- The Food and Drug Administration on Tuesday released draft guidance on how the industry should approach proving interchangeability between biosimilars and biologic drugs, filling a major gap in the regulatory framework surrounding the copycat biologics.
- In order for a biosimilar to be judged "interchangeable" with its reference biologic, drugmakers will need to prove the biosimilar produces the same clinical result as the other drug in any given patient and across all of that drug's approved indications.
- So far, four biosimilars have been approved by the FDA for use in the U.S., but none have been classified as an "interchangeable" product. The designation is important as it allows pharmacists to substitute a biosimilar without intervention from a healthcare provider.
Biosimilar development has rapidly gathered steam in the U.S. since approval of Sandoz's biosimilar of Amgen's Neupogen (filgrastim) in late 2015. Last year, three more biosimilars passed muster with the FDA, and Pfizer began marketing Inflectra (infliximab-dyyb), a copy of the blockbuster Remicade (infliximab) which it co-developed with Celltrion.
As the industry ramps up investment in biosimilars, the FDA has been working to further clarify the approval process. Tuesday's guidance was an important step to complete that work, laying out the regulator's expectations on how developers can prove their biosimilar products are interchangeable with the referenced biologic in question.
The Biologic Price Competition and Innovation Act (BPCIA), signed into law through the Affordable Care Act, created a regulatory pathway for approval of both biosimilars and interchangeable therapeutic protein products.
In order for a biosimilar to be approved, a drugmaker must demonstrate the drug is both highly similar to its reference product, and that there are no clinically meaningful differences between the two in safety, purity and potency.
Interchangeables, though, are considered a notch above. In addition to meeting all standards of biosimilarity, interchangeable drugs must produce "the same clinical result as the reference product in any given patient," the FDA wrote in its guidance. Furthermore, the regulator expects an interchangeable product will produce that result across all approved uses of the reference product.
Drugmakers who hope to secure an interchangeable classification for their proposed biosimilar will have to carry out switching studies that assess the risk of substituting a biosimilar for its reference product, the guidance said.
Notably, postmarketing data on products first licensed as a biosimilar won't be sufficient in and of itself to support interchangeability.
The FDA also indicated room for flexibility in the data required to support an application, depending on the complexity and immunogenicity risk of a potential biosimilar.
Comments on the draft guidance should be submitted by March 20, 2017 in order to be considered by the FDA for drafting of a final guidance.