Q: What is the background to the naming system?

The WHO established the International Nonproprietary Names (INN) system in 1953 to ensure the ‘clear identification, safe prescription and dispensing of medicines to patients, and for communication and exchange of information among health professionals and scientist worldwide’. The INN is intended to inform as to the active ingredient of a drug, otherwise known as the ‘generic’ name. In addition companies can choose a trademarked ‘brand’ name; for example, Advil and Mortin are different brands of the INN Ibuprofen.

Q: How does the system work for biosimilars?

For a biological substance that is non-glycosylated protein, the structure of the biosimilar is the same as that of the originator and the same INN applies.

Genotropin, Biotropin and Humatrope are different brands of the INN Somatropin. For glycosylated proteins the glycan profile may differ. To distinguish between different glycoform profiles the INN programme introduced in 1991 a Greek letter second word as part of the INN with the first part being constant; for example, Eprex is designated Epoetin Alpha and Neorecormon Epoetin Beta.

With the advent of biosimilars there has been ongoing debate on whether a biosimilar product proven through a comprehensive quality, non-clinical and clinical comparability studies to be similar to the originator should have the same INN, both the constant and the Greek letter; for example, all biosimilar epoetin licensed as biosimilars to Eprex should all be named Epoetin Alpha. Others argue that biosimilars are not ‘identical’ and therefore should have unique INNs; traceability and attributions of adverse reactions have often been cited as a reason.

As a result of differing approaches the WHO convened a consultation group to discuss potential revision of the naming system. After several meetings it was concluded that the WHO should devise a scheme applicable prospectively and retrospectively to all biological substances assigned an INN, the biological qualifier (BQ) scheme. The scheme proposed, open for comments before finalisation, will consist of a code of four letters and each code issued will be assigned at random; for example, two different Epoetins Alpha will be named ‘Epoetin Alpha bbbb’ or ‘Epoetin Alpha cccc’. This is a voluntary scheme and individual regulatory agencies can choose whether they adopt the scheme.

Q: What is the position of regulatory agencies globally?

There are differing opinions across the world. The majority of EU Member States strongly supported the current EU thinking that biosimilars should be closely aligned with their reference biological and an INN qualifier would be contrary to such an alignment. Several Member States also voiced concern that a distinct INN for biosimilars could undermine the trust of healthcare professionals and the public and they did not see traceability and attribution of adverse reactions as a reason. Furthermore, current Pharmacovigilance directive makes it a legal requirement for EU Member States to take all necessary measures to clearly identify the biological medicines that are prescribed, dispensed and sold in their country, including recording trade name and batch numbers as well as the INN.

In the US the FDA has yet to issue guidance. With the recent first filing for a marketing authorisation for a biosimilar product in the US, law makers are urging the FDA to publish biosimilar naming guidance.

In Australia the TGA requires that the Australian Biological Name for a biosimilar be composed of the reference product name and a biosimilar identifier consisting of a prefix ‘sim’ and ending with the letter code issued by the WHO; for example, a biosimilar epoetin alpha will be named ‘sim epoetin alpha bbbb’. Japan also requires a similar scheme with a prefix.

Q: Will the proposed WHO naming scheme result in global harmonisation if adopted?

The lack of global consistency for naming of biosimilars will result in confusion and uncertainty. While the proposed WHO BQ scheme may offer consistency globally, it is a voluntary scheme and unless every Regulatory Authority subscribes to it, it may have the opposite effect and create more confusion with different regulatory authorities applying differing naming conventions.

Q: What does it all mean to the business of biosimilars?

It is debatable whether unique naming for biosimilars offers any advantage to pharmacovigilance systems currently in place having been shown to work effectively. However, from a commercial stance, a distinct name for each biosimilar gives brand name drug makers and biotechs a marketing advantage, as substitution will be more difficult for an already established product.

On the other hand, the biosimilar drug makers argue that the rationale offered by those supporting unique identifiers, namely traceability, is just a tactic designed to put doubt in the minds of the prescribers and the consumers about the quality of a biosimilar product hence blunting competition. This naming issue has also come to the attention of investors. A group of 19 institutional investors wrote to the boards of several major pharma and biotech companies, asking them to agree to various business principles that would support the use of biosimilars. The investors also voiced concern about the naming debate, stating in their letter that it would be a mistake to give biosimilars different names from the products they emulate.

‘In our view, assigning different names communicates to providers that the biosimilar is less effective, causing providers not to prescribe it and ultimately making it difficult for pharmacists to dispense,’ they say. Pharmacy benefits managers have also voiced support for uniform naming policies.

Perhaps it is all about business, as summed up in the Editorial Nature Biotechnology Vol 31 No.12 Dec 13 p 1055: ‘moves to give biosimilars nonproprietary names different from brand products are more than a wrangle about words – they could mean biosimilars arrive stillborn to the market’.