Robert Popovian is a leader in health care and biopharmaceuticals who is accomplished in pharmaceutical science, business and government, with a distinctive array of academic and practical experience across a wide range of healthcare and business management functions. Positioned at the intersection of economics, policy, and innovation which maximizes patient access.

Robert Popovian, PharmD, MS

 the promise of reducing prices and drug spending in the United States. The unquestioned safety and efficacy of biosimilars have given providers, patients, and employers, amongst many others, the confidence that savings will be even more robust as we embark on the primary target: the launch of 

. Humira is by far the all-time biopharmaceutical revenue generator, with more than 

Adalimumab biosimilars will also be the first biosimilars introduced in the retail marketplace. To date, the majority of biosimilar competition has been for provider-administered medicines. Providers administer such drugs at their offices or infusion centers. As such, there is no need to worry about interchangeability designations since the prescriber and the medicine dispenser is the same health care professional. However, since adalimumab biosimilars may be dispensed directly to patients who self-administer the medicine by a pharmacist, the interchangeability policy for a biosimilar requires further examination. As in the past, when patients, providers, and employers were misinformed about the interchangeability designation by some brand biologic manufacturers. Today, certain biosimilar manufacturers are trying to downgrade the value of having a biosimilar designated by the FDA as interchangeable.

In 2019, a paper co-authored by several Pfizer colleagues discussed how the interchangeability policy was misused by various parties’ intent to create misinformation in the market. It is essential to review 

All biosimilars are deemed safe and effective upon approval by the FDA.

The Biologics Price Competition and Innovation Act of 2009 (BPCIA) created an abbreviated licensure pathway in the United States that allows for the development and approval of biologic products shown to be biosimilar to and/or interchangeable with a US FDA-licensed reference product.

The interchangeability designation is intended to meet an additional statutory standard that would enable substitution at the pharmacy level without the intervention of the health care provider who prescribed the reference product.

Without the interchangeability designation, pharmacy-level substitution may still occur but requires the additional administrative burden of a pharmacist contacting the prescriber, who must approve the substitution.

A designation of interchangeability, or lack thereof, does not relate to the quality, safety, or effectiveness of biosimilars or interchangeable biosimilar products.

The paper did not investigate whether there is a value to having an interchangeability designation. With the exception of insulins and retinal drugs, to receive an interchangeability designation, biosimilars must go through additional switching studies and, in some cases, clinical trials 

Hence, the level of scrutiny is more than a typical biosimilar approved by the FDA.

Besides additional clinical or pharmacokinetic studies, it is crucial to quantify the economic value of having an interchangeability designation. We deciphered the savings associated with the designation by utilizing a surrogate marker. The surrogate marker we chose was the requirement of prior authorization. According to 

, patients abandon 37% of prescriptions requiring prior authorization.

The lack of designation may discourage substitution since a pharmacist has to seek approval from the prescriber. Our calculation is based on a 

According to the study, there were 5.8 million units of Humira sold in the United States, leading to approximately net spending of $10.3 billion. If 100% of Humira prescriptions were switched to a biosimilar, there is a potential for roughly $2 billion in savings. Since the lack of interchangeability designation may lead to abandonment, like prescribed medicine requiring prior authorization, only 63% of Humira prescriptions would be substituted, leading to $1.3 billion in savings. The differential of around $765 million is the economic value of having an interchangeability designation. All of the calculations are based on assumptions. However, for the first time, we can put a dollar amount on how an interchangeable adalimumab biosimilar may garner savings since such biosimilars will have a more straightforward path to substitution.

The BPCIA is a federal law facilitating a path toward approval of biosimilars with or without an interchangeability designation. Interchangeability designations allows a pharmacist to substitute a biosimilar at the point of dispensing without receiving authorization ahead of time from the prescribing health care professional. The requirement is 

It is important to note that some manufacturers who continuously want to devalue the interchangeability designation were the ones who today support the adoption of the state requirement. Lack of interchangeability designations does not influence a biosimilar's safety or effectiveness. However, the lack of an interchangeability designation may create an environment where there may be reduced uptake of biosimilars.

For example, in Canada, the National Prescription Drug Utilization Information System has 

 as possibly reason for decreased uptake of biosimilars.

There is an intrinsic economic value that we have tried to quantify in this paper that requires closer scrutiny by patients, providers, employers, and state and federal government as we embark upon a vital milestone related to biosimilar uptake in the US marketplace: the introduction of Humira biosimilars.

Winegarden is a senior fellow and director center for medical economics and innovation at Pacific Research Institute. He received his PhD in economics from George Mason University.

Peter Pitts is president and co-founder of the Center for Medicine in the Public Interest. He also serves as a visiting professor at the University of Paris School of Medicine. Pitts is a former member of the United States Senior Executive Service and Associate Commissioner of the US Food & Drug Administration where he served as senior communications and policy adviser to the Commissioner.

 AbbVie reports 22.7% growth in full-year 2021 net revenues. Pharmaceutical Technology. February 3, 2022. Accessed November 3, 2022. 

https://www.pharmaceutical-technology.com/news/abbvie-full-year-net-revenues/

 McKinley L, Kelton JM, Popovian R. Sowing confusion in the field: the interchangeable use of biosimilar terminology. 

. 2019;35:4:619-621. doi: 10.1080/03007995.2018.1560223

 Considerations in demonstrating interchangeability with a reference product guidance for industry. FDA. May 2019. Accessed November 3, 2022. 

https://www.fda.gov/media/124907/download

 Prior authorization. CoverMyMeds. Accessed November 3, 2022. 

https://www.covermymeds.com/main/patient-journey/prior-authorization/

 Winegarden, W. Generating drug savings through competition—Estimating the potential savings from competition to Humira and Enbrel. November 2021. Accessed November 3, 2022. 

https://medecon.org/wp-content/uploads/2021/11/DrugSavings_Humira_Final.pdf

 Zhang Y; The National Prescription Drug Utilization Information System in Canada. Biosimilars in Canada: building momentum in the wake of recent switching policies presented at: 2021 CADTH Symposium; November 2-4, 2021; virtual. 

https://www.canada.ca/en/patented-medicine-prices-review/services/npduis/analytical-studies/slide-presentations/biosimilars-cadth-2021.html

Articles

If every adalimumab biosimilar had an interchangeability designation, the United States could save additional $765 million annually, according to calculations from 3 biosimilar experts.

Contributor: What Is the Value of the Interchangeability Designation for a Biosimilar?

For years, policymakers, insurers, pharmacy benefit management companies (PBMs), and certain health care professionals have claimed that market competition does not drive down drug spending or prices. These opinion leaders have seized this false narrative because we don’t know the actual net drug spending or pricing because of rebate contracting, which creates opacity in the economics of the biopharmaceutical marketplace. Fortunately for biosimilars, this untrue fable has been discredited.

We know today that the mere presence of a biosimilar competition suppresses the prices of reference biologics. According to Amgen, we have observed a 

 for reference biologics and biosimilars. ASP is as close to transparent net pricing as one can get to in the drug marketplace since it incorporates most rebate concessions in the final calculation of the price.

Biosimilars singularly are responsible for saving millions of dollars for the true payers of the health care system – patients, employers, and the government. Such savings have been realized despite hurdles erected by PBMs and insurers as they strive to maximize their rebate contracts, thus blocking biosimilar access. In 2020, 

biosimilars saved $7.9 billion, more than triple the $2.5 billion saved in 2019

 in average annual out-of-pocket savings for patients.

These savings will exponentially increase in 2023 as biosimilar competition is introduced for Humira in the United States. Humira is the number one selling biopharmaceutical globally, with 

annual sales of over $17 billion in the United States.

 market alone, according to Humira’s maker AbbVie. Starting in January and continuing throughout the year, 7 Humira biosimilars will be made available in the market with the potential for multi-billion dollar savings for patients, employers, and the United States. government. The path to savings is even more likely since 1 Humira biosimilar has gained interchangeability designation from the Food and Drug Administration (FDA) with others being considered. Hence, we need to do everything possible so that savings are realized.

Unfortunately, the potential success story has some potholes as the FDA has created unnecessary uncertainty in the competitive landscape. FDA has adopted a final policy that the “strength” of an injectable biological product is based on both the total content of the drug substance (in mass or units of activity) and the concentration of the drug substance (in mass or units of activity per unit volume). The FDA changing the regulatory rules regarding a biosimilar’s strength vs its potency can create probable consequences of disincentivizing both the development and, more importantly, uptake of biosimilars.

As most clinicians will attest to, in some therapeutic classes, medicine concentration is an important distinction as it could impact patient outcomes. However, in most cases, the issue of concentration is irrelevant. For example, the manufacturer of the Humira was granted a label extension by demonstrating that high- and low-concentrations of the brand medicine were equal in bioavailability without any expected differences in risk or benefit.

The continued failure of the FDA to address this regulatory conundrum is problematic as it provides a potential roadblock as the reference biologic companies will seize upon the uncertainty and thwart the adoption of biosimilars by introducing varying concentrations of an established product. As Peter Pitts, Wayne Winegarden, and I stated in an 

, “Business as usual” under the existing language of the Biologics Price Competition and Innovation Act of 2009 (BPCIA) means continued disincentives to promote a more aggressive uptake of FDA-approved biosimilars. Worse, reinforcing the status quo moves us even further away from a health care ecosystem based on competitive and predictable free-market principles – precisely the reverse of the intent of the BPCIA.

To ensure that the current definition of strength will not undermine biosimilar adoption today or in the future, Representative Schrader introduced 

 to allow the Secretary of HHS to clarify that the definition of strength should be irrespective of concentration when appropriate.

Biosimilars have provided significant savings and reaffirmed the economic principle of competition in the biopharmaceutical marketplace. We need to do everything to empower biosimilar uptake and address marketing, contracting, or regulatory barriers that undermine their successful adoption in the United States.

Biosimilars provide significant savings and encourages competition in the biopharmaceutical marketplace but the United States needs to do more to empower uptake and address adoption barriers, according to Robert Popovian PharmD, MS.

Robert Popovian, PharmD, MS

Contributor: What Is the Value of the Interchangeability Designation for a Biosimilar?

Opinion: Biosimilar Adoption Will Help Achieve a Bipartisan Goal