Revision of EU-GMP Annex 15: Increased Focus on Deviation Management

A concept paper on the revision of Annex 15 has been published on the EMA's website. One of the main objectives of the revision is to make the application of Annex 15 mandatory for active substances (APIs). Until now, its application has been optional for active substance manufacturers. This change will affect both manufacturers of chemically synthesized and biologically derived active substances. In addition, the updates to Quality Risk Management introduced in ICH Q9 (R1) will be incorporated.

In this context, the concept paper further emphasises the need for thorough investigations in cases where deviations from predefined acceptance criteria occur. This is intended to promote a deeper understanding of manufacturing processes among API manufacturers.

The document explicitly refers to the presence of N-nitrosamines in sartan products. According to the concept paper, one contributing factor "was the lack of sufficient process and product knowledge during the development stage and GMP deficiencies by active substance manufacturers, including inadequate investigation of quality issues …".

Why this matters to manufacturers of drug product and QPs?

• Strengthened oversight responsibilities: If Annex 15 becomes mandatory for APIs, drug product manufacturers and QPs will need to ensure that processes at API manufacturers meet the revised expectations.
• Supply chain implications: The changes will likely affect technical agreements, audit scopes and QP declarations for APIs.

A two-month public consultation period is planned until April 2026. A final draft version is expected to be available by the end of 2026. The full concept paper is available on the EMA's website