Basics of Biosimilars

Drugs vs. Biologics: What’s the Difference

If you ask a layperson about biosimilars, you are likely to hear comparisons to generic drugs, and that would not be completely wrong. Biosimilar products are not drugs and they are not generic, in the sense that they’re not identical to the reference product. They are similar in that they’re intended to offer potentially lower prices when made available for sale.

Drugs are made from chemicals and are smaller molecules compared to biologics, which are made from living organisms and are larger molecules. Oh, and biologics tend to be (much) more expensive than drugs.

Regulatory Landscape

Prior to 1984, generic drugs were required to undergo the same level of scrutiny as the drugs they were intended to substitute. In 1984, Congress passed the Drug Price Competition and Patent Term Restoration Act, more commonly known as the Hatch Waxman Act. As a result, generic drug approval was simplified, and the generic sponsor was required to demonstrate only that the generic version was equivalent to the reference (branded) drug. Branded drug companies received consolation through an extension of their market exclusivity equivalent to approval delays for new drugs from the FDA.

The evaluation and approval process ushered in by Hatch Waxman applied only to drugs, and not to biologics, of which there were precious few then. So, the approval system for biologics limped along until Congress approved the Biologics Price Competition and Innovation Act (Biosimilars Act) in 2010.

While drugs are evaluated by the FDA’s Center for Drug Evaluation and Research, biologics are reviewed by the Center for Biologic Evaluation and Research (CBER). The standards for approval of a biosimilar product are a bit more nuanced than that of a drug. Since biologics are more complex and subject to slight differences based on method of manufacture, the biosimilar standard is that the product must be determined to be highly similar to the reference product and that there are no clinically meaningful differences between the biosimilar and the reference product.

Biosimilar Interchangeability and Substitution

While (nearly) all generic drugs are interchangeable, that’s not necessarily true with biosimilars. In order to be considered interchangeable, biosimilars have to demonstrate interchangeability, normally through clinical trial.

You may be familiar with the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, more commonly referred to as the Orange Book. Is there a similar publication for biosimilars? Yes. It’s called “Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations,” and known as the Purple Book. Both books are the official FDA repository of information on whether a drug or biologic is interchangeable.

Adoption of Biosimilars

As with many new things, acceptance of biosimilars by physicians was a bit slow. Because most of the early biosimilars were oncology treatments, physicians were hesitant to use the new products. As time passed, manufacturers and insurers got more creative – discovering ways to encourage wider adoption of biosimilars. The initial reluctance has dissipated, and prescribers are now more comfortable with the efficacy and safety of the newer products.

Opportunities for Biosimilars in the Face of Major Drug Patent Expirations

Between now and 2030, drugs with more than $200 billion in annual sales will lose patent protection, opening up the opportunity for biosimilar introduction. As innovators see their sales decline, the push to find replacement products will intensify and the biopharma industry will adapt in ways we can’t yet predict.

X Factors on Biosimilars

• Learn everything you can about biosimilars and their regulatory landscape.
• Educate your team and your customers on the advantages and obstacles associated with biosimilars.
• Discuss with facility administrators and medical directors the potential impact of biosimilars on their operations.