Biologic products are crucial in the treatment of many conditions, most notably oncologic and autoimmune diseases. As many biologic drugs now possess expired or expiring patents, the development of biologics that are highly similar to these drugs, known as biosimilars, has increased. Though biosimilars have no clinically meaningful difference from their reference product, they are also not exact copies of the latter. Because of this, as development of these similar drugs increases there are many points to consider when creating a framework for the utilization of biosimilars in clinical practice.
Basis for FDA Approval
Biosimilars undergo stringent testing to demonstrate that any differences between the biosimilar and reference product are not clinically meaningful in terms of safety, purity, and potency (ie, safety and effectiveness). Prior to approval, the FDA reviews the totality of evidence submitted, including structural and functional characterization data, nonclinical evaluation, human pharmacokinetics and pharmacodynamics data, clinical immunogenicity data, and comparative clinical studies data. It is acceptable to have minor differences between the biosimilar and the reference product in clinically inactive components such as the stabilizer or buffer. During the manufacturing process of biosimilars or biologic products, these slight differences are expected and considered acceptable within-product variations.1
Once a biosimilar product is approved by the FDA, it must meet additional requirements described in the Biologics Price Competition and Innovation Act in order to be deemed interchangeable. In some states, should a product be deemed interchangeable, it can then be substituted for the reference product without consultation with the prescriber. Data must be supplied to show that an interchangeable product will produce the same clinical effect as the reference product in any given patient. The biosimilar also must be evaluated for safety and efficacy were patients to be switched between the reference product and the interchangeable biosimilar. Pharmacy laws and practices vary in each state, and the state may require prescriber consultation or notification.1 At the time of publishing, no currently approved biosimilars have been deemed interchangeable.
Pharmacy and Therapeutics Committee Considerations
The integration of biosimilar agents into clinical practice presents both operational and clinical challenges. Notably, as there are currently no approved interchangeable biosimilars, the pharmacy and therapeutics (P&T) committee must evaluate each biosimilar prior to formulary inclusion. The approach to adopting biosimilars differs between institutions, and most facilities have created a unique approach to evaluate these products as the standard review process for other FDA-approved novel agents is often insufficient. Each institution should describe its approach to biosimilar adoption in a detailed written policy so that all health care providers within the institution are aware of the evaluation process.
Common options for structured biosimilar approval reviews include full P&T Committee review, abbreviated review, or managing similar to a generic product. For a full P&T Committee review, a new drug monograph needs to be presented, including a comprehensive, unbiased review and analysis of the evidence available in the scientific literature. The committee should consider efficacy, safety, drug storage and preparation, cost, and patient access data (see TABLE 1). An abbreviated review may be used for drugs that are significantly similar to other available therapeutic alternatives, provided the committee agrees the drug is therapeutically equivalent to agents already on formulary. Generic drug products do not require review or approval by a P&T Committee since they are considered bioequivalent; however, a review of bioequivalency data and key safety concerns (eg, look-alike, sound-alike concerns) should be conducted. The main differences between the types of reviews is the depth of evaluation with full P&T reviews being the most comprehensive.
The timing of the P&T Committee’s evaluation of the biosimilar can also differ between institutions. The P&T Committee can either begin their review when the biosimilar is FDA approved or when the biosimilar is available for purchase. One limitation with evaluating biosimilars individually as they become available for purchase is a possible delay in the usage of the product, depending on frequency of committee meetings and lag time to product implementation. Additionally, an objective analysis of comparative data demonstrating the efficacy and safety of a biosimilar for specific patient populations treated at the institution must be completed with each FDA approved biosimilar.
Another approach an institution can utilize is approving each biosimilar once it is available on the market. This may allow for the biosimilar to receive the same formulary status as the reference product in order to utilize the newly available product in a timelier fashion. When utilizing this approach, a formal monograph will still need to be added to the next P&T Committee agenda. Nevertheless, this allows pharmacists to review each biosimilar in great detail without requiring a full committee discussion.
Regardless of the approach ultimately taken to add biosimilars to an institution’s formulary, consideration must be given to reimbursement issues as different payers will require the utilization of specific products.
A Framework for Biosimilar Integration
Adopting clinical and operational standard of practice policies will assist in integrating biosimilars into clinical practice (see TABLE 2). The following steps will help create a framework for the utilization of biosimilars in clinical practice:
The availability of biosimilars provides cost savings opportunities for hospital pharmacies; however, the FDA has yet to approve a biosimilar as interchangeable. As such, facilities should develop and document a detailed policy for evaluating biosimilars, including factors such as timing evaluations to market release dates, incorporating payer considerations into the review process, and steps for auditing reimbursements rates of newly adopted products. This framework will help support the integration biosimilars to benefit both the pharmacy and patients.
Megan May, PharmD, BCOP, received her doctor of pharmacy degree from Samford University’s McWhorter School of Pharmacy in Birmingham, Alabama. She provides comprehensive pharmaceutical care to patients at Baptist Health Lexington’s Cancer Center as a clinical oncology pharmacy specialist. In addition to direct patient care, Megan plays an active role in the education of pharmacy students and residents. Her research interests include oncology supportive care, oral chemotherapy specialty pharmacy, patient medication adherence, patient outcomes, and residency training.
Ashley E. Glode, PharmD, BCOP, graduated from Duquesne University School of Pharmacy in 2007 and is an assistant professor at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences. She works in the phase I/GI/sarcoma/head and neck multidisciplinary clinic, providing patient education and clinical consults for cancer patients receiving standard of care or study treatment. Ashley teaches at the School of Pharmacy and conducts scholarly activity. Her professional interests include the use of complementary and alternative medicine, the pharmacist’s role in optimizing supportive care, and patient education.