Senate Committee to US FDA: Where are the biosimilar guidelines?
During a hearing on biosimilar implementation before the US Senate Committee on Health, Education, Labor and Pensions (HELP) yesterday, Director of Center for Drug Evaluation and Research (CDER) Janet Woodcook was asked why industry, patients and physicians were still awaiting guidance on interchangeability and labelling, five years on since congress authorised a specific biosimilar pathway.
“We have to get the science right. We can’t have problems with the first biosimilars out of the block,” she told the committee. “The most important thing is setting the scientific framework as bulletproof.”
So far the US Food and Drug Administration (FDA) has issued eight guidance documents - three final, five draft – the latest on the naming of biosimilars published last month.
She added the Agency was spending much of its time and budget developing the necessary guidelines but also working with sponsors often on a one-to-one basis. There are 57 biosimilar development programmes referencing 16 proprietary products which the FDA is currently involved in.
Interchangeability timeline
Woodcook said the next important guidelines will be on interchangeability and labelling but the level of complexity and the multiple clearances needed may mean they will not be delivered this year.
INTERCHANGEABILITY STATUTORY STANDARD
The statutory standard for interchangeability, as quoted by Woodcook yesterday, is: “[The biosimilar] is expected to produce the same clinical result as the reference product in any given patient. Second of all it is a product that when administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the biosimilar product and its reference product is not greater than the risk of using the reference product alone.”
“When we approve a biosimilar we will find it is highly similar to its reference product, meaning it is expected to produce the same clinical effects, both safety and efficacy,” she explained. “What the concern has been is that the continued switching could raise that immunity and provide a booster effect and cause untoward effects.”
This was seen with erythropoietin (EPO), Woodcook continued. When small manufacturing changes to the reference product were made, the drug made patients produce antibodies against their own hormone that resulted in pure red cell aplasia, leaving them transfusion dependent.
Sandoz's Zarxio is the only product so far approved to be 'biosimilar' in the US, but it has not been demed interchangeable
Education and what we've learnt from generics
It was highlighted to Woodcock that the US is way behind other regions in bringing biosimilars to market, and the lack of guidance is further delaying potential cost-savings and patient access, and simultaneously undermining the physician and public perception of copycat biologics.
“Biosimilars can save an estimated $44bn but only if patients and doctors have confidence,” Senator Warren said to Woodcock. “I’m concerned that misunderstandings over biosimilars will hamper uptake in the market.”
“I understand that you are carrying out a plan but I want to underline the urgency,” she continued. “Generics have been on market for 30 years but even today it is not a fully open market where physicians have full confidence in the generic product.”
According to Woodcock, the FDA has proposed a plan of campaigns and focus groups to educate the public about biosimilars, involving targeting sub-specialty groups and state legislators.
“There are a menu of education tools laid out over the next few years,” she said, but admitted the FDA’s biosimilar programme budget – about $21m – did not contemplate a large education plan.
