Di Renzo® Regulatory Affairs
Di Renzo Regulatory Affairs is an Italian company providing regulatory consulting services in the field of medicines for human and veterinary use, medical devices, biocides, food supplements and cosmetics. The company has a large staff of technical experts and is based in Rome with a branch office in Milan.
|Di Renzo Regulatory Affairs|
|Headquarters||Viale Manzoni, 59 Rome, ROME 00185 Italy|
|Number of employees||51-200 employees|
- 1 History
- 2 Services
- 2.1 Medicinal products for human use
- 2.1.1 Antifraud stickers and traceability of medicines
- 2.1.2 eCTD regulatory consultancy
- 2.1.3 Clinical Trials
- 2.1.4 Pharmacovigilance Outsourcing
- 2.1.5 Scientific information
- 2.1.6 Advanced therapies
- 2.1.7 Insertion into XEVMPD database
- 2.1.8 Readability User Test and Bridging Study
- 2.1.9 Stock disposal
- 2.1.10 The regulation on bilingualism and the Unifarm database
- 2.2 Veterinary Medicines
- 2.3 Medical Device Consulting
- 2.3.1 Borderline products
- 2.3.2 Database and Repertorio – Medical Device Registration in Italy
- 2.3.3 Classification of medical devices
- 2.3.4 In Vitro Diagnostic Medical Devices
- 2.3.5 CE Certification
- 2.3.6 Technical File
- 2.3.7 Clinical Experimentation
- 2.3.8 Advertising of medical devices
- 2.3.9 Medical Device Post-Market Surveillance and Vigilance
- 2.3.10 The Authorized Representative
- 2.3.11 Quality Management System for Medical Devices
- 2.4 Presidi medico chirurgici and biocidal products
- 2.5 Regulatory consultancy for cosmetics
- 2.6 Particular Foodstuffs and Dietary Supplements
- 2.6.1 Consultancy for food supplements
- 2.6.2 Food for Special Groups
- 2.6.3 Labelling of Food Products
- 2.6.4 Nutritional claims
- 2.6.5 Advertising supplement foods
- 2.6.6 Food supplement labelling
- 2.6.7 Notification and registration dietary supplements
- 2.6.8 Phytovigilance and Surveillance natural substances
- 2.7 Legal advice to pharmaceutical companies
- 2.8 Translation services for the Pharmaceutical Industry
- 2.9 Free Sale Certificate
- 2.10 Training Courses in Regulatory Affairs
- 2.11 Registration of trademarks and patents
- 2.12 Quality service of ISO 9000 consultants
- 2.1 Medicinal products for human use
Di Renzo Regulatory Affairs cooperates with an International net of companies in the pharmaceutical regulatory consulting in all Member States of the European Community and in the main extra-EU countries.
The mission of Di Renzo Regulatory Affairs is to offer regulatory consultancy to pharmaceutical companies intending to obtain marketing authorizations for medicines for human use, veterinary medicines, food supplements and medical devices.
The Rome office, located near the historical city centre, allows us to reach the Ministry of Health, AIFA (Italian Medicines Agency) and the Health High Institute easily and quickly. The regulatory company has an office also in Milan, in order to facilitate pharmaceutical companies from the North Italy and North Europe.
At the end of the ’80s, the European Community started a harmonization of the regulations of pharmaceutical products in all Member States. Since then, pharmaceutical industry has undergone deep changes, with the introduction of complex, ever changing authorization procedures.
This radical transformation required a deep knowledge of the regulations of this field, highlighting the need to keep up with continual technical and normative updates. Therefore, the availability of experts able to deal with technical and scientific issues but also mastering National and European regulations has become essential. On the base of such needs, in 1985 Sante Di Renzo founded the company Di Renzo Regulatory Affairs.
Di Renzo Regulatory Affairs began its activities in 1985 and has, over time, developed its structure to an international level. Its employees, some Italian and others from countries inside and outside Europe, are for the most part graduates in scientific disciplines such as chemistry, medicine, pharmacy, pharmaceutical chemistry and technology, engineering, biology and biotechnology.
This is further proof of its choice to work with national and international companies who intend to market their products in Italy and abroad.
Di Renzo Regulatory Affairs collaborates with manufacturers, distributors, concessionaires, marketing authorization holders of medicinal products for human and veterinary use, medical devices, food supplements, cosmetics, biocides and medical-surgical devices. It has also developed activities relating to pharmacovigilance, devicevigilanza, cosmetovigilance and clinical trials.
The growth of the group Di Renzo Regulatory Affairs, in addition to the prestige it has acquired in recent years, it is also due to the increasing need on the part of various companies to identify consultants outside their own structure to delegate all or part of the regulatory activity.
Several years ago Di Renzo Regulatory Affairs opened an office in Milan and is in the process of opening an office in London and in other countries outside Italy. It collaborates with numerous regulatory consultants from all over Europe and many non-EU countries.
Medicinal products for human use
In the field of pharmaceutical consultancy on medicinal products for human use, Di Renzo Regulatory Affairs employs many technicians (doctors, chemists, biologists, engineers, pharmacists and graduates in chemical and pharmaceutical technology) and other administrative personnel including English, German, Italian-American, Greek, Brazilian and Spanish native speakers.
The services that Di Renzo Regulatory Affairs is able to offer are principally the following:
- Advice on national and international legislation
- Preparation of applications for marketing authorization for national , mutual recognition , decentralized and centralized procedures
- Preparation of variations, extensions , transfers of ownership and renewals
- Drafting and translation of SPC , labels and leaflets in accordance with current guidelines
- Readability Test for the patient information leaflet
- Sworn translation into German of leaflets and labels and insertion into the Unifarm network ( bilingualism )
- Consultation and preparation of pricing dossiers , HTA reports and price negotiation
- Registration and submission of data into the EudraVigilance database
- Due diligence , gap analysis and preparation of expertise
- Design and production of artwork for primary and secondary packaging
- Formatting dossier in eCTD or NeeS
- Advice on applications for authorization for the production of raw materials and finished products
- Audits at production sites of active ingredients (APIs) and finished products in Italy and abroad
The languages that are spoken, in addition to Italian, are English, German, French, Spanish, Greek, Chinese and Portuguese.
Antifraud stickers and traceability of medicines
The traceability of medicines has been created in order to collect, in a centralized database, information regarding medical packaging placed within the distribution system. The MA holder or the licensee must affixed a special antifraud sticker on each pack indicating the name of the MAH, the product name, the sequence number of the sticker, the MA number and the description of the package.
This consents to an ever increasingly appropriate procedure to counter potential fraud to the detriment of public health, the National Health Service and the Tax Authorities, for the prevention and suppression of any illegal activities and to monitor the supply of drugs to hospitals, pharmacies and direct distribution.
It also gives rise to a more effective national pharmacovigilance program and provides an increasingly more accurate view of the consumption of drugs and, consequently, the development of a prescriptive system which is ever more suited to the needs of consumers.
Di Renzo Regulatory Affairs is able to assist pharmaceutical companies in the following phases:
- Ordering antifraud stickers, pre-printing check, supervising the shipment from the printers to the production site
- Handling the collection of data regarding the used and discarded antifraud stickers
- Transmission to the database of the Ministry of Health of the information concerning the movements of the packs via XML format as required by the guidelines and the specifications of the Ministry of Health
- Updating the database on the number of antifraud stickers remaining with the company
eCTD regulatory consultancy
An e-Submission is any presentation of information in electronic format sent by the applicant to the regulatory agency, in support of applications for marketing authorizations, variations, extensions, etc..
Specifically, the eCTD is the electronic version of the Common Technical Document (CTD). The structure, folders and file names correspond to those of the CTD and its .xml structure allows for easy browsing of the dossier.
With regard to the management of the life cycle of pharmaceuticals, Di Renzo Regulatory Affairs avails itself of the EXTEDO eCTD Manager Suite, the software used by major regulatory agencies. This ensures full compatibility in the exchange of information between the company and agency.
As long as the e-Submission in e-CTD is not mandatory in all Member States, a transitional format called Non-eCTD electronic Submissions (NeeS) has been provided, which is accepted by national regulatory agencies. For applications in the NeeS format the same eCTD structure is used, which must be in conformity with the ICH Granularity Document. The name of the NeeS file must comply with the same name as the eCTD file.
Di Renzo Regulatory Affairs has the know-how and equipment to prepare dossiers in eCTD and NeeS format.
The services that Di Renzo Regulatory Affairs can offer in this area are as follows:
- Formatting the the dossier from paper to electronic format (eCTD and Nees)
- Creation of the dossier in electronic format (eCTD and Nees)
- Life cycle management of the dossier
A Clinical Trial is a study on humans designed to discover or verify the clinical, pharmacological and pharmacodynamic effects and safety of one or more medicinal products, medical devices or diagnostic/ therapeutic procedures and techniques, in order to identify the benefits and possible adverse reactions.
The authorization procedure for the initiation of a clinical trial on medicinal products involves the assessment by the Competent Authority and Ethics Committees involved of all documentation relating to clinical trials that are to be conducted. In particular the Clinical Protocol, the IMPD, the informed consent and documentation for patients, the insurance policy (Ministerial Decree of 14 July 2009), manufacturing site authorizations and agreements with clinical sites are all carefully assessed in order to provide public assurance regarding the feasibility and the scientific and ethical aspects of the clinical trial.
A particularly important role in the management of internal processes is held by the National Observatory on Clinical Trials (OsSC), coordinated and managed directly by the AIFA that, in addition to collecting information on clinical trials (phase I-IV) held in Italy since 2000, is a fundamental instrument for managing and monitoring the trials. The European Commission has recently developed the "Proposal for a Regulation of the European Parliament and of the Council concerning the clinical trials on medicinal products for human use, which repeals Directive 2001/20/EC. " In recent months, the text is currently under plenary review by the regulatory authorities of the Member States and aims, amongst other things, to render Europe more receptive to a greater number of trials, building a coordination structure capable of responding rapidly to the demands of the "sponsor".
Di Renzo Regulatory Affairs has set up an expert unit in the area of clinical trials of medicinal products and medical devices consisting of a doctor and highly qualified technicians.
In the field of clinical trials, currently in rapid evolution from a regulatory standpoint, Di Renzo Regulatory Affairs is able to provide regulatory and technical assistance for:
- Interventional and observational Clinical Trials
- Review of documentation to be submitted to the competent authority and the Ethics Committees
- Data entry into the OsSC and the National Register for Observational Studies
- Translation of the dossier, clinical protocols, informed consent and other documents to be included in the CTA.
Pharmacovigilance is the set of activities undertaken in order to ensure a safe and appropriate use of medicines. It is an essential tool for monitoring safety in the use of drugs, to protect public health, and consequently it imposes specific obligations on the health authorities and the companies that market pharmaceuticals. It also requires close collaboration between all professionals involved, supranational, national and local health authorities as well as pharmaceutical companies. Moreover a conscious involvement of end-users, i.e. citizens-patients, is highly desirable.
In compliance with current regulations and European and national guidelines, Di Renzo Regulatory Affairs has, for some time, set up a unit (consisting of three QPPVs, two doctors, a chemist, two pharmacists, three graduates in pharmaceutical chemistry, two biotechnical doctors, two IT specialists, a language graduate and three administrative personnel) able to offer clients a complete outsourcing of pharmacovigilance service. Di Renzo Regulatory Affairs has a validated Pharmacovigilance database that facilitates the recording and safe keeping of all Individual Case Safety Reports (ICSRs) relating to suspected adverse reactions, in accordance with the provisions of the current legislation.
The services offered are as follows:
- Assume the role of the European Qualified Person for Pharmacovigilance (EU-QPPV)
- Assume the role of Local contact point
- Validated Pharmacovigilance database
- Daily checks of the National Network of Pharmacovigilance (RNF)
- Periodic inspection of national and international scientific literature for medicinal products and active substances
- Inclusion of cases of Italian literature in the National Network of Pharmacovigilance (RNF)
- Information requests for follow-ups
- Translation into English of ADRs in CIOMS format and / or in xml format in accordance with the E2B standard
- Inserting ICSRs in EudraVigilance
- Insertion and update of medicinal products in the European database Extended EudraVigilance Medicinal Product Dictionary (XEVMPD)
- Audits and preparation for inspections by regulatory authorities
- Pharmacovigilance Training for pharmaceutical sales representatives and / or company personnel
- Preparation of Periodic Safety Update Reports (PSURs)
- Preparation of Standard Operating Procedures (SOPs)
- Preparation of the Risk Management Plan (RMP)
- Preparation, maintenance and updating the Pharmacovigilance System Master File (PSMF)
- Drafting, reviewing and updating the Safety Data Exchange Agreements (SDEA)
- Data Entry
Advice for scientific information provided by Di Renzo Regulatory Affairs to pharmaceutical companies is provided by a unit consisting of a technician and administrative personnel , under the supervision of a doctor.
The main services offered are as follows:
- Regulatory consultancy in the field of scientific information
- Evaluation of the promotional material and websites for health workers to verify their compliance with current regulations and guidelines
- Development of clinical expertise from literature
- Development of texts for scientific medical information
- Possibility to assume the role of scientific responsible person
- Refresher company courses on current regulations relating to advertising and scientific information
- Design and graphic layout of brochures, visuals, flyers, magazines and other means of dissemination
- Deposit of promotional materials aimed at healthcare professionals
- Request for authorization to participate in conferences and congresses
- Preparation of SOPs
The field of advanced therapy medicinal products has been regulated recently and for this reason the applicative aspects are still quite sketchy.
The Marketing Authorization Application of advanced therapy medicinal products prepared industrially and to be marketed in the Member States is issued by the CHMP of the EMA on the advice of the Committee for Advanced Therapies, through the centralized procedure.
The main European standard reference is the Directive 2001/83/EC and Regulation (EC) No. 1394/2007 establishing the European Committee for Advanced Therapies.
Di Renzo Regulatory Affairs has the expertise to provide companies with the necessary regulatory advice in this area.
Insertion into XEVMPD database
To comply with the provisions of the Regulation 1235/2010/CE and the European Directive 2010/84/EU pharmaceutical companies that are holders of marketing authorizations must fulfil the requirement to fill out the new XEVMPD database of the EMA with data relating to their authorized medicinal products in the European Union.
The authorization holders are also responsible for the correct maintenance of this information and are required to update the XEVMPD database when there are variations, transfers or new authorizations.
The XEVMPD database to be completed with the required data is accessible via a username and password from the site of EudraVigilance. In order to deal with these requirements there is a team of experts at Di Renzo Regulatory Affairs able to provide assistance to pharmaceutical companies.
Readability User Test and Bridging Study
To meet the latest requests issued by the AIFA with the Communiqué of the 07/23/2013 (updated with the Communiqué of the 25.09.2013), Di Renzo Regulatory Affairs has set up a unit for the preparation of readability tests of patient information leaflets for medicinal products for human use.
Based on these Communiqués as of the 1 July 2015 all marketing authorization holders of medicinal products for human use authorized nationally must submit a type IB variation to update module 1.3.4 for the adaptation of the patient leaflet carried out by means of a readability tests, along with the report containing the results of the test.
This deadline also applies to requests for new marketing authorizations and line extensions using the national procedure still being assessed at the date of the Communiqué of 07/23/2013. The obligation also extends to requests for new marketing authorizations and line extensions that will be presented with a national procedure with effect from 1 January 2014.
Below are some of the services that Di Renzo Regulatory Affairs is able to offer companies:
- Identification of products on which to carry out the readability test and bridging report
- Preliminary examination of the SPC and PIL
- Adaptation of PIL into QRD format
- Running the readability tests in all envisaged phases including the recruitment of personnel to be interviewed
- Preparation of all documentation required, including planned cycles of interviews
- and the final layout of PIL
- Delivery of the final report in Italian or English
- We are at your disposal for further information and clarifications.
On June 3rd 2014 a Decision dated April 14th 2014 by the Italian Medicine Agency (AIFA) entered into force, establishing the requirements for the application of the provisions regarding the stock disposal of the packs of medicinal products whose marketing authorizations were changed or renewed.
According to the new decision, the marketing authorization holders of medicines authorized for the Italian market have the obligation to make the updated patient information leaflet available to pharmacists within 30 days from the publication of the relevant decree in the Italian Official Gazette, so that pharmacists can in turn deliver it to the users.
For this aim it is possible to voluntarily provide Farmadati with an updated patient information leaflet. Farmadati is the information service provider that will manage the database available to pharmacies.
Di Renzo Regulatory Affairs is offering the following services to all companies intending to use Farmadati services to comply with the AIFA decision:
- preparation of the cover letter
- preparation of the documents to be sent to FarmaStampati
- preparation of the communication regarding the marketing of the first batch including the updated PIL
- relevant communication to Farmadati
The regulation on bilingualism and the Unifarm database
Article 14 of Legislative Decree 29th May 2001, no. 283 (Regulations on the implementation of the Special Constitution of the Region Trentino Alto Adige regarding the obligation of bilingualism in the preparation of labels and patient information leaflets of medicines) provides for that labels and PILs of medicines marketed in the Italian Region Trentino Alto Adige are supplied also in German and are made available to pharmacists through the database Unifarm.
In order to comply with this regulation, Di Renzo Regulatory Affairs has increased its relevant unit – now consisting of a mother-tongue translator, a graphic designer and an expert on data entry – to translate labels and PILs into German in a short time and at competitive prices, including legalization by an Italian court, lay out in the format required by Unifarm and database entry.
In order to market veterinary medicinal products they must be authorized by the Ministry of Health or the European Medicines Agency (EMA).
Our consultancy for veterinary medicines mainly covers:
- Advice on national and international legislation
- Preliminary examination of documents prepared by the commissioning company
- Advice and preparation of applications for marketing authorizations for national, mutual recognition and decentralized procedures
- Consultancy and preparation of variations, renewals and transfers of marketing authorizations
- Advice on applications for manufacturing authorizations of raw materials and finished products
- Advice, drafting and translation of SPCs, labels and leaflets in accordance with current guidelines
- Requests for certificates of free sale
- Relations with consulates for visa issuance
- Due diligence and gap analysis
- Veterinary Pharmacovigilance
- Assistance with meetings with the Ministry of Health, the ISS or other regulatory agencies
- Design and creation of mock-ups of the primary and secondary packaging, brochures, leaflets and, if required, the printing
- Refresher courses to be held at our headquarters in Rome or Milan, or at the commissioning company
In the field of veterinary pharmacovigilance Di Renzo Regulatory Affairs has a unit consisting of a doctor, a chemist, a graduate in Pharmaceutical Chemistry, a biologist and administrative personnel.
With regard to medicinal products for veterinary use and in compliance with current European and national guidelines and regulations Di Renzo Regulatory Affairs is able to offer the following services:
- Management of Adverse Drug Reactions (ADRs)
- Follow-ups of ADRs
- Preparation of CIOMS
- Weekly searches of cases in national and international scientific literature
- Preparation of Periodic Safety Update Reports (PSURs)
Advertisements for veterinary medicinal products
The advertising of veterinary medicines that do not require a medical prescription, so-called free sale, is permitted only after a specific authorization has been issued by the Ministry of Health, following the favourable opinion expressed by the Advisory Committee for the licensing of healthcare advertising.
The Commission for the licensing of health care advertising is responsible for evaluating the content of the advertising, ensuring that it contains the correct information for the purposes of the safe and harmless use to human and animal health.
Di Renzo Regulatory Affairs is able to assist pharmaceutical companies involved in this sector by:
- A preliminary examination of the advertising material
- The preparation of the application to be submitted to the Ministry of Health
- Advice on the bureaucratic process
Medical Device Consulting
In the field of medical devices, Di Renzo Regulatory Affairs provides consulting services to Italian and foreign companies that produce, market and import Medical Devices & IVDs into the Italian territory.
It has a unit composed of three biomedical engineers, a chemist and administrative staff with over thirty years of experience in the field of Medical Surgical Devices and Medical Devices. It also collaborates with international experts able to provide normative and procedural support to companies interested in European and non-European markets.
The activities that this unit is able to perform relate to the following items:
- Advice on current legislation in Italy, Europe and in certain non-European countries in relation to medical devices.
- Verification of compliance of the technical documentation and the requirements for the registration of medical devices in Italy, Europe and in certain non-European countries
- Notification of medical devices into the database /Repertoire of the Ministry of Health and in the relative databases of other countries belonging to the EEA Agreement zone.
- Notification of in vitro diagnostic devices at the Ministry of Health and other European countries
- Registration of manufacturers of custom-made devices
- Preparation of technical dossiers in order to obtain the CE mark
- Contacts with Notified Bodies and consultancy for obtaining CE marking
- Contacts with qualified laboratories to conduct tests on devices
- Gap analysis on the documentation available from companies for marketing authorizations for devices in non-European countries
- Device-vigilance in Italy and Europe
- Assistance with the submission of clinical trials to the competent authorities and Ethics Committees, together with the related consulting activities.
- Assuming the role of QA / RA as defined by the forthcoming European Regulation on medical devices.
- Assuming the role of Authorized representative (direct contacts with the competent authorities of the EU and management of post-marketing surveillance)
- Regulatory activities regarding the import / export of medical devices
- Verification of compliance of the documentation accompanying medical devices for customs authorities
- Audits at companies and suppliers of medical devices
- Collaboration with and participation in the development of start-up projects in the biomedical field (feasibility studies).
- Implementation of the quality system in accordance with the ISO 13485
- Training Courses in European regulations and technical standards.
- Preparation of documents required for Class I devices and technical declarations of compliance issued by Di Renzo Regulatory Affairs
- Analysis of customs requirements and health and safety clearance (Nulla Osta Sanitario)
- Preparation of advertising material and, if necessary, the preparation of applications for authorization
- Certificates of Free Sale
- Preparation of technical reports required for registration of trademarks and product patents.
According to the definition in the “Manual on Borderline and Classification in the Community Regulatory Framework for Medical Devices” prepared by the working group Borderline and Classification medical devices expert group of the European Commission, borderline products are those products which, due to their nature, do not clearly belong to a specific area and for which it is therefore difficult to define the reference regulations to be applied.
Alternatively, borderline products are those product falling into the definition of medical device, but excluded from the application of the relevant directives. When a product does not fall into the definition of medical device reported in the directive or is excluded from the application of the same directive, other directives or reference regulations are applied.
Products with such a difficult classification are defined as borderline since they are at the border between the definition of device and the definitions provided by regulations ruling other areas, such as IVDs, medicines, biocides, supplements, cosmetics and PPEs. It is for the manufacturers to decide whether their products fall into the definition of medical device (Legislative decree 46/97 art. 1, section 2). In case of doubts, it is for the Competent Authorities to determine the classification of borderline products.
When deciding whether a product falls into the definition of medical devices it is essential to identify the destination of use and the mechanism of action. Our consultancy company offers support to the manufacturer in the assessment/control of the applicability of the MD reference directive and in case in starting a certification procedure for these products.
Database and Repertorio – Medical Device Registration in Italy
The Ministerial Decree of February 20, 2007 set up the new database of medical devices, also in view of the establishment of a European database. The decree governs the new arrangements for the registration of products in the database by manufacturers, provided for by Legislative Decree no. 46/97, and registration in the Repertory of devices sold to the National Health Service provided by art.1, paragraph 409 of Law No. 266/2005 (as amended by Legislative Decree No. 1 of the 24 January 2012).
The database of medical devices collects information related to all medical devices released in the Italian territory by domestic manufacturers. However, the registration of medical devices by European or non-European manufacturers who wish to distribute their medical devices in Italy is limited to those belonging to classes higher than I.
The database of medical devices is an important instrument for market surveillance, as well as for the supervision of medical devices in the country.
The Repertory is a subset of the database. The registration of the devices in the Repertory allows for the visibility of information relating to these devices to all operators of the National Health Service. This characteristic facilitates manufacturers in tenders. On this occasion, additional documentation on the medical device, object of the tender, is not required from the manufacturer because it can be found via the Repertory itself.
The regulations for the method of enrolment in the database and the Repertory have been determined by the Decree of the 21 December 2009, "Changes and additions to the Decree of February 20, 2007 laying down “New methods for the requirements for the registration of active implantable devices as well as for registration in the Repertory of Medical Devices ". In March 2012, moreover, the fee of € 100.00 was abolished hitherto required for registration in the Repertory.
Classification of medical devices
A medical device, as defined in the Legislative Decree 46/97, is any instrument, apparatus, appliance, material or other article, whether used alone or in combination (including software necessary for its correct functioning) and intended by the manufacturer to be used for human beings for the purpose of diagnosis, prevention, monitoring, treatment or alleviation of disease; for diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap; for investigation, replacement or modification of the anatomy or of a physiological process; for conception intervention, for which the product does not achieve its principal intended action in or on the human body, by pharmacological or immunological means via a metabolic process, but which may be assisted in its function by such means.
Medical devices are classified into four classes depending on complexity and the increasing risk.
- Class I: Less critical devices, such as most of those non-active and non-invasive (within class 1 two subclasses can be identified: Class I sterile - those supplied in a sterile state - and Class I m - those that perform a measurement function).
- Class IIa: Medium risk devices, such as certain non-activedevices(invasive active devicesthat interact with thebodyin a non-threatening manner.
- Class IIb: Medium / high risk devices, such as certain non active devices(invasive types) andactive devicesthat interactwith the body ina dangerous manner.
- Class III: High risk devices, such as most implantable devices, those containingmedicinesanimal derivativesandcertain medical deviceswhich act on thefunctionsvital organs.
Medical devices can be be marketed in the EU after obtaining the CE certification. This certificationguarantees that the product has been subjected to a conformity assessment procedure that attests to its compliance with the essential requirements of the relative Directive.
The CE certification for Medical Devices higher than Class I is issued by Notified Bodies accredited for the certification of specific types of medical devices and for specific conformity marking procedures. The manufacturer may apply to any accredited Notified Body in Italy or in another EC country of his choice. All medical devices marketed in Italy must be registered in the database of the Ministry of Health, as required by the Ministerial Decree of December 21, 2009.
In Vitro Diagnostic Medical Devices
The Legislative Decree 332/2000 defines In-Vitro Diagnostic Medical Devices as any medical device consisting of a reagent, a reactive product, a calibrator, control material, a kit, an instrument, apparatus, equipment or system intended by the manufacturer to be used in vitro for the examination of specimens from the human body, including blood and tissue donations, solely or principally for the purpose of providing information concerning a physiological or pathological state, or a congenital abnormality, or allowing for the measurement of the safety and compatibility with potential recipients, or allowing for the monitoring of therapeutic measures.
Specimen containers are considered to be in vitro diagnostic medical devices. Specimen containers are devices, whether vacuum-type or not, specifically intended by their manufacturers to directly collect a specimen from the human body and store it for the purpose of an in vitro diagnostic examination. In vitro diagnostic medical devices, for the purposes of conformity assessment, are classified into four categories based on the intended use indicated by the manufacturer and on the risk to public health and / or for the treatment of the patient, in the case of error in the performance for which they are intended:
IVD medical devices are classified according to the risk associated with the type of analysis performed and the type of reagents used to carry this out:
- In vitro diagnostic medical devices covered by Annex II List A of the Legislative Decree no. 332/2000: High-risk for individual and to public health
- In vitro diagnostic medical devices covered by Annex II List B of the Legislative Decree no. 332/2000: High-risk for individual and / or moderate to public health
- Devices for self-testing: any device intended by the manufacturer to be used at home by layman, people not expert in diagnostic tests.
Other types of devices: all other devices that do not belong in Annex II and are not intended for self-testing. These products make up the vast majority of devices and do not pose a direct risk to the persons tested, as they are mainly used by adequately prepared professionals. Moreover, the results of the analysis, obtained with this type of reagents, must be confirmed by other means. In order to market in vitro diagnostic medical devices in the EU, they should possess the CE certification demonstrating their compliance with the relative directive. Following the entry into force of Eudamed on the 01/05/2011 there is a continuing obligation to notify the Ministry of Health of data which allows for the identification of devices referred to in Annex II and devices for self-testing placed on the market or put into service within the Italian territory, as provided for in Article 10, paragraph 2 of Legislative Decree 332/2000.
In order to obtain the CE Certification, a Technical File is required, depending on the assessment procedure to be followed, as well as a Quality Management System by the manufacturer.
Di Renzo Regulatory Affairs is able to support the manufacturer throughout the whole procedure of certification of a device. In particular, we offer the following services:
- Feasibility studies related to the EC Certification project
- Preliminary assessment regarding the need to perform non-clinical and clinical testing on the MD
- Interaction with analysis laboratories, CROs and Notified Bodies
- Preparation of the Technical File
- Implementation of the quality system according to the standard ISO 13485
- Consultancy for the authorization of Borderline medical devices by Notified Bodies
- Consultancy for the certification of medical electrical equipment and medical software
- Certification of medical devices with OBL (Own Brand Labelling) procedure
The technical dossier is a collection of information and documents that describe in detail the medical device under review and, in particular, aspects related to the safety and efficacy of the product, from the design stage right through to post-marketing surveillance. The technical dossier should also describe all possible solutions undertaken by the manufacturer to ensure the maximum safety of the device.
This document must be kept up to date and, with the exception of Class I medical devices, IVDs included in Annex II and auto diagnostic devices, should be submitted for assessment by a Notified Body in order to obtain the CE marking, a fundamental requirement for the commercialization of medical devices in the European market.
Once the medical device has been placed on the market, the competent national authorities have the right to inspect the technical dossier, regardless of the classification of the medical device, at any time. In addition, an incomplete or inadequate technical dossier may cause delays to market entry or the prohibition of the product release.
Di Renzo Regulatory Affairs assists many Italian and international companies in the certification process aimed at obtaining the CE marking. In particular, in order to obtain the CE marking, it deals with the compilation of the technical dossier and all the activities connected with it:
- Assist the manufacturer with the collection and production of the necessary documentation
- Maintaining relationships with analysis laboratories, the Notified Bodies and any production sites
- Review all existing documentation in support of compliance with the applicable essential requirements of the Directive
- Identify applicable standards based on the type of product
- Identify tests / analyzes to be performed on the medical device
- Assist the manufacturer in the identification and assessment of risks
- Review / prepare labels and instructions for use
- Develop / update and implement a risk management plan
- Draft the clinical evaluation in accordance with the European guidelines
- Design and create mock-ups for primary and secondary packaging
A clinical trial is a study on humans aimed at discovering or controlling the clinical, pharmacologic and pharmacodynamic effects as well as the safety of one or more medicinal products, medical devices or diagnostic/therapeutic procedures and techniques, in order to detect their benefits and any possible adverse reaction.
A clinical investigation is often required for MDs which are not marked yet, in order to obtain the EC mark. When a medical device presents high risks or is very innovative, for instance, it is not enough to include an assessment of the literature clinical data in the TF, but a new trial could be necessary. The manufacturer of medical devices with no EC mark and intended for clinical trials, or the European representative should submit a notification of the clinical trial to the Ministry of Health. The communication is due also if the clinical trials regards destinations of use which are different from those which were the subject of the EC mark or if the MDs are already EC marked but they were changed in their structure and composition.
The manufacturers, authorized representatives and other subjects sponsoring clinical trials with EC-marked medical devices (post marketing) and with a destination of use complying with the marking should communicate all information regarding the starting of the trial to the Ministry of Health.
The supporting tools to correctly design and carry out a clinical trial are the MEDDEV guidelines and the harmonized technical rules UNI-EN ISO 14155-1 and UNI-EN ISO 14155-1, defining the performance of clinical trials and the requirements for a clinical assessment plan (clinical protocol), respectively.
Di Renzo Regulatory Affairs set up a specific unit for the clinical trials of medicinal products and medical devices, including a graduate in Chemistry and Pharmaceutical Technologies, a physician and an experienced administrative clerk. The activities offered by Di Renzo Regulatory Affairs in this field are the following:
- Assistance with the submission of authorization applications for clinical investigations with medical devices at the Ministry of Health and the Ethics Committees
- Communications of initiation of post marketing clinical investigations
- Assist the manufacturer in the management of clinical trials
- Regulatory updates
Advertising of medical devices
The advertising of medical devices is regulated by Article 21 of the Legislative Decree of the 24 February 1997. In particular, it prohibits advertising to the general public of devices that can be sold only with a prescription from a doctor or be used possibly with the assistance of a physician or other healthcare professional, and states that advertising to the public of medical devices different from those mentioned above is subject to authorization from the Ministry of Health.
To this end, the manufacturer or person responsible for placing a product on the market must request an authorization to carry out health advertising by submitting a request to the Ministry of Health.
Di Renzo Regulatory Affairs, with his unit consisting of a pharmacist, a chemist and administrative personnel, is able to provide the following services:
- Advising on the current legislation
- Accurate examination of the documentation from the company, before being submitted to the Ministry of Health
- Preparation of the application, submission to the Ministry and monitoring of the entire bureaucratic process
Medical Device Post-Market Surveillance and Vigilance
The legislation on medical devices states that the manufacturer, or his authorized representative, is obliged to notify the Ministry of Health, if they become aware of any deterioration in the characteristics and performance of a device or any inadequacy in the instructions for use which might lead to or that have led to death or serious deterioration in the health of a patient or user, as well as safety reasons that led to the withdrawal from the market of a medical device by the manufacturer itself.
The reporting obligations also apply to the legal representatives of public and private healthcare facilities as well as public and private healthcare professionals, on the basis of findings in the course of their activities.
The medical devices vigilance unit of Di Renzo Regulatory Affairs is part of a broader monitoring unit which also covers the area of medicinal products for human and veterinary use (pharmacovigilance), biocides, cosmetics and food supplements.
Di Renzo Regulatory Affairs is able to offer its clients the following services:
- The role of Responsible person for vigilance Italy
- The role of Responsible person for vigilance at a European level and point of contact with the competent authorities of the various countries, having experienced partners in this sector in all EU Member States and in many non-European countries
- Assistance to manufacturers with the requirements provided for by European regulations relating to incidents in EU and non-EU territory (Management of notifications of incidents / near misses)
- Assistance to manufacturer / authorized representative during the follow-up of incidents and near misses
- Updates on national and European legislation
- Refresher courses for company staff
- Preparation of company standard operating procedures (SOP) for device-vigilance activities.
The Authorized Representative
The Authorized Representative is a natural or legal person, explicitly designated by the manufacturer and established within the Community, who acts on behalf of the manufacturer and may be consulted by the authorities and bodies within the Community in lieu of the manufacturer.
The Medical Devices Directive requires that the European authorized representative (EC REP) appear on the label. Moreover the EC REP is obliged to maintain the technical dossier of the Medical Device in order to reply to any requests from the Competent Authorities.
Di Renzo Regulatory Affairs, a company with offices in both Italy and the UK, has many years of experience in the medical device and in vitro diagnostic field. As is required by the forthcoming new regulation, the staff of the Medical Device Department consists of qualified people with expert knowledge and experience regarding the regulatory requirements for medical devices in the European Union.
As EC REP Di Renzo Regulatory Affairs is able to assist with the following:
- performing product registrations according to the MDD 93/42/EEC, IVDD 98/79/EC, AIMDD 90/385/EEC in EU countries
- manage incident reporting according to the relevant directives within Europe
- be the contact point for European Competent Authorities
- cooperating with the competent authorities on any corrective action that may be necessary to eliminate the risks posed by devices;
- immediately inform the manufacturer of any complaints or reports from healthcare professionals, patients and users regarding suspected incidents related to a device
All activity will be agreed on beforehand by means of a technical contract (mandate) between the manufacturer and Di Renzo Regulatory Affairs.
Quality Management System for Medical Devices
The Quality Management System is a system of control, which is a set of activities designed to check that the results of a given process comply with established expectations. The organization of a System of Quality Management is based on the documentation that defines the activities implemented by the company for quality assurance.
The ISO 13485 is a standard recognized as a harmonized technical standard for quality systems designed specifically for companies that deal with the production, storage and distribution of medical devices. The ISO 13485 standard integrates the ISO 9001 standard and has many things in common with the latter. However, there are additional requirements for the control of processes, design, archiving reports, distribution of responsibilities, traceability and so on.
The ISO 13485 is the path most commonly chosen by companies that deal with medical devices to meet the requirements of a quality system required in Europe, Canada, Japan, Australia and other countries. The application of this standard is voluntary for manufacturers who wish to sell their medical devices in Europe, but almost all companies choose to apply it because, generally, it meets the requirements of the directives and is considered suitable when applying the harmonized technical standards.
Di Renzo Regulatory Affairs provides the following services:
- Consultancy for the preparation and maintenance of the quality system according to ISO 13485
- Draw up the Quality Manual – that establishes the quality policy to be pursued and describes the system of quality management
- Draft SOPs - defining in detail, for each activity, actions, responsibilities, methods and means of operating, controls and registrations to be carried out
- Prepare data recording systems - that are intended to give objective evidence of activities performed, the checks carried out and the results obtained
- Taking on the role of Quality Assurance for the ISO 13485 systems
- Audit of the quality management system of the manufacturer and / or distributor
- Audits pre and post inspections by Notified Bodies and Competent Authorities at manufacturers of medical devices
- Audits at suppliers manufacturers / producers of medical devices to assess the level of compliance with ISO 13485
- Non-conformance management and CAPA (Corrective and preventive action)
- Participation in review meetings of the executive management
- Training of internal auditors
- Management of complaints and monitoring procedures on the market
- Control and update of the documentation of the quality system.
Presidi medico chirurgici and biocidal products
The so-called presidi medico chirurgici (PMC, literally meaning medical-surgical aids) are a series of products and substances placed on the market such as germicides or bactericides, insecticides, rat poisons for domestic and civil use and insect repellents.
The national legislation governing the marketing of these products will be completely replaced by the European legislation on biocidal products, entailing the integration of presidi medico chirurgici into the category of biocidal products.
The list of active ingredients present in products on the market is under review at the European level and, once approved, will be subsequently used for the preparation of biocides.
The availability on the market and use of biocidal products, as of the 1 September 2013, is subject to the Regulation of the European Parliament and of the Council no. 528/2012 of 22 May 2012, which repealed Directive 98/8/EC and that has been partially modified by the Regulation (EU) n. 334/2014. A definitive list of active ingredients, the use of which is accepted in Europe, is expected to be completed by the 31.12.2024, as determined by the Delegated Regulation (EU) 736/2013.
With the entry into force of Regulation 528/2012, Annex I of Directive 98/8/EC (that containing the authorised active substances) has been replaced by the Union list. The PMC, which are currently on the market containing the active ingredients included in this list will have to be newly authorised in accordance with the biocide regulations.
As a consultancy company, we are able to offer advice to companies wishing to market their biocidal products and PMC, providing accurate and up to date information on the status of the individual active substances and existing legislation, accompanying companies through the complex process of marketing authorisation during the biocide-PMC transition period, and prepare the dossier for authorisation for formulations as biocides.
In particular, Di Renzo Regulatory Affairs is able to offer the following services:
Presidi medico chirurgici (PMC)
- Advice on Italian and European regulations in force and on the evolution of the legislation on biocides, in particular on the period of transition PMC-biocides;
- Verification of the inclusion of the active substances in the Union list in order to classify the product as a PMC / biocide / product of free sale or otherwise in accordance with the Italian and European regulations (feasibility study);
- Verification of the requirements for the registration in European countries and in some non-EU countries;
- Assistance with the preparation and submission of the registration dossier at the competent authorities and relevant authorisation process for a PMC;
- Assistance with the preparation of the dossier for the manufacturing authorisation of the PMC and its authorisation procedure at the Ministry of Health;
- Evaluation of advertisements to the general public relating to PMC and to biocides and the authorisation process for the advertising of PMC;
- Translations of texts and labels to / from the following languages: Italian, English, Portuguese, Greek, Spanish, French, German;
- Training courses on Italian and European regulations relating to PMC and biocides;
- Request for certificates of free sale for PMC;
- Development of mock-ups of labels, logos, design and development of brochures, leaflets and advertising material;
- Registration of trademarks and patents for any type of device or process, even relative to PMC and biocides.
- Advice on Italian and European regulations in force and on the evolution of biocides legislation;
- Verification of the inclusion of the active substances in the approved list in order to classify the product as an PMC / biocide / product of free sale or otherwise in accordance with the Italian and European European (feasibility study);
- Verification of the requirements for the registration in European countries and in some non-EU countries;
- Preliminary evaluation, preparation and submission of a dossier for the authorisation of a biocidal product in accordance with the legislation in force, in all its parts and assistance in the relative authorisation procedure;
- Identification of studies to be performed (chemical and physical analysis, stability studies, toxicological and ecotoxicological studies, efficacy studies, etc.) according to the Product Type (PT) of interest, the active ingredient and the intended use of the product;
- Preparation and verification of labels of biocides in accordance with current legislation;
- Translations of texts and labels to / from the following languages: Italian, English, Portuguese, Greek, Spanish, French, German;
- Training courses on Italian and European regulations relating to PMC and biocides;
- Development of mock-ups of labels, logos, design and development of brochures, leaflets and advertising material;
- Registration of trademarks and patents for any type of device or process, even relative to the PMC and biocides.
Regulatory consultancy for cosmetics
In order to regulate the field of cosmetic products in a coordinated manner in all Member States, the European Community has, over the past few years, been working on a project to codify the numerous regulatory amendments of the Directive 76/768/EEC, adopted in Italy by the Law 713/86.
The Regulation (EC) No. 1223/2009 came into force in July 2013 and introduced a number of clarifications and definitions, as well as important new features such as a single centralized notification procedure across the EU, a system of in-market monitoring by the Member States and a central "cosmetovigilance" system, a new procedure for a rapid update of the inventory of ingredients in cosmetic products and technical details regarding the contents of the report on the safety of cosmetics.
It also specifies the rules for the importation of cosmetics from non-EU countries and the responsibilities of the various parties involved (manufacturer, importer, distributor).
Di Renzo Regulatory Affairs caters to all companies that manufacture, market or intend to import cosmetics and enables them to respond to the new regulations issued by the European Community by offering the following services:
- European Central Notification
- Consultancy for manufacturers of cosmetic products in order to comply with new provisions of Regulation (EC) no. 1223/2009
- Preliminary examination of printed material and verification of compliance with applicable regulations
- Review, revision and possible integration of the documentation provided by the company
- Preparation and signature of the safety assessment of the cosmetic product
- Coordination of activities for the preparation of Product Information File (dossier)
- Verification of documents that accompany imported cosmetics such as certificates of analysis, batch records, lists of ingredients
- Request for Certificates of Free Sale (CLV)
- Supplier evaluations and audits conducted by specialized technicians at manufacturingcompanies to verify the quality and compliance with GMP
- Graphic design for cosmetic packaging
- Supervision service of for those companies who are in possession of a PIF prepared in accordance with regulations outside Europe
Particular Foodstuffs and Dietary Supplements
Such products include dietary supplements, foods containing added ingredients, foods for infants, novel foods and dietary products (gluten-free, hypo / sodium-free, for sports, for diabetics, special medical purposes).
At the national level, the ministerial guidelines on food supplements contain a number of provisions relating to the intake of vitamins, minerals, amino acids, fatty acids, dietary fibre and probiotics.
Consultancy for food supplements
In Italy, the marketing of a dietary/food supplement can only occur after the product has been duly notified to the Ministry of Health, which is the competent authority to assess the correspondence of the formulation and the claims with current local regulations.
In the case of a positive outcome the supplement, subject of the notification, will be included in the Register of dietary supplements available on the website of the Ministry. In the field of food supplements, Di Renzo Regulatory Affairs engages highly qualified personnel in the chemical, pharmaceutical and food sciences sector, able to provide consulting services on:
- Preliminary examination of the text of the labels and verification of their compliance with current regulations
- Process for notification to the Ministry of Health
- Request for Certificates of Free Sale ( CLV )
- Formulation of new products and / or reformulation of products already on the market
- Identification of claims that can be used
- Assistance for imports from European countries and beyond
- Assistance in the preparation of technical and administrative documents for export to Europe and non-EU countries
- Design and development of packaging
- Regulatory up-dates
- Company courses on the relevant regulations
- Authorization procedure for production sites
- Preparation of brochures and leaflets
- Assistance with the process of phytovigilance
- Audits at domestic and foreign manufacturing companies
- Preparation of technical and scientific rationale for dietary supplements containing ingredients derived from plants ( botanicals )
Food for Special Groups
The entering into force of Regulation (EU) no. 609/2013 on 20th July 2016 has abolished the classification of products for special nutritional uses. This regulation, known as FSG (Food for Specific Groups) now includes provisions on the following food classes:
- infant formula and follow-on formula;
- cereal-based food and other baby food;
- food for special medical purposes;
- total diet replacement for weight control.
These product classes are intended for specific groups with special nutritional requirements. There are, for instance, infants and young children, subjects with nutritional problems due to disorders, diseases or medical conditions, overweighed subjects that need to fully satisfy their nutritional requirements with reduced or very reduced energy. Regulation 609/2013 does not include provisions on:
- gluten-free food intended for people suffering from celiac disease;
- delactosed food.
The indication about the absence or reduced presence of gluten as well as lactose may voluntarily be reported in labelling, according to Regulation (EU) no. 1169/2011. Regulation (EU) no. 828/2014 includes the claims accepted for the absence or reduced presence of gluten in food.
Based on the provision of Regulation 609/2013, also food for sportspeople shall be subject to a new classification: some as food supplements, others as enriched food.
Also the food for persons suffering from carbohydrate metabolism disorders (diabetes) is no longer a product for special nutritional uses. For this class there are no specific provisions at European level, as a Commission report to the European Parliament and to the Council concluded that the scientific basis for setting specific compositional requirements is lacking. Indications such as “sugar-free” or “low sugar”, can be included according to Regulation (EC) n. 1924/2006, but no explicit reference can be made to «diabetes»; therefore claims such as «product for diabetics» is not allowed as well, with potential exceptions only for food for special medical purposes, as in enteral regimes.
Labelling of Food Products
The European Community has in recent years established ever more complex and precise rules for traditional food products, as well as those enriched and functional products or for particular nutritional uses. The most important updates relate to the labelling of foodstuffs, additives and nutritional and health claims.
The new Regulation on food labelling, which will be fully operational with effect from 13 December 2014, is certainly one of the most significant regulations, primarily aimed at ensuring maximum transparency for the consumer in respect to that which is indicated in the labels. The Regulation clarifies and amends certain provisions relating to the nutrition table, the declaration of the presence of allergenic substances, the visibility and legibility of the wording, the indication of the place of origin and much more in order to rearrange and complement the current legislation on food labelling in a more rational manner.
The main services provided:
- Study and evaluation of the product for the preparation of the labelling and presentation of food product
- Any amendment to the formulation in order to be able to attach specific claims
- Evaluation and correction of the advertisements on the basis of provisions of the regulations on claims
- Updates on food legislation
- Creation of the graphic packaging
The use of words or information that directly or indirectly allows the placement of product in the field of medicines must be avoided. According to the Regulation 1924/2006 of the European Parliament and of the Council, of the 20th of December 2006, on nutrition and health claims made on food, all operators in the European Union are bound by the constraints, requirements and parameters associated with the use of nutritional claims
The purpose of the regulation is to enhance the level of health protection for consumers by providing correct information and more informed food choices, by defining the criteria for claims on labels or in advertising a particular requirement of a food. The claims must be truthful, based on scientific evidence, and must not attribute to food properties such as to prevent, heal and / or cure diseases.
The key innovation brought by the new regulations is that before the operator could move freely within the limits and the prohibition of deception in art. 2 of the Decree. 109 / 92, the new rules established a system of so-called "positive / mandatory" use of such messages, legitimizing its use only under certain conditions. The claims described in the regulation are essentially divided into 3 groups:
Nutritional and health indications referred to:
The role of a nutrient or other types for the growth, development and functions of the body Psychological and behavioural functions Weight loss or weight control or sense of satiety or the reduction of energy from the diet
Nutrition and health claims based on newly developed scientific evidence and / or for which one can apply for protection of confidential data. For these health claims, authorization is granted on a case-by-case basis subject to evaluation of the scientific dossier by the EFSA.
Nutrition and health claims referring to the reduction of disease risk and development and health of children. Even for these types of claims, authorization is granted on a case-by-case basis subject to the evaluation of the scientific dossier by the EFSA.
Advertising supplement foods
The advertising of food supplements to the public is not subject to any prior authorization from the Ministry. It is free, under the responsibility of those who place the product on the market.
However, one must pay special attention that pharmacological properties will never be attributed to a dietary supplement. In other words, claim referring to health should never be ascribable to healing activities and modification / improvement of medical conditions.
Food supplement labelling
Notwithstanding the general legislative provisions on food labelling, the label of a dietary supplement must indicate:
- the amount of product to be taken daily with a warning not to exceed
- the content of nutrients and / or characterizing substances with the possible name of the active ingredients per daily dose
- the nutritional or physiological effect of the product resulting from the collection of its ingredients
- that supplements are not intended as a substitute for a varied diet, or are not intended as a substitute for a varied and balanced diet and a healthy lifestyle, as quoted verbatim in Regulation 1924/2006
- the warning: "Keep out of the reach of children under three years of age"
- sources of vitamins and minerals used must appear in the list of ingredients
Notification and registration dietary supplements
Currently, the marketing of dietary supplements is subject to the notification procedure,i.e. the transmission to the Ministry of Health of the template of the label used for marketing. In order to standardize the procedures of notification a Circular of the Ministry of Health of the March 6, 2008, n. 4075-P was issued. The Ministry provides modules to use for both notifications and variations.
Ninety days from the date of receipt of the notification by the Ministry, the principle of tacit consent applied. In these 90 days the Ministry identifies any deficiencies or inaccuracies in the labelling and may require the company to make changes or to provide explanations and / or technical data sheets.
Dietary supplements with labelling in accordance with the regulations may be placed on the market at the same time as the notification of the label to the Ministry, except those coming from third countries, that must wait for the 90 days to expire. Supplements, for which the registration procedure has been completed positively, are inserted into a public register where they are also identified with a specific authorization code number.
If the Ministry considers that the product represents a health hazard, it will organize for its withdrawal from the market by sending a simultaneous request to the local Department of Health which has territorial jurisdiction, for appropriate investigations. The company is required to give timely and formal assurance to the Ministry that they have complied with the requirements.
Phytovigilance and Surveillance natural substances
The increasing use of natural products in food, cosmetics and in therapy has necessitated the regulation of this sector. The general trend is that of viewing the products of herbal origin, including so-called herbal medicines, as harmless since they are natural, and to use them as self-medication without consulting a doctor.
However, products based on plants can also present serious health risks, both for possible interactions with synthetic drugs taken concomitantly as well as for their quality (e.g. for the presence of residues of phytopharmaceuticles, herbicides and heavy metals) in addition to consumer hypersensitivity. To address the need for monitoring these products and the identification of potential risks associated with the use of natural products, since 2002 there has been a phytovigilance and natural substances surveillance system, which collects spontaneous reports of suspected adverse reactions arising after the intake and / or administration of the products used in "natural medicine" such as vitamins and minerals, dietary supplements, herbal products, homeopathic products (according to the Legislative Decree 219/2006), products of exotic origin, such as those of traditional Chinese medicine and Ayurvedic medicine, probiotics and other products, such as amino acids.
The system involves the participation of the ISS, the AIFA and the Ministry of Health and provides for the intensification of surveillance and control in order to ensure greater safety in the use of these products.
Di Renzo Regulatory Affairs offers a personalized service of post marketing phytovigilance for companies with supplements, herbal products and foods. We are also able to perform toxicological evaluations of herbal ingredients and food products.
Legal advice to pharmaceutical companies
As a consequence of recent requirements expressed by pharmaceutical companies with whom Di Renzo Regulatory Affairs collaborates, we have extended our expertise in the field of legal advice, in order to provide an effective and instantaneous service.
The team comprises of an administrative expert in regulatory affairs (in the field of biocide products, food supplements, medical devices, cosmetics) and two lawyers with extensive experience in administrative and civil law, who can provide support and assistance to corporate clients involved in litigation that may arise in the regulatory field.
Thanks to this team, Di Renzo Regulatory Affairs is able to collaborate with pharmaceutical companies in the requests for annulment, revocation or amendment of administrative measures and provide expert advice in litigation before the Administrative Court (TAR) and the Council of State (Consiglio di Stato).
Translation services for the Pharmaceutical Industry
All companies with international dealings that require translations of scientific texts, such as leaflets or summaries of product characteristics (SmPC), are forced, in many cases, to contact external agencies. Most of the time these translation agencies do not have staff experienced in this particular field. As they are not always familiar with the specific technical terminology, inevitably the translations may not always respond perfectly to the original text.
It should be clear-cut to to comprehend what the focus and the appropriateness of the translations should be in the field of medicinal products and related services. To overcome these frequent shortcomings, Di Renzo Regulatory Affairs has set up a unit made up of experts in the regulatory field of graduates in pharmaceutical chemistry and technology, pharmacy, biotechnology as well as native speakers of English, German, Spanish, Greek and Portuguese.
In particular, our experienced native German speaker, who has been employed in our group for over 20 years, is responsible for the translation of leaflets and labels in accordance with the laws of bilingualism, Legislative Decree 283/2001, for the region of Trentino-Alto Adige.
Free Sale Certificate
CERTIFICATES OF PHARMACEUTICAL PRODUCT (CPP)
These certificates can only be requested by the Marketing Authorisation Holders (MAH) for those countries where there is the intention to register or renew the authorisation or only to export a specific pharmaceutical product.
CPPs state that the medicinal package is registered in Italy and it is in accordance with the national legislation. It contains the Marketing Authorisation number (AIC number), the date of first registration, the pharmaceutical form, the methods and the routes of administration, the outer packaging, the shelf-life, the authorised manufacturers and the production phases, and the composition.
Furthermore, it states that the manufacturers producing the medical products are in accordance with Good Manufacturing Practice (GMP) norms recommended by the World Health Organization (WHO) and the Directive 2003/94/EC.
When a medicinal product does not have the Marketing Authorisation (AIC) in Italy, but is consistent with the model recommended by the World Health Organization (WHO), it can be exported by presenting a request for an Export Certificate, in accordance with and for the purposes set out in Article 156 of the Legislative Decree of the 24th of April 2006 n. 219 and the €œGuidelines on the implementation of the WHO certification scheme on the quality of pharmaceutical products moving in international commerce.
This type of certificate is only prepared for a single product as the production and the authorised information for the different pharmaceutical forms and the various dosages can vary.
An export certificate for a non-registered product may be requested for different reasons such as, for example:
- the product has been developed exclusively for the treatment of non-endemic pathologies (particular tropical diseases) in the exporting country;
- the product has been reformulated in order to enhance its stability in tropical climate condition;
- the product has been reformulated in order to eliminate an excipien not approved for pharmaceutical use in the importing country,
- the product has been reformulated in order to obtain a different maximum dose limit for the active substance.
MEDICAL DEVICES AND IN VITRO DIAGNOSTIC MEDICAL DEVICES (IVD)
CE marking certification (commonly indicated as CFS)
This consists of a declaration that is sometimes requested for the exportation of medical devices and in vitro diagnostic medical devices to Extra EU countries. Certificates of Free Sale for medical devices can be requested by the manufacturer or by the agent, the distributor or the importer. CFSs are issued by the Ministry of Health both in English and in Italian, according to the requirements of the company. If requested by the company, the address of the production site can be specified on the certificate of free sale.
Specific types of certificates of free sale can also be requested for food supplements, medical surgical aids, cosmetics and medicinal products for veterinary use.
The high quality of active ingredients and pharmaceutical products is guaranteed by compliance with the guidelines of Good Manufacturing Practice (GMP), as expressly provided for in Article 46 letter F) of the Directive 2001/83/EC of the European Parliament and of the Council of the 6th of November 2001, as amended by the Directive 2004/27/EC of the European Parliament and of the Council of the 31st of March 2004.
The strict observance of these rules are duly verified by the AIFA Italian Medicines Agency, the institutional body that has been given the task by the Community in Italy to make inspections at production sites of active substances, intermediaries or medicinal products for human use. Following an inspection, the AIFA issues a certificate of suitability, known as a GMP Certificate.
Training Courses in Regulatory Affairs
As is known to all professional in the fields of medicines, biocides, medical devices, food supplements, cosmetics and related sectors, the national and European regulations are in continuous evolution. This has gradually led to the establishment of the new highly specialized role of manager of regulatory affairs.
Company managers are sometimes unable to keep pace with the continuous development of regulations and obligations that need to be implemented. Di Renzo Regulatory Affairs has set up specific courses carried out by its experts, mindful of the business dynamics and the need for various executives to learn more about the fundamental notions of these standards and regulations.
These courses, for individuals or groups, can be held online, at our offices in Rome or Milan, or even at the company's headquarters. They may focus on themes of general interest or on specific topics suggested by companies.
Among the topics covered in our courses are:
- Principles and procedures for national and European drug registration in the following areas:
- Medical devices
- Food supplements
- The fundamentals of Pharmacovigilance
- Organization of internal regulatory activities and relationships with outsourced work
- Introduction to scientific information and related obligations
Participants will be supplied with the course material. It is possible to enter into agreements for the continuous maintenance of information on regulations and procedures concerning the abovementioned topics.
=== Pharmaceutical Graphics ===
In order to offer full service, the graphic department of Di Renzo Regulatory Affairs avails itself of advanced tools and software, and highly qualified staff. The services indicated below are mainly focused on companies and operators in the sectors of medicines, food supplements, biocides, medical devices and cosmetics.
The offer of these services is born out of the need to guarantee that any text used, any communication prepared as well as the preparation of the graphic material comply with the regulations in force. The main activities offered are the following:
- Preparation of mock-up and logos
- Creation and editing of brochures, folders, advertising materials
- Creation of PPT presentations
- Printing by specialized printers
- Design, creation and optimization of website SEOs
- Editing of books, magazines, catalogues and their printing by specialized printers
Registration of trademarks and patents
The services that Di Renzo Regulatory Affairs is able to offer companies involved in the registration of patents and trademarks are the following:
- Analysis of business plan and feasibility study
- Deposit trademarks and patents at a national, EU and international level
- Preparation and refinement of the documentation to be filed in order to obtain a trademark / patent
- Assistance with the of procedural steps (pre-and post-granting, maintenance)
- Support for any regulatory activities
- Translations into English by mother-tongue experts
- Set up company courses
Quality service of ISO 9000 consultants
Obtaining the ISO 9001 certification is a very complex process that can often lead to a series difficulties for a company or institution. Di Renzo Regulatory Affairs Consultancy seeks to assist companies in meeting all the requirements in order to obtain the ISO 9001 certification.
Any company that intends to initiate the process of obtaining this certification must be guided by experts in the field in order to avoid wasting time and money.
Our consultancy is aimed at companies and institutions who wish to comply with the necessary requirements in order to obtain the ISO 9001, or enhance their workflow and operations, by offering the following services:
- Drafting a company organisational chart
- Draw up the Job Description
- Prepare the Quality Manual
- Optimizing management practices
- Drafting of Standard Operational Procedures (SOP)
- Reviewing technical agreements with suppliers
- Assuming the role of Head of Quality
- Contacts with certification bodies
After obtaining the ISO 9001 certification, the staff of Di Renzo Regulatory Affairs will even accompany the customer in internal audits in order to confirm the quality attained by means of interviews with staff, review of documentation and the supervision of the progress of activities.
Regular audits after obtaining the ISO 9001 certification are usually carried out once a year, while extraordinary ones are performed after substantial changes to the working system have been implemented or in order to verify the instigation of corrective actions.