On January 26, 2016, the World Health Organization (WHO) unveiled the final version of its proposal for a worldwide biosimilar naming convention. The WHO proposes to add a “biologic qualifier” (BQ), which consists of four random consonants and an optional two-digit checksum, as an identifier that follows the nonproprietary name of each biologic and biosimilar product. This proposal resembles FDA’s biosimilar naming proposal, which adds four random consonants as a suffix to nonproprietary names. Industry and healthcare stakeholders have criticized FDA’s proposal to use random suffixes, instead of meaningful—and therefore memorable—ones, due to a greater likelihood of reporting and prescription errors with meaningless names. The WHO proposal, which uses a randomly generated separate identifier, is likely to draw similar criticism.
The WHO assigns an international nonproprietary name (INN) to each pharmaceutical substance—including biologics—so that each substance would have a unique global identifier. Unlike generic drugs, biosimilar products are not identical to the originator product. Many, including FDA, therefore believe that distinct nonproprietary names for originator products and biosimilars are necessary to protect patients.
But many biosimilar makers have argued that distinct names will impede the adoption of biosimilars. Some national regulatory authorities do not require biosimilars to bear distinctive nonproprietary names. Others have adopted distinctive naming conventions that differ from those proposed by the WHO and FDA. Japan, for instance, requires the biosimilar to have the nonproprietary name of the reference product, plus “biosimilar” and a number indicating the order in which the biosimilar was approved in Japan. Australia initially planned to use a biosimilar identifier consisting of the prefix “sim” and a three letter code but backed away from that plan in light of the WHO’s announcement in 2014 of its effort to develop a unified naming convention for biosimilars. Many hoped that a WHO naming convention would help facilitate a harmonized, global approach for identifying biosimilars.
In 1991, the WHO began to add Greek letters to the INNs of biologics to distinguish different glycoforms. In response to requests from national regulators, the WHO developed a new system to assign a BQ to biologic INNs to further distinguish biosimilars from the reference product. The WHO envisions that the BQ system would initially be used in conjunction with the Greek-letter system, and it may revisit the need to use both systems concurrently if and when BQ use becomes comprehensive.
Before homing in on its current naming proposal, the WHO considered assigning a three-letter code that included vowels that would be used with the nonproprietary name of a biologic. The organization abandoned this scheme because it determined that four letters were required to generate a sufficient number of BQ combinations for all future biologic and biosimilar products. The WHO also concluded that it was necessary to exclude vowels to avoid objectionable or promotional meanings. In the final proposal, the WHO INN Secretariat assigns a BQ consisting of four random consonants and an optional two digit checksum as a separate identifier to be used in conjunction with the INN assigned to each biologic or biosimilar product. The WHO included the optional two digit checksum to ensure data integrity and further distinguish the biosimilar from the originator biologic product.
The checksum is calculated based on an algorithm that takes into account each of the four randomly assigned consonants and their positions. Each national regulator would have discretion to adopt the checksum, which could be placed either at the end or inserted in the middle of the four consonants of the BQ. For instance, if a biosimilar was assigned the letters “bxsh” and those letters are associated with a checksum value of 08, the national regulatory authority would have the option of using “bxsh,” “bxsh08,” or “bx08sh” as the BQ. The WHO proposal currently applies only prospectively to new biologic and biosimilar products. The WHO is investigating mechanisms to apply its proposal retroactively.
The WHO proposal bears close resemblance to FDA’s proposed biosimilar naming scheme announced in August 2015. Although FDA does not use a separate identifier, FDA proposes to add a suffix consisting of four random consonants to the nonproprietary name of the originator product to distinguish biosimilars. Many stakeholders, including both innovators and biosimilar makers, have criticized FDA’s proposed random, and therefore not meaningful, suffixes. They argue that meaningful suffixes, such as those associated with the manufacturer’s name, would improve pharmacovigilance and reduce the risk of transcription and prescription errors.
The WHO also received suggestions to use an abbreviated form of the manufacturer’s name as the BQ and/or to use the same BQ for all of a particular’s manufacturer’s products so that a random BQ may come to be associated with a manufacturer. The WHO rejected these suggestions, preferring to use the optional checksum, rather than a meaningful identifier, to safeguard against transcription error and enhance pharmacovigilance. The WHO offered three reasons for rejecting meaningful BQs. First, the WHO expressed concern that such a system would make each BQ effectively a proprietary item of the manufacturer associated with the product. Second, the WHO was apprehensive that, through mergers and acquisitions, a company may come to manufacture a product with a BQ that is associated with another company, thereby causing confusion. Finally, national regulatory authorities expressed a preference for meaningless, random identifiers.
Public comments may persuade national regulators to revisit their preferences towards meaningless, random identifiers. If this occurs, the WHO may also come to reconsider its rejection of meaningful BQs.