South Centre Report Calls for "Biological Generics"

The South Centre, an intragovernmental organization of developing nations headquartered in Geneva, Switzerland, has issued a new report on biosimilars that calls on regulatory bodies to institute an approval pathway for “biological generics” in favor of biosimilars.

The report, titled “The International Debate on Generic Medicines of Biological Origin” and authored by German Velasquez, PhD, explains that the cost of biologic medicines is just as significant a barrier, if not an even higher one, to patient access in the developing world as it is elsewhere. “Whether or not there is an adequate supply of generic biological drugs available will be crucial to ensuring the economic viability of health systems in both developing and developed countries,” writes Velasquez.

Among the hurdles to affordable biologic therapies that the report addresses are the following:

Patents and Data Exclusivity

Velasquez argues that, while drugs are under patent protection, manufacturers are free to set prices based not on production or development costs, but on the supposed value of the medicine to an individual or to society, with an emphasis on the value of a product in terms of days of life gained or labor force recovered. “This new price-setting trend threatens the economic viability of our health systems,” he says, adding that data exclusivity—protection of a drug’s clinical data from competitors for a limited period of time—compounds the problem. Even in nations where a product is not protected by a patent, Velasquez argues, the inability of a competitor to gain access to data in order to develop a competitive product can “…[give] rise to the same type of monopolies as patents do.”

Approval Pathways

Velasquez says that the approval and regulation of biologic drugs is more complex than that of small-molecule drugs in part because the World Health Organization (WHO) has not set a global standard. This lack of a unifying regulatory approach has led nations like the United States to construct their own approval pathways, thereby complicating the biosimilar approval process.

Furthermore, Velasquez argues, guidelines for demonstrating biosimilarity in the European Union serve to block or delay biosimilar availability, because, he says, these guidelines are not intended to demonstrate therapeutic equivalence, but instead to demonstrate that 2 proteins are highly similar. “Indeed, the debate over whether two chemical substances or two proteins are or can be identical is of little interest in evaluating their biosimilarity from the perspective of public health since the aim is to establish therapeutic equivalency,” writes Velasquez.

The report also argues against the WHO’s adoption of a biological qualifier, or a code that would be assigned to biological products and used in conjunction with the drugs’ international nonproprietary names (INNs), which Velasquez says could cause unnecessary confusion in the prescribing and dispensing of drugs. (The WHO announced in October 2017 that it would not proceed with the use of biological qualifiers in the foreseeable future.)

Industry Strategies

Velasquez points to pay-for-delay settlements—arrangements under which an innovator product sponsor agrees to pay a biosimilar or generic developer a sum of money in order to delay market entry of its product—as a barrier to competition. So-called “authorized generics,” or drugs produced by a brand-name manufacturer under separate labels, are also “clearly contrary to the principle of free competition that should apply once a patent has expired,” he adds. Finally, Velasquez states that industry lobbying has made importation of international products into nations like the United States all but impossible.

The report concludes that the growing cost of biologic drugs hinges on a new focus on the “value” of a drug rather than on the cost of its development or production, and that patent and data protection erect further barriers to market competition.

Instead of allowing for biosimilars, Velasquez writes, regulatory bodies should instead focus on approving “biological generics,” or drugs that can produce the same patient outcomes as biologic medicines regardless of the generic’s molecular similarity to its reference. “What matters to the patient, after all,” he writes, “is whether or not the drug can prevent, cure, or mitigate the effects of the illness.”

The report does not address the feasibility of transitioning or switching between innovator biologics and so-called biological generics, nor does it propose guidelines for demonstrating therapeutic equivalence of these therapies.