All over the map

By Jan Bowers, Contributing Writer, March 1, 2022

When the Biologics Price Competition and Innovation Act, also known as the Biosimilars Act, was signed into law in 2010, it was supposed to usher in an era of broader access to the therapeutic benefits of biologic drugs by making biosimilars widely available at greatly reduced cost. It hasn’t quite worked out that way — yet. While the FDA has approved a steady stream of biosimilars in the past few years, their availability to physicians has bumped up against a logjam of patent litigation. Of the 16 FDA-approved biosimilars relevant to dermatology, only three are currently available (see sidebar). In 2020, a joint effort between the FDA and the Federal Trade Commission targeted anticompetitive behavior and misleading communications about biologics and biosimilars, “so, hopefully, it’s going to be a little bit easier [for biosimilars] to come to market,” said Robert E. Kalb, MD, FAAD, clinical professor of dermatology at SUNY at Buffalo. “There are seven biosimilars of adalimumab approved already, but they won’t be prescribed until 2023. A biosimilar of etanercept won’t be launched until 2029.”

Despite the delays and setbacks to market availability of biosimilars, state legislatures have been working to update their laws regarding pharmacy-level substitution of generic drugs to address the substitution of biosimilars. All 50 states have now passed laws that spell out the rules for pharmacy-level substitution of a biosimilar for a reference product. What do these laws mean for dermatologists? DermWorld investigates.

Interchangeable product vs. biosimilar

The FDA’s designation of a biosimilar as an “interchangeable product” is a key factor in state biosimilar substitution laws. In most states, a pharmacist may substitute a biosimilar for a reference product without a prescriber’s prior approval only if the FDA has deemed the biosimilar an interchangeable product. According to the FDA, “a manufacturer of a proposed interchangeable product must show that the product is biosimilar to a reference product and that it can be expected to produce the same clinical result as the reference product in any given patient. The manufacturer must also demonstrate that, for a product administered to a patient more than once, there is no additional risk or reduced efficacy if a patient switches back and forth between an interchangeable product and a reference product, compared to using the reference product without switching.”

The type and extent of data that manufacturers need to submit in order to support a demonstration of interchangeability depends on the specific product and its use, said Sarah Yim, MD, director of the FDA’s Office of Therapeutic Biologics and Biosimilars. An example cited in the FDA’s guidance for industry is that “clinical data needed to support a demonstration of interchangeability of a product expected to have a single target (e.g., a receptor) may be more limited than the clinical data that may be needed for a product acting on multiple targets or less-defined biological pathways.” For biological products that are administered to a patient more than once, one or more clinical studies demonstrating the safety and efficacy of switching a patient between the biosimilar and the reference product “will generally be expected,” according to the guidance document.

Biosimilar substitution laws

The state laws typically address the following areas:

• Whether a biosimilar must be deemed “interchangeable” by the FDA before a pharmacist may substitute it for a reference product without prior approval by the prescriber, and how the state defines “interchangeable;”

• Whether a prescriber can prevent a pharmacist’s automatic substitution of an interchangeable by writing “dispense as written” or “brand medically necessary;”

• Whether the pharmacist must communicate the substitution back to the prescriber and the patient, and the timeframe and the method of communication; 

• Whether, and for how long, the pharmacist must maintain a record of the substitution.

States typically require that a biosimilar be designated an interchangeable product before a pharmacist can make the substitution without prior permission from the prescriber, and nearly all rely on the FDA’s definition of “interchangeable.” Only four states — Alabama, Indiana, South Carolina, and Washington — do not allow the pharmacist to substitute an interchangeable product for a biosimilar without prior permission. Nearly all enable the prescriber to prevent a substitution by writing “dispense as written” or “brand medically necessary.”

Where state laws vary greatly is when and how pharmacists must notify prescribers when they substitute a biosimilar for a reference product, and whether (and for how long) pharmacists must maintain a record of the substitution. Patient notification is typically required at the time of dispensing. “This notification/communication piece is the part that’s most significant for our physicians, and we’ve been involved in advocacy work on this point at the state level since 2011,” said Lisa Albany, JD, the AADA’s director of state policy. “When we engaged on the written comments [on proposed legislation], that was our friendly amendment: We supported amending the generic therapeutic substitution laws to include the substitution of biosimilars, but we wanted that notification to the physician to occur before dispensing. Because biosimilars are so different from generics, our doctors had a huge concern about the substitution without their knowledge.” 

Despite the efforts of the AADA and other organizations, no state requires physician notification at the time of dispensing. “Generally, the response to our position was, if a physician feels strongly that they want the brand name or any specific medication, they can always write ‘dispense as written,’” Albany said. “As the laws stand now, the window that we see is typically three to five days after dispensing. But Delaware gives the pharmacist a full 10 days — we sent a letter to the governor in 2014 opposing that bill.” A few states have repealed their prescriber notification requirements altogether or have allowed them to sunset. Virginia’s five-business-day notification requirement expired in 2015. Oregon’s notification requirement regarding both patients and prescribers sunset on Jan. 2 of this year. 

The method of notification was another key issue for the AADA, Albany said. “Most of the state laws that allow for prescriber notification say you can do this in the electronic medical record. We had concerns about what happens with physicians and small practices that don’t have access to the same electronic record that’s being used by the pharmacist.” Many states use virtually identical verbiage to spell out the ways in which pharmacists may notify prescribers of a substitution. A typical example is Arizona, where prescribers can be notified “through an interoperable electronic medical records system, an electronic prescribing technology, a pharmacy benefit management system, or a pharmacy record or fax, telephone, electronic transmission, or other prevailing means.”

Some states do not stipulate that pharmacies must maintain a record of biosimilar substitutions. Others require a minimum time to retain such records, typically two to five years.

“In an ideal world, I would like to know if the patient was on a brand name and a biosimilar has been substituted,” said Dr. Kalb. “In all likelihood, I would authorize it. In almost all the studies that have been done, we really haven’t seen the problems that people thought might occur. But it’s just helpful to know because then if the patient doesn’t do well, you know that’s the reason, and you can go back and request the brand name.” Psoriasis expert Jashin Wu, MD, FAAD, founder and CEO of Dermatology Research and Education Foundation in Irvine, California, agreed, remarking that “it’s better to let the patient know that it’s possible that if you do get a substitution, you might get a slight reduction of your clearance of psoriasis or a rare side effect. This is better than having the pharmacist tell us three to five days later, and then we have to tell the patient, and maybe by then they already have the problem.” Dr. Kalb said he has been contacted on occasion by a pharmacist wanting to substitute infliximab-dyyb (a biosimilar for infliximab), “and in general, we say yes.” In contrast, on a few occasions while he was employed at another institution, Dr. Wu saw his patients switched from infliximab to infliximab-dyyb or infliximab-abda without his permission.

Formularies and forced switching

The next challenge for the AADA’s state advocacy regarding biosimilars will likely be addressing payer formularies, said Albany. “We’re having a huge issue with forced switching, where the health plan says it has to be this particular medication because it’s on the formulary. With biosimilars, we’re in a wait-and-see mode because there are no interchangeable biosimilars available yet in dermatology. But it will be interesting to see how the pharmacy benefit managers, the health plans, address this.” Dr. Kalb said he is already being told that an insurer will no longer approve brand name infliximab (Remicade) or rituximab (Rituxan) but will rather insist that the patient be prescribed the biosimilar version. “In some cases, I can still prescribe the brand name, but there is a higher copayment/coinsurance and in general the patient opts for the biosimilar due to the lower cost. This could be an issue with ‘dispense as written laws’ that some states enforce. They’ll say ‘Okay, you can have the brand name drug, but your co-pay is going to be higher.’”

“We’re having a huge issue with forced switching, where the health plan says it has to be this particular medication because it’s on the formulary.”

Currently, insurers tend to inform physicians about formulary changes involving originator, or reference biologics, said Dr. Wu. “But I’m not sure what they’re going to do about the biosimilars, because they could easily say, ‘adalimumab is basically the same as adalimumab-adbm [already designated as interchangeable], so we’re just going to make the switch and not necessarily feel the need to tell you. I think we’re not sure yet and we’ll find out — I guess, the hard way — whether they’ll tell us or not.”

The most common way for a dermatologist to circumvent a switch would be to obtain prior authorization from the payer to use the physician’s recommended treatment, or to appeal the switch based on medical necessity, said Louis Terranova, MHA, the AADA’s assistant director of practice advocacy. “Both of these options add to the physician practice administrative burden, are uncompensated, and add to the total cost of care,” he added. Dr. Wu remarked that the barrier to a successful appeal “is going to be very high, because in theory, it’s almost the same drug. If they were appealing a switch from one originator drug to another, I can see why an office would be willing to go through that effort. But if it’s from an originator to a biosimilar, the insurers are going to say ‘Why? This is FDA-approved.’ So, I don’t see how the doctor’s office can really fight it.”

The AADA position

The AADA updated its position statement on generic substitution, most recently in 2013, to address the substitution of biosimilars. The statement can be summarized as follows:

• A biosimilar must have a unique, non-proprietary name to eliminate confusion and allow providers to accurately track the therapeutic effect;

• A biosimilar must be designated as interchangeable by the FDA before it can be substituted for the reference drug;

• The prescriber must provide explicit permission to the pharmacist that a biosimilar may be used as a substitute to the original biologic medication;

• The patient or a representative must be informed and educated about a biosimilar substitution at the point of sale;

• The pharmacist must notify the prescriber in writing or electronic communication by the time of dispensing;

• Upon notification of a substitution, the pharmacy and the prescribing physician are encouraged to retain a permanent record in the patient’s medical record and document any adverse events.

State laws do not address the naming of biosimilars, but the FDA has issued guidance for industry on non-proprietary naming of biologic products. Many states do set out specific requirements for keeping records of substitutions, but there are few references to the reporting of adverse events.

For dermatologists seeking information about the biosimilar substitution law in a specific state, Cardinal Health provides a summary of biosimilar interchangeability laws in each state as of July 2021, with links to the authorizing legislation.

Are dermatologists ready?

As of January 2022, 97 programs were enrolled in the FDA’s Biosimilar Product Development Program, “and the Center for Drug Evaluation and Research has received meeting requests to discuss the development of biosimilars for 47 different reference products,” said Dr. Yim. “The pipeline for biosimilars is robust and we expect there to be more options for dermatology in the future, including more interchangeable products.” 

Dr. Wu believes most dermatologists are not familiar with the range of biologics set to come on the market in 2023. “I was lecturing about this from about 2015 to 2016, but after that there was little physician education because the originator companies kind of squashed the prospects of biosimilars with their litigation,” he remarked. “I think people forgot about it. Now it’s six to seven years later, and dermatologists should start reading up on this issue by the end of this year. Because in 2023, when all these adalimumab biosimilars start coming out, we need to know what this means. Is this going to change patient management? Is it going to affect advocacy? What do ‘interchangeable’ and all these other terms even mean?” In Dr. Kalb’s view, “it’s unfortunate the drugs have been approved years ago and we don’t have access to them, because there’s potential for significant savings. I really can’t wait until we get these drugs.”

Additional DermWorld Resources