Since 2010, the Food and Drug Administration (FDA) has been providing guidance and resources for the establishment of a biosimilar category of drugs. These drugs will be listed in the Purple Book, a reference for all biologic products licensed under section 351(k) of the Public Health Service Act. The goal of this article is to identify the appropriate action and resources available to determine if a new biologic drug is considered biosimilar to a reference product and if that drug is interchangeable with the reference product without the intervention of a prescriber.
The Biologic Price Competition and Innovation Act of 2009 (BPCIA) was signed into law on March 23, 2010 as part of the Affordable Care Act (ACA). The BPCIA created an abbreviated process for biologic products to be designated as biosimilar or interchangeable with an FDA licensed reference product. To be determined biosimilar the manufacturer of a product must first submit a Biologics License Application (BLA) which includes analytical, animal and clinical studies demonstrating that the product meets the following guidelines:
- The biological product is highly similar to the reference product not withstanding minor differences in clinically inactive components.
- There are no clinically meaningful differences between the new biological product and the reference product in terms of safety, purity and potency in one or more of the conditions for which licensure as a biosimilar is sought.
An interchangeable drug is a biosimilar product which may be substituted for an existing biologic product on the market without a new prescription or intervention by a healthcare professional. Currently there are no FDA approvals for interchangeable biologics. While the FDA continues to update guidance on biosimilars, it has not offered specific guidance on what, if any, additional studies are needed to designate a drug as interchangeable aside from certain broadly defined criteria:
- Must be biosimilar to an FDA approved reference product.
- Must be expected to produce the same clinical result as the reference product in any given patient.
- Must demonstrate the same safety and efficacy so that if multiple doses are required, switching between the reference product and the biosimilar would be the same as using only the reference product continuously.
The Purple Book
The Purple Book is a list of biological products licensed by the FDA under the Public Health Services Act. It identifies whether an agent is biosimilar or interchangeable with an already licensed FDA biological product. The Purple Book is composed of two organized lists prepared by the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). These lists contain the product name, proprietary name, date of licensure, reference product exclusivity expiration date, interchangeable or biosimilar status, and whether the drug has been withdrawn.
Per the current FDA guidance new biosimilar products will be designated by the addition of a four letter suffix to the core name of the drug and separated by a hyphen. In March 2015 the first and only biosimilar currently listed, filgrastim-sndz (Zarxio), was approved as a biosimilar drug for filgrastim (Neupogen). This drug can be prescribed for the same indications as Neupogen; however since it was not designated as interchangeable, switching between these products would require a new prescription order.
Recently the injectable Glatopa was approved as substitutable for the multiple sclerosis medication Copaxone. While Glatopa is substitutable for Copaxone, the drug product of both medications, glatiramer acetate, is not listed as a biologic product. It is instead listed as a class of medication known as a non-biologic complex drug (NBCP). Complex drugs are characterized as products where one specific molecular structure for a drug product does not exist but instead consists of a mixture of multiple similar structures. Theses mixture cannot be precisely characterized by chemical analytical means and are highly dependent on manufacturing processes. Non-biologic complex products are not listed in the Purple Book but are instead listed in the Orange Book where Glatopa is considered an A-rated injectable product (AP) for Copaxone and is considered substitutable.
Other Biologic Products
Some biologic products which may seem highly similar to one another are listed in the Purple Book. The product tbo-filgrastim (Granix) is the same class of drug as both Zarxio and Neupogen but based upon its designation is not considered biosimilar or interchangeable. Epogen and Procrit are identical formulations of epoietin alfa marketed by different companies under the same BLA, while Aranesp is a stand-alone formulation known as darbepoietin alfa. Though all three drugs have similar labeling , Aranesp is not biosimilar to Epogen or Procrit. Most states legally require a listing in the Orange Book to determine what formulations of a drug are substitutable without a new prescription. For this reason, Epogen and Procrit are generally not considered substitutable for one another without the intervention of a prescriber. Betaseron and Extavia are both versions of interferon beta-1b, and have the same dosage and indication for the treatment of multiple sclerosis. Though both drugs are produced through the same manufacturing process, Extavia is not considered biosimilar or interchangeable with the older drug Betaseron. Other drugs which some might consider biologics, such as synthetic insulins, are considered hormones, are regulated specifically under the Federal Food, Drug and Cosmetic Act, and are listed in the Orange book.
– Elijah Dawson, PharmD candidate, and Sarah Lawrence, PharmD, MA, CGP are with Sullivan University College of Pharmacy.