Bellevue, WA—Although biologics have been a potent addition to the rheumatologist’s armamentarium, they come with complications, too, including high costs and regulatory confusion. In other words, their complexity extends far beyond the manufacturing process.
At the National Organization of Rheumatology Managers 2015 annual meeting, Jerry D. Clewell, PharmD, Associate Scientific Director of Biotherapeutics Strategy at AbbVie, offered an overview of these complicated products and their even-more-confusing “offspring”—biosimilars.
1 Biosimilars are not generic biologic products.
Unlike small molecules, such as aspirin or antibiotics, biologics are created from living cells. Very precisely assembled proteins comprise their structure, which is highly sensitive to the environment. In addition, biologics cannot be copied exactly, which is why new versions of “innovator” products are called “biosimilars,” not generics.
“Biosimilars are not made from a clinical recipe, so to speak,” said Dr Clewell. “If you think about conventional small drugs, which have no amino acids and are not made up of proteins…it’s like comparing a bicycle to a space shuttle.”
Thus, biologics are thousands of times larger and more complex than traditional therapies, and to complicate matters further, biologics are delivered by unique infusion systems, the alteration of which can dramatically affect outcomes.
“We cannot treat these products the same in any respect,” said Dr Clewell.
By the US Food and Drug Administration (FDA) definition, biosimilars must be highly similar to the reference product, with no clinically meaningful difference in terms of safety, purity, or potency. Clinical trials will thus play a critical role in determining similarity, but the question becomes, how much can these clinical trials be minimized (to save costs) while still maintaining acceptable risk before release?
2 Biosimilarity does not imply interchangeability.
According to the FDA definition, a biologic product is interchangeable if it meets the standard of (1) being biosimilar and (2) being expected to produce the same clinical result as the FDA-approved reference product in any given patient.
Whereas interchangeability is decided by the FDA, substitution is decided by each state.
“The FDA does not regulate the practice of medicine or pharmacists,” Dr Clewell said. “That’s regulated at each state level by boards of medicine and boards of pharmacists.”
If the FDA determines that a product is interchangeable based on its assessment of the product, officials of each state still have to decide whether to accept that level of interchangeability and how its pharmacists should deal with substituting a product when presented with a prescription.
“The FDA has yet to provide clear guidance,” said Dr Clewell. “We are still waiting to hear from the FDA about the requirements to justify interchangeability.”
3 Science must lead policy, not the other way around.
The World Health Organization, Dr Clewell noted, discourages switching among biologic products for scientific reasons of immunogenicity and unknowns about what will happen when that occurs.
The decision to substitute a biosimilar product needs to be between the provider and the patient, not the payer, said Dr Clewell, who also encouraged patients to make sure that their voices are heard at the state and national levels.
“We aren’t quite there yet in fully understanding all of the science and all of the nuances,” he concluded. “But one thing is certain: We absolutely must make sure that the science is leading the policy and not the other way around.”