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Order Of 28 April 2005 On Good Pharmacovigilance Practices

Original Language Title: Arrêté du 28 avril 2005 relatif aux bonnes pratiques de pharmacovigilance

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JORF n ° 121 of May 26, 2005 page 9087
text # 14



April 28, 2005 Good Pharmacovigilance Practices Order

NOR: SANP0521624A ELI: https://www.legifrance.gouv.fr/eli/arrete/2005/4/28/SANP0521624A/jo/texte


The Minister of Solidarity of health and family,
Given the code of public health, and in particular Articles L. 5121-20 (13 °) and R. 5121-150 to R. 5121-180;
On the proposal of the Director General of the French Agency for Health Safety of products of Health,
Stop:

Item 1
The good pharmacovigilance practices provided for in Article R. 5121-179 of the Public Health Code, to which the speakers of the national pharmacovigilance system referred to in Article R. 5121-154, are described in the Annex to this Order.

Item 2 Read more about this Article ...


The Director General of the French Health Products Safety Agency, the Director General of Health and the Director of Hospitalization and Organization of Care are each responsible Relating to the execution of this Order, which shall be published in the Official Journal of the French Republic.

Annex
A N N E X E
INTRODUCTION


This annex is written in application of articles R. 5121-150 to R. 5121-180 of the Public Health Code, as the final result of Decree No. 2004-99 of 29 January 2004 on pharmacovigilance (OJ of 31 January 2004) and Decree No. 2004-802 of 29 July 2004 on Parts IV and V (statutory provisions) of the Public Health Code and amending certain provisions of this Regulation Code (OJ of 8 August 2004). The purpose of pharmacovigilance is to monitor the risk of adverse reactions, which includes in particular the identification, assessment and prevention of risk resulting from the use of health products for human use (see Below the scope of pharmacovigilance).
This health monitoring activity is carried out in particular on all medicinal products benefiting from a marketing authorisation (AMM) issued by the French Health Safety Agency Health products (AFSSAPS) or a Community marketing authorisation issued by the European Commission, as well as on medicinal products benefiting from temporary use authorisation (ATU)
Pharmacovigilance is based on:
-a network of thirty-one regional pharmacovigilance centres (CRLRs) distributed throughout the territory in order to promote proximity exchanges with health professionals;
-in case of investigation, The joint analysis of the data collected by the network of LRCs and the relevant pharmaceutical establishments;
-the use of a common method of accountability imposing de facto quality control of the information collected;
-the Centralization and evaluation of all drug risk information by the Technical Committee and the National Pharmacovigilance Commission, in order to give an opinion to the Director General of AFSSAPS on the measures to be taken, for To inform about the risk of adverse events related to the drug (s), to prevent or reduce the severity of the drug.
Pharmacovigilance is strongly involved in the management of iatrogenia, taking into account All drug risks in both the normal use of the drug and the misuse or abuse of the drug. It contributes to the proper use of the drug.
Pharmacovigilance now has a European dimension. The European pharmacovigilance system has evolved into a system for assessing and managing a pharmacovigilance problem on the Community territory. International collaboration is also established with the World Health Organization (WHO) and other health authorities (United States, Japan, ...).
This annex is the result of collaboration between AFSSAPS, LRCs, Representatives of the pharmaceutical industry and health professionals.
Good pharmacosurveillance practices define how health professionals, health authorities and the person responsible for placing it on the market Drug must meet their obligations. They shall be taken into account in the case of the establishment of a quality assurance system, where appropriate in conjunction with the relevant provisions of the guidelines published by the Commission of the European Communities in the Volume 9 " Pharmacovigilance of drugs for human and veterinary use " The regulation of medicinal products in the European Community.


Scope of pharmacovigilance


Pharmacovigilance is carried out on medicinal products and health products. The following human use:
-a pharmaceutical specialty: any drug prepared in advance, presented under special packaging and characterized by a special name;
-compounding: any drug prepared Extemporaneously in a pharmacy according to a prescription intended for a specific patient;
-hospital preparation: any medicinal product, except gene or cell therapy products, prepared according to the pharmacopoeial indications and Conformity with the good practices referred to in Article L. 5121-5 of the Public Health Code, due to the absence of a pharmaceutical speciality available or adapted in a pharmacy for use within a health care facility, or in The pharmaceutical establishment of that health facility authorised under Article L. 5124-9;
-pharmacopoeial preparation: any medicinal product prepared in a pharmacy according to the indications of the pharmacopoeia and intended to be dispensed Directly to patients supplied by this pharmacy;
-a divided pharmacopoeial product: any single drug, any chemical or any stable preparation described by the pharmacopoeia, prepared in advance by a pharmaceutical establishment and Divided either by him or by the pharmacy of the pharmacopoeia which puts it for sale, or by a pharmacy for internal use;
-immunological medicinal product: medicinal product consisting of an allergen (any product intended to identify or cause a modification Specific and acquired from the immunological response to an allergenic agent) or a vaccine, toxin or serum (any agent used to induce active or passive immunity or to diagnose the state of immunity);
-therapy product Authorisation for placing on the market: a medicinal product derived from preparations of human and animal living cells referred to in Article L. 1261-2, paragraph 2, of the Public Health Code;
- Radiopharmaceutical drug: any drug that, when it is ready for use, contains one or more radioactive isotopes, named radionuclides, incorporated for medical purposes;
-generator: any system containing a radionuclide A specified parent for the production of a parentage radionuclide obtained by elution or any other method and used in a radiopharmaceutical drug;
-kit: any preparation that is to be reconstituted or combined with Radionuclides in the final radiopharmaceutical;
-precursor: any other radionuclide produced for the radioactive labelling of another substance before administration;
-homeopathic medicine: any drug obtained from Products, substances or compositions called homeopathic strains, according to a process of homeopathic manufacturing described by the European Pharmacopoeia, the French Pharmacopoeia or, failing that, by the pharmacopoeias used in an official manner in a Other Member State of the European Community. A homeopathic medicine may also contain several principles;
-preparation of gene therapy: any medicinal product other than pharmaceutical specialities and industrially manufactured medicinal products referred to in Article L. 5121-8, Used to transfer genetic material and does not consist of cells of human or animal origin;
-preparations for xenogeneic cell therapy: any drug other than pharmaceutical specialities and manufactured medicinal products Industrially referred to in Article L. 5121-8, consisting of cells of animal origin and their derivatives used for therapeutic purposes, including cells used to transfer genetic material, irrespective of their level of Processing;
-a dietetic product that contains in its composition chemical or biological substances that are not themselves food, but whose presence confers on them special properties sought in Therapeutic dietetic therapeutic feeding properties;
-a product presented as the removal of the urge to smoke or reduce the addiction to tobacco; and
-a stable product prepared from blood and its components, which is a Blood-derived drug;
-insecticide and acaricide to be applied to humans;
-contraceptive products.
(Art. L. 1211-1, L. 1261-2, L. 5111-1, paragraph 2, L. 5111-2, L. 5121-1 to L. 5121-3 and L. 5136-1 of the code de la santé publique.)
All of these products are hereinafter referred to as " Drug " Or " Drug or product ".


Chapter 1
Glossary


The following definitions apply to the terms used in Section 13 of Chapter 1 of Title II of the Book I of Part V of the Public health code and in this annex. These terms can have other meanings in other contexts.


Abus


Excessive intentional, persistent or sporadic use of drugs, accompanied by physical reactions, or
Drug abuse is a data that the pharmacovigilance system must take into account to the extent that it affects the assessment of benefits and risks of the drug.
Drug abuse Containing no psychoactive substances must be reported to the pharmacovigilance system.
Historically, substance abuse has been defined specifically (art. R. 5132-97) and is the subject of a declaration to the pharmacodependence evaluation system, also managed by the French Health Products Safety Agency (AFSSAPS) (R. 5132-99 and R. 5132-100). Also for psychoactive medicinal products, reporting to the pharmacovigilance evaluation system of the Agency will inform the Agency's pharmacovigilance system, through the exchange procedures between them, to ensure that Information communicated specifically in one will be brought to the attention of the other.


European Medicines Agency
(European Medicines Agency)


This agency, whose seat is Located in London and which has been operating since 1 January 1995, is responsible for coordinating the scientific resources made available by the competent authorities of the Member States (external evaluation mechanism), with a view to providing them, As well as to the European Commission, the best possible scientific advice on any question of authorisation (quality, efficacy and safety) and surveillance of medicinal products of the European Community, which is submitted to it in accordance with the Provisions of Community legislation.
Its opinions on the evaluation of medicinal products for human use are prepared by the Committee for Medicinal Products for Human Use and shall, where appropriate, be forwarded to the European Commission for the purpose of Adopts a binding decision for the Member States.


Agence française de sécurité sanitaire
des produits de santé (AFSSAPS)


Public institution of the state of administrative character, placed Under the supervision of the Minister responsible for Health, who replaced the Medicines Agency in 1999. However, its field of competence is broader than that of the former Medicines Agency, since it extends to all human health products, including cosmetic products.
For these products, AFSSAPS has four main missions:
-scientific evaluation;
-control (including advertising);
-inspection;
-information for health professionals and the public.
It also has A health police power (set of legal and material resources to ensure health security).
The Agency organises and coordinates the implementation of vigilance systems for health products, in particular The collection and evaluation of information concerning the undesirable or unexpected effects associated with the use of these products and the health alert function in case of risk to public health.
(Art. L. 5311-1 et seq. And R. 5121-1 et seq. Of the Public Health Code.)


Alert


Unusual, qualitative and/or quantitative character of adverse reaction reports notified to a Pharmacovigilance structure, or published, advising of a potential hazard associated with the use of a drug or drug class.
In health care facilities, this term is also used to identify information, Recommendations or messages from health authorities
Marketing authorisation issued in accordance with a European procedure (centralised procedure and mutual recognition procedure)
There are two types of procedure European marketing authorisation (AMM): the centralised procedure and the mutual recognition procedure.


Centralised procedure


AMM's request is addressed to the European Agency Medicinal products by a person established in the European Community. After evaluation by the Committee for Medicinal Products for Human Use, the European Commission grants the applicant a single marketing authorisation (same summary of product characteristics, notice, labelling), valid in all the Member States of the Community The product may therefore be marketed.
The AMM thus issued is binding in all Member States and confers the same rights and obligations as the marketing authorisations issued by the national health authorities. This procedure is compulsory for high technology medicinal products derived from three biotechnological processes (as referred to in Part A of the Annex to Regulation (EEC) No 2309/93 of 22 July 1993) and optional for medicinal products qualified as ' Innovative " (cited in Part B).


Mutual Recognition Procedure


This is a procedure based on recognition by the national authorities of the Member States of the designated European Community By the applicant, of a first marketing authorisation issued by a Member State said ' Reference state ".
The use of this procedure is compulsory where the marketing of a speciality is envisaged in at least two Member States of the European Community, with the exception of:
-specialities before Must be the subject of a centralised procedure;
-specialties for which the applicant has already used the centralised procedure;
-homeopathic medicinal products.
As part of the procedure Mutual recognition, AMM are issued by the competent national authorities (in France, by AFSSAPS) and only summaries of product characteristics are harmonised.


Temporary authorisation of use


The national system of Temporary Use Authorisation (ATU) allows patients, on an exceptional basis and in a public health concern, to access new treatments before they are placed on the market to deal with Serious or rare diseases when:
-the efficacy and safety of the drug is assumed;
-there is no therapeutic alternative;
-inclusion in clinical trials is not possible.
The ATU known as Cohort and nominal ATU, both issued by the AFSSAPS Director General.


cohort ATU


The cohort ATU is for drugs whose efficacy and safety are strongly In the light of therapeutic trials conducted for an application for market authorization and for which the application for market authorization has been or is going to be filed. It shall be granted to the holder of the operating rights for a period of one year, after obtaining the opinion of the Marketing Authorisation Commission. Drugs subject to such authorization are subject to one or more of the restricted categories.
(Art. L. 5121-12 [a] of the Public Health Code.)


Nominal ATU


Nominal ATU refers to drugs prescribed to named patients, under the responsibility of a hospital doctor, as soon as When their efficacy and safety are presumed in the state of scientific knowledge and are likely to present a real benefit to the health of patients.
(Art. L. 5121-12 [b] of the Public Health Code.)


European Pharmacovigilance Base


Database, located at the European Medicines Agency, which groups the observations of adverse reactions Concerning authorised medicinal products within the European Community transmitted electronically by Member States and pharmaceutical establishments.
All observations of serious adverse reactions of registered medicinal products In the national pharmacovigilance base will eventually be integrated into the European pharmacovigilance base.


National pharmacovigilance base


Database located at AFSSAPS which groups together Observations of adverse reactions reported by health professionals seized by LRCs after evaluation, validation and imputation.


Regional Pharmacovigilance Centre (CRPV)


Structure Pharmacovigilance within a service or department of pharmacology, clinical pharmacology or clinical toxicology of a university hospital centre. LRCs are involved in the formal and decentralized organization of pharmacovigilance. They are approved by the Minister responsible for health, made on the proposal of the Director General of the French Health Products Safety Agency. This order determines the territory of the LRB's intervention. To date, there are 31 LRCs distributed throughout the French territory. In addition, an agreement between the Director General of the French Health Products Safety Agency and the health care facilities where the LRCs are approved sets out their operating procedures.
The list of LRBs (contact details and geographical area of intervention) is available on the Agency's website (www.afssaps.sante.fr) and in Chapter 9 of this Annex.

(Art. R. 5121-167 to R. 5121-169 of the Public Health Code.)


Committee for Medicinal Products
Human Use


Scientific Forum, composed of appointed members By each Member State of the European Community, which is the responsibility of the European Medicines Agency. This committee is in particular responsible for preparing the scientific opinion on the dossiers submitted to the Agency and facilitating the adoption by the Member States of joint recommendations concerning market authorisation and risk assessment of the Drugs for human use.


Pharmacovigilance Technical Committee


Constituent of the law members of the National Pharmacovigilance Commission and a representative of each LRB and chaired by The President (or, in his absence, by the Vice-President) of the National Pharmacovigilance Commission, he is responsible in particular for:
-preparing the work of the National Pharmacovigilance Commission;
-coordinating the data collection On adverse drug reactions or products and evaluate them;
-propose, coordinate, identify and evaluate surveys and work.
(Art. R. 5121-164 of the Public Health Code.)


National Pharmacovigilance Commission


AFSSAPS Consultative Forum to Assess Adverse Reaction Information The drugs and products referred to in R. 5121-150 and provide advice to the Director General of AFSSAPS on the measures to be taken to stop, prevent or reduce the risks associated with the use of a medicinal product or product. It consists of six members of the law and thirty-three members appointed by the Minister for Health for a term of three years. The role of the Commission is detailed in Chapter 4 of this Annex.
(Art. R. 5121-159 et seq. Of the Public Health Code.)


Confidentiality


Any personal data (identity, element of privacy, etc.) or medical that identifies the person For which an adverse reaction has been notified to a pharmacovigilance structure must be treated so as to remain secret.
Any person working in a pharmacovigilance structure shall be required to respect the medical confidentiality (identity of the Persons, medical data, etc.), as well as respect for professional secrecy for any information it may be required to learn in the course of its work (report of expertise, industrial secret, etc.).
The possible transmission of Case of pharmacovigilance outside the structure having received the original notification (health authorities, etc.) must respect the medical confidentiality (including the identity of the notifier) by any appropriate means.


Application for Information


A question posed to a pharmacovigilance structure by any interested person, most often a health professional.
The issue of a drug or product may be general, but Also concern prescription support, therapeutic counselling (including during pregnancy, lactation or drug interactions) or the occurrence of a possible adverse reaction in a person. In the latter case, if applicable, a follow-up to the request for information is made to form a pharmacovigilance file which, when completed, will become a notification.


Source Document


Any original document in relation to a pharmacovigilance file, including:
-telephone conversation report, initial letter of the notifier, internal note from the medical visitor;
-pharmacovigilance sheet (completed by the notifier or a person responsible for pharmacovigilance), copies of additional examinations or hospital records;
-letters (initial, restart [s], conclusion);
-transmission record, translations of the Data sheet;
-printouts of computer seizures (records, summaries, tables) about the file.


Adverse Reaction


Adverse and unintended response to a drug, occurring in dosages Normally used in humans for the prophylaxis, diagnosis or treatment of a disease or for the restoration, correction or modification of a physiological function, or resulting from a misuse of the drug or product.
(Art. R. 5121-153 of the Public Health Code.)


Serious Adverse Reaction


Lelethal adverse effect, or likely to endanger life, or result in significant disability or incapacity, or Sustained, or inducing or prolonging hospitalization, or manifested by congenital abnormality or malformation.
(Art. R. 5121-153 of the Public Health Code.)
May also be considered as serious any adverse reaction that is considered as such by the health professional but does not fall within the scope of this regulatory
. Serious clinical or voluntary overdose should be reported as a serious adverse reaction.


Unexpected adverse reaction


Adverse reaction Nature, severity/intensity or evolution do not correspond to the information contained in the summary of product characteristics referred to in R. 5121-21.
In practice, the term new effect is sometimes used as a synonym Unexpected adverse reaction.


Pharmacovigilance Survey


Evaluation work, conducted at the request of the competent authorities by a VLRB, in collaboration with the person responsible for the Pharmacovigilance of the undertaking or body operating the medicinal product or product concerned, whenever there is reason to believe that a medicinal risk must be assessed or re-evaluated. There are two types of "investigations" :
-the monitoring of pharmacovigilance, carried out in order to carry out a particular monitoring of the tolerance profile of the medicinal product or product as soon as it is placed on the market, during the first few years, or even throughout its duration Marketing;
-the pharmacovigilance survey, conducted to re-evaluate the risk of a drug or product as a result of an alert.


Post Market Authorization Security Study


Pharmaco-epidemiological study or clinical trial carried out in accordance with the provisions of the marketing authorisation, with the aim of identifying or quantifying a risk relating to the safety of use of a medicinal product Authorized.


Adverse Event


Every noxious and unwanted event occurring in a person during a treatment, whether or not it is considered to be related to a person Drug (s).
Pharmacovigilance sheet (drug or product adverse reaction reporting form)
A health care professional data sheet that collects the data necessary for the Establishment of a pharmacovigilance file. The information collected concerns the patient (sex, age, date of birth, weight, size, department of residence, history, etc.), medications taken (name, dosage, route of administration, start date and end of treatment, etc.). Indication etc.), the adverse reaction (description, date of occurrence, evolution, etc.) and the notifier (name, address, occupation, etc.). This form must, if applicable, be accompanied by copies of hospital records, medical letters, and additional examinations.
The form template registered under CERFA 10011 *01 is available on the site Internet:
www.afssaps.sante.fr or in the regional pharmacovigilance centers.


Accountability


Case analysis of the causal link between taking a drug and the occurrence of a drug Adverse reaction. It is an individual analysis for a given notification, which cannot claim to estimate the potential for dangerousness of the drug in the absolute or the magnitude of the risk induced by this drug in a population.
Methods Is used to harmonize and standardize the imputation approach, to make it reproducible from one evaluator to another. They are also used to improve the quality of the data, a case that can only be imputed if enough information is available.
The official French method is compulsory in France (Official Bulletin of the Ministry 84/50, 24 January 1985). It combines three criteria " Time series " And three criteria " Semiology " And is accompanied by a bibliographic score.


Pharmacovigilance Information
to Health Professionals


Information about the job security of one or more drugs (or even A therapeutic class) that requires rapid and direct communication to health care professionals. It can be implemented on the initiative of the company that exploits the drug or product or that of AFSSAPS.
The content and communication plan for this information are written in consultation between AFSSAPS and the company or A body operating the medicinal product or product and are always validated by the Director General of AFSSAPS, in particular when it is necessary to:
-implement administrative police actions;
-propose Therapeutic recommendations for the treatment of adverse reactions;
-changing the use of the drug or product and medical practices;
-reporting on a sudden increase in the number of adverse reactions Data are still insufficient at this stage to implement an action or to inform about an evaluated risk suspicion;
-communicate with the media.
This information must not contain any Advertising or commercial.
In practice, it may be addressed to health professionals in the form of mail by AFSSAPS or by the company or agency operating the drug or product, provided that it does Appear that it has been validated by AFSSAPS. It is available on the AFSSAPS site (www.afssaps.sante.fr) and, where appropriate, with a press release.


Adverse Reaction Intensity


Importance and Impact of an Effect Adverse to the daily life of a patient. The intensity of an effect can be measured in three degrees:
-low: does not affect the normal daily activity of the patient;
-Medium: disrupts the normal daily activity of the patient;
-strong: prevents daily activity Routine of the patient.


Misuse


Use not in accordance with the recommendations in the summary of product characteristics referred to in R. 5121-21.
As part of good practice Pharmacovigilance, misuse is more broadly defined as:
-inappropriate use in relation to baseline data, occurring in the chain of care and exposing a given patient to a proven or potential risk, with no correlative benefit ;
-use under normal conditions of use outside authorized indications.
In particular, the summary of product characteristics (RCP), the recommendations of good practice The AFSSAPS and the Haute Autorité de santé, the consensus conferences, the medical report cards (SMR) and the improvement of the medical services rendered (ASMR), the transparency sheets, the medical recommendations which are opposable (RMO) and the Literature.
"The" Chain of care " The whole circuit of the drug, prescription, preparation, dispensation, administration, surveillance, concerning all health actors, the patient and their environment.


Notice


Document Information accompanying the drug and intended for the user. The notice shall be established in accordance with the summary of the characteristics of the product and shall contain the particulars referred to in Article R. 5121-149 of the Public Health Code.


Notification/declaration


Transmission of the suspected adverse reaction of a drug or product to a pharmacovigilance structure or to AFSSAPS.
It must contain at least four elements: an identifiable notifier or an identifiable patient, an identifiable patient, The name of the suspect drug (s) or product (s) and the reference to the suspect (s). These four elements are complemented by any relevant and relevant data (see pharmacovigilance sheet).
Where the notification emanates from a non-prescriber health professional, additional information may be sought from The prescriber or the attending physician.
It is recommended that the notification be confirmed in writing by the notifier or based on the original elements of the clinical record.
In the particular case where the report originates from a Patient, the pharmacovigilance structure should encourage the patient to return to a health care professional, preferably the one who has taken care of it, as the facts must be confirmed by a health care professional.


Responsible Pharmacist


The person who organizes and monitors all drug operations, including pharmacovigilance, tracking, and batch removal.
(Art. R. 5124-36 of the Public Health Code.)


Pharmacovigilance


All techniques for identifying, evaluating and preventing the risk of adverse reaction of drugs or products placed on The market for consideration or free of charge, whether this risk is potential or proven.
Pharmacovigilance includes the prevention, identification, assessment and correction of potential or proven drug risk (iatrogenic drug). In particular, it focuses on assessing the avoidable factors of drug risk.


Health Professional


The obligation to report serious or unexpected adverse reactions Physicians, dental surgeons, midwives and pharmacists. However, any other health professional (nurse, physiotherapist, etc.) wishing to participate in the pharmacovigilance system may also notify the Regional Pharmacovigilance Centre.


Periodic report Update on pharmacovigilance
(Periodic Safety Update Report or PSUR)


A report written and forwarded by the company or agency operating the drug or product to AFSSAPS, with the objective of:
1. To assess the tracking of the job security profile of a drug or product, based on the knowledge acquired and the information available;
2. To consider, if necessary, a change in drug or product information, or even a reassessment of the benefit/risk ratio.
This document contains an update of the pharmacovigilance data collected around the world during the Period under review. It shall be transmitted immediately upon request of the AFSSAPS and/or at intervals defined after the registration of the medicinal product or product (see art. R. 5121-173 and R. 5121-176 of the code of public health).
In practice, it contains a summary of all the pharmacovigilance data which the company or body exploiting the medicinal product or product has been aware of, as well as any Information useful in assessing the risks and benefits associated with the use of this drug or product. This summary is accompanied by a scientific assessment of these risks and benefits.


Responsible for marketing/operator


A natural or legal person responsible for Provision, for consideration or for free, of a drug or product. In practice, it may be either the holder of the marketing authorisation or of a separate operator of the marketing authorisation holder, either of which, according to Article R. 5124-2, one or more categories of operations that constitute the operation of the drug or product.


Pharmacovigilance Manager


Responsible for a LRB or person, named by The company or organization operating a drug or product, to support and coordinate pharmacovigilance activities.
(Art. R. 5121-169 and R. 5121-178 of the Public Health Code.)


Summary of Product Characteristics (RCP)


A standard summary for any product that has market authorization. It corresponds to information for health professionals.
(Art. R. 5121-23 and R. 5121-24 of the Public Health Code.)


Severity


(See Intensity.)


Pharmacovigilance Structure


A term for a LRB, The service managed by the person responsible for the pharmacovigilance of a company or organization that operates a drug or product.


Pregnancy Tracking


Evolutionary Elements Manual Concerning the course of pregnancy and its outcome, following a request for information on the possible risk (preconception, embryonic, foetal, neonatal or longer-term for the child) related to exposure to a drug taken before or During pregnancy.


Pharmacovigilance Tracking


(See Pharmacovigilance Survey.)


Chapter 2
Health Professional Role


1. To report as soon as possible to the Regional Pharmacovigilance Centre (LRB) any serious adverse reactions or unexpected adverse reactions that may be due to one or more drugs or products, including the consequence thereof An abuse or misstatement. When the drug contains psychoactive substances, the declaration must be made to the national drug dependence system (see Glossary, at the Abus entry).
Declaration is mandatory, regardless of mode For physicians, dental surgeons and midwives, as well as for pharmacists for the drugs or products they have issued. Any other health care professional who has made the same finding may also inform the LRB.
In addition, it is strongly recommended that:
-any overdose;
-any exposure during pregnancy or Breastfeeding;
-any other effect or situation that has a negative, potential or proven adverse effect on health;
-any observation of loss of efficacy (including vaccines, contraceptives, or drugs intended for use in the Treatment of life-threatening conditions ...);
-any effect that they consider relevant to report.
These statements should be systematically addressed to the LRB, preferably to the one for which the health professional depends
The health professional may also inform the person responsible for the pharmacovigilance of the person responsible for placing the product on the market.
A declaration must include at least:
-a notifier and a patient Identifiable;
-the name of the drug (s) or suspected product (s);
-the nature of the suspected adverse reaction (s).
2. Provide the LRB with any information relevant to the assessment of suspected adverse reaction or follow-up Of exposed pregnancies. It is recommended that this information be transmitted in writing or through the pharmacovigilance sheet.
3. Keep all source documents relating to the notification and inform patients, in accordance with the provisions of the law of 6 January 1978 amended, of the declarations concerning them and their right of access.
4. Cooperate with pharmacovigilance structures, including through investigations or specific studies (including pharmacovigilance, safety after market authorization, pharmacoepidemiology or iatrogenics).
5. Be informed and take into account in the professional practice of the drug safety data that they prescribe, provide or administer.
6. Respect good publishing practices (see Chapter 8).
7. Any health care facility, including risk management and/or vigilance coordination structures, must ensure that serious adverse reactions or unexpected adverse reactions have been the subject of Report to LRRC.


Chapter 3
Role of the French Health Security Agency
of Health Products
Preamble


Agence française de sécurité sanitaire des produits de santé (AFSSAPS) On the basis of the tasks assigned to it, ensure the safety of the use of medicinal products or products and contribute to their proper use, in the context of the protection of public health and the information of health
. Implementation of the national pharmacovigilance system, defines the pharmacovigilance guidelines, animates and coordinates the actions of the stakeholders and ensures compliance with the procedures for the supervision of medicinal products and products entering the market. Field of pharmacovigilance (see Scope of pharmacovigilance).
It participates in the decisions and the preparation of national, Community and international regulatory texts on pharmacovigilance
Are insured, in accordance with the national and Community regulations in force, by AFSSAPS, in particular by the pharmacovigilance unit. This unit is responsible for coordinating the activities of the Regional Pharmacovigilance Centres (CRLRs) and for providing the secretariat of the Technical Committee and the National Pharmacovigilance Commission. It is the addressee of the updated periodic reports and reports of pharmacovigilance transmitted by those responsible for the marketing of medicinal products or products as well as any information on the medicinal risk arising from the Other Member States of the European Community or parties to the Agreement on the European Economic Area, the European Medicines Agency or a third country.


Organisation


It is the responsibility of AFSSAPS :
1. Equip itself with appropriate means to monitor the safety of the use of medicinal products in particular when they are new, by following up with all the partners and by informing the professionals regularly and meaningfully of Health;
2. To provide the necessary means for LRCs so that they can complete all their missions;
3. Establish links with other watchers and their networks, in particular with the national systems of veterinary pharmacovigilance, toxovigilance and evaluation of drug dependence.


Watch mission Health and alert


AFSSAPS is responsible for:
4. (a) Centralize any information on suspected adverse reactions to drugs or products, regardless of their source, including:
-LRBs;
-drug or product marketing officials;
- The European Medicines Agency, other Member States of the European Community or parties to the Agreement on the European Economic Area (1);
-of the World Health Organisation (WHO),
and to ensure that any information on The suspected adverse reactions to the drugs transmitted to it are taken into account by the national pharmacovigilance system;
(b) To evaluate this information, using, inter alia, all the necessary competences, and to promote Any evaluation to advance the knowledge of adverse reactions.
(c) To analyze updated Periodic Safety Update Reports to verify consistency of findings;
5. To ensure that any suspected serious adverse reaction on French territory is communicated to the European Medicines Agency using the European Pharmacovigilance Database. AFSSAPS shall also inform those responsible for the placing on the market of serious adverse reactions which may be due to their medicinal products, in accordance with the provisions of Article R. 5121-157 of the Public Health Code;
6. Promote post-market safety studies and any other studies to improve knowledge and prevent adverse reactions. Dispose of the results of pharmacovigilance studies conducted by the marketing manager;
7. To assess the appropriateness of any request for initiation of an investigation by the Technical Committee or the National Pharmacovigilance Commission, the Committee for Medicinal Products for Human Use or any other competent authority, and to take any action Necessary for the conduct of this investigation; to communicate, as soon as possible, any information that is of interest to the LRB responsible for the investigation and that it has designated;
8. To take appropriate measures in the field of public health in the light of the opinions issued by the relevant advisory committees, to inform the Minister responsible for health and to ensure that they are implemented;
9. To transmit as soon as possible any measure envisaged in the field of pharmacovigilance:
-to the other advisory committees concerned by the medicinal product or product for human use;
-to those responsible for placing the product on the market Drugs or products;
-to LRBs;
-to health professionals, if necessary in consultation with the drug or product marketing manager;
-at the community and international level;
-aux - Patients and/or patient associations if necessary.

(1) The European Economic Area comprises the Member States of the European Community as well as Iceland, Liechtenstein and Norway.


Honouring of obligations in Pharmacovigilance issues


AFSSAPS is responsible for:
10. To ensure compliance with the regulations in place of the operating procedures relating to pharmacovigilance within LRCs and those responsible for placing on the market and to take the necessary measures in accordance with the Non-compliance;
To ensure the quality of the pharmacovigilance system by observing operating procedures at the level of each actor involved;
11. To verify the conformity of pharmacovigilance actions by the companies or bodies exploiting the medicinal products or products, in particular with regard to declarations, with regard to the regulations in force, and, Taking into account the guidelines published in Volume 9 of the regulation of medicinal products in the European Community;
12. Ensure that data collection is consistent with good pharmacovigilance practices.


European Pharmacovigilance


It is up to AFSSAPS:
13. To participate in the relevant European pharmacovigilance working groups, in particular to the pharmacovigilance working group of the European Medicines Agency Committee on Medicinal Products for Human Use and to ensure links between Stakeholders in pharmacovigilance at national level and the European Community;
14. To participate as rapporteur/co-rapporteur or consignee in the Committee for Medicinal Products for Human Use of the European Medicines Agency for the Safety Assessment of the Use of Drugs or Products Subject to Referral To establish risk management programmes in order to identify and prevent the risk of undesirable effects when placing on the market;
15. To transmit in the event of necessity any new information which could influence the assessment of the benefits and risks of a medicinal product or product to the European Medicines Agency and other Member States of the European Community or Parties to the European Economic Area Agreement.


Training, information and communication


It is owned by AFSSAPS:
16. Remind health professionals of their role as health actors;
17. Promote information, training (academic, continuing medical education) prevention in pharmacovigilance and promote pharmacovigilance with institutions (health, national education, etc.);
18. To participate in the communication on pharmacovigilance in liaison with health professionals, other institutions, the professional press or the general public, as well as associations with patients and users of the Health system.


Chapter 4
Role of the National Pharmacovigilance Commission


The National Pharmacovigilance Commission is a consultative body that meets every two months at AFSSAPS. However, if necessary, it may meet in extraordinary session. Its secretariat is in practice provided by the pharmacovigilance unit of AFSSAPS.


Missions


The Commission is responsible for evaluating information on adverse drug reactions And products referred to in Article R. 5121-150 of the Public Health Code and to give an opinion to the Director General of AFSSAPS on the measures to be taken to prevent, reduce or stop the risks associated with the use of a medicinal product or
Minister responsible for health may refer the matter to the National Pharmacovigilance Commission for advice on any matter, as well as the investigation and work that it considers relevant.


Composition


The composition of the Commission has been established so that all the disciplines that may be affected by the Commission are represented. Pharmacovigilance.
It includes:
-six members of law: the Directors General of Health, the AFSSAPS, the National Institute of Health and Medical Research, the Director of Hospitalization and the Organization of Care, the President of the National Commission on Veterinary Pharmacovigilance and the President of the National Commission on Narcotic Drugs and Psychotropic Substances, or their representatives;
-thirty-three members appointed by the Minister responsible for health for a Duration of three years. These include clinicians, toxicologists, pharmacologists, pharmacists, individuals with expertise in pharmacoepidemiology, as well as representatives of associations of patients and users of the health system, associations of Consumers, the pharmaceutical industry and the toxicovigilance technical committee.
Thirty-three alternates are appointed under the same conditions as the incumbent members. They shall replace the latter in the event of the incapacity and their succession if a vacancy occurs during the term of office, for the remainder of the term of office.
The President and the Vice-President shall be appointed by the Minister responsible for health Members of the committee. The Vice-Chair supersedes the President in the event of an impediment.


Operation


The Commission, unless there is an emergency, decides on the conclusions of the files prepared by the Technical Committee, in particular Pharmacovigilance surveys. It shall have the right to hear any qualified person in order to benefit from experience and competence in the investigation of files submitted to it for opinion. In practice, after having heard the rapporteur of the case and the representatives of the companies or bodies concerned, the committee deliberates and gives an opinion on the measures to be taken to ensure the safety of the use of medicinal products or products (see Chapter 7: Procedure for Investigation and Monitoring of Pharmacovigilance).


Ethics Rules


The deliberations of the National Pharmacovigilance Commission are confidential. The members of the committee, as well as any person who is called to attend the meetings, shall be kept secret of the deliberations and of any facts or documents of which they are aware in this capacity. In addition, the members of the commission must declare to the director general of AFSSAPS their direct or indirect links with the companies or bodies whose products may be affected by the work of the commission and cannot take Neither the deliberations nor the votes if they have a direct or indirect interest in the matter under review.


Chapter 5
Role of the Regional Pharmacovigilance Centres


Regional Centres Pharmacovigilance (LRB) is responsible for monitoring, evaluating, preventing potential or proven drug risks, and promoting the proper use of the drug. VLRBs collect the information and send it to the Agence française de sécurité sanitaire des produits de santé (AFSSAPS), inform and train health professionals, and provide a mission of expertise.
These missions are carried out at: The national level with AFSSAPS, at the regional level at the intervention territory and at the local level within the health facility in which the LRB is located.
To ensure these missions, the LRVP or his/her deputy Must coordinate and control all pharmacovigilance activities.
The VLRB provides the following missions and health care in its health care facility:


1. Information collection and evaluation


1.1. Collect and record information about:
-adverse reactions occurring under normal conditions of use, including serious or unexpected adverse reactions and any other adverse effects Health, potential or proven;
-drug abuse;
-misuse;
-pregnancy and breastfeeding.
This information is provided to the LRB by:
-health care professionals;
-institutions Health and in particular local correspondents of other watchers;
-poison control centres;
-pharmacodependency assessment and information centres;
-veterinary pharmacovigilance centres.
1.2. Organize and stimulate adverse reaction reporting and any information on drugs or products that may result in a potential or proven risk in the patient.
Special vigilance will be exercised Serious and/or unexpected, particularly with regard to products recently marketed and subject to specific monitoring (pharmacovigilance investigation and national pharmacovigilance monitoring, see Chapter 7).
The circulation of this information Must respect the confidentiality of the patient's identity and that of the notifier.
Implement all means to ensure that the notifications are documented and validate the data in relation to the original documents
1.3. Evaluate notifications, especially in terms of severity, novelty, frequency, and verify that this new information does not change the benefit/risk ratio of the drug.
1.4. Assess the causal relationship between the drug or product and the occurrence of suspected adverse reactions, using the official method of
. Inform the notifier of the action of the adverse reaction report.
1.6. Complete the computer capture of the notifications, accompanied by a summary summary in the national pharmacovigilance database:
-immediately in case of public health problem;
-and no later than 15 days Following receipt of the oral or written notification for the serious effects (date on which the four essential elements are received: an identifiable notifier, an identifiable patient, one or more suspected medicines or products, one or more Suspect effects, allowing notification).
1.7. Document the development of the adverse reaction, particularly that of serious or unexpected effects, especially when the patient is not reinstated at the time of reporting, and update the computer data.
1.8. Follow up on any reports of a drug taking or product, during lactation or pregnancy, in order to know the outcome. If necessary, carry out a remote monitoring of children exposed in utero.
Retain any items relating to the collection and documentation of the case; any information, including that transmitted orally, shall be recorded in writing, Dated and initialled.
1.9. Archive in a secure location all requests for information or notifications collected in the form of informative files that include responses and ensure traceability.
1.10. Co-operate with the company or agency responsible for pharmacovigilance of the drug or product in particular in the case of suspected serious and unexpected adverse reactions and in cases where both have received the same Notification.
To ensure professional secrecy (see in the glossary: confidentiality) and to process with the necessary reserve any information not yet validated. Each centre may have its own data freely available.
In the specific case of information transmitted directly by a patient, encourage the patient to consult the health care professional, preferably the one who has taken charge of the information. The patient, and, if applicable, document the effects reported by the patient with the patient's agreement.


2. Health Professional Information and Training


2.1. To provide health care professionals with a mission of information on adverse reactions (including misuse and abuse), risks during pregnancy and breastfeeding, and any other data on the drug or drug Product.
2.2. Transmit information about them to other vigilance structures in accordance with the provisions of the Public Health
. Keep a record of inquiries.
2.4. Notify the notifier of the action taken on the adverse reaction report. If necessary, address a written response to the health professional.
2.5. Train health professionals by participating in initial, specialized and ongoing training in pharmacovigilance and drug risk prevention. Involve the LRB physicians and pharmacists in this training activity, in particular with the health care facility staff in which the centre is located.


3. Expertise, Advice and Investigation


Complete a mission of expertise and advice in terms of pharmacovigilance and drug risk prevention.
3.1. At the level of the public health institution:
-participate in the commission of the drug and sterile medical devices;
-complete a mission of expertise and advice to the consulting bodies of the institution Burden risk management and/or coordination of vigilance (Risk Management Committee, Coordinating Committee, etc.);
-collaborate effectively with other health watchkeeping and other bodies such as the Committee To combat nosocomial infections, the Blood Safety Committee and Blood Safety Committee, the Information and Care Centre for Human Immunodeficiency ...
3.2. At the level of the territory of intervention:
-cooperate and possibly participate, if possible, at the request of public and private health institutions and local, regional health authorities (departmental management Health and social affairs, regional health and social affairs directorate, regional hospital agency, regional union of health insurance funds ...), to risk management structures (iatrogenic risk management committee, Regional Coordinating Committee on Vigilance ...);
-promoting clinical pharmacology and pharmaco-epidemiology activities at the local and regional level as well as any other study to improve knowledge, understanding and Prevent adverse reactions;
-participate in the development of a network of local pharmacosurveillance referrals in health care facilities.
3.3. At the national level:
-to lead, as nominated by AFSSAPS, surveys and work on pharmacovigilance or the pharmacovigilance of a drug or product;
-to collaborate in studies of Pharmaco-epidemiology.


4. Contributing to scientific progress


Contributing to scientific progress by improving pharmacovigilance methods and knowledge and understanding of the nature and mechanisms of adverse reactions Medicinal products and products; value this contribution if necessary by publishing original or didactic articles in pharmacovigilance; exercise a watch on scientific literature.
To ensure all these missions, the LRB Must have standard operating procedures for pharmacovigilance that make up the regular audit repositories.


Chapter 6
Role of the
Manager in marketing a drug


In order to fulfil its obligations and responsibilities in the field of pharmacovigilance, the person responsible for marketing the drug or product must have at its disposal within the company on the national territory Permanently and continuously a person responsible for pharmacovigilance (hereinafter referred to as the pharmacovigilance supervisor). This is the correspondent and privileged interlocutor of the Agence française de sécurité sanitaire des produits de santé (AFSSAPS) for any problems related to the safety of use of medicinal products or products (see Scope of application of the Pharmacovigilance).
The person responsible for marketing a drug or product must comply with the provisions described in the various headings in this chapter.


1. Organization and staff of the
marketing manager


The marketing manager must:
-designate a person responsible for pharmacovigilance, physician or pharmacist, who has the The required skills and practical experience in pharmacovigilance to enable it to fulfil the tasks entrusted to it;
-make available to the Pharmacovigilance Manager a qualified and sufficient number of staff To carry out all the tasks assigned to it and to ensure the implementation of the material resources necessary for the proper functioning of the service;
-to have an updated organisational chart of the company indicating the hierarchical relations The person responsible for pharmacovigilance with the responsible pharmacist and other services.
The identity and quality of the person responsible for pharmacovigilance are communicated immediately upon appointment to AFSSAPS.


2. Training for
Marketing Manager


2.1. Ensure appropriate in-service training of pharmacovigilance staff with regard to the regulatory provisions, the organisation and functioning of pharmacovigilance and, in particular, its role in the collection, The registration, assessment and reporting of adverse reactions.
2.2. Regularly train the persons referred to in Article L. 5122-11 of the Public Health Code which make information by walking or prospecting for medicinal products (medical visitors), including provider networks and all Other person from the company or agency whose activities might concern pharmacovigilance on the regulatory provisions, the methods and objectives of pharmacovigilance and their role in the transmission of Information.


3. Primary missions of the Pharmacovigilance Manager


3.1. Establish and manage a pharmacovigilance service responsible for recording, centralising and evaluating information on adverse reactions which may be due to a medicinal product or product, including in the case of misuse, overdose or Drug abuse.
3.2. Ensure compliance with regulatory requirements for pharmacovigilance.
3.3. Ensure that any request from AFSSAPS to obtain additional information necessary for the exercise of pharmacovigilance is followed by as complete a response as possible within the deadlines set by AFSSAPS.
3.4. Provide any other information relevant to the exercise of pharmacovigilance, including the sale, dispensing and practices of consumption, prescription and administration to patients of the drug or
. To ensure an ongoing assessment of the risks and benefits of its drugs or products; communicate to AFSSAPS any new information that could influence the assessment of the risks and benefits of its drugs or products and propose Measures to improve job security.
3.6. Ensure that information on drugs or products is regularly updated with respect to pharmacovigilance data collected and evaluated.


4. Manage Pharmacovigilance Data
by the Pharmacovigilance Manager


4.1. Record any reports of adverse reactions that may be due to a drug or product including overwise, overdose or drug abuse reported directly to the operator or through its medical visitors or A service provider. Computer processing of data on adverse reactions that may be due to a drug or product is strongly recommended in order to build and maintain a database.
4.2. Record any information regarding the use of a drug or product during breastfeeding or pregnancy and follow up to determine the outcome of any pregnancy.
4.3. Validate the data against the original documents available and seek additional information relevant to the evaluation.
4.4. Document all cases, particularly serious or unexpected cases; contact the notifier if necessary to collect or complete an observation.
4.5. Conduct surveillance of scientific literature and databases accessible at least once a week for the purpose of identifying and recording observations of adverse effects associated with the use of the The active principle (s) of these medicinal products or products and declare these observations in accordance with the provisions laid down in Article R. 5121-171 to R. 5121-173 of the Public Health Code and in paragraph 5
. To assess the causal link between the medicinal product or product and the occurrence in France of the adverse reactions resulting from the spontaneous notification, which may be due to this medicinal product or product, compulsorily according to the method of accountability
4.7. Notify the notifier of the action taken on its adverse reaction report.
4.8. Keep all items related to the collection and documentation of the case reported. All information, including oral information, must be documented, dated, initialled, and archived in a secure location.
4.9. To estimate the incidence of adverse events that may be due to a drug or product (or failing the notification rate) and to investigate risk factors and pathophysiological mechanisms.
4.10. Ensure respect for the confidentiality of the identity of patients and notifiers; verify that the security of the means of storing and transmitting data, in particular IT, is ensured.
4.11. Ensure the traceability of adverse reaction reporting and the transmission of updated Periodic Safety Update Reports to health authorities.


5. Reporting obligations to AFSSAPS
by the Pharmacovigilance Manager


For the specific case of allergens prepared specifically for a single individual, reference should be made to the provisions of article R. 5121-176 of the Public Health Code.
5.1. Adverse events arising under normal conditions of employment or during a misuse.
Declare in accordance with the provisions of this Annex (see chapter 1, notification/declaration), no later than 15 days after the Receipt of information:
-serious adverse reactions in France that may be due to a drug or product reported directly to the operator by a health care professional.
-other serious adverse reactions Occurring in France and liable to be due to a medicinal product or product which the operator may be aware of, in particular those reported in publications or registered in accessible databases;
-the effects Serious and unexpected adverse events outside the European Community and the European Economic Area which may be due to a medicinal product or product and which the operator is aware of;
-serious adverse reactions In the other Member States liable to be due to a medicinal product or product whose AMM initially obtained in France has been the subject of a mutual recognition procedure in those other Member
. Serious adverse reactions performed directly by a patient or his or her entourage must be confirmed by a health professional prior to transmission to AFSSAPS within 15 days of receipt of this confirmation.
5.2. Adverse events resulting from overdose or abuse:
The reporting of adverse reactions resulting from overdose or abuse is subject to the same obligations and procedures as that for adverse reactions in Normal conditions of employment or during a misuse, as set out above. However, when the drug contains psychoactive substances, the declaration must be made to the national drug dependency system (see Glossary at the Abus entry).
5.3. Updated Periodic Safety Update Report (PSUR):
Transmit the updated Periodic Safety Update Reports immediately upon request and within the time limits of the current regulations.
5.4. Safety study after marketing authorisation:
Transmit any information relating to the implementation of a job security study carried out in accordance with the provisions of the authorisation for placing on the market. Market. In particular, the study protocol must be transmitted at least one month before the scheduled start of the study.
To ensure regular monitoring of pharmacovigilance information throughout the study and to ensure the quality of the Information obtained. The data collected for this study will need to be reported in accordance with the regulations in force.
Transmit the potential intermediate (s) and the final report (s) in the To be completed within six months of the end of the study.
Any job security study, conducted after the granting of market authorization and responding to the definition of biomedical research, must be Conducted in accordance with clinical trial and good clinical practice regulations.
5.5. Other information:
Transmit any other information that is relevant to the risk and benefit assessment of the drug or product.
Transmit a schedule for the submission of updated periodic reports Pharmacovigilance in order to obtain, as a derogation, a change in the periodicity as provided for by the regulations in force.


6. Other Obligations of the Market Leader


To communicate immediately to AFSSAPS any prohibition or restriction on the use of the medicine imposed by the competent authorities of another country, as well as Any other new information that may influence the assessment of the benefits and risks of the drug or product.
Immediately inform AFSSAPS of any action taken for pharmacovigilance reasons to suspend the Marketing or withdrawing from the market a drug or product or to remove a specified lot, as well as details (content of the message, distribution terms) of any communication measures related to this action.


7. Cooperation with the AFSSAPS and the regional pharmacovigilance centres



Cooperate with AFSSAPS and the CRPV designated as rapporteur in the framework of a pharmacovigilance survey, pooling useful data The assessment of the risks and benefits of the drug or product and, in particular, data on adverse reactions, sales and use of the drug or product (see Chapter 7).
Cooperate with LRCs, and in particular Respond to any request for information related to the use of the drug or product.


8. Information and Communication by the
Marketing Manager


To educate health professionals and the public about the use and safety of use of drugs or exploited products.
Promote Information on the safety of use of medicines or products used in communication with health professionals and the public.
Transmit to AFSSAPS, for validation prior to its release, any communication project relating to the Pharmacovigilance intended for health professionals, taken on the initiative of the undertaking or imposed by the competent authorities (when the communication meets the criteria defined in the glossary of the term pharmacovigilance information).


9. Activities granted subcontract by the
marketing manager


Subcontracting activity must be the subject of a written contract that expressly refers to the Articles R. 5121-150 to R. 5121-180 of the code of public health, concluded between the person responsible for marketing a medicinal product or product and the subcontractor with a view to clearly defining the obligations of each party
Have the effect or purpose of exempting the person responsible for placing the medicinal product or product concerned from the final responsibility for the implementation of pharmacovigilance obligations.


10. Procedures put in place by the
marketing manager


Have quality control procedures and techniques, as well as standard operating procedures for pharmacovigilance Constituting the regular audit repositories. These procedures must describe in a precise way the structure and organisation of the pharmacovigilance service set up within the company, the management of pharmacovigilance information and the functions and responsibilities of all Person involved in pharmacovigilance operations.


Chapter 7
Pharmacovigilance Investigation and Tracking Procedure
1. Pharmacovigilance Survey


Definition: The pharmacovigilance survey is conducted to evaluate or re-evaluate the risk of a drug or product following an alert (see Chapter 1).
Field Application: the pharmacovigilance investigation procedure may concern any medicinal product or product for health purposes falling within the scope of pharmacovigilance, which includes, in particular, medicinal specialities registered in accordance with A national procedure or in accordance with a European procedure for mutual or centralised recognition (see Scope of pharmacovigilance).
Objective: carried out in the context of the implementation of possible technical measures and In order to prevent, reduce or eliminate a drug or product risk, the pharmacovigilance investigation is intended to assess this risk.
1.1. Circumstances for the initiation of a formal investigation:
The Director General of the French Health Products Safety Agency (AFSSAPS) may decide to initiate a pharmacovigilance investigation. It can also be carried out in the wider context of a European investigation.
The Director General of AFSSAPS appoints, most often on the proposal of the President of the National Pharmacovigilance Commission, a rapporteur responsible for The conduct of the investigation among those in charge of the Regional Pharmacovigilance Centres (LRCs), possibly one or more Associate Rapporteurs among the LRCs. It shall notify the responsible person (s) of the investigation and the responsible person (s) of the placing on the market of the medicinal product or products concerned by mail.
The objectives of the pharmacovigilance investigation are defined in the mail AFSSAPS which specifies:
-the reasons for the investigation;
-the adverse reactions involved;
-the specialties or the class (pharmacological, therapeutic ...) concerned;
-the relevant pharmaceutical forms if necessary ;
-the name of the survey manager (s). In the event that several associate rapporteurs have been appointed, the terms of reference of each of them must be
. Tasks of the rapporteur, the Technical Committee and the National Pharmacovigilance Commission:
The rapporteur gathers, validates and analyses the data to assess the risk associated with the use of the medicinal product (s) or products Concerned. It seeks and identifies risk factors and justifies, before the Technical Committee, proposals to reduce or eliminate the risk. It shall coordinate, where appropriate, the work of the associated pharmacovigilance centres.
The Pharmacovigilance Technical Committee shall ensure the proper conduct of the investigation and validate the conclusions and proposals before its consideration by the Commission National pharmacosurveillance. It may also propose possible further investigation.
The National Pharmacovigilance Commission becomes aware of the data and the conclusions of the investigation presented by the Rapporteur and proposes, if necessary, to the Director General of The AFSSAPS measures to reduce or eliminate the risk of the medicinal product (s) or products, with the possible seizure of the marketing authorisation Commission with a view to re-evaluating the benefit/risk ratio of these medicinal products or Products.
1.3. Pharmacovigilance Investigation Process:


1. Initiation of Investigation


The opening date of the pharmacovigilance investigation is that of the mail addressed by the Chief Executive Officer of AFSSAPS to the person responsible for the marketing of the drug or product and to the Rapporteur designated to carry out the investigation.
If the drug or product under investigation is authorised but not marketed, the person responsible for placing the product on the market shall report it by mail to the rapporteur (s) and to AFSSAPS in the
After receipt of the letter from the Director General of AFSSAPS, the CRLRB designated as rapporteur (s) will send a letter within 15 days accompanied by the completed application form (see form Below) to the person responsible for the placing on the market concerned. The rapporteur must provide the rapporteur (s) with all the data requested within 45 days from the date of receipt of the letter from the rapporteurs.
A timetable is drawn up in agreement between the rapporteur (s) and the rapporteur (s). Responsible for placing on the market so that the investigation is presented to the technical committee no later than 6 months after the receipt of the documents by the rapporteur (s). This period may be extended by 6 months by AFSSAPS. In case of an emergency, the AFSSAPS may impose a shorter period of time.
The rapporteur of the survey shall determine with the person responsible for the placing on the market, the timetable and the date of the meetings, during which all available data is analysed In connection with the investigation. This collaborative work is conducted in principle on the premises of the investigating officer or AFSSAPS. A joint work with several marketing officials of the medicinal product (s), if any, is possible if they give their written consent. A record of the meetings is written and validated by the parties involved.
At the first meeting, are defined the scope of the survey, the period covered and the geographical area of the collection of the notifications.
In a first Time, the methodology to be used, particularly in terms of analysis, is defined to be adapted to the subject of the survey.
In consultation with the marketing manager, the investigator can:
-be taken to Define the observations to be retained;
-predict how the effects, and especially those that are by nature irreversible, will be sorted and imputed;
-decide if necessary in the form of a document that allows input Computer of an observation with the chronology data and all the examinations necessary for the differential diagnosis to establish the accountability;
-specify to the person responsible for the marketing of the medicinal product (s) Data (outside of the pharmacovigilance observations) necessary for the investigation.


2. Data collection


The rapporteur (s) and the product (s) responsible for marketing the drug (s) or products collect all available data in relation to the objective of the survey, including In particular the notifications collected (with as much information as possible) but also any information that may contribute to the evaluation (pharmaco-epidemiological studies, animal studies, relevant data from clinical trials, ...). This data is shared under the responsibility of the rapporteur. Any exchange of observations respects the anonymity of the person concerned by the effects and the notifier.


3. Evaluation and imputation of observations collected


At the outset, the existence of duplicates must be sought: observations collected by one or more centres and also by one or more managers of the Market for a medicinal product or product.
For the work of accountability, or more generally evaluation of data, the rapporteur and the person responsible for placing on the market may each join one or more experts, Specialists in the field (s) concerned whose contact details are provided to AFSSAPS and to the rapporteur (s) or responsible for the placing on the market as soon as possible. The observations are imputed in common and, to the extent possible, a consensus is sought on the accountability of each observation, based on the French method of accountability and the opinions of the selected
. This job is included in the rapporteur's final report.


4. Searching for Additional Elements



The head of the survey can ask the market leader for the following complementary and relevant elements:
-pre-clinical data (toxicology Animals, kinetics, pharmacodynamics, analytical data);
-results of pre-AMM clinical trials;
-results of post-AMM trials;
-notifications from other countries;
-useful publications to Survey;
-annual sales figures, monthly, by region or country;
-usage data, including misuse, drug or product, or any other data that can help assess the importance of risk;
-the Results of any pharmaco-epidemiological studies of which he or she is aware;
-a review of cases with expert analysis of the effects involved in the investigation.
Other elements may be requested on written justification of the Responsible for the investigation.


5. Defining the unique profile of the
adverse reaction and looking for motivating factors


A profile of the effect/effects is made, on the one hand, from the notifications with the highest accountability (likely and plausible) and, on the other hand, from all notifications.
In particular:
-the clinical and biological characteristics of the adverse reaction;
-the dosage;
-the onset time ;
-evolution;
-data on drug or product shutdown and possible readministration;
-stop regression;
-effect intensity;
-severity;
-the Specific characteristics of data subjects (gender, age, history, genetic background, pathology, etc.), to the extent possible, relative to those of all treated persons;
-possible mechanisms;
-the potential contributing factors for the occurrence of the adverse reaction.
At the end of this work, the arguments supporting or not the causal role of the drug are identified.


6. Attempt to estimate incidence of reported cases


Unless there is more accurate epidemiological data, the notification rate is calculated. It should be considered, preferably, in relation to " Number of treatments sold in days of treatment " Or in another suitable unit. If necessary, this estimate is completed on the basis of different degrees of accountability and severity.
Wherever possible, the number of people treated and the characteristics of drug use are evaluated Or products (prescription duration, indication, dosage).
1.4. Searching for comparison points:
With the help of the market leader (s), the head of the survey is looking for data to situate the observed or estimated risk in relation to other drug risks. The same therapeutic or pharmacological class compared to other therapeutic and non-therapeutic classes.
1.5. Survey Report:
A report is prepared by the person in charge of the investigation containing the findings and reflections on the various points mentioned above. It should contain a summary summarising the data presented in the different sections of the report.
The survey report should be sent to the market leader (s) and to the AFSSAPS one week before the committee meeting Before the National Pharmacovigilance Commission. Where a number of those responsible for placing on the market are concerned by the investigation, the rapporteur must ensure that the data covered by the trade and trade secret of the specialities exploited by the competitor (s) (including the number of cases) are concealed. Units sold or data used to estimate these figures) when submitting its report to those responsible for marketing the various drugs or products involved in the investigation.
After examination of the file, the committee If necessary, to the National Pharmacovigilance Commission for opinion.
At the end of the investigation and prior to the passage to the National Pharmacovigilance Commission, a consultation meeting with the responsible person (s) On the market can be organised at AFSSAPS. It is intended to take note of the joint proposals of the rapporteur and the person responsible for placing on the market and to discuss possible diverging proposals.
The rapporteur presents the investigation report to the Commission National pharmacovigilance in the presence of representatives of the responsible (s) for placing on the market, including the person responsible for pharmacovigilance. On this occasion, the person responsible for marketing may present his arguments if there is a disagreement.
1.6. Proposals/opinions:
The rapporteur sets out his conclusions and proposals for action to reduce or eliminate the risk. The National Pharmacovigilance Commission then makes an opinion to the Director General of AFSSAPS.
The responsible marketing manager and rapporteur (s) are informed by AFSSAPS of the proposals made by the Commission National pharmacovigilance by sending an extract of the minutes adopted by the National Pharmacovigilance Commission.
For medicinal products registered in accordance with a European procedure, the conclusions of the pharmacovigilance investigation May be transmitted, if necessary, to the European Medicines Agency, the rapporteur or the Member State of reference.
The decision to close the investigation shall be notified to the rapporteur (s) and to the person responsible for the placing on the market by a Mail of the Director General of AFSSAPS.
When a publication of the survey data is envisaged, the document shall be sent for information prior to its release or presentation to those responsible for the placing on the market concerned and AFSSAPS.


2. Pharmacovigilance monitoring


Definition: monitoring of pharmacovigilance is carried out in order to carry out a specific monitoring of the tolerance profile of the medicinal product or product as soon as it is placed on the market, during the For the first years or even for the duration of its marketing.
Scope: monitoring of pharmacovigilance may concern any medicinal product or product for health purposes falling within the scope of pharmacovigilance, which Includes pharmaceutical specialities registered in accordance with a national procedure or in accordance with a European procedure for mutual or centralised recognition (see Scope of pharmacovigilance)
Perspective on the implementation of possible technical and administrative measures to prevent, reduce or eliminate a risk associated with a drug or product, the monitoring of pharmacovigilance is intended to assess this risk.
2.1. Circumstances for initiation of post-marketing surveillance:
The opening of post-marketing surveillance can be decided by the Director General of AFSSAPS, mainly for new drugs placed on the market, when judged Need to strengthen the monitoring of their tolerance profile. Monitoring of pharmacovigilance can also be carried out in the wider context of a European investigation.
AFSSAPS Director-General appoints a rapporteur responsible for the conduct of follow-up among the heads of the regional centres Pharmacovigilance (LRB), possibly one or more Associate Rapporteurs among LRBs. It shall notify, by mail, this decision to the responsible (s) responsible for the follow-up and to the responsible marketing (s) of the medicinal product (s) concerned.
2.2. Conduct of pharmacovigilance monitoring:
The date of the opening of the pharmacovigilance follow-up is that of the mail addressed by the Director General of AFSSAPS to the responsible person (s) for marketing the drug and the designated rapporteur To follow up.
A first meeting is organised, in general with AFSSAPS, with the marketing manager (s), the rapporteur and representatives of AFSSAPS. The purpose of this meeting is to determine the information and documents to be exchanged between the various stakeholders and to schedule future meetings. An account of this meeting shall be drawn up and validated by the parties concerned.
At each meeting, the rapporteur presents, in the form of a report, an updated review of the data. If necessary, this report may be presented as a technical committee and, where appropriate, in the National Pharmacovigilance Commission.
Please refer to the pharmacovigilance procedure described above for the following points: :
-data collection;
-evaluation and imputation of feedback;
-searching for additional elements;
-defining the particular profile of the adverse reaction and looking for preferred factors;
- Attempt to estimate an impact.
2.3. Searching for comparison points:
With the help of the market leader (s), the monitoring officer looks for the data to situate the observed or estimated risk, on the one hand, in relation to other risks related to a Or several drugs of the same therapeutic or pharmacological class, on the other hand, compared to other therapeutic and non-therapeutic drugs.
2.4. Proposals/Opinions:
In the event of an emerging problem, follow-up may be the subject of a presentation to the Technical Committee and the National Pharmacovigilance Commission in accordance with the modalities foreseen for the pharmacovigilance survey described Above.
For medicinal products registered in accordance with a European procedure, the conclusions of the follow-up may be transmitted, if necessary, to the European Medicines Agency, the rapporteur or the Member State of reference
Publication of follow-up data is envisaged, the document is sent for information prior to its release or presentation to the marketing officials concerned and to AFSSAPS.



You can view the table in OJ
n ° 121 of 26/05/2005 text number 14



Chapter 8
Good publishing practices


General principles : Good publishing practices are intended for the authors of publications of adverse reactions associated with the use, misuse or abuse of one or more drugs or products, including during exposure during pregnancy or Breastfeeding, as well as editorial staff (editors, reading committees) of journals for health professionals and scientific committees of congresses, in order to ensure, for public health purposes, an optimal quality of these Publications. They apply to articles and oral or poster communications.


1. Role of publishing authors


Due to the possible use of published information, authors of any publication must take into account the media coverage of the formulations they use.
1. To rapidly disseminate relevant information in the form of good quality publications, be they health care professionals, responsible for marketing or competent authority.
2. Declare Prior to the competent authorities or the regional pharmacovigilance centres the serious or unexpected effects and, more generally, to report before the publication of the publications to their attention, as well as to the person responsible for the placing on the Market for the drug (s) involved.
3. Make available to editorial staff all elements to ensure the authenticity of the data.
4. Indicate in the title of the publication the adverse reaction and the drug (s) or suspect product (s).
5. Include in the publication the elements for assessing compliance in an optimal way:
-description of the characteristics of the subject matter: age, gender, history and current disease;
-the description of the adverse reaction Presumed: date of occurrence, clinical and biological elements of the positive diagnosis, evolution by specifying the duration of follow-up and the severity assessed according to international criteria;
-description of suspected and associated drugs: International common name, speciality name, pharmaceutical form, indication (s), dosage (s), dates of possible catch and arrest;
-the data used to assess the causal link: time limits, effect of the judgment and the Possible re-administration of the suspected drug (s), clinical or biological elements evocative of the possible role of the drug (s) involved;
-the proposed non-medicinal diagnoses and the elements enabling the drug (s) Eliminate;
-bibliographic elements for assessing the originality of the observation.
6. The publication of case series should allow for the same analysis as individual cases. If their number prohibits the detailed publication of each observation, a table presents the most important data (age, sex, onset and nature of the adverse reaction, evolution at the stop), knowing that all the elements The above must be available upon request of the editorial staff.
Note, in case of publication of case series, the various arguments common to the various observations, in favour of a causal relationship and of the identification of Risk factors; report, to the extent possible, the number of cases of suspected drug use in the population concerned, indicating the origin of the information.
7. Justify the precise wording of the title-in particular the possible causal relationship-and the findings by the reported facts and by a rigorous discussion. The terms used in the title of the publication to describe the causal relationship must be measured.
8. The discussion of the reported case (s) should be weighed against the concept of the benefit-risk of the drug concerned using the available data.
9. The publication of the adverse reaction (s) described must be in perspective with all published adverse reactions, including the effects of the same nature (novelty).
10. Avoid concluding with general public health recommendations from the description of an isolated case.


2. Role of editorials


1. Encourage the rapid publication of serious and unexpected adverse reactions.
2. Remind the authors of their obligation to notify the regional pharmacovigilance centres of the serious or unexpected effects. The date of notification appears on the publication, along with the date of receipt of the manuscript.
3. Submit publications to a reading committee with a qualified person in pharmacovigilance.
4. Remind the authors, and make sure, that the draft publication should be communicated to the responsible person (s) of the marketing of the medicinal product (s) concerned and to offer the possibility of publishing the possible responses following the article, Provided that the arguments presented are also rigorously justified.
5. Encourage the reading committee to perform the necessary checks for quality assurance.


Chapter 9
Contact Information for Regional Pharmacovigilance Centres


You can Consult the table in OJ
No 121 of 26/05/2005 text number 14


Done at Paris, April 28, 2005.


Philippe Douste-Blazy


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