Amended Directive 2001/83/EC includes stronger Guidance on GMP for APIs and Excipients

Recommendation

22/23 February 2024
Munich, Germany

API Regulatory Starting Materials
Definition, Manufacture, Assessment and handling post-approval Changes

On 15 February, the EU Parliament accepted with a large majority the amendmends to the EU directive 2001/83/EC regarding the prevention of the entry of counterfeit medicines into the legal supply chain of medicinal products. The revisions to the directive concern different fields of drug manufacture; especially the securing of quality of pharmaceutical APIs and excipients are concerned. 

The new guidance for APIs includes the following:

• Not only the manufacture but also the distribution, i.e. the supply chain must be GMP compliant. 
• The holder of the manufacturing authorisation is responsible for the proof of GMP compliant manufacture and GMP compliant distribution. He can do it himself or subcontract it.
• The authenticity and the quality (i.e. the consistent traceability of the supply chain) must be documented.

Considering pharmaceutical APIs, the following new provisions are applicable:

• The holders of the manufacturing authorisation must prove that the APIs used for the medicinal products are suitable for their purpose.
• The holders of the manufacturing authorisation must prove that the APIs have been manufactured in a GMP compliant way. This proof must be in accordance with a formal risk analysis. The principles for the formal risk analysis on verification of the APIs' GMP compliance will be laid down in guidelines yet to be elaborated and adopted by the EU Commission.
• The authenticity and the quality (i.e. the consistent traceability of the supply chain) must be proved.

The amended directive will come into force on the 20iest day after the publication in the Official Journal of the European Union. Further changes or a withdrawal of the tightened regulations won't be expectable any longer after the EU Parliament has adopted the revision. After the directive has become operative, the EU Member States will have a 18 month time period to implement the new regulations into their national laws.

Here you can find the currently applicable directive 2001/83/EC and here the final draft to the directive, which won't differ so much from the definitive document.

Author
Dr Gerhard Becker
CONCEPT HEIDELBERG (a service provider entrusted by the ECA Foundation)