Submitted: 21 April 2015; Revised: 8 May 2015; Accepted: 11 May 2015; Published online first: 25 May 2015
The Biologics Price Competition and Innovation (BPCI) Act of 2009 was signed into law on 23 March 2010 by President Barack Obama. The BPCI Act establishes an abbreviated approval pathway for biological products that are demonstrated to be ‘highly similar’ (biosimilar) to, or ‘interchangeable’ with a US Food and Drug Administration (FDA) approved biological product.
In the US, FDA, under the BPCI Act, has the authority to designate a biosimilar as interchangeable. The term ‘interchangeable’ is used in the US as a scientific designation to indicate that FDA has made a scientific determination that the product ‘can be expected to produce the same clinical result as the reference product in any given patient’, and for products administered more than once to an individual, ‘the risk in terms of safety or diminished efficacy of alternating or switching between the biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch’. The European Medicines Agency (EMA) does not have the authority to evaluate a product for its safety in terms of repeated switching1.
On 28 April 2015, FDA released three final biosimilars guidances  and US states are now contemplating substitution of interchangeables biosimilars . This follows the agency giving marketing authorization to its first biosimilar on 6 March 2015 . Sandoz’s Zarxio (filgrastim-sndz) injection became the first biosimilar ever to be approved in the US, for five of the indications for which the US-licensed originator biological, Neupogen, is approved. In anticipation of such an approval, many US states have been considering, or have introduced, laws related to the substitution of biosimilars at the pharmacy level .
Zarxio was approved as a biosimilar, not as an interchangeable product. Guidance on how to establish interchangeability is still lacking from FDA. Industry groups have called on the agency to promptly finalize guidance on establishing interchangeability, as well as to issue guidance on the issue of naming, given the fact that FDA has designated a placeholder non-proprietary name for Zarxio .
Most of the proposed legislation requires the retail pharmacist to communicate to the prescribing physician the identity of the product dispensed if an interchangeable product is available, regardless of which product (brand-name or interchangeable) was dispensed.
Compromise language developed by both biosimilar and originator manufacturers is supported by more than 20 companies and organizations, including the Biotechnology Industry Organization (BIO) and the Generic Pharmaceutical Association (GPhA). The compromise proposal requires the dispensing pharmacist to ‘communicate to the prescriber the specific product provided to the patient, including the name of the product and the manufacturer’ ‘within a reasonable time’. It does not require the pharmacist to wait for approval from the physician and thereby reduces any delays for patients. An option to provide the information via an interoperable electronic system, such as a prescribing system, also reduces the burden on pharmacists .
Biosimilar substitution bills, including those with physician notification after the product had been dispensed, began appearing in US states in 2013. Opposition came from manufacturers of generics and from organizations representing pharmacists, who objected to the extra workload communication requirements might entail. However, now a new batch of bills is appearing, many using the newly proposed ‘compromise wording’.
Communication periods vary from within 24 hours after dispensing in North Dakota to within 10 days in New Jersey. Record keeping is also a part of many of the proposed bills, with the length of time that records of biosimilars substitution have to be kept varying from two to 10 years as is consistent with each state’s policy for generics.
Thirteen states: California, Idaho, Illinois, Louisiana, Maryland, Michigan, Mississippi, New Jersey, Oklahoma, Oregon, Pennsylvania, Texas, Vermont are currently considering legislation on the substitution of biosimilars for brand-name biologicals.
Twelve states, including Colorado, Delaware, Florida, Georgia, Indiana, Massachusetts, North Carolina, North Dakota, Tennessee, Utah, Virginia and Washington; have passed legislation requiring prescriber communication and record keeping for biosimilars.
Virginia has also passed a biosimilar substitution law, but with a sunset clause on the prescriber communication provision, which expires on 1 July 2015. The state is currently considering an extension to the clause, see Table 1.
The wording in the different state legislation varies, but, where a time limit for prescriber communication is specified, it is similar to that of Utah:
‘Within five business days following the dispensing of a biological product, the dispensing pharmacist or the pharmacist’s designee shall make an entry of the specific product provided to the patient, including the name of the product and the manufacturer. The communication shall be conveyed by making an entry into an interoperable electronic medical records system, through an electronic prescribing technology, a pharmacy benefit management system, or a pharmacy record that is electronically accessible by the prescriber. Entry into an electronic records system as described in this Subsection (8) is presumed to provide notice to the prescriber.’
For the ‘compromise wording’ the text in the bills is similar to that of Colorado:
‘Within a reasonable time after dispensing a biological product, the dispensing pharmacist or his or her designee shall communicate to the prescribing practitioner the specific biological product dispensed to the patient, including the name and manufacturer of the biological product. The pharmacist or his or her designee shall communicate the information to the prescribing practitioner by making entry into an interoperable electronic medical records system, through electronic prescribing technology, or through a pharmacy record that the prescribing practitioner can access electronically. Otherwise, the pharmacist or his or her designee shall communicate to the prescribing practitioner the name and manufacturer of the biological product dispensed to the patient using facsimile, telephone, electronic transmission, or other prevailing means.’
‘The pharmacy from which the biological product was dispensed must retain a written or electronic record of the dispensed biological product for at least two years after the substitution.’
1The term ‘interchangeable’ is used to mean different things in the US and Europe. In the US, it is the result of a scientific evaluation by FDA. In Europe, no entity makes a scientific evaluation of the safety of repeated switching, but EU Member States have the authority to determine that pharmacists may distribute a different product.
Competing interests: None.
Provenance and peer review: Article prepared based on extensive research; externally peer reviewed.
Michelle Derbyshire, PhD, GaBI Online Editor
1. GaBI Online – Generics and Biosimilars Initiative. FDA finalizes biosimilars guidelines [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 May 8]. Available from: www.gabionline.net/Guidelines/FDA-finalizes-biosimilars-guidelines
2. Derbyshire M. US state legislation on biosimilars substitution. Generics and Biosimilars Initiative Journal (GaBI Journal). 2013;2(3):155-6. doi:10.5639/gabij.2013.0203.040
3. GaBI Online – Generics and Biosimilars Initiative. FDA approves its first biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 May 8]. Available from: www.gabionline.net/Biosimilars/News/FDA-approves-its-first-biosimilar
4. GaBI Online – Generics and Biosimilars Initiative. California and Illinois consider biosimilar substitution bills [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 May 8]. Available from: www.gabionline.net/Policies-Legislation/California-and-Illinois-consider-biosimilar-substitution-bills
5. GaBI Online – Generics and Biosimilars Initiative. Compromise reached on US legislation on biosimilars substitution [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 May 8]. Available from: www.gabionline.net/Policies-Legislation/Compromise-reached-on-US-legislation-on-biosimilars-substitution
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