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In 1984 the Hatch-Waxman Act made it cheaper and easier to put generic versions of a drug on the market. As a result of the expedited approval process, generics now make up more than 60 percent of prescription drugs sold in the U.S. and have saved the health care system $734 billion between 1999 and 2008 alone.

By the end of 2011 the FDA plans to release a similar set of guidelines to approve generic versions of biological drugs—a newer breed of pharmaceuticals that includes enzymes, antibodies and other molecules derived from living cells. Unfortunately, experts say, generic versions of biological drugs probably will not be able to reproduce the dramatic savings of the Hatch-Waxman bill.

Biological drugs are used to treat hundreds of types of diseases, including cancer (Herceptin), anemia (Epogen), arthritis (Enbrel), diabetes (Humulin) and human growth disorders (Genotropin). Demand is increasing rapidly for these drugs, even though they tend to be more expensive than traditional synthetic drugs. For example, Cerezyme treatments for a person with a life-threatening enzyme deficiency can cost up to $500,000 per year, and the cancer drug Avastin costs patients $100,000 a year. In the U.S., generic versions of these drugs are currently unavailable, at the expense of the patient and the health care system.

Biological generics will be less expensive than brand-name biologicals, says Dominique Gouty, laboratory director for Intertek Pharmaceutical Services, a company that helps pharmaceutical and biotech companies to test drugs, “but they will still be expensive.”

Under the Hatch-Waxman Act, as long as a manufacturer proved its generic drug was chemically identical to the pioneer drug, the generic could piggyback on the pioneer’s clinical research. By avoiding those expensive animal and human trials to assess the drug’s safety and efficacy, generic drugs were able to cut costs by up to 80 percent. Lowering prices will not be so easy for biological generics, however, largely because they will have a harder time avoiding those costly clinical trials. Here’s why:

1. Biological drugs are bigger and more complicated than traditional drugs

A traditional drug such as aspirin is synthesized entirely from precise chemical reactions carried out in a laboratory. Aspirin weighs a relatively light 180 daltons. Getting FDA approval for a generic drug such as this can be almost as simple as supplying the molecular formula.

In contrast, interferon beta—an antibody treatment for multiple sclerosis—is harvested from cultures of living cells. It weighs 19,000 daltons and contains complicated folds, twists and carbohydrate attachments. The drug can also come in combination with other cellular proteins.

Tools that would describe and compare these complex features are not fully developed yet. So, whereas analytical tools can tell the FDA whether two proteins have the same amino acid sequence, the higher-order features—folds, twists, carbohydrates and overall shape—largely remain in a black box. And nobody knows how differences in those higher-order features may affect patients taking the drug, Schellekens says.

Stephen Kozlowski, director of the FDA’s biotechnology products office, says that more and better analytical tools will make the approval process for biological generics easier. “We think that if you have a better molecular analysis, it reduces uncertainty about similarity,” he notes. “And if you have more confidence that molecules are structurally and functionally similar, then the number of clinical and animal studies should decrease.”

2. Biological drugs depend on touchy manufacturing processes

Because biological drugs are manufactured in living cells, there can be tremendous variation in the drug molecules produced. Getting exactly the right molecule depends on a precise culturing and extraction process, with very specific environmental conditions.

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