FDA’s updated guidance on interchangeable biosimilars gets mixed response

There has been a mixed response to the US Food and Drug Administration’s (FDA) recent draft guidance update stating that clinical switching studies are generally not necessary to demonstrate that a biosimilar product is interchangeable with its reference product.

In public comments on the guidance update, some groups applauded the FDA’s new direction as a way to improve patient access and lower costs, while some others raised concerns that the guidance would lead to automatic switching at the pharmacy and allow health plans to engage in medical decision making.

The updated draft guidance, which was released in June 2024, outlines the agency’s evolving position on the evidence needed to demonstrate interchangeability for a biologic product. Since the draft guidance was first published in 2019, FDA has found there is little risk to safety or for potential decreased efficacy after single or multiple switches between a reference product and biosimilar product.

FDA also noted that current analytical tools can assess biologic products in vitro and in vivo with a greater degree of accuracy than clinical switching studies, which compare outcomes for patients who receive only the reference biologic to patients who alternate between receiving the reference product and the biosimilar.

Reducing costs, improving competition

AHIP, the national association representing health insurance plans, urged FDA to quickly finalize the draft guidance to help speed the approval of interchangeable biosimilars. The group noted that clinical switching studies are expensive, with price tags of $100 million to $300 million.

“Biosimilar manufacturers will either pass along those costs to patients in the form of higher prices or try to compete without an interchangeable designation, limiting market uptake,” AHIP wrote in comments on the draft guidance update.

AHIP also urged FDA to recognize the validity of pharmacist substitution across various interchangeable biosimilars, essentially allowing auto substitution. “If an interchangeable biosimilar can only be substituted for a prescription written for the branded biologic, there is less opportunity for price competition at the pharmacy sourcing level, leading to a continued need for health plan formularies to prefer a particular manufacturer’s product to obtain volume discounts,” AHIP wrote.

The updated guidance will also “alleviate much of the uncertainty and remove impediments to a competitive biosimilar marketplace,” the Academy of Managed Care Pharmacy commented.

UnitedHealth Group noted that “deemphasizing” the interchangeability distinction for biosimilars will not only accelerate the entry of biosimilars into the market, but deter anticompetitive behaviors, ultimately improving affordability for patients.

The biosimilar manufacturer Celltrion USA commended the FDA for reducing the cost and complexity of receiving an “interchangeable” biosimilar designation. But the company also asked FDA to clarify what types of comparative clinical data are needed as part of showing that the product has met the standard as interchangeable.

The US Federal Trade Commission (FTC) also praised FDA’s move away from switching studies, noting that it would help dispel confusion about the safety and effectiveness of biosimilars and potential make biologics more affordable. “This is a step in the right direction to fully realizing the goals of the [Biologics Price Competition and Innovation Act of 2009] to increase competition and innovation among biologics, which could lead to lower prices and increased choice for consumers who depend on these life-saving medicines,” the FTC commented.

Safeguards needed

Physician groups also praised the updated draft guidance for its potential to increase access to biologic drugs. But they urged FDA to ensure there are safeguards, from proper labeling of interchangeable biosimilars to full transparency about switches at the pharmacy.

“The prescribing provider and the patient should be informed in a timely manner when a switch at the pharmacy counter occurs,” the American College of Rheumatology wrote. “FDA labels (package inserts) should clearly indicate whether a biosimilar is interchangeable with the reference (originator) biologic. FDA labels should also clearly delineate all indications for which a biosimilar is approved and specify whether the supporting clinical data for the indication are derived from studies of the biosimilar or the reference biopharmaceutical.”

The American Medical Association also supported the FDA’s updated guidance as a way to increase access to biologics but noted that prescribing physicians must receive adequate notification about pharmacy substitution of biosimilars.

Continued role for switching studies

However, the Pharmaceutical Research and Manufacturers of America (PhRMA) pushed FDA to embrace a “case-by-case” approach to determining when switching studies are needed to determine interchangeability.

“There are key open issues regarding FDA’s scientific standards for interchangeability,
including when switching studies are needed; what data and information FDA expects sponsors to submit to support interchangeability; and the expected data and information on the performance and usability of the delivery device or other presentation of a proposed
interchangeable product,” PhRMA wrote.

PhRMA recommended that FDA revise the draft guidance update or release additional guidance on well-designed switching studies and data generation approach to support interchangeability based on the product and situation.

The Infusion Access Foundation, which represents infusion patients and advocates, raised concerns that the guidance “blurs the line between interchangeable and biosimilar biologics” by removing studies that demonstrate interchangeability. Without robust evaluation, the biologic products could adversely affect patient outcomes and put a strain on the patient-provider relationship by taking biologic selection out of the hands of providers.

“In addition, we believe that the draft guidance will embolden more ‘medical decision making’ by health plans, eroding the patient-provider relationship even further. When health plans dictate substitution over the wishes of a patient’s provider and without a strong evidence base to do so, cost-cutting ends up taking precedence over drug efficacy,” the group wrote.

Comments on updated draft guidance

FDA’s updated guidance on interchangeable biosimilars gets mixed response

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