MARKETING MARKETING AUTHORIZATION AUTHORIZATION

PROCEDURES IN EUPROCEDURES IN EU

A. RAJANIA. RAJANI

Types Of MA ProceduresTypes Of MA Procedures

Roads to enter EURoads to enter EU

• NationalNational

• CentralizedCentralized

• Mutual RecognitionMutual Recognition

• De-centralizedDe-centralized

Types Of MA ProceduresTypes Of MA Procedures• What happens once the pharmaceutical company has submitted its application What happens once the pharmaceutical company has submitted its application

for a marketing authorisation?for a marketing authorisation?• Full copies of the marketing authorisation application file are sent to a rapporteur and a Full copies of the marketing authorisation application file are sent to a rapporteur and a

co-rapporteur designated by the competent EMEA scientific committee. They co-ordinate co-rapporteur designated by the competent EMEA scientific committee. They co-ordinate the EMEA's assessment of the medicinal product and prepare draft reports.the EMEA's assessment of the medicinal product and prepare draft reports.

• Once the draft reports are prepared (other experts might be called upon for this Once the draft reports are prepared (other experts might be called upon for this purpose), they are sent to the CHMP or CVMP, whose comments or objections are purpose), they are sent to the CHMP or CVMP, whose comments or objections are communicated to the applicant. The rapporteur is therefore the privileged interlocutor of communicated to the applicant. The rapporteur is therefore the privileged interlocutor of the applicant and continues to play this role, even after the marketing authorisation has the applicant and continues to play this role, even after the marketing authorisation has been granted.been granted.

• The rapporteur and co-rapporteur then assess the applicant's replies, submit them for The rapporteur and co-rapporteur then assess the applicant's replies, submit them for discussion to the CHMP or CVMP and, taking into account the conclusions of this debate, discussion to the CHMP or CVMP and, taking into account the conclusions of this debate, prepare a final assessment report. Once the evaluation is completed, the CHMP gives a prepare a final assessment report. Once the evaluation is completed, the CHMP gives a favourable or unfavourable opinion as to whether to grant the authorisation. When the favourable or unfavourable opinion as to whether to grant the authorisation. When the opinion is favourable, it shall include the draft summary of the product's characteristics, opinion is favourable, it shall include the draft summary of the product's characteristics, the package leaflet and the texts proposed for the various packaging materials.the package leaflet and the texts proposed for the various packaging materials.

• The time limit for the evaluation procedure is 210 days (the application formalities and The time limit for the evaluation procedure is 210 days (the application formalities and the detailed procedure are described in the the detailed procedure are described in the Notice to ApplicantsNotice to Applicants which is available in the which is available in the Eudralex volumes).Eudralex volumes).

• The Agency then has thirty days to forward its opinion to the Commission. This is the The Agency then has thirty days to forward its opinion to the Commission. This is the start of the second phase of the procedure: the decision-making process. The Agency start of the second phase of the procedure: the decision-making process. The Agency sends to the Commission its opinion and assessment report, together with annexes sends to the Commission its opinion and assessment report, together with annexes containing:containing:

• the summary of product characteristics (Annex 1); the summary of product characteristics (Annex 1); • the particulars of the manufacturing authorisation holder responsible for batch release, the particulars of the manufacturing authorisation holder responsible for batch release,

the particulars of and the manufacturer of the biological active substance and the the particulars of and the manufacturer of the biological active substance and the conditions of the marketing authorisation (Annex 2); conditions of the marketing authorisation (Annex 2);

• the labelling and the package leaflet (Annex 3). the labelling and the package leaflet (Annex 3).

Types Of MA ProceduresTypes Of MA Procedures

• The annexes are translated into the 21 Community languages.The annexes are translated into the 21 Community languages.• During the decision-making process, the Commission services verify that the During the decision-making process, the Commission services verify that the

marketing authorisation complies with Community law and turn the Agency's opinion marketing authorisation complies with Community law and turn the Agency's opinion into a binding decision for all the Member States.into a binding decision for all the Member States.

• The Commission has thirty days to prepare a draft decision. The medicinal product is The Commission has thirty days to prepare a draft decision. The medicinal product is assigned a Community registration number, which will be placed on its packaging if assigned a Community registration number, which will be placed on its packaging if the marketing authorisation is granted. During this period, various Commission the marketing authorisation is granted. During this period, various Commission directorates-general are consulted on the draft marketing authorisation decision. directorates-general are consulted on the draft marketing authorisation decision. They have ten days to deliver their opinions.They have ten days to deliver their opinions.

• The draft decision is then sent to the Standing Committee on Medicinal Products for The draft decision is then sent to the Standing Committee on Medicinal Products for Human Use, or the Standing Committee on Veterinary Medicinal Products (Member Human Use, or the Standing Committee on Veterinary Medicinal Products (Member States have one representative each in both of these committees) for their opinions. States have one representative each in both of these committees) for their opinions. The Rules of Procedure of these Committees are here [22 KB] .The Rules of Procedure of these Committees are here [22 KB] .

• Member States have fifteen days to return their linguistic comments and 22 days for Member States have fifteen days to return their linguistic comments and 22 days for scientific and technical ones. This procedure is conducted in writing but if a duly scientific and technical ones. This procedure is conducted in writing but if a duly justified objection is raised by one or more Member States, the committee holds a justified objection is raised by one or more Member States, the committee holds a plenary meeting to discuss it.plenary meeting to discuss it.

• When the opinion is favourable, the draft decision is forwarded to the Commission's When the opinion is favourable, the draft decision is forwarded to the Commission's Secretariat-General for adoption through an empowerment procedure, enabling the Secretariat-General for adoption through an empowerment procedure, enabling the Commissioner for Enterprise and Industry to issue the final decision.Commissioner for Enterprise and Industry to issue the final decision.

• When the decision is approved, the Commission's Secretariat-General notifies the When the decision is approved, the Commission's Secretariat-General notifies the Member States and the marketing authorisation holder in their respective languages. Member States and the marketing authorisation holder in their respective languages. The decision is then published in the Official Journal of the European Communities.The decision is then published in the Official Journal of the European Communities.

• Marketing authorisations are valid for five years. Applications for renewal must be Marketing authorisations are valid for five years. Applications for renewal must be made to the EMEA at least six months before this five-year period expires.made to the EMEA at least six months before this five-year period expires.

National ProcedureNational Procedure

• Marketing Authorization in one Marketing Authorization in one Member State onlyMember State only

• Abridged Application to nationally Abridged Application to nationally authorised originators /innovatorsauthorised originators /innovators

• Time-line : 210 days Time-line : 210 days

Centralized Procedure ( CP )Centralized Procedure ( CP )

• An approval in all EU countries An approval in all EU countries obtained by applying to the EMEA obtained by applying to the EMEA (European Medicines Evaluation (European Medicines Evaluation Agency) . Agency) .

• Mandatory for Biogenerics -if Mandatory for Biogenerics -if biotechnological products biotechnological products

• Generics –New Entrants Generics –New Entrants • Optional for GenericsOptional for Generics• Review Time : 210 daysReview Time : 210 days

Centralized Procedure ( CP )Centralized Procedure ( CP )

• The The centralisedcentralised procedure procedure, which is compulsory for , which is compulsory for products derived from biotechnology, for orphan medicinal products derived from biotechnology, for orphan medicinal products and for medicinal products for human use which products and for medicinal products for human use which contain an active substance authorised in the Community contain an active substance authorised in the Community after 20 May 2004 (date of entry into force of Regulation after 20 May 2004 (date of entry into force of Regulation (EC) No 726/2004) and which are intended for the (EC) No 726/2004) and which are intended for the treatment of AIDS, cancer, neurodegenerative disorders or treatment of AIDS, cancer, neurodegenerative disorders or diabetes. The centralised procedure is also mandatory for diabetes. The centralised procedure is also mandatory for veterinary medicinal products intended primarily for use as veterinary medicinal products intended primarily for use as performance enhancers in order to promote growth or to performance enhancers in order to promote growth or to increase yields from treated animals.increase yields from treated animals.Applications for the centralised procedure are made directly Applications for the centralised procedure are made directly to the European Medicines Agency (EMEA) and lead to the to the European Medicines Agency (EMEA) and lead to the granting of a European marketing authorisation by the granting of a European marketing authorisation by the Commission which is binding in all Member States. Commission which is binding in all Member States.

Centralized Procedure ( CP )Centralized Procedure ( CP )

• The centralised procedure, which came into operation in 1995, allows applicants to obtain a The centralised procedure, which came into operation in 1995, allows applicants to obtain a marketing authorisation that is valid throughout the EU. It is compulsory for medicinal products marketing authorisation that is valid throughout the EU. It is compulsory for medicinal products manufactured using biotechnological processes, for orphan medicinal products and for human manufactured using biotechnological processes, for orphan medicinal products and for human products containing a new active substance which was not authorised in the Community before 20 products containing a new active substance which was not authorised in the Community before 20 May 2004 (date of entry into force of Regulation (EC) No 726/2004) and which are intended for the May 2004 (date of entry into force of Regulation (EC) No 726/2004) and which are intended for the treatment of AIDS, cancer, neurodegenerative disorder or diabetes. The centralised procedure is treatment of AIDS, cancer, neurodegenerative disorder or diabetes. The centralised procedure is also mandatory for veterinary medicinal products intended primarily for use as performance also mandatory for veterinary medicinal products intended primarily for use as performance enhancers in order to promote growth of treated animals or to increase yields from treated animals.enhancers in order to promote growth of treated animals or to increase yields from treated animals.

• The centralised procedure is optional for any other products containing new active substances not The centralised procedure is optional for any other products containing new active substances not authorised in the Community before 20 May 2004 or for products which constitute a significant authorised in the Community before 20 May 2004 or for products which constitute a significant therapeutic, scientific or technical innovation or for which a Community authorisation is in the therapeutic, scientific or technical innovation or for which a Community authorisation is in the interests of patients or animal health at Community level.interests of patients or animal health at Community level.

• When a company wishes to place on the market a medicinal product that is eligible for the When a company wishes to place on the market a medicinal product that is eligible for the centralised procedure, it sends an application directly to the European Medicines Agency, to be centralised procedure, it sends an application directly to the European Medicines Agency, to be assessed by the assessed by the Committee for Medicinal Products for Human Use (CHMP)Committee for Medicinal Products for Human Use (CHMP) or the or the Committee for Medicinal Products for Veterinary Use (CVMP)Committee for Medicinal Products for Veterinary Use (CVMP)..

• The procedure results in a Commission decision, which is binding on all EU Member States, to The procedure results in a Commission decision, which is binding on all EU Member States, to authorise the product. Centrally-authorised products may be marketed in all Member States.authorise the product. Centrally-authorised products may be marketed in all Member States.

• Applications from persons or companies seeking 'orphan medicinal product designation' for products Applications from persons or companies seeking 'orphan medicinal product designation' for products they intend to develop for the diagnosis, prevention or treatment of life-threatening or very serious they intend to develop for the diagnosis, prevention or treatment of life-threatening or very serious conditions that affect not more than 5 in 10,000 persons in the European Union are reviewed by the conditions that affect not more than 5 in 10,000 persons in the European Union are reviewed by the Committee for Orphan Medicinal Products (COMP)Committee for Orphan Medicinal Products (COMP)..

• The The Committee on Herbal Medicinal Products (HMPC)Committee on Herbal Medicinal Products (HMPC) is responsible for establishing a list of herbal is responsible for establishing a list of herbal substances, preparations and combinations thereof for use in traditional herbal medicinal products. substances, preparations and combinations thereof for use in traditional herbal medicinal products. It is also responsible for establishing Community herbal monographs.It is also responsible for establishing Community herbal monographs.

Mutual Recognition Procedure Mutual Recognition Procedure (MRP)(MRP)

• Used for > 1 CountriesUsed for > 1 Countries• Generic Industry : Major user of MRPGeneric Industry : Major user of MRP• 1 St Step: Submission to one national 1 St Step: Submission to one national

authority - Reference Member State –authority - Reference Member State –RMS - for review.RMS - for review.

• If successful :RMS assessment report If successful :RMS assessment report => used in all EU countries - => used in all EU countries - Concerned Member States –CMSConcerned Member States –CMS

• Review Time : 210 + 90 +90 daysReview Time : 210 + 90 +90 days

Mutual Recognition Procedure Mutual Recognition Procedure (MRP)(MRP)

• The The mutual recognition proceduremutual recognition procedure, , which is applicable to the majority of which is applicable to the majority of conventional medicinal products, is conventional medicinal products, is based on the principle of recognition based on the principle of recognition of an already existing national of an already existing national marketing authorisation by one or marketing authorisation by one or more Member States. more Member States.

Mutual Recognition Procedure Mutual Recognition Procedure (MRP)(MRP)• The mutual recognition procedure is based on the principle of the mutual recognition The mutual recognition procedure is based on the principle of the mutual recognition

by EU Member States of their respective national marketing authorisations. An by EU Member States of their respective national marketing authorisations. An application for mutual recognition may be addressed to one or more Member States. application for mutual recognition may be addressed to one or more Member States. The applications submitted must be identical and all Member States must be notified The applications submitted must be identical and all Member States must be notified of them. As soon as one Member State decides to evaluate the medicinal product (at of them. As soon as one Member State decides to evaluate the medicinal product (at which point it becomes the "Reference Member State"), it notifies this decision to other which point it becomes the "Reference Member State"), it notifies this decision to other Member States (which then become the "Concerned Member States"), to whom Member States (which then become the "Concerned Member States"), to whom applications have also been submitted. Concerned Member States will then suspend applications have also been submitted. Concerned Member States will then suspend their own evaluations, and await the Reference Member State's decision on the their own evaluations, and await the Reference Member State's decision on the product.product.

• This evaluation procedure undertaken by the Reference Member State may take up to This evaluation procedure undertaken by the Reference Member State may take up to 210 days, and ends with the granting of a marketing authorisation in that Member 210 days, and ends with the granting of a marketing authorisation in that Member State . It can also occur that a marketing authorisation had already been granted by State . It can also occur that a marketing authorisation had already been granted by the Reference Member State. In such a case, it shall update the existing assessment the Reference Member State. In such a case, it shall update the existing assessment report in 90 days. As soon as the assessment is completed, copies of this report are report in 90 days. As soon as the assessment is completed, copies of this report are sent to all Member States, together with the approved summary of product sent to all Member States, together with the approved summary of product characteristics (SPC), labelling and package leaflet. The Concerned Member States characteristics (SPC), labelling and package leaflet. The Concerned Member States then have 90 days to recognise the decision of the Reference Member State and the then have 90 days to recognise the decision of the Reference Member State and the SPC, labelling and package leaflet as approved by it. National marketing authorisations SPC, labelling and package leaflet as approved by it. National marketing authorisations shall be granted within 30 days after acknowledgement of the agreement.shall be granted within 30 days after acknowledgement of the agreement.

• Should any Member State refuse to recognise the original national authorisation, on Should any Member State refuse to recognise the original national authorisation, on the grounds of potential serious risk to public health, the issue will be referred to the the grounds of potential serious risk to public health, the issue will be referred to the coordination group. Within a timeframe of 60 days, Member States shall, within the coordination group. Within a timeframe of 60 days, Member States shall, within the coordination group, make all efforts to reach a consensus. In case this fails, the coordination group, make all efforts to reach a consensus. In case this fails, the procedure is submitted to the appropriate EMEA scientific committee (CHMP or CVMP, procedure is submitted to the appropriate EMEA scientific committee (CHMP or CVMP, as appropriate), for arbitration. The opinion of the EMEA Committee is then forwarded as appropriate), for arbitration. The opinion of the EMEA Committee is then forwarded to the Commission, for the start of the decision making process. As in the centralised to the Commission, for the start of the decision making process. As in the centralised procedure, this process entails consulting various Commission Directorates General procedure, this process entails consulting various Commission Directorates General and the Standing Committee on Human Medicinal Products or the Standing Committee and the Standing Committee on Human Medicinal Products or the Standing Committee on Veterinary Medicinal Products, as appropriate. The Rules of Procedure of these on Veterinary Medicinal Products, as appropriate. The Rules of Procedure of these Committees are here [22 KB] .Committees are here [22 KB] .

Decentralized Procedure Decentralized Procedure (DCP)(DCP)• Used for > 1 CountriesUsed for > 1 Countries

• Generic Industry :will be major user of DCPGeneric Industry :will be major user of DCP

• Used for products that have not yet received Used for products that have not yet received authorisation in an EU country. authorisation in an EU country.

• RMS & CMS receives MAA at the same timeRMS & CMS receives MAA at the same time

• RMS & CMS also grants MA at the same timeRMS & CMS also grants MA at the same time

• Time : 210 days. Time : 210 days.

Decentralized Procedure Decentralized Procedure (DCP)(DCP)• The The decentraliseddecentralised procedure procedure, which was , which was

introduced with the legislative review of 2004, introduced with the legislative review of 2004, is also applicable to the majority of is also applicable to the majority of conventional medicinal products. Through this conventional medicinal products. Through this procedure an application for the marketing procedure an application for the marketing authorisation of a medicinal product is authorisation of a medicinal product is submitted simultaneously in several Member submitted simultaneously in several Member States, one of them being chosen as the States, one of them being chosen as the "Reference Member State". At the end of the "Reference Member State". At the end of the procedure national marketing authorisations procedure national marketing authorisations are granted in the reference and in the are granted in the reference and in the concerned Member States. concerned Member States.

Decentralized Procedure Decentralized Procedure (DCP)(DCP)• The decentralised procedure was introduced by The decentralised procedure was introduced by

Directive 2004/27/EC . As the mutual recognition Directive 2004/27/EC . As the mutual recognition procedure, it is also based on recognition by national procedure, it is also based on recognition by national authorities of a first assessment performed by one authorities of a first assessment performed by one Member State . The difference lies in that it applies Member State . The difference lies in that it applies to medicinal products which have not received a to medicinal products which have not received a marketing authorisation at the time of application.marketing authorisation at the time of application.

How does the decentralised procedure work?How does the decentralised procedure work?• An identical application for marketing authorisation is An identical application for marketing authorisation is

submitted simultaneously to the competent authorities of submitted simultaneously to the competent authorities of the Reference Member State and of the Concerned Member the Reference Member State and of the Concerned Member States. At the end of the procedure, the draft assessment States. At the end of the procedure, the draft assessment report, SPC, labelling and package leaflet, as proposed by report, SPC, labelling and package leaflet, as proposed by the Reference Member State, are approved.the Reference Member State, are approved.

• The subsequent steps are identical to the mutual The subsequent steps are identical to the mutual recognition procedure.recognition procedure.

MARKETING AUTHORIZATION MARKETING AUTHORIZATION PROCEDURES IN EUPROCEDURES IN EU