Notice - Acetonitrile Shortage Pertaining to Pharmaceutical Procedures

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Contact: Bureau of Pharmaceutical Sciences

August 20, 2010

Notice

Our file number: 10-117287-670

Acetonitrile Shortage Pertaining to Pharmaceutical Procedures

Currently there is a worldwide shortage of acetonitrile (ACN) that is impacting the pharmaceutical industry. Acetonitrile is a popular solvent used in some manufacturing processes for pharmaceuticals and in some testing procedures.

The shortage has resulted in a price increase and consequential manufacturing and testing changes within the pharmaceutical industry in order to either avoid or reduce the use of this important chemical. Various strategies have been proposed to deal with this shortage including; recycling, changing to alternative solvents and using methods that reduce ACN use.

Solutions related to testing include going to a shorter and/or narrower High Performance Liquid Chromatography (HPLC) columns. More specifically, the following changes have been proposed and these guidelines provide a straightforward approach to mitigating the effects of the ACN shortage on routine methods. Alcohol-based mobile phases can be substituted for ACN. In addition, temperature elevation of the separation improves the peak shape in all solvents. A change from an HPLC to Ultra Performance Liquid Chromatography (UPLC) method or to Rapid Resolution Liquid Chromatography (RRLC) method is another option to reduce ACN use.

Solutions related to synthesis and/or purification of Active Pharmaceutical Ingredients (API) include the use of Methanol or another solvent in-lieu of ACN. The change to Methanol or any other alternative solvent may result in different polymorphic forms and\or impurities. If ACN is to be replaced with another solvent, supporting documentation including validation of the new process and impurities will be required.

Health Canada considers a change in methodology to address the ACN shortage as a Level III change, that is [i.e.] Annual Notification. The use of alternative solvents in-lieu of ACN in the synthesis and/or purification of APIs is to be filed as a Level II change, i.e. a Notifiable Change. All conditions are to be met as per the Post-Notice of Compliance (NOC) Changes: Quality Document.

Should you have any questions or comments regarding the content of the guidance, please contact:

Bureau of Pharmaceutical Sciences
Therapeutic Products Directorate
Health Canada
101 Tunney’s Pasture Driveway
Ottawa, Ontario
K1A 0K9

Phone: (613)941.3195
Fax: (613)957.3989
E-Mail: bps_enquiries@hc-sc.gc.ca