The Evolution of Biologics and Biosimilars: Reducing Costs and Improving Accessibility Through Pharmacist Engagement

There has been significant growth in the development of biologic products since the approval of human insulin, the first recombinant biologic product in 1982.¹ In fact, 11 of the top 15 selling pharmaceutical products in the United States in 2017 were biologic products.¹ Biologic products include therapeutic proteins, vaccines, blood components, allergenic products, and monoclonal antibodies. Biologic drugs are defined as large complex molecule compounds that are typically produced in living systems using recombinant DNA technology.² Biologic drugs are innovative treatment options; however, their high cost can be a significant downside for patients.

The Biologics Price Competition and Innovation Act in 2010 was critical to biologic therapy because it established the classification of biosimilars. Biosimilar classification allows for a streamlined drug approval process which was intended to spur competition and reduce the cost of biological product therapies.¹ The FDA notes that there should be no clinically meaningful differences in terms of the safety and efficacy when biosimilars are compared to their reference product. Biosimilars are made from the same types of sources, are administered via the same mechanism, have the same strength, dose, potential treatment effects, and adverse effects as the reference product.²

Many view biosimilars as the generics of biologics. Biosimilars have a few key differences when compared to generic small molecule drugs. Generic small molecule drugs must demonstrate the active ingredient and the bioequivalence is the same as the refence drug. Biosimilars, on the other hand, must demonstrate they are highly similar to the reference product with only minor differences allowed or expected in inactive ingredients. Biosimilars do not demonstrate bioequivalence, instead they must demonstrate no clinically meaningful differences from the reference product.² Since biosimilars do not need to establish clinical safety and efficacy data for approval, there is no need for expensive lengthy clinical trials, which may reduce costs for patients. In fact, in 2022, biosimilar savings were noted to be $9.4 billion in the United States. Since the first biosimilar entry to the United States market in 2015, a total of $23.6 billion has been saved with the use of biosimilars.³

A July 2021 press release from the FDA announced the first interchangeable biosimilar insulin product. In the press release, the acting FDA Commissioner, Janet Woodcock, MD, explained, “Biosimilar and interchangeable biosimilar products have the potential to greatly reduce health care costs.”⁴

Image Credit: © Virtual Art Studio - stock.adobe.com

Interchangeable Biosimilar Products

Interchangeable biosimilar products are biosimilars that may be substituted for a reference product without the intervention of the prescribing health care provider, depending on state pharmacy laws.² Essentially, these biosimilars are substitutable at the pharmacy level without the intervention of the prescribing physician.

Interchangeable biosimilars are expected to produce the same clinical result as the reference product. The risk in terms of safety and efficacy should be no different between patients that are on the reference product vs those that are alternating or switching between the interchangeable product and the reference product. Therefore, manufacturers conduct switching studies to prove there is no decrease in effectiveness or increased risk when switching between products. However, it is important to note that an interchangeable biosimilar is not safer or more effective than another biosimilar or a biosimilar without the interchangeable designation.² All biosimilars go through the same process to establish clinical safety and efficacy data for approval, and those that choose to submit for the interchangeable designation have done the additional switching studies and submitted the data for review.

FDA’s Purple Book

Information about biologic products can be found in the FDA’s Purple Book. The Purple Book includes the categories available of a drug, such as original reference product, biosimilar, and interchangeable. The information is organized in a pictorial format with the drug’s proprietary name as a hyperlink to the different formulations available.

All biologics, regardless of classification, contain a proprietary name and a proper name. The proprietary name is the exclusive name of the product owned by the company under trademark law. The proprietary name is also referred to as the trade name or the brand name.⁵ The proper name is the nonproprietary name designated by the FDA. Proper names typically include a core name and a suffix (Figure 1).² The core name is the component shared among an original biologic product and any biosimilar or interchangeable products. The suffix is 4 lowercase letters, devoid of meaning, which are added to the core name to distinguish between different products.⁵ The core name and the unique suffix should be used when ordering, prescribing, dispensing, and recordkeeping.

This naming system was designed to help with pharmacovigilance and safe use for all biological products. In order to help prevent medication errors, it is critical to ensure the prescribing of biosimilars be distinguishable from the reference product within a formulary. Institutions must consider the most appropriate way to include biosimilars and references products within an electronic health record to minimize risk of prescribing and dispensing errors.⁶ Additional information available in the Purple Book includes the product label and the dosage form.²

Cost of Biosimilars

The creation of biologic products has changed the face of modern medicine for many patients suffering from different disease states. However, cost continues to be a challenge. Biologic drugs are associated with a high research and development expense and the indication is typically very specific for use in a smaller target patient population. When all put together, high medication costs emerge.1

Biosimilars were created to help reduce the cost of drugs by creating competition. As of August 2023, the FDA approved 42 biosimilars across 15 molecules.3 Considering the cost of research and development and the target market, it is not surprising that the number of biosimilars is limited. In order for cost reduction for biologics to occur, biosimilar availability is crucial, as seen by the fact that there are 36 biosimilars on the market with prices averaging 50% less than the reference brand biologic at launch.³

Implementing Biosimilars

Implementing biosimilars into practice has many limitations. The main barriers to biosimilar utilization can be broken down into prescribing, payor reimbursement, and patient perception. Prescribers may feel uncomfortable or uneducated on the topic of biosimilars as many of these medications are newly marketed.⁷ Further, payor reimbursement plays a role in drug selection, especially with the rebate system. Rebates occur between drug manufacturers, pharmacy benefit managers (PBMs), and other partners that incentivize listing higher priced original biologics over biosimilars on formularies. Since the retail price of biosimilars is only modestly lower than that of original biologics, rebates may result in original biologics having a lower post-rebate price than biosimilars.⁸

Insurance coverage including requirements for step therapy and/or prior authorization may limit coverage of biologic products. Since biologics and biosimilars are novel medical treatments, patients may also be unfamiliar with these products. The patient may then refuse biosimilar therapy due to lack of knowledge or understanding of what they are, placing a need for pharmacists to be able to act as educators regarding the benefit of biosimilars, when applicable.⁷

Pharmacists as Educators on Biosimilars

Pharmacists play a critical role in overcoming the educational barriers of implementation of biosimilars. Pharmacists can provide educational services to providers to improve their knowledge base of specific drugs or on the topic as a whole.

Pharmacists can also utilize their vast patient counseling skills to assist patients in understanding the differences between original biologic products and biosimilars; this can help patients make their own educated decisions regarding biologic use for themselves. In order to provide this education, pharmacists must ensure they are actively pursuing knowledge and advancement in the area of biologics and biosimilars through various modalities including continuing education programs, guideline reviews, journal clubs, etc.

At the end of the day, regardless of whether a patient is dispensed an original biologic or a biosimilar agent, the pharmacist must ensure the patient receives proper medication education on the product. This includes reviewing the indication, the dosing, the sometimes complex delivery systems, the adverse effects, the warnings, the monitoring requirements, storage, and so on. The pharmacist provides the unique link between the patient’s prescribed therapy and filled prescription that is integral to a biologic product’s success.

REFERENCES

1. Leber MB. Optimizing use and addressing challenges to uptake of biosimilars. Am J Manag Care. 2018;24(21 Suppl):S457-S461.
2. Curriculum Materials for Health Care Degree Programs - Biosimilars. FDA. December 20, 2021. Accessed May 17, 2024. https://www.fda.gov/drugs/biosimilars/curriculum-materials-health-care-degree-programs-biosimilars
3. The U.S. Generic & Biosimilar Medicines Savings Report. Association of Accessible Medications; 2023. Accessed May 16, 2024. https://accessiblemeds.org/sites/default/files/2023-09/AAM-2023-Generic-Biosimilar-Medicines-Savings-Report-web.pdf
4. FDA Approves First Interchangeable Biosimilar Insulin Product for Treatment of Diabetes. FDA. July 30, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-first-interchangeable-biosimilar-insulin-product-treatment-diabetes
5. SOPP 8426: Assignment of Biological and Drug Product Proper Names and Biological Suffixes; 2023. Accessed May 16, 2024. https://www.fda.gov/media/96219/download
6. Ismail S, Abu Esba L, Khan M, Al-Abdulkarim H, Modimagh H, Yousef C. An Institutional Guide for Formulary Decisions of Biosimilars. Hospital Pharmacy. 2023;58(1):38-48. doi:10.1177/00185787221138007
7. Dalpoas SE, Socal M, Proctor C, Shermock KM. Barriers to biosimilar utilization in the United States. Am J Health Syst Pharm. 2020;77(23):2006-2014. doi:10.1093/ajhp/zxaa297
8. Yazdany J. Failure to Launch: Biosimilar Sales Continue to Fall Flat in the United States. Arthritis Rheumatol. 2020;72(6):870-873. doi:10.1002/art.41203