Principles for Manufacturing, Importation and Distribution of Active Substances in Spain – AEMPS Overview

Regulatory Framework

Active substances (APIs) in Spain are governed by EU legislation, primarily Directive 2001/83/EC (as amended), Directive 2003/94/EC on GMP, and Regulation (EU) 2019/6 for veterinary medicines where applicable. Key implementing acts include the Falsified Medicines Directive (2011/62/EU), Delegated Regulation (EU) 2016/161 on safety features, and the GMP Guidelines (EudraLex Volume 4). National transposition occurs through Royal Decree 1345/2007 (human medicines) and related provisions. AEMPS, as the competent authority, authorises and inspects activities involving APIs to ensure compliance with Good Manufacturing Practice (GMP) and prevent falsified or substandard substances from entering the supply chain. Principios activos: fabricación, importación y distribución - AEMPS

Manufacturing of Active Substances

• GMP Compliance: All API manufacturing sites in Spain must operate under EU GMP standards (Part II of EudraLex Volume 4).
• Authorisation: Manufacturing requires prior AEMPS authorisation following inspection; sites receive a GMP certificate upon successful compliance.
• Quality System: Robust quality management system, including risk-based controls, validation, change control, and deviation management.
• Starting Materials: Suppliers of starting materials must be qualified; traceability back to the original source is mandatory.

Importation of Active Substances

• Third-Country Imports: APIs from non-EU/EEA countries require written confirmation of equivalent GMP standards issued by the exporting country's authority or EU GMP certification upon import.
• Import Authorisation: Importers must hold AEMPS authorisation as an importer of active substances.
• Verification: Importers verify authenticity, quality, and GMP compliance of imported APIs, including batch documentation and certificates of analysis.
• Safety Features: Where applicable, APIs subject to falsified medicines controls must comply with verification requirements.

Distribution and Wholesale of Active Substances

• Authorised Distributors: Only entities with AEMPS wholesale authorisation for active substances may distribute APIs.
• GDP Principles: Distribution follows Good Distribution Practice adapted for APIs (specific GDP guidelines for APIs).
• Traceability: Full batch-level traceability from manufacturer to end-user; records maintained for at least 5 years.
• Customer Verification: Distributors must confirm customers are authorised manufacturers or other qualified entities.

Inspections and Enforcement

AEMPS conducts routine and for-cause GMP inspections of API manufacturers, importers, and distributors. Non-compliance may result in suspension or withdrawal of authorisation, product recalls, or sanctions. AEMPS maintains a public register of authorised API manufacturers and importers, as well as GMP certificates.

This framework ensures that active substances used in Spain meet stringent quality standards, supporting the safety and efficacy of finished medicinal products. Detailed requirements, application procedures, GMP inspection reports, and contact information are published on the AEMPS dedicated page for active substances manufacturing, importation, and distribution. Principios activos: fabricación, importación y distribución - AEMPS