TGF β 3 immunoassay standardization: comparison of NIBSC reference preparation code 98/608 with avotermin lot...

Juvista™ drug product contains human recombinant active transforming growth factor beta 3 (TGFβ3; avotermin). Juvista is being developed for the prevention and reduction of human scarring. Phase II and III clinical and development batches of Juvista were assayed for content by an immunoenzymometric assay (IEMA) using a National Institute for Biological Standards and Control (NIBSC) TGFβ3 reference material (98/608) and avotermin standard (Lot 205-0505-005). Paired Juvista TGFβ3 data were compared directly, pooled, and processed using the statistical analysis described by Bland and Altman. A direct comparison of the two standards was also made. The Bland-Altman result was 1.958, the best estimate of the relationship between Lot 205-0505-005 and reference material 98/608. By IEMA, reference material 98/608 has approximately 50% of the immunoreactivity of Lot 205-0505-005. During clinical development, no change in Juvista TGFβ3 dosage was made, but the standard used for Juvista TGFβ3 assay was changed from 98/608 to 205-0505-005. The stated amount of Juvista TGFβ3 in phase III trials was approximately one-half of that in phase II trials. This article highlights the importance of early adoption of an appropriate and representative standard to achieve accurate quantification of protein drug during clinical development.