Despite their "conceptual parallels," biosimilars are in no way, shape or form to be confused with generics. That's the message the Australian Therapeutics Goods Administration (TGA) sent out repeatedly in its latest guidance on follow-on biologics as it made it clear there would be no automatic substitution down under for biosimilars.

"A biosimilar is not a generic biological medicine," the TGA said in the guidance. Because of the complexity and microterogeneity of biologics, the principles involved in the evaluation and use of generics "cannot be simply extrapolated to biosimilars," it added.

The guidance, released last week and modeled largely on European guidelines for evaluating biosimilar applications, shuts the door, at least for now, on interchangeability – a comparability standard many biosimilar sponsors are aiming for in the U.S. as it could allow pharmacists to automatically substitute a cheaper follow-on for a prescribed brand biologic. Such substitution would make it easier, and cheaper, to market a biosimilar. (See BioWorld Today, July 3, 2013.)

Unlike the FDA, the Australian agency doesn't believe it's "currently possible to determine a degree of similarity between a biosimilar and an already registered biological medicine sufficient to support a designation by the TGA of 'bioequivalence.'" The regulator intends to include a statement to that effect in its approval letters of future biosimilars.

To make sure prescribers and patients understand that biosimilars are not generics, the TGA also expects sponsors to include a paragraph in the product information indicating that the level of comparability shown isn't sufficient to designate a biosimilar as a generic version of the reference biologic and advising that substitution "should take place only under the supervision of the prescribing medical practitioner."

The guidance also draws the line between biosimilars and generics in requiring each follow-on "to have a clearly distinguishable trade name from all other products, especially the reference product and other biosimilars."

Noting that small variances in biosimilars of the same reference biologic "can give rise to differences in clinical behavior, in particular in immunogenic effects," the TGA said certain naming provisions are necessary to "ensure that it is possible to distinguish between biosimilars and clearly identify the reference product."

In addition to a trade name, each biosimilar is to have an Australian biological name (ABN) consisting of the ABN for the reference product and a biosimilar identifier made up of the prefix "sim(a)-" and a three-letter code issued by the World Health Organization's International Nonproprietary Name Committee.

While the generic naming practice of using the active pharmaceutical ingredient followed by the name of the drugmaker has been used for some biosimilars in Europe, the TGA said it isn't appropriate because it gives the impression that the follow-on is a generic drug. It also could:

• lead to confusion in prescribing and dispensing;

• contribute to difficulties in traceability following adverse event reports;

• be misleading.

Another difference between generics and biosimilars is extrapolation for other indications. While biosimilar sponsors may be able to extrapolate safety and efficacy data for other indications in certain cases, they will generally be required to justify or demonstrate the data separately for each claimed indication, according to the guidance.

When it comes to post-registration requirements and pharmacovigilance, biosimilars will be subject to the same requirements as other biologics. For instance, sponsors must develop a comprehensive risk management plan (RMP) outlining its pharmacovigilance procedures. However, that RMP may not necessarily mirror the plan for the reference biologic.

"Because all biotechnology-derived products are inherently variable, the established safety record of the reference product does not necessarily apply to the biosimilar," the TGA said. "For this reason, it is possible that after assessment of the risk management plan, active pharmacovigilance measures may be applied on a case-by-case basis."

The TGA approved its first biosimilar – Hospira Pty Ltd.'s Nivestim (filgrastim), a follow-on of Amgen Inc.'s Neupogen – three years ago on a regulatory path based on that of the European Union. Since then, a number of other biosimilars, including a vaccine, have been approved.