On New Year's Eve in 2005, the operators of Novartis' plant in Suffern, N.Y. were jubilant. The facility had just manufactured its 20 millionth treatment of Coartem (artemether/lumefantrine).

CEO Daniel Vasella had publicly promised that the site would produce 20 million treatment regimens of the antimalarial by the end of the year.

The production had previously been done solely at the company's Chinese plant. In just 12 months the Suffern facility learned the production process, purchased specialized equipment and hired staff to begin making the drug.

After the holiday, the leader of the Coartem process team sent an email to Vasella, announcing the plant's success and attaching a photo of the crew on the packaging line.

The drug is an anomaly among Novartis products. While the company makes no money on the drug - it is sold at cost - Novartis produces more of it than any of its other compounds. The charitable investment is good for public relations. But it offers an even greater benefit: The employees who manufacture Coartem are passionate about their work.

"I used to tell my friends that I work for the company that makes Ritalin ," said John Micheline, facilitator of the Coartem Process Team. "Now I tell them I work for the company that keeps people from dying of malaria."

Micheline and other Novartis staff discussed the history of the drug at the site in April. Located in a quiet village of about 11,000 people, the facility is unremarkable from the exterior. A cube-shaped building of white brick and glass, it was built in the 1960s as a Ciba-Geigy plant. Inside there is a hum of activity as workers manufacture and package about 50 different Novartis products.

Suffern Site Tackles Production

Novartis has been producing Coartem since the drug was approved by the Swiss Agency for Therapeutic Products (Swissmedic) in 1998. Until 2005 the drug was manufactured solely at Novartis' plant in China. But when demand for the drug surged the company decided to shift much of its production to the Suffern facility.

Novartis sent a technical team to China in January 2005 to learn the manufacturing process. The company also teamed up with a vendor in Germany that developed the manufacturing equipment and it hired about 58 more people, bringing the staff at the plant to 430.

The plant did not begin manufacturing the drug until August and reaching Vasella's manufacturing goal seemed impossible. But when workers learned how deadly malaria is - every 30 seconds a child dies of the disease and nearly one million people die annually - they were eager to ramp up production.

Micheline said one of his colleagues would hold up a blister pack of pills - known as a wallet - and say to the production crew: "This is a life, guys."

"Every wallet saves a life" became their mantra. The first batches were produced in September. When the Thanksgiving holiday came around the company posted a notice seeking volunteers to work over the long weekend. People readily gave up vacation time and did so again during the Christmas holiday. By working overtime they fulfilled Vasella's promise.

The Suffern plant produces on a daily basis what the factory in China manufactured annually in 2001. Last year it churned out 74 million treatments, or one billion pills, which Novartis says is enough to treat the entire population of France.

Novartis Teams Up with China

Coartem is a combination of two drugs, artemether and lumefantrine. The artemether compound is extracted from artemisinin, which is derived from the sweet wormwood plant. Used in ancient China to treat fever, the plant gained renewed attention in 1967 when North Vietnam asked China for help in coming up with a malaria treatment for its soldiers. The Chinese Army screened thousands of traditional remedies and by the mid-1970s China had isolated the active ingredient artemisinin.

In the 1990s Chinese officials formed a joint venture with Novartis, then Ciba-Geigy, to develop, test and manufacture Coartem. And in 2001 Novartis entered a private-public 10-year agreement with the World Health Organization to make Coartem available at no profit to developing countries where malaria is endemic.

Developing countries buy the drug primarily with grants from the Global Fund to Fight AIDS, Tuberculosis and Malaria, which receives support from G8 countries and the Bill and Melinda Gates Foundation.

Countries also receive funding from the President's Malaria Initiative, launched by the U.S. in 2006, and UNITAID, a charity that raises money from airline taxes. Countries pay Novartis the cost of making the drug, which is an average of 80 cents per treatment pack or 37 cents for a child's pack. Ninety-five percent of the drug goes to African countries.

Demand for Coartem Surges

When Novartis and WHO teamed up they estimated that demand for Coartem would not exceed 2.5 million treatments per year within the next five years. But requests for the drug skyrocketed in 2005.

Hans Rietveld, Global Access and Marketing Director of Malaria Initiatives at Novartis, said there was growing awareness that older products like chloroquine did not work in Africa.

In addition, Rietveld said a 2004 article in Lancet by a group of researchers and public health officials also boosted demand for the drug. Entitled "WHO, the Global Fund, and Medical Malpractice in Malaria Treatment," the piece accused WHO and the Global Fund of allowing member states to use medicines that were known to be no longer effective in treating malaria.

"That caused a landslide," Rietveld said. "WHO became more forceful in demanding member states change their treatment guidelines."

Coartem cures 95 percent of patients infected with the Plasmodium falciparum strain of malaria within three days. WHO added the artemether and lumefantrine combination to its Model Lists of Essential Medicines in 2002.

Rietveld has seen first hand what a difference the drug makes during his visits to health outposts in Africa, where people walk miles to get treatment.

"When you see a mother walk away with a child carrying a packet of Coartem you know this child will make it," he said.

The Coartem Production Line

Micheline, the head of Coartem production, led a tour of the Suffern plant, describing each step in the manufacturing process. Workers first go through changing rooms where they put on paper gowns, booties and caps to prevent contamination of the production sites.

The first stop is the dispensing area, where active ingredients and other materials are doled out according to a recipe and placed in bins. The batch then goes on to the granulation process.

In one room water is added to a bin of powder, which is then poured into a vat with blades that chop up lumps in the material. The concoction is then sent down a chute into dryers. Once the drying is done the batch is taken into a milling room, sifted into a bin and spun in a blender.

The next step is the compression process. The material is put into a machine and compressed into tablets, which are spit into another bin. The tablets are taken to another area to be coated and the finished tablets then go to a warehouse-like room with rows of packaging machines.

The Coartem tablets are fed through the machines into blister packs. Foil is applied to the packs, which are inserted into cardboard cards (wallets) that are then folded and pressed. The machine also forms a dispenser box into which 30 wallets are distributed.

The lot and expiration date are embossed on top of the box, which is then fed into a shipping box. That box is then folded and taped and ready to be sent out.

Coartem for Children and U.S. Market

Novartis is now producing a formulation for children, Coartem Dispersible, which dissolves in water. Swissmedic and several regulatory authorities in Africa approved the drug and Novartis launched it outside the U.S. in January.

Parents used to crush the bitter-tasting Coartem tablets for their children, Rietveld said, and Novartis sought to make something that would be easier for children to take. Novartis developed the cherry-flavored Coartem Dispersible in partnership with the nonprofit group Medicines for Malaria Venture.

The CEO of the group, Chris Hentschel, discussed the development of Coartem at the Pharmaceutical Research and Manufacturers of America's annual meeting in April. He said Vasella wanted to pursue the drug to inspire his scientific staff and have them feel they were doing something good for society.

Hentschel said the development was a boon for both Novartis, which established a relationship with the Chinese pharmaceutical community, and the developing world.

Novartis reached another milestone with FDA's approval of Coartem in April. As an extra bonus, Novartis received a voucher from FDA to obtain priority review of a future new drug application. Novartis is the first recipient of the voucher program, which FDA initiated to award sponsors of drugs for certain tropical diseases.

"We would hope with this new voucher scheme more companies would think of doing something in neglected disease research," Rietveld said. "We were ahead of the pack."

Novartis has shown that giving employees something to feel good about is another reason to follow its path.

- Brenda Sandburg (b.sandburg@elsevier.com)

The Coartem Story: Novartis Workers In NY Feel Uplift In Battling Malaria

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