The conclusions from Fimea released last week come as the agency looks to define its current position on the interchangeability of biosimilars and their reference products approved in the EU. But unlike in the US, Fimea defines interchangeability as “the medical practice of changing one medicine for another that is expected to achieve the same clinical effect in a given clinical setting,” but “does not deal with substitution at the pharmacy level.”
Since the approval of 21 biosimilars in the EU by the end of 2014, Fimea says that biosimilars have been widely used and their safety profiles “have been the same” as those of their reference products.
The comments by Fimea echo earlier sentiments expressed by the Netherlands Medicines Evaluation Board, which also said biosimilars have “no relevant differences” compared to reference products.
Breakdown of Potential Issues
“In theory, changes in safety and efficacy might be associated with a switch from reference product to biosimilar if either of the products has a higher inter-individual variation in pharmacokinetics. Such a difference has not been observed with current biosimilars,” Fimea adds.
And in terms of immunogenicity, which Fimea says is “the remaining potential problem,” a person could react to a structural difference between the reference product and biosimilar. “Such a reaction is highly unlikely with licensed biosimilars, since the products have been shown to have comparable structure and immunogenicity in pre-licensing clinical trials,” Fimea says.
However, according to Fimea, increased immunogenicity “has, in rare cases, been associated with manufacturing changes of a given biological product. In these cases, no immunogenicity studies were performed before transition from the old to the new version.”
Another potential cause for concern is that the reference product “is immunogenic and the immunoglobulin class or specificity will change upon the switch to a biosimilar.” But Fimea says that in both cases, “the activation of T lymphocytes is required. Activation of T-lymphocytes would require recognition of new linear peptide epitopes in the biosimilar. This is unlikely since the active substance of the biosimilar has the same amino acid sequence and a similar posttranslational profile as compared to its reference product.”
In conclusion, Fimea makes the following statements in support of biosimilars as its current position “is that biosimilars are interchangeable with their reference products under the supervision of a health care person”:
- Switches between biological products are common and usually not problematic, for example in the context of hospital tendering processes;
- For the time being, there is no evidence for adverse effects due to the switch from a reference product to a biosimilar; and
- The theoretical basis of such adverse effects is weak and the risk of adverse effects can be expected to be similar to the risk associated with changes in the manufacturing process of any biological product.