Key Benefits:
Publics concerned: holders of marketing authorization; companies or organizations operating a drug or product for human use; health professionals; patients; approved patient associations; Pharmaceutical institutions, including those managed by public health institutions referred to in Articles R. 5124-68 to R. 5124-73 of the Public Health Code ; pharmacies for internal use referred to in Article L. 5126-1 of the same code; holders of the authorization provided for in theArticle L. 4211-6 of the Public Health Code.
Purpose: Strengthen the safety regulations for human-use drugs subject to market authorization and pharmacovigilance.
Entry into force: the text comes into force on the day after its publication, subject to the following transitional provisions provided for in Article 8:
- for market authorizations issued prior to July 21, 2012, the obligations relating to the permanent record of the pharmacovigilance system must be met at the time of the renewal of the authorization and no later than July 21, 2015;
―the new renewal application period is not applicable to those of these authorities that expire before July 21, 2013;
― the updating of the supplemental surveillance drug record must take place within one year of the publication by the European Commission of the elements required by Community regulations;
― the National Drug Safety Agency and Health Products transmits to the European Commission the results of the periodic evaluation of its pharmacovigilance system by 21 September 2013;
― the provisions relating to the declaration of adverse reactions come into force on the announcement by the European Drug Agency of the effective implementation of the new features of "Euravigilance" for the National Drug Safety Agency and Health Products, and within six months of this announcement for companies or organizations operating a drug or a product for human use;
― the obligation to transmit the updated periodic report of security to the European directory applies within one year following the announcement by the European Drug Agency of the implementation of the updated directory of periodic reports of safety.
Notice: This text concludes the implementation of the above-mentioned Directive 2010/84/EU. First, it completes the list of parts to be added to any application for marketing authorization. In the second place, it amends the conditions for the renewal of the marketing authorization and the reasons for modification, suspension or withdrawal. The decree also reviews the provisions of Public Health Code on pharmacovigilance by specifying the field. It introduces new obligations in this area to the National Drug and Health Products Safety Agency, companies or organizations operating a drug or product referred to in theArticle R. 5121-150 of the Public Health Code, pharmaceutical establishments, pharmacies for indoor use, doctors, dental surgeons, midwives and pharmacists.
References: the provisions of Public Health Code Amended by this decree may be consulted, in their writing resulting from this amendment, on the website Légifrance (http://www.legifrance.gouv.fr). This text is being implemented articles 9, 11, 22 and I of thearticle 28 Act No. 2011-2012 of 29 December 2011 on strengthening the health safety of the drug and health products and implementing Directive 2010/84/EU of the European Parliament and of the Council of 15 December 2010 amending, with regard to pharmacovigilance, Directive 2001/83/EC establishing a Community Code for Human Drugs.
The Prime Minister,
On the report of the Minister of Social Affairs and Health,
Considering Regulation (EU) No. 1235/2010 of the European Parliament and of the Council of 15 December 2010 amending Regulation (EC) No. 726/2004 on the pharmacovigilance of drugs for human use, establishing Community procedures for authorization and monitoring with regard to drugs for human use and veterinary use and establishing a European Agency for Drugs and Regulation (EC) No. 1394/2007 on innovative therapy drugs;
In view of Directive 2010/84/EU of the European Parliament and of the Council of 15 December 2010 amending Directive 2001/83/EC of 6 November 2001 establishing a Community Code for Human Drugs;
Vu le Public Health Codeincluding articles L. 5121-8, L. 5121-8-1 and L. 5121-26;
The State Council (Social Section) heard,
Decrete:
The provisions of chapter I, section 5, title II, of Book I of Part 5 of the Public Health Code are thus amended:
1° Article R. 5121-25 is amended as follows:
(a) In the first paragraph, after the words: "the following documents", the words are inserted: ", updated as needed";
(b) The 3° is replaced by the following:
« 3° A summary describing the pharmacovigilance system of the future holder of the authorization or company that operates the pharmaceutical specialty and includes the following:
“(a) A declaration signed by the applicant by which it certifies that the future holder of the authorization or the company operating the pharmaceutical specialty has a qualified person responsible for pharmacovigilance in a Member State of the European Union or a State Party to the Agreement on the European Economic Area;
“(b) The Member State in which the qualified person resides and operates;
"(c) Coordinates of the qualified person responsible for pharmacovigilance;
"(d) A statement signed by the applicant by which it certifies that the future holder of the authorization or the company operating the pharmaceutical specialty has the means necessary to carry out its duties and responsibilities with respect to pharmacovigilance;
“e) The address of the location of the permanent file of the pharmacovigilance system corresponding to the drug concerned; » ;
(c) After the 3°, it is added a 3° bis as follows:
« 3° bis The risk management plan describing the risk management system for which the model is set by the European Commission, to be put in place by the future holder of the authorization or the company operating the pharmaceutical specialty for the drug concerned, along with its summary; » ;
(d) At 7°, the words "the Community" are replaced by the words "the Union";
(e) At 10°, the words: "Community" are replaced by the words: "the Union" and after the word: "accompanied" are added the words: "summaries of security information including the data contained in the updated periodic security reports, when available, and notifications of suspected adverse effects,"
(f) At 11°, the words "the Community" are replaced by the words "the Union";
(g) The 12th is thus modified:
- in the first paragraph, the words: "the Community" are replaced by the words: "the Union";
the second paragraph is deleted;
2° In the third paragraph of section R. 5121-35, the words: "as well as preclinical and clinical trials of the drug concerned" are replaced by the words: "preclinical tests and biomedical research, as well as the risk management and pharmacovigilance system established for the drug or product concerned. » ;
3° A. R. 5121-36, before the last paragraph, is inserted a paragraph as follows:
"It indicates the frequency of transmission of the updated periodic security report referred to in R. 5121-168. » ;
4° Article R. 5121-36-1 becomes article R. 5121-36-2;
5° After the article R. 5121-36, an article R. 5121-36-1 is inserted as follows:
"Art. R. 5121-36-1.-The marketing authorization may impose one or more of the following conditions, which must be mentioned in the risk management system:
« 1° Implementation of measures to ensure safe use of the drug or product;
« 2° Post-authorization security studies;
« 3° Respect for specific obligations with respect to the registration or notification of suspected adverse effects;
« 4° Any other condition or restriction intended to ensure the safe and effective use of the drug or product;
« 5° The existence of an adequate pharmacovigilance system;
« 6° Post-authorization effectiveness studies are carried out where the acquisition of additional data is required after the drug or product is marketed.
"The marketing authorization specifies, where applicable, the deadlines in which these conditions must be implemented.
"The licensee of the marketing authorization assesses whether the results of the studies referred to in 2° and 6° of this article have an impact on this authorization. The licensee shall, where appropriate, file an appropriate request to amend the marketing authorization with the Director General of the National Drug Safety Agency and Health Products, following the schedule for its implementation. » ;
6° Section R. 5121-37-1 is amended as follows:
(a) The first paragraph is replaced by the following:
"After the issuance of the marketing authorization, the licensee shall promptly transmit to the National Drug and Health Products Safety Agency, by indicating the scope, any new information available or known to it, which may result in a change in the assessment of the relationship between the benefits and risks associated with the drug or product as defined in the first paragraph of section L. 5121-9. It transmits the results of all studies, in particular safety and efficacy studies, and the results of biomedical research carried out in or outside the European Union or the European Economic Area, whether favourable or unfavourable, for all indications and populations, whether or not mentioned in the marketing authorization, as well as data concerning any use of the drug not in accordance with the terms of market authorization. » ;
(b) After the second paragraph, two sub-items are inserted:
"The licensee shall ensure that the information on the drug or product is updated on the basis of current scientific knowledge, including the conclusions of the evaluations and recommendations made public through the European Drug Web Portal, established by Article 26 of Regulation (EC) No. 726/2004 of the European Parliament and the Council of 31 March 2004.
"The licensee shall inform the Director General of the Agency and the European Agency of Drugs when new risks, existing risks or changes in the relationship between the benefits and risks associated with the drug or product are identified. » ;
7° Section R. 5121-37-2 is replaced by the following provisions:
"Art. R. 5121-37-2.-Posted to the issuance of a marketing authorization, including for an authorization issued prior to July 21, 2012, the Director General of the National Agency for the Safety of Medicine and Health Products may, by reasoned and notified in writing, require the licensee to put in place the risks associated with the drug or the authorized product in place of a specified time limit. This decision can only intervene after the licensee has been invited to submit its comments within 30 days. Based on written comments provided by the licensee of the marketing authorization, the National Drug and Health Products Safety Agency withdraws or confirms the obligation. If it confirms the obligation, the marketing authorization is amended to include the measures to be taken within the framework of the risk management system as conditions of the marketing authorization, in accordance with the 1st of Article R. 5121-36-1. » ;
8° After article R. 5121-37-2, an article R. 5121-37-3 is inserted as follows:
"Art. R. 5121-37-3.-Posted to the issuance of a marketing authorization, the Director General of the National Agency for the Safety of Medicine and Health Products may require the licensee to conduct a post-authorisation safety or efficacy studies or a specific monitoring of the risk, its complications and its medical-social care, as provided for in section-1.
"The Director General of the Agency may request that these studies or specific follow-up be carried out jointly by several licensees of marketing authorization.
"The Director General shall inform the holder(s) of his intention by specifying the objectives and deadlines of the proposed studies and specific follow-up. He or she invites them to submit their comments within 30 days.
"According to the comments provided by the licensee(s), the Director General of the Agency shall motivate and notify the Agency in writing of its decision.
"If it confirms the obligation, the marketing authorization is amended to mention this obligation, and the risk management system is adapted accordingly.
"After conducting a safety or efficacy study as provided for in section L. 5121-8-1, the licensee of the marketing authorization assesses whether the results of the study have an impact on the said authorization. The licensee shall, where appropriate, file an appropriate request to amend the marketing authorization with the Director General of the Agency, following the schedule for its implementation. » ;
9° Section R. 5121-43 of the Public Health Code is amended as follows:
In the first paragraph, after the words "of Article L. 5121-9", the words "and which are to be mentioned in the risk management system" are added;
10° Section R. 5121-45 is amended as follows:
(a) In the first paragraph, the word "six" is replaced by the word "new";
(b) In the second paragraph, after the words: "including", the words are added: "The assessment of the data contained in the notifications of suspected adverse events and in the updated periodic reports of security, as well as";
(c) After the fourth preambular paragraph, a sub-item reads as follows:
"If a request for additional justification or if a proposed refusal of renewal is sent to the applicant before the expiry date of the marketing authorization, the authorization is extended until the Agency's decision is notified. » ;
(d) The last paragraph is amended to read:
―after the word "decision", is added the word "in particular";
―after the word "pocophagilance," the words are added: "including an exposure of an insufficient number of patients to the drug or to the product concerned,"
― the word "extra" is replaced by the word "five";
11° Article R. 5121-45-1 is repealed;
12° Section R. 5121-47 is amended as follows:
(a) The first six paragraphs are replaced by the following:
"The Director General of the National Agency for the Safety of Medicine and Health Products may, by a reasoned decision indicating the avenues and time limits of appeal, amend ex officio, suspend, for a period not exceeding one year, or withdraw a marketing authorization for the reasons referred to in section L. 5121-9. However, when the authorization is suspended, either on a provisional basis pending the outcome of an arbitration procedure of the European Union, or in accordance with a decision of the European Commission following this procedure, the suspension remains in effect until the European Commission orders that it be terminated.
"The marketing authorization is also ex officio, suspended or withdrawn by the Director General of the Agency:
« 1° Where it appears that the information provided on the occasion of the application for a marketing authorization is incorrect or has not been modified in accordance with sections R. 5121-37 and R. 5121-37-1, that the conditions set out in this section are not or are no longer being met or that the controls have not been performed;
« 2° Where the labelling or leaflet of the drug or product does not comply with the general or specific requirements of this heading;
« 3° When obligations under articles R. 5121-36-1 and R. 5121-43 are not implemented;
« 4° When the authorization must be in conformity with the decision of the European Commission following an arbitration procedure of the European Union;
« 5° When the authorization is to be in conformity with an agreement that has been the subject of consensus within the coordination group referred to in Article 27 of Directive 2001/83/EC of the European Parliament and the Council. » ;
(b) The seventh paragraph is amended to read:
― after the words: "Unless in case of emergency," the words are added: "office change,"
― the words "as mentioned in the preceding three paragraphs" are deleted;
13° Section R. 5121-48 is replaced by the following provisions:
"Art. R. 5121-48. -The Director General of the National Drug Safety Agency and Health Products may prohibit the prescription and issuance of a pharmaceutical specialty and remove it from the market for the reasons mentioned in section L. 5121-14-2. The decision is motivated and, except in the event of an emergency, may intervene only after the licensee has been invited to submit its comments.
"For a pharmaceutical specialty that has been prohibited, the director general of the agency may, in exceptional circumstances and for a transitional period, authorize the grant of speciality to patients who are already treated, especially when one of the following conditions is met:
« 1° It is necessary to implement a gradual decline in treatment to prevent or limit a rebound effect or the effect of a withdrawal syndrome;
« 2° A deadline is required to adapt the recommendations for the management of the disease concerned;
« 3° A deadline is needed for health professionals to define the best possible therapeutic alternative for their patients.
"The duration of the proposed transitional period is indicated in the letter by which the licensee is invited to submit its comments in accordance with the first paragraph. » ;
14° After R. 5121-48, an article R. 5121-49 was reinstated as follows:
"Art. R. 5121-49.-When, on the occasion of the implementation of Article 20, paragraph 4, of Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004, an urgent action is required to protect human health or the environment, pending a final decision by the European Commission, the Director General of the National Agency for the Safety of Medicine and Health Products may suspend the application The decision of the director general of the agency is motivated. The licensee of the marketing authorization is previously informed of the decision and, if the situation permits, it is previously invited to submit its comments.
"When acting on its own initiative, the director general of the agency informs the European Commission and the European Agency of Drugs of the reasons for this measure no later than the first working day following its decision. » ;
15° Section R. 5121-50 is amended as follows:
(a) In the second paragraph, after the words: "report" are added the words: "in particular by the agency's website:"
(b) The 1° is replaced by the following:
« 1° Decisions to authorize the marketing of the drugs or products that it has issued, together with the summary of the characteristics of the corresponding product, the notice, of any condition fixed pursuant to the third paragraph of Article L. 5121-9, Article R. 5121-36-1 and Article R. 5121-37-3, with their deadline for execution; »
(c) After 1°, it is inserted a 1° bis as follows:
« 1° bis The public assessment report, as well as the reasons for the decision for each claimed therapeutic indication, excluding any information of an industrial or commercial nature. This report contains a summary, in easy-to-understand terms for all users, including a section on the conditions of use of the drug or product; »
(d) After the 2°, are added a 3°, 4° and 5° as follows:
« 3° The list of drugs referred to in Article 23 of Regulation (EC) No 726/2004 of the European Parliament and the Council of 31 March 2004;
« 4° Syntheses of drug or product risk management plans;
« 5° Important information on pharmacovigilance issues related to the use of a drug or product. » ;
(e) The provisions of the last paragraph shall be replaced by the following provisions:
"The decisions set out in the third paragraph of Article L. 5121-9 and R. 5121-36, R. 5121-36-1, R. 5121-37-3, R. 5121-42, R. 5121-43 and R. 5121-47 or their cancellations are immediately communicated by the Director General of the National Agency for the Safety of Drugs and Health Products to the European Agency for Drugs. » ;
16° Section R. 5121-51-9 is amended as follows:
(a) In the first paragraph, the words: "community interest" are replaced by the words: "interest for the European Union" and the words: ", especially on the pharmacovigilance database" are deleted;
(b) After the first preambular paragraph, it is added a subparagraph to read:
"When emergency measures are deemed necessary, the procedure provided for in section R. 5121-157 applies. » ;
17° Article R. 5121-51-10 is repealed;
18° In R. 5121-51-11, the words "at R. 5121-51-10" are replaced by the words "and R. 5121-51-9".
In the second paragraph of section R. 5121-140 of the Public Health Code, the word "provided" is replaced by the word "delivered" and after the word "may" are added the words: ", subject to the measures it deems necessary to protect human health."
In the fourth paragraph of section R. 5121-148 of the Public Health Code, the word "provided" is replaced by the word "delivered" and after the word "may" are added the words: ", subject to the measures it deems necessary to protect human health."
Section R. 5121-149 of the Public Health Code is amended as follows:
1° The first paragraph is replaced by the following:
"The notice is prepared in accordance with the summary of product characteristics. It contains a standard text, specifically inviting patients to report any suspected adverse reactions to their doctor, pharmacist or other health care professional or directly to the regional pharmacovigilance centre, and specifying the different modes of notification available to them. It also includes, in order, the following indications:";
2° At 5°, the words: "as well as an express invitation for the patient to communicate to his doctor or pharmacist any suspected adverse effects that would not be mentioned in the notice" are deleted;
3° After the 8th it is added a sub-paragraph as follows:
"For the drugs on the list referred to in Article 23 of Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004, the notice must, in addition to the information mentioned above, include the mention: "This drug is subject to additional supervision". This mention is preceded by the black symbol mentioned in Article 23 of Regulation (EC) No 726/2004 of the European Parliament and the Council of 31 March 2004 and followed by an explanatory sentence determined by the European Commission. »
Section 13 of Chapter I of Book I, Title II of Part 5 of the Public Health Code is amended to read:
1° Subsection 1 is replaced by the following:
"Subsection 1
“General provisions
"Art. R. 5121-150.- Pharmacovigilance:
« 1° For drugs and products to be subject to market authorization provided for in Article L. 5121-8, after the issuance of such authorization;
« 2° For drugs referred to in Article L. 5121-12, after the issuance of temporary authorization for use, subject to the specific rules for these drugs in Article R. 5121-169;
« 3° For homeopathic medicines referred to in Article L. 5121-13, after the registration provided for in this article;
« 4° For traditional herbal medicines referred to in Article L. 5121-14-1, after the registration provided for in this article;
« 5° For other products referred to in Article L. 5121-1 after delivery;
« 6° For allergens, specially prepared for a single individual, referred to in Article L. 4211-6, after the issuance of the authorization provided for in this article;
« 7° For blood-derived drugs and other medicines of human origin, subject to the specific rules for these drugs by the 14th of Article L. 5121-20;
« 8° For drugs referred to in section L. 5121-9-1 after the issuance of the authorization provided for in that section.
"Art. R. 5121-151.- Pharmacovigilance includes:
« 1° Reporting of adverse reactions suspected of being due to a drug or product referred to in section R. 5121-150, including overdosing, misuse, abuse and drug error as defined in section R. 5121-152, as well as monitoring of adverse effects related to occupational exposure and collecting information about them. For drugs subject to market authorization or registration, this means in cases of use that is in conformity with or inconsistent with the terms of such authorization or registration;
« 2° The collection, registration, evaluation and operation of this information for the purpose of prevention or risk reduction and where necessary to take appropriate action. This information is analysed taking into account the available data relating to the sale, delivery and consumption, prescription and administration of the drugs and products referred to in R. 5121-150 to patients;
« 3° The completion of all studies and work on the safety of use of the drugs and products referred to in R. 5121-150.
"The exercise of pharmacovigilance may require the research and analysis of data contained in the preclinical animal experimentation record or in the biomedical research file of a drug or product referred to in R. 5121-150, as well as information relating to its manufacture and conservation.
"The provisions of this section do not impede the application of the provisions of this Code relating to pharmacodeity and toxicovigilance.
"Art. R. 5121-152.-For the purposes of this chapter, the following are:
"1°" Undesirable effect”: a negative and unintended reaction to a drug or product referred to in R. 5121-150;
"2°" Serious adverse effect”: a lethal adverse effect, or likely to put life at risk, or resulting in significant or lasting disability or disability, or causing or prolonging hospitalization, or manifesting itself by a congenital abnormality or malformation;
"3°" Unexpected adverse effect”: an adverse effect whose nature, severity or evolution do not correspond to the information contained in the summary of product characteristics referred to in R. 5121-21;
"4° "Mesuse": an intentional and inappropriate use of a drug or product in relation to the authorized or prescribed dose, the route of administration, the indications, or not in accordance with the terms of the marketing or registration authorization and the recommendations of good practices;
"5° Abus": intentional, persistent or sporadic excessive use of drugs or products referred to in R. 5121-150, accompanied by harmful physical or psychological reactions;
"6° "Surdosing": administration of a quantity of medication or product, by taking or daily, which is greater than the maximum recommended dose in the summary of the product characteristics referred to in R. 5121-1. The cumulative effects due to overdose are taken into account;
"7°" Post-authorization safety studies”: any study of a drug or product authorized to identify, characterize or quantify a safety risk, confirm the drug safety profile or measure the effectiveness of risk management measures;
"8°" Post-authorization effectiveness studies”: any biomedical research or any observational study on the efficacy in common medical practice of a drug or product;
"9°" Risk Management System”: a set of pharmacovigilance activities to identify and describe the risks associated with a drug or product referred to in R. 5121-150 and a set of measures to prevent or minimize these risks, including the assessment of the effectiveness of these activities and measures. This set of activities and measures is proportionate to the proven risks and potential risks of the drug or product, as well as to the need for security information after the marketing authorization;
"10°" Risk Management Plan”: a detailed description of the risk management system defined at 9°;
"11°" Pharmacovigilance System: a system established and used by any company or agency operating a drug or product referred to in R. 5121-150 and by the National Agency for Safety of Medicine and Health Products in order to meet their obligations with respect to pharmacovigilance and to monitor the safety of the drugs or products referred to in R. 5121-150 and to identify any changes to the drug or product(s) referred to in R. 5121-150 and to
"12°" Permanent record of the pharmacovigilance system”: a detailed description of the pharmacovigilance system established and used by any company or agency operating a drug or product referred to in R. 5121-150 concerning one or more of these drugs or products;
"13°" Drug error”: an unintentional error of a health care professional, a patient or a third party, as the case may be, occurred during the treatment process involving a drug or health product referred to in R. 5121-150, particularly during prescription, dispensation or administration;
"14°" Occupational exposure”: exposure to a drug or product referred to in article R. 5121-150 as part of professional activity. » ;
2° Sub-section 2 is amended as follows:
(a) Paragraph 1 is replaced by the following:
“Paragraph 1
“National System
"Art. R. 5121-153.-The actors of the pharmacovigilance system as referred to in Article L. 5121-23 are:
« 1° The National Drug and Health Products Safety Agency;
« 2° The regional pharmacovigilance centres referred to in R. 5121-158;
« 3° Health professionals referred to in article R. 5121-161, pharmacies for domestic use referred to in article L. 5126-1 and holders of the authorization provided for in article L. 4211-6;
« 4° Companies or organizations operating a drug or product referred to in R. 5121-150 and any third party performing all or part of the constitutive operations of pharmacovigilance referred to in the fourth paragraph of Article R. 5124-47 on behalf of the companies and organizations mentioned above;
« 5° Pharmaceutical establishments, including those managed by public health institutions' pharmaceutical establishments referred to in articles R. 5124-68 to R. 5124-73 for their hospital preparation and masterly preparation activities.
"The patients and approved patient associations referred to in R. 5121-161 are involved in this system";
(b) Paragraph 2 is replaced by the following:
“Paragraph 2
" Role of the National Drug Safety Agency
and Health Products
"Art. R. 5121-154.-I. ― The National Drug and Health Products Safety Agency ensures national implementation of the pharmacovigilance system to meet its obligations with respect to pharmacovigilance and participation in European Union activities in this area. A periodic evaluation of the pharmacovigilance system is carried out. The results of this evaluation are transmitted to the European Commission every two years from the first transmission.
“II. ― The agency is the recipient of the following documents:
« 1° Notifications, transmitted electronically by the European database "Euravigilance" of adverse events in France, reported in this database by companies and organizations operating a drug or product referred to in article R. 5121-150;
« 2° Reports transmitted by companies and organizations operating drugs or products referred to in R. 5121-150 pursuant to Article II R. 5121-168 and Article R. 5121-170;
« 3° Information transmitted by regional pharmacovigilance centres pursuant to Article R. 5121-159;
« 4° Reports transmitted pursuant to Article R. 5121-175 by pharmaceutical establishments, including pharmaceutical establishments of public health institutions referred to in Articles R. 5124-68 to R. 5124-73 for their activities in the conduct of hospital preparation and masterful preparation;
« 5° Reports transmitted pursuant to Article R. 5121-176 by pharmacies for internal use referred to in Article L. 5126-1 for their completion or subcontracting of hospital preparation and masterful preparation;
« 6° Reports transmitted under section R. 5121-174 by the licensee of the authorization provided for in section L. 4211-6.
"The agency receives duplicate reports from companies and organizations operating drugs or products referred to in R. 5121-150 pursuant to R. 5121-167.
"It reports to the European Medicines Agency and to the company or agency operating a product referred to in Article R. 5121-150 any duplicate that it would have detected in the notification of adverse effects.
"III. ― The agency assesses the updated periodic security reports it received in accordance with section R. 5121-170 and transmits its evaluation reports to the committee for the assessment of the risks of pharmacovigilance referred to in Article 56 of Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004.
"In collaboration with the European Medicines Agency, the agency monitors the results of the risk reduction measures set out in the risk management plans, the results of the obligations referred to in articles R. 5121-36-1, R. 5121-37-3 and R. 5121-43, assesses the updates of the risk management system and monitors the information recorded in the European database "Eurravigilance" to determine if new risks are changed
"It informs the European Medicines Agency and the company or agency operating a drug or product referred to in section R. 5121-150 when new risks, existing risk changes or changes in the relationship between the benefits and risks associated with the drug are found under the preceding paragraph.
"It shall inform, no later than 24 hours before the public has been distributed to the general public of a notice relating to pharmacovigilance information, the European Medicines Agency, the European Commission and the Member States of the European Union or the States parties to the agreement on the European Economic Area of such communication, except in the event of an emergency. Any personal or commercial confidentiality information is deleted, unless the disclosure of such information is necessary for the protection of public health.
"When the notice referred to in the previous paragraph relates to drugs or products that contain the same active substance or combination of active substances and that are authorized in several Member States of the European Union or States Parties to the European Economic Area Agreement, the National Agency for the Safety of Medicine and Health Products, in collaboration with other EU Member States or States Parties to the Agreement on the European Economic Area, shall prepare a joint message concerning the safety of the drug or product concerned. The agency distributes this notice to the general public according to the schedule provided by the European Agency for Drugs. Any personal or commercial confidentiality information is deleted, unless the disclosure of such information is necessary for the protection of public health.
"Art. R. 5121-155.-I. ― The Director General of the agency may request the regional pharmacovigilance centres to complete all investigations and pharmacovigilance work.
"It may also request the drug addiction assessment and information centres referred to in Article R. 5132-112 and the poison control centres referred to in Article L. 6141-4 to provide the information and to conduct the studies it considers useful for the purpose of pharmacovigilance.
"The Director General of the Agency may involve any company or agency operating a drug or product referred to in section R. 5121-150 that has declared an adverse reaction suspected under the provisions of section R. 121-166 to follow up on that statement.
"It may also involve health professionals, patients and registered associations of patients who reported an adverse reaction suspected under section R. 5121-161 to follow up on this statement.
"It may request any company or agency operating a drug or product referred to in section L. 5121-1 to provide any information referred to in the 2° and the foreword-last paragraph of section R. 5121-151 or to conduct any investigation, study or work relating to the benefits and risks of adverse effects that these drugs or products may present. This request is motivated.
“II. ― After the use of the information collected in particular pursuant to section R. 5121-154, the Director General of the National Agency for the Safety of Medicine and Health Products shall, where appropriate, take appropriate measures to ensure the safety of use of the drugs and products referred to in section R. 5121-150 and to stop the incidents and accidents that have proved to be related to their use, or to the competent authorities.
"Art. R. 5121-156.-The Director General of the National Drug and Health Products Safety Agency:
« 1° Record any undesirable effects suspected of being due to a drug or product referred to in article R. 5121-150, which occurred in France, which was declared or notified to it;
« 2° Electronically declares to the European database "Eurdravigilance" :
“(a) Any serious adverse event suspected, occurring in France, within fifteen days of receipt of the declaration or notification;
“(b) Any non-serious adverse event that occurred in France within 90 days of receipt of the declaration or notification.
"Art. R. 5121-157.-The Director General of the National Drug Safety Agency and Health Products immediately informs the European Commission of the European Medicines Agency and other Member States of the European Union when it considers that an urgent action is necessary, following the assessment of data resulting from pharmacovigilance activities, in one of the following situations:
« 1° It plans to suspend or withdraw a marketing authorization;
« 2° It envisages prohibiting the issuance of a drug or product with a marketing authorization;
« 3° He plans to refuse the renewal of a marketing authorization;
« 4° It is informed by a company or agency operating a drug or product referred to in R. 5121-150 that due to concerns about the safety of a drug, the company or agency has interrupted the marketing of the drug or product or has taken or is considering taking action to remove the marketing authorization of the drug or product;
« 5° It considers it necessary to report a new contraindication, reduce the recommended dosage or restrict the indications.
"In exceptional cases resulting from the assessment of the data of the pharmacovigilance activities, when the Director General of the National Agency for the Safety of Medicine and Health Products decides to suspend, as a matter of urgency, the authorization to put on the market and to prohibit the use of the drug or product in order to protect public health, pending a final decision to be taken in accordance with the arbitration procedure of the European Union, he informs the European Union
"The Director General of the Agency shall make available to the European Medicines Agency any relevant scientific information it holds, as well as any assessment that the National Drug and Health Products Safety Agency would have done";
(c) Paragraph 4, entitled "Regional Pharmacovigilance Centres" becomes paragraph 3 and is thus amended:
― sections R. 5121-167 to R. 5121-169 of the Public Health Code become R. 5121-158 to R. 5121-160 of the same code respectively;
― 1° of article R. 5121-158 of the Public Health Code, the reference to R. 5121-170 is replaced by the reference to R. 5121-165;
― 2° of article R. 5121-159 of the Public Health Code, the reference to R. 5121-167 is replaced by the reference to R. 5121-158;
- in the last paragraph of section R. 5121-160 of the Public Health Code, the words: "as well as the designation of their representatives to the technical committee referred to in article R. 5121-164," are deleted;
(d) Paragraph 4 and paragraph 5 are added:
“Paragraph 4
"Health professionals and patients
"Art. R. 5121-161.-The physician, dentist, midwife or pharmacist immediately declares any undesirable effects suspected of being due to a drug or product referred to in R. 5121-150, of which he is aware, at the regional pharmacovigilance centre.
"Other health professionals, patients and approved patient associations may report any adverse reactions suspected of being due to a drug or product referred to in R. 5121-150, of which they are aware, at the regional pharmacovigilance centre.
"The Director General of the National Agency for the Safety of Medicine and Health Products makes public, on the agency's website, information on the various modes of notification of adverse reactions suspected of being due to a drug or product referred to in article R. 5121-150 by health professionals and patients as well as the reporting form for these adverse effects.
“Paragraph 5
"Companies or organizations operating a drug
or a product referred to in R. 5121-150
"Art. A. 5121-162.-Any company or agency operating a drug or product referred to in section R. 5121-150 shall implement a pharmacovigilance system to comply with its obligations with respect to pharmacovigilance, including the collection and scientific assessment of all information relating to the adverse effects referred to in section R. 5121-151, for the purpose of prevention and reduction of appropriate measures.
"A company or organization operating a drug or product referred to in section R. 5121-150 shall manage a permanent record of the pharmacovigilance system and shall make available within seven days, upon request of the Director General of the National Drug Safety Agency and Health Products, a copy of that record.
"An audit of the pharmacovigilance system is performed and recorded in the permanent file of the pharmacovigilance system. Based on these results, an action plan to address the problems identified must be implemented. Once the corrective actions are fully implemented, recorded statements may be deleted.
"Art. R. 5121-163. -As part of the pharmacovigilance system, any company or organization operating a drug or product referred to in R. 5121-150:
« 1° Implement a risk management system for each drug or product that has been licensed to market after July 21, 2012;
« 2° Monitors the results of the risk reduction measures described in the risk management plan or taken under articles R. 5121-36-1, R. 5121-37-3 and R. 5121-43;
« 3° Keeps the risk management system up-to-date and monitors pharmacovigilance data to identify new risks, existing risk changes or changes in the relationship between benefits and risks associated with drugs or products;
« 4° Ensure that notifications of undesirable effects suspected of being due to a drug or product referred to in Article R. 5121-150 in a Member State of the European Union or a State Party to the Agreement on the European Economic Area or a third country are accessible in the "Eurdravigilance" basis.
"Art. A. 5121-164.-Any company or agency operating a drug or product referred to in Article R. 5121-150 shall have the services of a person responsible for pharmacovigilance resident and in a Member State of the European Union or a State Party to the Agreement on the European Economic Area and justifying appropriate pharmacovigilance qualifications. The identity, quality and function as well as the contact details of this person are communicated to the Director General of the National Agency for the Safety of Medicine and Health Products and to the European Medicines Agency upon appointment.
"In addition, any company or agency operating a drug or product referred to in R. 5121-150 has the services of a pharmacovigilance reference person attached to the qualified person responsible for pharmacovigilance activities. This reference person, doctor or pharmacist, resides and exercises in France and must justify a pharmacovigilance experience. The identity and quality as well as the contact details of this person are communicated to the Director General of the National Drug and Health Products Safety Agency upon appointment.
"These people work together to:
"1° Gather, process and make accessible to any authorized person the information made known to the company or body operating the drug or product, as well as to the persons referred to in section L. 5122-11 who make information by demarcation or prospecting for drugs and products, and related to the suspected adverse effects of being caused by drugs or products that are exploited by the company;
"2° Implement and manage the pharmacovigilance system provided for in R. 5121-162 and the risk management system provided for in R. 5121-163;
"3° Prepare and submit the declarations and reports referred to in R. 5121-166, R. 5121-168 and R. 5121-170;
« 4° Ensure the implementation and monitoring of post-authorization security studies and the specific monitoring of the risk, its complications and its medical-social care referred to in articles R. 5121-36-1 and R. 5121-37-3;
"5° Ensure the implementation of the procedures and the collection of the information mentioned in the first paragraph of Article R. 5121-167 and send the new elements to the European database "Eurdravigilance" ;
« 6° Ensure that it is fully and expeditiously responded to the requests of the Director General of the National Agency for the Safety of Medicine and Health Products referred to in the third paragraph I of section R. 5121-155 and to the requests of the regional pharmacovigilance centres referred to in section R. 5121-158 and of the drug dependence assessment and information centres referred to in section R. 5132-112;
« 7° Provide the Director General of the National Agency for the Safety of Medicine and Health Products with any other information of interest in the assessment of the risks and benefits associated with a drug or product, including the positive and negative results of biomedical research and safety and efficacy studies for all indications and populations, whether or not mentioned in the marketing authorization, as well as data concerning any use of the drug not in accordance with the terms and conditions
"Art. R. 5121-165.-The company or agency operating a drug or product referred to in section R. 5121-150 may not communicate to the general public, on this drug or product, information relating to pharmacovigilance without transmitting it, in advance or, in the event of an emergency, simultaneously to the Director General of the National Drug Safety Agency and Health Products, to the European Medicines Agency and to the European Medicines Agency. This information is presented objectively and not misleadingly.
"The company or body that operates a drug or product referred to in section R. 5121-150 that informs, pursuant to section L. 5124-6, the Director General of the National Drug Safety Agency and health products that it has undertaken an action to suspend the marketing of a drug or product or to remove it from the market, or to remove a specified lot, shall indicate the contents of the communication messages,
"Art. R. 5121-166.-Any company or agency operating a drug or product referred to in R. 5121-150 is required to:
« 1° Record all undesirable effects suspected of being due to a drug or product referred to in Article R. 5121-150, which occurred in a Member State of the European Union or a State Party to the Agreement on the European Economic Area or a third country, of which it is aware, that these effects were reported spontaneously or solicited by health professionals or patients, or observed during a post-report study
« 2° To declare, electronically, to the European database "Eurdravigilance" :
“(a) Any serious adverse event suspected, occurring in a Member State of the European Union or a State Party to the Agreement on the European Economic Area or a third country, of which it is aware, without delay and no later than fifteen days after the receipt of the information;
“(b) Any non-serious adverse reactions, which occurred in a Member State of the European Union or a State Party to the Agreement on the European Economic Area, of which it is aware, within ninety days of receiving the information.
"The company or body operating a drug or product referred to in Article R. 5121-150 is required to notify, at the European database "Eurdravigilance" of the adverse effects of the medications referred to in medical publications other than those reported for certain active substances of a bibliographical monitoring by the European Medicines Agency pursuant to Article 27 of the European Parliament Regulation (EC) No. 726/2004
"Art. R. 5121-167.-Any company or agency operating a drug or product referred to in R. 5121-150 shall establish procedures for obtaining accurate and verifiable information for the scientific assessment of suspected adverse reaction notifications, collects follow-up information regarding these notifications and sends new information to the European database "Eurdravigilance".
"A company or agency operating a drug or product referred to in section R. 5121-150 is involved in the detection of duplicates in suspected adverse reaction notifications, including by reporting to the National Drug and Health Products Safety Agency and the European Agency for any duplicate drugs it would have detected.
"Art. R. 5121-168.-I. ― Any company or organization operating a drug or product referred to in R. 5121-150 is required to transmit electronically to the European Medicines Agency an updated periodic safety report containing:
« 1° All information related to the benefits and risks associated with this drug or product, including the results of studies that are likely to have an impact on the marketing authorization;
« 2° A scientific assessment of the relationship between the benefits and risks associated with the drug or product carried out on the basis of all available information, including those resulting from biomedical research for indications and populations not authorized by the marketing authorization;
« 3° All information about the sale, prescription and population exposed to the drug or product.
"The frequency of transmission of the report referred to in the first paragraph is determined in the marketing authorization. The transmission date in accordance with this frequency is calculated from the date of issuance of the marketing authorization. The European Medicines Agency publishes a list of reference dates for the European Union and the frequency of submission of updated periodic safety reports.
“II. ― Any company or organization operating a drug or product with a market authorization issued prior to July 21, 2012, which is not subject to a specific condition referred to in this authorization setting the frequency of submission of the updated periodic safety report is required to forward this report to the Director General of the National Agency for the Safety of Drugs and Health Products or to the European Agency for Drugs:
« 1° Immediately upon request;
« 2° Semi-annually:
“(a) During the period between the issuance of marketing authorization and the effective marketing of the drug or product;
“(b) During the first two years following the first bet on the market;
« 3° Annually, during the next two years;
« 4° Every three years for the following years.
"These provisions also apply to drugs that are permitted only in France and to which the provisions of the following III do not apply.
"III. ― When several drugs or products contain the same active substance or combination of active substances or are permitted in several Member States of the European Union or States parties to the Agreement on the European Economic Area, the frequency and date of submission of updated periodic security reports may be modified and harmonized with a view to conducting a single assessment. This harmonized frequency for the submission of updated periodic safety reports is made public by the European Medicines Agency. Where applicable, the licensee of the marketing authorization submits to the Director General of the National Drug and Health Products Safety Agency an application to amend its authorization accordingly. The change in dates and frequency of submission of these reports takes effect six months after the date of publication by the European Medicines Agency.
"Art. R. 5121-169.-The holder of the marketing authorization may, by written request and motivated, refer to the committee of drugs for human use referred to in Article 56 of Regulation (EC) No 726/2004 of the European Parliament and of the Council or the coordination group referred to in Article 27 of Directive 2001/83/EC of the European Parliament and of the Council to request the setting of reference dates for the European Union or a modification of the public health status
"The changes in the reference dates for the European Union and the frequency of submission of updated periodic safety reports are made public by the European Medicines Agency and take effect six months after the date of publication.
"The licensee of the marketing authorization in question submits to the Director General of the National Agency for the Safety of Medicine and Health Products an application to amend its authorization in this regard.
"Art. R. 5121-170.-By derogation from the provisions of section R. 5121-168, any company or agency operating a drug or product authorized or registered, in accordance with the procedure provided for in 1° of sections R. 5121-26 and R. 5121-28 and R. 5121-97 is required to transmit an updated periodic safety report:
« 1° Under the conditions determined by the marketing or registration authorization;
« 2° Upon request by the Director General of the National Drug and Health Products Safety Agency:
“(a) When the latter has concerns about pharmacovigilance data;
“(b) Or where there is no updated periodic safety report for an active substance after the issuance of marketing authorization.
"Art. R. 5121-171.-In the event of an agreement of the coordination group, following the single assessment procedure of the updated periodic safety reports provided for in Article 107 octies, paragraph 1, of Directive 2001/83/EC of the European Parliament and Council, recommending the amendment of the authorization to market, the holder of the said authorization shall submit to the Director General of the National Health Agency of the Medicine and of Changes
"Art. R. 5121-172.-For the drugs mentioned in 1° of I of Article L. 5121-12 and for the drugs mentioned in 2° of I of the same article subject to a protocol of therapeutic use and information collection, the obligations provided for in Article R. 5121-161 and Articles R. 5121-166 to R. 5121-170 shall be exercised according to the terms and conditions specified in the protocol.
"For the drugs referred to in 2° of I of Article L. 5121-12 that are not subject to a protocol of therapeutic use and information gathering, the modalities and model of the updated periodic safety reports referred to in R. 5121-168 to R. 5121-170 are determined by decision of the Director General of the National Agency for Safety of Medicine and Health Products.
"Art. R. 5121-173.-The statements and the updated periodic report of security referred to in articles R. 5121-161, R. 5121-168 and R. 5121-170 shall be prepared in accordance with the terms and model established by the European Commission.
"Art. R. 5121-174.-The holder of the authorization under section L. 4211-6 is required to report to the Director General of the National Drug and Health Products Safety Agency:
« 1° Any serious adverse effects suspected of being due to allergens that he has prepared and issued, of which he is aware, without delay and no later than fifteen days after receiving the information;
« 2° Any non-serious adverse reaction suspected of being due to the allergens he has prepared and issued, of which he is aware, within ninety days of receiving the information.
"The holder of an authorization under section L. 4211-6 shall transmit to the Director General of the Agency, annually and immediately upon request, a report presenting the synthesis of the information relating to the adverse effects that he or she has reported to him or her and of all information relevant to the assessment of the risks and benefits associated with the use of the products he uses.
"Art. R. 5121-175.-Pharmaceutical establishments, including those managed by public health institutions referred to in R. 5124-68 to R. 5124-73 for their performance, hospital preparation and masterful preparation activities, are subject to the provisions of R. 5121-162, R. 5121-163, excluding 4°, R. 5121-164, excluding 3° and 5° and R.
"They declare to the regional pharmacovigilance centre:
« 1° Any serious adverse reaction suspected of being due to the hospital and magisterial preparations they perform, of which they are aware, without delay and no later than fifteen days after the receipt of the information;
« 2° Any non-serious adverse reaction suspected of being due to the hospital and magistraral preparations they realize, of which they are aware, within ninety days of receiving the information.
"They transmit to the Director General of the National Agency for the Safety of Medicine and Health Products, annually and immediately upon request a report presenting the synthesis of the information on the adverse effects they have reported or reported to them, and all information relevant to the assessment of the risks and benefits associated with the use of these preparations.
"Art. R. 5121-176.-The pharmacies for internal use referred to in Article L. 5126-1 shall transmit to the Director General of the National Agency for the Safety of Medicine and Health Products, immediately upon request, a report presenting the synthesis of the information relating to the adverse effects that they have reported or that have been reported to them and all information useful to the assessment of risks and benefits related to the use of hospital preparations
"Art. R. 5121-177.-The terms and the standard model of the statements and the report referred to in R. 5121-174 to R. 5121-176 are determined by decision of the Director General of the National Drug and Health Products Safety Agency. » ;
3° Sub-section 3 is replaced by the following:
"Subsection 3
« Monitoring post-authorization security studies
"Art. R. 5121-178.-This subsection applies to post-authorization security studies that are non-interventional in the meaning of section R. 1121-2, which provide for the collection of safety information from patients or health professionals.
"These studies are conducted under the responsibility of the licensee of the marketing authorization referred to in Article L. 5121-8, which manages them and verifies that its funding is provided.
"These studies may also be carried out, on behalf of the licensee and under its responsibility, by another company or other organization.
"The procedure for carrying out these studies must in no way promote the use of the drug.
"Art. R. 5121-178-1.-This section applies to post-authorization security studies referred to in section R. 5121-178 that are carried out either on a voluntary basis by the licensee of the marketing authorization referred to in section L. 5121-8, either at the request of the competent national authorities or to comply with an obligation imposed under sections R. 5121-36-1 and R. 5121-37-3
"The Director General of the National Agency for the Safety of Medicine and Health Products may require the holder of the authorization provided for in Article L. 5121-8 to submit to him, as well as to the competent authorities of the Member States in which the study is conducted, the protocol and reports on the status of the study.
"The holder of the authorization provided for in Article L. 5121-8 shall send the final report to the competent authorities of the Member States in which the study was carried out within one year from the end of the data collection.
"During the completion of the study, the licensee of section L. 5121-8 supervises the data produced and examines their impact on the relationship between the benefits and risks associated with the drug.
"The licensee shall transmit to the competent authorities of the Member States in which the drug has been authorized and, where appropriate, to the Director General of the National Drug Safety Agency and Health Products, any new information that may influence the assessment of the relationship between the benefits and risks associated with the drug, in accordance with the provisions of section R. 5121-37-1.
"Art. R. 5121-178-2.-I. ― This section applies to post-authorization studies referred to in section R. 5121-178 that are carried out by the licensee of the authorization referred to in section L. 5121-8 to meet an obligation imposed under sections R. 5121-36-1 and R. 5121-37-3.
“II. ― Prior to the completion of a study, the holder of the authorization provided for in Article L. 5121-8 shall submit a draft protocol to the Committee for the Assessment of Pharmacovigilance Risks referred to in Article 56 of Regulation (EC) No. 726/2004 of the European Parliament and of the Council of 31 March 2004. The draft protocol is submitted to the only Director General of the National Agency for the Safety of Medicine and Health Products in case the study is carried out on the request of this authority exclusively in France.
"The above-mentioned committee or the director general of the agency shall, within sixty days of the submission of the draft protocol and by written letter to the licensee, make its decision, as the case may be:
« 1° To approve the draft protocol;
« 2° To reject the protocol in a circumstantial and motivated manner by one of the following reasons:
“(a) The conduct of the study promotes the use of the drug;
“(b) The study methodology does not achieve the objectives it pursues;
« 3° Requalify the study as a biomedical research.
"The study can only start from the written approval of the above-mentioned committee or when the study is exclusively carried out in France, from the approval of the director general of the agency.
"When the protocol was approved by the above-mentioned committee in accordance with 1°, the holder of the authorization provided for in Article L. 5121-8 shall transmit this protocol and the decision to approve the relevant authorities of the Member States in which the study will be carried out.
"III. ― During the study, the holder of the authorization provided for in section L. 5121-8 submits, for approval, any substantial amendment to the protocol to the above-mentioned committee or, where the study is conducted exclusively in France, to the Director General of the National Agency for the Safety of Medicine and Health Products, prior to its implementation.
"After the evaluation of these amendments, the board or director general of the agency shall inform the licensee of its approval or objection.
"When the decision comes from the committee, the licensee shall communicate it to the Member States in which the study is conducted.
"IV. ― At the end of the study, the holder of the authorization provided for in section L. 5121-8 shall submit a final report with a summary of the results of the study electronically, to the above-mentioned committee, or, if not, to the Director General of the National Drug Safety Agency and Health Products, within one year of the end of the data collection, unless an exemption has been granted to him. » ;
4° Sub-section 4 is amended as follows:
(a) The title of the subsection is replaced by the following title: "Good pharmacovigilance practices";
(b) In R. 5121-179, the reference to R. 5121-154 is replaced by the reference to R. 5121-153;
(c) Section R. 5121-180 is repealed.
After section R. 5313-2 of the Public Health Code, an article R. 5313-2-1 is inserted as follows:
"Art. R. 5313-2-1.-The inspections conducted under this heading are carried out in accordance with existing regulations and good practices defined in sections L. 5121-5 and R. 5121-179. »
In the second paragraph of article R. 5313-3 of the Public Health Code, the words "transfer immediately" are replaced by the words "electronic sending" and after the words "Member State" are added the words "or to the European Medicines Agency".
I. ― For drugs or products that have been licensed to market prior to July 21, 2012, or for which the application for marketing authorization was made before July 21, 2012, the obligation to manage and make available, upon request, a permanent record of the pharmacovigilance system, as provided for in section R. 5121-162, must be satisfied at the time of the renewal of the release authorization on the market, when July 21, 2012 is requested.
However, the Director General of the National Drug Safety Agency and Health Products may at any time request the licensee of the marketing authorization to provide a copy of the permanent record of the pharmacovigilance system.
II. - By derogation from first paragraph of section R. 5121-45 of the Public Health Code, the application for renewal of the marketing authorizations whose validity expires before July 21, 2013 must be sent no later than six months before the expiry date of the authorization.
III. ― provisions of the former paragraph of section R. 5121-149 of the Public Health Code, with respect to drugs subject to additional supervision, are applicable within one year from the publication by the European Commission of the symbol and the explanatory sentence accompanying the specific mention of these drugs.
IV. ― The first transmission to the European Commission of the results of the periodic evaluation of the pharmacovigilance system implemented by the National Agency for the Safety of Medicine and Health Products, referred to in first paragraph of section R. 5121-154 of the Public Health Code, takes place on or before September 21, 2013.
V. ∙ Provisions set out in 2° of article R. 5121-156 of the Public Health Code come into force within six months of the announcement by the European Agency of the drug of the effective implementation of the new features of the European database "Eudravigilance".
Until the expiry of this period, any company or agency operating a drug or product referred to in R. 5121-150 shall declare:
1° Any serious adverse reaction suspected of being due to a drug or product in France, having been notified to the Director General of the National Agency for the Safety of Medicine and Health Products, within fifteen days of receiving the information;
2° Any serious adverse reaction suspected of being due to a drug or product, which occurred in a third country, having been brought to its knowledge, to the database "Eurdravigilance", within fifteen days of receiving the information.
However, companies or organizations operating a drug or product referred to in Article R. 5121-150, which declare during the transitional period defined in the V this information to the "Euravigilance" base, are not required to the reporting obligations to the agency mentioned in 1° and 2°.
VI. ― The provisions of Article R. 5121-156 come into force from the announcement by the European Agency of the drug of the effective implementation of the new features of the European database "Eurdravigilance".
Until this announcement, provisions of section R. 5121-157 of the Public Health Codein their writing before this decree remain in force.
VII. – The provisions of the four first paragraphs of Article R. 5121-168 of the Public Health Code come into force within one year of the announcement by the European Agency of the drug of the effective implementation of the new features of the updated periodic safety reports directory.
Until the expiry of this period, any company or agency operating a drug or product referred to in R. 5121-150 is required to forward the updated periodic safety report to the Director General of the National Drug Safety Agency and Health Products.
VIII. ― The provisions of section R. 5121-168, section II, of the Public Health Code, apply to drugs for which the application for marketing authorization was made before July 21, 2012 and whose marketing authorization is not provided with a specific condition setting the frequency of submission of the updated periodic report.
The Minister of Social Affairs and Health is responsible for the execution of this Order, which will be published in the Official Journal of the French Republic.
Done on 8 November 2012.
Jean-Marc Ayrault
By the Prime Minister:
Minister of Social Affairs
and Health,
Marisol Touraine
