The Biosimilar: Branded or Generic? Interchangeable or Not?

Depending on how one approaches the questions posed by this article’s title, the answers are either crystal clear or clear as mud. And here’s why.

Health Canada is clear. Authorization of a subsequent entry biologic (SEB) by Health Canada is “not a declaration of pharmaceutical or therapeutic equivalence to the reference drug.”^[1] Furthermore, Health Canada does not “support automatic substitution of an SEB for its reference drug.”^[2] Historically, a drug is only considered interchangeable in Canada if Health Canada declares equivalence to the reference drug upon authorization. So far, everything appears straightforward in the world of small molecules.

Since SEBs, also referred to as biosimilars, can not be thought of as generic drugs without a declaration of equivalence, does this make them brand-name drugs? The answer is “not exactly”; although they are fashioned to be as similar as possible to innovators, they come to market, as per guidelines, with significantly fewer clinical studies than innovators. So far, the status of biosimilars is totally clear: they are neither brand-name drugs nor generics. That’s why they have their own set of guidelines, which are still evolving.

Let’s return to that pesky question of interchangeability.

Up until now in Canada, innovators and biosimilars have not been interchangeable. Let’s keep in mind that interchangeability is determined at the provincial level. The decision-makers, liability holders, and equivalence criteria for four key provinces are summarized in Table 1 below.

Table 1: Provincial Decisions on the Interchangeability of Innovators and Biosimilars

<table> <thead> <tr class="header"> <th>Province</th> <th>Decision Maker</th> <th>Liability Holder</th> <th>Criteria</th> <th>SEB Interchangeability</th> </tr> </thead> <tbody> <tr class="odd"> <td>BC</td> <td>Pharmacist</td> <td>No one</td> <td><ul> <li>Health Canada declaration of equivalence</li> </ul></td> <td>No</td> </tr> <tr class="even"> <td>AB</td> <td>Health minister</td> <td>No one</td> <td><ul> <li>Safe</li> <li>Same therapeutic effect</li> </ul></td> <td>No</td> </tr> <tr class="odd"> <td>ON</td> <td>Executive officer</td> <td>No one</td> <td><ul> <li>Same active, equal quantity</li> <li>In the public interest</li> </ul></td> <td>Possible</td> </tr> <tr class="even"> <td>QC</td> <td>Pharmacist</td> <td>Prescriber/dispenser</td> <td><ul> <li>Same generic names in equal quantity</li> </ul></td> <td>No</td> </tr> </tbody> </table>

Other jurisdictions are working to support interchangeability. In the United States, Food and Drug Administration (FDA) approvals are now expected to designate each biosimilar as falling into one of two categories: biosimilar or interchangeable biosimilar (see Table 2 below)^[3]. The market is curious to see what the requirements for the interchangeable biosimilar designation will be and how such a classification will impact both pricing and competition. It should be noted that, in the US, individual states determine interchangeability.

<b>Table 2: United States FDA Biosimilar Categories</b>

	Definition	Comment
Biosimilar	Highly similar to the reference with no clinically meaningful differences	Substitution by prescriber only
Interchangeable Biosimilar	A biosimilar (as above) that can be expected to produce the same clinical effect in any given patient as the reference	"May be substituted for the reference product by a pharmacist without the intervention of the prescriber

FDA approval includes designation of interchangeability status. Individual states determine interchangeability (FDA designation required).

In Europe, the European Medicines Agency (EMA) does not mandate interchangeability; member countries do. A number of EU members have legislations in place that prohibit autosubstitution at pharmacies. France, however, allows substitution for treatment-naive patients, and Germany permits interchangeability when the biosimilar and innovator have both been manufactured in the same country (not really a substitution).

Although the interchangeability landscape is interesting, it may not be as important as one might conclude.[^4] As we are seeing here in Canada, the factors driving product selection, which are often financial, are also directing the use of the biosimilar for patients with de novo diagnoses across most public payers. For existing infliximab prescriptions, the innovator Remicade is still being reimbursed. Some private payers are following this initiative. If future policy should remove the grandfathering that currently renews coverage for patients already on the innovator, there will be a significant risk for innovators. It is clear that pricing policies (in addition to designation of interchangeability) will promote biosimilar uptake to preferentially support a robust SEB market in Canada. Some contend that doing so will limit authentic market competition.

If it wasn’t already clear, this is how I see it as a pharmacist: Biosimilars are not brand-name drugs or generic drugs; rather, they are in a class of their own. While they may not be interchangeable, it might not matter as much as you might think – especially if we see policies that challenge grandfathering for those already on treatment. Perhaps, we should be asking the following questions instead: Are biosimilars really similar enough to be substituted for innovators? And, what is the very best way to support competition, innovation, and sustainability all at the same time? Let’s also not forget to ask: What types of therapy offer the best individualized patient treatment and outcome?

Questions? Contact Marc Lafoley, Director, The Pangaea Group

Originally published in Canadian Pharmaceutical Marketing November/ December 2016

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1. Health Canada Guidance for Sponsors: Information and Submission Requirements for Subsequent Entry Biologics, 21010/03/05 pg 2. ↩︎

2. Health Canada Guidance for Sponsors: Information and Submission Requirements for Subsequent Entry Biologics, 21010/03/05 pg 2. ↩︎

3. <a href="http://www.raps.org/Regulatory-Focus/News/2016/09/08/25812/Biosimilar-Interchangeability-%E2%80%98Careful-What-You-Wish-For%E2%80%99/#.">Brennan Z: Biosimilar Interchangeability: ‘Careful What You Wish For’. Regulatory Affairs Professionals Society.</a> Accessed: October 5, 2016. ↩︎