What happens when regulatory ambiguity displaces sound scientific guidance, deterring the legislative intent of Congress? This is precisely the situation regarding the FDA changing the regulatory rules of the road regarding a biosimilar’s strength versus its potency. It is a distinction with a difference – with the potential unintended consequence of disincentivizing both the development and uptake of biosimilars. It is also important to consider the implications of the legislative intent of the Biologics Price Competition and Innovation Act of 2009 (BPCIA) and how it can be improved.

This is not an academic exercise. Although biologics only account for 2% of all prescriptions written in the US, they are responsible for $120 billion or 37% of net drug spending and, since 2014, for 93% of the overall growth in total spending.1

The BPCIA gave the FDA authority to create a regulatory pathway for biosimilar biological products. The BPCIA amended the Public Health Service Act to create an abbreviated approval pathway for biological products shown to be biosimilar to, or interchangeable with, an FDA-licensed reference biological product.

The development of this legislation included many different legislative iterations and scientific approaches. Two key issues, however, laid the groundwork for final passage:

1. That the intent of the legislation was to expedite the introduction of biosimilars into the US market to expand patient access to lower cost, safe and effective biologics; and
2. To maintain the FDA’s regulatory flexibility in determining the scientific “rules of the road.”

The FDA must ensure that the regulatory process for biosimilars is one that instills confidence. Speeding products to market for commercial reasons minus the appropriate required regulatory science can have just the opposite effect. The FDA knows this. Quality is in in their DNA. Regulatory predictability is the critical element in driving investment, without which there will be no biosimilars to consider.

An agency requirement that a biosimilar medicine must be the same strength as the brand-name biologic treatment creates a tension between these two key issues.

The FDA has adopted a final policy that the “strength” of an injectable biological product (i.e., parenteral solution) is based on both the total content of drug substance (in mass or units of activity) and the concentration of drug substance (in mass or units of activity per unit volume). The FDA thus takes the position that the “same strength” requirement in section 351(k) of the Public Health Service Act2 (PHS) requires a biological product approved under the 351(k) pathway to have the same concentration of drug substance as the reference product (RP), not just the same total drug content.  On the other hand, “Potency” is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity.

The FDA’s definition of strength is too restrictive since the agency requires a biosimilar to have the same total concentration of the active ingredient found in the injectable originator biologic, not just the total drug content, even if both treatments have the same clinical effect on patients. This just doesn’t make sense and could present a roadblock to the intent of federal legislation. If an innovator biologics manufacturer wins FDA approval for a new formulation of an existing treatment with a different dosage and concentration, a rival manufacturer would likely be told its product is only considered to be a biosimilar version of the older formulation; similar in “strength” but not “potency” to the newer formulation. What messages does this send to payers, healthcare professionals, and patients? It isn’t a message of “similarity” or therapeutic parity. But should we trade either for the value of incremental innovation? We must always be wary of a regulatory Hobson’s Choice.3

The clear intent of the BPCIA was to allow the FDA significant latitude in determining the scientific requirements for biosimilar development and regulatory review. But what happens when the agency’s best scientific judgment comes into direct conflict with legislative intent?

Making BPCIA Better

There are many roadblocks preventing a more rapid penetration of biosimilars into the US market that are not within the purview of the Food and Drug Administration. One such impediment is “exclusionary contracting.”4 Pharmaceutical company rebates to pharmacy benefit managers that are tied to formulary restrictions create an incentive for entrenched market leaders to “bid” incremental rebates to prevent or limit access to competitive medicines. This model, coupled with escalating cost-sharing requirements, harms patients by driving up prices, which results in reducing access to innovative drugs.

“Business as usual” under the existing language of the BPCIA means continued disincentives to promote a more aggressive uptake of FDA-approved biosimilars. Worse, reinforcing the status quo moves us even further away from a healthcare ecosystem based on competitive and predictable free market principles – precisely the reverse of the intent of the BPCIA.

We can (and indeed must) embrace the best, most current thinking in regulatory science. Intelligent members of the healthcare ecosystem can disagree on issues such as “strength vs. potency.” But we must all be cognizant of the bigger picture: providing broader access to safe and effective medicines be they generic drugs or biosimilars. If we fail to embrace this shared mission, we do a tremendous disservice to advancing the value and accessibility of healthcare in America.