Generic / hybrid applications: questions 1 to 10

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This page lists questions 1 to 10 of the European Medicines Agency's questions and answers on generic and hybrid applications.

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 generic or hybrid medicinal product eligible for evaluation under the Centralised Procedure?

Regulation (EC) No 726/2004, creates 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 Community market. The types of products, which fall within the scope of the Regulation, are set out in Article 3 and the Annex to that Regulation.

For generic and hybrid medicinal products eligibility can be granted to the Centralised procedure as follows:

Generic/Hybrid medicinal product of a Centrally authorised product:

Generic/hybrid medicinal product applications of medicinal products authorised via the Centralised procedure have automatic access to the Centralised procedure under Article 3(3) of Regulation (EC) No 726/2004.

For generic/hybrid applications of a centrally authorised product, the applicant should state in their ‘Letter of intention to submit’ that they have automatic access to the Centralised procedure under Article 3(3).

Before submission of the dossier, applicants should notify the EMA of their intention to submit an application, preferably 6-18 months in advance (see Pre- Submission guidance on letter of intention and documentation to submit and justify why the product should qualify for the eligibility for the centralised procedure, citing the relevant specific provision(s) of Regulation (EC) No 726/2004.

EMA will inform the applicant on the outcome of the eligibility request.

Generic/Hybrid medicinal product of a National/MRP/DCP product:

Generic/hybrid medicinal product applications of medicinal products authorised via the national/MRP/DCP procedure could, at the request of the applicant, be accepted for consideration under the centralised procedure, when the applicant shows that the medicinal product constitutes:

  • a significant therapeutic, scientific or technical innovation, or
  • the granting of a Community authorisation for the medicinal product is in the interest of patients at Community level.

For further guidance, reference is made to the ‘Guideline on Article 3(2) of Regulation (EC) No 726/2004 – Optional scope of the Centralised procedure

Before submission of the dossier, applicants should notify the EMA of their intention to submit an application, preferably 6-18 months in advance (see Pre- Submission guidance on letter of intention and documentation to submit and justify why the product should qualify for the eligibility for the centralised procedure, citing the relevant specific provision(s) of Regulation (EC) No 726/2004.

EMA will inform the applicant on the outcome of the eligibility request.

References:

2. What is the legal basis for my application?

The legal requirements and the procedures for making an application for a marketing authorisation are set out in Directive 2001/83/EC and in Regulation (EC) No 726/2004.

For generic and hybrid applications the legal basis can be found in Article 6 of Regulation (EC) 726/2004 and Article 10 of Directive 2001/83/EC.

It should be noted that at the time of submission of the generic/hybrid application, the protection period of the reference medicinal product should have expired in order to allow the applicant to rely on the dossier of the reference medicinal product (see Q12).

Generic medicinal product

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 Union. The period of 8 years from initial authorisation of the reference medicinal product, providing a period of so-called “data exclusivity”, applies only for reference medicinal products for which the marketing authorisation application has been submitted as of 30 October 2005 for MRP, DCP and national procedures and as of 20 November 2005 for centralised procedure according to the revised Community Legislation. (See Question 12).

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

  • the same qualitative and quantitative composition in active substance(s) 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.

Hybrid medicinal product

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.

The type of applications mentioned above refer 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 Union on the basis of a complete dossier in accordance with article 8(3), 10a, 10b or 10c of Directive 2001/83/EC.

References

3. What is the so-called ‘reference medicinal product’ referred to in the application for a generic or hybrid medicinal product?

The reference medicinal product is a medicinal product which has been granted a marketing authorisation by a Member State or by the Commission on the basis of a complete dossier, i.e. with the submission of quality, pre-clinical and clinical data in accordance with Articles 8(3), 10a, 10b or 10c of Directive 2001/83/EC and to which the application for marketing authorisation for a generic/hybrid medicinal product refers, by demonstration of bioequivalence, usually through the submission of the appropriate bioavailability studies.

Applicants will have to identify in the application form for the generic/hybrid medicinal product the reference medicinal product (product name, strength, pharmaceutical form, MAH, first authorisation, Member State/Community), as follows:

  1. The medicinal product which is or has been authorised in the EEA, used as the basis for demonstrating that the data protection period  defined in the European pharmaceutical legislation has expired (see Question 12). This reference medicinal product, identified for the purpose of calculating expiry of the period of data protection, may be for a different strength, pharmaceutical form, administration route or presentation than the generic/hybrid medicinal product.

  2. The medicinal product, the dossier of which is cross-referred to in the generic/hybrid application (product name, strength, pharmaceutical form, MAH, marketing authorisation number). This reference medicinal product may have been authorised through separate procedures and under a different name than the reference medicinal product identified for the purpose of calculating expiry of the period of data protection. The product information of this reference medicinal product will, in principle, serve as the basis for the product information claimed for the generic/hybrid medicinal product.

  3. The medicinal product (product name, strength, pharmaceutical form, MAH, Member State of source) used for the bioequivalence study(ies) (where applicable).

References

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

For generic/hybrid medicinal products the same criteria apply as for any other medicinal products in respect to the acceptability of the proposed name by the name review group. Please see the EMA pre-submission guidance - “How will I know if the proposed invented name of my medicinal product is acceptable from a public health point of view?”

The use of a single name is also a requirement for generic/hybrid medicinal products regardless of whether the applicant/MAH wishes to use an invented name or a common name or scientific name, together with a trademark or the name of the Marketing Authorisation Holder.

It should be noted that the applicant/MAH will be required to identify the ‘reference medicinal product’ and the legal basis for submission of the application within the invented name notification.

 The name review group should also be consulted where the applicant/MAH wishes to use the common or scientific name, together with a trademark or the name of the Marketing Authorisation Holder.

In such cases the Marketing Authorisation Holder should take into account the following rules:

  • If an INN recommended by the World Health Organisation exists for the active moiety it should be used within the name of the medicinal product exactly as published without omissions or abbreviations. All the linguistic versions of the INN, including translations officially recognised at the national level, shall be considered to be the same name. If one does not exist, the usual common name should be used.
  • If a Modified INN (INNM) recommended by the World Health Organisation exists for the active moiety, it should be used within the name of the medicinal product exactly as published without omissions or abbreviations.
  • Where the active moiety is an unpublished INNM the name of the medicinal product should be that as agreed by users of INNs (pharmacopoeia, regulatory bodies, stakeholders), in accordance with the WHO INNM working document 05.167/3.
  • The ‘name of the MAH’ within the name of the medicinal product should correspond to all or part of the official name of the MAH as presented in the proof of establishment of the applicant/MAH.

The requirement for a single name for a generic medicinal product of a reference medicinal product authorised through the Centralised Procedure applies also in case the generic medicinal product is authorised by Member States via the Mutual Recognition or Decentralised Procedure.

References

4.1. What are the dates for submission of invented name requests?

See EMA pre-submission guidance for users of the centralised procedure.

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

See EMA pre-submission guidance for users of the centralised procedure.

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

See EMA pre-submission guidance for users of the centralised procedure.

7. When and how are Rapporteur and Co-Rapporteur appointed?

The principles outlined in Section 2 of the paper “CHMP Rapporteur/Co-Rapporteur appointment: principles, objective criteria and methodology” shall apply.

However, due to the particularities of generic/hybrid applications (e.g. legal basis, data requirements), the following principles shall be considered as regards the appointment of CHMP/PRAC Rapporteur/Co-Rapporteur 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.

Methodology on the appointment of Rapporteur/Co- Rapporteur and their assessment teams for Generic/Hybrid medicinal products

Normally, for generic applications the appointment procedure of the Rapporteur and her/his assessment team will be initiated at a CHMP meeting preferably 3-7 months prior to the MAA submission date, to allow the actual Rapporteur /Co-Rapporteur appointment 2-6 months prior to the MAA intended submission date. At the same time the PhV Rapporteur and PRAC Rapporteur will be identified.

Normally, for hybrid applications the appointment procedure of Rapporteur/Co-Rapporteur and her/his assessment teams will be initiated as early as 7 months prior to the MAA submission date, to allow Rapporteur /Co-Rapporteur appointment 6 months prior to the MAA intended submission date. At the same time the PhV Rapporteur and PRAC Rapporteur will be identified.

The methodological steps for the appointment procedure of Rapporteur/Co-Rapporteur (where relevant) and their assessment teams as outlined in Section 4.2 of the paper “CHMP Rapporteur/Co-Rapporteur appointment: principles, objective criteria and methodology” shall apply.

Re-examination of a CHMP opinion of a Generic/hybrid medicinal product

Legal Framework
  • Article 62(1) of Regulation (EC) No 726/2004 of 31 March 2004 (fourth subparagraph).

The principles and the methodology on the re-examination of a CHMP opinion as outlined in Section 5.1 of the paper “CHMP Rapporteur/Co-Rapporteur appointment: principles, objective criteria and methodology“ shall apply.

See: EMA pre-submission guidance for users of the centralised procedure - List of questions

References

8. What fee do I have to pay and how is the appropriate fee for my application calculated? Rev. December 2015

Fees for obtaining and maintaining a Community authorisation to market medicinal products for human use are levied in accordance with Regulation (EC) No 297/95.

For information on the fee applicable for applications according to article 10(1) and 10(3) of Directive 2001/83/EC (“generic” and “hybrid” applications), please refer to the explanatory note on fees payable to the European Medicines Agency.

For Post-Authorisation applications (extension applications, Type IA/IB, Type II, Renewals) the same fees as for any other medicinal product will apply. This includes the possibility for a reduced fee when the extension application only concerns quality data.

Generic and hybrid medicinal products benefit from a reduced annual fee.

Reduced fees also apply to scientific advice, when the advice requested relates to quality and/or bio-equivalence study issues only.

Calculation of fees

The EMA uses a specific definition to determine the number of ‘strengths’ for the purpose of calculation of fees. This definition is based on the NTA ”Guideline on the categorisation of New Applications versus Variation Applications”, and applies to all types of medicinal products.

Payment of fees

The fee will become due on the date of the notification of the administrative validation to the applicant and fees will be payable within 45 calendar days of the date of the said notification.

After approximately 15 days an invoice will be sent to the applicants billing address held on the Agency’s file. 

The invoice will contain details of the product and type of procedure involved, the fee amount, the customer purchase order number associated with the procedures invoiced and financial information.

Applicants requiring a purchase order number or similar references on the invoice are requested to clearly indicate it on the cover letter or application form accompanying the dossier. The Agency does not accept stand-alone notifications of purchase order numbers that are not associated with a dossier. Applicants not requiring a purchase order number on the invoice should also clearly state this in the cover letter. Applicants are requested to provide this information in the cover letter.

The Agency’s contacts point for any queries on fee payment are:

Product and Application Business Support (PA-BUS): pa-bus@ema.europa.eu

Fee waivers / reductions

In addition to the reduced fees provided for in the Fee Regulation, fee deferrals, waivers or further fee reductions may be granted to:

  • Applicants which meet the definition of a micro, small or medium-sized enterprise (SME)
  • Medicinal products designated as “orphan medicinal product”
  • Multiple applications on usage patent grounds

In addition, fee reductions may be granted by the EMA Executive Director in exceptional circumstances and for imperative reasons of public health, after consultation of the relevant scientific committee. This also applies in cases where an applicant disagrees on the classification by the EMA of an application under one of the fee categories described in the Fee Regulation.

References

9. What is the fee for a GMP/GCP inspection?

See EMA pre-submission guidance for users of the centralised procedure.

10. When could a fee waiver / fee reduction be granted?

See EMA pre-submission guidance for users of the centralised procedure.

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