Will U.S. Learn From Other Nations' Biosimilar Interchangeability Regulations?

By Anna Rose Welch, Editorial & Community Director, Advancing RNA

Frustration over the lack of FDA guidance on interchangeability and labeling reached a peak late last week following a speech by Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER), in front of the Senate Subcommittee on Primary Health and Retirement Security. Woodcock was met with pushback from Sen. Elizabeth Warren, whose proposed pharma “swear jar bill” last winter disgruntled many pharmaceutical leaders. This time around, she reproached Woodcock over the length of time it’s taking the agency to release guidance on interchangeability and labeling — two hot topics on which the healthcare and pharmaceutical industries are waiting with bated breath for FDA insights.

The agency currently has eight guidance documents for biosimilars, three of which have been finalized, and five of which are still currently in draft form, including the most recently issued guidance on biosimilar names, BioPharma-Reporter says. However, the pathway for regulatory approval for biosimilars has been in existence for five years, and the industry and government officials are anxious to learn just how prominent and prescribed biosimilars will be in the U.S.

But Woodcock defended the pace at which the agency is moving, stating to the senators, “We have to get the science right. We can’t have problems with the first biosimilars out of the block. The most important thing is setting the scientific framework as bulletproof.” So how long exactly will “bulletproof” take? According to BioPharma-Reporter’s account of the speech, Woodcock said to not expect the complex guidances for interchangeability and labeling anytime within this year.

When it comes to biosimilar interchangeability, the FDA is, naturally, focused on maintaining patient safety, especially since small changes in the manufacturing process of biologics can lead to changes in how the body reacts to the medicine. As a biologic will never be identical from batch to batch, and because a biosimilar will never be a perfect mirror image of its reference, the FDA has concerns about switching patients from biologics to biosimilar versions without increasing safety risks. The interchangeability statutory standard defines a drug as interchangeable only if, “when administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the biosimilar product and its reference product is not greater than the risk of using the reference product alone.” The U.S. only has one biosimilar available now, but there are many different versions of each biosimilar being made by a number of different drug companies. Should interchangeability be permitted for a particular reference/biosimilar, there most likely will be safety concerns about what would happen should a patient receiving a biosimilar from one manufacturer begin receiving a biosimilar from another company.

The U.S. is certainly not the only country confronting these concerns. In fact, just as this news broke this week, I was sitting down to read the Pharmaceutical Society of Australia’s (PSA) position statement on biosimilars. The statement was similarly addressing some of the lingering concerns surrounding the topic of biosimilar substitution, in particular the concern over patient safety “were patients to receive different biosimilars from month to month.”

However, despite these concerns, Australia decided to throw caution to the wind, making some significant waves in June when the Prescription Benefits Advisory Committee (PBAC) recommended that biosimilars could be “a” flagged, giving pharmacists permission to dole out a biosimilar in place of a reference drug at the pharmacy counter. There are, of course, several characteristics that the biosimilar must meet in order to earn an “a” flag, which are outlined in this Generics and Biosimilars Industry (GaBI) article.

In making this recommendation, Australia became the first and only nation to institute interchangeability at the pharmacy level — though, like with generics substitution, the PBAC recommended the patient be given the choice of the reference or biosimilar. Australia's decision to permit substitution led to disagreements from the U.S.’s Alliance for Safe Biologic Medicines (ASBM) and BIO. In particular, the ASBM was adamant that “treatment decisions involving these complex and sensitive medicines should be made by the physician and patient, not a third party.” I acknowledge that giving pharmacists, who don’t know the patient the same way their doctor does, this ability to swap between a biologic with a biosimilar is a risk and takes away some of patients’ agency to make their own health decisions (especially in the age of patient- centricity). But, no matter how much is understood about the science, labeling a biosimilar as interchangeable will always be a huge leap of faith because of the nature of the treatments and the biological differences among patients and their varying responses to medical treatments.

I admire Australia’s moxie to take this leap into new territory, not only to lower healthcare costs, but to help give the biosimilar market strong footing within its country. I imagine one of the motives behind the PBAC’s decision was an attempt to improve Australia’s standing in the biosimilar realm, considering one Frost & Sullivan healthcare consultant told BioPharma-Reporter that the country “has a small generic and biosimilar medicine market. This is not very lucrative for the big pharmaceutical companies.” Making biosimilars interchangeable could encourage both reference and biosimilar makers (especially biosimilar makers) to grow their presence within the country and lead to a more competitive and cost-effective model of healthcare. Who knows, maybe someday they’ll serve as a model for the U.S.

But my divergence into Australia and its risk-taking is still perfectly relevant to the U.S. today, even as the FDA remains cautious about interchangeability and all other things biosimilar. This week, the biotech industry and the FDA got a wake-up call from presidential candidate Hillary Clinton, who has begun to outline a plan to rein in drug costs. If she could pull it off, biologics would be limited to a seven-year exclusivity period. This would be excellent news for biosimilar makers and payers. (Well … at least if biosimilars are prescribed and/or a majority are found to be interchangeable by the FDA. Though, honestly, I don’t expect her to succeed in chiseling exclusivity periods quite this much if the recent Trans-Pacific Partnership debates over biologics exclusivity are any indication.)

However, another part of this platform that struck me was her call for the FDA to “give prioritized, expedited review to biosimilar applications that only have one or two competitors in the marketplace.” Not only does an expedited review imply the FDA would have to speed up the formation of the biosimilar market, but it seems to me the more competition entering the market, the more need we as a country will have for interchangeability between a majority of biosimilars and reference products. After all, what good would a populated biosimilar market be if few doctors are prescribing biosimilars (especially in the beginning) and drug costs keep escalating?

In fact, a recent Reuters article revealed that biosimilars account for 80 percent of infliximab use in Poland. Norway closely follows, while countries like Germany, Spain, and the U.K. have lower biosimilar penetration rates. Why might this be? Norway has a steep discount for biosimilars (69 percent from the reference product [whoa]), while Poland does not have any guidelines restricting biosimilar substitution. Germany and Spain currently forbid interchangeability, and the U.K.'s NHS recommends doctors prescribe the brand name to avoid substitution. (To be fair, Poland doesn’t have written legislation permitting substitution either, but perhaps its less stringent approach here is worthy of reference for us.) And then, there’s Australia jumping into biosimilar interchangeability with both feet. No doubt, because of this decision, the nation will learn valuable information about biosimilar performance — and hopefully, through their experience, we will too.

As an industry we’ve experienced the launch of a generics industry that has grown into a successful and acceptable form of treatment. Biosimilars have been used to successfully treat patients in Europe for upwards of 10 years. They might not be interchangeable in every country, but the growth of the global biosimilar market, and the fact that, according to the NHS, there have yet to be any safety issues arising from biosimilars, should serve as reassurance that we are not forging entirely new ground here. I’m hoping that someday soon we’ll take a page from the bravery of other nations, like Australia, and be a little less afraid of biosimilars.