Conditional Marketing Authorisations, Exceptional Circumstances Authorisations, and National Scientific Advice in the UK

Conditional Marketing Authorisations (CMA)

Conditional marketing authorisations are granted for medicines addressing unmet medical needs when comprehensive clinical data are not yet complete but the benefit-risk balance is positive based on available evidence. The applicant must commit to providing the missing data within an agreed timeframe after authorisation.

Eligibility Criteria

• The medicine targets a seriously debilitating or life-threatening condition with no satisfactory treatment or significant improvement over existing options.
• Comprehensive clinical data are not yet complete but available data demonstrate positive benefit-risk.
• It is likely that comprehensive data can be provided within a reasonable timeframe post-authorisation.
• Unmet medical need is justified, and the benefit of immediate availability outweighs risks from incomplete data.

Key Features and Obligations

• Validity is typically one year, renewable annually upon review of new data.
• Specific obligations include completion of ongoing studies or new studies to confirm safety and efficacy.
• Annual renewal requires demonstration of progress towards obligations and positive ongoing benefit-risk.
• The summary of product characteristics (SmPC) and patient information leaflet must indicate the conditional nature.

Exceptional Circumstances Marketing Authorisations (ECMA)

Exceptional circumstances authorisations are granted when, due to the rarity of the condition or other justified reasons, comprehensive data cannot be obtained even post-authorisation (e.g., ultra-rare diseases with very small patient populations).

Eligibility Criteria

• The applicant demonstrates that comprehensive data cannot reasonably be provided (e.g., due to disease rarity making trials infeasible).
• Available data provide reasonable assurance of positive benefit-risk.
• The medicine addresses a serious condition with significant clinical benefit.

Key Features and Obligations

• No fixed renewal period like CMA; authorisation is granted with specific obligations for ongoing monitoring and data collection where possible.
• Annual review of safety and efficacy data is required.
• The authorisation remains under exceptional circumstances status, with continued pharmacovigilance and potential restrictions on use.
• SmPC and labelling clearly state the exceptional circumstances basis.

National Scientific Advice (NSA)

The MHRA provides national scientific advice to applicants on quality, non-clinical, clinical, and regulatory aspects of medicine development. This is separate from EMA scientific advice but can complement it.

Scope and Process

• Advice covers proposed clinical trial designs, qualification of biomarkers, paediatric development plans, and post-authorisation commitments.
• Requests are submitted via the MHRA portal with briefing material; meetings (face-to-face, video, or written) are held.
• Advice is non-binding but provides valuable regulatory insight to reduce development risks.
• Fees apply based on the scope and format of advice.

Relation to CMA and ECMA

• Applicants often seek NSA early to discuss eligibility for conditional or exceptional authorisation pathways.
• Advice can help design studies that support conditional approval or justify exceptional circumstances.
• For conditional authorisations, NSA may address post-authorisation obligation proposals.

Practical Considerations

• For both CMA and ECMA, the MHRA assesses the benefit-risk balance rigorously, considering the severity of the condition and availability of alternatives.
• Applicants should engage early via NSA to align development plans with these pathways.
• Post-authorisation, compliance with specific obligations is critical; failure may lead to suspension or revocation.
• These mechanisms support accelerated access for innovative medicines in areas of high unmet need while maintaining safeguards through enhanced monitoring.

Source: Conditional marketing authorisations, exceptional circumstances marketing authorisations and national scientific advice - GOV.UK