Remove Roadblocks to Streamline the Biosimilar Approval Process, Industry Veteran Says

It’ll take a long time for the public to overcome its hesitancy over accepting biosimilars and, similarly, a while for official descriptions of biosimilars to reflect their true merits, said Sarfaraz K. Niazi, PhD, an adjunct professor at the University of Illinois, Chicago, and chief executive officer of PharmaSci, a consultancy firm that focuses on speeding market acceptance of biosimilars.

“’Similar’ doesn’t mean much to me, because it doesn’t say what context,” he told an audience at the recent Specialty Therapies and Biosimilars Congress in Miami, Florida. In his talk, Niazi discussed logical inconsistencies in the struggle for regulatory approval of biosimilars that complicate approvals and add expense, as well as regulatory and procedural improvements that might simplify acceptance of these agents in the future.

Mvasi was the first bevacizumab biosimilar to gain approval, in 2017, and yet developing this product was an expensive process that involved more than 90 tests, some of which could have been avoided, Niazi said. Some of the redundancy involved testing for responses in animals, such as mice and rats, that did not have comparable human-like features such as receptors to bind monoclonal antibodies, which would have yielded meaningful data, Niazi said. “They did animal studies that weren’t necessary.”

Niazi also gave the example of studies in mice, rats, and monkeys done for the etanercept biosimilars Eticovo and Erlzi. The monkey studies were acceptable, but the rodent tests were unnecessary because rodents lack the receptors necessary to respond to etanercept.

Various forms of testing are often pursued by biosimilar developers in their efforts to cover all bases for reviewing agencies, but they often are contrary to the policies of the regulators themselves, who may recognize that these tests can be irrelevant to the demonstration of comparable safety and efficacy to an originator product, he said.

Toxicology studies done in animals do provide value in helping to convince regulators that a biosimilar passes the test, he said. “These [pharmacokinetic] PK studies are not intended to evaluate bioequivalence, but to look at how the body is looking at the molecule. PK is what the body does to the molecule. This is one of the most subtle ways of looking at structural differences.” Niazi has previously called upon the FDA to provide more guidance for biosimilar developers on the what types of animal studies are inappropriate for the purposes of approval.

The value and importance of pharmacokinetic (PK) studies are misunderstood, he said. Among biosimilar developers, a disproportionate amount of value is placed on clinical efficacy studies, whereas what will bring significant value in the development process, in the eyes of regulators, is knowing how the biosimilar is going to interact with the human body.

“If your PK study fails and your clinical study passes, your product doesn’t get accepted,” he said. A drug that is more active than the originator product poses the risk of producing more adverse events.

“In their newest guideline on interchangeability, the FDA stated that clinical efficacy studies [alone] do not provide the necessary confidence that they need for biosimilars,” Niazi said.

His position is that clinical efficacy testing is expensive and time consuming and not always relevant to the agency’s determination, and that developers need to challenge the FDA to relax these requirements.

Niazi said that structural and functional differences in a biosimilar are not necessarily detrimental to the approvals process if they have no clinical relevance. In statements, Niazi has called upon the FDA to list structural differences that are less relevant to clinical efficacy.

In further discussion of biosimilar acceptance, Niazi said he believes that pricing is going to play a large role. “Prices have to come down,” he said, “but I see that coming.” For instance, he said, doctors still prescribe Neupogen, the originator filgrastim product, for patients regardless of the availability of biosimilars.

When it comes to acceptance, it’s also important to understand that biologics have a good safety profile. “I think we’re coming to a rational understanding that biosimilars are much safer than any other product. Biological products have a better safety history than chemical drugs. This part has to be understood, but not, of course, in the realm of economics,” Niazi said.