Compliance Problems through Acetonitrile Shortage?

Acetonitrile is widely used in many HPLC analyses in the laboratories of the pharmaceutical quality control. It is a by-product of the manufacture of acrylonitrile. Acrylonitrile itself is used to produce a number of different synthetic products.

Present prognoses predict that the demand for acrylonitrile will continue to decrease and thus acetonitrile will remain scarce also in 2009.

The main reason for the scarcity of acetonitrile is the worldwide economic crisis. There are no dedicated manufacturing sites for acetonitrile. Raw acetonitrile is merely a by-product of the manufacture of acrylonitrile, a synthetic that is used among other things in the automotive industry. Due to the crash in the automotive industry and the resulting decrease in the demand for acrylonitrile, there is now a significant shortage in the acetonitrile supply.

An aggravating circumstance is the fact that an acetonitrile supplier is completely closing his site for extension works in January/February this year. Therefore, an extreme shortage is forecast for the first quarter of 2009. This goes so far that some suppliers can only make deliveries to "good" customers with a long-standing business relationship.

In other industries, the customers can react to the shortage and the resulting drastic price increases (price 6 or 8 times as high since summer 2008!) by replacing acetonitrile with other solvents (methanol or similar).

This is not possible in the pharmaceutical industry! Here, all applied methods (including the mobile phases of the HPLC) are laid down at the registration authorities in the marketing authorisations of the individual medicinal products. These cannot simply be changed. In order to escape this situation, it would not only be necessary to develop and validate new analytical test methods, but one would also have to submit cost-involving variation applications for every registered product in all countries concerned. These variation applications would, of course, take a certain amount of time to be approved.

Quite recently, the English registration and supervision authority MHRA has published a note on this topic: "Global shortage of acetonitrile: Advice to the pharmaceutical industry on changes requiring variation submissions to update Marketing Authorisations." The MHRA reminds the industry of the requirement to submit a variation application for registered medicinal products in case a solvent used in an analytical test has been changed. The note identifies the following main groups concerned:

  • Changes to the test procedure of the active substance
  • Changes to the test procedure of the finished product
  • Change of solvent used for synthesising the active substance

The MHRA emphasises again that all conditions for changes of Type IA and Type IB have to be met and that sufficient supporting documentation has to be provided, accompanied by the Notice to Applicants checklist. From the point of view of the pharm. industry, it is to be welcomed that, in very urgent cases, one can ask for an especially swift assessment by MHRA with reference to "acetonitrile shortage". The complete document can be viewed here: http://www.mhra.gov.uk/Howweregulate/Medicines/Medicinesregulatorynews/CON036276

The topic of acetonitrile shortage is also addressed and discussed at the ECA Education Course "Maximising HPLC Productivity" in Copenhagen, Denmark, from 1-3 April 2009 in addition to the regular programme. The programme of the HPLC Education Courses can be found here.

Author:
Dr Günter Brendelberger 
On behalf of the European Compliance Academy (ECA)

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