Key Benefits:
Public concerned: promoters and investigators of biomedical research requiring express authorization; High Council of Biotechnology; National Drug and Health Products Safety Agency; Research and Environment Departments.
Subject: procedure for authorizing biomedical research requiring express authorization.
Entry into force: the text comes into force on the day after its publication.
Notice: This Decree updates the regulatory provisions for biomedical research requiring express authorization, with respect to the intervention of Regulation No. 1394/2007 of 13 November 2007 on innovative therapy drugs. It also develops, in a dual concern for clarification and relief, the procedure for authorizing biomedical research on products composed in whole or in part of genetically modified organisms (GMOs).
References: the provisions of Public Health Code and environmental code Amended by this decree may be consulted, in their drafting, on the website Légifrance (http://www.legifrance.gouv.fr).
The Prime Minister,
On the report of the Minister of Ecology, Sustainable Development and Energy and the Minister of Social Affairs, Health and Women's Rights,
Having regard to Regulation (EC) No. 1394/2007 of the European Parliament and Council of 13 November 2007 concerning innovative therapy drugs and amending Directive 2001/83/EC and Regulation (EC) No. 726/2004;
Considering Directive 2001/18/EC of the European Parliament and the Council of 12 March 2001 on the voluntary release of genetically modified organisms in the environment and repealing Council Directive 90/220/EEC;
Having regard to Directive 2001/20/EC of the European Parliament and the Council of 4 April 2001 on the approximation of the legislative, regulatory and administrative provisions of the Member States relating to the application of good clinical practices in the conduct of clinical trials of drugs for human use;
Considering Directive 2009/41/EC of the European Parliament and the Council of 6 May 2009 on the confined use of genetically modified microorganisms;
Vu le environmental codeincluding articles L. 532-2, L. 532-3 and L. 533-3;
Vu le Public Health Codeincluding articles L. 1125-3 and L. 1125-4;
Vu la Act No. 2000-321 of 12 April 2000 the rights of citizens in their relations with administrations;
Vu le Decree No. 2007-358 of 19 March 2007 relating to voluntary release for any purpose other than the marketing of all or part of genetically modified organisms;
The State Council (Social Section) heard,
Decrete:
I. - Section 2 of Chapter II of Title III of Book V of the Environmental Code Regulatory Part is amended as follows:
1° In the second paragraph of article R. 532-8, the words "staff and population" are replaced by the words "staff, population or environment";
2° After the last paragraph of article R. 532-9, it is added a paragraph as follows:
"When an application for confined use of all or part of genetically modified products is considered as part of a research referred to in theArticle L. 1125-3 of the Public Health Code, the High Council of Biotechnology Scientific Committee specifies in its opinion whether this research involves a phase of voluntary release of the genetically modified organism requiring authorization under section L. 533-3. » ;
3° After the third paragraph of article R. 532-11, it is added a paragraph as follows:
"When a research on a product composed in whole or in part of genetically modified organisms, referred to in theArticle L. 1125-3 of the Public Health Code, is envisaged, the Minister for Research shall transmit to the applicant, in addition to the order issuing the approval, the advice of the Scientific Committee of the High Council of Biotechnology, as provided for in section R. 532-9 of this Code, specifying whether this research involves a phase of voluntary release requiring authorization under section L. 533-3 of the same Code. This notice is transmitted as information. » ;
4° In article R. 532-15, two paragraphs are added:
"When the High Council for Biotechnology is informed that a statement of use of genetically modified organisms is made as part of a research referred to in section L. 1125-3 of the Public Health Code relating to products composed in whole or in part of genetically modified organisms, it specifies to the Minister for Research whether this research involves a phase of voluntary release of genetically modified organisms in the environment.
"In addition to the receipt of the declaration of use referred to in this section, the Minister for Research shall transmit to the applicant, for information, the advice of the Scientific Committee of the High Council of Biotechnology, as provided for in section R. 532-9 of this Code, which specifies whether this research involves a phase of voluntary release of genetically modified organisms into the environment. »
II. - In subsection 2 of subsection 2 of section 1 of Chapter III of Title III of Book V of the Environmental Code Regulatory Part, section R. 533-21 is replaced by the following provisions:
"Art. R. 533-21. - In addition to the provisions mentioned in R. 532-9, R. 532-11, R. 532-15, the specific provisions applicable to the research referred to inArticle L. 1125-3 of the Public Health Code are set out in sections R. 1125-1 to R. 1125-6-1 of this code. »
Section 1 of Chapter V of Title II of Book I of Part I of the Public Health Code Regulatory Part is replaced by the following:
“Section 1
Research on all or part of genetically modified organisms referred to in Article L. 1125-3
"Art. R. 1125-1.-I.-When the research relates to products composed in whole or in part of genetically modified organisms referred to in Article L. 1125-3, the application file referred to in Article R. 1123-30 also includes:
« 1° Classification of the genetically modified organism by the High Council of Biotechnology Scientific Committee;
« 2° The opinion of the latter, referred to in the articles R. 532-9 and R. 532-15 the environmental code, specifying whether the use in this framework involves a phase of dissemination;
« 3° Accreditation of the Minister for Research or receipt of a statement to that Minister as referred to in theArticle L. 532-3 of the Environmental Code.
"II.-The application for authorization is addressed to the Director General of the National Agency for the Safety of Medicine and Health Products, who decides on the admissibility of the case by ensuring that the application contains all the information referred to in article R. 1123-30 of this Code and the documents referred to in I of this article. It shall notify the proponent of the date of receipt of the file. If the file is not complete, it shall notify the proponent of a list of missing documents and set a maximum time limit to provide them.
"Art. R. 1125-2.-I.-The Director General of the National Agency for the Safety of Medicine and Health Products shall notify the applicant of his decision within 90 days of the date of receipt of the complete record subject to the provisions of the II.
"II.-If the Director General of the National Agency for the Safety of Medicine and Health Products considers that additional information, consultations or special studies are necessary to allow him to decide on the application, he may extend the time limit set out in I to a maximum of ninety days. The thirty-day period referred to in R. 1125-5 for public consultation is included within this maximum period of one hundred and eighty days. The Director-General shall inform the applicant of the extension of the deadlines and, in cases where he requests additional information, he shall set a time limit to provide them. The proponent who does not produce the additional information requested within the specified time limits is deemed to have waived the request.
"III.-The Director General of the National Agency for Drug Safety and Health Products may notify the sponsor by letter of its objection to the implementation of the research. It informs the protection committee of the persons concerned. It sets a deadline for the proponent to submit its amended project. This period does not suspend the time limit for making a decision on the application for authorization pursuant to I and II of this article. The proponent may modify the content of its research project and send it to the Director General of the Agency within the time limit. This modification procedure can only be implemented once in each research project. The proponent who does not produce an amended project within the specified time limits is deemed to have renounced the application.
"IV.-In the absence of a response from the Director General of the National Drug Safety Agency and Health Products within the time limits mentioned in I and II, the application for authorization is deemed to be rejected.
"Art. R. 1125-3.-I.-When the application for authorization relates to a research referred to in section L. 1125-3 and that this research involves a phase of voluntary release of genetically modified organisms requiring the authorization referred to in section L. 1125-3.Article L. 533-3 of the Environmental Codethe provisions of this section shall apply in addition to the provisions referred to in Article R. 1125-2 of this Code.
"II.-May be the subject of a single application for authorization referred to inArticle L. 533-3 of the Environmental Code disseminations of the same genetically modified organism or combination of genetically modified organisms during a specified period of time, at the same site or at different sites that are performed during a research referred to in I of this article and carried out for the same purpose.
"III.-The promoter of the research referred to in Article L. 1121-1 of this Code shall, as the person responsible for the dissemination, simultaneously at the request for authorization, make the payment referred to in theArticle L. 535-4 of the Environmental Code for the benefit of the state budget.
"IV.-In addition to the documents referred to in I of section R. 1125-1, the technical record referred to in section R. 1123-30 of this code includes the technical record referred to in section R. 1125-1.Article R. 533-3 of the Environmental Code and a summary of this technical file to be forwarded to the European Commission for information and a fact sheet for the public. Any person who has access to the technical record is held in professional secrecy under the conditions and penalties provided for inArticle 226-13 of the Criminal Code.
"V.-The summary of the technical record referred to in paragraph IV of this article is prepared in accordance with Council Decision 2002/812/EC of 3 October 2002 establishing in accordance with Directive 2001/18/EC of the European Parliament and the Council, the consolidated form of the notification concerning the marketing of genetically modified organisms as products or product elements. The Director General of the National Drug Safety Agency and Health Products transmits this summary to the European Commission within 30 days of the date of registration of the application.
"VI.-When genetically modified organisms meet the criteria set out in Appendix V of Directive 2001/18/EC of 12 March 2001, the Director General of the National Agency for the Safety of Medicine and Health Products can propose to the European Commission after the advice of the High Council for Biotechnology the implementation of the differentiated procedure under the conditions set out in theArticle R. 533-7 of the Environmental Code.
" VII.-As soon as the file is complete, the Director General of the National Agency for the Safety of Medicine and Health Products transmits to the High Council of Biotechnology the file referred to in section R. 1125-1 of this Code and the technical file referred to in the technical fileArticle R. 533-3 of the Environmental Code to collect its opinion on the risk of release for the environment and public health. The High Council of Biotechnology shall forward its notice to the Director General of the National Agency for the Safety of Medicine and Health Products and to the Minister responsible for the environment within forty days of the date of receipt of the notice.
" VIII.-The Director General of the National Agency for the Safety of Medicine and Health Products transmits the proposed search authorization for release pursuant to section L. 1125-3 of this Code to the Minister for the Environment. The Minister of the Environment's agreement on voluntary release is deemed to have been reached if the Minister did not demonstrate his or her objection to the granting of voluntary release authorization within ten days of the date on which the Minister received the proposed authorization. In the event of a reasoned opposition from the Minister for the Environment, the Director General of the National Drug Safety Agency and Health Products shall notify the proponent of the refusal of a search authorization.
" IX.-The Director General of the National Agency for the Safety of Medicine and Health Products shall decide on the application for a search authorization after having examined, if any, any comments made by other Member States:
"i.e. by indicating that it has ascertained the conformity of the application with the provisions relating to the voluntary release of genetically modified organisms in the environment and that the research may take place;
"that is, by indicating that experimentation does not meet the conditions for the voluntary release of genetically modified organisms into the environment and that, accordingly, the application is rejected.
"X.-The authorization of the Director General of the National Agency for the Safety of Medicine and Health Products indicates that genetically modified organisms used for dissemination must be labelled under the conditions set out in 8 of the A of Appendix IV of Directive 2001/18/EC of 12 March 2001 on the voluntary release of genetically modified organisms in the environment and specifies whether it is necessary to complete this labelling in the same manner.
"Art. R. 1125-4.-I.-Any substantial amendment requires the issuance of a new authorization under the conditions set out in R. 1125-1 to R. 1125-3 subject to the special provisions referred to in II, III and IV of this Article.
"II.-The silence kept by the Director General of the National Agency for the Safety of Medicine and Health Products on a request for a substantial amendment of the sponsor is deemed to be denial of the application upon the expiry of a period of thirty-five days from the receipt of all the required information regarding the amendment application.
"III.-If the Director General of the National Agency for the Safety of Medicine and Health Products considers that additional information, consultations or special studies are necessary to enable him to decide on the application, the time limit provided for in II may be extended. In this case, the proponent shall inform the proponent of the extension of the time limit and, in cases where the proponent requests further information, the proponent shall set a time limit to provide it. Without response within the time limit, the proponent is deemed to have waived the application.
"IV.-If the Director General of the National Agency for the Safety of Medicine and Health Products is of the opinion that the amendment application cannot be accepted, he informs the sponsor of his intention and sets a time limit for submitting his comments. Without response within the time limit, the proponent is deemed to have waived the application.
"Art. R. 1125-5.-I.-Before issuing a research authorization on products composed in whole or in part of genetically modified organisms with a phase of voluntary release, the Director General of the National Agency for the Safety of Medicine and Health Products publishes on this Agency's website within fifteen days of receiving the notice of the High Council of Biotechnology, the information sheet of the public referred to in 533 Public comments should be addressed to the Director General of the National Drug and Health Products Safety Agency within 30 days of this publication.
"II.-The Director General of the National Agency for the Safety of Medicine and Health Products publishes on this Agency's website the date of voluntary release authorization, the name of the licensee and the synthetic description of the genetically modified organism(s). It states that the form provided for in section L. 533-3-1 of the Environmental Code is made available to the public. Any person may comment on this authorization and the information accompanying it to the Director General of the Agency.
"Art. R. 1125-6.- provisions of Article R. 533-15 of the Environmental Code relating to the management of public health risks and the environment of voluntary release are applicable to the research referred to in section R. 1125-3 of this Code relating to all or part of genetically modified products.
"Art. R. 1125-6-1.-The report presenting the results of the release referred to in theArticle R. 533-17 of the Environmental Code is annexed to the final report referred to in Article R. 1123-60 of this Code. »
Section 2 of Chapter V of Title II of Book I of Part I of the Public Health Code Regulatory Part is amended to read:
1° The title of section 2 is supplemented by the words: "related to the products mentioned in articles L. 1125-1 to L. 1125-3";
2° Section R. 1125-7 is replaced by the following provisions:
"Art. R. 1125-7. - Research on the following products is expressly authorized by the Director General of the National Agency for the Safety of Medicine and Health Products:
« 1° Organs and tissues of human origin and labial blood products;
« 2° Somatic cell therapy medications, tissue engineering products and combined innovative therapy drugs defined in Article 2 of Regulation (EC) No 1394/2007 of the European Parliament and Council of 13 November 2007, somatic cell therapy medications, tissue engineering products and combination drugs of innovative therapy defined at 17° of Article L. 5121-1, the cells of human origin referred to as the cells of human origin and
« 3° The xenogenic cell therapy preparations mentioned in the 13th of Article L. 5121-1;
« 4° The gene therapy medications defined in Article 2 of Regulation (EC) No 1394/2007 of the Parliament and Council of 13 November 2007 and the gene therapy medications listed in Article L. 5121-1 17;
« 5° Drugs whose active principle contains components of human or animal biological origin or in the manufacture of which such components are entered and the drugs mentioned in the Schedule to Regulation (EC) No 726/2004 of 31 March 2004 establishing community procedures for authorization and monitoring with respect to drugs for human use and veterinary use and establishing a European Medicines Agency and which do not have an authorization to place on the market in the sense of the market.
« 6° Medical devices incorporating products of human or animal origin or in the manufacture of which products of human or animal origin do not have CE markings;
« 7° Cosmetic products containing ingredients of animal origin, the list of which is determined by order of the Minister of Health on the proposal of the Director General of the National Drug Safety Agency and Health Products;
« 8° Organs and tissues of animal origin that are neither medical devices nor intended for drugs";
3° In the second paragraph of section R. 1125-8, the sentence: "Without a reply from the proponent within the time limit, the application for authorization is deemed to be rejected. is replaced by the sentence: "Without response within the time limit, the proponent is deemed to have waived the application. » ;
4° Section R. 1125-9 is amended as follows:
(a) The first paragraph is deleted;
(b) In the second paragraph, the first sentence is replaced by the following sentence:
"When the application relates to organs and tissues of human origin or animal origin referred to in 1° and 8° of Article R. 1125-7, on medications and cell therapy preparations referred to in 2° of Article R. 1125-7, as well as on xenogenic cell therapy preparations referred to in 3° of Article R. 1125-7, the exemplary director of the National Agency for the Safety of Drugs and » ;
5° Section R. 1125-10 is replaced by the following provisions:
"Art. R. 1125-10. - The deadlines for the Director General of the National Drug Safety Agency and Health Products to notify the applicant's response are as follows:
« 1° Sixty days from the date of receipt of the complete file for the research on the products mentioned in 5°, 6° and 7° of article R. 1125-7;
« 2° Ninety days from the date of receipt of the complete file for research on the products mentioned in 1° and 8° of Article R. 1125-7;
« 3° Ninety days from the date of receipt of the complete file for research on the products mentioned in 2°, 3° and 4° of article R. 1125-7.
"The period referred to in the 3rd may be extended by ninety days if the Director General of the National Agency for the Safety of Medicine and Health Products considers that additional information, consultations or special studies are necessary to enable him to decide on the application.
"In all cases, the silence kept by the Director General of the National Agency for the Safety of Medicine and Health Products is deemed to be denial of authorization at the expiry of the time limits mentioned above. » ;
6° Section R. 1125-11 is replaced by the following provisions:
"Art. R. 1125-11. - The Director General of the National Drug Safety Agency and Health Products may notify the sponsor by letter of its objection to the implementation of the research. It informs the protection committee of the persons concerned. It sets a deadline for the proponent to submit its amended project. The proponent may modify the content of its research project and send it to the Director General of the Agency within the time limit. This period does not suspend the time limit available to the Director General to decide on the application for authorization pursuant to section R. 1125-10. This modification procedure can only be applied once to each research project. The proponent who does not produce an amended project within the specified time limits is deemed to have renounced the application. » ;
7° The second paragraph of Article R. 1125-12 is amended as follows:
(a) The words: "with the limit of sixty days except for the drugs mentioned in the fourth paragraph of Article R. 1125-7" are deleted;
(b) The last sentence is replaced by the sentence: "Without response within the time limit, the proponent is deemed to have waived his request. »
Sections 29 and 30 of the above-mentioned Decree of 19 March 2007 are repealed.
I. - Applications for confined use referred to inArticle R. 532-6 of the Environmental Code or the declarations of confined use referred to in Article R. 532-14 of the same code filed before the publication of this Order shall be governed by the provisions in force prior to the publication of this Order.
II. - Applications for authorization for biomedical research relating to all or part of genetically modified organisms remain governed by the provisions of Public Health Code in force prior to the publication of this Order in Council when the entrusted applications for registration of use referred to inArticle R. 532-6 of the Environmental Code or the declarations of confined use referred to in section R. 532-14 of the same code were filed prior to this publication.
The Minister of Ecology, Sustainable Development and Energy, the Minister of National Education, Higher Education and Research and the Minister of Social Affairs, Health and Women's Rights are responsible, each with regard to her, for the execution of this decree, which will be published in the Official Journal of the Republic.
Done on June 18, 2015.
Manuel Valls
By the Prime Minister:
Minister of Social Affairs, Health and Women ' s Rights,
Marisol Touraine
Minister of Ecology, Sustainable Development and Energy,
Royal
Minister of National Education, Higher Education and Research,
Najat Vallaud-Belkacem
