Commission Delegated Regulation (EU) 2024/1701of 11 March 2024amending Regulation (EC) No 1234/2008 as regards the examination of variations to the terms of marketing authorisations for medicinal products for human use(Text with EEA relevance)

1. The reference authority may reduce the period referred to in paragraph 4, having regard to the urgency of the matter, or may extend it to 90 days for variations listed in Annex V or for grouping of variations in accordance with Article 7(2), first subparagraph, point (c), or Article 13d(2), first subparagraph, point (c).

;

(d) in paragraph 6, point (c) is replaced by the following:

(c) the reference authority may extend the period referred to in paragraph 4 to 90 days.;

(e) paragraph 7 is replaced by the following:

1. Where the reference authority is the Agency, Article 9(1) and (2) of Regulation (EC) No 726/2004 shall apply to the opinion referred to in paragraph 4.

The Agency’s opinion on the application shall be transmitted to the holder and the Member States, together with the assessment report. Where the outcome of the assessment is favourable and the variation affects the terms of a Commission decision granting the marketing authorisation, the Agency shall also transmit to the Commission its opinion and the grounds for its opinion as well as the revised versions of the documents set out in Article 9(4) of Regulation (EC) No 726/2004.

Where the Agency issues a favourable opinion, the following shall apply:

(a) if the opinion recommends the variation to the terms of a Commission decision granting the marketing authorisation, the Commission shall, having regard to the final opinion and within the time limits provided for in Article 23(1a), amend the decision accordingly, provided that the revised versions of the documents set out in Article 9(4) of Regulation (EC) No 726/2004 have been received. The Union Register of Medicinal Products provided for in Article 13(1) of Regulation (EC) No 726/2004 shall be updated accordingly;

(b) the Member States concerned shall, within 60 days following receipt of the final opinion of the Agency, approve that final opinion, inform the Agency thereof and, where necessary, amend the marketing authorisations concerned accordingly, provided that the documents necessary for the amendment of the marketing authorisation have been transmitted to the Member States concerned.

;

(f) the following paragraph 11 is added:

1. In justified cases, in accordance with the guidelines referred to in Article 4(1), when agreed by the competent authorities of the Member States and the Agency, the holder may choose to follow the worksharing procedure laid down in paragraphs 3 to 9 for the marketing authorisations referred to in Chapters II, IIa and III, where a minor variation of type IB, a major variation of type II, or a group of variations where at least one of the variations is a minor variation of type IB or a major variation of type II that does not contain any extension, relates to several marketing authorisations owned by several holders in more than one Member State.

;

(21) Article 21 is replaced by the following:

Article 21

Public health emergency

1. By way of derogation from Chapters I, II, IIa and III, where a public health emergency at Union level is recognised by the Commission pursuant to Regulation (EU) 2022/2371 of the European Parliament and of the Council the relevant authorities, or in the case of centralised marketing authorisations, the Commission may, where certain pharmaceutical, non-clinical or clinical data are missing, exceptionally and temporarily accept a variation to the terms of a marketing authorisation for a human vaccine pertaining to the pathogen causing the public health emergency.

1. The relevant authority may request the holder to provide supplementary information in order to complete its assessment within a time limit set by it.

1. Variations may be accepted pursuant to paragraph 1 only if the benefit-risk balance of the medicinal product is favourable.

1. Where a variation is accepted pursuant to paragraph 1, the holder shall submit the missing pharmaceutical, non-clinical and clinical data within a time limit set by the relevant authority.

1. In the case of centralised marketing authorisations, the missing data and the time limit for submission or compliance shall be specified in the conditions to the marketing authorisation. Where the marketing authorisation has been granted in accordance with Article 14-a of Regulation (EC) No 726/2004 this may be done as part of the specific obligations referred to in paragraph 4 of that Article.

Regulation (EU) 2022/2371 of the European Parliament and of the Council of 23 November 2022 on serious cross-border threats to health and repealing Decision No 1082/2013/EU (OJ L 314, 6.12.2022, p. 26, ELI: http://data.europa.eu/eli/reg/2022/2371/oj).;

(22) Article 22 is amended as follows:

(a) in paragraph 1, the first subparagraph is replaced by the following:

Where, in the event of a risk to public health in the case of medicinal products, the holder takes urgent safety restrictions on its own initiative, it shall forthwith inform all relevant authorities and, in the case of a centralised marketing authorisation, the Agency.;

(b) paragraph 2 is replaced by the following:

1. In the event of a risk to public health in the case of medicinal products, relevant authorities or, in the case of centralised marketing authorisations, the Commission may impose urgent safety restrictions on the holder.

;

(23) in Article 23(1a), point (a) is amended as follows:

(a) points (iv), (v) and (vii) are deleted;

(b) point (viii) is replaced by the following:

(viii) other type II variations that are intended to implement changes to the decision granting the marketing authorisation due to a significant public health concern;;

(c) the following point (x) is added:

(x) variations related to the replacement or addition of a serotype, strain, antigen or coding sequence or combination of serotypes, strains, antigens or coding sequences of a human vaccine that has the potential to address a public health emergency;;

(24) in Article 23a, the following title is inserted:

Compliance with the paediatric investigation plan;

(25) in Article 24(5), the second subparagraph is replaced by the following:

By way of derogation from the first subparagraph, urgent safety restrictions and variations related to safety issues which concern marketing authorisations granted in accordance with Chapter 4 of Directive 2001/83/EC shall be implemented within a time frame agreed by the holder and the competent authority of the reference Member State, in consultation with the other relevant authorities.;

(26) Article 26 is deleted;

(27) Annexes I, II, and III are amended in accordance with Annex I to this Regulation;

(28) Annex V is replaced by the text set out in Annex II to this Regulation.

Article 2

This Regulation shall enter into force on the twentieth day following that of its publication in the Official Journal of the European Union.

It shall apply from 1 January 2025.

This Regulation shall be binding in its entirety and directly applicable in all Member States.

Done at Brussels, 11 March 2024.

For the Commission

The President

Ursula von der Leyen

Annex

ANNEX I

Annexes I, II, and III to Regulation (EC) No 1234/2008 are amended as follows:

(1) Annex I is amended as follows:

(a) in point 1, point (c) is replaced by the following:

(c) replacement of a biological active substance with one of a slightly different molecular structure where the efficacy or safety characteristics are not significantly different, with the exception of the following:

changes to the active substance of a seasonal, pre-pandemic or pandemic vaccine against human influenza;

replacement or, upon agreement of the relevant authorities, addition of a serotype, strain, antigen or coding sequence or combination of serotypes, strains, antigens or coding sequences for a human coronavirus vaccine;

replacement or, upon agreement of the relevant authorities, addition of a serotype, strain, antigen or coding sequence or combination of serotypes, strains, antigens or coding sequences, for a human vaccine other than for human influenza or coronavirus that has the potential to address a public health emergency in the Union;;

(b) in point 2, point (e) is replaced by the following:

(e) change or addition of a new route of administration.

For parenteral administration, it is necessary to distinguish between intra-arterial, intravenous, intramuscular, subcutaneous and other routes.;

(c) point 3 is deleted;

(2) Annex II is amended as follows:

(a) point 1 is amended as follows:

(i) point (f) is replaced by the following:

(f) variations related to the tightening of specification limits, where the change is not a consequence of any commitment from previous assessment to review specification limits and does not result from unexpected events arising during manufacture;;

(ii) the following point (g) is added:

(g) variations related to changes to a medical device that is an integral part of or in exclusive use with the medicinal product which have no impact on the quality, safety or efficacy of the medicinal product.;

(b) point 2 is amended as follows:

(i) point (e) is deleted;

(ii) point (f) is replaced by the following:

(f) variations related to the introduction of a new design space, where the design space has been developed in accordance with the relevant European and international scientific guidelines;;

(iii) the following point (fa) is inserted after point (f):

(fa) variations related to the introduction of a post approval change management protocol where the protocol has been developed in accordance with the relevant European and international scientific guidelines;;

(iv) points (g), (h), (i) and (k) are deleted;

(v) point (l) is replaced by the following:

(l) variations related to the replacement or, upon agreement of the relevant authorities, addition of a serotype, strain, antigen or coding sequence or combination of serotypes, strains, antigens or coding sequences for a human coronavirus vaccine;;

(vi) the following points (m) and (n) are added:

(m) variations related to the replacement or, upon agreement of the relevant authorities, addition of a serotype, strain, antigen or coding sequence or combination of serotypes, strains, antigens or coding sequences of a human vaccine that has the potential to address a public health emergency;

(n) variations related to changes to a medical device that is an integral part of or in exclusive use with the medicinal product which may have a significant impact on the quality, safety or efficacy of the medicinal product.;

(3) Annex III is amended as follows:

(a) points 6, 7 and 8 are replaced by the following:

1. All variations in the group relate to a project intended to improve the manufacturing process and the quality of the medicinal product concerned or its active substances, including related administrative changes.

1. All variations in the group are changes affecting the quality of a human pandemic influenza or coronavirus vaccine.

1. All variations in the group are changes to the pharmacovigilance system referred to in Article 8(3), point (ia) of Directive 2001/83/EC.;

(b) point 13 is deleted;

(c) point 14 is replaced by the following:

1. All variations in the group are consequential to a specific procedure or condition carried out pursuant to Article 14(8) of Regulation (EC) No 726/2004 or Article 22 of Directive 2001/83/EC..

Annex

ANNEX II

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Annex

ANNEX V

Variations concerning a change to or addition of therapeutic indications.