The 1st International standard for transforming growth factor-ß3 (TGF-ß3).

One candidate preparation of human sequence recombinant transforming growth factor-ß3 (TGF-ß3) was formulated and lyophilized at NIBSC prior to evaluation in a collaborative study for its suitability to serve as an international standard. The preparation was tested by 8 laboratories using in vitro bioassays and immunoassays. The candidate preparation 09/234 was judged suitable to serve as an international standard based on the data obtained for biological activity and stability. On the basis of the results reported here, the preparation coded 09/234 was established by the WHO Expert Committee on Biological Standardisation (ECBS) as the WHO 1st IS for human TGF-ß3 with an assigned value for TGF-ß3 activity of 19,000 IU/ampoule.

TGF ß 3 immunoassay standardization: comparison of NIBSC reference preparation code 98/608 with avotermin lot 205-0505-005.

Juvista™ drug product contains human recombinant active transforming growth factor beta 3 (TGFß3; 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) TGFß3 reference material (98/608) and avotermin standard (Lot 205-0505-005). Paired Juvista TGFß3 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 TGFß3 dosage was made, but the standard used for Juvista TGFß3 assay was changed from 98/608 to 205-0505-005. The stated amount of Juvista TGFß3 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.