New class of drugs brings quandary

[Guest guest]

New class of drugs brings quandary

Benson and Sherri Rombach

May 23, 2004FORUM0523

A new class of drugs, biopharmaceuticals, brings in billions of dollars for

the companies that develop them.

But patents covering some of the early biopharmaceuticals -- including the

hepatitis B vaccine and drugs to treat anemia -- will expire during the next

few years, making them prime candidates for the generic drug market.

All drugs must be approved by the Food and Drug Administration (FDA).

However, the proper way to approve generic versions of biopharmaceuticals --

called biogenerics -- is a hotly debated issue. Billions of dollars depend

on the answer.

For traditional drugs, the FDA has shortened the generic approval process,

allowing the maker of a generic drug to piggyback on much of the testing

done by the maker of the original drug. Because the generic version of the

drug has the same active ingredients as the name-brand drug, the FDA relies

on safety and efficacy studies done by the original manufacturer. This

allows generic drugs to get to market relatively quickly.

But what does it mean to call two drugs the " same " ? Sameness is a legal

standard that requires a generic drug to have a molecular structure

identical to the original drug. Usually, proving sameness is not terribly

difficult.

Biopharmaceuticals, however, present a problem. They typically are big,

complicated molecules, which makes it harder to prove sameness.

But the problems don't end there. Biopharmaceuticals are made using

cutting-edge biotechnology. Typically, the process begins by isolating a

gene. Genes are unique to individual plants and animals. So, for example, if

a process begins by isolating a gene from me, someone who begins the same

process by isolating a gene from my brother might end up with a different

end product.

After the gene is isolated, it is inserted into a cell. This host cell is

used to make the biopharmaceutical. The type of host cell used can introduce

variation into the process. Say, for example, that a bacterial cell is used

as the host cell. Even if the maker of a generic drug uses another cell from

the same strain of bacteria, a small variation is introduced. If a mouse

cell is used, the end result could be very different.

Next, the cells are replicated. These cells become millions of little

factories, allowing for mass production of the biopharmaceutical. But the

conditions under which the cells are grown -- such as temperature, light,

nutrients, even the size of the container they are grown in -- can affect

the end result.

All of these variables make it hard to produce two biopharmaceuticals that

are the same.

Name-brand drug companies argue that the maker of a generic drug can never

show that its drug has the exact same structure as the original.

Additionally, unless the generic manufacturer uses the exact same process

and the exact same starting materials as the original drug manufacturer, the

biogeneric drug will never be the same as the original drug.

Safety and effectiveness are the issue, claim the drug companies. Because a

generic drug manufacturer cannot make a drug that is exactly the same as the

original drug, the public might be put at risk. Alterations to the drug will

result in generic drugs that are less effective than the original drug or,

even more serious, that could be dangerous to the user.

Because of this, name-brand drug companies argue that biogenerics should be

subjected to the full drug approval process of the FDA. In other words,

there never can be such a thing as a generic version of a biopharmaceutical.

Manufacturers of generic drugs, not surprisingly, disagree. They argue that

a complete ban on biogenerics is unnecessary. While it is true that

biogenerics are more complicated than traditional drugs, it still might be

possible in some cases to show that the drugs are the same. They say each

biogeneric drug should be treated separately; if they have sufficient

evidence that the generic version is the same as the patented drug, they can

use the shortened approval process.

Billions of dollars hinge on the outcome of this dispute. If the FDA decides

that biogenerics are too complicated for the shortened approval process,

competition will be severely limited. Cheaper generic versions of

biopharmaceuticals will not be available, and drugs will get even more

expensive.

Conversely, what if the safety concerns are valid? A biogeneric drug might

not work as well as the original drug. Or, even worse, it might have

dangerous side effects that were not present in the original drug. This

would undermine public confidence in the safety and effectiveness of drugs

as a whole and also could raise the overall cost of health care.

Many industry observers believe that legislation is needed to resolve this

issue. In the meantime, the FDA has said it will publish proposals regarding

approval of biogenerics soon. Undoubtedly, these proposals will generate

more controversy as the government attempts to balance the benefit of the

availability of low cost biogeneric drugs with the possible risk to their

safety and effectiveness.

About the authors

Benson is a lawyer with Kinney & Lange in Minneapolis. She has a

master of science degree in molecular, cellular and developmental biology

and genetics and a law degree from the University of Minnesota.

Sherri Rombach also is a lawyer with Kinney & Lange. She has a bachelor of

science degree in pharmacology and toxicology from the University of

Wisconsin-Madison and a law degree from the College of Law.