Medical

Introduction:

In May the MDCG Guideline 2022 – 5 “Guidance on Borderline between medical devices and medicinal products under MDR 2017/745” was published, at the conclusion of a long comparison within the Community.

Borderline products are those products that by their nature are not immediately traceable to a particular sector, for which it is therefore difficult to define what is the reference legislation to be applied.

The demarcation between Regulation (EU) 2017/745 on medical devices (MDR) on the one hand and Directive 2001/83/EC on medicinal products (MPD) for human use on the other is crucial for the implementation of these legislative acts and for their correct interpretation and application.

 

General aspects:

As a general rule, a product is regulated either by the MDR or by the MPD but not both. The conformity assessment procedure or the marketing authorisation procedure to be followed prior to placing a given product on the market will therefore be governed either by the MDR or by the MPD.  The procedures of both regulatory regimes do not apply cumulatively. However, for products that have properties of both medicinal products and medical devices (e.g. medical devices incorporating as an integral part, a substance which, if used separately, would be considered to be a medicinal product), some cross-references are made within one regime to specific provisions of the other regime.

The wording of Article 2(2) of the MPD shows that it only applies if, after a case-by-case assessment, taking in consideration all the characteristics of a product, the product in question may fall within the definition of both, medical device and medicinal product. In such a case, the provisions of the MPD applies5. The MDR and the MPD may not be applied cumulatively.

The aim of this guideline is to support the uniform application of the Regulation throughout the European Union.

The document starts with the general discussion of the borderline between medical devices and medicinal products, including relevant definitions and examples. Separate chapters are dedicated to herbal products, substance-based devices and medical device and medicinal product combinations.

According to Article 1(6)(b) of the MDR, in deciding whether a product falls under the MDR or the MPD particular account shall be taken of the principal mode of action of the product. The nature of the principal mode of action i.e. whether it is pharmacological, immunological or metabolic or other is generally the same irrespective of the quantity.

According to Article 2(1) MDR a medical device does not achieve its principal intended action by pharmacological, immunological or metabolic means, in or on the human body, but may be assisted in its function by such means. The concept that a medical device may be assisted in achieving its principal intended action by pharmacological, immunological or metabolic means should be understood as covering those cases when the medical device incorporates, as an integral part, a substance which, if used separately, would be considered to be a medicinal product, and that has an action ancillary to that of the device.

Typically, the medical device’s principal intended action is achieved by physical means (including mechanical action, physical barrier such as a film, lubrication, heat transfer, radiation, ultrasound, replacement of or support to organs or body functions). Furthermore, hydration or dehydration and pH modification may also be means by which a medical device achieves its principal intended action.

The determination of the nature of the substance, i.e. whether it is “considered to be a medicinal product” is independent of the intention of the manufacturer, of the quantity of the substance in the device and of the method or route of administration.

 

Conclusion:

The document may be revised in the light of the update of technical-scientific knowledge and in the light of the results of discussions within the Borderline and Classification medical devices expert group (B&C) of the Medical Device Coordination Group.

 

For more information: https://ec.europa.eu/health/latest-updates/mdcg-2022-5-guidance-borderline-between-medical-devices-and-medicinal-products-under-regulation-eu-2022-04-26_en

One of the most significant changes introduced by the Scientific Committee on Consumer Safety (SCCS) in the Notes of Guidance with the eleventh revision of March 2021 is the use of two mathematical models for the calculation of inhalation exposure.

Cosmetic products, by definition, are designed to be applied to the external surfaces of the human body, teeth and mucous membranes of the mouth. However, sometimes these products, or some of the ingredients that compose them, can be inhaled in the form of vapours, powders and aerosols.

The first model applies to products that can generate vapours (for example liquid products that contain volatile solvents). For these products, the inhalation Systemic Exposure Dose (SEDinh) of the ingredients is calculated by multiplying the daily exposure to the product by the concentration and evaporation fraction (a value between 0 and 1).

The second model applies to powder and spray products. Spray products fall into two categories: propellant sprays (which produce a finer aerosol) and pump sprays (which produce a less fine and more difficult to inhale aerosol).

For the assessment of inhalation exposure to these types of products, the SCCS proposed the use of a 1- or 2-Box model.

In a classical 1-Box model it is assumed that the entire spray amount is instantaneously released into the air and distributed in a box of a specific size, which e.g. simulates the breathing zone. The resulting air concentration is then multiplied by the breathing rate and the time spent in the box to calculate the exposure. A 2-Box model takes into account the dilution of the substance over time. As in the 1-Box model, the assumption is that the spray is instantly released and distributed in a box around the head. There the aerosol is present for exposure over a defined time, after which the full amount of aerosol in the first box is transferred to a larger second box (representing a room where the product is used), where it is available for inhalation for a second defined time period. For a conservative approach, the air exchange (fresh air getting in, exhaust air getting out) can be assumed as zero.

In addition to the size of the two boxes and the time that the product remains in suspension, the size of the aerosol generated by the product must also be taken into account for the calculation of the SEDinh, which vary according to the type of spray used. A finer aerosol is more easily breathable and consequently the substances contained within will be more systemically available.

The application of these mathematical models allows a better characterization of exposure to the ingredients contained within cosmetic products and is a further step towards a greater guarantee of safety for the final consumer.

For more details see:

https://ec.europa.eu/health/system/files/2021-04/sccs_o_250_0.pdf

Introduction:

The end of the state of emergency will be the end of the derogation regime which, in view of the exceptional situation resulting from the SARS-cov-2 pandemic, has introduced into our legislation the possibility of placing on the market surgical masks authorised by derogation. From 1 April 2022, manufacturers who want to continue to market surgical masks in Italy will have to comply with the ordinary legislation on medical devices.

For authorised masks already placed on the market, the Circular of 4 March 2022 (https://www.trovanorme.salute.gov.it/norme/renderNormsanPdf?anno=2022&codLeg=86093&parte=1%20&serie=null ) indicates that they may be made available only until 31 May 2022 and that only masks that are part of existing stocks available to personnel participating in efforts to contain the virus and prevent its further spread may be made available until such stocks are exhausted and at the latest by 31 July 2022.

The circular of 4 March 2022 clarified certain aspects of the procedures for placing surgical masks on the market in view of the imminent expiry of the state of emergency.

The circular recalls that from 26 May 2021 it is no longer possible to place on the market surgical masks marked CE pursuant to Directive 93/42/EEC, implemented in Italy with the d.lgs. 46/97, and it is stressed that manufacturers who intend to place on the market surgical masks, must ensure compliance with the requirements of Regulation (EU) 2017/745.

 

Technical Documentation:

According to MDR 2017/745 before placing a device on the market, the manufacturer is obliged to prepare the technical documentation that must enable it to assess its compliance with the general performance and safety requirements(GSPR) set out in Annex I to the Regulation.

This documentation shall be presented in a clear, organised, unambiguous and easily searchable format and shall include methods and test results to support compliance with the specifications. For surgical masks, these are mainly tests of bacterial filtration (BFE) efficiency, respirability (Pa/cm2), microbial contamination (cfu/g), splash resistance (kPa) (only in the cases provided, type IIR masks) and biocompatibility.

The manufacturing, design and performance requirements and test methods for surgical masks are set out in UNI EN 14683:2019 “Medical face masks – Requirements and test methods”, which, although not yet harmonised in accordance with the Regulation (cf. Circular of 12 November 2021) is the main tool for the manufacturer to demonstrate the conformity of the device.

 

Quality Management System (QMS):

To ensure that series production continues to comply with the requirements of the Regulation, the manufacturer establishes, documents, applies, maintains, updates and constantly improves a quality management system, in accordance with the obligations laid down in art. 10, paragraph 9 of the Regulation.

 

Post Market Surveillance:

The manufacturer shall establish and update a post-market surveillance system throughout the life cycle of the device.

 

In conclusion, the manufacturers of surgical masks already CE marked, in accordance with Directive 93/42/EEC, and persons who have obtained derogation authorisations for the production and marketing of surgical masks having an interest in continuing to regularly place on the EU market its own masks such as medical devices, must follow all the indications contained in the Circular and in the reference standards indicated.

 

For more information:

https://www.salute.gov.it/portale/news/p3_2_1_1_1.jsp?lingua=italiano&menu=notizie&p=dalministero&id=5834

 

 

 

 

What is IFRA?

The International Fragrance Association (IFRA), founded in 1973, represents the interests and is the voice of the fragrance industry worldwide. It promotes the safety and benefits of the fragrance industry’s products through stakeholder dialogue on a global basis.

When warranted by concerns regarding the safe use of a specific ingredient identified by the Research institute for Fragrance Materials (RIFM) safety assessment program, IFRA will issue an IFRA Standard as part of an IFRA Amendment.

IFRA Standards

To ensure the safety of fragrances, IFRA has established rules (known as IFRA Standards) recognized by government authorities and commercial entities around the world.

IFRA Standards can either prohibit, restrict or set purity requirements for specific ingredients. The safety of ingredients, whether the subject of an IFRA Standard or not, remains the responsibility of IFRA members. Compliance with IFRA Standards is therefore necessary for compliance with the IFRA Code of Practice but may not be sufficient to ensure regulatory compliance and the safety of fragrance mixtures or ingredients.

The IFRA Standards and related documents are subject to regular changes as new information relevant to the safety of fragrance ingredients become available. All these changes are part of an IFRA Amendment, which is designed pursuant to an inclusive procedure and is subject to a broad consultation of all relevant stakeholders before its Notification. Last one is the 50th Amendment, an ‘off-cycle’ amendment for one ingredient, Mintlactone, published on 30 June 2021.

The Expert Panel for Fragrance Safety is an independent panel of experts that reviews the activities of the Research Institute for Fragrance Materials (RIFM). They determine safety of use for fragrance ingredients through consideration of available information and active generation of additional data. If the Expert Panel for Fragrance Safety determine that a restriction of use is necessary for consumer and environmental protection, an IFRA Standard will be published.

All fragranced consumer products are in the scope of the IFRA Standards except for products clearly not covered in the RIFM Safety Assessments, such as:

– medical devices;

– prescriptive drugs;

– aromatherapy applications;

– consumer products used in occupational settings (e.g. shampoos applied in hair salons, hand sanitizers applied in hospitals, etc.).

A detailed list of the products covered under the scope of the IFRA Standards is provided in “Guidance for the Use of IFRA Standards”. In case a final product application is not included therein, it remains the responsibility of the final consumer product manufacturing company to adequately categorize this final product application in order to comply with the requirements of the IFRA Standards.

For practical reasons, IFRA Standards are set per product category, each covering a range of product types which can be grouped together based on risk assessment considerations.

With IFRA 49th Amendment, issued at the beginning of 2020, the number of categories in the IFRA Standard has changed from 11 categories for dermal sensitization Standards and 4 for systemic toxicity-based Standards to 12.

Product categorization is achieved by grouping consumer product types based on functional type, and major factors in habits and practices of consumers such as area of use (head, face, axillae, etc.) and whether they are rinse-off or leave-on applications.

Certificate of conformity

The Certificate of Conformity to the IFRA Standards is a document established by companies creating fragrance mixtures, which declares compliance with the requirements expressed in the IFRA Standards and confirms that a specific fragrance mixture up to a certain concentration can be used in a specified consumer product in compliance with up to and including a specific Amendment (the number and the Notification date of the Amendment should be stated in the Certificate).

The Certificate is only applicable for fragrance mixtures intended to be directly included in a finished consumer product. By using a Certificate, a fragrance supplier assures its customer that the product they supply is in compliance with the requirements set by the IFRA Standards for an intended use.

It is important to note that IFRA is not involved in its preparation and that the Certificate of Conformity declares compliance with the requirements expressed in the IFRA Standards but does not replace a safety assessment.

 

Source: https://ifrafragrance.org

Fraunhofer ITEM leading an EMA-funded research project

 

Nitrosamines (NAs) are a class of organic chemical compounds that humans may be exposed to by tobacco smoking or consuming certain foods. N-nitrosamines have been classified as probable human carcinogens and are categorized in the ICH M7 guideline as belonging to the “cohort of concern” group of high-potency mutagenic carcinogens. Some active pharmaceutical ingredients (APIs) carry NAs as impurities from production and/or storage or may cause their formation in the gastrointestinal tract.

A joint research project funded by the European Medicines Agency (EMA) and led by Fraunhofer ITEM will shed light on the mutagenicity of different classes of NAs to distinguish highly potent from less potent carcinogens. Besides classical nitrosamine structures, API-like nitrosamine derivatives will also be investigated. It will be of particular importance to look for their ability to undergo metabolic activation and to form different DNA adducts. Additionally, corresponding DNA repair mechanisms will be addressed for the first time. By developing novel in-silico as well as in-vitro test systems, the consortium aims to improve risk assessment and to derive reference doses such as acceptable intake (AI) values.

Initially, the focus will be placed on nitrosamine metabolites and their potential to damage DNA when not adequately repaired. The obtained data will be used to correlate the structure of NAs to their potential toxic/mutagenic effects. By means of a quantitative structure-activity relationships (QSAR) approach, this will allow derivation of acceptable intake values for compounds lacking appropriate in-vivo cancer studies, i.e. following a read-across approach.

Secondly, the effect of the physiological environment of the gastrointestinal tract (including the microbiome) on the formation of NAs from drugs or their degradation products will be studied. Due to the lack of knowledge about endogenous nitrosamine formation, it is of utmost importance to elucidate potential mechanisms in order to reduce the carcinogenic risks for patients. Research findings of these laboratory studies will be integrated and generalized in order to develop predictive QSAR models for the susceptibility of drugs to be nitrosated.

Finally, current bacterial mutagenicity test systems as well as novel in-vitro genotoxicity tests, such as the comet assay in liver cell models (primary human and rat hepatocytes, human liver cell lines), will be evaluated, optimized and validated. Metabolic competence will represent one key topic, to reach the final aim of reliably detecting mutagenicity of different NAs.

 

 

Source:

https://www.item.fraunhofer.de/en/press-and-media/press-releases/mutagenicity-of-nitrosamines.html

THE MEDICAL DEVICE COORDINATION GROUP RELEASED A NEW GUIDANCE DOCUMENT REGARDING general principles of clinical evidence for In Vitro Diagnostic medical devices (IVDs) (mdcg 2022-2)

 

Scope:

This document outlines the general principles of clinical evidence and provides guidance on the continuous process of performance evaluation for in vitro diagnostic medical devices (hereafter referred to as IVDs), as set out in Regulation (EU) 2017/746 – In Vitro Diagnostic Medical Device Regulation (IVDR).

In this guidance is described the approach by which collection, generation and documentation of supporting data for an IVD may be conducted prior to the placing on the market or putting into service. As the performance evaluation will be updated throughout the life cycle of an IVD.

Definition of IVD according to Regulation (EU) 2017/746 – In Vitro Diagnostic Medical Device Regulation (IVDR).

Article 2(2)

IVD: any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, piece of equipment, software or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally for the purpose of providing information on one or more of the following:

  1. a) concerning a physiological or pathological process or state;
  2. b) concerning congenital physical or mental impairments;
  3. c) concerning the predisposition to a medical condition or a disease;
  4. d) to determine the safety and compatibility with potential recipients;
  5. e) to predict treatment response or reactions;
  6. f) to define or monitoring therapeutic measures.

Specimen receptacles shall also be deemed to be in vitro diagnostic medical devices.

As accessories for an IVD fall under the scope of the IVDR, this document also provides guidance on these devices.

 

Introduction:

Prior to placing an IVD on the market or putting it into service, the manufacturer must demonstrate compliance with all applicable requirements of the IVDR, in accordance with the appropriate conformity assessment procedure(s). Therefore, the manufacturer must demonstrate that the IVD achieves its intended purpose in accordance with the claimed performance over the lifetime of the device.

The IVDR outlines that evidence for an IVD’s conformity is established by demonstrating and substantiating the scientific validity, analytical performance and clinical performance.  Furthermore, the IVDR underlines that the necessary clinical evidence should be based on a sufficient amount and quality of data in order to allow a qualified assessment of whether the IVD is safe, performant and achieves the intended clinical benefit(s), when used as intended.

General principles of Clinical Evidence:

Clinical evidence for IVDs is established through the collection of data as a result of a performance evaluation. Performance evaluation covers the assessment and analysis of data to establish and verify the scientific validity, analytical performance and, where applicable, clinical performance of an IVD. Each indication and claimed clinical benefit specified in the intended purpose should be assessed and have the appropriate supporting clinical evidence.

Performance Evaluation:

Performance Evaluation is a structured, transparent, iterative and continuous process which is part of the quality management system and is conducted throughout the life cycle of an IVD. The general performance evaluation principles are laid down in Article 56 and Annex XIII, Part A, 1 of the IVDR and can be summarised as follows:

  • Planning (Performance Evaluation Plan, PEP);
  • Data establishment;
  • Analysis, conclusions and documentation (Performance Evaluation Report, PER);
  • Continuous monitoring and updates (Periodic <safety Update Report, PSUR; Post Market Performance Follow-up, PMPF).

The performance evaluation of an IVD must consider the benefit-risk ratio in light of the state-of-the-art. The three essential pillars of performance evaluation can be summarised as:

  • Scientific validity: the extent to which the analyte, or marker to be determined by the IVD is associated with the targeted physiological state or clinical condition.
  • Analytical performance: demonstration of the IVD’s ability to correctly detect or measure a particular analyte.
  • Clinical performance: demonstration of an IVD’s ability to yield results that are correlated with a particular clinical condition or a physiological/pathological process or state in accordance with the target population and intended user.

The risk management system should be carefully aligned with and reflected in the performance evaluation process of the IVD, considering the clinical risks to be addressed as part of the performance evaluation, performance studies, and post-market performance follow-up(s).  Due to their nature, in the majority of cases, deficiencies of IVDs do not directly lead to physical injury or damage to the health of people. If any, these devices may lead to indirect harm, rather than direct harm.

For more information: https://ec.europa.eu/health/latest-updates/mdcg-2022-2-guidance-general-principles-clinical-evidence-vitro-diagnostic-medical-devices-ivds-2022-01-27_en

New concentration limits proposed by SCCS for BHT in cosmetic products

 

Butylated Hydroxytoluene (BHT) is a lipophilic organic compound, a synthetic antioxidant widely used in multiple sectors, including food additives, cosmetics and personal care products, pharmaceuticals, plastics/rubbers and other petroleum products. Butylated hydroxytoluene is reducing the free-radical induced damage and spoilage; therefore, it helps maintain the properties and performance of products when exposed to air.

BHT is not currently regulated under the Cosmetics Regulation, however, it is included in the European database for information on cosmetic substances and ingredients (CosIng) with the reported function of antioxidant and fragrance.

On 7th November 2018, the Commission adopted the review of Reg. (EC) 1223/2009 on cosmetic products regarding substances with endocrine disrupting (ED) properties and concluded that the Regulation provides the adequate tools to regulate the use of cosmetic substances such as ED.

At the beginning of 2019, the Commission carried out a public call of data for 28 potential EDs substances, including BHT. Following the data collection, the commission began asking for opinions from the SCCS about the safety of those substances. In March 2021, the SCCS was asked to evaluate BHT safety, also considering data provided by stakeholders during the call for data.

On 3rd December 2021 the SCCS released its final opinion about BHT, which establishes the safety of BHT for human health within these limits:

  • maximum concentration up to 0,001% in mouthwash;
  • maximum concentration up to 0,1% in toothpaste;
  • maximum concentration up to 0,8% in other rinse-off and leave-on products.

BHT is also considered safe for combined use of mouthwash at a concentration of 0.001%, toothpaste at a concentration of 0.1% and other leave-on and rinse-off products at the concentration of 0.8%.

This opinion, together with the next ones that will be published in the coming months, is expected to lead the Commission to amend the Regulation annexes.

Proposal to lower the level from 0,05% to 0,001%

 

Formaldehyde is a substance classified as Carcinogen 1B and Skin sensitizer 1. It is listed in Annex II/1577 of Reg. (EC) 1223/2009, so it is forbidden in cosmetic products. However, a number of substances listed in Annex V release formaldehyde in order to achieve a preservative function. For this reason, products containing formaldehyde releaser (FR) preservatives must be labelled with the warning “contains formaldehyde” where the concentration of free formaldehyde in the final product exceeds 0,05%. FR substances are, for example, DMDM Hydantoin, Imidazolidinyl Urea, Diazolidinyl Urea, Polyoxymethylene Urea, Sodium Hydroxymethylglycinate and Glyoxal. Those substances are quite commonly used in nail and hair products.

In 2020 the Commission received additional information suggesting that formaldehyde exposure to levels below 0,05% could cause contact dermatitis in persons with formaldehyde allergy. In the light of data provided, the commission asked in February 2021 the SCCS if the 0,05% threshold for labelling FR substances adequate to protect consumers and if considered necessary to change it.

In May 2021 SCCS published an opinion in response to the Commission request. SCCS stated that the 0,05% threshold is insufficient to protect the formaldehyde-sensitive subjects and proposed to reduce the threshold from 0,05% to 0,001%. This new threshold applies to the total free formaldehyde irrespective of whether a product contains one or more formaldehyde releasers, both for leave-on and rinse-off products.

This new restriction is likely to be adopted soon questioning product formulations containing FRs and new analyses on free formaldehyde will be needed.

THE CLASSIFICATION OF MEDICAL DEVICES (MDCG 2021-24)

 

The classification of medical devices in use by the EU medical device legislation is a risk-based system taking into account the vulnerability of the human body and the potential risks associated with the devices. This approach uses a set of criteria that can be combined in various ways in order to determine classification, e.g. duration of contact with the body, degree of invasiveness, local vs. systemic effect, potential toxicity, the part of the body affected by the use of the device and if the device depends on a source of energy. The criteria can then be applied to a vast range of different medical devices and technologies.

In this guidance is given a general overview on the impact of the classification of medical devices on different aspects of the device’s compliance with the legal requirements:

  • all medical devices must comply with all relevant obligations of the Medical Device Regulation (MDR), however, some requirements depend on the device classification.
  • The technical documentation to be drawn up by the manufacturer must include the risk class of the device and the justification for the classification rule(s) applied in accordance with Annex VIII of the MDR.
  • Demonstrating conformity is in the first instance the responsibility of the manufacturer and for most devices classes the conformity is then assessed by a notified body. The higher the class of the device, the greater the involvement of a notified body in conformity assessment. Annex I (general safety and performance requirements) and Annexes II (technical documentation) and III (technical documentation on post-market surveillance) apply to all devices regardless of class. Further relevant conformity assessment procedures (laid down in Annexes IX to XI) will depend on the class of the device.
  • For any device regardless of class, the manufacturer must ensure the general safety and performance requirements are satisfied (MDR Article 5, MDR Annex I). This includes carrying out a clinical evaluation (MDR Article 5 (3), MDR Article 61, MDR Annex XIV.
  • The manufacturer must update the clinical evaluation with clinically relevant information coming from post-market surveillance, in particular the post-market clinical follow-up.
  • Traceability, for class III implantable devices, economic operators and health institutions are obliged to have a record of the UDI of the devices they have supplied or with which they have been supplied (MDR Article 27). For class II and III devices, the economic operator is obliged to provide information on the Member State(s) where the device is or is to be, made available when registering the device (Annex VI Part A 2.4). In the case of implantable and class III devices, the economic operator must provide a summary of safety and clinical performance (Annex VI Part A 2.14).  For single-use class I and IIa devices packaged and labelled individually, the UDI carrier does not have to appear on the packaging but must appear on a higher level of packaging (Annex VI Part C 4.3).
  • Generally, instructions for use must be supplied together with the device. By way of exception, class I and IIa devices may be supplied without instructions for use if such devices can safely be used without the instructions and no other provisions of Annex I Section 23 state otherwise.

Before applying the classification rules, the manufacturer should first determine if the product concerned, based on its specific medical purpose, falls in the scope of the MDR as a medical device, accessory for a medical device (Article 2 MDR), medical device part or component for replacement (Article 23(2) MDR) or as a device without an intended medical purpose listed in Annex XVI.

It is the intended and not the accidental use of the device that determines the class of the device.

In case several rules, or if, within the same classification rule, several sub-rules, apply to the same device based on the device intended purpose, the strictest rule and sub-rule resulting in higher classification will apply.

In addition to the classification rules set out in Annex VIII of MDR, the manufacturers must also take account of any applicable legal acts and consider guidance documents that may support the classification of their device.

In the guidance are presented explanations of individual rules with different graphical summaries.

Link for the Guidance: https://ec.europa.eu/health/sites/default/files/md_sector/docs/mdcg_2021-24_en.pdf

 

 

The Medical Device Coordination Group released a new guidance document regarding the requirements on the quality management system (QMS) to be established by distributors and importers carrying out any of the activities mentioned in points (a)2 and (b)3 of Article 16(2) concerning relabelling and repackaging of devices.

 

Introduction

Article 16(4) of the MDR / IVDR provides for a notified body to certify that the quality management system of the distributor or importer complies with the requirements laid down in the abovementioned Article 16(3). Notified bodies need to establish the assessment activities necessary in order to certify the quality management system of a distributor or importer intended to relabel and / or repackage a device. This guidance document is mainly focused on activities performed by notified bodies, providing also clarification on the quality management system they are expected to assess. A separate MDCG guidance document, in the form of Questions & Answers, is being developed to complement and address implementation of other relevant requirements for distributors and importers introduced by Article 16 of MDR / IVDR.

The scope of this guidance is to provide assistance to notified bodies with regard to certification activities to be carried out according to Article 16(4), attesting that the quality management system of the distributor or importer complies with the relevant requirements.

This guidance is also addressed to distributors and importers in respect to their quality management system to be certified by a notified body.

 

Quality Management System for distributors or importers.

Without prejudice to general obligations that apply to all distributors (Article 14 MDR / IVDR) and importers (Article 13 MDR / IVDR), distributors or importers carrying out any of the activities mentioned in points (a) and (b) of paragraph 2 of Article 16 of the MDR or IVDR are required to ensure that they have in place a quality management system. This quality management system includes procedures, which ensure that the translation of information supplied with the device is accurate and up-to-date. These procedures also ensure that those activities are performed by means and under conditions that preserve the original condition of the device. In addition, they ensure that the packaging of the repackaged device is not defective, of poor quality or untidy. Furthermore, the procedures established under the quality management system should address elements related to contractual relationships to ensure compliance with certain provisions established by Article 16:

  • Contracts with any economic operator the distributor or importer is purchasing the device from should ensure that the distributor or importer is informed in a timely manner about any corrective action taken by the manufacturer in relation to the device in question in order to respond to safety issues or to bring it into conformity with the Regulation;
  • In addition, the contract between the notified body and the distributor or importer should specify the possibility for the notified body to perform on-site audits at the premises of the distributor and importer or their subcontractors if needed, as specified in section 6 of this document.

The quality management system should govern the structure, responsibilities, procedures, processes and management of resources required to implement the principles and actions necessary to achieve compliance with the provisions of Article 16(3) of the MDR / IVDR and is expected to cover and address at least the following:

  • documentation of the management system, including responsibility of the management, and development of policies and procedures, Medical Devices Medical Device Coordination Group Document MDCG 2021-23 Page 4 of 7
  • resource management, including premises and equipment necessary to carry out activities referred to in points (a) and (b) of Article 16(2) as well as selection and control of suppliers and sub-contractors,
  • policies for assignment of activities and responsibilities to personnel ensuring the availability of resources and information necessary to support the operation and monitoring of the activities mentioned,
  • procedures ensuring that the distributor or importer is informed of any corrective action taken by the manufacturer in relation to the device in question in order to respond to safety issues or to bring it into conformity with the Regulation5 (Article 16 paragraph 2 points (a) and (b)),
  • management of corrective actions including procedures for handling non-conforming devices and market recalls due to the activities carried out under point (a) and (b) of Article 16(2), including, when necessary, field safety corrective actions and verification of their effectiveness,
  • procedures to ensure traceability of the devices as well as labels, instructions for use and outer packaging indicating the changes made to the product,
  • control of documents,
  • control of records,
  • supervision of the implementation and maintenance of the quality management system, including internal audits and management review.

 

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