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Regulatory Processes for Nanomedicine in Europe

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Regulatory Processes for Nanomedicine in Europe

 

(An overview of regulatory processes in non-European countries is available here)

To get a first introduction to the regulatory ecosystem for nanomedicine please take a look at the publication of the European Medicines Agency (EMA) which can be downloaded here.

In addition, EMA has published four reflection papers on nanomedicine-specific issues.

The procedure for medicinal products such as drugs is different from the process for medical devices.

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Medicinal Products are defined in the Directive 2001/83/EC on Medicinal Products for Human Use as:

(a) Any substance or combination of substances presented as having properties for treating or preventing disease in human beings; or

(b) Any substance or combination of substances which may be used in or administered to human beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis.

A complete list of regulation agencies in all Member States and at the European level including contact data can be found here.

Our advice is to contact a National Agency or the European Medicines Agency (EMA) as early as possible to discuss the requirements to be fulfilled to get their approval. Start with a National Agency is recommended.

The centralised procedure is mandatory for the following diseases and products :

  • AIDS, cancer, diabetes
  • Neurodegenerative diseases
  • Advanced therapy medicinal products (for advice on classification, click here)
  • Medicinal products derived from biotechnology processes such as genetic engineering
  • Orphan medicines.
An option exists of submitting an application for medicines:

  • that stand for a significant therapeutic, scientific or technical innovation
  • whose authorisation would be in the interest of public or animal health.
Centralised procedure for authorising medicinal products is laid down in Regulation EC No 726/2004:

 

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In case of a positive decision, EU commission grants centralised market authorisation valid in all EU/EEA states for 5 years and publishes a European Public Assessment Report (EPAR) on the EMA homepage.

The Common Technical Document (CTD) is a mandatory and internationally agreed documentary format which proves pharmaceutical quality, safety and efficacy of a medicinal product. Developed by EMA (Europe), FDA (USA) and the Ministry of Health, Labour and Welfare (Japan), it is required for all medical product applications submitted to regulatory authorities in the above-mentioned countries. The dossier can be also submitted electronically (eCTD).

To cover the cost for the long and expensive regulatory process a number of different European sources of financing for SMEs exist. A list of currently available EU initiatives to assist SME's with financing can be consulted here.

In addition, EMA has published some valuable information on EU and national incentives for SMEs.

EMA and the National Agencies provide customised advice sessions for applicants which are dutiable. EMA, for example, has an Innovation Task Force which is happy to learn and discuss about general very new nanotechnological and biomaterial developments.

More recently, EMA has launched two new initiatives to speed up the development process and the availability of new medicines for patients.  With PRIME (PRIORITY MEDICINES) EMA issues guidance on a company’s overall development plan and regulatory strategy by providing scientific advice at key development milestones, involving additional stakeholders such as health technology assessment bodies or patients. The prerequisite to enter this process is the availability of preliminary data indicating a major therapeutic advantage to patients with an unmet medical need.

The second new process is called MAPP's (Medicines Adaptive Pathways to Patients). In this case the efficacy and safety of new medicines are tested on a small group of patients selected to be a good target by biomarkers, for example. The preliminary market access based on these data has to be extended and confirmed with “real life” data from patient registers and follow-up studies.

Published four times a year by the European Medicines Agency, the SME OFFICE NEWSLETTER provides helpful information for SMEs in the EU regulatory environment for medicines.

Regulatory Process for Medical Devices:

As stated in the beginning, the regulatory process to get market approval for a Medical Device is different and based on the Directive on Medical Devices 93/42/EEC.

(a) 'Medical Device' means any instrument, apparatus, appliance, software, material or other article, whether used alone or in combination, including the software intended by its manufacturer to be used specifically for diagnostic and/or therapeutic purposes and necessary for its proper application, intended by the manufacturer to be used for human beings for the purpose of:

- diagnosis, prevention, monitoring, treatment or alleviation of disease,

- diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap,

- investigation, replacement or modification of the anatomy or of a physiological process,

- control of conception,

and which does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means but which may be assisted in its function by such means.

The above mentioned Directive 93/42/EEC had been under revision.

The resulting Medical Device Regulation (MDR) and the in vitro Diagnostic Medical Devices Regulation (IVDR) were officially published on May 5th 2017 and entered into force on May 25th 2017. The MDR (EU) 2017/745 replaces EU current Medical Device Directive (MDD 93/42/EEC) and EU Directive on active implantable medical devices (AIMDD 90/385/EEC). The IVD (98/79/EG) does not merge into MDR but has been replaced by an own regulation: (EU)2017/746. As these are regulations and not directives, they require no particular transformation into national law.

Both regulations will substantially change the process and will make it more demanding and time and resource consuming. The biggest changes are:

  • Notified Bodies lose their status. They will have to be audited again which is earliest possible six months on the effective date of MDR. Thus, Notified Bodies will first be able to start accepting applications according to MDR in summer 2018
  • The technical documentation needs to be much more detailed
  • More products will require clinical trials which also need to be updated by post market monitoring
  • Additional oversight of the complete supply chain including importers and distributors. To achieve this, a central data bank for medical products (EUDAMED) will be introduced and a Unique Device Identification (UDI) number will be implemented which has to be put on each MD. As UDI data bank has not been introduced yet and EUDAMED specifications still have to be defined by the EU commission until 26th May 2018, a practical realisation of these regulations will take time
  • Unannounced audits by Notified Bodies in post market surveillance
  • Manufacturers need an authorised representative knowledgeable and responsible for regulatory compliance ensuring the declaration of conformity, performance evaluations and vigilance requirements are kept up-to-date.

 

It is expected that 80 – 90% of all IVDs will require regulatory review by Notified Bodies in contrast to the current 20%. The transition phase for issuing certifications according to MDR will be three years, for the IVDR it will last five years.

At present, the regulatory process is as follows:

Regulatory Process for Medical Devices.png

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Role of Notified Bodies:

A Notified Body is an organization that has been accredited by a Member State. It assesses medical devices whether they conform to fixed standards, e. g.: the EU Medical Devices Directive (MDD). Assessment can include inspection and examination of a product, its design and manufacture.

The EU member state will inform the European Commission whether a product complies with standards or not, and the name of the Notified Body will be disclosed. With a Declaration of Conformity, the manufacturer is entitled to label the product with the CE Mark which is required for distribution and sale in the EU.

Manufacturers may individually choose a Notified Body within the EU insofar as it is accredited for the execution of the relevant conformity assessment procedure. To view a complete list of Notified Bodies within the EU, please click here.

In case you need further help do not hesitate to contact us directly.

 

An overview of regulatory processes in non-European countries is available here!

 

Ecosystem of Nanomedicine:

EU Regulatory Process  >> International Regulatory Processes >> Clinical trials >>  Pricing and Reimbursement

Contact:

Should you have any question or require further information related to the ecosystem of Nanomedicine, please contact:

Dr. Klaus-Michael Weltring
Gesellschaft für Bioanalytik Münster e. V.
Tel. +49 (0)251 38450333
weltring@bioanalytik-muenster.de

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