Type-II variations: questions and answers

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This page lists questions that marketing-authorisation holders (MAHs) may have on type-II variations. It provides an overview of the European Medicines Agency's position on issues that are typically addressed in discussions or meetings with MAHs in the post-authorisation phase. Revised topics are marked 'New' or 'Rev.' upon publication.

A PDF version of the entire post-authorisation guidance is available:

These questions and answers have been produced for guidance only and should be read in conjunction with the rules governing medicinal products in the European Union, volume 2, notice to applicants.

MAHs must in all cases comply with the requirements of Community legislation. Provisions that extend to Iceland, Liechtenstein and Norway by virtue of the European Economic Area agreement are outlined in the relevant sections of the text.

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1. What changes are considered type-II variations? Rev. August 2014

Commission Regulation (EC) No 1234/2008 (the Variations Regulation) defines a major variation of type II as a variation that is not an extension and that may have a significant impact on the quality, safety or efficacy of a medicinal product.

The Variations Regulation and the variations guideline set out a list of changes to be considered as type-II variations. In addition, any other change that may have a significant impact on the quality, safety or efficacy of the medicinal product must be submitted as a type-II variation. Refer also to 'when will my variation application be considered a type-II variation or an extension application?' below.

During validation of an ‘unforeseen’ variation, submitted by the MAH as a type-IB variation, the Agency may consider that the proposed variation may have a significant impact on the quality, safety or efficacy of the medicinal product. In such cases, the MAH will be requested to revise and supplement its variation application so that the requirements for a type-II variation application are met (see 'how shall my type-IB variations be handled (timetable)?').

References

2. Is the co-rapporteur involved in type-II variations? - Rev. March 2013

The Committee for Medicinal Products for Human Use (CHMP) co-rapporteur is normally not involved in the assessment of a type-II-variation application concerning quality, pre-clinical and most of the clinical summary-of-product-characteristics (SmPC) changes.

The involvement of the CHMP co-rapporteur is however deemed necessary for new indications.

The MAH should therefore inform the Agency of an upcoming type-II application for a new indication at least two months before submission, so that the CHMP can agree on the co-rapporteur’s involvement and be informed of the future submission.

The involvement of the CHMP co-rapporteur in other type-II variations will be decided by the CHMP on a case-by-case basis.

Furthermore, a PRAC rapporteur may be involved, where applicable.

The Agency will inform the MAH accordingly.

Regarding the submission of a type-II-variation application to the (co-)rapporteurs, see 'how and to whom should I submit my type-II-variation application?'

3. Can I group the submission of type-II variations? Can they be grouped with other types of variations? Rev. Oct 2013

MAHs may choose to group the submission of several type-II variations for the same product into one application, provided that this corresponds to one of the cases listed in annex III of the Variations Regulation or when this has been agreed upfront with the Agency.

It is also possible for an MAH to group a type-II variation with other variation submissions (e.g. extensions, or type-IB or -IA variations) where applicable. Such grouped submissions will follow the review procedure of the highest variation in the group. Please also refer to 'what types of variations can be grouped?'

Where the same type-II variations affect one or more marketing authorisations from the same holder, the MAH may choose to submit these variations as one application for worksharing. Please refer to 'what is worksharing and what types of variations can be subject to worksharing?'

References

4. How shall I present my type-II-variation application? Rev. Oct 2013

A type-II-variation application should contain the elements listed in annex IV of the Variations Regulation and should be presented in accordance with the appropriate headings and numbering of the European Union (EU) common-technical-document (CTD) format.

The Commission Variations Guidelines further specify the elements that should be included in a type-II-variation application:

  • Cover letter (for groupings, include a short overview of the nature of the changes and indicate whether it is submitted under Article 7.2(b), i.e. it falls within one of the cases listed in annex III of the variations regulation or it is submitted under Article 7.2.(c), i.e. the grouping has been agreed with the Agency). The cover letter should contain the template table to facilitate submission and registration.
  • The completed electronic EU variation application form (eAF) or the application form including the details of the marketing authorisation concerned. Where a variation leads to or is the consequence of other variations, a description of the relation between these variations should be provided in the appropriate section of the application form. All proposed changes should be declared in the ‘type of changes’ section of the form, and be clearly described in the 'scope' section of the form.
  • Reference to the part of the variation code as laid down in the annex to the Variations Guidelines or reference to the published Article-5 recommendation, if applicable, used for the relevant application.
  • Supporting data relating to the proposed variations.
  • Update or addendum to quality summaries, non-clinical overviews and clinical overviews, as relevant. When non-clinical or clinical study reports are submitted, even if only one, their relevant summaries should be included in module 2.
  • For variations submitted to implement changes requested by the Agency or for generic, hybrid or biosimilar medicinal products, a copy of the request should be annexed to the cover letter.
  • If the changes affect the SmPC, labelling or package leaflet, the revised product information annexes must be submitted (see 'when do I have to submit revised product information? In all languages?').

It should be noted that the responsibility for the quality of the submitted documentation lies with the MAH and is crucial to the overall process.

For queries relating to the presentation of the application, please contact the Agency.

References

5. How and to whom shall I submit my type-II-variation application? Rev. August 2014

See Other question 5. How and to whom shall I submit my application?.

6. When should I submit my type-II-variation application? Rev. Oct 2013

The MAH should submit type-II applications at the latest by the recommended submission dates published under submission dates.

MAHs are reminded, especially for safety issues, that once new information becomes available that might entail variation of the marketing authorisation, MAHs should submit any variation application resulting from the fulfilment of the post-authorisation measure (PAMs) or specific obligations (SOs) at the same time as the fulfilment of the PAM or SO, rather than awaiting the assessment of those data by CHMP.

Where the CHMP requests the submission of a variation following the assessment of a PAM or SO, MAHs must submit the corresponding variation application at the latest within two months following the adoption of the relevant assessment conclusion.

Variation applications reflecting the outcome of an urgent safety restriction (USR) shall be submitted immediately and in any case no later than 15 days after the initiation of the USR to the Agency. This applies to USRs initiated by the MAH or imposed by the European Commission.

Implementation of agreed wording changes following the abovementioned procedures for which no additional data are submitted by the MAH will follow a type-IB-variation procedure.

References

7. How will my type-II application be handled (timetable)? Rev. Oct 2013

The Agency will acknowledge receipt of a valid application of a type-II variation and start the procedure in accordance with the official starting dates published on this website.

The submission deadlines and full procedural detailed timetables are published as a generic calendar: see submission dates.

The published timetables identify the submission, start and finish dates of the procedures as well as other interim dates and milestones that occur during the procedure.

One of the following timetables (TT) shall apply:

60-day standard timetable

Condition:

  • All standard type-II variations; i.e. excluding those qualifying for a 30- or 90-day timetable.
DayAction
Day 1Start of evaluation
Day 30Receipt of (co-)rapporteur's assessment report
Day 50Comments by other CHMP members
Day 60Adoption of the CHMP opinion or request for supplementary information

30-day timetable

Condition:

  • Changes that, in the opinion of the Committee, would benefit from a shortened assessment, having regard to the urgency of the matter, in particular for safety issues.
DayAction
Day 1Start of evaluation
Day 17Receipt of rapporteur's assessment report
Day 25Comments by other CHMP members
Day 30Adoption of the CHMP opinion or request for supplementary information

In exceptional cases, this timetable can be shortened.

90-day timetable

Condition:

  • For variations concerning changes to or addition of therapeutic indications.
DayAction
Day 1Start of evaluation
Day 55Receipt of (co-)rapporteur's assessment report
Day 80Comments by other CHMP members
Day 90Adoption of the CHMP opinion or request for supplementary information

 

In cases where the PRAC is involved in the assessment of a type-II variation, e.g. when a risk-management plan (RMP) is submitted within the variation, the following timetables with PRAC milestones will apply:

60 day standard timetable with PRAC involvement

DayAction
Day 1Start of evaluation
Day 30Receipt of (co-)rapporteur's assessment report
Day 37Draft PRAC rapporteur's assessment report
Day 47Adoption of PRAC advice
Day 51Comments by other CHMP members
Day 60

Adoption of the CHMP opinion or request for supplementary information

30-day timetable with PRAC involvement

DayAction
Day 1Start of evaluation
Day 9Receipt of rapporteur's assessment report
Day 13Draft PRAC rapporteur's assessment report
Day 17Adoption of PRAC advice
Day 20Comments by other CHMP members
Day 30Adoption of the CHMP opinion or request for supplementary information

90-day timetable with PRAC involvement

DayAction
Day 1Start of evaluation
Day 53Receipt of (co-)rapporteur's assessment report
Day 67Draft PRAC rapporteur's assessment report
Day 76Adoption of PRAC advice
Day 80Comments by other CHMP members
Day 90

Adoption of the CHMP opinion or request for supplementary information

 

In cases where PRAC is leading in the assessment of a type-II variation (see practical questions and answers to support the implementation of the variations guidelines in the centralised procedure) the following timetables will apply:

60 day timetable with PRAC involvement

DayAction
Day 1Start of evaluation
Day 30Receipt of PRAC rapporteur's assessment report
Day 34Comments by other committee members
Day 47Adoption of committee assessment report by PRAC
Day 60

Adoption of the CHMP opinion or request for supplementary information

MAHs are encouraged to contact the Agency in advance of submission, in case clarification on the timetable for a specific variation is needed.

The MAH will be informed of the adopted timetable at the start of the procedure.

If issues are identified that prevent the adoption of an opinion, the CHMP will adopt a request for supplementary information together with a timetable stating the date by when the MAH must submit the requested data. The clock will be stopped until the receipt of the supplementary information.

Any response to a request for supplementary information must be sent directly to the Agency, all CHMP members and the (co-)rapporteur.

As a general rule, a clock-stop of up to one month will apply. For clock-stops longer than one month, the MAH should send a justified request to the Agency for agreement by the CHMP. Such requests should be sent after receipt of the assessment report, and at the latest before the CHMP meeting at which the request for supplementary information will be adopted. In exceptional cases (e.g. in the case of new indications or where the variation requires an inspection) a clock-stop of up to a maximum of six months may be applied.

For any follow-on requests for supplementary information, an additional clock-stop of up to one month will generally be applied. A maximum of two months may be applied when justified.

The MAH will receive the adopted timetable together with the request for supplementary information or follow-on request.

The CHMP assessment of responses will take up to 30 or 60 days depending on the complexity and amount of data provided by the MAH.

An oral explanation to the CHMP can be held at the request of the CHMP or the MAH, where appropriate.

References

8. Which post-opinion steps apply to my type-II variation and when can I implement the approved changes? Rev. Oct 2013

Upon adoption of the CHMP opinion, the Agency will inform the MAH within 15 days as to whether the CHMP opinion is favourable or unfavourable (including the grounds for the unfavourable outcome), as well as whether the Commission decision granting the marketing authorisation requires any amendments.

Where the outcome of the procedure is favourable and the Commission decision granting the marketing authorisation requires amendment, the Agency will inform the Commission accordingly.

Re-examination

Art. 9(2) of Regulation (EC) No 726/2004 also applies to CHMP opinions adopted for type-II variation applications. This means that the MAH may give written notice to the Agency or CHMP that it wishes to request a re-examination within 15 days of receipt of the opinion (after which, if it does not appeal, the opinion shall be considered as final). The grounds for the re-examination request must be forwarded to the Agency within 60 days of receipt of the opinion. If the MAH requests that the Committee consult a scientific advisory group in connection with the re-examination, the applicant should inform the CHMP as soon as possible.

The CHMP will appoint different CHMP (co-)rapporteurs to co-ordinate the re-examination procedure. If a PRAC rapporteur is deemed necessary, he or she will be appointed. Within 60 days from the receipt of the grounds for re-examination, the CHMP will consider whether its opinion is to be revised. If considered necessary, an oral explanation can be held within this 60-day timeframe.

Decision-making process

Upon receipt of a favourable CHMP opinion that requires amendments to the decision granting the marketing authorisation, the Commission will amend the marketing authorisation to reflect the variation within two months for the variations listed under Article 23(1a)(a) or within one year for other type-II variations.

Article 23(1a)(a) provides for a two-month timeframe for amending the decision granting the marketing authorisation for the following variations:

  • variations related to the addition of a new therapeutic indication or to the modifications of an existing one;
  • variations related to the addition of a new contra-indication;
  • variations related to a change in posology;
  • variations related to changes to the active substance of a seasonal, prepandemic or pandemic vaccine against human influenza;
  • other type-II variations that are intended to implement changes to the decision granting the marketing authorisation due to a significant public-health concern or significant animal-health or environmental concern in the case of veterinary medicinal products.

All the other type-II variations will follow a yearly timeframe for update of the respective Commission decision.


 

Where a group of variations to the terms of one marketing authorisation submitted as part of one variation have been approved, the Commission will update the marketing authorisation with one single decision to cover all the approved variations.

Implementation

Type-II variations listed in Article 23(1a)(a) may only be implemented once the Commission has amended the marketing authorisation and has notified the MAH accordingly. Variations related to safety issues, including urgent safety restrictions, must be implemented within a timeframe agreed by the MAH and the Agency.

Type-II variations that do not require any amendment of the marketing authorisation or follow a yearly update of the respective Commission decision can be implemented once the MAH has been informed of the favourable outcome by the Agency. However, it is expected that where the variation includes changes to the product information, the MAH will wait for the finalisation of the linguistic-review process by the Agency before implementing the variation, as appropriately checked translations are considered essential for correct implementation of the variation.

The agreed changes should be included in the annexes of any subsequent regulatory procedure.

Date of revision of the text

The date of revision of the text to be included in section 10 of the SmPC and corresponding section of the package leaflet for variations affecting the product information should be as follows:

  • For type-II variations listed in Article 23(1a)(a) this should be the date of the Commission decision amending the marketing authorisation.
  • For type-II variations not listed in Article 23(1a)(a), which follow a yearly timeframe for update of the respective Commission decision, this should be the date of the adoption of the positive CHMP opinion on the variation to the terms of the marketing authorisation.

References

9. What fee do I have to pay for a type-II variation? Rev. February 2013

For information on the fees applicable for type-II variations, please refer to fees payable to the European Medicines Agency. Such fees cover all authorised strengths, pharmaceutical forms and presentations of a given medicinal product. Reduced type-II fees may apply to certain variations.

For type-II variations that introduce additional presentations or pack sizes, each additional presentation or pack size attracts separate fees (x additional presentations = x separate fees). Each presentation and pack size should therefore be declared as a separate variation on the variation application form.

Grouped type-II variations, whether consequential or not, will each attract a separate type-II fee.

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 notification. After approximately 15 days, an invoice will be sent to the applicant's 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 this 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 formatted table template.

Guidance on how to pay an invoice is available.

For type-II variations, if the variation is considered ‘invalid’ (i.e. an assessment process can not be started), an administrative fee will be charged by the Agency. See fees payable to the European Medicines Agency.

If an inspection is required, an inspection fee will be requested in addition (see 'what is the fee for a good-manufacturing-practice inspection?').

References

10. Do I have to submit mock-ups and specimens? Rev. July 2013

For information concerning submission of mock-ups and specimens in the framework of post-authorisation procedures, please refer to the document ‘Checking process of mock-ups and specimens of outer/immediate labelling and package leaflet of human medicinal products in the centralised procedure, 3.4 Other post-authorisation procedures

References

11. When do I have to submit revised product information? In all languages? Rev. August 2014

If the type-II variation affects the SmPC, labelling or package leaflet, the revised product information annexes must be submitted as follows:

At submission (day 0):

  • English language: Complete set of annexes electronically only in Word format (highlighted).

After CHMP opinion (day +5):

  • All EU languages (plus Norwegian and Icelandic): Complete set of annexes electronically only in Word format (highlighted).

After linguistic check (day +25):

  • All EU languages (plus Norwegian and Icelandic): complete set of annexes electronically only in Word format (highlighted) and in PDF (clean).

Overview:

DayLanguage*Post-opinion linguistic review timetable
0EnglishElectronically
Word format (highlighted)
+5All European Economic AreaElectronically
Word format (highlighted)
+25All European Economic AreaElectronically
Word format (highlighted)

*Complete set of annexes, i.e. annexes I, II, IIIA and IIIB submitted as one document per language.

The ‘complete set of Annexes’ includes Annex, I, II, IIIA and IIIB i.e. all SPC, labelling and PL texts for all strengths and pharmaceutical forms of the product concerned, as well as Annex II.

The complete set of Annexes must be presented sequentially (i.e. Annex I, II, IIIA, IIIB) as one document for each official EU language. Page numbering should start with "1" (bottom, centre) on the title page of Annex I. The ‘QRD Convention’ published on the Agency’s website should be followed. When submitting the full set of Annexes in PDF format, this should be accompanied by the completed formatting checklist which provides guidance on how to correctly prepare the PDF versions.

The electronic copy of all languages should be provided as part of the variation application on the Gateway / Web Client package. Highlighted changes should be indicated via ‘Tools – Track changes’. Clean versions should have all changes ‘accepted’.

Icelandic and Norwegian language versions must always be included.

The annexes provided should only reflect the changes introduced by the variation concerned. However, in exceptional cases where MAHs take the opportunity to introduce minor linguistic amendments in the texts (e.g further to a specimen check) this should be clearly mentioned in the cover letter and in the scope section of the application form.

In addition, the section 'present / proposed' in the application form should clearly list the minor linguistic amendments introduced for each language. Alternatively, this listing may be provided as a separate document attached to the application form. Any changes not listed will not be considered as part of the variation application.

In such cases, and in cases where any other ongoing procedures may affect the product information annexes, the MAH is advised to contact the Agency in advance of submission or finalisation of the procedure concerned.

For those variations that affect Annex A (e.g. introduction of a new presentation), the following principles apply:

  • upon adoption of the opinion, the Agency will prepare and send the revised English Annex A reflecting the new or amended presentation to the MAH;
  • after CHMP opinion (day +5), the MAH should provide the Agency with the electronic versions of the complete set of annexes in all languages as well as the translations of the revised Annex A as a separate Word document.
12. What is the procedure for assignment of new European Union sub-numbers for a type-II variation concerning additional presentations? New November 2012

At the time of the adoption of a CHMP opinion for a type-II variation that includes additional presentations, the Agency will assign the new European Union sub-numbers and include them in the revised annex A of the medicinal product, which will be transmitted to the MAH together with the CHMP opinion and respective annexes.

The MAH should include the newly assigned numbers in all language versions of annex A and in all applicable sections of the product information, which are submitted following the CHMP opinion for linguistic review.

13. Will there be any publication on the outcome of my type-II variation? - Rev. October 2012

The meeting highlights following each CHMP meeting give information on opinions in relation to new indications, changes to an existing indication, and additions, changes to or removals of contraindications. This includes the name of the product, the name of the MAH and the indication. Where applicable, the CHMP gives also an update on safety information.

14. What specific requirements apply to my type-II variation for a new orphan indication?

Type-II variations for a new indication that is the same as the indication of an authorised orphan medicinal product should include relevant information in module 1.7 of the application, based on the following considerations:

  • in accordance with Article 8.1 of Regulation (EC) No 141/2000, where a marketing authorisation in respect of an orphan medicinal product has been granted in all Member States, the Community and the Member States shall not, for a period of 10 years, accept another application for marketing authorisation, or grant a marketing authorisation or accept an application to extend an existing marketing authorisation, for the same therapeutic indication, in respect of a similar medicinal product;
  • where a designated orphan medicinal product has been authorised for a condition that covers the proposed therapeutic indication being applied for, and a period of market exclusivity is in force, the MAH must submit a report addressing the possible similarity with the authorised orphan medicinal product (even if the concerned product does not have orphan designation);
  • if the medicinal product is deemed to be similar to an authorised orphan medicinal product, the MAH must furthermore provide justification that one of the derogations laid down in Article 8.3, paragraphs (a) to (c) of the same Regulation applies, namely:
    • the holder of the marketing authorisation for the original orphan medicinal product has given his consent to the second applicant, or;
    • the holder of the marketing authorisation for the original orphan medicinal product is unable to supply sufficient quantities of the medicinal product, or;
    • the second applicant can establish in the application that the second medicinal product, although similar to the orphan medicinal product already authorised, is safer, more effective or otherwise clinically superior.

Further details can be found in the European Commission guideline on aspects of the application of Article 8(1) and (3) of Regulation (EC) No 141/2000: Assessing similarity of medicinal products versus authorised orphan medicinal products benefiting from market exclusivity and applying derogations from that market exclusivity.

Even if the variation does not concern an orphan designated product, all MAHs should still check whether their claimed new indication would potentially overlap with the indication of authorised orphan medicinal products, as listed in the Community register of designated orphan medicinal products, and include the relevant documentation in their variation application as set out above.

References

15. What should I consider if I wish to add a new non-orphan therapeutic indication to my orphan medicinal product? New February 2013

As it is not possible to combine orphan and non-orphan indications within the same marketing authorisation, as provided for in Article 7(3) of Regulation (EC) No 141/2000 (the Orphan Regulation), if you wish to extend the therapeutic indications of your orphan medicinal product to include additional non-orphan therapeutic indications, you will have to consider the following options:

References

16. Do I need to address any paediatric requirements in my type-II variation application? Rev. April 2012

Regulation (EC) No 1901/2006, as amended (the Paediatric Regulation) lays down obligations, rewards and incentives for the development and placing on the market of medicines for use in children. The Paediatric Regulation places some obligations for the applicant when developing a new medicinal product as well as new uses of an authorised product, in order to ensure that medicines to treat children are subject to ethical research of high quality and are appropriately authorised for use in children, and to improve collection of information on the use of medicines in the various subsets of the paediatric population. The paediatric population is defined as the population between birth and the age of 18 years (meaning up to but not including 18 years).

As set out in Article 8 of the Paediatric Regulation, applications for new indications, new pharmaceutical forms or new routes of administration concerning an authorised medicinal product protected either by a supplementary protection certificate or by a patent that qualifies for the granting of such a certificate must include one of the following documents or data in order to be considered valid:

  • the results of all studies performed and details of all information collected in compliance with an agreed paediatric investigation plan (PIP). This means that the application will have to include the PIP decision but also the results in accordance with the agreed PIP;
  • an Agency decision on a PIP including the granting of a deferral. This means that the application will have to include the PIP decision including the deferral granted and if applicable, any completed studies;
  • an Agency decision granting a product-specific waiver;
  • an Agency decision granting a class waiver, together with the Agency’s confirmation letter of applicability if requested by the MAH.

This requirement applies irrespective of the type of application submitted for such a change, i.e. variation or extension (or new marketing-authorisation application), and irrespective of whether the change is related to adult or paediatric use.

To define what a ‘new indication’ is for the purpose of the application of Article 8, please refer to what is a new indication in the context of Article 8?

Where results of PIP studies do not support a paediatric indication, the corresponding proposal for amending the product Information may be submitted as part of a variation C.I.4 as per the guideline on the details of the various categories of variations: variations related to significant modifications to the SmPC.  Applicants are requested to mention the following sentence in the application form of the variation including the paediatric results and in the cover letter the following statement in the section ‘precise scope and background for change’: ‘submission of paediatric study results performed in compliance with a <completed> paediatric investigation plan which do not support a paediatric indication.'

Applicants should include a rationale supporting the proposed changes to the product information  in the clinical overview. In particular, if the PIP is completed and the results of all studies are available, the applicant should discuss whether the generated data support or not the intended paediatric indications stated in the PIP.

Inclusion of the results of all studies performed in compliance with an agreed PIP requirement in the product information is a prerequisite for benefiting from the paediatric reward (Article 36(1) of Regulation (EC) No 1901/2006).

As for all applications including results of studies performed in compliance with an agreed PIP, the applicant should also include an overview table of the PIP results in module 1.10, indicating which applications they were or are going to be submitted in, the status of the applications and their location in the present application.

In addition, in accordance with Article 8, the PIP or waiver application and the related decision should cover both the new and existing indications, routes of administration and pharmaceutical forms of the authorised medicinal product, taking into account the global-marketing-authorisation (GMA) concept together with the notion of the ‘same MAH’. Further information can be found in the procedural advice on applications for PIPs, waivers and modifications.

The data and documents required should be included in module 1.10 of the EU CTD dossier.

The following types of application are exempt from the application of Article 8:

  • generic medicinal products (Art 10(1) of Directive 2001/83/EC);
  • hybrid medicinal products (Art 10(3) of Directive 2001/83/EC);
  • similar biological medicinal products (Art 10(4) of Directive 2001/83/EC);
  • medicinal products containing active substances of well-established medicinal use (Art 10a of Directive 2001/83/EC).

Furthermore, when planning submission of their marketing-authorisation application, the applicant has to take into account also the need for a PIP compliance check.

Such a compliance check consists of verifying that the fulfilments of the measures as mentioned in the PIP decision including the timelines for the conduct of the studies or collection of the data are fulfilled. The compliance check procedure is explained in the questions and answers on the procedure of PIP compliance verification at the European Medicines Agency. Applicants are strongly recommended to apply for the compliance check before submission of the marketing-authorisation application in order not to delay the validation phase.

Further details on the format, timing and content of PIP or waiver applications as well as on the compliance check can be found in the Commission guideline. In addition, deadlines for submission of PIP or waiver applications, application templates as well as procedural advice regarding applications for PIPs, waivers and modifications and validation of new marketing-authorisation applications, variation or extension applications and compliance check with an agreed PIP are available.

References

17. Who should I contact if I have a question when preparing my application? New April 2014

If you cannot find the answer to your question in the Q&A when preparing your application, please contact us using the following email address: IIquery@ema.europa.eu

The Agency aims to respond to your query within 5 working days. To help us deal with your enquiry, please provide as much information as possible including the name of the product in your correspondence.

You should submit your query once and it is important that you submit it only to one dedicated email address. If you are uncertain of on a classification of a variation as type IB or type II please choose one of the relevant email addresses available to you (either IBquery@ema.europa.eu or IIquery@ema.europa.eu). Your query will be channelled internally to the relevant service(s) that will respond to you.

The above email address is only applicable when you have a pre-submission query. A dedicated Procedure Manager (PM) will be assigned to the procedure once your application has been validated. You will be able to contact this PM throughout the procedure.