1.6 The drug registration process and expertise sequence under the decentralized procedure in the reference state and in the states of recognition
For the purpose of drug registration according to the decentralized procedure, the applicant shall choose the reference state and the state of recognition.
The duration of the decentralized procedure for drug registration and examination of the medicinal product shall not exceed 210 calendar days from the day of filing of the last of the applications for registration of the medicinal product in the State of recognition until the day the registration certificates of the drugs are issued by the authorized bodies of all Member States participating in the decentralized procedure.
The drug registration process for a decentralized procedure consists of the following stages, conducted simultaneously:
- registration of a drug in the reference state;
- recognition of the expert evaluation report and drug registration in states of recognition.
For the purpose of registration of a medicinal product, the applicant submits the following documents to the authorized body (expert organization) of the reference state:
- An application for registration of a drug in the established form on paper and (or) in the electronic form in accordance with Appendix No. 2 to these Regulations;
- Documents confirming the payment of the fee (tax) for drug registration and examination of the medicinal product according to the procedure established by the legislation of the reference state;
- Drug registration dossier in accordance with Annexes 1 to 5 to these Regulations on electronic media;
- Samples of medicinal products.
Within 14 working days from the date of submission of documents to the authorized body (expert organization) of the reference state, the applicant shall submit to the authorized bodies (expert organizations) of the states of recognition the following documents:
- A statement on paper and (or) in soft copy in the established form in accordance with Appendix No. 2 to these Regulations;
- Electronic version of Module 1 of the drug registration dossier;
- Documents confirming the payment of the fee (tax) for drug registration and examination according to the procedure established in accordance with the legislation of the state of recognition.
The examination of a drug in a reference state according to the decentralized registration procedure includes:
- evaluation of completeness and correctness of preparation of the submitted documents of the registration dossier of the drug;
- evaluation of documents and data submitted by the applicant in the registration dossier of the medicinal product for safety, efficacy and quality;
- conduction of the laboratory tests for compliance with the requirements of the normative document on the quality and reproducibility of the declared quality control procedures carried out in the accredited testing laboratories;
- initiation, if necessary, of an unscheduled or planned pharmaceutical inspection in the cases specified in these Regulations;
- preparation of an expert report on evaluation of the drug by the reference state.
Expertise of the pharmaceutical product in the states of recognition according to the decentralized drug registration procedure is carried out by consideration of:
- statements, documents and data of the registration dossier of the drug;
- an expert evaluation report prepared by the reference state.
The authorized body (expert organization) of the reference state shall, within 14 working days from the date of submission of the application for drug registration, evaluate the completeness and correctness of the submitted documents of the registration dossier of a drug before sending the materials of the registration dossier for expertise. The applicant is granted no more than 90 calendar days not included into the registration and examination period of the drug, for submission of missing materials to the registration dossier to consider the remarks of the authorized body (expert organization) of the reference state.
The authorized body (expert organization) of the reference state shall, not later than in 14 calendar days from the date of filing the application for registration of the drug in the reference state, after evaluating the completeness of the submitted registration dossier files, submits the registration dossier of the pharmaceutical rpoduct to the authorized bodies (expert organizations) according to the procedure of decentralized registration of a drug through an integrated system.
The authorized body (expert organization) of the reference state rejects the application for drug registration in case the documents and materials of the registration dossier on the remarks of the authorized body (expert organization) of the reference state are not submitted in due time and (or) in case of failure to confirm payment of the fee (tax) for registration and examination of a pharmaceutical product in cases and in the manner established by the legislation of the reference state, and informs the applicant and the authorized bodies (expert organizations) of the states of recognition through the integrated system within a period of not more than 5 working days from the date of the decision.
The authorized body (expert organization) of the reference state within the period of drug registration and examination of the medicinal product has the right to send the request on submission of the missing additional information, necessary explanations or clarifications concerning the submitted documents and data of the registration dossier to the applicant, in writing and (or) electronically, in accordance with the application No.6,7, 8 attached to these Regulations.
The authorized body (expert organization) of the reference state shall, within 90 calendar days from the date of commencement of the examination, send to the authorized bodies (expert organizations) of the states of recognition a copy of the reports with the formulation of comments and requests to the applicant in accordance with the Appendices No 6,7, 8 to these Regulations and the preliminary report on evaluation in accordance with the Appendix No. 11 to these Regulations.
If there are requests sent to the applicant, the authorized body (expert organization) of the state of recognition within 30 calendar days from the date of receipt of the preliminary report on evaluation of the reference state shall send the requests to the authorized body (expert organization) of the reference state, which within 5 working days from the date of receiving the last request from the state of recognition, forms a unified request and sends it to the applicant in accordance with clause 93 of these Regulations.
The period for submitting a response to the above request by the applicant should not exceed 90 calendar days. Procedures for sending requests and presenting the answers are established by requirements of the legislation of the Member States.
If necessary, on the basis of the relevant application of the applicant, the response time to the request may be extended by the authorized body of the reference state. The total period for responding to inquiries should not exceed 180 calendar days.
The examination is resumed after the applicant responds to the inquiries of the authorized body (expert organization) of the reference state.
If the applicant fails to submit the documents and materials requested by the authorized body (expert organization) in due time, the expertise and registration of the drug shall be terminated. The authorized body (expert organization) notifies the applicant and the authorized bodies (expert organizations) within 14 working days from the date of adoption of such decision in the written and (or) electronic form.
Expertise of the drug in case of initiating a pharmaceutical inspection for compliance with the proper pharmaceutical practices of the Union shall not be suspended. Upon that the preparation of an expert evaluation report is completed by the reference state only after the expert organization of the reference state receives the results of the inspection. An unscheduled pharmaceutical inspection with a report on the inspection carried out should be conducted within the period of registration of the drug, but not exceeding 180 calendar days from the date the decision on initiating the inspection was made by the authorized body (expert organization).
The applicant organizes a visit to the production site, the research center, the pharmacovigilance system of the holder of the registration certificate within 30 calendar days after receiving information on the need for an inspection or specifies a specific visit period, but no more than 90 calendar days after receipt of the information.
In case of no information from any state of recognition regarding the expertise of the medicinal product (the submission of comments, the results of the examination of the preliminary assessment report), the reference state considers that the state of recognition agrees with the opinion (including comments, if applicable) contained in the preliminary report on evaluation.
Written consultations between the authorized bodies (expert organizations) of the reference state and the recognition states, if necessary, are carried out electronically using the means of an integrated information system.
The expert reports on quality aspects, pre-clinical, clinical aspects, final expert evaluation report are compiled in accordance with the instructions given in Annexes 13,14, 15 and 23 to these Regulations. The final expert report on evaluation of the reference state is drawn up in accordance with the form provided in Appendix No. 16 to these Regulations.
Within 155 calendar days from the date of submission of the application for drug registration, the authorized body (expert organization) of the reference state shall send the draft of final evaluation report to the recognition state and the applicant in accordance with Appendix No. 16 to these Regulations along with the applicant's responses to the requests, the draft summary of product characteristics, the draft guidelines for instruction for medical use (leaflet), the draft of package mock-ups, the draft of Normative Document, and, if necessary, the draft of risk management plan for the use of the drug. If the expert organization of the reference state prepares a negative draft of the final expert evaluation report and decides not to register a drug in accordance with clause 114 of this Regulation, the examination and registration of the drug shall be terminated. The authorized body (expert organization) notifies the applicant about the decision made within 14 working days from the date of adoption of such decision in the written and (or) electronic form with the above-mentioned final expert evaluation report attached. If the expert organization of the reference state prepares a positive draft of the final expert evaluation report, it is reviewed by the authorized bodies (expert organizations) of the states of recognition.
In case of no comments were received from the authorized bodies (expert organizations) of the states of recognition or after their withdrawal in accordance with paragraph 106 of these Regulations, the authorized body (expert organization) of the reference state and the recognition states complete the expertise procedure for the pharmaceutical product within 10 working days (175th calendar Day from the date of application for registration).
If the comments from the competent authorities (expert organizations) of the states were issued regarding the draft of final evaluation report, the draft of summary of the product characteristics, the draft of instruction on medical use, the draft of package mock-up or the draft of Normative Document, the draft of risk management plan for the use of the drug (if necessary), the authorized bodies (expert organizations) of the recognition states, if necessary, carry out consultations with the authorized body (expert organization) of the reference state or recognition states in the electronic form within 10 working days in accordance with the form provided in Appendix 18 to this Regulation (the 165th calendar day from the date of application for registration of the drug).
In case there are unresolved disputes as a part of mutual consultations, the authorized body (expert organization) of the state of recognition within a period not exceeding 10 working days from the date of receipt of the final expert report on evaluation of the reference state, taking into account the conditions of paragraph 106 of these Rules, using the means of the integrated system, produces the impossibility of recognizing the expert evaluation report prepared by the expert organization of the reference state, with justification of reasons for a negative decision to the authorized body (expert organization) of the reference state and states of recognition, as well as to the Committee of Experts, including issuing such report on paper.
The expert committee shall conduct a dispute settlement procedure in accordance with the procedure established by the Commission, within a period not exceeding 60 calendar days from the date of conclusion declared by the states that it is not possible to recognize a positive expert evaluation report prepared by an expert organization of the reference state.
In case the disagreements between the authorized bodies of the reference State and the States of recognition regarding the recognition of the expert evaluation report are settled, they proceed to completion of drug expertise and issuance of the final documents in accordance with paragraphs 105 and 109 to 113 of these Rules.
In case the disagreements between the authorized bodies of the reference State and the States of recognition regarding the recognition of the expert evaluation report are not settled, the authorized bodies of the reference state and the recognition states that have accepted the positive decision to recognize the expert evaluation report shall proceed to completion of expertise and the procedure for issuing the final documents in accordance with paragraphs 105 and 109 - 113 of these Rules. Upon the request of the applicant, the issuance of a registration certificate by the authorized bodies of such Member States may be suspended until the disagreements of the authorized bodies of other recognition and reference States are settled.
The authorized bodies (expert organizations) of the reference state and states of recognition that have made a positive decision on the expertise results and consider to issue registration of the drug in accordance with paragraphs 105 and 108 of these Rules, proceed to the procedure for issuing final documents within a 30-calendar-day period. As well as within the specified period of 10 working days, the applicant is obliged to translate the summary of product characteristics, the draft of instruction for medical use, the mock-ups of the packages into the languages of the Member States, if there is a corresponding requirement in their legislation.
Within no more than 30 calendar days (the 205th calendar day from the date of submission of the application for drug registration):
- the authorized body of the reference state issues the registration certificate of the drug to the applicant in accordance with Appendix No. 17 to these Regulations, approved by the summary of product characteristics, the medical application guidelines, Normative Document, the package mock-ups, the evaluation expert report (if necessary, the applicant is given the approved summary of product characteristics, the guidelines for medical use and package mock-ups of the medicinal product in the national language of the reference state), and also, if necessary, the agreed risk management plan for the use of the drug;
- the authorized bodies of the recognition states issue the registration certificates of the drugs to the applicant in accordance with the form provided in Appendix No. 17 to these Regulations, approved by the summary of product characteristics, the instruction for medical use, package mock-ups of the drug in the official languages of the recognition states (if applicable in the legislation of the Member States), and, if necessary, an agreed risk management plan for the use of the medicinal product.
The authorized bodies of the reference state and the states of recognition publish the information on registration of the drug and the active pharmaceutical substances that are included in its composition into the unified register with the attachment of the approved summary of product characteristics, instructions for medical use, package mock-ups, Normative document, and the final expert evaluation report, compiled in accordance with Appendix No. 16 to these Regulations, after confiscation of confidential data and data on the experts, summary of an agreed risk management plan for the use of the medicinal product (If necessary) in accordance with the procedure for forming and maintaining the unified register.
The registration certificate of the medicinal product is issued by the authorized body of the state of recognition with the validity period of the drug registration certificate established by the authorized body of the reference state.
The authorized body of the reference state refuses drug registration under a decentralized procedure in the following cases:
- the ratio of the expected benefit to the possible risks associated with the use of the medicinal product is not favorable;
- the effectiveness of the drug is not confirmed by the data provided by the applicant;
- the quality of the medicinal product is not confirmed;
- the proposed methods and techniques of quality control are impracticable;
- the applicant provided false information;
- according to the results of the designated inspection, compliance with the relevant pharmaceutical practices of the Union has not been confirmed during the drug registration process.
The authorized body of the state of recognition does not recognize the expert evaluation report prepared by the expert organization of the reference state and thereby denies drug registration under the decentralized procedure if following the results of examination of the registration dossier of the medicinal product and conclusions of the dispute resolution procedure in the Expert Committee, a decision has been taken that the data presented in the expert evaluation report cannot be deemed sufficient to confirm quality, and (or) objectivity, and (or) favorable benefit - risk ratio of the medicinal product.