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Tom Sam Head Global CMC Regulatory Affairs Merck Sharp & Dohme Oss, the Netherlands
My Career ..
Implanon NXT
fun excitement
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time
Technological Innovation
Ascher Shmulewitz & Robert Langer Nature Biotechnology 24, 277 - 280 (2006)
revolution in healthcare.
Electronics and communications will be integrated into these devices,
allowing the processing and analysis of vast amounts of data in near real-time.
In the near future environment information will be used to
- manage medication, - monitor patient compliance and to - modify treatments in response to diagnostics.
Increasingly, these devices will provide
the: - value-for-money evaluation of product/ treatment on a patient-by-patient basis, - the increasing integration of electronics and communication and - the move towards diagnostic test kits and medical devices directly linked to individual health portals. Drugs combined with medical devices or as single integral products will provide exciting ways to enhance efficacy and safety of these drugs beyond what could be achieved without these devices.
An array of devices, medical devices, combination products and single integral products
- medicine / packaging - cosmetic - device - medical device (still different risk classes) - combination product - components - accessories - single integral products, etc.
The Regulatory Landscape for medical devices is different from that of pharmaceuticals
Medicinal Product
Submission to Competent Authority: - National - Mutual Recognition - Decentralised Procedure Submission to EMA: - Centralised Procedure
US
US
Submission to FDA/CBER: - Biologic License Application (BLA) Submission to FDA/CDER: - New Drug Application (NDA)
Medical Devices:
Certificate by the Manufacturer / /..etc. Technical documentation (STED) Standards, MEDDEVs Global Harmonization Task Force (GHTF) ISO 13485:2003 / CFR 820.20 ISO 14155:2009 Market Surveillance Vigilance User Instructions For Use
What are the major challenges for pharmaceutical companies when dealing with medical devices?
1. 2.
Obtain an in-depth understanding of the regulatory environment (EU / US / MOW) Learn how to
classify medical devices follow conformity assessment routes leading to CE marking work with the Health Authorities / Notified Bodies adhere to the Essential Requirements use Quality Risk Management throughout the product lifecycle obtain Clinical Evidence develop and maintain the Technical Documentation / STED use the Quality Management System suitable for medical devices fulfill the requirements for post-market surveillance as part of life cycle management Make suitable Quality Agreements
Regulatory environment
The Medical Device Directives regulate the placing on the market and
putting into service of medical devices: Active implantable Medical Device Directive (AIMDD) 90/385 EEC, 1st January 1995 Medical Device Directive (MDD) 93/42/EEC, 13th June 1998 In Vitro Diagnostic Devices (IVD) 98/79/EC, 7th December 2003.
CE-marking process for each Medical Device showing conformity with the European Directive and the Essential Requirements therein.
Drug-device combinations
In deciding how a drug-device combination is to be regulated, it is the
ancillary action, the medicine or drug used must already have regulatory approval for use in that particular application and intended use.
Examples of medical devices that incorporate
medicines and are regulated as medical devices are - catheters with anticoagulant coatings, - drug eluting coronary stents and - antiseptic wound dressings.
Examples of medicinal products that
incorporate an ancillary medical device are - pre-filled syringes, - nicotine patches and - contraceptive implants.
medicinal product when the drug is incorporated or contained within the device for later release.
The device part of a drug-device combination that is regulated as a
medicinal product, must still meet the requirements of the Medical Devices Directive, but CE marking is not applied.
Classification
CLASSIFICATION
NOTIFIED BODY
A Notified Body is a certification organisation
which the national authority (the Competent Authority) at a Member State designates to carry out one or more of the conformity assessment procedures described in the annexes of the Directives.
The Medicines and Healthcare products
Regulatory Agency (MHRA) is the UK Competent Authority under the 3 Medical Devices Directives.
A Notified Body must be qualified to perform
all the functions set out in any annex for which it is designated. The designation may be restricted to specified types of devices and/or Annexes.
CE marking (1)
A CE mark is given by a Notified Body to a medical device once
it has been assessed that the device is conform the Medical Device Directive.
Class I devices are self certified Conformance to the MDD is demonstrated by showing
CE marking (2)
All EU Member States
accept CE marked devices and can CE mark devices for circulation in the EU.
Mutual Recognition
Agreements are being, or have been, negotiated with Switzerland, Australia, New Zealand, USA and Canada.
Turkey, Croatia and
Macedonia are candidate countries to join the EU; they also accept CE marked devices.
'the device must meet the Essential Requirements set out in Annex 1 which apply to them, taking into account the intended purpose of the device concerned'.
Within the EU, meeting the Essential Requirements is
necessary when registering the product with an appointed EU representative registered with a Competent Authority or the Competent Authority itself.
Once a product has been successfully classified as a
E S S E N T IA L R ESSENTIAL REQUIREMENTS E Q U I R E M E N T S (2) Requirements regarding design and construction: Safety of materials including: toxicity flammability animal origin compatibility biological tissues, cells and bodily fluids medicinal products Sterilising methods and suitability Use of sterile products and conditions of use Safety of devices that are connected to an energy source Mechanical, electrical, electromagnetic and devices that radioactive safety Accuracy of devices with measuring functions Labelling and information supplied with a device Specific requirements for instructions for use.
investigations are appropriate and the requirements for each of the routes.
repeated use (if designed to be re-used on separate multiple occasions e.g. as part of a surgical procedure)
lifespan of e.g., implantable devices.
Non-clinical data on e.g. 'wear testing' can be taken into account, but ultimately clinical use and in vivo testing can provide more reliable data
gather, compile and monitor post-marketing information about the device derived from various sources, including - customers and users, - market feedback, - competitor product information, - published literature.
Appropriate effective actions must be taken to ensure product safety. The updated MEDDEV guidance reflects the heightened importance of
post marketing surveillance, and the efforts underway to broaden the scope and awareness of device safety information on a global basis.
Continual improvement
Implanon Implanon NXT
X-ray visible, new applicator and new lidding
as non-sterile products.
This recall has been initiated due to concerns from a customer
about potential contamination of the products with an objectionable organism, namely Bacillus cereus.
Third parties: Cardinal Health,
PSS Select, VersaPro, Boca/ Ultilet, Moore Medical, Walgreens, CVS, Conzellin
January 5, 2011
with the Finnish branch of one of the worlds leading medical companies, Novartis. The companies have started up a pilot project, the aim of which is to develop more targeted care for those suffering from Type 2 diabetes. Taking part in the pilot project will be 12 Helsinki clinics as well as 500 Finnish patients with Type 2 diabetes.
All patients will receive common directions to time their blood
glucose measurements, but the timing will nonetheless follow the individuals daily routines. The medical staff will then get an indication of how the blood glucose behaves and evaluate the different treatment options.
Physicians can use mobile phones to calculate prescription dosages, review disease treatment guidelines, and expliain diagnoses and procedures to patients. The FDA expects that by 2015, 500 million smartphone users will rely on health care apps.
Conclusion
When medicine meets technology new combinations are formed, that
provide new exciting solutions to users; pose different/extra requirements to development