Alle items (29)
Via our strategic partner in the US we're able to support you with US Agent Service. Please contact us if you need more information.
US Agent
Every company that is involved with production or distribution of medical devices intended for the USA (manufacturer, packager, exporter, importer, specification developer, etc) must: register with US FDA, list the devices by category, and if foreign, must have a US Agent.
Each year by December 31st, each registered company must renew its registration.
Economic Operators:
Contract Manufacturer
Manufactures a finished device to another establishment's specifications.
Contract Sterilizer
Provides a sterilization service for another establishment's devices.
Foreign Exporter
Exports or offers for export to the United States (U.S.), a device manufactured or processed by another individual, partnership, corporation or association in a foreign country, including devices originally manufactured in the United States. A foreign exporter must have an establishment address outside the U.S.
Initial Distributor
Takes first title to devices imported into the U.S. An Initial Distributor must have a U.S. address.
Manufacturer
Makes by chemical, physical, biological, or other procedures, any article that meets the definition of "device" in Section 201(h) of the Federal Food, Drug, and Cosmetic (FD&C) Act.
Repackager
Packages finished devices from bulk or repackages devices made by a manufacturer into different containers (excluding shipping containers).
Relabeler
Changes the content of the labeling from that supplied from the original manufacturer for distribution under the establishment's own name. A relabeler does not include establishments that do not change the original labeling but merely add their own name.
Reprocessor of Single Use Devices
Performs remanufacturing operations on a single use device.
Specification Developer
Develops specifications for a device that is distributed under the establishment's own name but performs no manufacturing. This includes establishments that, in addition to developing specifications, also arrange for the manufacturing of devices labeled with another establishment’s name by a contract manufacturer.
U. S. manufacturer of export only devices
Manufactures medical devices that are not sold in the U.S. and are manufactured solely for export to foreign countries.
Via our strategic partner in the US we're able to support you with US Agent Service. Please contact us if you need more information.
US Agent
Every company that is involved with production or distribution of medical devices intended for the USA (manufacturer, packager, exporter, importer, specification developer, etc) must: register with US FDA, list the devices by category, and if foreign, must have a US Agent.
Each year by December 31st, each registered company must renew its registration.
Establishment Registration
Establishments involved in the production and distribution of medical devices intended for marketing or leasing (commercial distribution) in the United States (U.S.) are required to register with the FDA. This process is known as establishment registration. Registration provides FDA with the location of medical device manufacturing facilities and importers. The regulations for establishment registration are provided in 21 CFR 807. All establishment registrations must be submitted electronically unless a waiver has been granted by FDA. Congress has also authorized FDA to implement a user fee for certain types of establishment registrations processed after September 30, 2007. Your registration is not considered complete until FDA has been notified that all requirements have been met.
Establishment
Any place of business under one management at one physical location at which a device is manufactured, assembled or otherwise processed for commercial distribution.
Owner / Operator
The corporation, subsidiary, affiliated company, partnership, or proprietor directly responsible for the activities of the registering establishment. The owner/operator is responsible for registering the establishment.
Registration of an establishment is not an approval of the establishment or its products by FDA. That is, it does not provide FDA clearance to market. Unless exempt, premarketing clearance or approval is required before a device can be placed into commercial distribution in the U.S.
Misbranding by Reference to Establishment Registration Number: Title 21 of the Code of Federal Regulations, Section 807.39, states, "Registration of a device establishment or assignment of a registration number does not in any way denote approval of the establishment or its products. Any representation that creates an impression of official approval because of registration or possession of a registration number is misleading and constitutes misbranding." Product labeling and Internet sites cannot reference your establishment registration number or make reference to your establishment being registered or approved by FDA. If your product labeling or Internet sites list your establishment registration number or makes reference to your establishment being registered and approved by the FDA, then these references must be removed.
Who Must Register
Manufacturers
An owner/operator of an establishment not exempt under 21 CFR 807.65 who is engaged in the manufacture, preparation, propagation, compounding, assembly, or processing of a medical device intended for commercial distribution (marketing) is required to register. This includes manufacturers, contract manufacturers and contract sterilizers that place the device into commercial distribution, specification developers, repackagers or relabelers, reprocessors of single-use devices, remanufacturers, U.S. manufacturers of export only devices, and manufacturers of components or accessories that are ready to be used for any intended health-related purpose and are packaged or labeled for commercial distribution for such health-related purpose (that is, manufacturers of components or accessories that are intended to be sold or leased directly to the end user.)
Initial Distributor
An initial distributor (or importer) takes first title to the devices imported into the U.S. and further distributes the devices. Initial distributors/importers are required to register. However, they are NOT required to list the devices that they import.
Foreign establishments (manufacturers and exporters)
Foreign establishments that manufacture, prepare, propagate, compound, or process a device that is imported, or offered for import, into the U.S. are required to register their establishments. This includes contract manufacturers and contract sterilizers. Foreign establishments must also list the devices that they export to the U.S.
Definitions of establishment activities are provided below. Prior to registering your establishment, please review the definitions and determine what type of activities your establishment is performing. Please note that most establishments are also required to list their devices.
Please note that the following groups are not required to register:
- Wholesale distributors of devices who do not manufacturer, repackage, process or relabel a device. A "wholesale distributor" is defined as any person (other than the manufacturer or the initial importer) who distributes a device from the original place of manufacture to the person who makes the final delivery or sale of the device to the ultimate consumer or user.
- Refurbishers and domestic distributors.
Establishment Registration Fee
The following types of establishments are required to pay the establishment registration fee to the US FDA:
- Device manufacturers Contract sterilizers Contract manufacturers Single-use device reprocessors Specification developers.
- US Agent for Foreign Establishments
- All foreign establishments must advise and notify FDA of the name, business name, address, phone number, and email address of their designated US Agent.
Responsibilities of US Agent
The responsibilities of the US Agent include:
- assisting FDA in communications with the foreign establishment,
- responding to questions concerning the foreign establishment's products that are imported or offered for import into the United States, and
- assisting FDA in scheduling inspections of the foreign establishment.
If the FDA is unable to contact the foreign establishment directly or expeditiously, FDA may provide information or documents to the US Agent, and such an action shall be considered equivalent to providing the same information or documents to the foreign establishment.
- The US agent has no responsibility to report adverse events under the Medical Device Reporting regulation (21 CFR Part 803), or to submit Premarket Notifications [510(k)] (21 CFR Part 807, Subpart E)
- The US Agent must be designated at the time of electronic submission of establishment registration information.
When to Register
Domestic establishments must register within 30 days of the establishment entering into any activity requiring registration, including processing devices for exportation outside of the U.S. If you are required to list your devices, you must submit device listing information at the time of initial registration.
Foreign establishments must register, notify their US Agent, as well as list their devices prior to exporting to the U.S.
Your registration must be renewed annually each year. The registration period extends from October 1st through September 30th.
How to Register
In September, 2007, Section 207 of the Medical Device User Fee Modernization Act of 2002 (MDUFMA) amended section 510 of the Federal Food, Drug and Cosmetic Act (the Act) to require electronic submission of device registration and listing information unless FDA grants a waiver request. MDUFMA also authorizes FDA to collect a user fee for annual registration of certain types of establishments. Effective October 1, 2007, all establishment registrations are to be submitted electronically using FDA’s Unified Registration and Listing System (FURLS), unless a waiver has been granted by FDA.
Note:
If you are required to list your devices, you must submit that information at the same time as you submit establishment registration information. Establishments must register within 30 days after entering into any activity requiring registration or prior to importing or exporting a device.
Establishments must pay their establishment registration fee and receive notification from FDA that their payment has been received by December 31 of each year for their registration to be considered active and current for the fiscal year (October 1st through September 30th). It can take up to two weeks for your payment to be processed. You are not considered registered for the new fiscal year until FDA has notified you that your payment has been received.
Updating Registration Data
All registration information must be verified annually between October 1st and December 31st of each year. Establishments must pay their establishment registration fee by December 31 of each year for their registration to be considered active and current for the fiscal year (October 1st through September 30th).
Definitions of establishment activities
Contract Manufacturer
Manufactures a finished device to another establishment's specifications and places the device into commercial distribution. (Please note that contract manufacturers are also required to list their devices).
Contract Sterilizer
Provides a sterilization service for another establishment's devices and places the device into commercial distribution. (Please note that contract sterilizers are also required to list the devices sterilized at their establishment).
Foreign Exporter
Exports or offers for export to the United States, a device manufactured or processed by another individual, partnership, corporation or association in a foreign country, including devices originally manufactured in the U.S. A foreign exporter must have an establishment address outside the U.S.
Manufacturer
Makes by chemical, physical, biological, or other procedures, any article that meets the definition of "device" in section 201(h) of the Federal Food, Drug, and Cosmetic (FD&C) Act.
Re-Manufacturer
Processes, conditions, renovates, repackages, restores, or does any other act to a finished device that significantly changes the finished device's performance, safety, specifications, or in any way changes the intended use.
Repackager and / or Relabeler
Repackager: Packages finished devices from bulk or repackages devices made for the establishment by a manufacturer into different containers (excluding shipping containers).
Relabeler: Changes the content of the labeling from that supplied from the original manufacturer for distribution under the establishment's own name. A relabeler does not include establishments that do not change the original labeling but merely add their own name.
Initial Distributor / Importer
Takes first title to devices imported into the United States. An initial distributor must have a U.S. address.
Specification Developer
Develops specifications for a device that is distributed under the establishment's own name but performs no manufacturing. This includes establishments that, in addition to developing specifications, also arrange for the manufacturing of devices labeled with another establishment's name by a contract manufacturer.
Reprocessor of Single-Use Devices
Performs remanufacturing operations on a single-use device.
U.S. Manufacturer of Export Only Devices
Manufactures medical devices that are not sold in the U.S. and are offered solely for export to foreign countries.
Frequently Asked Questions
How much does registration cost? Appropriate fees are charged annually.
How long is my registration valid? Each establishment registration is valid for one fiscal year. Firms must complete their annual registration establishment requirement each year for the registration to be valid.
Does registration or device listing fulfill my Premarket Notification 510(k) requirements? No. The establishment registration and device listing requirement is a separate requirement from the Premarket Notification 510(k) submission process. See Device Advice for information on how FDA regulates devices including how to submit a 510(k).
I am a distributor located outside the U.S. Do I have to register? Yes, foreign exporters must register their establishment, list the devices exported to the U.S., and identify the designated US Agent.
Are foreign dental and optical laboratories required to register and list? Yes, foreign dental and optical laboratories are required to register and list. They are not exempt from registration and listing. The exemption in 21 CFR 807.65(i) only applies to domestic establishments.
My establishment only does design work. Am I required to register the establishment? Company owned design facilities must register. That is, if a manufacturer owns a manufacturing facility and a separate facility for design work, both must register. Third party design facilities (design contractors) are not required to register. The manufacturer that contracts out the design work is responsible for maintaining the design control documentation in accordance with 21 CFR 820.30.
In addition to registration, foreign companies must also designate a qualified U.S. Agent.
<< Content copyright US FDA and obtained from the US FDA website at www.fda.gov >>
Via our strategic partner in the US we're able to support you with US Agent Service. Please contact us if you need more information.
US Agent
Every company that is involved with production or distribution of medical devices intended for the USA (manufacturer, packager, exporter, importer, specification developer, etc) must: register with US FDA, list the devices by category, and if foreign, must have a US Agent.
Each year by December 31st, each registered company must renew its registration.
Medical Device Listing
All medical devices that are manufactured and imported into the U.S. are required to be listed with the FDA. Firms that are required to list their devices are those that:
- manufacture
- repackage and relabel
- develop specifications
- reprocess single-use devices
- remanufacture
- manufacture accessories and components sold directly to the end user
A separate device listing form must be submitted for each type of device.
Medical Device Listing as required by the US FDA to export your product to the USA
What Is Medical Device Listing
Most medical device establishments required to register with FDA must also identify to FDA the devices they have in commercial distribution including devices produced exclusively for export. This process is known as 'medical device listing' and is a means of keeping FDA advised of the generic category(s) of devices an establishment is manufacturing or marketing. The regulations for medical device listing are provided in 21 CFR 807.
Each generic category is represented by a separate classification regulation found in Title 21 Code of Federal Regulations Parts 862-892 or FDA assigned device name. Each regulation number or device name is associated with one or more product codes. Regulation numbers with more than one product code identifies the product in further detail. For example, "Manual Surgical Instruments for General Use," 21 CFR 878.4800, contains several product codes including GAB (disposable suturing needle), GDX (scalpel), HTD (forceps) and HRQ (hemostat).
Listing of a medical device is not approval of the establishment or a device by FDA. Unless exempt, premarketing clearance is required before a device can be marketed (placed into commercial distribution) in the U.S.
All device types classified as exempt from the Premarket Notification 510(k) requirements are subject to the limitations of exemptions. Limitations of device exemptions are found in the device classification chapters in 21 CFR xxx.9, where xxx is replaced with Parts 862-892 (e.g., 862.9, 864.9, etc.). Please be aware that it is your responsibility to ensure that you meet the exemption criteria and that your device does not exceed the limitations of exemption. If your device exceeds the limitations of exemption, you must submit a 510(k) and receive a letter from FDA stating that your device may be commercially distributed in the U.S. prior to marketing your device.
While there is no separate fee for listing your device, device listing is completed as part of the annual registration process. Many device establishment types are subject to an annual registration fee.
Who Must List
An owner/operator of an establishment not exempt under 21 CFR 807.65 who is engaged in the manufacture, preparation, propagation, compounding, assembly or processing of a medical device intended for commercial distribution (marketing) is required to list its device with FDA within 30 days of entering the device into commercial distribution in the U.S. This includes manufacturers, repackagers and relabelers, specification developers, reprocessors of single-use devices, remanufacturers, U.S. manufacturers of export only devices, and manufacturers of accessories and components that are ready to be used for any intended health-related purpose and are packaged or labeled for commercial distribution for such health-related purpose (that is, manufacturers of components or accessories that are intended to be sold or leased directly to the end user.) (21 CFR 807.20). Foreign manufacturers and foreign exporters must list their devices prior to importing into the U.S.
Domestic contract manufacturers and contract sterilizers are required to register their establishment and list their devices if they commercially distribute the devices. Initial importers located in the U.S. are required to register their establishment; they are not, at this time, required to list their devices.
The following establishment types are required to list their devices:
Contract Manufacturer
Manufactures a finished device to another establishment's specifications and places the device into commercial distribution.
Contract Sterilizer
Provides a sterilization service for another establishment's devices and places the device into commercial distribution.
Manufacturer
Makes by chemical, physical, biological, or other procedures, any article that meets the definition of "device" in section 201(h) of the Federal Food, Drug, and Cosmetic (FD&C) Act.
Remanufacturer
Processes, conditions, renovates, repackages, restores, or does any other act to a finished device that significantly changes the finished device's performance or safety specifications, or in any way changes the intended use.
Repackager and / or Relabeler
Repackager: Packages finished devices from bulk or repackages devices made for the establishment by a manufacturer into different containers (excluding shipping containers).
Relabeler: Changes the content of the labeling from that supplied from the original manufacturer for distribution under the establishment's own name. A relabeler does not include establishments that do not change the original labeling but merely add their own name.
Specification Developer
Develops specifications for a device that is distributed under the establishment's own name but performs no manufacturing. This includes establishments that, in addition to developing specifications, also arrange for the manufacturing of devices labeled with another establishment's name by a contract manufacturer.
Foreign Exporter
Exports or offers for export to the United States, a device manufactured or processed by another individual, partnership, corporation or association in a foreign country, including devices originally manufactured in the U.S. A foreign exporter must have an establishment address outside the U.S.
Reprocessor of Single-Use Devices
Performs remanufacturing operations on a single-use device.
U.S. Manufacturer of Export Only Devices
Manufactures medical devices that are not sold in the U.S. and are offered solely for export to foreign countries.
Note: Initial distributors (importers) located in the U.S. are not required to list their devices. However, they are required to register their establishment. Refurbishers and domestic distributors are not required to list their devices or register their establishment.
When to List
When an owner/operator of a domestic establishment enters into an activity that requires registration, device listing much be completed at the time of registration for the establishments that are required to list as discussed above under "Who Must List."
The owner/operator must also submit a device listing when it introduces a device into commercial distribution that has a classification name or product code that is not currently listed.
Foreign establishments must to submit device listings prior to exporting their devices to the United States. Registered establishments are also required to review and update their listing information once per year, during the registration period of October 1st to December 31st of each year. You can update your device listing(s) at any time. We encourage you to update your device listings at time the change occurs.
Sunglasses, Spectacle Frames, Spectacle Lens and Magnifying Spectacles
Sunglasses, spectacle frames, spectacle lens, and magnifying spectacles are medical devices exempt from the Premarket Notification 510(k) submission to the Food and Drug Administration (FDA). Although these devices are 510(k) exempt, several other FDA regulations apply:
- U.S. manufacturers and initial U.S. distributors (importer) must register their establishment with FDA;
- foreign manufacturers must register their establishment with FDA and name a United States Agent;
- manufacturers must list their device with FDA.
- manufacturers must meet Quality System (QS) requirements,
- the lens for spectacles and/or sunglasses must be certified as impact resistant.
How to List
All listing information (new, updates or annual review) must be submitted electronically unless FDA grants you a waiver. Electronic registration and listing is completed through FDA’s United Registration and Listing System (FURLS).
Updating Listing Data The official correspondent of each establishment is responsible for keeping their listing records current. You can update your device listing(s) at any time through FURLS.
The owner/operator must submit a device listing when it introduces a device into commercial distribution that has a classification name or product code that is not currently listed. We encourage you to update your device listings at time the change occurs. Updating is required when one of the following occurs: All models or variations of a listed device is removed from commercial distribution. That is, the product is discontinued. The commercial distribution of a previously-discontinued device is resumed. There is a change in the type of activity performed on a device, such as where it is being manufactured. You are encouraged to identify proprietary names or trade names to distinguish various models of the same device.
<< Content copyright US FDA and obtained from the US FDA website at www.fda.gov >>
What is the practical impact for a medical device manufacturer that has a UK-based Authorized Representative?
This is going to have a huge impact if a manufacturer has their Authorized Representative (EU AR) currently based in the UK.
As indicated in the European Commission notice, there is an Implication of the Brexit is that an UK office based AR will no longer be valid under EU law. We suggest that manufacturers must discuss the situation with their AR. Alternatively, contact a professional (qualified, registered, and has an PRRC in their team) AR service provider.
The significant impact for manufacturers is that all product labeling must identify the Authorized Representative, including their address and contact information. If a company sells thousands of products with a UK AR, the change to labeling alone is a significant impact.
If you are based in the UK, it’s important to remember that we anticipate that as of March 30, 2019, you will need to appoint an EU-based Authorized Representative, and that AR needs to be added and/or updated on your product labeling.
What we do?
We assist manufacturers and consultants by delivering integrated business solutions, which include European Authorized Representative (AR) services (MDR / IVDR) and Legal Representative Services (pharma companies). We act as legal entity towards the European Competent Authorities to ensure all issues will be handled effectively and in compliance of the European requirements.
We representate your company to all member states of the European Union (EU) as required by law: 'Act and to be addressed by authorities and notified bodies in the EU instead of you as manufacturer, with regard to the obligations of the manufacturer under EU Directive, as and when required ‘.
A manufacturer of a medical device or of an in vitro diagnostic device cannot simply have a post office box located in the EU, but is obliged by EU law to appoint an authorized representative to competent authorities. In this way, there is no need to open an office within the EU.
As your EU Authorized Representative (AR) we are legally responsible and accountable for:
- Retention of all technical documentation and certificates so that this can be readily provided to both Competent Authorities (CA) and Notified Bodies (NB)
- Notification and reports concerning Post-Market Clinical Follow-up (PMCF) issues, (i.e. incident reporting, product recalls and Field Safety Corrective Actions (FSCA) to any CA according to the local requirements and to Meddev guidelines in each EU Member state
- Notification of significant changes of your medical device to any CA
- Notification of clinical investigations to any CA
- Maintenance of clinical reports required by any CA
As your EU AR it is required that our contact information must be included in all product related communication materials, such as product labels, IFU, inserts, and manuals.
As your EU AR we
- represent you as a non EU manufacturer to all EU member states, including UK after the Brexit
- submit to the electronic system information as referred to in Annex V (part A) before your medical device is placed on the market and or before applying to a notified body (MDR requirement)
- notify you when your CE-marked medical devices is registered as approved by any Competent Authority
- maintain your technical product documents and files, as required by the MDR (art 9,3)
- provide Competent Authorities all information and documents necessary to demonstrate the conformity of your medical device
- cooperate with the Competent Authority on any corrective action
- notify EU Competent Authorities in case of severe adverse event (SAE) and serious incidents
- interface on your behalf between Competent Authorities, Notified Body and your distributors or end-users
- monitor changes in regulatory requirements and contact you when there are issues that deserve your attention
- perform an annual review of your technical file content to confirm the accuracy of the data
- Co-sign the Declaration of Conformity (DoC)
- support you to arrange covering product liability as required in the MDR
Optional services we can provide may include the following:
- Post market Vigilance and feedback
- Apostille and legalization of Free Sales Certificates (FSC)
- Post market clinical evaluation
- Handling notifications of clinical investigations
- Supply chain control
- Preparations for unannounced audits or inspections
- Product liability insurance
- Risk management
- Logistics solutions
MRM is proud to be a full Associate of EAAR
, which stands for Quality, Reliability, and Professionalism.
If you already have an EU AR, but would like to maximize the services you receive, then engage MRM; we provide a smooth and transparent transition. Our transition procedure is seamless and simple. Please contact This email address is being protected from spambots. You need JavaScript enabled to view it. for a quotation.
ISO 13485:2016 (ISO/TC 210)
The new ISO 13485:2016 (Published February 25, 2016) specifies an effective framework to implement and to be in compliance of regulatory requirements specific for medical technology organizations and or related service providers.
Implementation of ISO 13485:2016 ensures effectiveness of operational processes such as research, design & development, production, installation, delivery of medical devices. Further, adequate implementation ensures the medical devices are safe for their intended purpose. The ISO 13485:2016 is also applicable across the whole supply chain and seeks the entire lifecycle of a medical device.
Implementation of ISO 13485:2016 ensures compliance with regulatory requirements, adequate risk management, and best practice for quality and safety.
In the process of implementation we’ll suggest to consider to implement also relevant key requirements of the Medical Device Regulations (MDR) and the In Vitro Diagnostic Regulations (IVDR). The impact of the mandatory requirements of ISO 13485:2016, the MDR (MDD and AIMDD) and the IVDR (IVDD) is significant! Consequently requires these standards higher investments from medical technology manufacturers and related companies to be in compliance with the new EU regulations & requirements. Although the transition period of maximum three years we advise you to anticipate on these changes in a pro-active and timely manner to avoid having CE certificates suspended or revoked.
In summary, there are basically five sections in the standard of the ISO 13485 where major changes have been made:
Regulatory requirements
The first section establishes an emphasis on regulatory requirements that we see across the standard. This includes not only the local requirements that apply to your facility, but if you are an organization that commercializes its products globally, you also need to take into consideration all relevant international requirements. There are many references to this throughout the ISO 13485:2016 standard.
Risk management
Another theme that permeates the standard is the need to incorporate risk management into all the main quality system processes within your organization. Almost everything you do needs to be based on that risk, justifying that what you are doing is adequate and conforms to what you defined as part of your design and production activities.
Validation, verification, and design transfer
The ISO 13485:2016 standard puts a lot more structure into place surrounding these activities. You must have plans in place and documented evidence to show what you have been doing for validation, verification, and design transfer activities.
Outsourced processes and supplier control
The ISO 13485:2016 standard asks organizations to do a lot more when it comes to outsourcing processes and putting into place controls for assessing your suppliers — again based on risk.
Feedback
Finally, the ISO 13485:2016 requires you to monitor and measure the performance of your quality management system not only during production, but also post-market. You also have to incorporate those activities as part of your risk management process.
Interconnection of other requirements
The linkage between all the different clauses within the standard is improved. Everything is more interconnected. Expectation is that you have systems in place that allow you to demonstrate conformity across the requirements in a more streamlined manner. For example, there is not just one section that discusses risk-management or regulatory requirements or CAPA — instead we see these topics addressed throughout the standard. It is a much more integrated approach.
If you need support, training and or if you would like to maximize your QA / RA services you, please contact us via This email address is being protected from spambots. You need JavaScript enabled to view it..
Als producent van een medisch hulpmiddel bent u eindverantwoordelijk dat uw CE gemarkeerde medische producten in overeenstemming zijn en blijven met die EU Directieven die van toepassing zijn. Het maakt hierbij niet uit of u de productie van een deel of van componenten aan anderen uitbesteedt hebt.
CE Markering
Verkrijgen van een CE markering vereist een tweetal items: veelal ISO 13485 certificatie van het kwaliteitssysteem; en review van het Technisch Dossier.
Het kwaliteitssysteem is primair gericht op controles in ontwikkeling en productie en vereist daarmee ook het ontwerpen van standaard procedures (SOP's). Tijdens het certificatieproces zal de Notified Body (NB) de mate van overeenstemming tussen de werkelijkheid en de SOP's verifiëren en beoordelen.
Training van personeel, identificatie en traceerbaarheid van producten, specificaties in het ontwerp, borging in productie en risico management zijn belangrijke onderwerpen die in het kwaliteitssysteem geborgd dienen te zijn en ook bijzondere aandacht krijgen van de NB.
Het Technisch Dossier dient te bestaan uit overzichten van informatie en data die aantonen dat het medisch product voldoet aan geldende veiligheid- en prestatie-eisen die in verschillende standaarden zijn vastgelegd. Typische aanvullende informatie die in het technisch dossier behoort opgenomen te zijn: biocompatibiliteit, sterilisatie en productprestatie.
Het risico management dossier omvat een samenvatting zoals deze is vastgelegd in de ISO 14971; en een klinisch evaluatierapport gebaseerd op literatuuronderzoek of data verkregen bij uitgevoerd onderzoek dan wel via clinical trials.
Risico Classificatie in het EU Proces en de impact op de CE Markering
In de EU kennen we een viertal risicoklassen, namelijk I (Is - Im), IIa, IIb, III. De beschrijving van ' beoogd gebruik' - ofwel de medische claim - bepaald uiteindelijk de risicoclassificatie. Dit is van belang omdat de notified body uiteindelijk akkoord geeft of de producent een literatuuronderzoek mag uitvoeren of een prospectief clinical trial. Deze beslissing is uiteraard van belang op het te doorlopen tijdspad, waarbij het tijdspad bij enkel een literatuuronderzoek aanzienlijk korter is. Het is verstandig om vooraf al met de (kandidaat) notified body contact op te nemen om ze in een vroeg stadium te betrekken bij het te volgen traject. Dit is niet alleen van belang voor het tijdspad maar ook voor het project budget.
Minder Data, Minder Tijd
Om een CE markering te kunnen en mogen plaatsen moet de producent aantonen dat een medisch hulpmiddel veilig is en presteert zoals beschreven in de handleiding (IFU).
Het presteren van het hulpmiddel kan redelijk snel aangetoond worden, namelijk door bijvoorbeeld een beperkt en niet gerandomiseerd klinisch onderzoek uit te voeren.
Vreemd genoeg vallen deze vereisten in scherp contract met de Amerikaanse klinische vereisten voor veel medische hulpmiddelen waarbij veelal een gerandomiseerd trial de norm is. Zodra de nieuwe 'Medical Device Regulations' (MDR) van kracht is zal deze significante veranderingen met zich meebrengen in het Europese regulatieve landschap. De criteria voor klinische evidentie zullen dan explicieter zijn.
Kortere Tijdslijnen
Gezien het redelijk eenvoudige classificatieproces en de focus op veiligheid en prestaties, kan een CE-markering meestal in een relatief korte tijd verkregen worden. Als de producent een kwaliteitssysteem heeft dat in overeenstemming is met de ISO 13485 en het Technisch Dossier is volledig, dan kan de tijdlijn variëren van twee tot drie - vier maanden vanaf het moment dat de audit uitgevoerd en het dossier ingediend is.
Gebruikmakend van EU data in de US
Als de producent de CE-markering met een kleine klinische trial kan verkrijgen, kunnend verkregen data en gegevens ondersteunend zijn bij de FDA.
De EU-gegevens kunnen vaak als ondersteuning bij een trialopzet worden gebruikt om de steekproefomvang te bepalen. In bepaalde omstandigheden kunnen deze meegenomen worden om te voldoen aan de Amerikaanse eisen. De rol van Europese data en gegevens bij de Amerikaanse aanvraag moet worden beoordeeld door de FDA tijdens een 'pre-submission' bespreking in het IDE-proces.
Wanneer geprobeerd wordt om EU data en gegevens te gebruiken is het van vooraf belangrijk te realiseren of de EU onderzoekssite op een eerder moment door de FDA beoordeeld is geweest bij uitgevoerde studies die bij de FDA zijn ingediend. Je wilt immers niet dat je studie een leerervaring van de site wordt.
Belangrijke Selecties
Selectie van de notified body is een belangrijke beslissing, omdat tussen de producent en de notified body overeenstemming bereikt moet worden met betrekking tot de classificatie en of er een literatuuronderzoek dan wel een prospectieve trial vereist is.
Aanvullend, als de producent geen fysiek kantoor in de EU heeft moet deze een Authorized Representative (AR) aanwijzen. Deze AR is verantwoordelijk voor productregistraties en vigilantie rapportages. Contactgegevens van de AR dienen op het label en IFU terug te vinden zijn.
Onze dienstverlening omvat o.a.
- Ondersteuning bij product classificatie en hulp bij de identificatie van de juiste standaarden bij een medische hulpmiddel (AIMDD - MDD > MDR; and IVD > IVDR)
- Opstellen en review van het technische product dossier ter verkrijging van de CE markering
- Verificatie van de Essentiele Eisen
- Implementatie, modificatie en onderhoud van het kwaliteitsmanagementsysteem - veelal ISO 13485
- Authorized Representative services in de EU
- Risicomanagement (ISO 14971)
- Opzet van vigilance en post -market surveillance procedure - inclusief 'Post Market Clinical Follow Up' (PMCF)
- QP Services - synoniem voor 'person responsible for regulatory requirements'
- Logistic Management
- Product aansprakelijkheid
Section 4 – Quality Management System
4.1.2 – General Requirements: The standard specifically states that a risk-based approach is needed when developing processes. That tells you that you can't just come up with, for example, a new preventative maintenance system. Have you considered a risk as well? Anything you do that affects the quality system needs to be viewed from that risk perspective. The standard also states that roles undertaken by the organization under regulatory requirements shall be documented.
4.1.3 – General Requirements: Records needed to demonstrate compliance with the standard and appropriate regulatory requirements shall be established and maintained.
4.1.5 – General Requirements: When you outsource processes, the standard wants you to look at the controls that are going to be put in place for that supplier, from a risk perspective. What happens if the supplier doesn't meet the specifications you provided? How will that affect your production cycle or anything that's related to that component? The standard wants organizations to consider those things ahead of time, so that you have controls in place to mitigate such issues right away.
4.1.6 – General Requirements: The standard will require validation of all computer software that is used as part of the quality system. While it has never been a requirement of ISO 13485, software validation has long been discussed in the industry, and not without some controversy. For example, questions arise like, “What if you use an Excel spreadsheet to control a process? Do you have to validate that spreadsheet?” Sometimes organizations don't even know where to begin with software validation — what to validate and how to validate it.
Under these revisions, computer software can be used for, but is not limited to, product design, testing, production, labeling, distribution, inventory control, data management, complaint handling, equipment calibration and maintenance, and corrective and preventive action. If software involves or affects the quality system, you need to validate it. Plus, you need to have a very specific justification for how you validated that software, keeping records associated with what you did and demonstrating that the software tool is doing what it's supposed to.
4.2.3 – Documentation Requirements: Another addition is the requirement to keep a file for the device that you're manufacturing, basically a technical file. In the past, this was addressed through the Medical Devices Directive, but it’s being added as part of ISO 13485. It lists 26 elements that ISO expects manufacturers to keep as part of the file, including product description, drawings, specifications, procedures, packaging specifications, instructions for use (IFU), labeling, clinical data, etc. This technical file concept is not new, but the standard will specifically require you to have it.
Section 5 — Management Responsibility
5.4.2 – Quality Management System Planning: This section contains a note clarifying what quality systems planning normally includes, namely quality objectives consistent with quality policy, action items to accomplish objectives, monitoring progress, and revision.
5.5.1 – Responsibility and Authority: The standard already requires that you specifically appoint personnel who will have responsibility and authority for execution and implementation of your quality system. However, the standard seeks more clarity about how those specific individuals are nominated as responsible for activities having to do with monitoring of the product, and also for post-production activities. Again, this goes back to the international aspect of every country having its own requirements of how they want quality issues reported, managed, and controlled. Going forward, you must determine what kinds of skills will be required of quality personnel and what responsibilities they need to have, and that has to be clearly defined.
5.5.2 – Management Representative: A note has been added stating that the responsibility of a management representative can include liaison with external parties, including regulatory authorities, on matters relating to the quality management system.
5.6.1 – Management Review; General: Although the revised standard still does not stipulate how often you should conduct management review meetings, it does ask for your rationale behind the frequency you choose. You can't just say, “I'm going to have them once a year.” You have to explain why you think holding them once a year is appropriate for your organization.
5.6.2 – Review Output: The standard states that Outputs of the Management Review shall include improvement needed to maintain the suitability and adequacy of the quality management system and its processes, the current standard only requires improvement to maintain effectiveness of the quality system and its processes.
Section 6 — Human Resources
6.2.– Human Resources, General: The ' old' standard requires personnel performing work affecting product quality, safety, or effectiveness to be “competent,” but the new standard breaks down the type of personnel to which this refers. For example, it is very specific about personnel who are involved with fulfilling process requirements, regulatory requirements, and quality system compliance. It also requires the organization to define what education, skills, and training those individuals need to have to perform each role.
6.2. – Competence, Training and Awareness: A new aspect of this section is the need to check the effectiveness of any training you're conducting. It states that, as an organization, you need to have a methodology to evaluate if the effectiveness of the training is commensurate with the risks associated with the work that an individual is performing. You won’t be able to just say, “Well, we trained them, we had a class, and they passed the exam.” Now, you need conduct risk assessment. What happens if the training was not clear enough? What are the consequences? What mitigation activities should we have in place in the organization to prevent mistakes from happening?
6.3 – Infrastructure: There is a heightened emphasis on maintenance-related activities. If you decide, as an organization, that maintenance is important, then you need to have very clearly documented procedures that specify how those activities are being performed, planned intervals for maintenance, and how records associated with how those activities are being maintained.
This section also now discusses ensuring that you handle orders in a streamlined way to prevent mix-ups that may affect the supply chain of your product.
Also in this section, information systems (IS) are now viewed as infrastructure, which isn’t the case in the current version of ISO 13485. The standard doesn’t require you to do anything differently; however, if this is something that may affect the quality of your product, you should have procedures, training, and personnel in place to manage related activities.
6.4 – Work Environment: The last part under section 6 deals with the work environment. The new standard has added a lot of stress on cleanliness and monitoring in clean rooms and manufacturing areas that deal with sterilized products, to ensure that you are monitoring for particles that could have an adverse effect on the product. They reference ISO 14644, the standard used for controlled environments, as guidance for medical device companies to use in managing clean rooms.
In general, this section contains more specificity about what is meant by the term “work environment.” They point out conditions to be considered such as noise, temperature, humidity, lighting, or weather, and areas of infrastructure such as inspection areas, storage areas, and distribution areas — but it can denote any area within an organization that is dealing with manufacturing the product.
6.4.2 – Contamination Control: Finally, then there is now a section on sterile medical devices. The standard asks you to take additional measures for these particular products, where you really need to prevent contamination with particulate matter or microorganisms, and maintain the degree of cleanliness during assembly or packaging operations.
Section 7 – Product Realization
7.1 – Planning of product realization: As with previous clauses, there is an increased focus on risk management in this section. One of the biggest changes to section 7.1 is a requirement to document how the risk management activities are being handled for product planning. The standard highlights several areas where risk management should be incorporated: verification, validation, revalidation, monitoring, testing, and traceability. You will need to conduct an assessment considering the risk as you’re planning for those activities, and that process has to be documented.
Also, a note was added asking organizations to look at IEC-62304, which is a guidance related to software lifecycle processes. If your device incorporates software, the guidance wants you to look at all the different lifecycles of that software, so you're planning ahead of time for future changes.
7.2.1 – Determination of requirements related to the product: The main elements that changed in this section, which is under 7.2 – Customer-related processes, is the addition of a requirement to determine user training to ensure that the product will be used in a safe and effective manner. (By user, it means the physician or the person who will install the device.) While training is sometimes taken into account by manufacturers, it's not always done consistently. This change seeks to ensure that the training process gets firmed up, and that there are more controls in place when it comes to training.
The other element that's new in section 7.2.1 is the requirement that organizations protect confidential health information from their customers. This information could arrive in two ways: It could be customer-provided feedback for the organization to incorporate into the requirements for making the product, or it could be post market surveillance data. Any kind of information that comes from the customer needs to be protected in a confidential manner.
7.2.3.– Communication with Customers and Regulatory Authorities: This is a new clause. Mainly, it says that there should be documented arrangements in place for communicating with clients and regulatory authorities regarding four matters: product information, regulatory inquiries, complaints, and advisory notices. You need to have a documented procedure explaining how you're going to be handling these communications.
7.3.2 – Design and development planning: The standard requires that you document your planning. The previous version (ISO 13485:2003) mandated that you plan design- and development-related activities, but the revision insists upon a more robust approach to documenting those activities.
Another addition to this section says that you should have a process in place to ensure traceability of your design and development outputs to design and development inputs. Also, it indicates that you should look at the resources that you will need for design and development, including the competence of the personnel will be involved with those activities. You really need to evaluate the personnel conducting design activities and not just appoint someone without the appropriate background. A new note clarifies that design and development review, verification, and validation have distinct purposes and can be conducted and recorded separately or in any combination as suitable for the product and the organization.
7.3.6 – Design and development verification: There is more emphasis in this section on developing a documented process for planning design and development verification activities. It also specifically indicates that verification plans should cover acceptance criteria and sample sizes that you will utilize, along with the rationale behind selecting them. Also, if the intended use requires the device to be connected with other devices, design verification activities have to confirm that design outputs still meet design inputs when connected — you have to look at the verification and validation from that perspective, not just the device itself. Will the device continue to do what it’s supposed to do once it's connected to another device or another system?
7.3.7 – Design and development validation: The changes to this section are similar to those in 7.3.5, only they are related to validation rather than verification: documented methods, acceptance criteria, and sample sizes.
One addition that is unique to 7.3.6 is ensuring that validation is conducted on product that is representative of what you are manufacturing.
7.3.8 – Design and development transfer: This is another new clause, basically requiring a documented plan if you are going to transfer your design to another facility or an outsourcing partner, for example. You must also ensure that your design and development outputs are suitable for production specifications. In other words, if you move your product, will the new site be able to take your specifications and start manufacturing the products the same way you would have at the existing site? Can this be demonstrated with objective evidence?
The revisions point out eight aspects the organization should consider: supplier quality and capability, manufacturing personnel capability and training, manufacturing process and process validation, materials, manufacturing tools and method, manufacturing environment, installation, and service. You need to have a process in place that explains how each of these items will be addressed if you transfer the design to another supplier.
7.3.10 – Design and development files: Also a new clause, this one mainly just explains the types of records you need to keep in a file as part of your design and development activities. Previously, it was pretty much up to the manufacturer to decide how it were going to manage its records and provide evidence it was meeting all the requirements. Now, the draft standard is very prescriptive about the types of documentation to keep in the file, as appropriate. Examples include:
- Results of preclinical tests related to the device and its conformance with specifications
- Biocompatibility studies
- Electrical safety and electromagnetic compatibility
- Software verification and validation
- Report on clinical evaluation
- Post Market Clinical Follow-up (PMCF) - plan and evaluation report
While manufactures are required to keep a file, they may determine what is important to include in their file, so they can have records available. For example, biocompatibility is not applicable to all devices, so it will not appear in every device’s file.
7.4.1 – Supplier approval: Revisions to this section clarify the types of criteria to consider before approving a supplier. You need to have a plan on how you will select suppliers — how you will evaluate, re-evaluate, and then approve them based on their ability to meet your requirements.
And again, we see an emphasis on risk analysis. Now, you really need to determine whether you will have more strict controls, depending on how important their product is to your manufacturing operations. In cases where the product is extremely important, you will probably want to audit that supplier more frequently, require them to be ISO 13485 certified, and ask them to have periodic meetings to assess how they are performing. If, on the other hand, the supplier is not as critical, you might not be so stringent. The expectation is that you show that you performed a risk assessment to justify requirements for all of your critical suppliers.
7.4.1 – Monitoring of suppliers: Organizations must demonstrate that they are checking in on how their suppliers are performing and are utilizing that data as part of the re-evaluation process. If a supplier is not meeting your requirements, you have to show what you are doing to help the supplier improve their performance, or that you are disqualifying them, or that you are engaging in other activities that take into account your risk assessment. You need to have evidence that you are reviewing the data.
7.4.1 – Supplier documentation: Following up on 7.4.1.2, this new section asks that you keep records of your supplier evaluations, including any actions taken as a result of the evaluations.
7.4.2 – Purchasing information: The new addition to this section is having quality agreements with your suppliers. Say, for example, a supplier makes a change related to your product or deviates from the original plan — there are very specific roles and responsibilities that need to take place there. The supplier needs to communicate with you amend contracts if needed. Suppliers can't simply change something without letting you know. This is not a new concept, but now the draft standard wants you to make the process more official.
7.5.6 – Validation of production and service provision: Here, the committee is adding a requirement to include procedures for validation of sterilization and packaging. If you comply with the European Medical Device Directive (MDD), you should already be doing this; now, ISO is going to call for it.
They also added a reference to the ISO 11607 standard for packaging terminally sterilized medical devices. This is just another reference you can use as a guidance to help comply with ISO 13485 requirements.
7.5.8 – Product identification and traceability: Another new section states that if unique device identification (UDI) is required by the regulatory agency in a country where you sell your product, you need to establish and maintain a UDI for your device. This is likely an FDA-driven clause (since FDA recently implemented UDI rules in the U.S.), but as it becomes a more established practice, additional regulatory bodies will start asking for UDI.
Also important to point out is that the section requires that you have procedures in place to separate and distinguish returned products from conforming products. If you receive returns from a hospital or distribution center, for example, you need to prevent that product from getting mixed up with your existing product.
7.5.10 – Customer property: Again, the standard asks you to look at the regulatory requirements from all countries in which you must preserve confidential health information. If confidentiality is a requirement in a country where your product is sold, you need to have a procedure to address how you will to safeguard confidential information and treat it as customer property.
7.5.5 – Preservation of product: This new section instructs you to evaluate your packaging and shipping containers to ensure they are designed to protect the device from contamination and damage — not only during the processing of the device, but also during handling, storage, and distribution. It forces you to look at the complete lifecycle for that package and perform the necessary validations.
For example, if you plan to ship your devices to a region that is extremely cold, do you know that your package will be able to protect the product? Or is the product going to freeze, resulting in an adverse effect? The same thing goes for high temperatures or other environmental factors. You have to take that into account as you perform your validation.
7.5.5 – Particular requirements for sterile medical devices: The last section of section 7 (also new) elaborates on particular requirements for sterile medical devices. If you have a sterile product, you have to take additional measures to make sure that sterility will be preserved, wherever you plan to ship it and however long it will take to get there. How do you demonstrate that the product is going to remain sterile? Again, you really need to have the validation to prove that that package is appropriate.
Section 8 – Measurement, Analysis, And Improvement
8.2.1 – Feedback: Basically, what changed here is that the draft standard asks organizations to come up with a documented process for gathering data from production and post-production activities. While the current standard is rather general, stating that you have to gather feedback and providing guidance on how to do so, the draft standard is more prescriptive about documenting how you gather that data.
Not only would it require you to gather feedback, but also to incorporate that feedback as part of your risk management program. Any data that you obtain should become inputs of your risk management process, to help you determine what effects the feedback will have on the product and whether any changes are necessary within your design or production activities to address concerns.
In addition, you would have to evaluate that data using some kind of statistical methodology, where appropriate. Each organization would have to decide what method makes the most sense, based on your product and your processes and activities. And if you aren't using any statistical methods, then you have to provide rationale justifying why you have chosen not to.
Once you have that analysis, then you need to determine if that needs to go into your corrective and preventative action (CAPA) process. If the notified bodies start seeing trends and issues in your data, but you aren’t having any CAPAs related to them, that would probably become an issue. They want to make sure that you are really acting upon feedback, not just reviewing it.
The last change worth mentioning relates to regulatory requirements, something we have seen across the draft. It asks organizations to look beyond just their local requirements to all international regulations that apply to your product, especially related to post-market activities. Certain countries have very unique requirements regarding conducting and handling the data from post-market activities, so you have to make sure that is incorporated into your policies.
8.2.5 – Monitoring and measurement of processes: This section added a note about the type and extent of monitoring and measurement appropriate to each process, and its impact on the conformity to product requirements and on the effectiveness of the quality system. Organizations need to determine the best way to monitor their processes, depending on their environment and process complexity.
For instance, if you are analyzing production data and you find there is an issue with calibration, the action you take might be different than if you are evaluating data from your post-market activities or your preventative maintenance system. The calibration monitoring for a tool used in-process might be different than the calibration monitoring for a tool used in final inspection to release product. You need to be able to justify how tight your controls are based on the circumstances and complexity of each process.
8.2.6 - Monitoring and measurement of product: This section now includes a note that says, "Records shall identify the test equipment used to perform measurement activities and the person(s) authorizing release of product." For every batch that you manufacture, you need to show what equipment was used. So if you have 10 measuring gauges, for example, you need to be able to trace it down to which one you used to measure some aspect of the device before final release. And not only do you have to trace it back to that instrument, you have to show who in your organization authorized the approval.
We think it is also important to mention that this was brought up with the latest revision of ISO 14971, the risk management standard. Now, ISO is tying it in with this section in ISO 13485, so that it is consistent across the standards.
8.3.1 – Control of nonconforming product (general): Section 8.3 in the standard has been broken down in several different subsections, the first of which is 8.3.1. This clause requires that the evaluation of non-conformance includes a determination of the need to investigate. You have to be able to show how an issue was investigated and how you notified everybody who needed to be involved in the investigation and was associated with the nonconformity.
Also, there is now a link between the nonconformity and the CAPA system. You must be able to show if the issue warranted a CAPA or if it was just managed within the system itself. Obviously, you would have to justify why you decided to not escalate it to a CAPA versus just leaving it within the nonconformance management system.
8.3.2 – Actions in response to nonconforming product before delivery: This section discusses the actions necessary to handle the nonconformities before you ship the product out of your facility. If you identify the nonconformities before the product leaves the facility, it provides an outline of all the actions that must completed before you release the product. For example, you need to make sure you eliminate the nonconformity, document your criteria for releasing it, ensure the product meets all specifications, and have addressed the relevant regulatory requirements that other countries may impose.
8.3.3 – Actions in response to nonconforming product after delivery: This section is very similar to 8.3.2, except it applies to nonconformities you identify after the product has been released. Organizations need to have a documented procedure for issuing and implementing an advisory notice.
8.3.4 – Rework: This clause is not new — rework was already included in the current standard as part of controlling nonconforming products. However, now they have added a section for it.
The section states that if you establish rework, you need to look at any potential adverse effects on the product. Not only that, but it also has to become part of your risk-management process. When you decide that a product needs to be reworked, you need to also consider the implications and retest the product. How will does the rework affect the design of the product or any other manufacturing process?
8.3.4 – Records: Again, there is not much new here. They just added a specific clause to make sure that you keep all the records associated with your management of nonconformities. These records could include any decisions, people involved, and authorizations that took place before the product was released.
8.4 – Analysis of data: Basically, this section asks you to gather data to demonstrate that your quality system is suitable and effective, you are making improvements, and you are taking appropriate actions. If you think about it, the standard is all about making sure that you have a solid system in place that is continually evolving.
Two requirements were added at the end of this section. The first is audits. You need to look at your data from audits to see if you are having more issues in a given area that could potentially become a larger problem. And since the draft guidance doesn’t specify the types of audits, we think you have to take supplier audits into account as well.
Then second new requirement is to review data from service reports, as applicable. So if you manufacture a device on which you will perform service, you have to review the data, looking for potential issues. If your product is an implantable device, for example, most likely this requirement wouldn’t apply to you. But if you make capital equipment, you will need to have data that shows what servicing activities you are engaged in and an analysis of how that data is behaving.
8.5.2 – Corrective action: Moving to the last section — 8.5.2 (improvement) — they have added a subsection that asks you to come up with a corrective action plan that is commensurate with the risk. Depending on the risk of the problem you are experiencing, you would need to establish why you decided to go one way or another with your response to it.
And the other thing that they added was two requirements that organizations should address in a documented procedure. One is reviewing product and process data analysis to identify nonconformities for corrective action. This is just tying it back to what we covered earlier in the section under control of nonconforming product. The other is determining and implementing action needed, including, where appropriate, updating documentation.
Finally, there is a comment about analyzing your corrective actions as part as your management review process. This is not something new, but they added a line to really make it clear that you need to have feedback incorporated as part of your management review.
8.5.3 – Preventive action: The changes to this section are very similar to the previous section. There is a requirement that you review product and process data analysis to identify potential nonconformities in order to prevent their occurrence. And at the end, there is the same request that analysis of preventive action should provide feedback to the management review.
In de nieuwe MDR / IVDR worden producenten verplicht tot (a) het aangaan van een gepaste product aansprakelijkheidsverzekering met een voldoende minimale dekking - of (b) het instellen van een equivalent financiële garantie - zodat geborgd wordt dat benadeelde patiënten gecompenseerd kunnen worden bij letselschade en eventuele bijkomende (na)behandeling(en) als gevolg van een defect medisch hulpmiddel.
Door deze aanvullende verplichting wordt nagestreefd dat
- de kosten bij defecte hulpmiddelen gedekt zijn
- preventief het risico op schade beperkt zal blijven
- bij een eventueel financieel onvermogen bij de producent de kosten veroorzaakt door een defect hulpmiddel niet bij de patiënt neergelegd zal worden
- vergelijkbare incidenten zoals het frauduleuze PIP incident voorkomen wordt.
Ref. Article 8 (par. 13)
"Natural or legal persons may claim compensation for damage caused by a defective device in accordance with applicable Union and national law."
"To this end, manufacturers shall consider taking out appropriate insurance or arranging for an equivalent financial guarantee, to cover the costs associated with defective devices."
Het is goed als producenten kennis nemen van Artikel 50d die handelt over compensatie bij schade voor die patiënten die deelnemen in een klinisch onderzoek.
Article 50d (par. 1)
"Member States shall ensure that systems for compensation for any damage suffered by a subject resulting from participation in a clinical investigation conducted on their territory are in place in the form of insurance, a guarantee, or a similar arrangement that is equivalent as regards its purpose and which is appropriate to the nature and the extent of the risk."
Door samen te werken met o.a. beursverzekeraars - die gespecialiseerd zijn in productaansprakelijkheid bij medische technologieën c.q. life sciences - zijn we in staat om u te ondersteunen in dit proces alsook indien de WMO-M van toepassing is (WMO-M > Wet Medisch Wetenschappelijk Onderzoek bij Mensen).
Hoewel we niet actief zijn als distributeur dan wel betrokken zijn bij ontwerp en of productie bieden we diensten aan in de logistieke keten door gebruik te maken van een unique web-based applicatie. Deze applicatie is bijzonder gebruiksvriendelijk en geeft u op ieder moment toegang tot uw logistiek (deel)proces wanneer en waar u wilt.
We voorzien in transport en op voorraad houden van high-end en gevoelige medische producten. We beschikken over een gespecialiseerd en geconditioneerd warehouse. Onze staf is specifiek getraind hoe om te gaan met medische producten. Aanvullend hierop hebben we een Warehouse Management Systeem ontwikkeld zodat parameters altijd vastgelegd worden voor ieder medisch product. Hiermee is historische logistieke informatie steeds beschikbaar. Onze processen op warehouse en logistiek vallen onder een ISO 13485 certificaat. We zijn bekend met FSCA en recalls; als ook met risico- en kwaliteitsmanagement elementen binnen onze Logistieke Solution Service.
De nieuwe 'Medical Device Regulation' (MDR) wil bestaande EU reguleringen op klinisch onderzoek op elkaar afstemmen, zodat de huidige eisen in artikel 15 en Annex X van Richtlijnen Medische Hulpmiddelen [MDD - 93/42/EC] opgaan met het clinical trial regime voor farmaceutische producten. De MDR zal gaan eisen dat klinisch onderzoek met medische hulpmiddelen gelijk of vergelijkbaar zal zijn met die voor medicinale producten. Deze worden onder de Clinical Trial Directive (2001/20/EC) uitgevoerd, waarbij tevens een gecentraliseerde Europese databank zoals de EudraCT (European Clinical Trial Database) in werking is.
De ISO 14155:2011 werkt 'Good Clinical Practice' (GCP) uit voor klinische evaluaties met mensen. Hierbij kijkende naar ontwerp, uitvoering, vastlegging en rapportages van het uitgevoerd onderzoek met als doel de prestaties van medische hulpmiddelen te beoordelen. Op dit moment is de ISO 14155:2011 nog niet van toepassing voor in vitro diagnostica (IVDR).
De ISO 14155 standaard bevat richtlijnen voor de belangrijkste processen in een klinisch onderzoek met medische hulpmiddelen. Er zijn relaties met de ISO 14971 standaard die van toepassing is op risico management van medische hulpmiddelen. Anders gezegd: de producenten en betrokken partijen moeten twee aanvullende standaarden kennen en gezamenlijk begrijpen.
Ons team van professionals - o.a. medische specialisten, wetenschappers, artsen, onderzoeksverpleegkundigen, CRA's, etc. - kijken uit om u te ondersteunen in dit complexe proces van het verkrijgen van de CE markering.
Onze dienstverlening kan o.a. bestaan uit ondersteuning in:
- registratieproces bij een multinationale klinisch onderzoek in of buiten de EU
- communicatie met de locale Ethische Commissie
- patiënten communicatieproces (zie ook toevoeging annex XIV, part I en II)
- Post-Market Clinical Follow-up (PMCF) eisen en implementatie van de PMCF MEDDEV 2.12/2 Rev2.
- medical writing
- monitoring activiteiten
- clinical trial liability insurance (verplicht)
- etc.