Will there soon be obligatory GMP Regulations for Excipients?

On 17th and 18th March 2010 the Committee on the Internal Market (IMCO) and the Committee on Industry, Research and Energy (ITRE) in the European Parliament voted on a total of 114 amendments to draft directives on combating counterfeit medicines. These proposals were put forward by representative Amalia Sartori (member of the European People's Party, the Christian Democrats, in the European Parliament) and relate to concrete GMP requirements for APIs and excipients. Provided these modifications are accepted by both committees, making it through to further legislative procedures - a ballot in the leading Environment Committee at the end of April 2010, and in the plenum of the European Parliament in June 2010 - they will be included in the new guideline on the combating of counterfeit medicines. This will have far-reaching implications for the pharmaceutical industry and also for the manufacturers of APIs and excipients - something which has become apparent, for instance in the following amendment (Amendment No. 60) to the GMP for active pharmaceutical ingredients and excipients (text passages which are to be amended vis-à-vis original formulation of the draft guideline, are highlighted):

"(13) The manufacture of active pharmaceutical ingredients or excipients should be subject to the relevant good manufacturing practices in force within the Community irrespective of whether those ingredients were manufactured in the Community or imported. With regard to the manufacture of active pharmaceutical ingredients in third countries, it should be ensured that the rules for the manufacture of active pharmaceutical ingredients intended for export to the Community, including inspection and enforcement, provide for a level of protection of public health equivalent to that provided for by Community legislation."


Rationale for this:
"Both excipients and active pharmaceutical ingredients should be subject to relevant good manufacturing practices developed at the European level taking into account their own specificities. The European Commission is called to develop specific GMP for APIs and specific GMPs for Excipeints taking into account the very characteristics of those two different categories of ingredients and specially the fact that excipients have no therapeutic activity."


In the event that these amendments are taken on unchanged into the new counterfeit medicines directive, it is to be expected that there will be special binding GMP regulations for pharmaceutical excipients.


Amalia Sartori is very much involved in safety issues concerning imported APIs and excipients, along with patient protection, and is campaigning for obligatory and strict official inspections of active ingredient production plants outside the EU. A further amendment (Amendment No. 10) from Amalia Sartori is directed at this topic. Article 46f of the 2001/83/EG guideline shall read as follows:

'(f) to comply with the principles and guidelines of good manufacturing practice for medicinal products and 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. To this end, the holder of the manufacturing authorization shall ensure that production operations are conducted in accordance with the guidelines and standards of good manufacturing practice in force within the Community through the performance of mandatory inspections by the competent Community authorities or the authorities of countries with which mutual recognition agreements covering, inter alia, active pharmaceutical ingredients, are in force.'

A legally prescribed official inspection of active ingredient manufacturers would be a first, and would have far-reaching implications for health-care authorities, especially in relation to their staff resources and budgets. Amalia Sartori is expressly in favour of this obligatory inspection and is against inspections by accredited private companies, since she fears that "... the ambiguous relationship betweens firm being inspected and the bodies inspecting them could give rise to a risk of corruption."


It will be fascinating to follow which of the amendments will ultimately be assumed in the new guidelines.


A draft of the guideline on combating counterfeit medicines can be found here. Amalia Sartori's representations, with amendments 1 - 41, can be read here and the document with further applications 42 - 114 can be found here.



Dr Gerhard Becker

On behalf of the European Compliance Academy (ECA)

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