A marketing authorisation under exceptional circumstances permits the approval of a medicinal product even though comprehensive data on efficacy and safety under normal conditions of use are not available and cannot, in principle, be fully obtained even after authorisation. It is linked to specific obligations whose fulfilment status and impact on the benefit-risk balance are reassessed annually. For centrally authorised medicinal products, Article 14(8) of Regulation (EC) No 726/2004 is the governing legal basis.
When Comprehensive Data Cannot Be Obtained
This authorisation type is intended for particular situations in which the normally required complete evidence cannot be available on a permanent basis. Directive 2001/83/EC identifies three typical grounds: the intended indication occurs so rarely that comprehensive evidence cannot reasonably be expected; according to the present state of scientific knowledge, comprehensive information cannot be provided; or data collection would be inconsistent with generally accepted principles of medical ethics.
The exception does not mean that the authority waives a benefit-risk assessment. The submitted data package must still support a positive decision. What is decisive, however, is the legal and scientific determination that a complete dossier is not achievable under the given circumstances. The authorisation is granted following consultation with the applicant on the condition that the applicant introduces particular procedures and measures.
These specific obligations relate in particular to the safety of the medicinal product, the reporting of incidents to the competent authorities, and necessary follow-up measures. They may also include requirements concerning use, information to healthcare professionals, or supplementary data collection. Their purpose is to characterise the safe and effective use on an ongoing basis in greater detail, not merely to fulfil a formal condition.
Annual Reassessment and Authorisation Status
A marketing authorisation under exceptional circumstances is initially time-limited like a standard authorisation and is simultaneously subject to annual reassessment of the specific obligations. This annual reassessment examines whether the conditions have been met and what significance the newly obtained information has for the benefit-risk balance. It is therefore distinct from the general renewal of the authorisation after expiry of the initial period of validity.
The obligations are made visible in the authorisation and the accompanying product information. In practice, this requires a robust system for safety monitoring, data tracking, deadline control, and regulatory communication. A change in the indication or the conditions may be possible provided the requirements for marketing authorisation under exceptional circumstances remain met. A standard authorisation already granted cannot, however, be converted retrospectively into this authorisation type.
Distinction from Conditional Marketing Authorisation
The distinction from conditional marketing authorisation is the core of the concept. In the case of a conditional marketing authorisation, comprehensive data are still lacking, but it is likely that the holder can submit them within an agreed timeframe. The authorisation is then limited to one year and renewable annually; after submission of the data it can convert into a standard authorisation.
In the case of a marketing authorisation under exceptional circumstances, by contrast, complete data are in principle not obtainable. The annual reassessment therefore examines the specific obligations and the benefit-risk status, but does not normally lead to the completion of a full dossier. A marketing authorisation under exceptional circumstances should not be granted when conditional marketing authorisation is the more appropriate route. It is not the volume of missing data alone, but rather their fundamental obtainability, that separates the two forms.
Relevance for clinical trials
Clinical development and post-authorisation planning must be closely linked for this authorisation type. Even before application, it must be justified why certain data cannot be comprehensively obtained, what evidence nevertheless permits a positive benefit-risk assessment, and what information can realistically be collected after authorisation. Studies, registries, safety measures, and product information should therefore be planned as a coherent risk management concept. The annual reassessment requires a traceable data chain over the entire lifecycle.
Full-service CROs such as Mediconomics support study planning, safety management, pharmacovigilance, data management, medical writing, and regulatory documentation. They can translate specific obligations into actionable study and reporting plans, coordinate the collection of safety and use data, and prepare documentation for the annual reassessment consistent with the summary of product characteristics and risk management.
Frequently Asked Questions (FAQ)
When may a marketing authorisation under exceptional circumstances be considered?
When comprehensive data on efficacy and safety under normal conditions of use cannot be submitted for legally recognised reasons, but authorisation is nevertheless appropriate.
Are the missing data always submitted later?
No. Unlike conditional marketing authorisation, comprehensive data cannot in principle be fully obtained even after authorisation.
Is the annual reassessment a renewal of the authorisation?
No. It examines the specific obligations and their impact on the benefit-risk balance annually; renewal concerns the period of validity of the authorisation.
Regulatory References
- Regulation (EC) No 726/2004, Article 14(8) — permits marketing authorisation under exceptional circumstances in the centralised procedure.
- Directive 2001/83/EC, Annex I Part II — describes the requirements for incomplete data on exceptional grounds.
- EMA, Pre-authorisation guidance — distinguishes exceptional circumstances and conditional marketing authorisation in detail.