Civil Law

The European Commission (the “Commission”) wants to “avoid unnecessary administrative and financial burdens for applicants and competent authorities.”  As such, the Commission’s proposal for a revised Directive on the Union Code Relating to Medicinal Products for Human Use (the “Directive”) retains the Decentralized Procedure (“DCP”) and Mutual Recognition Procedure (“MRP”).  Chapter III of the Directive sets out the new procedures for national marketing authorizations (“MAs”).  This includes a purely national MA procedure granted in a single Member State (Article 32), as well as MAs granted through the DCP (Article 33 and 34) and MRP (Article 35 and 36) in multiple Member States.  These procedures are broadly aligned with  the procedures set out in Directive 2001/83/EC (the “Old Directive”). 

However, there are some key changes.  Notably the Directive allows Member States to “opt-in” to procedures, it potentially blocks MRP for a year after an initial marketing authorization (“MA”) is granted and  it provides for a shorter examination period (now 180 days). 

In addition, the MRP/DCP will be less relevant as the mandatory scope of the centralised procedure is significantly broadened.  It covers all new active substances since 2004 (except for allergens and herbals).  Generic versions, for instance, of innovative products approved under the MRP/DCP since 2004 will have to be approved centrally.  This is of course not consistent with the option for generics of centrally approved products to be approved nationally. 

This blog summarizes the MRP and DCP, plus discusses key changes under the Directive.

General Provisions for National MAs

Section 1 of Chapter III sets out the general provisions that apply to all national MAs, regardless of the procedure through which they are granted.  Article 29 sets out the rules on examination of the MA application (“MAA”).  It provides that Member States must examine the application submitted and can impose certain requirements in order to validate the applications (e.g., requiring applicants to supplement their application).  If the Member State considers that the application is incomplete or deficient, it must set a time limit for the applicant to submit the missing information.  Additionally, if the application contains data of insufficient quality or maturity, the examination can be terminated in 90 days of validation of the MAA.  The applicant will be given a time limit to address the deficiencies and if that time limit is not respected, the application is considered withdrawn.

Article 30 provides that the examination must be completed within 180 days after submission of a valid application.  This means that the standard procedure for granting MAs should speed up by 30 days.

Purely National MAs

Section 2 covers the purely national MA procedure, i.e., where an applicant only applies for an MA in one Member State.  Applicants following this procedure need to follow the “General Provisions for National MAs” in Section 1, Articles 29 and 30 (see above) and the “General Provisions on Granting/Renewing National MAs” in Section 6, Articles 43 – 45 (see below).

MAs Valid in Several Member States – MRP and DCP

Section 3 covers the procedures for MAs granted in several Member States, i.e., under the MRP or DCP.  Applicants for MAs under these procedures must also follow the “General Provisions” in Section 1 and 6 but then must follow the specific DCP (Articles 33 – 34) and MRP (Articles 35 – 36) procedures.

Like the Old Directive, the Directive  confirms that the MAs will only be valid in the Member States that grant MAs.  Additionally, in both the MRP and DCP applicants must submit a list of all Member States concerned in the procedure.  The applicant must request one Member State act as the RMS, who will prepare/update an assessment report, if applicable. 

In terms of the specific procedures, the DCP is mainly aligned with the Old Directive as:

• it is used where a medicinal product has not already received an MA;
• applicants must submit an identical dossier to the competent authorities of the RMS and “Concerned Member States” (“CMS”); and
• the RMS must prepare draft documents (a draft AR, a draft summary of product characteristics and a draft of the labelling and package leaflet) within 120 days of validation of the application and send them to the CMS. 

The MRP is also broadly aligned with the Old Directive as:

• it is used when a medicinal product has already received an MA; and
• CMS can request the RMS to update the assessment report (“AR”), which should be updated within 90 days of validation of the application (if no update is required the AR should be provided within 30 days).

In both the MRP and DCP:

• the CMS shall approve the AR, summary of product characteristics, labelling and packaging leaflet within 60 days and shall inform the RMS (unless the Member States disagree, in which case the procedure of divergent decisions must be followed, as discussed below); 
• the RMS should record the agreement, close the procedure and inform the applicant; and
• the CMS should adopt a decision in conformity with the AR within 30 days of acknowledgement of the agreement in accordance with the General Provisions on Granting/Renewing National MAs (see below).

However, the Directive has made some key changes to the procedures versus the Old Directive: 

• Member States can “opt-in”:  For both MRP and DCP, a key change is that the Directive allows Member States that were not part of the original application to “opt-in” to an MRP/DCP for public health reasons.  This provision requires that the Member State(s) must opt-in within 30 days of the applicant’s submission of its application and then the applicant must provide the Member State(s) with an identical dossier.  As such, under the Directive, it may not be possible for applicants to tactically avoid particular Member States in their MRP/DCP applications.  This might have an impact on an applicant’s ability to obtain RDP as it is only possible to obtain two additional years of data protection under Article 82 if the medicinal product is supplied in a sufficient quantity to all Member States in which the marketing authorization (“MA”) is valid (see our blog on RDP here).  Additionally, this requirement may pose practical issues for companies (particularly small and medium-sized enterprises (“SMEs”)).  For example, there might be financial issues if the applicant is required to pay an application fee for the countries that opt-in.  There could also be supply chain and/or resourcing issues if an SME does not have the necessary infrastructure to actually supply the products to particular Member States.

• Addressing Deficiencies or Termination of the Application: The Directive now allows the RMS in the DCP to terminate the application if it considers it considers the data is “not of sufficient quality or maturity for the completion of the examination of the application the examination.”  Applicants will be given a time limit to address deficiencies and if they fail to do so, the application is considered withdrawn.

• MRP Blocked for One Year:  For the MRP, Article 36(3) expressly states the RMS should reject an application under the MRP “within a year from the granting of that marketing authorisation unless the [CMS] informs the reference Member State of its interest in this procedure.”  Therefore, if applicants want MAs in a number of Member States around the same time, the Commission is forcing applicants to use the DCP.

Divergent Decisions

As under the current rules, Member States may not agree on whether to approve an MA.  Section 5 of the Directive set out the procedure for coordination of national MAs, with Articles 38 – 42 covering the procedure for where there are divergent positions of Member States in the MRP or DCP.  This procedure also broadly aligns with the Old Directive.  The procedure sets out three main steps of review, which in summary are:

• Referral to the coordination group for MRP/DCP: If Member States cannot agree whether to approve an application within 60 days, the application should be referred to the coordination group (established by Article 37).  If the coordination group reaches agreement the CMS have 30 days to adopt the decision in accordance with the General Provisions on Granting/Renewing National MAs.    
• Review by the European Medicines Agency (“EMA”): If there is no agreement, the majority decision of the coordination group is forwarded to the Commission (although Member States that agreed to approve the product can grant the authorization without waiting for the results of this procedure).  The EMA’s Committee for Medicinal Products for Human Use (“CHMP”) carries out a scientific evaluation and issues an opinion within 60 days (although this can be extended by an additional 90 days or reduced if the CHMP agree).  The EMA informs the applicant of the CHMP’s opinion and the applicant can choose to request a re-examination.
• Decision by the Commission: The Commission adopts a decision based on the CHMP opinion through the comitology procedure.  If Member States raise new questions of a scientific or technical nature, the Commission can send the dossier back to the EMA for review.  The RMS and CMS have 30 days to comply with the Commission decision.

General Provisions on Granting/Renewing National MAs

Section 6 sets out the rules relating to the results of examination of a national MAA.  These apply to all MAAs, regardless of the application procedure followed. 

Article 43 provides the procedure for granting a national MA.  Article 44 states that MAs can be granted subject to one or more conditions (e.g., on risk management, post-authorization studies, pharmacovigilance etc.).  Article 45 provides the possibility to grant MAs under exceptional circumstances.  This means, if the applicant is unable to provide comprehensive data on efficacy and safety under normal conditions, it is possible to grant an MA under Article 43 if certain conditions are met. 

Validity and Refusal

Section 6 also sets out the rules on validity, renewal and refusal of MAs.  Article 46 now means that most MAs will be valid for an unlimited period.  Only MAs granted under exceptional circumstances or where competent authorities think there are objective and duly justified grounds will be limited to five years.  Article 47 lists the grounds on which national MAs can be refused.  Notably, these now include environmental grounds.

Implications

Therefore, the MRP and DCP will likely remain very similar under the Directive.  However, applicants will need to consider the changes to the Directive as these could impact an applicant’s ability to obtain RDP due to the opt-in provision.  It could also impact an applicant’s regulatory strategy.  For example, the applicant will need to consider where and when to submit the application to ensure the applicant is not suspended or cancelled due to lack of data.  Additionally, it will need to consider what procedure to use to ensure it is not blocked for subsequent applications (i.e., due to the one year block on the MRP after an initial application).

This blog is based on the wording of the EU’s proposal published on 26 April 2023.  This wording could significantly change during the legislative process.  Our Dublin, Brussels, Frankfurt and London teams will continue to monitor this legislation. We will be hosting a webinar to discuss the impact on 9 May. To sign up for the webinar please click here.  Please contact either Peter Bogaert or Grant Castle is you have any questions in the meantime.

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