Icahn turns up the heat on Genzyme

Icahn, who wants Genzyme shareholders to elect him and three associates to Genzyme’s 10-member board of directors at the company’s annual shareholder meeting next month, called Genzyme’s manufacturing system “broken’’ in a public filing with the Securities and Exchange Commission Tuesday.

And Icahn, who now controls 4.9 percent of Genzyme shares directly or through his partners, urged shareholders to oust four current directors, including Genzyme chief executive and chairman Henri A. Termeer.

Icahn also asked shareholders to replace former Thermo Electron Corp. chief executive Richard F. Syron, former US Senator Connie Mack III of Florida, and Massachusetts Institute of Technology engineering professor Charles L. Cooney.

The move comes at a time when Termeer, who has led Genzyme almost since its founding 29 years ago, is already under pressure after a raft of manufacturing problems at Genzyme’s flagship Allston plant, which sits on the banks of the Charles River.

The company’s production was temporarily crippled last summer after a virus infected the plant, creating a shortage of two of key drugs, Cerezyme and Fabrazyme, which are used to treat rare genetic disorders.

Last fall, inspectors found bits of steel, rubber, and fiber in some drugs processed at the plant. And just two weeks ago, Genzyme reported that the shortages for Cerezyme and Fabrazyme would likely be extended because of problems with its water system exacerbated by an electrical outage. Genzyme also said it expects to have to pay at least $175 million in fines to settle complaints by federal drug regulators that it put patients at risk by violating stringent manufacturing rules.

Genzyme spokesman Bo Piela declined to comment on Icahn’s filing, but said the company has already recruited new executives to help address its manufacturing problems and has “a very well balanced, experienced board.’’

By contrast, Piela argued Icahn’s nominees “don’t bring any manufacturing or operational experience.’’ In addition, Genzyme argued that two of Icahn’s nominees, Alexander J. Denner and Richard C. Mulligan, have a key conflict of interest because they sit on the board of another Cambridge biotech, Biogen Idec Inc.

Though historically Genzyme and Biogen Idec developed drugs for different diseases, they have gradually started to invade each other’s turf as they have grown larger, making them potential rivals.

Genzyme, for instance, is testing one of its cancer drugs, Campath, for use as a treatment against multiple sclerosis, where it would potentially compete against Biogen Idec’s stable of MS drugs. And both companies now market drugs designed to fight cancer.

Denner is an Icahn fund manager and his key adviser on biotechnology issues, while Mulligan is a genetics professor at Harvard Medical School. In addition to himself, Denner, and Mulligan, Icahn also nominated Dr. Stephen Burakoff, director of the Tisch Cancer Institute at Mount Sinai Medical Center in New York.

To help thwart Icahn, Genzyme struck a deal earlier this year with activist investor Ralph Whitworth, principal and cofounder of Relational Investors. The company agreed to put Whitworth on its board and give him the opportunity to help select another director in return for his promise to support Genzyme’s proposals at the shareholder meeting.

And Termeer is likely to address Icahn’s complaints at the company’s annual briefing for Wall Street analysts today.

As he was getting an award from the Greater Boston Chamber of Commerce Tuesday night, Termeer couldn’t help but make reference to Icahn. After the chamber played a video tribute to Termeer, the Genzyme chief executive said, “I hope you send this to Carl Icahn.’’

Todd Wallack can be reached at twallack@globe.com.