UK MHRA Guidance: How Marketing Authorisation Applications referred under Article 29 are Handled

The UK MHRA updated its Guidance on "How Marketing Authorisation Applications referred under Article 29 are Handled" and outlines the process by which disagreements between Member States in a decentralized procedure (DCP) or mutual recognition procedure (MRP) are resolved. This guidance ensures that high-quality, safe, and effective medicines are authorized consistently across the UK and globally.

Article 29 Referrals

Article 29 of Directive 2001/83/EC addresses situations where Member States involved in the MRP or DCP fail to reach an agreement on a marketing authorization application.

Referrals under Article 29 involve elevating the application to a coordination group or, in some cases, to the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) for arbitration. Referrals occur when:

• There is a scientific disagreement between Member States over the evaluation of a product's quality, safety, or efficacy.

• One or more Member States refuse to grant marketing authorization during the DCP or MRP process.

Key Steps in the Article 29 Referral Process

1. Notification of Referral

   • When a disagreement arises, the Reference Member State (RMS) notifies the applicant and other Member States involved in the procedure.

   • The referral is forwarded to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh).

2. Coordination Group Review

   • The CMDh, comprising representatives from each Member State, reviews the application and aims to reach a consensus.

   • The review includes a detailed scientific discussion and consideration of the RMS's assessment report.

3. Outcome of CMDh Review

   • If the CMDh achieves consensus, the application proceeds as agreed upon, and the Member States grants the marketing authorization.

   • If the CMDh fails to reach a consensus, the referral is escalated to the EMA's CHMP.

4. CHMP Arbitration

   • The CHMP conducts a detailed review of the application and issues an opinion based on its scientific evaluation.

   • The opinion may recommend granting, modifying, or refusing the marketing authorization.

5. Final Decision by the European Commission

   • For referrals involving the EU (pre-Brexit), the European Commission issues a legally binding decision based on the CHMP’s opinion.

   • Post-Brexit, decisions in the UK are managed by the MHRA.

Applicants may be required to submit additional clinical or non-clinical data to address the issues raised. Once the referral process concludes, the Member States follow the agreed-upon decision:

• If positive, marketing authorizations are granted in the concerned Member States.

• If negative, the application is refused, and the applicant must address the identified deficiencies before resubmitting. For more information, refer to the full MHRA guidance here.

Also, check out this guidance "Medicines that you cannot export from the UK or hoard" which sets out medicines that cannot be exported from the UK or hoarded because they are needed for UK patients.