The FDA draft guidance, issued in January 2017, is the first recommendation the FDA has issued on interchangeability. It provides detailed information about demonstrating the interchangeability of a biosimilar product with a reference biological product, including the type and amount of data and information needed to support a demonstration of interchangeability, the design and analysis of switching studies, the use of US-licensed reference products in switching studies, and considerations for developing presentations, container closure systems, and delivery device constituent parts for the proposed interchangeable product.
It is likely that the FDA draft guidance been issued now in response to the number of biosimilar products that are currently in clinical development. The first biosimilar product was approved by the FDA in 2015, three more were approved in 2016 and there are currently many applications being reviewed by the FDA.
The full market potential for biosimilar products has not yet been realised because of the lack of interchangeability and lingering uncertainties about efficacy and safety among both health care providers and patients when switching from an original reference product to a biosimilar product. More defined requirements in the FDA Guidance provide clarity for pharma and pave the way for more development.
The importance of Interchangeability
In theory, once the biosimilar product is deemed ‘interchangeable’, it can be automatically substituted for the prescribed biological product by the pharmacist without the consent of the prescribing physician. The concept of interchangeability designation is unique to the US and FDA. The FDA has approved 4 biosimilars since 2015. To date however, the FDA has not designated any of the four approved biosimilar products as interchangeable.
Health care providers need more data to demonstrate that the efficacy and safety of a biosimilar product is similar to that of the reference biological product so that they can be sure that when they prescribe it, the effects will be similar to the reference product. In particular, because biological products are large complex molecules, they can be very antigenic compounds that elicit antibody responses. The potential production of antibodies is a cause for concern regarding the safety and efficacy of a biosimilar product.
Regulators require that data and information is provided to show that a proposed interchangeable product can be expected to produce the same clinical result as the reference product. This should include but is not limited to, for example, identification and analysis of the critical quality attributes, analysis of mechanism(s) of action, pharmacokinetics, biodistribution and immunogenicity risk of the product in different patient populations.
The designation of a biosimilar as an interchangeable product is important as it will not only provide this reassurance but also the opportunity for the full market potential for biosimilar products to be realised.
For biosimilars requiring multiple administration, switching studies should be designed to determine whether alternating between a biosimilar and the reference biological product two or more times, has an impact on safety or efficacy. The FDA recommends that sponsors conducting switching studies should use a US-licensed reference product because “Rather than being used only as a control, the comparator product is used in a switching study in both the active switching arm and the control non-switching arm” and subtle differences between biological products licensed in different countries or regions could affect patients’ immune responses.
Any differences could create uncertainty as to whether the results of a switching study using a non-US-licensed reference product would be applicable to a US-licensed reference product.
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