Presubmission guidance: questions 1 to 11

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This page lists questions 1 to 11 of the European Medicines Agency's questions and answers on presubmission guidance.

The page is updated regularly to reflect new developments, to include guidance on further pre-authorisation procedures and to reflect the implementation of new European legislation. Revised topics are marked 'New' or 'Rev.' on publication.

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1. Is my medicinal product eligible for evaluation under the Centralised Procedure?

Regulation (EC) No 726/2004 of the European Parliament and of the Council lays down a centralised Community procedure for the authorisation of medicinal products, for which there is a single application, a single evaluation and a single authorisation allowing direct access to the single market of the Community.

A marketing authorisation granted under the centralised procedure is valid for the entire Community market, which means the medicinal product, may be put on the market in all member states.

I - Article 3 of Regulation (EC) No 726/2004 defines the scope and eligibility of applications for evaluation under the centralised procedure through which medicinal products must ("mandatory scope") or may ("optional scope" or "Generic/Hybrid") be authorised by the Community.

a) Mandatory scope (Article 3(1)):
For medicinal products falling within the mandatory scope of the Annex of Regulation (EC) No 726/2004, applicants are obliged to use the centralised procedure by submitting their marketing authorisation application to the European Medicines Agency. Medicinal products under the mandatory scope belong to one of the following categories:

1. Medicinal products developed by means of one of the following biotechnological
processes:

  • recombinant DNA technology;
  • controlled expression of genes coding for biologically active proteins in prokaryotes and eukaryotes including transformed mammalian cells;
  • hybridoma and monoclonal antibody methods;

Similar biological ("biosimilar") medicinal products which are developed by one of the above biotechnological processes also fall under the mandatory scope of the centralised procedure.

1a. Advanced therapy medicinal product as defined in Article 2 of Regulation (EC) No 1394/2007

  • Gene therapy medicinal products
  • Somatic cell therapy medicinal products
  • Tissue engineered products

"Transitional period" applies (Article 29):
Advanced therapy medicinal products, other than tissue engineered products, which were legally on the Community market in accordance with national or Community legislation on 30 December 2008, shall comply with this Regulation no later than 30 December 2011.

Tissue engineered products which were legally on the Community market in accordance with national or Community legislation on 30 December 2008 shall comply with this Regulation no later than 30 December 2012.

2. Medicinal products for human use containing a new active substance which, on the date of entry into force of the Regulation (20 November 2005), was not authorised in the Community and for which the therapeutic indication is the treatment of any of the following diseases:

  • Acquired immune deficiency syndrome;
  • Cancer;
  • Neurodegenerative disorder;
  • Diabetes;

And with effect from 20 May 2008

  • Auto-immune diseases and other auto-immune dysfunctions;
  • Viral diseases;

Clarifications on the working definitions of the diseases listed above are available in the Scientific aspects and working definitions for the mandatory scope of the centralised procedure.

3. Medicinal products that are designated as orphan medicinal products pursuant to Regulation (EC) No 141/2000.

b) Optional Scope (Article 3(2)):
For medicinal products falling under the optional scope, applications for the following categories may, at the request of the applicant, be accepted for assessment under the centralised procedure:

1. A medicinal product containing a new active substance which, on the day of entry into force of the Regulation (20 November 2005) was not authorised in the Community (Article 3(2)a).

A new chemical, biological or radiopharmaceutical active substance, as defined in Annex III to Chapter 1 of the Notice to Applicants, includes:

  • a chemical, biological or radiopharmaceutical substance not previously authorised as a medicinal product in the European Union;
  • an isomer, mixture of isomers, a complex or derivative or salt of a chemical substance previously authorised as a medicinal product in the European Union but differing in properties with regard to safety and efficacy from that chemical substance previously authorised;
  • a biological substance previously authorised as a medicinal product in the European Union, but differing in molecular structure, nature of source material or manufacturing process;
  • a radiopharmaceutical substance which is a radionuclide, or a ligand not previously authorised as a medicinal product in the European Union, or the coupling mechanism to link the molecule and the radionuclide has not been authorised previously the European Union;

2. A medicinal product, which constitutes a significant therapeutic, scientific or technical innovation or that the granting of authorisation is in the interest of patients at Community level (Article 3(2)b).

For the purpose of determining whether &quota medicinal product constitutes a significant therapeutic, scientific or technical innovation&quot, the Agency will consider if:

  • the medicinal product provides a new alternative to patients in treating, preventing or diagnosing a disease, or,
  • the medicinal product development is based on significant new scientific knowledge or on the application of a new scientific knowledge, or,
  • a new technology or a new application of technology is used for the development or the manufacture of the medicinal product.

Regarding the criteria of ‘interest of patients’, a medicinal product which does not constitute a significant therapeutic, scientific or technical innovation, can be of patient interest at Community level when it addresses a specific health issue, allows access to medicines, or provides another type of contribution to patient care in the Community.

c) Generic/Hybrid of centralised medicinal product applications (Article 3(3)):
A generic or hybrid medicinal product of a reference medicinal product authorised via the centralised procedure has ‘automatic’ access to the centralised procedure under Article 3(3).

d) Duplicate/multiple marketing authorisations:
Multiple/duplicate or informed consent applications from the same or different marketing authorisation holder for a specific medicinal product with an active substance(s) already authorised via the centralised procedure, have automatic access to the centralised procedure.

II - Applications for certain medicinal products for paediatric use may also be eligible for evaluation through the centralised procedure in accordance with the Paediatric Regulation (Regulation (EC) No 1901/2006)

  1. Marketing Authorisation application including paediatric indication(s) for a medicinal product which is not authorised in the Community (Article 28):
    A marketing authorisation application for a medicinal product not authorised in the Community on the date of entry into force of the Paediatric Regulation (26 July 2008) and which includes one or more paediatric indication(s) on the basis of studies conducted in compliance with an agreed paediatric investigation plan (PIP).
  2. Applications for a new paediatric indication, a pharmaceutical form and/or a route of administration for nationally authorised medicinal products (Article 29):
    Applications for a new paediatric indication, a pharmaceutical form and/or a route of administration for a nationally authorised medicinal product falling under Article 8 of Regulation (EC) No 1901/2006 and which include results of studies conducted in compliance with an agreed PIP. Article 8 of Regulation (EC) No 1901/2006 applies to authorised medicinal products which are protected either by a supplementary protection certificate under Regulation (EEC) No 1768/92, or by a patent which qualifies for the granting of the supplementary protection certificate.
  3. Paediatric Use Marketing Authorisation (PUMA) application (Article 31):
    Applications for a PUMA concerns only a medicinal product for human use which is not protected by a supplementary protection certificate under Regulation (EEC) No 1768/92 or by a patent which qualifies for the granting of the supplementary protection certificate, and which covers exclusively paediatric therapeutic indications, including the appropriate strength, pharmaceutical form or route of administration for that product.

In all cases listed above, the eligibility of a medicinal product for evaluation via the centralised procedure must be requested by the applicant by submitting a Pre-submission request form (Eligibility) to: CPeligibility@ema.europa.eu

References:

2. How and when should the eligibility request be sent to the European Medicines Agency?

Regardless of whether the product falls into the mandatory or optional scope, or would have "automatic access" or access in accordance with the Paediatric or Advanced Therapy Regulation, an 'eligibility request' should always be submitted using the specific form and accompanied by a justification of eligibility for evaluation under the centralised procedure. The applicant should clearly address the specific criterion fulfilled by the product to be eligible for the centralised procedure. See: Question 1 "Is my medicinal product eligible for evaluation under the Centralised Procedure?".

Please note that:

  1. In cases where products fall under the 'mandatory scope' criterion (Art. 3(1) of the Regulation (EC) No. 726/2004), the relevant justification should be provided.

    For Advanced Therapy Medicinal Products (ATMPs), the relevant justification and documentation (including the European Medicines Agency scientific recommendation on classification of ATMPs by the Committee for Advanced Therapies (CAT) if available) should be provided.
    NB: Only one criterion can be chosen.
  2. In cases where products fall under one of the 'optional scope' criteria (Art. 3(2) of the Regulation (EC) No. 726/2004), the justification should consist of a concise summary document of preferably two pages stating why the product should qualify for evaluation through the centralised procedure. The applicant should clearly state in the request which criterion the appended justification concerns:
  • Art. 3(2) a New active substance; or
  • Art. 3(2) b Significant therapeutic innovation, or
  • Art. 3(2) b Significant scientific innovation or
  • Art. 3(2) b Significant technical innovation; or
  • Art. 3(2) b Interest of patient at the community level.
  • NB: Only one criterion can be chosen and must be adequately justified; e.g. eligibility in accordance with Art 3(2)b of Regulation (EC) No. 726/2004 – Significant therapeutic innovation
  1. In the following cases where the medicinal product applied for may have "automatic access" to the centralised procedure, this should be the basis for the justification to be submitted.

    When the medicinal product applied for, is either:
  • a "generic/hybrid" (Art. 3(3) of the Regulation (EC) No. 726/2004); or
  • a duplicate/multiple; or
  • an informed consent
  • to a centrally authorised medicinal product, adequate and relevant information on the already centrally authorised medicinal product should be provided as background information (such as invented name/INN/ Commission Decision date/ type of application submitted and criteria/ indent under which the medicinal product was eligible to access the centralised procedure at the time (EMA letter to be annexed)).
  1. When the medicinal product applied for, is either:
  • an application including paediatric indication(s) in compliance with an agreed PIP (Art. 28 of Regulation (EC) No 1901/2006); or
  • an application consisting of a new paediatric indication, a new pharmaceutical form and/or a new route of administration in compliance with an agreed PIP for a nationally authorised medicinal product (Art. 29 of Regulation (EC) No 1901/2006); or
  • an application for a Paediatric Use Marketing Authorisation (PUMA) (Art. 31 of Regulation (EC) No 1901/2006),
  • adequate and relevant information should be provided (such as copy of the European Medicines Agency PIP decision to be provided in annex), details of the paediatric indication/form/route applied for and a listing of the study data collected in accordance with the PIP which will be submitted in the planned application).

When submitting a request, the applicant should use the Pre-submission request form (Eligibility) and send it electronically to: CPeligibility@ema.europa.eu, together with a separate Annex 1 (draft Summary of Product Characteristics) and Annex 2 (Justification for Eligibility) especially required for medicinal products falling under the optional scope of Article 3(2) b.

The European Medicines Agency recommends providing the eligibility request preferably, at the earliest, 18 months before submission of the marketing authorisation application (MAA) and, at the latest, 7 months before the MAA is filed with the European Medicines Agency, at which point it could be submitted as part of the "letter of intent to submit". For Eligibility requests submitted as part of the "letter of intent to submit", Rapporteurs will be automatically appointed following the confirmation of the eligibility to the centralised procedure provided that the planned submission date is within 6-7 months.

The eligibility request and supporting documentation should be submitted to the European Medicines Agency 10 calendar days before the CHMP meeting, see: Question 3, "What are the dates for submission of eligibility requests?", so as to ensure its inclusion in the next CHMP agenda.

Any request received after the deadline will be considered the following month.

The eligibility will be evaluated on a case-by-case basis by the European Medicines Agency/CHMP. The applicant will, in all cases, be informed of the CHMP opinion, the week following the CHMP meeting where the discussion took place.

NB: Review of eligibility applications made under Article 3(2)b will take place over 2 consequent CHMP meetings because of the need to appoint a sponsor(s) to assess the request.

References:

2a. What are the dates for submission of eligibility requests? Rev. January 2016

Deadlines for submission of eligibility requests and dates of CHMP meetings, as follows:

20162017
Submission DeadlineDiscussion/Adoption1Submission DeadlineDiscussion/Adoption1
13 January25-28 January11 January23-26 January
10 February22-25 February8 February20-23 February
14 March29 March - 1 April8 March20-23 March
13 April25-28 April3 April18-21 April
11 May23-26 May3 May15-18 May
8 June20-23 June7 June19-22 June
6 July18-21 July5 July17-20 July

No plenary CHMP meeting in August

No plenary CHMP meeting in August

No plenary CHMP meeting in August

No plenary CHMP meeting in August

31 August12-15 September30 August11-14 September
28 September10-13 October27 September9-12 October
24 October7-10 November23 October6-9 November
30 November12-15 December29 November11-14 December

1 Please note that if your proposed basis for eligibility falls under Article 3(2)b of Regulation EC 726/2004, the Committee will have preliminary discussions on such request and appoint a sponsor to review the documentation submitted. Therefore you will not receive a formal response to your request until the following month.

3. What will be the legal basis for my application?

The applicant should clearly indicate the legal basis for the submission of their application in the EU Application Form, i.e. select one of the following articles of Directive 2001/83/EC:

  • Article 8(3) - Full application
  • Article 10 - Generic, hybrid or similar biological application
  • Article 10a - Well-established use application
  • Article 10b - Fixed combination application
  • Article 10c - Informed consent application

At pre-submission meetings, it is strongly recommended to discuss the proposed legal basis in view of the available data, with the European Medicines Agency in order to prevent difficulties at validation.

Article 8(3) - Full application:

For full applications according to Article 8(3) of Directive 2001/83/EC, the results of pharmaceutical tests (physico-chemical, biological or microbiological), pre-clinical tests (pharmacological and toxicological), and clinical trials need to be submitted. Detailed data requirements are set-out in Annex I to Directive 2001/83/EC, as amended by Commission Directive 2003/63/EC.

Any deviations from these requirements, in particular, absence of a study/test report, requires a justification as to why the results are not provided and whether the requirements as set out in the Annex I to Directive 2001/83/EC, are considered fulfilled.

Justifications are to be provided in the respective non-clinical and clinical overviews in Module 2. Further guidance on the drafting of such justifications is provided below. There is a possibility to use “umbrella” justifications to cover absence of more than one study report or more than one indent provided that is clear that the justification applies to several study reports. There is no need, however, to create and include a document in Module 4 and 5 which (only) refers to the presence of a justification in Module 2.

'Full-mixed' application:

Where Module 4 and/or 5 consists of a combination of reports of limited non-clinical and/or clinical studies carried out by the applicant and of bibliographical references this kind of application has also to be submitted according to Article 8(3) of Directive 2001/83/EC (So-called ‘full-mixed’ application - see also section on ‘mixed’ marketing authorisation application in Part II of Annex I to the Directive).

A justification for not having performed certain tests/trials and for providing literature references instead, should be provided as to why the references provided by the applicant can replace the study reports, and how the results presented fulfil the requirements as set out in the Annex I to Directive 2001/83/EC. The general principles for ‘justifications’ as outlined above also apply to full-mixed applications.

Such literature references, when replacing required study reports, should be included in the relevant Module 4/5 indents and should be summarised in Module 2 as required for any other study report. “Supportive-only” literature references (i.e. provided in addition to study reports), should be provided in the CTD sections for "references" and do not need to be summarised in Module 2.

Guidance for the preparation of the Non-clinical and/or clinical Overviews in case of Art 8.3 (Full or "Full-mixed") marketing authorisation applications:

  • For each item of section 4.1 and 5.1 of Part I of the Annex I to Directive 2001/83/EC, the Applicant should indicate whether the Application contains the results of pre-clinical tests or clinical trials in the format of detailed study reports (hereafter referred to as “study reports”), and/or in the format of bibliographical references, or no information at all.
  • If study reports are provided and cover all the requirements for a specific section, no further justifications are required.
  • If results are submitted in the form of bibliographical references for a specific item, a justification is required as to why the references provided by the applicant can replace the study reports, and how the results presented fulfil the requirements as set out in Annex I to Directive 2001/83/EC.
  • If no results are provided for a certain test or trial, a justification is required as to why the results are not provided and whether the requirements as set out in Annex I to Directive 2001/83/EC, are considered fulfilled. A simple statement such as "Not Applicable" is not an acceptable justification.

Justifications for absence of study reports in each of the sections can be based, for example, on the following principles:

  • Specific derogations foreseen in Directive 2001/83/EC;
  • Animal welfare1 and ethical considerations 2 coupled with expert assessment that further tests or trials are unlikely to extend scientific knowledge of subject area;
  • Expert assessment that repetition of certain tests or trials is unlikely to extend scientific knowledge of subject area (e.g., extent of clinical experience with active substance at the time of development to replace certain non-clinical tests);
  • Scientific argumentation regarding inapplicability of such tests and trials;
  • Inability to provide comprehensive data in accordance with Article 14(8) of Regulation (EC) No 726/2004 and as outlined in general provisions of Section 6 of Part II of the Annex to Directive 2001/83/EC (applications in exceptional circumstances);
  • Request for granting of a conditional marketing authorisation in accordance with Article 14(7) of Regulation (EC) No 726/2004 and Regulation (EC) No 507/2006.

1 Council Directive on Animal Welfare 86/609/EEC and Council Decision on the European Convention of the Protection of Vertebrae Animals
2 Declaration of Helsinki

Article 10 - Generic, hybrid or similar biological applications:

Generic applications:

According to Article 10(1) of Directive 2001/83/EC, the applicant is not required to provide the results of pre-clinical tests and clinical trials if he can demonstrate that the medicinal product is a generic medicinal product of a reference medicinal product which is or has been authorised under Article 6 of Directive 2001/83/EC for not less than 8 years in a Member State or in the Community.

A generic medicinal product is defined as a medicinal product that has:

  • the same qualitative and quantitative composition in active substances as the reference product,
  • the same pharmaceutical form as the reference medicinal product,
  • and whose bioequivalence with the reference medicinal product has been demonstrated by appropriate bioavailability studies.

This type of application refers to information that is contained in the dossier of the authorisation of the reference medicinal product, for which a marketing authorisation has been granted in the Community on the basis of a complete dossier in accordance with article 8(3), 10a, 10b or 10c of Directive 2001/83/EC.

It should be noted that the period of 8 years from initial authorisation of the reference medicinal product, providing a period of so-called “data exclusivity”, only applies to those reference medicinal products for which the initial application for authorisation was submitted through the centralised procedure after 20 November 2005.

Hybrid applications:

Hybrid applications under Article 10(3) of Directive 2001/83/EC differ from generic applications in that the results of appropriate pre-clinical tests and clinical trials will be necessary in the following three circumstances:

  • where the strict definition of a 'generic medicinal product' is not met;
  • where the bioavailability studies cannot be used to demonstrate bioequivalence;
  • where there are changes in the active substance(s), therapeutic indications, strength, pharmaceutical form or route of administration of the generic product compared to the reference medicinal product.

In such cases the results of tests and trials must be consistent with the data content standards required in the Annex to the Directive 2001/83/EC as amended by Directive 2003/63/EC.

These applications will thus rely in part on the results of pre-clinical tests and clinical trials for a reference product and in part on new data. Some guidance on the appropriate additional studies required is indicated in Annex IV of the Chapter 1 of the Notice to Applicants.

Similar biological application:

In Article 10(4) of Directive 2001/83/EC, as amended it is stated that where a biological medicinal product which is similar to a reference biological product does not meet the conditions in the definition of generic medicinal products, owing to, in particular, differences relating to raw materials or differences in manufacturing processes of the similar biological medicinal product and the reference biological medicinal product, the results of appropriate pre-clinical tests or clinical trials relating to these conditions must be provided. The type and quantity of supplementary data to be provided must comply with the relevant criteria stated in Annex I to Directive 2001/83/EC and the related detailed guidelines. The results of other tests and trials from the reference medicinal product's dossier shall not be provided.

The chosen reference medicinal product must be a medicinal product authorised in the Community, on the basis of a complete dossier in accordance with the provisions of Article 8 of Directive 2001/83/EC, as amended.

Article 10a - Well-established use application:

According to Article 10a of Directive 2001/83/EC, as amended it is possible to replace results of pre-clinical and clinical trials by detailed references to published scientific literature (information available in the public domain) if it can be demonstrated that the active substances of a medicinal product have been in well-established medicinal use within the Community for at least 10 years, with recognised efficacy and an acceptable level of safety. In this regard, the provisions of Annex I (Part II.1) to Directive 2001/83/EC shall apply.

The following criteria for the demonstration of such well-established use should be taken into account:

  • the time over which a substance has been used with regular application in patients; quantitative aspects of the use of the substance, taking into account the extent to which the substance has been used in practice, the extent of use on a geographical basis and the extent to which the use of the substance has been monitored by pharmacovigilance or other methods;
  • the degree of scientific interest in the use of the substance (reflected in the published scientific literature) and the coherence of scientific assessments;
  • For such applications, the provisions of the Annex I to Directive 2001/83/EC apply in like manner. They are considered as full and independent applications. Applicants should submit Modules 1, 2 and 3 as described in Part I of Annex I to Directive 2001/83/EC. For Modules 4 and 5, a detailed scientific bibliography shall address all required pre-clinical and clinical characteristics, and should be summarised in Module 2. As with any other full application, if parts of the dossier are incomplete, particular attention must be paid to justify such absences in the non-clinical/clinical overviews.
  • It should be noted that, if well-known substances are used for entirely new therapeutic indications, it is not possible to solely refer to a well-established use and additional data on the new therapeutic indication together with appropriate pre-clinical and human safety data should be provided. In such case, Article 8(3) of Directive 2001/83/EC should be used as legal basis.

Article 10b - Fixed combination application:

According to Article 10b of Directive 2001/83/EC, in the case of medicinal products containing active substances used in the composition of authorised medicinal products but not hitherto used in combination for therapeutic purposes, the results of new pre-clinical tests or new clinical trials relating to that combination shall be provided in accordance with Article 8(3)(i) of the same Directive, but it shall not be necessary to provide scientific references relating to each individual active substance.

The combination of active substances within a single pharmaceutical form of administration according to this provision is a so-called ‘fixed combination’.

Applications for fixed combination medicinal products can be accepted and validated under Article 10b on condition that the individual substances have been authorised as a medicinal product in the EEA via a Community or national procedure.

It follows from the wording of Article 10b as well as from Part II.5 of Annex I to the Directive 2001/83/EC as amended, that a full dossier, comprising all the information of modules 1 to 5, has to be provided in relation to the fixed combination. Any absence of specific fixed combination data should be duly justified in the Non-clinical and/or clinical Overviews (see general guidance above).

Although there is no requirement for the inclusion of data on the individual active substances, it is possible to include information on the individual substances (literature or actual data), especially in order to justify the absence of certain specific data on the combination.

Article 10c - Informed consent application:

According to Article 10c of Directive 2001/83/EC as amended, following the granting of a marketing authorisation, the authorisation holder may allow use to be made of the pharmaceutical, non clinical and clinical documentation contained in the dossier of the medicinal product for the purpose of examining subsequent applications relating to other medicinal products possessing the same qualitative and quantitative composition in terms of active substances and the same pharmaceutical form.

It is a prerequisite for the use of Article 10c as legal basis that consent has been obtained from the marketing authorisation holder of the reference product for all three modules containing the pharmaceutical, pre-clinical and clinical data (modules 3, 4 and 5), and the applicant of the informed consent application should have permanently access to this documentation or should be in possession of the information.

For such informed consent applications, only a complete module 1 should be submitted, including the Application Form with relevant Annexes (e.g. copy of correspondence with the European Commission for multiple applications, if applicable, see also question "Is my medicinal product eligible for an accelerated Assessment?", and the letter of consent from the MAH of the authorised medicinal product allowing access to modules 2, 3, 4, 5 of the initial dossier and any subsequent documentation submitted).

If the dossier of the authorised medicinal product includes an ASMF, a new letter of access should be included in module 1 of the informed consent application.

References:

4. How will I know if the proposed (invented) name of my medicinal product is acceptable from a public health point of view? Rev. February 2015

In accordance with Article 6 of Regulation (EC) No 726/2004, “each application for the authorisation of a medicinal product for human use (…), otherwise than in exceptional cases relating to the application of the law on trade marks, shall include the use of a single name for the medicinal product.” The Centralised Procedure, therefore, requires one single name for the medicinal product to be authorised.

According to Article 1(20) of Directive 2001/83/EC, as amended, the name of the medicinal product “may be either an invented name not liable to confusion with the common name, or a common name or scientific name accompanied by a trademark or the name of the Marketing Authorisation Holder”. It is also understood by legislation that a common name is according to Article 1(21) of Directive 2001/83/EC, as amended, “The international non-proprietary name (INN) recommended by the World Health Organisation, or, if one does not exist, the usual common name”.

Although it is not mandatory under Community legislation, in practice, many companies submitting marketing authorisation applications under the Centralised Procedure wish to use invented names for their medicinal products.

As part of the EMA’s role in evaluating the safety of medicinal products in the centralised procedure, it is obliged to consider whether the (invented) name proposed for a medicinal product could create a public-health concern or potential safety risks.

In particular, the (invented) name of a medicinal product:

  • should not be liable to cause confusion in print, handwriting or speech with the (invented) name of an existing medicinal product.
  • should not convey misleading therapeutic or pharmaceutical connotations;
  • should not be misleading with respect to the composition of the product;

In order to identify, at an early stage, potential difficulties presented by the (invented) name(s) proposed by an applicant, the EMA/CHMP set up the Name Review Group (NRG), to perform the review of names. The NRG is also responsible for updating the “Guideline on the acceptability of names for human medicinal products processed through the centralised procedure” (EMA/CHMP/287710/2014 ).

It should be highlighted that when an applicant/ MAH wishes to use instead of an invented name the common name or scientific name, together with a trademark or the name of the Marketing Authorisation Holder, this is also subject to NRG review.

The Name Review Group (NRG)

The NRG is composed of representatives of EU Member States and is chaired by an EMA representative. Representatives of the European Commission and the EMA Secretariat also participate in the work of the group. Other relevant experts (e.g. WHO experts) are consulted on a case-by-case basis.

The NRG meets 6 times a year (approximately every 2 months). Its conclusions are presented for adoption at the subsequent CHMP plenary meeting. 

The criteria applied by the NRG when reviewing the acceptability of proposed invented names are detailed in the “Guideline on the acceptability of names for human medicinal products processed through the centralised procedure” (EMA/CHMP/287710/2014 ), hereafter referred to as the ‘Guideline’.

The EMA procedure for checking proposed (invented) names

Submission of the (invented) name request by the Applicant/MAH

Provided that the medicinal product is eligible for evaluation under the Centralised Procedure, the applicant should inform the EMA of the proposed (invented) name(s) for their medicinal product at the earliest 18 months and preferably 4-6 months prior to the planned submission date of the marketing authorisation application. See also Question 4a. What are the dates for submission of invented name requests for the deadlines for submission of Proposed (Invented) Names.

Applicants may submit a name review request after eligibility has been confirmed by the CHMP or in parallel to the eligibility request. Applicants are advised to contact the NRG secretariat prior to submission of the name review request form for advice if eligibility is not yet confirmed at that time.

The ‘Proposed Name Request form’, along with either a draft Summary of Product Characteristics (SmPC) or a product profile and any other relevant information, should be sent to the EMA at the following e-mail address: NRG@ema.europa.eu. An electronic request form (in PdF format) has been developed and replaces the current form in Word format.

Up to two (invented) names can be accepted per Marketing Authorisation Application from which the applicant should select the final name to be used. Up to two newly proposed (invented) names can be considered at each NRG meeting per Marketing Authorisation Application.

It should be noted that once two (invented) names have been deemed acceptable by the NRG for a Marketing Authorization Application, no further review of newly proposed names is allowed unless agreed with EMA on duly justified grounds (i.e. identification of safety issue/health concern after acceptance of (invented) names, conditional acceptability of previously reviewed (invented) names, constraints achieving a global (invented) name, issues relating to the application of the law on trademarks, etc.).

Applicants should follow the criteria described in the ‘Guideline’ when proposing (invented) names and would be expected to review the proposed (invented) name, applying the criteria before requesting that an invented name be considered. Where the applicant deviates from these criteria, justification should be provided.

Where the applicant submits proposed (invented) names intended to be used in the context of multiple marketing authorisations/applications, it shall specifically request the NRG to consider whether the proposed (invented) names cannot be considered potentially confusing with each other (see also question on Multiple Applications).

Consultation with the Member States and NRG discussion/CHMP adoption

The proposed (invented) name(s) and all the background information provided by the applicant(s)/MAH(s) are sent to every NRG contact point nominated by National Competent Authorities (NCAs) of EU Member States for their review and will subsequently be discussed at the NRG meeting. The detailed procedure is described in the ‘Guideline’.

The NRG conclusions/recommendations are presented for adoption to the subsequent CHMP plenary meeting, after which the applicant will be informed of the outcome of the discussion on the acceptability of the proposed (invented) name(s) for their medicinal product together with the reasons and source for the objections(s) raised, where applicable. See also Question 4a. for the dates of NRG discussion/CHMP adoption.

Rejection by NRG/CHMP of a proposed (invented) name

In case of rejection of a proposed (invented) name by NRG/CHMP, the applicant/MAH has the following possibilities:

  • To submit up to two new (invented) names proposals, which are checked through the same procedure as described above. In the case that a name has already been accepted in a previous NRG meeting and two new names are submitted, the applicant is required to indicate in the ‘Proposed (Invented) Name Request form’ which two names should be finally retained in the NRG database.
  • To provide a justification to retain the (invented) name (addressing specifically all the objections raised) using the ‘Proposed (Invented) Name Request form’ and selecting ‘Justification Form’ in the ‘Form Type’ area. Such justification will be reviewed as described in the ‘Guideline’. If the proposed (invented) name cannot be accepted prior to submission, the Marketing Authorisation Application can be submitted under either any of the proposed (invented) names or the common name or scientific name accompanied by a trademark or the name of the MAH.

Applicants may submit justifications for rejected names in addition to the entitlement of 2 (invented) names reviewed per meeting. However, only two accepted names can be retained in the NRG database and therefore the applicant should indicate in advance which two names should be retained in case that they are accepted.

At the latest one month prior to the adoption of the CHMP opinion on the concerned MAA, the applicant will in such case have to inform the EMA and the NRG Secretariat on the acceptable invented name of their choice.

  • If no suitable invented name has been identified at that stage, the opinion will be adopted using the common name or scientific name accompanied by the name of the MAH. Applicants are hereby reminded that such name also needs NRG review and acceptance by the CHMP prior to the adoption of the opinion. In this case, as soon as the Commission Decision is granted, the MAH may submit a variation to introduce an invented name, on the condition that such name has been considered acceptable by the NRG.
  • Exceptionally, provided all means have been exhausted, the applicant/MAH may request the matter to be presented to the CHMP within the context of the evaluation of the medicinal product (e.g. oral explanation).

Change of the (invented) name after the marketing authorisation is granted

In accordance with Commission Regulation (EC) No 1234/2008, the (invented) name of a medicinal product may be changed after a marketing authorisation is granted through a Type IAIN (No A.2) variation procedure.

This can be done either in case of a marketing authorisation being granted under INN or common name together with a trademark or the name of the MAH or in case the MAH wants to change the initial invented name.

Such Type IAIN variation is possible provided that the check by the Agency on the acceptability of the new name had been finalised and was positive before implementation of the new name. Immediately upon implementation of the change, the MAH must submit a Type IAIN variation notification to the Agency for review (see the EMA Post-Authorisation Procedural Advice on Type IA variations).

Taking into account that the MAH will be required to submit the EMA letter of acceptance of the concerned (invented) name as part of the variation application, it is recommended that the proposed invented name be submitted at least 4-6 months in advance of the foreseen implementation date and submission of the Type IAIN variation notification.

References

4a. What are the dates for submission of (invented) name requests? Rev. July 2016

Deadlines for submission of proposed (invented) names and dates of NRG discussion/CHMP adoption follow the CHMP time schedule:

20162017
Submission deadline for new (invented) name applications and justificationsNRG meeting/discussionSubmission deadline for new (invented) name applications and justificationsNRG meeting/discussion
27 November 20153 February25 November 20161 February
12 February6 April3 February29 March
15 April1 June7 April31 May
20 May6 July19 May6 July
8 July21 September7 July20 September
30 September23 November29 September22 November

CHMP will adopt the conclusions at the next plenary meeting following the NRG meeting.

5. How shall I compose the complete name of my medicinal product?

Each medicinal product should be placed on the market under a name and in a package suitable to ensure identification and differentiation. A medicinal product authorised under the Centralised Procedure must have the same name in all EU Member States.

The medicinal product should be identified in the product information according to the following rule: the name of the medicinal product should be followed by the strength and the pharmaceutical form. However, when otherwise referring to the medicinal product throughout the product information text, the strength and the pharmaceutical form do not have to be mentioned in the name.

In the SPC, the INN or the common name of the active substance should be used when referring to properties of the active substance(s) rather than the invented name. The use of pronouns (e.g. “it”) is encouraged whenever possible.

Thus, whenever the "name of the medicinal product" is specifically required to be provided in the SPC, labelling (on the outer or immediate packaging or on blisters) or the Package Leaflet, it should be written in the following order as:

{(invented) name strength pharmaceutical form}, whereby

  • invented name: no ® ™ symbols attached
  • Pharmaceutical form:
    The pharmaceutical form should be stated according to the full "Standard Terms" published by the Council of Europe, in the singular (except for tablets and capsules). Where the Council of Europe short standard term is used on small immediate packaging materials (blisters, strips, small immediate packaging units) in case of space limitation, the short term should be added in brackets in section 3 of the SPC.

    E.g. (invented name) X mg hard capsules
    (invented name) Y mg/g cream
  • The different strengths of fixed-combination products should be presented separated by a "/".

    E.g. (invented) name 150 mg/12.5 mg tablets

    For mock-ups and specimens, this information may be presented on different lines of text or in different font sizes if necessary, provided that the appearance of the name is as an integrated item.

    E.g. (invented) name Z mg/ml
    Solution for injection

    Where the INN or the common name is to be provided in addition to an invented name, this should preferably be given on the line of text directly below the complete name.

References:

6. What legal status can I obtain for my medicinal product?

In accordance with Article 9(4)(b) of Regulation (EC) No 726/2004, the documents annexed to the CHMP favourable opinion to the granting of a Marketing Authorisation for a medicinal product shall include "details of any conditions or restrictions which should be imposed on the supply or use of the medicinal product concerned, including the conditions under which the medicinal product may be made available to patients, in accordance with the criteria laid down in Title VI of Directive 2001/83/EC, as amended".

The classification for the supply of the medicinal product to the patient is also referred to as 'Legal Status'.

Categories for the Legal Status of a medicinal product

At the first level, 'main categories', the medicinal product is classified either as:

  • subject to medical prescription or
  • not subject to medical prescription

To this end, the criteria laid down in Article 71(1) of Directive 2001/83/EC, as amended, should be taken into account.

For products subject to medical prescription, where applicable, there is a second level and the European Medicines Agency may have to apply one of the following additional 'sub-categories', in accordance with Article 70(2) of Directive 2001/83/EC as amended:

  • Medicinal product subject to special medical prescription
  • Medicinal product on restricted medical prescription, reserved for use in certain specialised areas

To this end, the factors laid down in Article 71 paragraphs 2 and 3 should be taken into account.
Medicinal products, which meet the criteria for both above-mentioned 'sub-categories', will be subject to special and restricted medical prescription.

There is another 'sub-category' foreseen in Article 70(2) of Directive 2001/83/EC, as amended, i.e.: 'medicinal products on medical prescription for renewable or non-renewable delivery'. The definition and therefore also the implementation may vary in those Member States where the 'sub-category' exists. Therefore it has been decided that for centrally authorised products such 'sub-category' will not be explicitly mentioned in the Opinion/Decision, leaving for Member States the possibility of the implementation of the 'sub-category' in accordance with national measures and in compliance with the content of the SPC.

Implementation of the Legal Status in the CHMP Opinion

At the pre-submission stage applicants should include a proposed classification for the supply of the medicinal product in their "notification of intention to submit an application" to be sent to the European Medicines Agency at least 7 months before submission. At the time of the submission of the application applicants should indicate their proposal for Legal Status in the section 2.3 of the Module 1 application form (available in the Notice to Applicants (NTA) Volume 2B - Application Form: Module 1.2 Application form (PDF or WORD).

The CHMP refers to the above-mentioned criteria and factors where it comes to take a decision on the Legal Status.

The Legal Status will be mentioned in the CHMP opinion and in the Commission decision.

In the CHMP opinion, the Legal Status will be reflected in the following annexes:

  • Annex I of the CHMP opinion (Summary of Product Characteristics)
    Wherever appropriate, the SPC will include in section 4.2 an explanation on how the medicinal product should be supplied to patients (e.g. to be administered in a hospital setting or prescribed by specialists only, or specific type of care during the treatment of a chronic disease).
  • Annex II.B of the CHMP opinion (Conditions or restrictions regarding supply and use) should mention one of the categories below:
    • medicinal product not subject to medical prescription
    • medicinal product subject to medical prescription
    • medicinal product subject to special medical prescription
    • medicinal product subject to restricted medical prescription (See Annex I: Summary of Product Characteristics, section 4.2)
    • medicinal product subject to special and restricted medical prescription (See Annex I: Summary of Product Characteristics, section 4.2)
  • Annex III.A of the CHMP opinion (Labelling)

The outer packaging should mention either "medicinal product not subject to medical prescription" or "medicinal product subject to medical prescription" (without specifying "restricted" and/or "special").

As regards mock-ups and specimens, the use of any 'sub-category' at national level (e.g. renewable/non-renewable) and the information required to express this, should be addressed in the blue box. See question "When shall I submit mock-ups and/or specimens?".

This information may concern either one, or more, 'sub-categories' listed in Article 70(2) of Directive 2001/83/EC as amended, or a specific way of conveying particular information about the Legal Status. Some Member States use symbols or expressions/specific wordings. Such symbols or expressions are set out in the Annex to the Guideline on the packaging information of medicinal products for human use authorised by the Community. The European Medicines Agency strongly advises Applicants to follow this guideline since compliance with the guideline ensures compliance with Community legislation.

Change of Legal Status

According to Article 74 of Directive 2001/83/EC as amended, when new facts are brought to its attention, the EMA shall examine and, as appropriate, amend the classification of a centrally authorised medicinal product, by applying the criteria listed in Article 71 of that Directive.

The data requirements for an application to change the classification for the supply of a medicinal product from to prescription to non-prescription ("Switch") are outlined in Part 2 of the Guideline on changing the classification for the supply of a medicinal product for human use.

In addition, according to Article 74a of the same Directive, a change of classification may benefit from one year of protection. This 1-year period of protection covers significant pre-clinical tests or clinical trials carried out for the purpose of substantiating an application for a change of classification. Commission decisions authorising a change of classification will contain a clear statement of whether the change is based on significant pre-clinical tests or clinical trials. A change of classification authorised after 20 November 2005 may benefit from this year of protection.

Further information on Legal Status is provided in the Guideline on legal status for the supply to the patient of centrally authorised medicinal products.

References:

7. What is the procedure for appointment of CHMP/PRAC/CAT Rapporteurs/Co-Rapporteurs and their assessment teams?

General principles

For any scientific evaluation in respect of a procedure, a Rapporteur, and if relevant a Co-Rapporteur, shall be appointed from amongst the members of the Committee for Medicinal Products for Human Use (CHMP) and alternate members. In addition, for activities covering all aspects of the risk management of the use of human medicinal products, a Rapporteur, and if relevant a Co-Rapporteur, shall be appointed from amongst the members of the Pharmacovigilance Risk Assessment Committee (PRAC) and alternate members. For Advanced Therapy Medicinal Products (ATMP), a Rapporteur, and if relevant a Co-Rapporteur, shall be appointed from amongst the members of the Committee for Advanced Therapies (CAT) and alternate members. In addition two CHMP Co-ordinators will be appointed (one supporting the CAT Rapporteur assessment team and another supporting the CAT Co-Rapporteur assessment team). 

The appointment of any Rapporteur/Co-Rapporteur is made on the basis of objective criteria, which will ensure the provision of objective scientific opinions and will allow the use of the best and available expertise in the European Economic Area (EEA) on the relevant scientific area.

Requesting the appointment of CHMP/PRAC/CAT Rapporteurs/Co-Rapporteurs and their assessment teams

Applicants shall request the appointment of CHMP/PRAC/CAT Rapporteurs/Co-Rapporteurs (in the following only described as (Co-) Rapporteurs) by sending a completed Pre-submission request form (selecting the indent “Intent to submit MA”) to pa-bus@ema.europa.eu. The pre-submission request form can be accompanied by a cover letter. This notification is also called the “letter of intent”.

We advise applicants to notify the EMA of their intent to submit and request assignment of (Co-) Rapporteurs 7 months prior to the intended submission date. Although applicants may submit the letter of intent earlier than 7 months prior to the intended submission date, the (Co-) Rapporteurs appointment procedure will not be initiated prior to that date.

Intended MAA submission dates must be as realistic and accurate as possible as such information is crucial to the EMA and to the future appointed (Co-) Rapporteurs and their assessment teams for planning purposes.

The (Co-) Rapporteurs appointment procedure takes one month and applicants are notified about the outcome. It is the responsibility of the applicant to liaise with the EMA in due course to confirm its intended submission date and request (Co-) Rapporteurs appointment.

For submission deadlines for letters of intent see Q&A 7a.

Please be aware that separate pre-submission forms have to be submitted for requesting eligibility and the appointment of (Co-) Rapporteurs (selecting the corresponding indents on the first page of the pre-submission form), even if an applicant submits both requests in parallel.

Please note that the Applicant’s proposals/preferences are not considered for the appointment of (Co-) Rapporteurs.

Appointment of (Co-) Rapporteurs and their assessment teams for different application types / procedures

Full applications

In the pre-authorisation phase of a full Marketing Authorisation Application (MAA), two Rapporteurs (i.e. a Rapporteur and a Co-Rapporteur) are appointed. The two Rapporteurs are usually members/alternate members of the CHMP, except for ATMPs, where the Rapporteur and Co-Rapporteur are appointed amongst the CAT members/alternate members with two Co-ordinators appointed from the CHMP.

Furthermore a PRAC Rapporteur and a Co-Rapporteur will be appointed.

Generic/hybrid medicinal products

Due to the particularities of generic/hybrid applications (e.g. legal basis, data requirements), the following principles are considered for the appointment of CHMP/PRAC Rapporteurs/Co-Rapporteurs and their assessment teams:

  • A CHMP Rapporteur is appointed for the scientific evaluation of a generic/hybrid medicinal product. For the scientific evaluation of a generic application there is usually no Co-Rapporteur required.
  • For the scientific evaluation of a hybrid medicinal the appointment of a Co-Rapporteur is considered on a case-by-case basis (depending on the particularity of the applied hybrid medicinal product).
  • For a generic/hybrid medicinal product, a CHMP pharmacovigilance (PhV) Rapporteur is appointed. The CHMP PhV Rapporteur is the same CHMP member/alternate as the CHMP Rapporteur of the reference medicinal product as applicable.
  • Furthermore a PRAC Rapporteur will be appointed.
Similar biological medicinal products

For the scientific evaluation of a similar biological medicinal product CHMP and PRAC Rapporteurs and Co-Rapporteurs will be appointed.

Non-prescription medicinal products

Due to the particularities of non-prescription medicinal products (e.g. self-care environment, data requirements), the following principles are considered for the appointment of CHMP/PRAC Rapporteurs/Co-Rapporteurs and their assessment teams:

  • For the scientific evaluation of a non-prescription medicinal product CHMP and PRAC Rapporteurs and Co-Rapporteurs shall be appointed.
    • In the pre-authorisation phase the CHMP/PRAC Rapporteurs and Co-Rapporteurs shall be involved.
    • In the post-authorisation phase, when a change in legal status is foreseen (e.g. switch from prescription to non-prescription), a CHMP peer reviewer shall be appointed to work with the existing CHMP/PRAC Rapporteurs and Co-Rapporteurs already in place for the given medicinal product.
Re-examination of a CHMP opinion

In cases of re-examination of a CHMP opinion a CHMP/CAT Rapporteur and a Co-Rapporteur shall be appointed. In case a PRAC Rapporteur is deemed necessary, he/she will be appointed. For CHMP opinions where the CHMP/CAT Co-Rapporteur was not involved in the initial evaluation, no re-examination Co-Rapporteur needs to be appointed. A different CHMP/CAT Rapporteur and, where applicable, a different CHMP/CAT Co-Rapporteur from those appointed for the initial evaluation shall be appointed in order to adequately assess the grounds for the re-examination of the CHMP opinion. These Rapporteurs will coordinate the evaluation for the duration of the re-examination procedure only.

The Rapporteur, Co-Rapporteur (if applicable) appointment process will be initiated as soon as the EMA/CHMP receives written notice that the applicant/MAH wishes to request a re-examination of the CHMP opinion.

Ancillary medicinal substances or ancillary human blood derivatives incorporated in medical devices

The notified body is requested to submit the letter of intent at least 6 months before the expected date of submission.

A CHMP Rapporteur and Co-Rapporteur, if appropriate, will be appointed.

References

7a. What are the submission dates for Rapporteur appointment requests? Rev. June 2016
20162017
Submission DeadlineAppointmentSubmission DeadlineAppointment
13 January22-25 February11 January20-23 February
10 February29 March - 1 April8 February20-23 March
14 March25-28 April8 March18-21 April
13 April23-26 May3 April15-18 May
11 May20-23 June3 May19-22 June
8 June18-21 July7 June17-20 July
6 July12-15 September5 July11-14 September
No plenary CHMP meeting in AugustNo plenary CHMP meeting in AugustNo plenary CHMP meeting in AugustNo plenary CHMP meeting in August
31 August10-13 October30 August9-12 October
28 September7-10 November27 September6-9 November
24 October12-15 December23 October11-14 December
30 November23-26 January 201729 November22-25 January 2018

 

8. How should I notify a change in the intended submission date of my application? NEW May 2015

In case the previously indicated submission date of an upcoming application for marketing authorisation is changed, the applicant shall inform the EMA by re-sending to pa-bus@ema.europa.eu the completed Pre-Submission request form (pre-submission request form), where the scope of request should be selected as “notification of change” and the new intended date of submission indicated in the corresponding field. The text of the e-mail should also describe the type of the change requested.

The change in intended MAA submission date must be notified as soon as possible. Since this information is crucial to the EMA and to the appointed (Co-) Rapporteurs and their assessment teams for planning purposes the intended submission date should be accurate and realistic. In some cases, a change in the planned submission data could lead to re-appointment of one or several Rapporteurs, if the previously appointed Rapporteur(s) will not be able to perform the assessment according to the new timings. In such case the applicants will be informed accordingly.

References

9. What is the role of the EMA product team? NEW April 2015

An EMA 'Product Team' is set up for each medicinal product submitted through the centralised procedure. The Product Team is responsible for providing support to the evaluation activities of the EMA scientific committees. In particular this includes:

  • Provision of procedural guidance concerning all pre authorisation activities directly preceding the application and liaison with the (Co-)Rapporteurs in the conduct of such activities;
  • Provision of advice to (Co-)Rapporteurs/committee members/applicant concerning all questions of a regulatory or procedural nature;
  • Provision of advice to the applicant in the technical preparation of the marketing authorisation application and subsequent validation of such applications;
  • In collaboration with the (Co-)Rapporteurs assessment teams production of the List of Questions, List of Outstanding Issues, draft summary of product characteristics to support committees discussion/adoption:
  • Supporting the (Co-)Rapporteurs with regulatory, technical advice in briefing / debriefing / clarification meetings with applicants;
  • To support planning and conduct of oral explanations, ad-hoc expert groups, referral to Working Parties, Scientific Advisory Groups etc;
  • Managing the timeframe of the procedure to ensure it remains within legal timeframe;
  • Co-ordinating the linguistic check of product information to ensure consistency and high quality;
  • Informing the (Co-)Rapporteurs on elements of regulatory and scientific consistency of the application of quality, safety and efficacy guidelines in the conduct of the evaluation procedure;
  • To prepare the committee assessment report and subsequent Summary of Opinion (SMOP) and European Public Assessment Report (EPAR).

The Product Team is established during the pre-submission phase of the initial marketing authorisation application and is in place post-authorisation. It ensures oversight of all elements of product knowledge through the complementary contributions of the various team members. The composition of the team is adapted over time depending on the complexity of the product and procedure as well as the type of issues raised during the product’s lifecycle. From an applicant’s perspective the following team members are particularly relevant:

  • the procedure manager, or PM, to oversee all aspects of the management of specific procedures. Procedure Managers ensure regulatory consistency at EMA and are responsible for managing the regulatory process for each application. The PM is supported by the procedure assistant (PA) in terms of administrative and secretarial aspects.
  • the EMA product lead, or EPL, to maintain oversight of a medicine as it moves through the different stages of its lifecycle.

The applicant will be notified of the appointed PM, including their contact details via the eligibility outcome letter and of the EPL in the CHMP Rapporteur appointment letter. Any subsequent change to the resource allocation for these functions will be communicated to the applicant/marketing authorisation holder.

Further team members assigned for each product are representing the functions of quality, risk management, labeling review and regulatory affairs. Specialised functions, like inspections and signal validation, will be involved as required.

Please see other relevant questions and answers in the EMA pre-authorisation guidance "Who is my contact at the European Medicines Agency during a marketing authorisation application (MAA) evaluation procedure?" and in the EMA post-authorisation guidance "Who is my contact at the European Medicines Agency during post-authorisation procedures?", "Who is my contact at the European Medicines Agency during an application procedure for extension of indication?" and "Who is my contact at the European Medicines Agency during the post-authorisation phase outside any evaluation procedures?".

10. Who is my contact at the European Medicines Agency during a marketing authorisation application (MAA) evaluation procedure? NEW April 2015

In the context of an initial marketing authorisation application (MAA) evaluation in the centralised procedure, the Procedure Manager (PM) is the primary contact for the applicant prior to submission and throughout the procedure until the decision is granted by the European Commission.

The applicant will be notified of the allocated PM at time of confirmation of eligibility to the centralised procedure.

The PM will serve as the main liaison person between the EMA product team, the Rapporteurs and the applicant. The PM, in close co-operation with the EMA Product Lead (EPL) and the rapporteurs, will ensure that the applicant is kept informed of all aspects related to the MAA evaluation.

The applicant should contact the PMfor all questions regarding the evaluation procedure, including

  • Requests for guidance in the pre-submission phase, such as the pre-submission meeting;
  • Any type of procedural questions during the evaluation, such as availability of assessment reports and Opinion documents;
  • Discussion on timetables including requests for extension of clock-stops;
  • Any question where guidance related to the evaluation procedure is needed; in such cases the PM will address or liaise and redirect as appropriate.

Questions concerning the validation of the MAA, once submitted, will be dealt with by an assigned Validation Officer.

At certain milestones during the evaluation procedure, the EPL will contact the applicant for a direct exchange to facilitate the discussion on the scientific evaluation. These include:

  • Preparation and conduct of clarification meetings (where applicant requests such meeting);
  • Immediate feedback regarding scientific aspectsfrom committee plenary discussions, where required ;
  • Expectations relating to the Oral Explanation, including topics to be addressed;
  • Discussion of required post-authorisation measures;
  • Late-stage revisions of the product information before adoption of the final Opinion.

These interactions occur in close co-operation with the Rapporteurs. Occasionally other members from the EMA Product team may contact the applicant directly to facilitate the discussion on specific aspects (e.g. quality, risk management, mock-up review).

Where the applicant is in direct contact with the EPL or another member of the EMA Product Team the PM should always be copied in the correspondence.

Please see other relevant questions and answers in the EMA pre-authorisation guidance "What is the role of the EMA product team?" and in the EMA post-authorisation guidance "Who is my contact at the European Medicines Agency during post-authorisation procedures?", "Who is my contact at the European Medicines Agency during an application procedure for extension of indication?" and "Who is my contact at the European Medicines Agency during the post-authorisation phase outside any evaluation procedures?".

11. Is my product eligible for an accelerated Assessment? Rev. March 2016

Legal basis and general principles

According to Articles 6(3) and 7c of Regulation (EC) No 726/2004, the maximum timeframe for the evaluation of a marketing authorisation application under the Centralised Procedure is 210 days, excluding clock stops when additional written or oral information is to be provided by the applicant in response to questions asked by the CHMP.

However, according to Recital 33 and Article 14(9) of Regulation (EC) No 726/2004, the applicant may request an accelerated assessment procedure in order to meet, in particular the legitimate expectations of patients and to take account of the increasingly rapid progress of science and therapies, for medicinal products of major interest from the point of view of public health and in particular from the viewpoint of therapeutic innovation.

Applicants requesting an accelerated assessment procedure should justify that the medicinal product is expected to be of major public health interest. Based on the request, the justifications presented, and the recommendations of the Rapporteurs, the CHMP will formulate a decision. Such a decision will be taken without prejudice to the CHMP opinion (positive or negative) on the granting of a marketing authorisation.

Applicants are reminded that evidence requirements for applications to be assessed under accelerated assessment are the same as for other applications.

If the CHMP accepts the request, the timeframe for the evaluation will be reduced to 150 days. This time frame will be split into 3 phases of 90+30+30 days of assessment. The applicants will be allowed to have one month clock-stop by default for preparation of responses to Day 90 List of Questions and no clock stop by default after Day 120 List of Outstanding Issues.

In case of advanced therapy medicinal products, due to the need to include more scientific committees in the review of the application, the 150-day timetable will be adapted differently and split into 2 phases of 120+30 days of assessment.


Request for an accelerated assessment: timing and justification

Before the submission of a potential request for accelerated assessment, applicants should seek guidance from the Procedure Manager to ensure timely submission of their request.

It is strongly recommended that applicants request a pre-submission meeting six to seven months before submission to prepare for evaluation under accelerated assessment. In this meeting, they can discuss their proposal for accelerated assessment with rapporteurs from the CHMP, the PRAC (and CAT in case of an advanced therapy medicinal product) and the EMA and present the data package and risk management plan they intend to include in their application.

Any request for accelerated assessment should be made as early as possible before the actual submission of the marketing authorisation application (and at least 2-3 months before the actual submission).

Applicants requesting an accelerated assessment procedure should duly substantiate the request and in particular, justify their expectation that the medicinal product is of major public health interest particularly from the point of view of therapeutic innovation. There is no single definition of what constitutes major public health interest. This should be justified by the applicant on a case-by-case basis.

The justification should include the major benefits expected and present the arguments to support the claim that the medicinal product introduces new methods of therapy or improves on existing methods, thereby addressing to a significant extent the greater unmet needs for maintaining and improving public health.

The key items to be described in the justification, and the appropriate level of detail, should be evaluated on a case-by-case basis. The request should be presented as a short but comprehensive document (ideal length 5-10 pages).

For further guidance on aspects that could be considered in the justification please refer to section 4 of the CHMP guideline on the scientific application and the practical arrangements necessary to implement the procedure for accelerated assessment pursuant to Article 14(9) of Regulation (EC) No 726/2004 (EMA/CHMP/697051/2014).


Early identification of a need for pre-authorisation inspection(s)

The EMA has a legal obligation to verify the Good Clinical Practices (GCP) and Good Manufacturing Practices (GMP) compliance of studies and manufacturers for applications for marketing authorisation. In order to better anticipate and integrate routine GCP and pre-approval GMP inspections into the accelerated assessment procedure the applicants should provide with their request for an accelerated assessment also the following information (using the published templates) that should be accurate, complete and reflect the content of the application dossier that will be submitted:

Concerning GMP aspects (template to be used)

For all manufacturers to be included in the planned dossier:

  • name and address of the manufacturer,
  • short description of manufacturing activities performed by the manufacturer,
  • past GMP compliance history of the manufacturing site and details of any inspections by other authorities anticipated during the marketing authorisation assessment,
  • confirmation of GMP inspection readiness of the manufacturer.

If any of the third country manufacturing sites have never been inspected by a competent authority of an EU/EEA member state or a country with appropriate Mutual Recognition Agreement, the applicants intending to request accelerated assessment are advised to contact EMA inspection services at GMPINS@ema.europa.eu at least three months prior to the submission of the application for marketing authorisation. Applicants are also advised to include this as a topic for discussion in the pre-submission meeting with the EMA.

Concerning GCP aspects (template to be used)

The Applicant should provide the list of all the pivotal clinical studies (protocol number and title) and for each pivotal study:

  • the study synopsis (or a mature draft with information at least on the design and conduct of the study),
  • a short discussion of the GCP compliance status (listing any GCP non-compliance identified, any breach of GCP, providing information on any site excluded including the reasons etc.),
  • list of investigators and their addresses,
  • number of subjects enrolled at each site,
  • information on study administrative structure,
  • list of GCP inspections conducted/plannedby any regulatory authority (indicating the site inspected/to be inspected, the date of inspection and the regulatory authority involved). Alternatively, a confirmation that no inspections had been requested nor taken place and that no inspections are planned.

In case a need for an inspection is identified, the inspection will be requested as early as possible in the evaluation procedure in order to accommodate the inspection within the accelerated timetable (please refer also to questions "When can I expect a pre-approval GCP inspection and how are they conducted?" and "When can I expect a pre-authorisation GMP inspection and how are they conducted?". It should also be noted that when a triggered GMP and/or GCP inspection cannot be accommodated within the agreed time frame, the procedure timetable may need to be amended as necessary.


Submission and assessment of the request

When submitting an accelerated assessment request, the applicant should use the templates for:

which should be sent, electronically, to: pa-bus@ema.europa.eu.

Following receipt of the request, the Rapporteurs will produce a briefing note including the Rapporteurs’ recommendations as to the appropriateness of an accelerated assessment. The CHMP will consider the request submitted by the applicant, the Rapporteurs’ recommendations and the views of other CHMP members, in order to conclude on the acceptability or not of the request. If necessary, the CHMP may request clarifications from the applicant about the request. The CHMP conclusions will be communicated to the applicant and the outcome of the request made public in the CHMP meeting highlights and minutes. The reasons for accepting or rejecting the request will also be summarised in the CHMP assessment report.

If a request for an accelerated assessment procedure is granted, the CHMP will take into consideration the standard timetable agreed for the accelerated assessment procedure (see, Section 6 of the Guideline on the procedure for accelerated assessment pursuant to Article 14(9) of Regulation (EC) No 726/2004” (EMA/CHMP/697051/2014) and the detailed assessment timetables published on the EMA website.

References

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