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Granting a marketing authorization in the EAEU
| 작성자 | 관리자 | 카테고리 | 전문가 인사이트 |
|---|---|---|---|
| 작성일 | 2018-12-18 | 조회수 | 3,019 |
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| 출처 | |||
한국보건산업진흥원 해외제약전문가 라빌 니야조프
Granting a marketing authorization in the EAEU
According to paragraph 20 of the Rules, a marketing authorization for medicinal products may be granted at the request of an applicant in the several Member States in accordance with the mutual recognition procedure performed successively or in the several Member States in accordance with the decentralized marketing authorization procedure performed simultaneously.
Authorization of active substances of medicinal products in the EAEU is not envisaged.
It is worth mentioning that within the Rules, the wording ‘competent authority or assessment organization’ is used. This is done to take into account different regulatory systems in place in the different Member States. For instance, Belarus, Kazakhstan, and Russia have two-tiered systems where both a Ministry of Health and an assessing body exist. Moreover, in Belarus and Kazakhstan, the assessing body or assessment organization may directly communicate with an applicant or marketing authorization holder and send various requests. In Russia, all communications with the applicant are carried out via the Ministry of Health, so the wording takes into account this diversity in regulatory systems.
Mutual recognition procedure
This procedure is based on the mutual recognition by concerned Member State or States of a marketing authorization granted by the reference Member State.
The concerned Member State refers to the reference Member State that issued the marketing authorization on which the mutual recognition procedure is based. Such an authorization issued by the reference Member State is based on the assessment conducted pursuant to the Union rules. However, this is sometimes called a national marketing authorization, emphasizing that the authorization is valid only for one national market.
The reference Member State should issue a marketing authorization within 210 days. Where a mutual recognition procedure is triggered by an applicant in the concerned Member States, granting a marketing authorization should be completed within 90 days in the relevant Member States concerned. At the end of the mutual recognition procedure, a national marketing authorization will be issued in the concerned Member States. The harmonization is maintained through the procedures for the examination of variations as laid down in Annex 19 to the Rules.
Within a mutual recognition procedure, the competent authority of the reference Member State should complete granting a marketing authorization and assessment of the marketing authorization application dossier within 210 days.
Within the first 14 days upon submission, the competent authority should validate the dossier. Should any questions arise, the competent authority may furnish the applicant with a notice to provide additional information or clarification. Applicant should respond to such a notice within 90 days. Where the competent authority considers the application to be invalid having taken into account the response provided by the applicant or where the applicant does not respond in a timely manner, the competent authority will refuse to accept the application.
Where the competent authority considers the application to be valid, the assessment of the dossier begins. During the assessment period, the competent authority or assessment organization where it differs from the competent authority may request the applicant to provide additional information or data. The response period is set to 90 days per request, and the total response period may not exceed 180 days should several requests occur. Where the applicant fails to respond to the request in a timely manner, the assessment will be terminated, and the applicant will be noticed thereof.
Within the assessment period, the competent authority of the reference Member State may trigger an unscheduled GMP, GCP, GLP or GVP inspection if it considers it appropriate to do so having thoroughly examined the particulars and documents submitted within the marketing authorization application dossier.
An unscheduled GMP inspection may also be triggered where the applicant applies for such an inspection due to the absence of the GMP certificate of the Union and if the competent authority grants the application for an inspection.
The inspection needs to be concluded within 180 days and not later than the expected outcome of the authorization procedure.
By the 210th day after the application submitted, the competent authority of the reference Member State must decide on whether to issue a marketing authorization or refuse the application. The marketing authorization may be granted subject to one or more conditions. After the final decision is made, the applicant will be notified within 10 business days of that decision.
The competent authority of the reference Member State shall refuse to grant the marketing authorization for a medicinal product in the following cases:
a) the risk-benefit balance is not considered to be favorable;
b) its therapeutic efficacy is insufficiently substantiated by the applicant;
c) the quality of the medicinal product has not been demonstrated;
d) the proposed quality control test methods are not verifiable;
e) the applicant has submitted false information;
f) compliance with the GxP of the Union has not been demonstrated based on the outcome of the inspection within the procedure of granting a marketing authorization for a medicinal product.
It is worth noting that verification of test methods is obligatory, and this is where issues may arise because the assessment organization does not perform any method transfer.
In case of a positive decision, the competent authority will issue a certificate of marketing authorization, final versions of the Summary of Product Characteristics, Patient Leaflet, labelling, assessment report, Risk Management Plan, and normative document. The Risk Management Plan is issued only in specific cases determined by the Union GVP rules.
The normative document is a compilation of information from the selected sections of the quality module of the MAA dossier such as a specification, description of test methods, stability and packaging information. The problems with the normative document were described in our paper which has an English version for those who are interested.
This document is widely used in Russia, Belarus, and Kazakhstan, and it has major drawbacks. Keeping this in mind, the Union rules were drafted to overcome these drawbacks. To this end, a specific provision was enacted banning any discrepancies between the quality module information and the normative document.
The competent authority of the reference Member State should enter the information contained in the mentioned documents into the Union Common Register of the Authorized Medicinal Products.
After the marketing authorization is granted by the competent authority of reference Member State, the applicant may trigger the mutual recognition procedure by submitting an application to the desired Member State or States which become in this case the Member States concerned. At the same time, the applicant should send a request to the competent authority of the reference Member State asking it to grant access to the MAA dossier to the competent authorities of the Member States concerned where the applications for granting a marketing authorization were submitted. When applying for a marketing authorization in the Member States concerned, only limited information needs to be submitted, limited to the completed application form, Module 1 information in electronic format, confirmation that relevant fees have been paid, and the SmPC, PL, etc. in the official languages of the Member States concerned where those languages differ from Russian and where there is an appropriate provision in the national legislation of the Member States concerned.
Within 14 days, the competent authorities of the Member States concerned should validate the application and either start the assessment or refuse the application if the applicant fails to meet the legal requirements set out in the Rules.
If the application is successfully validated, the assessment of the medicinal product starts and needs to be completed within 50 days. The whole procedure shall be concluded within 90 days. The assessment principles are the same as those used by the reference Member State while the assessment period is shorter. Although the Member States concerned receive access to the whole MAA dossier, the scope of the assessment is limited to the assessment report drawn up by the competent authority of the reference Member State. The competent authorities of the Member States concerned may send a notice to the applicant requesting the provision of additional data or clarification via direct communication with the applicant. The Member States concerned should also grant the reference Member State access to all communications between the Member State concerned and the applicant.
The assessment procedure shall be terminated and the application refused if the applicant fails to respond in a timely manner to requests sent by the Member States concerned.
If the applicant was furnished with a notice to provide additional data and the applicant responds in a timely manner, then the competent authorities of the Member States concerned have additional 20 days to consider the application taking into account the newly submitted information. By the end of this period, the competent authorities of the Member States concerned should conclude the procedure and communicate their decisions to the reference Member State which should inform the applicant of the decisions made.
In case of a favorable decision, the competent authorities of the Member States concerned shall issue a certificate of marketing authorization which will be valid within the period approved by the reference Member State and the product information (i.e., the SmPC, PL, and labelling). The assessment report drawn up by the reference Member State, the normative document, and Risk Management Plan not to be issued since these documents coincide with the versions approved by the reference Member State.
Should an unfavorable decision is made by any of the Member States concerned taking part in the mutual recognition procedure, the subject of disagreement shall be referred to the Expert Committee for Medicinal Products for Human Use established within the Eurasian Economic Commission as well as to the reference Member State and the applicant. The reasons for making the unfavorable decision are provided in the Rules and limited to those under which the reference Member State may make the unfavorable decision.
In this case, the applicant may apply to the Expert Committee to trigger the dispute resolution procedure which should be concluded within 60 days. There are a few basic outcomes of the dispute resolution; the Member States involved may resolve all disagreements and thus make a single decision on the application or may agree to disagree. In the latter case, the Member States concerned which made the unfavorable decision refuse to grant a marketing authorization while the Member States concerned which made a positive decision issue a certificate of a marketing authorization together with other appropriate documents.
The decentralized procedure is conducted concurrently by the several Member States. The list of the Member States and the reference Member State are determined by the applicant.
The whole procedure should be completed within a maximum of 210 days beginning with the day the last of the applications for a marketing authorization for a medicinal product is submitted to the Member States concerned. At the end of the decentralized procedure where an agreement on a positive outcome has been reached, a national marketing authorization will be issued by the reference Member State and the concerned Member States. The harmonization is maintained through the procedures for the examination of variations as laid down in Annex 19 to the Rules.
The decentralized procedure for granting a marketing authorization takes place simultaneously in all Member States to which the application was submitted. The deadline for decision is the same as for the mutual recognition procedure and is limited to 210 days. The general logic of activities carried out by the participants of the procedure is quite similar to those in the mutual recognition procedure.
First of all, validation of the MAA dossier takes place which shall be carried out by the reference Member State within 14 days. Should any questions arise, the reference Member State may furnish the applicant with a notice to provide additional information or clarification. If the reference Member State validates the dossier, then the assessment of the dossier will begin. If the reference Member State refuses to accept the application, the applicant and the Member States concerned will be informed within 5 days of the decision being made.
If the dossier is considered to be valid, then the competent authority of the reference Member State will start the assessment procedure. During the assessment period, the competent authority or assessment organization may request the applicant to provide additional information or data. The response period is set to 90 days per request, and the total response period may not exceed 180 days should several requests occur. Where the applicant fails to respond to the request in a timely manner, the assessment will be terminated and the applicant will be noticed thereof.
By day 90 of the assessment period, the competent authority of the reference Member State, having considered the applicant’s response or responses as appropriate, should draft a provisional critical assessment report and send it to the competent authorities of the Member States concerned for consideration.
Within the assessment period, the competent authority of the reference Member State may trigger an unscheduled GMP, GCP, GLP or GVP inspection if it considers it appropriate to do so having thoroughly assessed particulars and documents submitted within the marketing authorization application dossier. An unscheduled GMP inspection may also be triggered where the applicant applies for such an inspection due to the absence of the GMP certificate of the Union and if the competent authority grants the application for an inspection.
The inspection needs to be concluded within 180 days and no later than the expected outcome of the authorization procedure.
Having received the provisional assessment report drawn up by the competent authority of the reference Member State, the competent authorities of the appropriate Member States concerned should evaluate the provisional conclusions made by the competent authority of the reference Member State. Should additional observations arise, competent authorities of the Member States concerned may refer those observations to the reference Member State. The competent authority of the reference Member State, having considered the observations made by the competent authorities of the Member States concerned, either resolves those observations within close communications with the competent authorities of the Member States concerned or upholds the observations and sends a request to the applicant. When determining the deadline periods for response by the applicant, the same rules apply as mentioned previously for the mutual recognition procedure.
Any communications between the Member States concerned and the applicant are to be carried out via the reference Member State. This means that the competent authority of the reference Member State is the single contact point between the applicant and all participating competent authorities of the Member States during the whole procedure.
Where the competent authorities of the Member States concerned do not raise any observations within the appropriate time period, the competent authority of the reference Member State considers that the competent authorities of the Member States concerned agree with the provisional assessment report and proceeds towards the next step of the procedure.
Having duly considered all applicant’s responses and observations of the competent authorities of the Member States concerned, the competent authority of the reference Member State draws up a draft final assessment report and sends it to the competent authorities of the Member States concerned and the applicant.
Having received the draft final assessment report, the competent authorities of the Member States concerned should scrutinize the report and discuss all the outstanding issues and comments with the competent authority of the reference Member State.
Within the following 10 days, the competent authority of the reference Member State should reconsider its conclusions based on the observations and comments of, and the discussion with, the Member States concerned and proceed towards the finalization of the procedure.
Within 30 days the competent authority of all Member States involved in the procedure should issue the approved documents. An additional 10 business days will be given to translate the approved documents into the official languages of the appropriate Member States where their national legislation provides so.
Both the reference Member State and the Member States concerned issue the same set of documents. However, the period of validity of the marketing authorization is determined by the date the reference Member State makes its favorable decision.
Where during the deliberation period, at least one Member State concerned disagrees with the draft final assessment report drawn up by the competent authority of the reference Member State, the subject of disagreement is referred to the reference Member State, other Member States concerned, and the Expert Committee. The dispute resolution procedure is triggered in this case under the remits of the Expert Committee and should be concluded by the end of a 60-day period. If the disagreements are resolved, the competent authority of the reference Member State proceeds towards finalization of the procedure. If the disagreements are unresolved, then the disagreed Member States may make their own decisions. This is the main difference between the European Union and the Eurasian Economic Union marketing authorization procedures since the EAEU rules allow making discordant decisions which prevent full harmonization. The Member States which made favorable decisions proceed towards the finalization of the procedure.
Once the final decision is made, the competent authority of the reference Member State notifies the applicant of that decision within 10 days.
