By Anna Rose Welch, Director, Cell & Gene Collaborative
Over the past few months, I’ve been doing a deeper dive into the U.S. healthcare settings in which biosimilars are beginning to star. While we hear regularly of the access blockades, rebate walls, patent thickets (and all other types of walls imaginable), biosimilars are actually gaining footholds in a variety of care settings. In addition to Kaiser Permanente, the unicorn of all U.S. biosimilar uptake, I’ve also spoken to doctors and nurses from rheumatology practices and independent oncology centers around the U.S. that have built frameworks for biosimilar usage.
Throughout a majority of these discussions, there was one integral process that had to be completed to successfully introduce biosimilars into that patient population: they had to be added to the health system’s formulary. Obviously, this cannot be done without pharmacists and the work they do to support the P&T committee. Over the years, I’ve penned several articles discussing the pharmacist’s critical role in building physician trust in biosimilars. Of all the stakeholders within the hospital setting, the pharmacist has the most holistic view of a product’s clinical and financial profiles, as well as other logistical considerations — for example, storage, shelf life, refrigeration, and administration. As we continue to see multiple biosimilar competitors launched within each health system, formulary management will be one of the determining factors as to which of these biosimilars will gain the greatest uptake.
Unless we’re pharmacists ourselves, we rarely get a look into the formulary-building process and what this can mean for the usage of biosimilars overall. At the U.S. World Biosimilars Congress in March, I had the chance to connect with Dr. Sophia Humphreys, the Director of System Pharmacy Clinical Services for Providence St. Joseph Health (PSJH). This nonprofit hospital system comprises 51 hospitals and over 1,000 clinics across six states in the U.S. Dr. Humphreys and I connected post-conference, so I could pick her brain on the art of formulary building and the role pharmacists can play as biosimilar usage expands deeper into the curative oncology sector.
Biosimilar Integration Practices Informed By Long-Established AHSP Guidelines
Though biosimilars are relatively new to the U.S., the protocol for implementing more cost-effective products into hospitals is hardly novel; in fact, guidelines for pharmacists seeking implementation have been in place since the 90s. As the healthcare system became acutely aware of the rising costs of medicines, the American Health System Pharmacists Foundation (AHSP) established a set of guidelines laying out a multidisciplinary approach for formulary management and drug utilization management.
These guidelines remain an important practice for pharmacists today. “You do a high-cost drug evaluation, you follow the pipelines of drugs forthcoming to the market, and you examine your evidence-based criteria,” Dr. Humphreys spelled out. “The evaluation structure is the same. The only difference will be the focus of each IDN.” For example, instead of focusing on biosimilar uptake, an IDN may prioritize treating HIV or myocardial infarction over the course of that year, and, in turn, the class or subclasses of medications used to treat these conditions.
Prior to becoming the Clinical Director, Dr. Humphreys was the Drug Information Manager at PSJH. In that position, she designed an evidence-based annual formulary review process, which standardized the annual review of all formulary medications. All medications are classified into the 15 Medispan therapeutic classes, so that they can be reviewed systematically each year. Dr Humphreys and her team also identifies the subclasses of drugs which require a more in-depth review to further improve patient care, standardize clinical practice, and evaluate potential cost saving strategies.
One of the most important processes in the annual review is evaluating the 80/20 factor. In most formularies, high cost medications may make up 20 percent of the health system’s utilization, but usually account for 80 percent of the overall drug spend. In looking through PSJH’s formulary, Dr. Humphreys determined that more than 70 percent of the total drug costs were spent on biologic medications in the last two calendar years, which make up less than 20 percent of the system’s utilization. Naturally, she turned to the concept of using biosimilars to save money and provide the same level of care. Her insight, combined with the well-established AHSP-outlined practices, ultimately informed the inclusion of biosimilars onto the PSJH health system formulary. In 2019, PSJH maintained its high level of clinical care and favorable patient outcomes while also seeing $10 million in savings.
PSJH-Centric Strategy: Expediting Biosimilar Formulary Review
There has been one interesting difference between the emergence of lower cost biosimilars, as compared to lower-cost generics: it’s the fact that interchangeability is not a given for biosimilars. As we all know, back in 1984 when the Hatch-Waxman Act became law, interchangeability of generics — or substitution at the pharmacy level — was permitted without any additional clinical data or a secondary regulatory approval. Biosimilars, on the other hand, are not currently eligible for pharmacist substitution, Dr. Humphreys explained.
The current lack of interchangeability has an impact on the P&T committee review process. Pharmacists have had to usher biosimilars into the IDN P&T review as new products, instead of equivalent alternatives to the original reference product. This meant that Dr. Humphreys and her team had to write a monograph for each new biosimilar that came to the market, regardless of whether they’d reviewed several other previously approved biosimilars for the same original reference product. Though creating a monograph is a standardized procedure for all pharmacists, it is still a time-consuming process and led to delays in implementing biosimilars.
Seeing that original reference products today have anywhere from two to five biosimilars available, Dr. Humphreys recognized the need to implement a more streamlined, expedited approval process for biosimilars at PSJH. “We call them mini-subclass reviews, during which we bring all of the biosimilars for one original reference product into one subclass review before the P&T committee,” she explained. “For example, if you are a reviewing a biosimilar for Avastin, you include all the other approved Avastin biosimilars into that discussion.” Not only did this improve efficiency, but this also utilized the breadth of evidence available for each biosimilar and built up the confidence of the various stakeholders involved.
In light of the success of the mini-subclass reviews for biosimilars, PSJH began placing all new FDA approved biosimilars on a consent agenda at the end of 2019. This allowed these biosimilars to be approved for the formulary more rapidly.
Dr. Humphreys stated that the formulary approval process for a biosimilar needs to begin as soon as the FDA has approved the product, rather than waiting for an official product launch. Putting the biosimilar on the formulary permits the contracting team to begin working with the individual manufacturer on pricing and supply for the PSJH system before the product hits the market.
She noted that having multiple biosimilar products on the IDN’s formulary is helpful for several reasons. One reason is that it provides negotiating power to help the contracting team to secure discounts, rebates, and the appropriate supply.
Additionally, having multiple biosimilar products on the formulary helps the IDN deal with the complex payer network in each location. For example, in Washington State, where Dr. Humphreys is based, the primary payer changes depending on the region, and sometimes by city and even county.
Dr. Humphreys cautioned that the best strategy for smaller healthcare providers may be different from a large IDN. “If I have an infusion clinic with only 10 chairs, it is not realistic for me to stock all biologic medications on the market in my pharmacy. A small infusion clinic should consider purchasing only the medications, which they plan to administer within a few weeks.” Dr. Humphreys noted the importance of obtaining prior authorization from the payer: “It is exceedingly important to obtain prior authorizations before the purchase and administration of the medication. In addition, the patient assistance program should always be explored, in order to maximize access of care.”
For a larger healthcare setting — for example, a hospital with 600 beds that will be treating multiple oncology patients over the following weeks — Dr. Humphreys added that stocking considerations will be a bit different. “It is prudent to have sufficient supplies of commonly used medications on hand in order to streamline care, provided that payer preferences is considered and prior authorization process standardized,” she said.
An important tool in the utilization of biosimilars is the EMR. Thanks to the Affordable Care Act, most health systems today have some type of system in place to quickly and efficiently provide physicians with essential information about medications appropriate for a specific condition and a patient’s particular situation. “These systems can be excellent time savers for busy physicians,” said Dr. Humphreys, especially in large IDNs. “If you have a 50 provider practice, you could go to your oncology group and alert them to the existence of the biosimilar. A large IDN that covers multiple geographic regions with over 25,000 providers and a complex payer mix, on the other hand, is more likely to benefit from biosimilar savings if the products are built into the EHR, for example, the EPIC system.” (For a deeper-dive into how PSJH structured its inpatient and outpatient formularies in the EHR system, be sure to check out Dr. Humphrey’s article in The Center for Biosimilars.)
Education Must Move Beyond The Current Biosimilar Regulatory Pathway
Education regarding the efficacy, safety and immunogenicity is a vital part of encouraging acceptance of the biosimilars. The FDA has multiple resources for healthcare professionals which highlight the regulatory process and the science behind the biosimilars. Nevertheless, questions regarding the effectiveness of biosimilars remain. Dr. Humphreys believes in providing extensive education and information about the nature of large molecule biologic medications, and how biosimilars are highly similar to their reference compounds, with no meaningful clinical differences.
In particular, she pointed to the education concerning which types of data demonstrate biosimilarity. Not only have technological advancements enabled us to see the original reference molecule and biosimilar molecule much more clearly, but the assay development, toxicology, and PK/PD studies add to the clinical certainty. Physicians trust clinical data above all else; and this remains the case today with biosimilars. Physicians have embraced biosimilars, thanks in large part to the fact that they understand these biosimilars have undergone a stringent approval process by the FDA to ensure quality, safety and efficacy.
In today’s industry however, conversations about shifting the emphasis from clinical trials to analytical characterization are increasingly commonplace. In fact, in recent weeks, we celebrated the release of a new publication in BioDrugs entitled, “The Path Towards A Tailored Biosimilar Development.” This will no doubt be only one of forthcoming efforts to dig deeper into the data behind biosimilars’ approvals and determine which data are the most necessary for manufacturers to provide to regulators.
In addition to reworking the regulatory framework (to some extent), another part of preparing for tailored development — whatever that may look like — will require our understanding on the specific purpose of the large comparative efficacy studies. “According to the FDA ‘The goal of a biosimilar development program is to demonstrate biosimilarity between the proposed biosimilar product and the reference product, not to independently establish the safety and effectiveness of the proposed product,’” Dr. Humphreys pointed out. “As such, we need more information and education on why the FDA may not require the expensive randomized controlled trials in a large population for these already highly similar molecules.”