stretch
6. High pressure
7. Good guidewire movement
"These devices tend to be high-end catheters that are very complicated to design and manufacture,"
Berhow says. "Microcatheters are designed with very small walls, thin lubricious liners, high counts of
reinforced braid, antikink characteristics, and they need to maintain visibility under fluoroscopy." …
(Source: MD+DI)
 Renal denervation: Analysis highlights 'confounding' factors in
Medtronic's Symplicity-3 trial
A post-study analysis of data from Medtronic's failed Symplicity-3 trial of renal denervation in treating
hypertension reveals several "confounding factors" that may have contributed to the trial missing its
efficacy endpoint.
Early this year the results of the Symplicity-3 trial, widely expected to be a home fun for RDN in
hypertension, shocked the medical device world when Medtronic reported no significant difference
between treatment with its Symplicity device and a sham procedure.
The results prompted Medtronic to suspend enrollment in 3 other RDN trials around the world and led to
other companies in the space either suspending their programs or abandoning them altogether.
But a Medtronic-sponsored examination of the data from Symplicity-3, published last month in the
European Heart Journal, suggest that medication adherence, changes in drug regimens and variations in
the RDN procedure may have led to the surprising results of the trial. … (Source: MassDevice)
 TAVI: Transcatheter Technologies to develop transfemoral valve
Transcatheter Technologies said today that it's adding a new version of its Trinity transcatheter aortic
valve implant, designed to be delivered transfemorally, in addition to the existing transapical version of
the device.
The transapical approach is performed via an incision between the ribs; in the transfemoral approach the
device is introduced via the femoral artery in the thigh.
Regensburg, Germany-based Transcatheter Technologies touts its Trinity valve as the only TAVI device
that's "truly" repositionable, even after full implantation. Trinity is also designed to minimize or eliminate
the paravalvular leakage that's plagued early TAVI devices, according to a press release. … (Source:
MassDevice)
56
 Targeted Adsorption of Molecules in the Colon With the Novel
Adsorbent-Based Medicinal Product, DAV132: A Proof of Concept
Study in Healthy Subjects
Gunzburg J., Ducher A., Modess C., et al. The Journal of Clinical Pharmacology / Vol XX No XX (2014)
Abstract
During antibiotic treatments, active residuals reaching the colon profoundly affect the bacterial flora
resulting in the emergence of resistance. To prevent these effects, we developed an enteric-coated
formulated activated-charcoal based product, DAV132, meant to deliver its adsorbent to the ileum and
neutralize antibiotic residues in the proximal colon. In a randomized, control, crossover study, the plasma
pharmacokinetics of the probe drugs amoxicillin (500 mg) absorbed in the proximal intestine, and
sulfapyridine (25 mg) metabolized from sulfasalazine in the cecum and rapidly absorbed, were compared
after a single administration in 18 healthy subjects who had received DAV132, uncoated formulated
activated charcoal (FAC) or water 16 and 8 hours before, concomitantly with the probe drugs, and 8 hours
thereafter. The AUC0–96 h of amoxicillin was reduced by morethan 70% when it was taken with FAC, but
bioequivalent when it was taken with water or DAV132. By contrast, the AUC0–96 h of sulfapyridine was
reduced by more than 90% when administered with either FAC or DAV132 in comparison with water. The
results show that DAV132 can selectively adsorb drug compounds in the proximal colon, without
interfering with drug absorption in the proximal small intestine, thereby constituting a proof of concept
that DAV132 actually functions in humans.
 Australia's VCGS Inks Deal with Illumina to Develop NIPT
Victorian Clinical Genetics Services, a genetic testing subsidiary of the Murdoch Children's Research
Institute in Melbourne, Australia, has struck a deal with Illumina for non-invasive prenatal testing.
Under the agreement, VCGS will develop its own non-invasive prenatal test using Illumina's sequencing
technology, which it will begin offering in early 2015. Prior to launching its own test, VCGS will send
samples to Illumina for testing.
"This agreement positions VCGS at the frontier of prenatal testing in Australia, and offers patients exciting
and powerful new options for genetic testing," Damien Bruno, deputy laboratory director at VCGS, said in
a statement.
VCGS currently provides maternal serum screening for more than 58,000 women annually. It also offers
genetic services, including genetic counseling and education. … (Source : GenomeWeb)
 Novel Wearable Patch Allows Pregnant Women to Measure
Contractions
Back in 2012, Eric Dy and Julien Penders developed wearable health technologies for corporate partners
in consumer and medical markets, then at the electronics research center Imec. The aim was to combine
clinical quality in consumer form factors.
When Penders had his first child, both were stricken by the fact that pregnancy was a time full of
questions and concerns for expecting mothers who often encountered a lack of reliable information.
“Care teams are working with limited data while there are no solutions out there to answer their
57
questions and help them live a healthy pregnancy,” Penders explained. Dy and Penders decided to found
the start-up Bloom to help pregnant women to find answers to the questions they have.
Their first product are clinically accurate patches that measure and track contractions. The patch is based
on technology from Imec, where the founders have been developing ultra low power wearable systems
for physiological tracking for more than a decade. The patch communicates to a smartphone where a
woman can easily visualize the frequency and duration of her contractions, and share this with her
partner or care team.
While contractions are measured at the hospital using a tocodynamometer, which is a pressure-based
measurement, Bloom takes a different approach. “Our method to contraction monitoring is based on
measuring the electrical activity of the uterus. Just like you measure the electrical activity of the heart
when doing an ECG check,” Penders explained. “The electrical activity of the uterus is the source of the
contraction, while pressure is its consequence. Measuring the source of the contractions provides a more
direct and accurate measurement.” He points out that different types of contraction have different
electrical signatures, which makes it possible to to differentiate different types of contractions.
“We also plan to release upgrades to distinguish between Braxton Hicks and labor inducing contractions
as well as track other parameters of fetal and maternal health. The consumer focused platform aims to
capture the most comprehensive dataset on maternal health ever collected,” Penders told EMDT. With
this information, Bloom looks to partner with clinical researchers to help understand and solve large and
growing pregnancy complications such as gestational diabetes, preeclampsia, and preterm birth.
While the technology reassures mothers-to-be by helping them to identify contractions, it also produces
valuable data that might provide women with personalized feedback and notifications to manage their
health. “Lifestyle related pregnancy complications result in a significant increase in healthcare costs
during pregnancy and labor, and after delivery for both mother and baby,” Penders explains. “For
example, more than one half of pregnant women are overweight or obese which has been shown to
increase the risk of c-section. Gestational diabetes mellitus rates are increasing and affect 7-18% of
pregnancies in US.” According to Penders, hypertension complicates 6-8% of pregnancies in the US. “It
is projected that improving the health of women around pregnancy can result in over $26B worth of
savings annually by just addressing lifestyle related disease.” … (Source : EMDT)
58
 Oxford Scientists Develop Zinc-Based Blood Test for Breast Cancer
Breast cancer is the most common cancer in the UK accounting for 30% of all new cancer diagnoses each
year. Globally it is the second most common cancer after lung carcinoma. Treatment for breast cancer is
in general extremely effective, although mortality is age dependant 96% of women are expected to live
beyond a year following diagnosis, and 87% are expected to survive beyond 5 years. 10 year and 20 year
survival rates are also amongst the best within oncology, however the earlier the cancer is detected, the
higher the chance of effective treatment and prolonged mortality.
It has been well documented for around a decade that breast tumours appear to have high
concentrations of zinc within them; however the physiological processes by which this occurs has never
been fully understood. By using techniques normally used by metallurgists to analyse trace isotopes
involved in climate change, the Oxford based group has been able to analyse the metabolic processes the
human body uses to metabolise trace metals. In doing so the group has been able to illustrate changes in
the composition of the zinc found within breast cancer tissues and presented the possibility that it could
potentially be used as a biomarker to detect sub-clinical presence of breast tumours.
The new work has concentrated on investigating the behaviour of cancer cells specifically considering the
role of sulphur-containing proteins and their involvement in processing zinc. The research group has then
undertaken a research study investigating the difference in zinc content of blood and blood serum in
cancer patients and a healthy control group. By using hypersensitive techniques (over 100 times more
sensitive than used current clinical techniques) significant and key differences in the way that zinc is
processed by cancerous cells were detected. … (Source: EMDT)
 Novel Automated Device Cultures Heart Stem Cells
It’s a simple idea: making heart tissue from patients' own cells to repair heart damage caused by acute
myocardial infarction. But it took Professor Philippe Hénon, chairman/CSO and co-founder of
59
CellProthera, and president of the Haematology and Transplant Research Institute in Mulhouse, around
ten years to bring it to completion.
His start-up based in Mulhouse (Haut-Rhin, France), which pioneers cardiac regeneration therapy, has
developed treatment that could provide a real alternative to heart transplants. The technology involves
selecting, collecting, purifying and multiplying stem cells from patient blood samples and then directly reinjecting a cell graft into their damaged heart area. Opening up the thorax to carry out heart transplants
or bypass operations might no longer be necessary. Consequently, the overall cardiac grafting process has
become a straightforward interventional cardiology treatment equivalent to inserting a coronary stent.
The technology enables heart tissue necrosed by acute myocardial infarction to regenerate within a few
months. Cardiac regeneration therapy is expected to significantly reduce the cost of treating the 1 million
congestive heart patients recorded annually throughout the main Western countries.
The cell grafts are produced by a patented, automated device enabling mass production of the autologous
grafts needed for heart tissue regeneration and myocardial revascularization. This automated device
comprises culture medium reservoirs, an incubator with a thermostatic chamber containing the cell
culture vessel, and a control system to agitate and support the culture vessel. The cell expansion bag walls
have special properties that reduce adhesion by culture cells. This so-called StemXpand device also has a
peristaltic pump controlling the supply of culture medium to the cell expansion bag and reservoirs of
growth factors and culture cells. “Using a simple patient blood sample, several million CD34+ blood stem
cells are isolated and cultured in our automated device and associated production kit,” explains JeanClaude Jelsch, CellProthera's CEO. These cells are multiplied up to twentyfold and then re-injected into
patients via an intra-arterial catheter extending as far as the infarction-induced myocardial injury. This
regenerates its anatomy and functioning. Nine days are required to produce these stem cells. … (Source :
EMDT)
60
Le Cabinet WHITE-TILLET est enregistré pour la formation et agréé pour
le Crédit Impôt Recherche (lorsque les prestations le justifient)
61
COSMETICS & BIOCIDES
Corinne BENOLIEL, Docteur en pharmacie et Directrice scientifique des laboratoires SCIENTIS
vous présente « SCIENTIFIQUEMENT VOTRE » :
 La notification des produits cosmétiques
La notification à la Commission européenne concerne la personne responsable et/ou les distributeurs.
Elle nécessite, dans certains cas, une interaction entre la personne responsable d’un produit cosmétique
et le distributeur de ce produit.
-1. Avant la mise sur le marché d’un produit cosmétique, la personne responsable doit transmettre à la
Commission européenne un certain nombre d’informations sur le produit dans le cadre de la notification.
La notification à la Commission européenne s’effectue par voie électronique sur un « portail » dédié aux
produits cosmétiques commercialisés au sein de l’Union européenne (article. 13).
Les autorités nationales compétentes ainsi que les centres antipoison ont accès à certaines informations
transmises par la personne responsable dans le cadre de cette notification, les formules étant
uniquement accessibles aux centres antipoison.
Les informations à fournir sont les suivantes :
- la catégorie du produit cosmétique et son ou ses nom(s) commercial(aux) complet(s)
- le nom et l’adresse de la personne responsable (physique ou morale) où le dossier d’information sur le
produit (DPI) est tenu à disposition des autorités compétentes
- le pays d’origine si le produit est importé
- l’Etat membre dans lequel le produit doit être mis sur le marché
- les coordonnées d’une personne physique à contacter en cas de nécessité
- en cas de présence de substances sous forme de nanomatériaux, leur identification et les conditions
d’exposition raisonnablement prévisibles
- le nom et le numéro CAS ou CE des substances CMR de catégorie 1A ou 1B
- la formulation cadre
Si l’une de ces informations change, la personne responsable fournit sans délai une mise à jour.
La personne responsable doit en outre communiquer
- l’étiquetage original
62
- la photographie de l’emballage si elle est lisible.
Les informations transmises aux autorités compétentes pourront être utilisées à des fins de surveillance
et d’analyse du marché ainsi que d’évaluation et d’information des consommateurs.
Manuel d’utilisation destiné aux utilisateurs du portail européen de notification (CPNP)
Conformément à l’article 16 du règlement cosmétique, la personne responsable doit notifier les produits
cosmétiques contenant des nanomatériaux à la Commission européenne (CE), six mois avant leur mise sur
le marché, sauf s’ils ont déjà été mis sur le marché par la même personne responsable avant le 11 janvier
2013 (voir point 24 de ce document).
Manuel d’utilisation spécifique pour la notification sur le CPNP des produits cosmétiques contenant des
nanomatériaux
-2. La notification doit être effectuée par les distributeurs lorsqu’ils mettent à disposition dans un Etat
membre un produit cosmétique déjà mis sur le marché d’un autre Etat membre et qu’ils traduisent de
leur propre initiative tout élément de l’étiquetage afin de se conformer à la législation nationale.
Les informations à fournir sont les suivantes :
- la catégorie du produit cosmétique
- son nom dans l’Etat membre d’origine et son nom dans l’Etat membre où il est mis à disposition
- l’Etat membre dans lequel le produit est mis à disposition
- ses nom et adresse
- le nom et l’adresse de la personne responsable où le DIP est tenu à disposition.
Si l’une des informations change, le distributeur fournit sans délai une mise à jour.
-3. La communication doit être effectuée par le distributeur auprès de la personne responsable lorsqu’il
introduit dans un état membre un produit cosmétique après le 11 juillet 2013 alors que ce dernier a été
mis sur le marché avant cette date mais n’est plus mis sur le marché à compter de cette date par la
personne responsable.
Les informations à fournir à la personne responsable par le distributeur sont les suivantes :
- la catégorie du produit cosmétique
- son nom dans l’Etat membre d’origine et son nom dans l’Etat membre où il est mis à disposition
- l’Etat membre dans lequel le produit est mis à disposition
- ses nom et adresse.
Sur la base de ces éléments, la personne responsable devra réactualiser la mise à jour de sa notification
sans délai.
Si l’une des informations change, la personne responsable fournit sans délai une mise à jour.
www.scientis.fr/ scientis@scientis.fr
 Date de durabilite et PAO
L’indication de la date de durabilité minimale (DDM) n’est pas obligatoire pour les produits cosmétiques
dont la durabilité minimale excède trente mois. Ces produits portent l’indication de la PAO.
L’obligation de détermination d’une PAO dépend tout d’abord de la durabilité minimale du produit:
63
Durabilité minimale :
< 30 mois
Indication de la DDM
Obligatoire
> 30 mois
Indication de la PAO
Facultative
Facultative
Obligatoire*
* Sauf si le concept de PAO n’est pas pertinent, comme dans les cas suivants:
- les produits à usage unique (forme unidose,…) ;
- les produits qui ne s’ouvrent pas (formes sans possibilité de contact avec l’environnement extérieur.
Ex : aérosols si pas d’entrée d’air, etc.) ;
- les produits ne présentant pas de risque de dégradation (Ex : un parfum).
www.scientis.fr/ scientis@scientis.fr
 Rapport nano 2014
Le ministère de l’écologie, du développement durable et de l’énergie a publié un rapport d’étude issu des
déclarations effectuées en 2014 relatives aux substances à l’état nanoparticulaire (toutes catégories
confondues). … (Source: ministère de l’écologie, du développement durable et de l’énergie)
 Opinion SCCS ELA
Le SCCS a été sollicité dernièrement pour compléter son opinion avant fin Décembre 2014 sur l’Ethyl
Lauroyl Arginate HCl (ELA) , substance réglementées aux annexes V et III du Règlement Cosmétique CE
1223/2009 .
Il devra également indiquer toutes autres préoccupations scientifiques liées à l'utilisation de cette
substance dans les produits cosmétiques
http://ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_q_107.pdf
http://ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_miwg_205.pdf
 Identification des phtalates
NF EN 16521 Juillet 2014
Cosmétiques - Méthodes analytiques - Méthode GC-MS pour l'identification et l'analyse de 12 phtalates
dans des échantillons de produits cosmétiques prêts à être injecté dans un système analytique. … (Source:
AFNOR)
Depuis 2008, SCIENTIS est reconnu comme organisme ayant la capacité d’exécuter des
travaux de recherche et développement pour le compte d’entreprises.
64
Nos donneurs d’ordre peuvent donc déclarer les montants des opérations de R&D éligibles au
crédit d’impôt recherche (CIR) conformément aux articles 244 quater B du code général des
impôts, 49 septies F et 49 septies M de son annexe III.
N’hésitez pas à nous contacter à l’adresse scientis@scientis.fr : les experts formulateurs
et réglementaires de SCIENTIS sont à votre écoute pour vous accompagner dans tous
vos projets de recherche innovants (produits cosmétiques, détergents, désinfectants,
biocides) :
 Optimisation de formules existantes
 Création de nouvelles formules
 Préexpertises Toxicologiques de vos formules
Cosmétiques - Détergents – Désinfectants - Probiotiques
Laboratoire de recherche appliquée et d’expertise scientifique
FORMATIONS SCIENTIS 2014
COSMETIQUES
Microbiologie
 M1C La microbiologie des produits cosmétiques
 M2C La gestion d’un laboratoire de microbiologie : microorganismes et cultures selon la norme
EN 12353 (formation pratique)
 M3C Comment analyser le risque de contamination d’un produit cosmétique : ISO 29621?
 M4C Comment réaliser un challenge test selon la norme ISO 11930 sur un produit cosmétique?
(formation pratique)
 M5C Comment réaliser les contrôles de propreté des produits cosmétiques selon les normes ISO
en vigueur ? (formation pratique)
Règlementation
 R1C La règlementation des produits cosmétiques
 R2C Le Dossier d’Information Produit cosmétique (DIP)
 R3C L’évaluation de la sécurité des produits cosmétiques
 R4C La notification des produits cosmétiques
Formulation
 F1C Les bonnes pratiques de Fabrication des produits cosmétiques : ISO 22716
 F2C La formulation des produits cosmétiques (formation pratique)
BIOCIDES
Microbiologie
 M1B La microbiologie des produits biocides désinfectants et détergents désinfectants
 M2B La gestion d’un laboratoire de microbiologie : microorganismes et cultures selon la norme
EN 12353 (formation pratique)
 M3B Les normes européennes d’efficacité antimicrobienne des antiseptiques et désinfectants
65

M4B Comment réaliser une norme d’efficacité antimicrobienne sur un antiseptique, un
désinfectant ou un détergent désinfectant? (formation pratique)
Règlementation
 R1B La règlementation des produits biocides
 R2B La pré-expertise toxicologique des produits biocides à destination cutanée
 R3B Les exigences réglementaires des produits biocides en période transitoire
 R4B Comment créer une fiche de données de sécurité ? (formation théorique et pratique sur
logiciel)
Formulation
 F1B Le bionettoyage en milieu industriel
 F2B La formulation des produits biocides à destination cutanée, désinfectants et détergents
désinfectants (formation pratique)
DISPOSITIFS MEDICAUX
Microbiologie
 M1DM La microbiologie des dispositifs médicaux désinfectants et détergents désinfectants
 M2DM Les normes européennes d’efficacité antimicrobienne des antiseptiques et désinfectants
 M3DM Comment réaliser une norme d’efficacité antimicrobienne sur un antiseptique, un
désinfectant ou un détergent désinfectant) ? (formation pratique)
Règlementation
 R1DM La règlementation des dispositifs médicaux
 R2DM Comment créer une fiche de données de sécurité ? (formation pratique sur logiciel)
Formulation
 F1DM La formulation des dispositifs médicaux désinfectants et détergents
désinfectants (formation pratique)
DETERGENTS
Règlementation
 R1D La règlementation des détergents
 R2D Les réglementations transversales (REACH, CLP)
 R3D Comment créer une fiche de données de sécurité ? (formation pratique sur logiciel)
 R4D Les labels écologiques
Formulation
 F1D Le bionettoyage en milieu industriel
PROBIOTIQUES ET COMPLEMENTS ALIMENTAIRES

CA1 Les généralités, la réglementation, le marché, la formulation
Formations intra et interentreprises/Web conférences.
Les formations pratiques intègrent une partie théorique.
Descriptifs et tarifs communiqués sur demande en nous écrivant à l’adresse
scientis@scientis.fr ou par téléphone au +33 (0)1 41 50 59 89 (référence de la formation à
indiquer).
Programmes ciblés sur demande.
Organisme de formation enregistré sous le n°11 93 06199 93
Parc Biocitech-102 av Gaston Roussel
93230 Romainville
www.scientis.fr
scientis@scientis.fr / 01.41.50.59.89
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SCIENTIS NOTRE PARTENAIRE POUR LES PRODUITS COSMETIQUES & BIOCIDES
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Cosmétiques - Détergents - Désinfectants
Laboratoire de recherche appliquée et d’expertise scientifique
VOUS VENDEZ DES PRODUITS DETERGENTS, DESINFECTANTS, COSMETIQUES ?
POUR LE MILIEU PROFESSIONNEL OU POUR LE GRAND PUBLIC ?
VOS ETIQUETTES & FICHES DE DONNES DE SECURITE SONT-ELLES CONFORMES?
Outil indispensable de communication
entre le fabricant
et l’utilisateur de produits chimiques.
Elle informe sur les risques humains et
environnementaux liés à l'utilisation
de substances (matières premières) et
de mélanges (produits finis).
La fiche de données de sécurité (FDS)
une mine d’informations !
Elle fournit aussi les informations
concernant le stockage, la manipulation
et l’élimination du produit.
Elle permet ainsi de connaître les
mesures nécessaires à prendre en
matière de gestion de risques.
REACH
Règlement n°1907/2006
Enregistrement, Evaluation et
Autorisation des produits
chimiques.
FDS
Règlement n°453/2010
Exigences concernant
l'établissement de la fiche de
données de sécurité.
CLP
Règlement n°1272/2008
Classification, Etiquetage et
Emballage des substances et
mélanges.
A NOUVEL ETIQUETAGE...
.nouvelles classes de danger :
Nature des dangers physiques, pour la santé et pour l’environnement.
.nouveaux pictogrammes :
Losanges blancs sur fond blanc
.nouvelles mentions : danger (H), mise en garde (P), avertissement (EUH)
CALENDRIER DES MISES A JOUR: Êtes-vous prêt ?
1er déc 2012
1er Juin 2017
1er juin 2015
C
L
P
Double étiquetage DPD/CLP
autorisé sur les FDS des
Passage au CLP obligatoire
mélanges
R
E
A
C
H
La FDS doit être en conformité
avec le Format 2010-I
la FDS doit être en
(Pour les produits mis sur le marché avant conformité avec le
le 01/12/2010, passage au nouveau Format Format 2010-II
au 1er/12/2012)
Parc Biocitech-102 av Gaston Roussel
93230 Romainville
www.scientis.fr
scientis@scientis.fr / 01.41.50.59.89
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Cosmétiques - Détergents - Désinfectants
Laboratoire de recherche appliquée et d’expertise scientifique
Le Règlement cosmétique européen (1223/2009 du 30/11/2009)
a été publié le 22 décembre 2009.
Il est entré en vigueur le 11 janvier 2010 et est en application
depuis le 11 juillet 2013.
Description du produit cosmétique
Rapport sur la sécurité
Partie A: informations sur le produit
Partie B: évaluation de la sécurité
Dossier d’information
Produit
Méthode de fabrication selon les BPF
Preuves de l’effet revendiqué
Dossier
cosmétique
Données relatives aux expérimentations
animales
Règlement n°1223/2009
Notification
Portail CPNP
Personne
responsable
de la mise sur
le marché
Calcul
d’exposition
et marge de
sécurité
Évaluation
de la
sécurité
Microbiologie
Profil
toxicologique
des substances
Impuretés
(substances et
emballage)
Compatibilité
contenu /
contenant
Cosmétovigilance
européenne
Stabilité
L’effet rétroactif prévu dans le Règlement implique que tous les dossiers
cosmétiques des produits déjà sur le marché doivent être mis à jour.
Organisme de formation enregistré /agrément du Ministère au Crédit Impôt Recherche
Parc Biocitech-102 av Gaston Roussel
93230 Romainville
www.scientis.fr
scientis@scientis.fr / 01.41.50.59.89
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Experience & Expertise
Associate Consultants & Experts
Tel : + 33 1 600 843 85
E-mail : white-tillet@white-tillet.com
Website: www.white-tillet.com
Pour abonner vos ami(e)s écrire à : white-tillet@white-tillet.com
Pour vous désabonner écrire à : contact-wt@wanadoo.fr
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