Replies to post #5203 on Insmed Inc (INSM)

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NO european "issues" that make it all thin air as you suggest wjklnew

key item there for doubt was the production moves

"A complication of this application is the historical multiple sites of manufacture. The drug substance was
first produced at Insmed Santa Clara Ca. USA and was then moved to Avecia, and was then transferred to
Insmed, Boulder. The Applicant has attempted to demonstrate that the drug substance produced at each
site is comparable. One difficulty is that there is very limited material from the Santa Clara and no
opportunity to manufacture any more as this site has closed.
The Applicant has attempted to show comparability using analytical techniques such as mass
spectrometry, differential scanning colorimetry (DSC) and peptide mapping. Analytical data indicated
that material from the Santa Clara and Avecia sites was similar. Physical methods and bioassay data does
not support a claim of comparability. In addition, tentative similarity has only been demonstrated on a
limited number of batches and in the case of material produced at Insmed Santa Clara this evidence takes
the form of one reference batch produced at this site. The greatest changes in manufacturing processes are
between the Insmed Santa Clara site and the Avecia and Insmed Boulder sites and it is between these sites
that the data regarding batch numbers is at its weakest. The comparability study presented does not
conform to ICH Q5E and therefore does not demonstrate comparability.
The binding affinity of the recombinant products has not been compared with native proteins. The data
concerning the rhIGF-I – rhIGFBP-3 binding affinity is based on a published report. It is not known
whether the materials involved in this study were prepared by any of the three technologies described in
the application. The published binding affinity data concerning IGF-1 and IGFBP-3 was not obtained
using the Applicant’s IGF-1 or IGFBP-3 and this study should be performed and the results compared to
the binding affinities of native IGF-1 and IGFBP-3."

another item was the time that patient were on the drug which would require more data