Other Regulatory Considerations

Interchangeability

Interchangeability is defined by statute in the United States to mean that the product may be substituted for the reference product without the intervention of the physician who prescribed the reference product. The legal standard for interchangeability is an additional standard beyond demonstration of biosimilarity.

According to draft guidance from the FDA that was released on January 17, 2017, in order for a biological product to be deemed interchangeable, the information submitted must be sufficient to show that:

  • The biological product is biosimilar to the reference product and can be expected to produce the same result as the reference product in any given patient
  • For a biologic product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch.

Substitutions

In the United States, although Federal law gives the FDA authority to license biologic products as interchangeable, it is the state laws that govern the substitution of biologics and pharmaceuticals. A number of states have passed laws that allow for substitution at the pharmacy, without consulting the prescribing physician, only if the biological product has been designated as interchangeable by FDA. In effect, an FDA interchangeability designation is a prerequisite for pharmacy-level substitution.

Pfizer's position on interchangeability and substitution

Pfizer believes that the regulatory requirements for an FDA interchangeability designation should go beyond those required for approval as a biosimilar. In many states, an interchangeability designation allows for substitution of the biological product without the intervention of a physician. If state laws allow for pharmacy substitution of interchangeable biosimilars, both the prescribing physician should be notified and the patient be made aware of such substitutions. State laws should permit the substitution of only biosimilars that have been designated as interchangeable by the FDA.

Physician-mediated switching

Pfizer believes that decisions regarding treatment choice or physician‐mediated switching must be a clinical decision made by a treating physician on an individual patient basis, supported by scientific evidence, and with patient awareness. Such physician‐directed decisions are part of usual medical practice and are considered to be within the scope of approval and use of biosimilars, and they are independent of and not in any way related to substitution or interchangeability. The Biologics Price Competition and Innovation Act (BPCIA) does not require a biosimilar to be interchangeable in order for a physician to implement a switch. There are no switch data currently available to support switching from one biosimilar to another biosimilar; clinical data supporting switching from an originator product to a specific biosimilar are not transferable across other biologics or biosimilars.

How are biosimilars named?

A biosimilar cannot carry the same proprietary brand name as the reference product. Guidance issued by the FDA on January 12, 2017 indicates that it also is not appropriate for noninterchangeable biosimilars and reference products to share the same nonproprietary name. Rather, biosimilars should include an FDA‐designated suffix, consisting of 4 lowercase letters that are devoid of meaning. There is a need to clearly identify and distinguish biologic products that have not been determined to be interchangeable, for the purposes of safe use and to improve pharmacovigilance. Approved biosimilars, therefore, should have both names and labels that are readily distinguishable from the reference product and reflect their unique manufacturing processes and origins.

The FDA recommends use of a brand name in the label, where feasible and appropriate, in order to make distinctions between products as clear as possible. In addition to this, a clearly distinguishable nonproprietary name is necessary to track adverse events related to the specific biosimilar or reference product, to help ensure appropriate prescribing and dispensing, and to allow prescriber choice in health care systems where the nonproprietary name is typically used.

FDA intends to apply a naming convention to interchangeable products that will feature a core name and a suffix included in the proper name; however, FDA is continuing to consider the appropriate format of the suffix for these products.

The FDA approach to labeling biosimilars

Biosimilar labeling incorporates relevant data and safety information from the reference product labeling, with appropriate product‐specific modifications. There is generally no mention of the head-to‐head clinical studies that may have been undertaken on the biosimilar. Biosimilar labels also include a biosimilarity statement highlighting that the biosimilar product is biosimilar to its reference product.