BETHESDA, MD 26 April 2013—The state of Virginia on March 16 became the first in the nation to pass a law regarding biosimilars, a move that precedes the availability of these products on the U.S. market.
Virginia's law earned both praise and criticism from various sectors of the drug and health care industries.
The Biotechnology Industry Organization (BIO), which represents more than 1100 biotechnology companies worldwide, lauded Virginia's law for incorporating all of the organization's "Principles on Patient Safety in the Substitution of Biologic Products."
Released in late January, BIO's principles require that a biosimilar be dispensed in place of the originally prescribed product only if FDA has declared the products to be interchangeable. The prescribing physician may forbid the substitution. When a substitution is made, the prescriber must be notified of the event, and the patient must be made aware of the substitution.
Finally, the pharmacist and the prescribing physician must maintain records about the substitution in case adverse events occur or other concerns arise. In Virginia, these records must be maintained for at least two years.
Virginia additionally mandates that the pharmacist's notification of substitution to the prescriber must occur within five business days after the product is dispensed or as described in a collaborative agreement between the pharmacy and the prescriber. And the pharmacy staff must inform the patient of the "retail cost" of the prescribed medication and the substituted biosimilar. These requirements, but no other portions of the law, will expire in 2015.
The Pharmaceutical Research and Manufacturers of America filed a brief in support of a version of the Virginia legislation that contained all of BIO's principles.
The Alliance for Safe Biologic Medicines, whose members include BIO, patient advocacy groups, and biotechnology companies, lobbied for changes to Virginia's law as it advanced in the legislature. Among other things, the alliance emphasized that only biologics that are truly interchangeable should ever be substituted, as opposed to biologics that are highly similar but not interchangeable.
The Generic Pharmaceutical Association on March 21 called Virginia's law well-intentioned but preemptive and said it "carries burdensome administrative 'red tape' that threatens the positive impact biosimilars will have in Virginia."
None of the requirements in Virginia's law apply to substitutions that involve a nonbiologic drug and its generic equivalents.
The Pharmaceutical Care Management Association (PCMA), before Virginia's law was passed, had decried coordinated attempts by the biotechnology industry to influence state laws on biosimilars. PCMA, which represents pharmacy benefit management companies, stated that the campaign would restrict the use of biosimilars and create a confusing patchwork of conflicting state and federal laws regulating the products.
Other entities that announced their opposition to Virginia's law include Teva Pharmaceuticals, Express Scripts, and the Virginia Association of Health Plans.
Biosimilarity versus interchangeability. Federal law requires FDA to create an approval process for two types of biosimilars, or follow-on biologics, as the agency sometimes calls them: those that are biosimilar, and those that are interchangeable.
According to FDA, a biosimilar product is highly similar to an already approved biologic except for minor differences in clinically inactive components. No clinically meaningful differences may exist between the safety, purity, and potency of a biosimilar product and the reference biologic.
Products determined by FDA to be interchangeable must meet these criteria. In addition, they must be expected to have the same clinical benefits as the reference biologic and pose no additional safety or diminished efficacy risks for patients who alternate between the reference product and one that is interchangeable.
Although FDA has not yet approved a biosimilar product, 15 biosimilars have been authorized by the European Union. Of these, six are versions of filgrastim and three are versions of epoetin alfa—biologics whose patents have expired.
The patent for rituximab expires in October, and patents for trastuzumab, cetuximab, and infliximab expire next year, creating opportunities for U.S. sales of biosimilars. IMS Health predicted in 2011 that biosimilars will enter the U.S. market in 2014 and total at least $1.9 billion in annual sales by 2015.
In the states. Brian M. Meyer, director of government affairs at ASHP, said legislation to regulate biosimilar substitution is in the works in more than 20 states, including North Dakota and Utah, which recently passed laws similar to Virginia's (see sidebar).
In general, states' proposed legislation requires that biosimilars must be declared by FDA to be interchangeable before substitution is allowed. States are also proposing that dispense-as-written instructions from prescribers be followed and that prescribers be notified whenever a substitution is made.
Legislation under consideration in Arkansas in late March additionally stipulates that pharmacists may not charge more than the "normal" amount for a biosimilar and its dispensing, compared with the prescribed product. In addition, patient consent is required if a dispensed product costs more than the prescribed one, and the originally prescribed product must be dispensed if the patient insists.
Under this proposed legislation, the determination of interchangeability is made by the state board of pharmacy on the basis of FDA's designation of a product as interchangeable. The pharmacy board would have the power to forbid the substitution of specific products.
In Colorado, legislation pending in early April would require pharmacies, but not prescribers, to retain a record for at least five years of all instances in which a biosimilar was dispensed in place of the prescribed biologic. The proposed legislation would allow pharmacists to meet prescriber notification requirements by entering information about the substitution into "an electronic system between the prescribing physician and the pharmacist, including an electronic medical record."
The Florida legislature is working on a law that adheres to BIO's principles and also covers Class II institutional pharmacies. An amendment proposed in March would allow these institutions to incorporate biosimilar products into their formulary system, as long as accepted formulary procedures are followed.
Meyer said ASHP has been working with its state affiliates to advocate for language in proposed legislation that allows pharmacists in settings with a formulary system "to substitute biosimilar products without the intervention of the prescriber" when the biosimilar is interchangeable with its reference product.