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Definition and the need for PAES

PAES are efficacy studies recommended by the competent authority, as a condition of marketing authorization (MA), or after the MA grant, to evaluate if the previous efficacy evaluations need to be revised significantly.

PAES imposed in accordance with the Commission Delegated Regulation (EU) No 357/2014 it is meant an efficacy study which is requested by a Competent Authority pursuant to at least one of the situations set out in this said regulation. The data resulting from such a PAES conducted within an authorised therapeutic indication are required to be submitted as they are considered important for complementing available efficacy data in the light of well-reasoned scientific uncertainties on aspects of the evidence of benefits that is to be or can only be, addressed post-authorisation. The results of the PAES have the potential to impact the benefit-risk of the medicinal product or product information.

Such efficacy study conducted post-authorisation can be imposed either:

  • at the time of granting the initial marketing authorisation (MA) where concerns relating to some aspects of the efficacy of the medicinal product are identified and can be resolved only after the medicinal product has been marketed; or
  • after granting of a MA where the understanding of the disease or the clinical methodology or the use of the medicinal product under real-life conditions indicate that previous efficacy evaluations might have to be revised significantly.

It is also possible to impose the conduct of post-authorisation efficacy studies in the specific situations of a conditional MA, a MA granted in exceptional circumstances, a MA granted to an advanced therapy medicinal product, the paediatric use of a medicinal product, a referral procedure initiated under Article 31 or Article 107i of Directive 2001/83/EC or Article 20 of Regulation (EC) No 726/2004, however these fall outside the scope of the Delegated Regulation.

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The Agency will keep a record of the post-authorisation measure and its due date in its database.

In case of overdue condition or a MAH being found non-compliant in satisfying such condition, the competent authorities will consider the need for appropriate actions to be taken.

In such situations, the Rapporteur (or a lead Rapporteur nominated by the Committee in case of more than one affected product) may draft an assessment report on the impact of the lack of data on the benefit/risk balance of the affected medicinal product(s). Based on the outcome of such assessment and/or discussion, one or more of the following actions may be taken:

  • Letter to the MAH by the Chair of the Committee
  • Oral Explanation by the MAH to the Committee
  • Initiation of a referral procedure with a view to vary/suspend/revoke the MA
  • Inspection to be performed upon request of the Committee(s)

Such regulatory action in regards to non-compliance of the MAH may be made public on the Agency website, e.g. in the EPAR(s) of the affected medicinal product(s).

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