Pfizer fined in solvent release case

The world's largest drug company, Pfizer, has been fined $22,500 for failing to properly notify state and federal officials about a chemical release at a Connecticut research and development plant.

The US Environmental Protection Agency said yesterday that an explosion in 2002 at the company's Groton plant released about 1,400 pounds of tetrahydrofuran, a solvent used in pharmaceutical manufacturing. Seven people were injured in the blast.

Tetrahydrofuran is widely used in pharmaceutical manufacturing and has a number of toxic effects on health, as well as decomposing to form greenhouse gases and peroxides that can be explosive.

Pfizer was found guilty of failing to notify the National Response Centre of the release immediately, according to the EPA, which out the company in violation of federal law. It also failed to immediately notify the state Emergency Response Commission.

Most synthetic reactions are solvent based, and look set to continue so for the foreseeable future. Cases like the Groton explosion exemplify the need to search for alternative solvents that are safer and more environmentally friendly.

Pfizer itself won an EPA award in 2002 for developing a new production process for its antidepressant sertraline that eliminated the use of tetrahydrofuran and three other organic solvents in favour of the more benign ethanol.

Tetrahydrofuran is often used to reactions involving strong bases, and the workup of strong base reactions often includes an aqueous extraction. This creates the problem of contaminated aqueous waste, because tetrahydrofuran is completely water-miscible. Typically, elaborate steps such as solvent exchange by distillation are taken to avoid the solvent coming into contact with water, but this is an energy-intensive process.

Seeking a solution, other research programmes at the EPA and elsewhere have designed derivatives of tetrahydrofuran that retain their solvent ability but are safer to use, by making them insoluble and immiscible with water.

One derivative, n-octyl tetrahydrofurfuryl ether, has already been shown to be a suitable replacement for tetrahydrofuran in a series of reactions in the synthesis of the human immunodeficiency virus (HIV) protease inhibitor Crixivan (indinavir sulfate), sold by Merck & Co.