By Kurt R. Karst –
Although FDA has yet to accept an application for a biosimilar version of a biological product licensed under the Public Health Service Act (“PHS Act”) pursuant to the provisions of the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”) – let alone consider whether a biosimilar product is also interchangeable with the reference product – the groundwork is already being laid in various states for the consideration and passage of legislation governing the substitution of interchangeable biosimilar biological products. In some respects, the battle is a continuation of what happened way back in the 1970s when state antisubstitution laws were changed to drug product selection (or substitution) laws permitting (or directing) pharmacists to substitute therapeutically equivalent generic drug products for their brand-name counterparts. After many of the state drug substitution laws were put in place, FDA prepared the Orange Book to assist state health agencies in administering those laws with respect to generic drug substitution. (Here’s a copy of the first edition of the Orange Book from 1980.)
State legislation concerning the substitution of an interchangeable biosimilar biological product for the brand-name reference product counterpart has already started cropping up, and 2013 may be the year when legislation takes off and is enacted. For example, in 2012, House Bill 5581 (here and here) was introduced in the Illinois General Assembly to amend the state Pharmacy Practice Act to permit interchangeable biosimilar product substitution provided certain conditions are met by both the prescribing physician and pharmacy. Among other things, House Bill 5581 would permit a pharmacy to substitute a prescription biosimilar product for a prescribed product only if:
(1) the biosimilar product has been determined by the FDA to be interchangeable with the prescribed product for the specified indicated use;
(2) the prescribing physician does not designate in writing on the prescription that substitution is prohibited;
(3) the patient (or patient’s authorized representative) provides written consent for the substitution;
(4) the pharmacist notifies the prescriber in writing within 24 hours after the substitution; and
(5) the pharmacy and the prescribing physician retain a written record of the biosimilar substitution for a period of no less than 5 years.
House Bill 5581 did not gain much traction in the Illinois General Assembly last year and may be reintroduced this year; however, efforts to create a biosimilar substitution law in Virginia are moving along. House Bill 1422 (see here and here) was recently introduced and would amend Virginia law such that:
A. A pharmacist may dispense a biosimilar that has been licensed by the [FDA] as interchangeable with the prescribed product unless (i) the prescriber indicates such substitute is not authorized by specifying on the prescription “brand medically necessary” or (ii) the patient insists on the dispensing of the prescribed biological product. In the case of an oral prescription, the prescriber’s oral dispensing instructions regarding dispensing of an interchangeable biosimilar shall be followed. No pharmacist shall dispense a biosimilar in place of a prescribed biological product unless the biosimilar has been licensed as interchangeable with the prescribed biological product by the [FDA] for the specific use.
B. When a pharmacist dispenses an interchangeable biosimilar in the place of a prescribed biological product, the pharmacist or his designee shall inform the patient prior to dispensing the interchangeable biosimilar and shall provide electronic, written, or telephonic notification of the substitution to the prescriber or his staff within five business days of dispensing the interchangeable biosimilar or as set forth in a collaborative agreement as defined in § 54.1-3300. Such notification shall be documented on the record of dispensing. The pharmacist or his designee shall also indicate, unless otherwise directed by the prescriber, on both the record of dispensing and the prescription label, the brand name or, in the case of an interchangeable biosimilar, the product name and the name of the manufacturer or distributor of the interchangeable biosimilar. Whenever a pharmacist substitutes an interchangeable biosimilar pursuant to a prescription written for a brand-name product, the pharmacist or his designee shall label the drug with the name of the interchangeable biosimilar followed by the words “Substituted for” and the name of the biological product for which the prescription was written. Records of substitutions of interchangeable biosimilars shall be maintained by the pharmacist and the prescriber for a period of not less than two years from the date of dispensing.
Earlier this week, the Committee on Health, Welfare and Institutions of the Virginia House of Delegates favorably reported the bill by a 6-2 vote. House Bill 1422 has garnered the support of several organizations, including the Biotechnology Industry Organization, the Colon Cancer Alliance, the Global Healthy Living Foundation, the Kidney Cancer Association, and the Alliance for Safe Biologic Medicines (“ASBM”). Also in the works is a bill from Pennsylvania State Senator Patricia Vance. According to a recent memo from Senator Vance, she plans to introduce a bill in the near future to amend Pennsylvania’s Generic Equivalent Drug Law regarding biosimilar products, such that “[s]ubstitution will only be permitted if certain minimal thresholds are met including a decision by the [FDA] that the prescribed product and the biosimilar product are interchangeable.”
ASBM, which is a self-described organization “composed of diverse healthcare groups and individuals – from patients to physicians, innovative medical biotechnology companies and others who are working together to ensure patient safety” with respect to biosimilars, has been particularly vocal about both biosimilar substitution and naming issues (see our previous post here). The organization has devised its own “principles on interchangeability,” under which:
(1) Physicians have the authority to specify “do not substitute” for biological products and that specification overrides any policy – e.g. by payers or state law – that would have substitution be the standard or default practice;
(2) Physicians and pharmacists should work collaboratively to ensure that the treating physician is aware of the exact biologic – by manufacturer – given to a patient in order to facilitate patient care and accurate attribution of any adverse events that may occurs; and
(3) The timing of the notification process must not impose an undue burden on the pharmacist and need not be in advance of a substitution being made but must be timely enough to facilitate accurate record keeping and attribution of adverse events by the physician.
Similar principles have been set out by other groups, such as the American Academy of Dermatology (see here).
On the other side of the debate – both with respect to biosimilar substitution and naming issues – are groups such as the American Pharmacists Association, the National Association of Chain Drug Stores, and the National Community Pharmacists Association. In a letter sent to FDA last year, these groups support automatic substitution of interchangeable biosimilar biological products and take the position that “if the FDA deems interchangeability between products, pharmacists should be able to automatically substitute biosimilar interchangeable products as it is currently regulated under the PHS Act.” As the letter points out, PHS Act § 351(i)(3) provides that “interchangeable products may be substituted for the reference product without the intervention of the prescribing healthcare provider.”