The annual re-assessment is the recurring regulatory review of a marketing authorisation under exceptional circumstances. It evaluates whether the specific obligations established for this purpose are being met and whether the newly submitted data alter the benefit-risk balance of the medicinal product. This procedure accompanies an authorisation when comprehensive data on efficacy and safety under normal conditions of use cannot be provided.
Starting Point: Marketing Authorisation under Exceptional Circumstances
A marketing authorisation under exceptional circumstances may be granted for a medicinal product if the applicant is unable to provide comprehensive data on efficacy and safety. The reasons for this may include the rarity of the condition, the state of scientific knowledge, or ethical considerations. The authorisation is then linked to certain conditions, referred to as specific obligations. These may involve a study programme, a registry, the reporting of specific events, or further measures for safe use.
The annual re-assessment makes these obligations verifiable. The authorisation holder submits data and a critical appraisal of their fulfillment status. The decisive factor is not merely whether an individual measure was formally carried out; the assessment also evaluates the consequences of the resulting data for the benefit-risk balance. The outcome may lead to the authorisation being maintained unchanged, amended, or suspended.
Process and Assessment Priorities
In the centralised procedure, the EMA coordinates the re-assessment with the Committee for Medicinal Products for Human Use (CHMP) and the Pharmacovigilance Risk Assessment Committee (PRAC). The CHMP rapporteur and the PRAC rapporteur assess the documentation; the CHMP co-rapporteur is not regularly involved. For advanced therapy medicinal products, the relevant Committee for Advanced Therapies (CAT) takes the lead role.
The dossier includes a clear overview of the specific obligations with descriptions, due dates, submission dates, and current status. The clinical overview must critically appraise the new data, the status of each outstanding obligation, and the implications for the benefit-risk balance. Changes to the Summary of Product Characteristics (SmPC), labelling, or package leaflet may only reflect the results of this re-assessment. A regularly submitted Periodic Safety Update Report (PSUR) does not replace the procedure and is not part of the re-assessment dossier.
Distinction from Marketing Authorisation Renewal
The annual re-assessment is not to be equated with the renewal of the marketing authorisation. Renewal considers the validity of an authorisation after its regular period and is based on a separate application. In contrast, the re-assessment is tied to the specific obligations of a marketing authorisation under exceptional circumstances. Its focus is on outstanding data gaps and their significance for continued safe and effective use.
It is also distinct from the annual renewal of a conditional marketing authorisation. In a conditional authorisation, missing data are fundamentally expected and the approval is renewed annually. In a marketing authorisation under exceptional circumstances, comprehensive data may remain unavailable even in the long term. Therefore, the continuous review of the established obligations remains the central mechanism.
The re-assessment therefore requires a clear separation between data serving the fulfillment of a specific obligation and changes to be submitted via other regulatory procedures. New indications or independent quality changes do not become part of the re-assessment simply because they appear technically relevant at the same time. The dossier must clearly state the period covered and link each open obligation to its actual progress. This ensures that committees and authorisation holders can identify which uncertainty remains and which measure addresses it.
Relevance for clinical trials
For clinical development programmes, the annual re-assessment determines which follow-up studies, registries, or evaluations must be reliably available by which date. The study protocol, endpoints, data quality, and safety monitoring must be planned to effectively address the respective specific obligation. Particularly important are a consistent data lock point, the traceability of deviations, and the timely assessment of whether new findings require adjustments to the product information or the risk management plan.
Full-service CROs like Mediconomics support the planning and operational implementation of such obligations through study management, monitoring, data management, pharmacovigilance, and medical writing. This includes translating regulatory requirements into study and registry concepts, managing submission documents, verifying data quality, and preparing clinical overviews that transparently consolidate fulfillment status and benefit-risk impacts.
Frequently Asked Questions (FAQ)
Is the annual re-assessment a new marketing authorisation?
No. It reviews the continuation of a marketing authorisation already granted under exceptional circumstances based on the applicable specific obligations.
Which data are the focus of the re-assessment?
The focus is on data regarding the fulfillment of outstanding obligations and their impact on safety, efficacy, and the overall benefit-risk balance.
Can a re-assessment lead to changes in the product information?
Yes. If the submitted data justify it, the annexes of the marketing authorisation can be adapted as part of the procedure.
Regulatory References
- Regulation (EC) No 726/2004, Article 14(8) – regulates marketing authorisation under exceptional circumstances in the centralised procedure.
- Directive 2001/83/EC, Article 22 – contains the corresponding regulation for national authorisations.
- Directive 2001/83/EC, Annex I Part II Number 6 – specifies the reasons for incomplete data.
- EMA guideline on marketing authorisation under exceptional circumstances – specifies specific obligations and their review.