Advances in ADCs

New ADC therapies must overcome manufacturing challenges to reach market.
Jul 02, 2017
Volume 41, Issue 7, pg 63

Along with innovations in manufacturing equipment and facilities, improvements in starting materials, such as antibody selection, have made a difference in the efficiency of biopharmaceutical manufacturing. Catalent’s SMARTag technology, for example, improves antibody-drug conjugate (ADC) manufacturability. Pharmaceutical Technology spoke with Jennifer Mitcham, director of Business Development, Antibody-Drug Conjugates at Catalent, about this new technology. 

PharmTech: How does SMARTag improve manufacturability of ADCs?

Click cover to read more 40th anniversary features.Mitcham (Catalent): Although SMARTag is a chemoenzymatic method, the ‘enzymatic’ portion of the approach refers to a natural, endogenous enzyme that performs a co-translational modification during expression of the SMARTag antibody. We’ve observed that insertion of the enzyme’s recognition sequence does not impact expression levels or target reactivity as compared to the native antibody, and standard purification methods yield antibody material ready to proceed directly into a one-step conjugation. This simplicity is key to robust, efficient scalability of the required manufacturing process for ADCs. We’ve currently scaled multiple SMARTag antibodies up through a number of 500-L runs, observing productivity in excess of 75 pg/cell/day (yielding ~5 g/L) with essentially quantitative conversion to the aldehyde tag. Similarly, the aldehyde-specific chemistry, Hydrazino-Pictet-Spengler (HIPS), which is designed specifically to be well tolerated by proteins and to yield no off-target reactivity, has now been demonstrated to scale very efficiently for the generation of clinical material. Manufacture of SMARTag ADCs also offers an advantage in terms of release analytics since no off-target reactivity has been observed, and lots consistently produce highly homogeneous and stable ADC preparations. We expect the first SMARTag ADC to enter the clinic in early 2018.

Article Details

Pharmaceutical Technology
Vol. 41, No. 7
Page: 62

Citation

When referring to this article, please cite it as J, Markarian, “Advances in ADCs,” Pharmaceutical Technology 41 (7) 2017.

 

 

 

 

 

Article Details

Pharmaceutical Technology
Vol. 41, No. 7
Page: 62

 

Citation

When referring to this article, please cite it as J, Markarian, “Advances in ADCs,” Pharmaceutical Technology 41 (7) 2017.

 

 

native1_300x100
lorem ipsum