When it comes to guidance on interchangeables, the Pharmaceutical Research and Manufacturers of America (PhRMA) has some guidance for the FDA: Be more definite.
In recent comments on a draft guidance the agency released in February, PhRMA said the FDA should revise the guidance to “expressly state” that sponsors must show interchangeability – whether through clinical trials or scientifically justified extrapolation – for every approved indication of the reference biologic, even if the sponsor isn’t seeking licensure for each indication.
Such a requirement would be in keeping with the Biologic Price Competition and Innovation Act (BPCIA), which created interchangeability as a unique feature of the U.S. biosimilar market. Unlike biosimilars that must be prescribed by name in the U.S., interchangeables can be substituted automatically at the pharmacy when the reference drug is prescribed. As a result, interchangeables will bring a more generic-like competition to some biologics.
If interchangeability was not shown for every condition of use of the reference product, the follow-on wouldn’t meet the BPCIA’s interchangeability requirement that says it “can be expected to produce the same clinical result as the reference product in any given patient,” PhRMA said.
Citing pharmacy practice in the generic realm, the trade group added that pharmacies likely would substitute interchangeables for the reference biologic without regard to the indication for which the drug was prescribed. After all, doctors don’t include the indication on prescriptions. And even if they did, the FDA’s Purple Book of approved biologics apparently won’t list interchangeability determinations by indication, PhRMA said.
Although the trade group didn’t go there in its comments, payers also may have a voice in determining which version of a drug an insured patient gets at the pharmacy, based on negotiations with drug manufacturers.
Thus, requiring sponsors to show interchangeability for every indication of the reference biologic “is in the best interests of patients, as any other approach would create the risk of inappropriate pharmacy substitution,” PhRMA said.
As written, the draft guidance relegates the question to a footnote in which the agency said it “expects” applicants will submit data and information to support interchangeability for all the reference drug’s approved conditions of use. The language needs to be strengthened and moved into the body of the guidance, PhRMA said.
In another word of advice to the FDA, PhRMA encouraged it to provide more guidance on labeling for interchangeables. “Existing guidance on biosimilar labeling is expressly inapplicable to interchangeable products,” the trade group noted, and the February draft only addresses a few labeling issues pertaining to interchangeables.
The draft guidance focuses on the labeling of biosimilars and interchangeables that are licensed for fewer indications than the reference biologic since some indications may still be protected by patents or exclusivities – or the reference product may be approved for new indications after a follow-on was licensed. The guidance also discusses how the carved-out indications can be added into the follow-on labeling once the patents or exclusivities expire.
Other industry comments on the guidance homed in on the timing of adding those indications to a follow-on label once protections expire, patents are invalidated or license agreements are negotiated.
Although several companies have announced plans to develop interchangeables, interchangeability hasn’t been much of a regulatory issue yet, mainly because all the biosimilars approved to date are administered in a health care setting, not picked up at the pharmacy. Now that products such as insulin and hormones have been deemed biologics, the demand for more FDA guidance on interchangeability will continue to grow.