Biologic Drugs Are like Siblings

Though they are made up of similar genetic material, siblings are very different people. Michael Jackson is different from La Toya Jackson. Julia Roberts is different from Eric Roberts. They share many characteristics, but they certainly are not the same.

This basic concept explains the complex drugs known as biologics, and what some consider "generic" versions of those biologics. In reality, there is no such thing as a generic biologic. Unlike traditional medicines, which are small, simple entities, the large and highly complex biologic is impossible to mimic exactly. Scientists can make a drug similar to the original biologic, but-like a sibling-it will never be identical to the original.

Not the Same
Traditional drugs are made through predictable chemical reactions. Take Claritin, the allergy drug. Chemically, it's a compound called loratadine. Anybody with the right equipment and materials can assemble the 49 atoms of carbon, hydrogen, chlorine, and oxygen to manufacture loratadine. Many manufacturers do just that. Nearly every drug store and retail chain sells its own version of this drug. And at the molecular level, all these drugs are exactly the same.

That's also why insurance companies and doctors consider these generic drugs interchangeable with the expensive brand names. Once one company has tested loratadine and found it safe and effective, we can assume that everybody's loratadine is safe and effective, as long as it has the same formula.

This is not true for the more complicated biologic drugs, which are made from and grown in living sources like yeast, specialized cells, and microorganisms. The sheer size of these drugs also reflects their complexity; it often takes tens of thousands of atoms to make a biologic, compared to the 49 of loratadine. Hence, making biologics requires intensive genetic engineering methods, with more steps, more variables, and the impossibility of exact replication.

Despite the inherent differences between biologics and traditional drugs, some are arguing for an abbreviated federal approval mechanism for copied versions, or "follow-on" biologics. In fact, the Federal Trade Commission recently announced that it would convene a public workshop on how to structure a shortened regulatory pathway for follow-ons.

Proponents of an abbreviated pathway hope to avoid time-consuming and expensive safety trials, just as traditional generics are allowed to do. But biologic drugs are not like small molecules, where a generic form can be made identical to the original. Equating the two groups is like assuming that siblings are all the same.

This misconception is not merely academic. For example, consider the case of erythropoietin, a biologic intended to aid red blood cell production. Originally developed by Amgen and marketed as Epogen, follow-on versions of the drug have been produced and sold in Europe by two other firms under the names Eprex and NeoRecormon. Those drugs, like brother and sister, are similar-made from much of the same genetic code-but they are not identical. And like siblings, they have behaved differently once they’re out in the world.

French investigators found that a number of patients taking Eprex and NeoRecormon developed a devastating condition called pure red-cell aplasia. These patients' bodies completely shut down red blood cell production-the exact opposite of what the drug is supposed to do. Although all the forms were considered identical, pure red-cell aplasia has not been found to be a side effect of treatment with Epogen.

Proceed with Caution
The lesson is clear: Each biologic is a unique compound. Unlike small-molecule drugs that are identical to each other and can rely on original safety data, there should be no "piggy-backing" of original safety data and clinical trials with biologics. Follow-on siblings should go through the same rigorous clinical trials and safety testing as their brothers and sisters, because that is the only way to ensure patient safety. Indeed, this is how Europe has decided to regulate these drugs.

Additionally, in order to track potentially deadly side effects and interactions of these drugs after they come to market, each biologic and follow-on should receive a unique name or identifier and not be classified as a "generic" of a particular biologic. Likewise (and for the same safety reasons), insurance companies should be expressly forbidden from declaring biologics "interchangeable," unless a regulatory authority has specifically identified them in that way.

Biologics hold great promise for the future of medicine. But we must proceed cautiously and with the understanding that two biologic drugs, just like two siblings, are not quite the same and may behave differently in clinical use.