Both Amgen and Pfizer took particular notice of EMA’s reference to ICH guideline Q5E and both companies criticized the use of it. The EMA noted in its draft that as outlined in Q5E, “scientific principles of such a biosimilar comparability exercise are based on those applied for evaluation of the impact of changes in the manufacturing process of a biological medicinal product.”
But Amgen clarified: “We consider that there remains an important opportunity to be clear about the use of ICH Q5E in the biosimilar comparability exercise and in the use and limitations of the principle of PD fingerprinting. It is also key for the guideline to be clear that the Agency has no remit to provide guidance or instruction on switching or interchange."
Amgen says that it “needs to be recognized” that ICH Q5E describes a risk assessment process that can only work for a sponsor evaluating a change to its own manufacturing process. “Also, the objective of ICH Q5E is not to provide guidance for the biosimilarity exercise, but rather when changes are made in the (proprietary) manufacturing process for biologics. This fundamental difference in terms of objective/purpose should be reflected in the final guideline,” Amgen says.
Pfizer similarly notes that although the scientific principles are similar to those of ICH Q5E, the guideline should say that the regulatory context of the assessments are “very different since ICH Q5E applies to a manufacturer making changes to their own process.”
“The standard and level of evidence for biosimilarity assessment must necessarily be higher since the biosimilar developer has developed their own manufacturing process and does not therefore have access to the full development and manufacturing history which the reference product developer would have,” Pfizer says.
But the EMA, in acknowledging the comments, says that the principles of ICH Q5E and biosimilar comparability exercise may be the same, though “the data requirements may differ as outlined in the biosimilar guidelines.”
In addition, Pfizer says that because the guideline “is the only place where the subject of bridging to a non-European Economic Area (EEA) comparator product is discussed,” it may be helpful to provide more detail on some general principles, such as widening the scope of biological products which could be developed as biosimilars “as theoretically no product categories are ruled out, although in practice the high hurdle of developing a similar product will be practically challenging for certain classes of product.”
Pfizer also believes the agency should make note of cases where a clinical efficacy study may not be necessary for structurally simpler biologics as “such cases would be the exception rather than the rule and no mention is made of how assessment of immunogenicity would be made.”