Replies to post #654129 on NorthWest Biotherapeutics Inc (NWBO)

[The Danish Dude]

From the MHRA document on biosimilar

A biosimilar should be highly similar to the RP in physicochemical properties, biological activity/potency and clinical profiles. In addition, biosimilar development requires that the impurity profile and the nature of excipients of the biosimilar itself do not give rise to concerns. Any observed differences must be duly justified with regard to their potential impact on safety and efficacy. For an active substance that is a protein, the amino acid sequence is expected to be the same, other than justified post-translational modifications.

The posology (dose and frequency of dosing) and route of administration of the biosimilar must be the same as those of the RP but deviations from the RP are possible, such as the strength (for example, higher concentration to allow for a smaller injection volume, more suitable for paediatric indications), pharmaceutical form, formulation, excipients or presentation. These require justification and may need additional data. Patient acceptability should also be considered.

[antihama]

This reminds me when TFF manufacturing was being discussed, a process which brought increased potency. RKmatters et al (including me and others) didn't think it would be a problem, And now w Biosimilar Development familiarity I think even less so. As a blast from the past, I'm pasting part of a post in an exchange RKmatters had w evil Voldemort (Pyrrhonian). Note - TFF manufacturing was being discussed when many were wondering if it was being used in the manufacture of DCVax-L. She finally concluded that it wasn't (it was being used to manufacture Direct) but still a relevant post.

Where we disagree is that you have taken your own "formulation" interpretation too far. The formulation does not change by use of the Tangential Flow Filtration (TFF) patent. No biological "composition" ingredient is being added or taken away. Their Phase III IND formula uses leukocytes. The TFF patent removes non-leukocyte, leaving an enriched leukocytes. The end result is said to be a composition of monocytes. The composition is the IND. But with biologics products, “the process is the product”. They consider their manufacturing process to be as integral to the product as is the composition of the product itself. They, however, do not view the two as the same. The manufacturing process is not the composition. The composition is not the manufacturing process. The changes in manufacturing processes can be implemented as long as the quality, efficacy or safety of the "product" is equivalent or better to the original IND manufacturing process. But if you still disagree, consider DCVax-Direct. The DCVax-Direct IND came well before that TFF patent was issued. Your own argument would imply that they would be unable to use the TFF patent in manufacturing the DC in that study. Yet, they disclosed they in fact use the newly minted TFF patent grant in the DCVax-Direct trial. That effectively proves that no new IND was needed to implement that particular patent. Post# 63189