Follow-On Biologics Create Challenge for Congress

Follow-On Biologics Create Challenge for Congress
June 1, 2009

Sometimes small differences can have profound effects.

Look at how very similar the three molecules shown in the accompanying illustration appear. But what a difference they can make in the human body! Molecule #1 is testosterone and makes boys. Molecules #2 and #3, respectively, are progesterone and estradiol. They make girls.

Drugs can look very similar but act very differently. This has major implications for the safety and efficacy profiles of what are called biosimilar drugs.

Although these medications are called biosimilars, it is important to realize it is not only the similarities that are important but also the differences. As we see in the molecules in the illustration, seemingly small difference can have a profound effect.

Not So Simple

Traditionally, when innovator chemical drugs have gone off-patent generic manufacturers have been able to manufacture drugs with the identical active ingredient and bring them to the marketplace through an abbreviated approval process. Because the drugs were of small molecular weight and relatively straightforward, identical copies could be made. And since they were truly identical, they did not have to undergo the same exhaustive testing before entering the marketplace as the innovator products they copied.

But with the advent of the “biologic” class of medications, the situation has become much more complicated. Biologic drugs have high molecular weights and are extremely complex when compared with the low molecular weight drugs of the past.

Examples of drugs considered to be biologics are Humatrope, a growth hormone; Epogen, used to treat anemia; and Herceptin, for the treatment of breast cancer.

Challenges, Concerns

Currently biologics are licensed under section 351 of the Public Health Service Act. The act does not include abbreviated approval processes for follow-on biologics similar to 505(b)(2) or 505(j) of the Food, Drug, and Cosmetic Act. These sections are used only to bring generic chemical drugs to the marketplace. Congress is now considering proposals that would create an abbreviated approval pathway unique to biologics.

The complexities of these biologic products create significant challenges and concerns in the crafting of any such legislation.

Biologic products are made from living cells and are not merely the result of chemical reactions in a test tube. Instead, they are the result of complex biologic interactions occurring in living cells. Because living cells are used, the biologics are all unique, and those natural variations make such medications impossible for other companies to replicate exactly.

Thus the term “generic drugs” does not apply to this class of medications. For a drug to be considered generic, the active ingredient must be identical to that in the innovator drug. Since the biosimilar products are not identical to the innovator drugs they attempt to copy, they can only be deemed similar.

And since they are similar but not identical to the innovator drug, the efficacy and safety profiles of biosimilar drugs cannot be known until they are thoroughly tested.

As an endocrinologist, I treat adults with diabetes. I make decisions regarding their treatment based on clinical data. If Congress were to pass legislation that did not mandate clinical and nonclinical testing, I would have no data upon which to base my treatment decisions. In essence, I would be flying blind.

‘Patient Safety’ Paramount

We can learn much from the European experience. Any legislation regarding biosimilar drugs should have patient safety at its core. Both clinical and nonclinical testing should be required before approval, in order to identify potential differences in clinical efficacy, unanticipated immunogenicity, and other adverse events with use of these drugs.

Pharmaco-vigilance with post-marketing studies should also be required of all biosimilars just as they are of the innovator drugs they reference. In addition, because biosimilars are not identical to the innovator drugs, decisions regarding interchangeability should be made by the physician based on each individual patient. The American Medical Association passed a resolution in November 2008 expressing this sentiment.

We all want to make medicines more affordable, but as a physician I know how important it is to make sure patients are getting exactly the treatment they need, not just something “similar.” That’s why it’s important for Congress to be thoughtful in this process and let science guide their judgment. The United States has been the gold standard for medicine, and patients are counting on us to get this right.


Richard Dolinar, M.D. (drdolinar@dolinar.com) is an endocrinologist, a senior fellow of The Heartland Institute, and a consultant to the pharmaceutical industry.

For more information ...

Public Health Service Act: http://www.fda.gov/opacom/laws/phsvcact/phsvcact.htm

Food, Drug, and Cosmetic Act: http://www.fda.gov/opacom/laws/fdcact/fdctoc.htm