Revision of Directive 2001/83/EC - Consequences for the API Industry

GMP News No. 401

GMP News
31 March 2004

Revision of Directive 2001/83/EC –
Consequences for the API Industry

The Directive of the European Parliament and of the Council amending Directive 2001/83/EC on the Community Code relating to medicinal products for human use has been accepted by the Parliament in December last year and by the Council in the beginning of March 2004 and will be effective from March 31, 2004, on *1

There are three major consequences for the API manufacturers:

(A) APIs have to be manufactured in accordance to Annex 18 EG GMP Guide:

The EG GMP Guide obliges pharmaceutical companies to purchase APIs from approved suppliers only. The amended Directive increases the pressure on the pharmaceutical company: according to article 46f the pharmaceutical company is obliged "(…) to use as starting materials only active substances, which have been manufactured in accordance with the detailed guidelines on good manufacturing practice for starting materials (comment: reference is made to the Annex 18 to the EU GMP Guide). This point shall also be applicable to certain excipients, the list of which as well as the specific conditions of application shall be established by a Directive adopted by the Commission in accordance with the procedure referred to in Article 121(2).

Annex 18 to the EU GMP Guide can be found here:

(B) Annex 18 of the EU GMP Guide (GMP for APIs) becomes mandatory for the EU:

Article 47
The principles of good manufacturing practice for active substances used as starting materials referred to in point (f) of Article 46 shall be adopted in the form of detailed guidelines. (…)

(C) Inspections at the premises of API manufacturers may be carried out:

Article 111
The competent authority may also carry out unannounced inspections at the premises of manufacturers of active substances used as starting materials, or at the premises of marketing authorisation holders whenever it considers that there are grounds for suspecting non-compliance with the principles and guidelines of good manufacturing practice referred to in Article 47. These inspections may also be carried out at the request of a Member State, the Commission or the Agency.

In order to verify whether the data submitted in order to obtain a conformity certificate comply with the monographs of the European Pharmacopoeia, the standardisation body of the nomenclatures and the quality norms within the meaning of the Convention relating to the elaboration of the European Pharmacopoeia (European Directorate for the quality of Medicinal Products) may ask the Commission or the Agency to request such an inspection when the starting material concerned is the subject of a European Pharmacopoeia monograph.

The competent authority of the Member State concerned may carry out inspections of starting material manufacturers at the specific request of the manufacturer himself.

Unfortunately the different wordings of 'APIs' in Annex 18 and in the Directive may cause confusion: Annex 18 uses the word 'active pharmaceutical ingredient', the amended Directive uses 'starting material'.

The Pharmaceutical Review and its consequences for the API Industry will be presented by Dr Paul Weissenberg, European Commission, at the 7th APIC/CEFIC European Conference on Active Pharmaceutical Ingredients that will take place from 20 – 22 October 2004 in Lisbon / Portugal.

Dr Barbara Jentges

*1: Many thanks to Dr Chris Oldenhof from DSM, Netherlands, for the link and the latest information on the new Directive.


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