How Similar Is Biosimilar? FDA Has Some Ideas

By John T. Aquino

Drug companies seeking a profitable “interchangeable” designation for their lower-cost biosimilar products now have a road map with a long-awaited FDA draft guidance released Jan. 17.

Patients have easier access to a biosimilar, a copy of an original brand-name biologic drug, that's deemed interchangeable by the Food and Drug Administration because pharmacists can make the substitution without a physician's authorization.

Biosimilars are expected to cost from 15 percent to 30 percent less than brand biologics used to treat diseases such as cancer and hepatitis C. For a biosimilar to be approved as interchangeable, the applicant must show that it produces the same clinical results as the brand biologic.

The draft guidance describes the types of evidence, including results of “switching” studies where patients alternate or switch between the original drug and the biosimilar, that a biosimilar applicant should provide to support interchangeability. The FDA requested comments on the draft guidance by March 20. The notice was published in the Jan. 18 Federal Register (82 Fed. Reg. 5,579).

No Meaningful Clinical Distinction?

Deborah M. Shelton, head of the food and drug law practice of McCarter & English LLP, told Bloomberg BNA Jan. 17 she was pleased that the draft guidance is out and with some of its details. She particularly noted the draft guidance’s encouragement that biosimilar product sponsors seeking an interchangeable designation meet the biosimilar standards for all conditions of use for the original biologic product whether they are seeking licensure for those conditions or not.

“That’s really important for patient safety,” she said. And yet, Shelton expressed disappointment that the FDA is taking fundamental concepts, such as looking at residual uncertainty and the totality of evidence it uses to determine biosimilarity, and not really doing more than applying them to interchangeability.

“I worry that in the end there might not be an appropriate clinical and regulatory distinction between interchangeability and biosimilarity,” Shelton said.

Deborah Lu, a patent attorney at Vedder Price, New York, said she is pleased the FDA has issued the draft guidance. But she’s also wary of its longer-term importance in light of the Supreme Court’s decision to review an appeals court ruling interpreting the biosimilar statute and the Trump administration’s goal of repealing the Affordable Care Act (ACA), which contains the biosimilar statute.

“I don’t think the FDA will push anything through with uncertainty looming,” Lu said.

Totality of Evidence Approach

A biosimilar is a biologic drug product that is highly similar to an FDA-approved biologic, also known as a brand biologic or a reference product (RP). The ACA’s Biologics Price Competition and Innovation Act (BPCIA) provides an abbreviated approval pathway for biosimilars that partly relies on data submitted for FDA approval of the RP. Relying on the RP’s data can reduce the cost of developing the biosimilar. Under the BPCIA, the applicant can seek additional review by the FDA that the product is interchangeable with the RP.

The FDA’s draft guidance is one of a series the agency is issuing interpreting the BPCIA. It says the FDA will use a “totality of evidence approach” in determining interchangeability.

According to the draft guidance, one factor that can be used in determining interchangeability is the demonstration that, for a biosimilar that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the biosimilar and the RP isn’t greater than the risk of using the RP exclusively. The FDA says it expects applications for interchangeability will generally include data from a switching study or studies.

Leah Christl, associate director for therapeutic biologics in the FDA’s Office of New Drugs, wrote in a Jan. 17 FDA blog, “The complex nature of biological products means that there is no one-size-fits-all approach across the product landscape to the data needed to demonstrate biosimilarity. It follows that the data needed to demonstrate interchangeability are also determined on a case-by-case basis depending on considerations such as the complexity of the product, the reference product’s indications and the potential for immune system complications.”

No Mention of Naming, Labeling

Shelton noted that the FDA says it expects applicants to do a switching study or studies, but only if the product is to be administered more than once.

“As for switching study or studies, I would have thought more than one would be required to meet the [interchangeability] standard, and, regardless, that additional clinical data would be required for the standard to be satisfied, whether or not the product is to be administered more than once. Instead, the FDA suggests that extrapolation may be sufficient,” Shelton said.

She added she was also disappointed the guidance doesn’t address naming and labeling of interchangeable biosimilars.

“In the FDA guidances on these topics, the agency kept alluding to the fact that these issues would be covered later, and we all assumed it would be covered in the interchangeability guidance. But it isn’t there. Still, it’s a draft.”

To contact the reporter on this story: John T. Aquino in Washington at

To contact the editor responsible for this story: Randy Kubetin at

For More Information

The draft guidance is at

The Federal Register notice is at

Christl's FDA blog is at

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